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Conway RB, Snell-Bergeon J, Honda-Kohmo K, Peddi AK, Isa SB, Sulong S, Sibomana L, Gerard Gonzalez A, Song J, Lomax KE, Lo CN, Kim W, Haynes A, de Bock M, Burckhardt MA, Schwab S, Hong K. Disparities in Diabetes Technology Uptake in Youth and Young Adults With Type 1 Diabetes: A Global Perspective. J Endocr Soc 2024; 9:bvae210. [PMID: 39703363 PMCID: PMC11655873 DOI: 10.1210/jendso/bvae210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Indexed: 12/21/2024] Open
Abstract
Globally, nearly 9 million people are living with type 1 diabetes (T1D). Although the incidence of T1D is not affected by socioeconomic status, the development of complications and limited access to modern therapy is overrepresented in vulnerable populations. Diabetes technology, specifically continuous glucose monitoring and automated insulin delivery systems, are considered the gold standard for management of T1D, yet access to these technologies varies widely across countries and regions, and varies widely even within high-income countries. This review focuses on disparities in diabetes technology use among adolescents and young adults with T1D, barriers to access and use, and summarizes common themes emerging across countries and regions. We conducted a survey among medical technology manufacturers and physicians in various countries across diverse geographical regions and performed extensive literature searches. Across all countries and regions, economic barriers stand out as the largest and most common barriers, either preventing market penetrance of technology into a country or limiting its access to the individual with diabetes due to high out of pocket costs. Other common barriers include structural or accessibility barriers, such as stringent eligibility requirements by insurance providers, regardless of whether the insurance was private or government-based, and provider/individual level barriers. Based on the evidence presented, we suggest the need for a joint effort involving governments, private health insurers, technology manufacturers, and healthcare providers to address the global disparities of diabetic technology utilization and ensure equitable access for all individuals living with T1D worldwide.
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Affiliation(s)
- Rebecca Baqiyyah Conway
- Department of Epidemiology, University of Colorado, Aurora, CO 80045, USA
- American Academy of Epidemiology, Inc., Tyler, TX 75701, USA
| | - Janet Snell-Bergeon
- Department of Pediatrics, Barbara Davis Center for Diabetes, University of Colorado, Aurora, CO 80045, USA
| | - Kyoko Honda-Kohmo
- Division of Preventative Healthcare, National Cerebral and Cardiovascular Center, Suita, Osaka 564-8565, Japan
| | | | - Salbiah Binti Isa
- Universiti Sains Malaysia, Advanced Medical and Dental Institute, 130200 Pulau, Pinang, Malaysia
| | - Shakira Sulong
- Division of Medical Operations, Metro Sihat Sdn Bhd, 60000 Kuala Lumpur, Malaysia
| | - Laurien Sibomana
- Department of the Director, Pillar of Health, Pittsburgh, PA 15237, USA
| | - Andrea Gerard Gonzalez
- Department of Pediatrics, Barbara Davis Center for Diabetes, University of Colorado, Aurora, CO 80045, USA
| | - Jooyoun Song
- Department of Psychiatry, Jooyoun's Psychiatry, 07938 Seoul, Korea
| | - Kate Elizabeth Lomax
- Department of Endocrinology and Diabetes, Perth Children's Hospital, Nedlands, WA 6909, Australia
- Children's Diabetes Centre, Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6909, Australia
| | - Ching-Nien Lo
- GM Office, EPS BIO Technology Corp., Hsinchu 30076, Taiwan
| | - Wondong Kim
- Management (Including R&D Director), CareforU Co., Ltd., 14042 Anyang, Korea
| | - Aveni Haynes
- Children's Diabetes Centre, Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6909, Australia
| | - Martin de Bock
- Department of Pediatrics, University of Otago, Christchurch 8140, New Zealand
| | - Marie-Anne Burckhardt
- University Children's Hospital Basel UKBB, Pediatric Endocrinology and Diabetology, 4056 Basel, Switzerland
| | - Savannah Schwab
- Department of Epidemiology, University of Colorado, Aurora, CO 80045, USA
| | - Kwanho Hong
- Management (Marketing & Development), CareforU Co., Ltd., 14042 Anyang, Korea
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Suzuki D, Shima H, Kawashima S, Kamimura M, Kikuchi A, Kanno J. Trends in endogenous insulin secretion capacity and anti-islet autoantibody titers in two childhood-onset slowly progressive insulin-dependent diabetes mellitus cases. Clin Pediatr Endocrinol 2024; 33:238-243. [PMID: 39359664 PMCID: PMC11442699 DOI: 10.1297/cpe.2024-0039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 07/24/2024] [Indexed: 10/04/2024] Open
Abstract
Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is a subtype of type 1 diabetes. Although SPIDDM is not rare among Japanese children, there are few reports on endogenous insulin secretory capacity and anti-pancreatic islet autoantibodies in pediatric SPIDDM. We followed the trends in endogenous insulin secretory capacity and anti-pancreatic islet autoantibody titers in two pediatric SPIDDM cases over several years. Case 1 developed insulin deficiency eight months after diabetes diagnosis; as her insulinoma-associated antibody test result was positive, insulin therapy was initiated. Fourteen months after the diagnosis, she tested positive for glutamic acid decarboxylase autoantibodies (GADA) and was diagnosed with SPIDDM. Case 2 was mildly positive for GADA at the onset of diabetes, but became a high titer during the course of the disease. Fourteen months after the diagnosis of diabetes, he became mildly insulin deficient, and insulin therapy was initiated. However, his insulin secretory capacity was preserved for 60 mo after the onset. SPIDDM is generally indistinguishable from type 2 diabetes at diagnosis; therefore, repeated evaluation of the insulin secretory capacity and anti-islet autoantibodies facilitates early diagnosis and appropriate treatment, especially in nonobese children with type 2 diabetes.
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Affiliation(s)
- Dai Suzuki
- Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hirohito Shima
- Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Sayaka Kawashima
- Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Miki Kamimura
- Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan
- Department of Pediatrics, National Hospital Organization Sendai Medical Center, Sendai, Japan
| | - Atsuo Kikuchi
- Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Junko Kanno
- Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan
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Haisa A, Oikawa Y, Satomura A, Suzuki S, Nakanishi S, Fujisawa M, Morita H, Katsuki T, Shimada A. High glutamic acid decarboxylase antibody titers may be associated with a decline in β-cell function over time and future insulin deficiency in latent autoimmune diabetes in adults. Diabetes Res Clin Pract 2024; 215:111799. [PMID: 39084295 DOI: 10.1016/j.diabres.2024.111799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 06/29/2024] [Accepted: 07/29/2024] [Indexed: 08/02/2024]
Abstract
AIMS Latent autoimmune diabetes in adults (LADA) is characterized by positive islet-associated autoantibodies including glutamic acid decarboxylase antibody (GADA), and gradual decline in insulin secretion, progressing to insulin dependency. This cross-sectional study aimed to determine whether GADA by enzyme-linked immunosorbent assay (GADA-ELISA) titer of ≥180 U/mL could be associated with decline in β-cell function in participants with LADA. METHODS Sixty-three participants with LADA were recruited and an association between insulin secretion capacity and disease duration was investigated. Insulin peptide-specific inflammatory immunoreactivity was investigated to determine the disease's activity. RESULTS There was a significant inverse correlation between disease duration and C-peptide index in participants with GADA-ELISA titer of ≥180 U/mL (Spearman's r (rs) = -0.516, p < 0.01). The positivity rate of insulin peptide-specific inflammatory immunoreactivity was significantly higher in those with ≥180 U/mL than in those with <180 U/mL (p < 0.05). In participants with human leukocyte antigen (HLA)-DRB1*04:05, a significant inverse correlation was observed between disease duration and C-peptide index in those with ≥180 U/mL (rs = -0.751, p < 0.01). CONCLUSIONS GADA-ELISA titer of ≥180 U/mL, especially with HLA-DRB1*04:05, might reflect higher disease activity and may be associated with decline in β-cell function over time and future insulin dependency in LADA.
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Affiliation(s)
- Akifumi Haisa
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan
| | - Yoichi Oikawa
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
| | - Atsushi Satomura
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan
| | - Seiya Suzuki
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan
| | - Shumpei Nakanishi
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan
| | - Masashi Fujisawa
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan
| | - Hideo Morita
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan
| | - Takeshi Katsuki
- Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo 108-0073, Japan
| | - Akira Shimada
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama 350-0495, Japan
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Kawasaki E, Awata T, Ikegami H, Imagawa A, Oikawa Y, Osawa H, Katsuki T, Kanatsuna N, Kawamura R, Kozawa J, Kodani N, Kobayashi T, Shimada A, Shimoda M, Takahashi K, Chujo D, Tsujimoto T, Tsuchiya K, Terakawa A, Terasaki J, Nagasawa K, Noso S, Fukui T, Horie I, Yasuda K, Yasuda H, Yanai H, Hanafusa T, Kajio H. Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes. J Diabetes Investig 2024; 15:835-842. [PMID: 38451108 PMCID: PMC11215668 DOI: 10.1111/jdi.14178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 02/18/2024] [Accepted: 02/22/2024] [Indexed: 03/08/2024] Open
Abstract
AIMS/INTRODUCTION This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state. MATERIALS AND METHODS We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively. CONCLUSIONS Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.
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Affiliation(s)
| | - Takuya Awata
- Pancreatic Islet Cell Transplantation CenterNational Center for Global Health and MedicineTokyoJapan
| | - Hiroshi Ikegami
- Department of Endocrinology, Metabolism and DiabetesKindai University Faculty of MedicineOsakaJapan
| | - Akihisa Imagawa
- Department of Internal Medicine (I)Osaka Medical and Pharmaceutical UniversityTakatsukiJapan
| | - Yoichi Oikawa
- Department of Endocrinology and Diabetes, School of MedicineSaitama Medical UniversityIrumaJapan
| | - Haruhiko Osawa
- Department of Diabetes and Molecular GeneticsEhime University Graduate School of MedicineToonJapan
| | - Takeshi Katsuki
- Department of Diabetes and EndocrinologyTokyo Saiseikai Central HospitalTokyoJapan
| | - Norio Kanatsuna
- Department of Internal Medicine (I)Osaka Medical and Pharmaceutical UniversityTakatsukiJapan
| | - Ryoichi Kawamura
- Department of Diabetes and Molecular GeneticsEhime University Graduate School of MedicineToonJapan
| | - Junji Kozawa
- Department of Metabolic Medicine, Graduate School of MedicineOsaka UniversitySuitaJapan
| | - Noriko Kodani
- Department of Diabetes, Endocrinology, and MetabolismCenter Hospital of the National Center for Global Health and MedicineTokyoJapan
| | | | - Akira Shimada
- Department of Endocrinology and Diabetes, School of MedicineSaitama Medical UniversityIrumaJapan
| | - Masayuki Shimoda
- Pancreatic Islet Cell Transplantation CenterNational Center for Global Health and MedicineTokyoJapan
| | | | - Daisuke Chujo
- Center for Clinical ResearchToyama University HospitalToyamaJapan
| | - Tetsuro Tsujimoto
- Department of Diabetes and EndocrinologyToranomon Hospital KajigayaKawasakiJapan
| | - Kyoichiro Tsuchiya
- Department of Diabetes and EndocrinologyUniversity of Yamanashi HospitalYamanashiJapan
| | - Aiko Terakawa
- Department of Diabetes, Endocrinology, and MetabolismCenter Hospital of the National Center for Global Health and MedicineTokyoJapan
| | - Jungo Terasaki
- Department of Internal Medicine (I)Osaka Medical and Pharmaceutical UniversityTakatsukiJapan
| | - Kan Nagasawa
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal MedicineIwate Medical UniversityYahabaJapan
| | - Shinsuke Noso
- Department of Endocrinology, Metabolism and DiabetesKindai University Faculty of MedicineOsakaJapan
| | - Tomoyasu Fukui
- Division of Diabetes and EndocrinologyShowa University School of MedicineTokyoJapan
| | - Ichiro Horie
- Department of Endocrinology and MetabolismNagasaki University HospitalNagasakiJapan
| | - Kazuki Yasuda
- Department of Diabetes, Endocrinology, and MetabolismKyorin UniversityMitakaJapan
| | - Hisafumi Yasuda
- Division of Health Sciences, Department of Public HealthKobe University Graduate School of Health SciencesKobeJapan
| | - Hidekatsu Yanai
- Department of Endocrinology and Metabolism, Kohnodai HospitalNational Center for Global Health and MedicineIchikawaJapan
| | | | - Hiroshi Kajio
- Department of Diabetes, Endocrinology, and MetabolismCenter Hospital of the National Center for Global Health and MedicineTokyoJapan
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Sakane N, Hirota Y, Yamamoto A, Miura J, Takaike H, Hoshina S, Toyoda M, Saito N, Hosoda K, Matsubara M, Tone A, Kawashima S, Sawaki H, Matsuda T, Domichi M, Suganuma A, Sakane S, Murata T. Association of scan frequency with CGM-derived metrics and influential factors in adults with type 1 diabetes mellitus. Diabetol Int 2024; 15:109-116. [PMID: 38264231 PMCID: PMC10800315 DOI: 10.1007/s13340-023-00655-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/27/2023] [Indexed: 01/25/2024]
Abstract
Introduction This study aimed to investigate the association between scan frequency and intermittently scanned continuous glucose monitoring (isCGM) metrics and to clarify the factors affecting scan frequency in adults with type 1 diabetes mellitus (T1D). Methods We enrolled adults with T1D who used FreeStyle® Libre. Scan and self-monitoring of blood glucose (SMBG) frequency and CGM metrics from the past 90-day glucose data were collected. The receiver operating characteristic curve was plotted to obtain the optimal cutoff values of scan frequency for the target values of time in range (TIR), time above range (TAR), and time below range (TBR). Results The study was conducted on 211 adults with T1D (mean age, 50.9 ± 15.2 years; male, 40.8%; diabetes duration, 16.4 ± 11.9 years; duration of CGM use, 2.1 ± 1.0 years; and mean HbA1c, 7.6 ± 0.9%). The average scan frequency was 10.5 ± 3.3 scan/day. Scan frequency was positively correlated with TIR and negatively correlated with TAR, although it was not significantly correlated with TBR. Scan frequency was positively correlated with the hypoglycemia fear survey-behavior score, while it was negatively correlated with some glycemic variability metrics. Adult patients with T1D and good exercise habits had a higher scan frequency than those without exercise habits. The AUC for > 70% of the TIR was 0.653, with an optimal cutoff of 11 scan/day. Conclusions In real-world conditions, frequent scans were linked to improved CGM metrics, including increased TIR, reduced TAR, and some glycemic variability metrics. Exercise habits and hypoglycemia fear-related behavior might affect scan frequency. Our findings could help healthcare professionals use isCGM to support adults with T1D.Clinical Trial Registry No. UMIN000039376.
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Affiliation(s)
- Naoki Sakane
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555 Japan
| | - Yushi Hirota
- Division of Diabetes and Endocrinology, The Department of Internal Medicine, Kobe University Graduate School of Medicine Hyogo, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe City, Hyogo, 650-0017 Japan
| | - Akane Yamamoto
- Division of Diabetes and Endocrinology, The Department of Internal Medicine, Kobe University Graduate School of Medicine Hyogo, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe City, Hyogo, 650-0017 Japan
| | - Junnosuke Miura
- Division of Diabetology and Metabolism, Department of Internal Medicine Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Hiroko Takaike
- Division of Diabetology and Metabolism, Department of Internal Medicine Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Sari Hoshina
- Division of Diabetology and Metabolism, Department of Internal Medicine Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan
| | - Masao Toyoda
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1143 Japan
| | - Nobumichi Saito
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1143 Japan
| | - Kiminori Hosoda
- Division of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565 Japan
| | - Masaki Matsubara
- Division of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565 Japan
- Department of General Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522 Japan
| | - Atsuhito Tone
- Department of Internal Medicine, Okayama Saiseikai General Hospital, 2-25 Kokutai-cho, Kita-ku, Okayama-shi, Okayama, 700-8511 Japan
| | - Satoshi Kawashima
- Kanda Naika Clinic, 5-21-3 Hannan-cho, Abeno-ku, Osaka-shi, Osaka, 545-0021 Japan
| | - Hideaki Sawaki
- Sawaki Internal Medicine And Diabetes Clinic, 1-1-501A Konyamachi, Takatsuki-shi, Osaka, 569-0804 Japan
| | - Tomokazu Matsuda
- Matsuda Diabetes Clinic, 78-7 Ohtsukadai, Nishi-ku, Kobe City, Hyogo, 651-2135 Japan
| | - Masayuki Domichi
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555 Japan
| | - Akiko Suganuma
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555 Japan
| | - Seiko Sakane
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555 Japan
| | - Takashi Murata
- Department of Clinical Nutrition, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555 Japan
- Diabetes Center, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555 Japan
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Edwards M, Kudzinskas A, Alazawi A, Hughes W, Goodall R, Harbinson E, Salciccioli J, Marshall D, Shalhoub J. Type 1 diabetes mellitus disease burden in high health expenditure countries between 1990 and 2019. Diab Vasc Dis Res 2023; 20:14791641231221763. [PMID: 38128564 DOI: 10.1177/14791641231221763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2023] Open
Abstract
OBJECTIVE This observational study assesses trends in type 1 diabetes mellitus (T1DM) disease burden across the 19 countries of the European Union (EU) 15+ between 1990 and 2019. METHODS The Global Burden of Disease Study database was used to gather T1DM age-standardised incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life-year (DALY) rates per 100,000 for each EU15+ country (1990 - 2019). Joinpoint regression analysis was used to describe the trends. RESULTS From 1990 to 2019, T1DM ASIRs and ASPRs increased globally except for females in Finland (-2.9% and -9.4%), the largest increase in ASPR for males and females was observed in France (+144.4% and +137.5% respectively). All had reductions in ASMRs for males and females, with the largest observed in Spain (-56.7% and -79.0% respectively). Trends in DALYs were variable across countries, with increases in DALYs noted in 14/19 for males, and 9/19 for females. Denmark, Finland, Norway, Netherlands, and Sweden had a reduction in DALYs for both males and females. CONCLUSIONS Mortality from T1DM is reducing across EU15+ countries, despite concomitant increases in incidence and prevalence rates. Trends in DALYs are variable across countries, reflecting differential trends in the disease burden across countries with similarly high health expenditure.
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Affiliation(s)
- Michael Edwards
- Queen Victoria Hospital NHS Foundation Trust, East Grinstead, UK
| | | | - Andrew Alazawi
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
| | | | - Richard Goodall
- Queen Victoria Hospital NHS Foundation Trust, East Grinstead, UK
| | | | | | | | - Joseph Shalhoub
- Imperial College London and Imperial College Healthcare NHS Trust, London, UK
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Kawasaki E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int J Mol Sci 2023; 24:10012. [PMID: 37373160 PMCID: PMC10298549 DOI: 10.3390/ijms241210012] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/08/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. A combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate a more accurate diagnosis and prediction of autoimmune disorders. The aim of this review is to summarize what is known about the clinical significance of anti-islet autoantibodies in the pathogenesis and diagnosis of T1D.
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Affiliation(s)
- Eiji Kawasaki
- Diabetes Center, Shin-Koga Hospital, Kurume 830-8577, Japan
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Liu YC, Liu H, Zhao SL, Chen K, Jin P. Clinical and HLA genotype analysis of immune checkpoint inhibitor-associated diabetes mellitus: a single-center case series from China. Front Immunol 2023; 14:1164120. [PMID: 37359544 PMCID: PMC10288983 DOI: 10.3389/fimmu.2023.1164120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 05/25/2023] [Indexed: 06/28/2023] Open
Abstract
Objective To investigate the clinical characteristics and HLA genotypes of patients with immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in China. Methods We enrolled 23 patients with ICI-DM and 51 patients with type 1 diabetes (T1D). Clinical characteristics of the patients were collected. HLA-DRB1, HLA-DQA1, and HLA-DQB1 genotyping was conducted via next-generation sequencing. Results The ICI-DM patients had a male predominance (70.6%), a mean body mass index (BMI) of 21.2 ± 3.5 kg/m2, and a mean onset of ICI-DM in 5 (IQR, 3-9) cycles after ICI therapy. Most (78.3%) ICI-DM patients were treated with anti-PD-1, 78.3% presented with diabetic ketoacidosis, and all had low C-peptide levels and received multiple insulin injections. Compared to T1D patients, ICI-DM patients were significantly older (57.2 ± 12.4 vs 34.1 ± 15.7 years) and had higher blood glucose but lower HbA1c levels (P<0.05). Only two (8.7%) ICI-DM patients were positive for islet autoantibodies, which was lower than that in T1D patients (66.7%, P<0.001). A total of 59.1% (13/22) of ICI-DM patients were heterozygous for an HLA T1D risk haplotype, and DRB1*0901-DQA1*03-DQB1*0303 (DR9) and DRB1*0405-DQA1*03-DQB1*0401 were the major susceptible haplotypes. Compared to T1D, the susceptible DR3-DQA1*0501-DQB1*0201 (DR3) and DR9 haplotypes were less frequent (17.7% vs 2.3%; P=0.011 and 34.4% vs 15.9%; P=0.025), whereas the protective haplotypes (DRB1*1101-DQA1*05-DQB1*0301 and DRB1*1202-DQA1*0601-DQB1*0301) were more frequent in ICI-DM patients (2.1% vs 13.6%; P=0.006 and 4.2% vs 15.9%; P=0.017). None of the ICI-DM patients had T1D-associated high-risk genotypes DR3/DR3, DR3/DR9, and DR9/DR9. Among the 23 ICI-DM patients, 7 (30.4%) presented with ICI-associated fulminant type 1 diabetes (IFD), and 16 (69.6%) presented with ICI-associated type 1 diabetes (IT1D). Compared to IT1D patients, IFD patients exhibited marked hyperglycemia and low C-peptide and HbA1c levels (P<0.05). Up to 66.7% (4/6) of IFD patients were heterozygous for reported fulminant type 1 diabetes susceptibility HLA haplotypes (DRB1*0405-DQB1*0401 or DRB1*0901-DQB1*0303). Conclusion ICI-DM shares similar clinical features with T1D, such as acute onset, poor islet function and insulin dependence. However, the lack of islet autoantibodies, the low frequencies of T1D susceptibility and high frequencies of protective HLA haplotypes indicate that ICI-DM represents a new model distinct from classical T1D.
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Matsuda F, Itonaga T, Maeda M, Ihara K. Long-term trends of pediatric type 1 diabetes incidence in Japan before and after the COVID-19 pandemic. Sci Rep 2023; 13:5803. [PMID: 37037893 PMCID: PMC10085994 DOI: 10.1038/s41598-023-33037-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 04/06/2023] [Indexed: 04/12/2023] Open
Abstract
Type 1 diabetes incidence has increased worldwide, although the long-term trends on pediatric type 1 diabetes in Japan remain elusive. To investigate the incidence and secular trend of pediatric type 1 diabetes from 1999 to 2021, including the coronavirus disease 2019 (COVID-19) pandemic years, in Oita Prefecture, Japan. We investigated the number of newly diagnosed patients with type 1 diabetes aged < 15 years from 1999 to 2021. We surveyed hospital databases in Oita Prefecture in Japan. The type 1 diabetes incidence in children aged < 15 years increased annually by 5.3% among all children, especially in boys aged 10-14 years by 8.1%, over the past 23 years. The average incidence rate of 3.9/100,000/year was nearly consistent with the previous reports on Asian countries. No significant change was found in the increasing incidence trend of type 1 diabetes before and during the COVID-19 pandemic. The incidence of pediatric type 1 diabetes has significantly increased over the past 23 years in Oita Prefecture, Japan, which is consistent with the worldwide trend.
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Affiliation(s)
- Fumika Matsuda
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan
| | - Tomoyo Itonaga
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan
| | - Miwako Maeda
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan
| | - Kenji Ihara
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan.
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10
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Kawasaki E, Shimada A, Imagawa A, Abiru N, Awata T, Oikawa Y, Osawa H, Kawabata Y, Kozawa J, Kobayashi T, Takahashi K, Chujo D, Fukui T, Miura J, Yasuda K, Yasuda H, Kajio H, Hanafusa T, Ikegami H. Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes. J Diabetes Investig 2023; 14:570-581. [PMID: 36691729 PMCID: PMC10034953 DOI: 10.1111/jdi.13980] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 12/17/2022] [Accepted: 01/11/2023] [Indexed: 01/25/2023] Open
Abstract
AIM/INTRODUCTION To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA-GADA) and ELISA (ELISA-GADA) in patients with type 1 diabetes. METHODS A total of 415 patients with type 1 diabetes were enrolled, including 199 acute-onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C-peptide (F-CPR) were examined. RESULTS While the ELISA-GADA displayed a higher sensitivity than the RIA method in diagnosing type 1 diabetes in acute-onset patients, about 40% of SPIDDM patients with low-titer RIA-GADA were determined as negative by the ELISA method. Patients with type 1 diabetes with RIA-GADA alone had an older age of onset, less diabetic ketoacidosis, a higher BMI, and a higher F-CPR compared with patients positive for both RIA-GADA and ELISA-GADA. Additionally, 36% of RIA-GADA-positive patients had low-affinity GADA (<1010 L/mol), which was significantly higher than in the ELISA-GADA-positive patients (4%, P < 0.0001). Furthermore, over a 3 year monitoring period, F-CPR levels decreased in ELISA-GADA-positive SPIDDM, whereas it was maintained in patients with RIA-GADA alone, regardless of GADA affinity. CONCLUSIONS These results suggest that bivalent ELISA for GADA is superior to the RIA method in diagnosing type 1 diabetes. Moreover, the diagnostic superiority of the ELISA-GADA made possible the concurrent identification of SPIDDM patients at high-risk of early progression, and allowed for more accurate clinical diagnosis and management.
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Affiliation(s)
| | - Akira Shimada
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Iruma, Japan
| | - Akihisa Imagawa
- Department of Internal Medicine (I), Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Norio Abiru
- Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki, Japan
| | - Takuya Awata
- Pancreatic Islet Cell Transplantation Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yoichi Oikawa
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Iruma, Japan
| | - Haruhiko Osawa
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yumiko Kawabata
- Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka, Japan
| | - Junji Kozawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan
| | | | | | - Daisuke Chujo
- Center for Clinical Research, Toyama University Hospital, Toyama, Japan
| | - Tomoyasu Fukui
- Division of Diabetes and Endocrinology, Showa University School of Medicine, Tokyo, Japan
| | - Junnosuke Miura
- Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Kazuki Yasuda
- Department of Diabetes, Endocrinology, and Metabolism, Kyorin University, Mitaka, Japan
| | - Hisafumi Yasuda
- Division of Health Sciences, Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - Hiroshi Kajio
- Department of Diabetes, Endocrinology, and Metabolism, National Center for Global Health and Medicine, Tokyo, Japan
| | | | - Hiroshi Ikegami
- Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka, Japan
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11
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Waernbaum I, Lind T, Möllsten A, Dahlquist G. The incidence of childhood-onset type 1 diabetes, time trends and association with the population composition in Sweden: a 40 year follow-up. Diabetologia 2023; 66:346-353. [PMID: 36264296 PMCID: PMC9807495 DOI: 10.1007/s00125-022-05816-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 08/24/2022] [Indexed: 01/07/2023]
Abstract
AIMS/HYPOTHESIS During the 1980s and 1990s, the incidence of childhood-onset type 1 diabetes more than doubled in Sweden, followed by a plateau. In the present 40 year follow-up, we investigated if the incidence remained stable and whether this could be explained by increased migration from countries reporting lower incidences. METHODS We used 23,143 incident cases of childhood-onset type 1 diabetes reported between 1978 and 2019 to the nationwide, population-based Swedish Childhood Diabetes Registry and population data from Statistics Sweden. Generalised additive models and ANOVA were applied to analyse the effects of onset age, sex, time trends and parental country of birth and interaction effects between these factors. RESULTS The flattening of the incidence increase seems to remain over the period 2005-2019. When comparing the incidence of type 1 diabetes for all children in Sweden with that for children with both parents born in Sweden, the trends were parallel but at a higher level for the latter. A comparison of the incidence trends between individuals with Swedish backgrounds (high diabetes trait) and Asian backgrounds (low diabetes trait) showed that the Asian subpopulation had a stable increase in incidence over time. CONCLUSIONS/INTERPRETATION In Sweden, the increase in incidence of childhood-onset type 1 diabetes in the late 20th century has been approaching a more stable albeit high level over the last two decades. Increased immigration from countries with lower incidences of childhood-onset type 1 diabetes does not provide a complete explanation for the observed levelling off.
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Affiliation(s)
| | - Torbjörn Lind
- Department of Clinical Science, Paediatrics, Umeå University, Umeå, Sweden
| | - Anna Möllsten
- Department of Clinical Science, Paediatrics, Umeå University, Umeå, Sweden
| | - Gisela Dahlquist
- Department of Clinical Science, Paediatrics, Umeå University, Umeå, Sweden
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12
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Miyabayashi M, Onishi S, Yoshida T, Takemoto M. A case of doxorubicin and cyclophosphamide therapy-induced type 1 diabetes: a case report. J Med Case Rep 2023; 17:26. [PMID: 36703182 PMCID: PMC9881334 DOI: 10.1186/s13256-023-03755-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 01/02/2023] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Patients receiving immune checkpoint inhibitors have been reported to develop autoimmune endocrine diseases, including type 1 diabetes, although few drugs have been shown to induce type 1 diabetes. Additionally, it is important to note that drugs other than immune checkpoint inhibitors could lead to the development of type 1 diabetes. CASE PRESENTATION A 54-year-old Filipino female patient underwent surgery for left-sided breast cancer. Postoperative chemotherapy was initiated, including doxorubicin (Adriamycin) and cyclophosphamide therapy. The patient was brought to our hospital by ambulance after consciousness disturbance following three courses of doxorubicin and cyclophosphamide therapy and was hospitalized. Her blood glucose and hemoglobin A1c levels were 1661 mg/dL and 11.9%, respectively. The patient was diagnosed with diabetic ketoacidosis after arterial blood gas analysis indicated a blood pH of 7.120. Her insulin secretion was impaired, and her anti-glutamic acid decarboxylase antibody test result was significantly positive. CONCLUSIONS The present case shows that doxorubicin and cyclophosphamide therapy may cause unexpected adverse responses, such as type 1 diabetes, though rarely, and highlights the importance of careful patient follow-up. This report is the first to present a case of type 1 diabetes that suddenly developed after doxorubicin and cyclophosphamide treatment.
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Affiliation(s)
- Makoto Miyabayashi
- grid.411731.10000 0004 0531 3030International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita City, Chiba 286-8520 Japan
| | - Shunichiro Onishi
- grid.411731.10000 0004 0531 3030International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita City, Chiba 286-8520 Japan ,grid.411731.10000 0004 0531 3030Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, 4-3, Kozunomori, Narita, Chiba 286-8686 Japan
| | - Tomohiko Yoshida
- grid.411731.10000 0004 0531 3030International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita City, Chiba 286-8520 Japan ,grid.411731.10000 0004 0531 3030Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, 4-3, Kozunomori, Narita, Chiba 286-8686 Japan
| | - Minoru Takemoto
- grid.411731.10000 0004 0531 3030International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita City, Chiba 286-8520 Japan ,grid.411731.10000 0004 0531 3030Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, 4-3, Kozunomori, Narita, Chiba 286-8686 Japan
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13
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Li J, Arafa A, Kashima R, Teramoto M, Nakao YM, Honda-Kohmo K, Sakai Y, Watanabe E, Dohi T, Kokubo Y. Liver enzymes, alcohol consumption and the risk of diabetes: the Suita study. Acta Diabetol 2022; 59:1531-1537. [PMID: 35972542 DOI: 10.1007/s00592-022-01949-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 07/21/2022] [Indexed: 11/01/2022]
Abstract
AIM We aimed to investigate the combined impact of liver enzymes and alcohol consumption on the diabetes risk. METHODS Data on 5972 non-diabetic participants aged 30-79 years from the Suita study were analyzed. Diabetes incidence was surveyed every 2 years. Current daily alcohol consumption was defined as light drinking (< 23.0 g ethanol/day in men and < 11.5 g in women), moderate drinking (23.0-45.9 g and 11.5-22.9 g), and heavy drinking (≥ 46.0 g and ≥ 23.0 g). The nondrinkers category included both never-drinkers and former drinkers. RESULTS During the median follow-up of 13 years, 597 incident diabetes cases were diagnosed. Higher levels of γ-glutamyltransferase (GGT), alanine aminotransferase (GPT), and aspartate aminotransferase (GOT) were associated with an increased diabetes risk, and current light drinkers had a lower risk of diabetes than nondrinkers. No sex differences were observed in these associations. Compared to nondrinkers having the lowest quartiles of liver enzymes, nondrinkers and current moderate/heavy drinkers having the highest quartiles had an increased risk of diabetes. However, no association was observed for current light drinkers having the highest quartiles of liver enzymes; the multivariable hazard ratios (95% CIs) in current light drinkers with the highest quartile of liver enzymes were 1.27 (0.68-2.37) for GGT, 1.05 (0.59-1.89) for GPT, and 0.76 (0.40-1.47) for GOT, respectively. CONCLUSION High liver enzymes were associated with an increased diabetes risk. No increased diabetes risk was observed in current light drinkers, even in these who had high levels of liver enzymes.
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Affiliation(s)
- Jiaqi Li
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan.
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
| | - Ahmed Arafa
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
- Department of Public Health, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Rena Kashima
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
- Department of Cardiovascular Pathophysiology and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
| | - Masayuki Teramoto
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
| | - Yoko M Nakao
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
- Department of Medical and Health Information Management, Open Innovative Center, National Cerebral and Cardiovascular Center, Suita, Japan
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Kyoko Honda-Kohmo
- Division of Preventive Healthcare, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Yukie Sakai
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
| | - Emi Watanabe
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
- Department of Food and Nutrition, Faculty of Contemporary Human Life Science, Tezukayama University, Nara, Japan
| | - Tomoharu Dohi
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yoshihiro Kokubo
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shinmachi, Suita, Osaka, 564-8565, Japan
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Serum uric acid levels and the risk of diabetes mellitus in premenopausal and postmenopausal women: the Suita study. Menopause 2022; 29:1184-1188. [PMID: 36150117 DOI: 10.1097/gme.0000000000002035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The association between serum uric acid levels and the risk of diabetes mellitus in women stratified by menopausal status is not well-established. Therefore, we investigated this association among a cohort of Japanese urban women. METHODS We conducted a prospective cohort study on 3,304 women (1,252 premenopausal and 2,052 postmenopausal), aged 30 to 79 years, with no prior cardiovascular disease or diabetes mellitus, and enrolled from a general urban population. Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals (CIs) for incident diabetes mellitus according to serum uric acid quartiles. RESULTS During 13.8 years of median follow-up, 219 incident diabetes mellitus cases were diagnosed. The incidence rate per 1,000 person-years was 3.42 in premenopausal women and 6.19 in postmenopausal women. After adjustment for potential risk factors, the multivariable hazard ratios (95% CIs) of the highest versus lowest serum uric acid quartiles were 1.56 (0.77-3.16) in premenopausal women, 2.00 (1.19-3.34) in postmenopausal women, and 1.81 (1.21-2.73) in all women. The interaction based on menopausal status was not significant ( P = 0.872). The corresponding population attributable fractions (95% CIs) were 13.3% (-8.9% to 31.1%), 19.1% (5.3%-30.9%), and 17.0% (5.6%-27.0%), respectively. CONCLUSIONS Serum uric acid levels were positively associated with the risk of diabetes mellitus in postmenopausal women, but not in premenopausal women. However, the lack of an association in premenopausal women may have been due to limited power, so further research is required to confirm this menopausal status-specific association.
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Redondo MJ, Gignoux CR, Dabelea D, Hagopian WA, Onengut-Gumuscu S, Oram RA, Rich SS. Type 1 diabetes in diverse ancestries and the use of genetic risk scores. Lancet Diabetes Endocrinol 2022; 10:597-608. [PMID: 35724677 PMCID: PMC10024251 DOI: 10.1016/s2213-8587(22)00159-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/16/2022] [Accepted: 05/06/2022] [Indexed: 02/06/2023]
Abstract
Over 75 genetic loci within and outside of the HLA region influence type 1 diabetes risk. Genetic risk scores (GRS), which facilitate the integration of complex genetic information, have been developed in type 1 diabetes and incorporated into models and algorithms for classification, prognosis, and prediction of disease and response to preventive and therapeutic interventions. However, the development and validation of GRS across different ancestries is still emerging, as is knowledge on type 1 diabetes genetics in populations of diverse genetic ancestries. In this Review, we provide a summary of the current evidence on the evolutionary genetic variation in type 1 diabetes and the racial and ethnic differences in type 1 diabetes epidemiology, clinical characteristics, and preclinical course. We also discuss the influence of genetics on type 1 diabetes with differences across ancestries and the development and validation of GRS in various populations.
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Affiliation(s)
- Maria J Redondo
- Division of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
| | - Christopher R Gignoux
- Department of Medicine and Colorado Center for Personalized Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - William A Hagopian
- Division of Diabetes Programs, Pacific Northwest Research Institute, Seattle, WA, USA
| | - Suna Onengut-Gumuscu
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
| | - Richard A Oram
- Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, UK; The Academic Kidney Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Stephen S Rich
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
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CD4+ Cytotoxic T Cells Involved in the Development of EBV-Associated Diseases. Pathogens 2022; 11:pathogens11080831. [PMID: 35894054 PMCID: PMC9330826 DOI: 10.3390/pathogens11080831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/17/2022] [Accepted: 07/22/2022] [Indexed: 11/17/2022] Open
Abstract
Activated cytotoxic CD4 T cells (HLA-DR+) play an important role in the control of EBV infection, especially in cells with latency I (EBNA-1). One of the evasion mechanisms of these latency cells is generated by gp42, which, via peripherally binding to the β1 domain of the β chain of MHC class II (HLA-DQ, -DR, and -DP) of the infected B lymphocyte, can block/alter the HLA class II/T-cell receptor (TCR) interaction, and confer an increased level of susceptibility towards the development of EBV-associated autoimmune diseases or cancer in genetically predisposed individuals (HLA-DRB1* and DQB1* alleles). The main developments predisposing the factors of these diseases are: EBV infection; HLA class II risk alleles; sex; and tissue that is infiltrated with EBV-latent cells, forming ectopic lymphoid structures. Therefore, there is a need to identify treatments for eliminating cells with EBV latency, because the current treatments (e.g., antivirals and rituximab) are ineffective.
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Kibirige D, Sekitoleko I, Balungi P, Kyosiimire-Lugemwa J, Lumu W, Jones AG, Hattersley AT, Smeeth L, Nyirenda MJ. Islet autoantibody positivity in an adult population with recently diagnosed diabetes in Uganda. PLoS One 2022; 17:e0268783. [PMID: 35604955 PMCID: PMC9126391 DOI: 10.1371/journal.pone.0268783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 05/07/2022] [Indexed: 12/02/2022] Open
Abstract
Aims This study aimed to investigate the frequency of islet autoantibody positivity in adult patients with recently diagnosed diabetes in Uganda and its associated characteristics. Methods Autoantibodies to glutamic acid decarboxylase-65 (GADA), zinc transporter 8 (ZnT8-A), and tyrosine phosphatase (IA-2A) were measured in 534 adult patients with recently diagnosed diabetes. Islet autoantibody positivity was defined based on diagnostic thresholds derived from a local adult population without diabetes. The socio-demographic, clinical, and metabolic characteristics of islet autoantibody-positive and negative participants were then compared. The differences in these characteristics were analysed using the x2 test for categorical data and the Kruskal Wallis test for continuous data. Multivariate analysis was performed to identify predictors of islet autoantibody positivity. Results Thirty four (6.4%) participants were positive for ≥1 islet autoantibody. GADA, IA-2A and ZnT8-A positivity was detected in 17 (3.2%), 10 (1.9%), and 7 (1.3%) participants, respectively. Compared with those negative for islet autoantibodies, participants positive for islet autoantibodies were more likely to live in a rural area (n = 18, 52.9% Vs n = 127, 25.5%, p = 0.005), to be initiated on insulin therapy (n = 19, 55.9% Vs n = 134, 26.8%, p<0.001), to have a lower median waist circumference (90 [80–99] cm Vs 96 [87–104.8], p = 0.04), waist circumference: height ratio (0.55 [0.50–0.63] vs 0.59 [0.53–0.65], p = 0.03), and fasting C-peptide concentration (0.9 [0.6–1.8] Vs 1.4 [0.8–2.1] ng/ml, p = 0.01). On multivariate analysis, living in a rural area (odds ratio or OR 3.62, 95%CI 1.68–7.80, p = 0.001) and being initiated on insulin therapy (OR 3.61, 95% CI 1.67–7.83, p = 0.001) were associated with islet autoantibody positivity. Conclusion The prevalence of islet autoantibody positivity was relatively low, suggesting that pancreatic autoimmunity is a rare cause of new-onset diabetes in this adult Ugandan population. Living in a rural area and being initiated on insulin therapy were independently associated with islet autoantibody positivity in this study population.
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Affiliation(s)
- Davis Kibirige
- Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Non-Communicable Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
- * E-mail:
| | - Isaac Sekitoleko
- Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Priscilla Balungi
- Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Clinical Diagnostics Laboratory Services, Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Jacqueline Kyosiimire-Lugemwa
- Clinical Diagnostics Laboratory Services, Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - William Lumu
- Department of Medicine, Mengo Hospital, Kampala, Uganda
| | - Angus G. Jones
- Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter, United Kingdom
- Department of Diabetes and Endocrinology, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
| | - Andrew T. Hattersley
- Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter, United Kingdom
- Department of Diabetes and Endocrinology, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
| | - Liam Smeeth
- Department of Non-Communicable Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Moffat J. Nyirenda
- Non-Communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Non-Communicable Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
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Takeda M, Abe T, Toyama Y, Tominaga K, Yano S, Nabika T, Yamasaki M. Combined association of oral and skeletal muscle health with type 2 diabetes mellitus among community-dwelling older adults in Japan: a cross-sectional study. J Rural Med 2022; 17:67-72. [PMID: 35432640 PMCID: PMC8984617 DOI: 10.2185/jrm.2021-042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 01/04/2022] [Indexed: 11/27/2022] Open
Abstract
Objective: Although oral health and skeletal muscle status are known to be
risk factors for type 2 diabetes mellitus (T2DM), there is limited information on their
combined effects among community-dwelling older adults. The purpose of this study was to
investigate the association between oral health and skeletal muscle status among older
adults with T2DM in Japan. Participants and Methods: This cross-sectional study included data from
individuals aged ≥60 years. T2DM was defined as a glycosylated hemoglobin A1c level ≥48
mmol/mol (≥6.5%) or the use of hypoglycemic agents. For oral health status, dental
hygienists assessed the number of teeth (NT) and masticatory function (MF). Skeletal
muscle status was assessed using skeletal muscle mass index (SMI) and handgrip strength
(HGS). Logistic regression analysis examined T2DM in nine-category combinations of oral
health status (each of the three categories in NT and MF) and skeletal status (each of the
three categories in SMI and HGS). Results: T2DM was prevalent in 83 participants (16.4%) and was significantly
associated with low NT and SMI (odds ratio [OR] = 5.93, 95% confidence interval [CI]:
1.37–25.73) and low MF and SMI (OR = 4.48, 95% CI: 1.23–16.35) compared to high NT and SMI
and high MF and SMI, respectively. Conclusion: Our findings indicate that low muscle mass with tooth loss or
masticatory dysfunction is associated with T2DM among community-dwelling older adults.
This suggests that maintaining oral health and muscle mass may be an effective strategy
for the prevention of T2DM.
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Affiliation(s)
- Miwako Takeda
- Center for Community-Based Healthcare Research and Education (CoHRE), Head Office for Research and Academic Information, Shimane University, Japan
| | - Takafumi Abe
- Center for Community-Based Healthcare Research and Education (CoHRE), Head Office for Research and Academic Information, Shimane University, Japan
| | - Yuta Toyama
- Center for Community-Based Healthcare Research and Education (CoHRE), Head Office for Research and Academic Information, Shimane University, Japan
| | | | - Shozo Yano
- Center for Community-Based Healthcare Research and Education (CoHRE), Head Office for Research and Academic Information, Shimane University, Japan
| | - Toru Nabika
- Center for Community-Based Healthcare Research and Education (CoHRE), Head Office for Research and Academic Information, Shimane University, Japan
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19
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Current clinical state of type 1 diabetes in Saitama prefecture. Diabetol Int 2021; 13:436-446. [DOI: 10.1007/s13340-021-00557-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 10/24/2021] [Indexed: 10/19/2022]
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20
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Kanatsuka A, Sato Y, Higashi Y, Goto Y, Kawai K, Maegawa H. Combination of disease duration-to-age at diagnosis and hemoglobin A1c-to-serum C-peptide reactivity ratios predicts patient response to glucose-lowering medication in type 2 diabetes: A retrospective cohort study across Japan (JDDM59). J Diabetes Investig 2021; 12:1967-1977. [PMID: 33837666 PMCID: PMC8565405 DOI: 10.1111/jdi.13558] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 02/17/2021] [Accepted: 04/04/2021] [Indexed: 01/22/2023] Open
Abstract
AIMS/INTRODUCTION Knowing the collective clinical factors that determine patient response to glucose-lowering medication would be beneficial in the treatment of type 2 diabetes. We carried out a retrospective cohort study to explore the combination of clinical factors involved in its therapeutic efficacy. MATERIALS AND METHODS The results of cohort studies retrieved using the CoDiC® database across Japan from January 2005 to July 2018 were analyzed based on criterion that using insulin therapy indicates severe type 2 diabetes. RESULTS A logistic regression analysis showed that age at diagnosis, disease duration, hemoglobin A1c (HbA1c) and serum C-peptide reactivity (CPR) at medication commencement were associated with the probability of insulin treatment. Receiver operating characteristic curve showed that these clinical factors predicted insulin treatment positivity with an area under the curve of >0.600. The area under the curve increased to 0.674 and 0.720 for the disease duration-to-age at diagnosis ratio and HbA1c-to-CPR ratio, respectively. Furthermore, area under the curve increased to 0.727 and 0.750 in the indices (duration-to-age ratio at diagnosis × 43 + HbA1c) and (duration-to-age ration at diagnosis × 21 + HbA1c-to-CPR ratio), respectively. After stratification to three groups according to the indices, monthly HbA1c levels during 6 months of treatment were higher in the upper one-third than in the lower one-third of patients, and many patients did not achieve the target HbA1c level (53 mmol/mol) in the upper one-third, although greater than fourfold more patients were administered insulin in the upper one-third. CONCLUSIONS The combination of disease duration-to-age at diagnosis and HbA1c-to-CPR ratios is a collective risk factor that predicts response to the medications.
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Affiliation(s)
| | - Yasunori Sato
- Department of Preventive Medicine and Public HealthKeio University School of Medicine Graduate School of MedicineTokyoJapan
| | | | | | | | - Hiroshi Maegawa
- Department of MedicineDivision of Diabetology, Endocrinology, and NephrologyShiga University of Medical ScienceOtsuJapan
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21
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Abiru N, Shimada A, Nishimura R, Matsuhisa M, Ozaki A, Ikegami H. Glycemic control status, diabetes management patterns, and clinical characteristics of adults with type 1 diabetes in Japan: Study of Adults' Glycemia in T1DM subanalysis. Diabetol Int 2021; 12:460-473. [PMID: 34567927 DOI: 10.1007/s13340-021-00504-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 03/29/2021] [Indexed: 11/26/2022]
Abstract
Aims/introduction Type 1 diabetes is rare in the general Japanese population, but becoming more common in adults with increased longevity owing to advancements in treatment. We aimed to examine the current state of glycemic control and diabetes management using real-world data on Japanese adults with type 1 diabetes in different age groups. Materials and methods This was a subanalysis of Japanese participants from a multinational, cross-sectional, observational study of adults with type 1 diabetes aged ≥ 26 years conducted in 2018 (Study of Adults' Glycemia in T1DM). Glycemic control achievement rate and goal setting, incidence of hypoglycemia, and diabetes management of individuals aged 26‒44 years, 45‒64 years, and ≥ 65 years were summarized. Results The data on 528 participants were analyzed. The mean glycated hemoglobin (HbA1c) value was 7.8% (61.3 mmol/mol). Of the participants, 25.8% achieved an HbA1c level of < 7.0% (26-44 years, 33.7%; 45‒64 years, 18.9%; and ≥ 65 years, 24.3%). In total, 71.4% participants reported ≥ 1 symptomatic hypoglycemic episode within the last 3 months, and 5.5% participants reported ≥ 1 severe hypoglycemic episode within the last 6 months. A less stringent individualized goal was set for participants aged ≥ 65 years; they had the lowest incidence of ≥ 1 symptomatic hypoglycemic episode. Insulin pumps and continuous glucose monitoring were used in 23.5% and 33.9% participants, respectively. Conclusion Glycemic control was suboptimal; the low incidence of severe hypoglycemia suggests careful glycemic control, balancing benefits and risks, particularly in Japanese adults aged ≥ 65 years with type 1 diabetes. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-021-00504-7.
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Affiliation(s)
- Norio Abiru
- Department of Endocrinology and Metabolism, Division of Advanced Preventative Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akira Shimada
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan
| | - Rimei Nishimura
- Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Munehide Matsuhisa
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | | | - Hiroshi Ikegami
- Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka, Japan
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22
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Murata T, Kuroda A, Matsuhisa M, Toyoda M, Kimura M, Hirota Y, Kato K, Sawaki H, Tone A, Kawashima S, Okada A, Watanabe T, Nirengi S, Suganuma A, Sakane N. Predictive Factors of the Adherence to Real-Time Continuous Glucose Monitoring Sensors: A Prospective Observational Study (PARCS STUDY). J Diabetes Sci Technol 2021; 15:1084-1092. [PMID: 32762345 PMCID: PMC8442175 DOI: 10.1177/1932296820939204] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Information about factors related to better adherence to continuous glucose monitoring (CGM) sensor adherence is quite limited. MATERIALS AND METHODS Forty-six participants with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) without CGM were recruited. The participants' characteristics and diabetes-related quality of life (QOL) were evaluated at baseline and one year after starting to use CGM. Participants wearing the sensor for ≥60% of the time were considered as adherent. RESULTS The mean age of the 46 participants was 44.1 ± 15.0 years old and the mean glycohemoglobin (HbA1c) was 7.7 ± 1.0%; 60.9% of the participants were classified as adherent. The duration of using CSII was longer in the adherent group, and the degree of diabetic retinopathy was significantly different. There were no significant differences in age, frequency of self-monitoring of blood glucose, or Hypoglycemia Fear Survey (HFS-B for behavior, HFS-W for worry) score at baseline between the adherent and nonadherent groups. The Problem Areas in Diabetes (PAID) score at baseline was significantly higher and the total CSII-QOL score at baseline was significantly lower in the adherent group. The usage of dual-wave bolus was significantly increased in the adherent group (34.6%-61.5%, P = .016), but not in the nonadherent group (33.3%-33.3%, P > .999). The HbA1c level showed a significant improvement in the adherent group (7.8%-7.3%, P < .001), but not in the nonadherent group (7.5%-7.2%, P = .102). CONCLUSIONS Higher adherence to CGM sensors may be associated with a heavier emotional burden of diabetes and a worse QOL in relation to CSII at baseline.
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Affiliation(s)
- Takashi Murata
- Diabetes Center, National Hospital
Organization Kyoto Medical Center, Kyoto, Japan
- Takashi Murata, MD, PhD, Diabetes Center,
National Hospital Organization Kyoto Medical Center, 1-1 Fukakusamukaihata-cho,
Fushimi-ku, Kyoto 612-8555, Japan.
| | - Akio Kuroda
- Diabetes Therapeutics and Research
Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima,
Japan
| | - Munehide Matsuhisa
- Diabetes Therapeutics and Research
Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima,
Japan
| | - Masao Toyoda
- Division of Nephrology, Endocrinology
and Metabolism, Department of Internal Medicine, Tokai University School of
Medicine, Isehara, Japan
| | - Moritsugu Kimura
- Division of Nephrology, Endocrinology
and Metabolism, Department of Internal Medicine, Tokai University School of
Medicine, Isehara, Japan
| | - Yushi Hirota
- Division of Diabetes and Endocrinology,
Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe,
Japan
| | - Ken Kato
- Diabetes Center, National Hospital
Organization Osaka National Hospital, Osaka, Japan
| | - Hideaki Sawaki
- Diabetes Center, Arisawa General
Hospital, Hirakata, Japan
- Sawaki Internal Medicine and Diabetes
Clinic, Takatsuki, Japan
| | - Atsuhito Tone
- Diabetes Center, Okayama University
Hospital, Okayama, Japan
- Department of Internal Medicine, Okayama
Saiseikai General Hospital, Okayama, Japan
| | | | | | - Tomokazu Watanabe
- Diabetes Center, National Hospital
Organization Kyoto Medical Center, Kyoto, Japan
| | - Shinsuke Nirengi
- Division of Preventive Medicine,
Clinical Research Institute, National Hospital Organization Kyoto Medical Center,
Kyoto, Japan
| | - Akiko Suganuma
- Division of Preventive Medicine,
Clinical Research Institute, National Hospital Organization Kyoto Medical Center,
Kyoto, Japan
| | - Naoki Sakane
- Division of Preventive Medicine,
Clinical Research Institute, National Hospital Organization Kyoto Medical Center,
Kyoto, Japan
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23
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Critical Amino Acid Variants in HLA-DRB1 and -DQB1 Allotypes in the Development of Classical Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Japanese Population. Curr Issues Mol Biol 2021; 43:107-115. [PMID: 34065159 PMCID: PMC8928954 DOI: 10.3390/cimb43010009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/04/2021] [Accepted: 05/07/2021] [Indexed: 12/11/2022] Open
Abstract
The effects of amino acid variants encoded by the human leukocyte antigen (HLA) class II on the development of classical type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) have not been fully elucidated. We retrospectively investigated the HLA-DRB1 and -DQB1 genes of 72 patients with classical T1D and 102 patients with LADA in the Japanese population and compared the frequencies of HLA-DRB1 and -DQB1 alleles between these patients and the Japanese populations previously reported by another institution. We also performed a blind association analysis with all amino acid positions in classical T1D and LADA, and compared the associations of HLA-DRB1 and -DQB1 amino acid positions in classical T1D and LADA. The frequency of DRß-Phe-13 was significantly higher and those of DRß-Arg-13 and DQß-Gly-70 were significantly lower in patients with classical T1D and LADA than in controls. The frequencies of DRß-His-13 and DQß-Glu-70 were significantly higher in classical T1D patients than in controls. The frequency of DRß-Ser-13 was significantly lower and that of DQß-Arg-70 was significantly higher in LADA patients than in controls. HLA-DRß1 position 13 and HLA-DQß1 position 70 could be critical amino acid positions in the development of classical T1D and LADA.
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24
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Saito T, Kobayashi K, Kobayashi K, Mochizuki M, Yagasaki H, Makino K, Narusawa H, Watanabe D, Mitsui Y, Sato K, Sano T, Ohta M, Yokomichi H, Amemiya S. Incidence of childhood type 1 diabetes mellitus in Yamanashi Prefecture, Japan, 1986-2018. Endocrinol Diabetes Metab 2021; 4:e00214. [PMID: 33855216 PMCID: PMC8029530 DOI: 10.1002/edm2.214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 10/19/2020] [Accepted: 11/19/2020] [Indexed: 11/27/2022] Open
Abstract
Introduction Several studies have examined the incidence of childhood T1DM in Japan from the 1970s onwards, but none have been long-term studies using registration data. We estimate the incidence of childhood type 1 diabetes mellitus (T1DM) from 1986 to 2018 in Yamanashi Prefecture, Japan. Methods We began a population-based, long-term study of childhood T1DM in 1986 involving every hospital paediatrics department in Yamanashi Prefecture. In the Prefecture, every child newly diagnosed with T1DM is referred to a hospital, and therefore, almost 100% of new patients aged <15 years are registered. We calculated the incidence of T1DM among children aged <15 years from 1986 to 2018. All cases met the Japan Diabetes Society diagnostic criteria and were tested for T1DM-related autoantibodies whenever possible. Results Ninety-nine patients (44 boys and 55 girls) were newly diagnosed with T1DM. The annual incidence among 5- to 9-year-olds increased by 5.35% over the study period (95% confidence interval 2.34%-8.35%, p = .0005), and there was a trend towards increasing 3-year incidence (15.52% increase, p = .0516). There were also trends towards increasing annual and 3-year incidence among 0- to 14-year-olds. However, there were no changes over time in annual or 3-year incidence in the 0-4 year or 10-14 year age groups. Conclusions The incidence of T1DM in Yamanashi Prefecture increased among children aged 0-14 years over the study period, with the most significant increase occurring among 5- to 9-year-olds. These data suggest that the number of children aged <15 years with T1DM is gradually increasing in one of the local prefectures in Japan, Yamanashi Prefecture and that the age of onset is decreasing.
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Affiliation(s)
- Tomohiro Saito
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsYamanashi Prefectural HospitalYamanashiJapan
| | - Koji Kobayashi
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsYamanashi Kosei HospitalYamanashiJapan
| | - Kisho Kobayashi
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Kobanyashi Kids’ ClinicYamanashiJapan
| | - Mie Mochizuki
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsKyonan Medical Center Fujikawa HospitalYamanashiJapan
| | - Hideaki Yagasaki
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
| | - Koichi Makino
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsFujiyoshida Municipal HospitalYamanashiJapan
| | - Hiromune Narusawa
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
| | - Daisuke Watanabe
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsYamanashi Prefectural HospitalYamanashiJapan
| | - Yumiko Mitsui
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Ryuoh Mitsui ClinicYamanashiJapan
| | - Kazumasa Sato
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsKyonan Medical Center Fujikawa HospitalYamanashiJapan
| | - Tomoaki Sano
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsYamanashi Red Cross HospitalYamanashiJapan
| | - Masanori Ohta
- Department of PediatricsFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
- Department of PediatricsTsuru Municipal General HospitalYamanashiJapan
| | - Hiroshi Yokomichi
- Department of Health SciencesFaculty of MedicineGraduate School of MedicineUniversity of YamanashiYamanashiJapan
| | - Shin Amemiya
- Department of PediatricsFaculty of MedicineSaitama Medical UniversitySaitamaJapan
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Okui T, Nojiri C, Kimura S, Abe K, Maeno S, Minami M, Maeda Y, Tajima N, Kawamura T, Nakashima N. Performance evaluation of case definitions of type 1 diabetes for health insurance claims data in Japan. BMC Med Inform Decis Mak 2021; 21:52. [PMID: 33573645 PMCID: PMC7879626 DOI: 10.1186/s12911-021-01422-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 01/25/2021] [Indexed: 12/18/2022] Open
Abstract
Background No case definition of Type 1 diabetes (T1D) for the claims data has been proposed in Japan yet. This study aimed to evaluate the performance of candidate case definitions for T1D using Electronic health care records (EHR) and claims data in a University Hospital in Japan. Methods The EHR and claims data for all the visiting patients in a University Hospital were used. As the candidate case definitions for claims data, we constructed 11 definitions by combinations of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. (ICD 10) code of T1D, the claims code of insulin needles for T1D patients, basal insulin, and syringe pump for continuous subcutaneous insulin infusion (CSII). We constructed a predictive model for T1D patients using disease names, medical practices, and medications as explanatory variables. The predictive model was applied to patients of test group (validation data), and performances of candidate case definitions were evaluated. Results As a result of performance evaluation, the sensitivity of the confirmed disease name of T1D was 32.9 (95% CI: 28.4, 37.2), and positive predictive value (PPV) was 33.3 (95% CI: 38.0, 38.4). By using the case definition of both the confirmed diagnosis of T1D and either of the claims code of the two insulin treatment methods (i.e., syringe pump for CSII and insulin needles), PPV improved to 90.2 (95% CI: 85.2, 94.4). Conclusions We have established a case definition with high PPV, and the case definition can be used for precisely detecting T1D patients from claims data in Japan.
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Affiliation(s)
- Tasuku Okui
- Medical Information Center, Kyushu University Hospital, Maidashi 3-1-1 Higashi-ku, Fukuoka City, Fukuoka Prefecture, 812-8582, Japan.
| | - Chinatsu Nojiri
- Medical Information Center, Kyushu University Hospital, Maidashi 3-1-1 Higashi-ku, Fukuoka City, Fukuoka Prefecture, 812-8582, Japan
| | - Shinichiro Kimura
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
| | - Kentaro Abe
- National Hospital Organization Kokura Medical Center, Fukuoka, Japan
| | | | | | | | - Naoko Tajima
- Jikei University School of Medicine, Tokyo, Japan
| | | | - Naoki Nakashima
- Medical Information Center, Kyushu University Hospital, Maidashi 3-1-1 Higashi-ku, Fukuoka City, Fukuoka Prefecture, 812-8582, Japan
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26
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Zhao W, Tong J, Li J, Cao Y. Relationship between Body Roundness Index and Risk of Type 2 Diabetes in Japanese Men and Women: A Reanalysis of a Cohort Study. Int J Endocrinol 2021; 2021:4535983. [PMID: 35003255 PMCID: PMC8731295 DOI: 10.1155/2021/4535983] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 12/13/2021] [Indexed: 12/25/2022] Open
Abstract
PURPOSE The purpose of this study was to investigate the association between body roundness index (BRI) and type 2 diabetes (T2DM) in each sex, explore the dose-response relationship between them, and evaluate the predictive value of BRI for T2DM. MATERIALS AND METHODS A retrospective cohort study was performed on 15,464 Japanese patients at the Murakami Memorial Hospital. Data on anthropometric indices and biochemical parameters were obtained. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) of incident T2DM associated with BRI. Dose-response relationships were evaluated using a smoothing function analysis and the threshold effect. Receiver operating characteristic curves were used to evaluate and compare the predictive values of BRI, body mass index (BMI), and waist circumference (WC) for T2DM. RESULTS During a median 5.4-year follow-up period, 373 subjects were diagnosed with T2DM. After adjusting for age, alcohol intake, smoking status, fatty liver, systolic blood pressure, fasting plasma glucose, glycated hemoglobin, high-density lipoprotein cholesterol, triglycerides, and total cholesterol, the relationship between BRI and T2DM was linear in women (HR (95% CI) for BRI Z score = 1.48 (1.26,1.74)) and curvilinear in men (HR (95% CI) on the left and right of the inflection point = 0.70 (0.44, 1.10) and 1.46 (1.27, 1.67), respectively). Compared with BMI (area under the curve (AUC) = 0.684; p < 0.001) and WC (AUC = 0.700; p=0.007), BRI was the strongest predictor of T2DM in men (AUC = 0.715). Similarly, the AUC of BRI was larger than that of BMI (AUC = 0.757; p=0.966) and WC (AUC = 0.733; p=0.015) in women. CONCLUSIONS BRI was positively linearly associated with an elevated risk of incident T2DM in women. In men, the relationship between BRI and T2DM was J-shaped. BRI is an effective indicator of predicting T2DM. Its discriminatory power was higher than that of BMI and WC in both sexes.
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Affiliation(s)
- Wei Zhao
- Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jingjing Tong
- Liver Failure Treatment and Research Center, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
| | - Jinghua Li
- Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yongtong Cao
- Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, China
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27
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Chae HW, Seo GH, Song K, Choi HS, Suh J, Kwon A, Ha S, Kim HS. Incidence and Prevalence of Type 1 Diabetes Mellitus among Korean Children and Adolescents between 2007 and 2017: An Epidemiologic Study Based on a National Database. Diabetes Metab J 2020; 44:866-874. [PMID: 33142054 PMCID: PMC7801766 DOI: 10.4093/dmj.2020.0212] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The incidence of type 1 diabetes mellitus (T1DM) among children is high in Europe and the USA and relatively low in Asia, including Korea. The present study aimed to investigate the incidence and prevalence of childhood-onset T1DM in Korea and examine trends in incidence. METHODS This study was conducted using the national registry data provided by the Health Insurance Review and Assessment Service in Korea from 2007 to 2017. We included children aged 0 to 14 years who were newly registered with a T1DM diagnosis each year (code E10). RESULTS A total of 29,013 children were registered. The overall incidence of T1DM was 4.45 per 100,000 persons (girls, 4.93; boys, 4.01). The overall incidence of childhood-onset T1DM in Korea increased from 3.70 in 2008 to 4.77 in 2016 (P=0.002). The incidence of T1DM increased from 3.07 in 2008 to 4.89 in 2016 (P<0.001) among boys. Although the incidence of the disease increased significantly among boys aged 5-9 and 10-14 years, it remained constant among girls (4.39 in 2008, 4.64 in 2016). The overall prevalence of childhood-onset T1DM in Korea increased from 32.85 in 2007 to 41.03 per 100,000 persons in 2017 (girls, 35.54 to 43.88; boys, 32.85 to 41.03). CONCLUSION We calculated relatively accurate incidence and prevalence of childhood-onset T1DM from a nation-based registry. The incidence increased by 3% to 4% every year from 2007 to 2017. The increasing trend is noteworthy compared with previous reports.
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Affiliation(s)
- Hyun Wook Chae
- Department of Pediatrics, Endocrine Research Institute, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hyeon Seo
- Korean Health Insurance Review and Assessment Service, Seoul, Korea
| | - Kyungchul Song
- Department of Pediatrics, Endocrine Research Institute, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Han Saem Choi
- Department of Pediatrics, Endocrine Research Institute, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Junghwan Suh
- Department of Pediatrics, Endocrine Research Institute, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ahreum Kwon
- Department of Pediatrics, Endocrine Research Institute, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sangmi Ha
- Korean Health Insurance Review and Assessment Service, Seoul, Korea
| | - Ho-Seong Kim
- Department of Pediatrics, Endocrine Research Institute, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
- Corresponding author: Ho-Seong Kim Department of Pediatrics, Endocrine Research Institute, Severance Children’s Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea E-mail:
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Alhazmi A, Sane F, Lazrek M, Nekoua MP, Badia-Boungou F, Engelmann I, Alidjinou EK, Hober D. Enteroviruses and Type 1 Diabetes Mellitus: An Overlooked Relationship in Some Regions. Microorganisms 2020; 8:microorganisms8101458. [PMID: 32977495 PMCID: PMC7598226 DOI: 10.3390/microorganisms8101458] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 09/15/2020] [Accepted: 09/16/2020] [Indexed: 02/07/2023] Open
Abstract
Enteroviruses (EVs) infect millions of people annually. EV infections can be asymptomatic or symptomatic with conditions ranging from mild illnesses to serious diseases such as dilated cardiomyopathy. A causal relationship between EV infections and type 1 diabetes mellitus (T1DM) has been heavily debated, with some studies suggesting that this relationship is not yet conclusive and requires additional evidence, whereas others strongly argue for this correlation. While this relationship is well investigated in some developed countries like the USA and Finland, it is understudied or neglected in other countries like Russia for many reasons such as the low incidence of T1DM. Although the Middle East and North Africa (MENA) are highly affected by T1DM, the role of EVs in the disease in MENA has not been investigated extensively. Therefore, we aimed to address the relationship between T1DM and EVs in MENA and other regions globally.
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Affiliation(s)
- Abdulaziz Alhazmi
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
- Microbiology and Parasitology Department, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia
| | - Famara Sane
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
| | - Mouna Lazrek
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
| | - Magloire Pandoua Nekoua
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
- Laboratoire de Biologie et Physiologie Cellulaires, Institut des Sciences Biomédicales Appliquées (ISBA), Faculté des Sciences et Techniques (FAST), Université d’Abomey-Calavi, 01 BP 526 Cotonou, Benin
| | - Francis Badia-Boungou
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
| | - Ilka Engelmann
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
| | - Enagnon Kazali Alidjinou
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
| | - Didier Hober
- Laboratoire de Virologie ULR3610, Univ Lille, CHU Lille, F-59000 Lille, France; (A.A.); (F.S.); (M.L.); (M.P.N.); (F.B.-B.); (I.E.); (E.K.A.)
- Correspondence: ; Tel.: +33-3-20-44-66-88
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Terauchi Y, Yabe D, Kaneto H, Amano A, Baxter M, Watanabe D, Watada H, Inagaki N. Benefits of the fixed-ratio combination of insulin glargine 100 units/mL and lixisenatide (iGlarLixi) in Japanese people with type 2 diabetes: A subgroup and time-to-control analysis of the LixiLan JP phase 3 trials. Diabetes Obes Metab 2020; 22 Suppl 4:35-47. [PMID: 33404200 DOI: 10.1111/dom.14139] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/30/2020] [Accepted: 07/04/2020] [Indexed: 12/11/2022]
Abstract
AIMS To explore the impact of baseline characteristics on clinical outcomes in the phase 3 LixiLan JP trials which evaluated the efficacy and safety of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 units/mL (iGlar) and GLP-1 RA lixisenatide (Lixi), vs Lixi (JP-O1, NCT02749890) or iGlar (LixiLan JP-O2, NCT02752828; JP-L, NCT02752412) in Japanese people with type 2 diabetes uncontrolled on oral antidiabetes drugs (OADs; JP-O1, JP-O2) or OADs and basal insulin (JP-L). MATERIALS AND METHODS Glycated haemoglobin (HbA1c) change from baseline to week 26 was assessed within patient subgroups. Subgroups were defined by dipeptidyl peptidase-4 inhibitor use at screening (JP-O1, JP-O2 only), baseline HbA1c (<8%, ≥8%), baseline BMI (<25, ≥25 kg/m2) and age (<65, ≥65 years). Incidences of hypoglycaemia (baseline HbA1c, BMI and age subgroups) and gastrointestinal disorders (age subgroup) were evaluated over 52 (JP-O1) or 26 weeks (JP-O2, JP-L). Time to control (first HbA1c <7% or fasting plasma glucose [FPG] ≤130 mg/dL; JP-O2 only) was also assessed. RESULTS HbA1c reductions were consistently greater with iGlarLixi vs iGlar or Lixi across all subgroups, and iGlarLixi was equally effective in all subgroups. Incidences of documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L) were higher with iGlarLixi vs Lixi and generally comparable with iGlar. Across age subgroups, incidences of gastrointestinal disorders with iGlarLixi were higher vs iGlar, but lower vs Lixi. Median time to HbA1c or FPG control was shorter with iGlarLixi vs iGlar. CONCLUSIONS iGlarLixi was consistently effective across all baseline characteristic subgroups, with more patients achieving glycaemic control vs iGlar early in treatment.
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Affiliation(s)
- Yasuo Terauchi
- Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokahama, Japan
| | - Daisuke Yabe
- Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, Gifu, Japan
- Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Osaka, Japan
- Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideaki Kaneto
- Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan
| | | | - Mike Baxter
- Primary Care, Medical, Sanofi, Guildford, UK
- University of Swansea, Swansea, UK
| | | | - Hirotaka Watada
- Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Nobuya Inagaki
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Kawasaki E, Oikawa Y, Okada A, Kanatsuna N, Kawamura T, Kikuchi T, Terasaki J, Miura J, Itoh Y, Hanafusa T. Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8. J Diabetes Investig 2020; 12:510-515. [PMID: 32696593 PMCID: PMC8015838 DOI: 10.1111/jdi.13370] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/22/2020] [Accepted: 07/16/2020] [Indexed: 12/16/2022] Open
Abstract
Aims/Introduction This study aimed to investigate the dynamics associated with autoantibodies to insulinoma‐associated antigen‐2 (IA‐2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes. Methods Using bridging‐type enzyme‐linked immunosorbent assay, IA‐2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.8–86 years; median diabetes duration 7 years, range 0–58 years). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using the Cochran–Armitage trend test and multivariate logistic regression analysis. Results The prevalence of IA‐2A, ZnT8A and glutamic acid decarboxylase autoantibodies in patients with duration of ≤3 years was 41.1, 36.7 and 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration (P < 0.005). Both IA‐2A and ZnT8A were more frequently observed in younger patients, whereas glutamic acid decarboxylase autoantibodies was more common in older patients. Multivariate logistic regression analysis showed that there was a significant interaction between the onset age and duration of diabetes in patients diagnosed when aged ≤10 years regarding all anti‐islet autoantibodies (P < 0.05). However, for patients diagnosed in the middle tertile (aged 11–30 years), the interaction was significant only for ZnT8A, and for those with late‐onset diabetes (aged ≥31 years) only for IA‐2A. Conclusions The current study showed that the rate of disappearance of anti‐islet autoantibodies is faster in patients aged ≤10 years, and that even though both proteins are localized in the insulin granule membrane, humoral autoimmunity to IA‐2 and ZnT8 differs according to the age of onset.
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Affiliation(s)
| | - Yoichi Oikawa
- Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan.,Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan
| | | | - Norio Kanatsuna
- Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan
| | - Tomoyuki Kawamura
- Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Jungo Terasaki
- Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan
| | - Junnosuke Miura
- Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
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Sugihara S, Yokota I, Mukai T, Mochizuki T, Nakayama M, Tachikawa E, Kawada Y, Minamitani K, Kikuchi N, Urakami T, Kawamura T, Kawasaki E, Kikuchi T, Amemiya S. Increased diagnosis of autoimmune childhood-onset Japanese type 1 diabetes using a new glutamic acid decarboxylase antibody enzyme-linked immunosorbent assay kit, compared with a previously used glutamic acid decarboxylase antibody radioimmunoassay kit. J Diabetes Investig 2020; 11:594-602. [PMID: 31756289 PMCID: PMC7232289 DOI: 10.1111/jdi.13184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 10/24/2019] [Accepted: 11/12/2019] [Indexed: 12/19/2022] Open
Abstract
AIMS/INTRODUCTION We compared the results of testing for glutamic acid decarboxylase antibodies (GADAb) using a radioimmunoassay (RIA) and an enzyme-linked immunosorbent assay (ELISA) in individuals with childhood-onset type 1 diabetes mellitus. MATERIALS AND METHODS Serum specimens were collected from 1,024 Japanese children (426 boys and 598 girls) in 2013. The median age at diagnosis was 7 years (0-18 years). The blood specimens were obtained at a median age of 13 years (2-22 years). RESULTS Among the 628 children whose serum specimens were collected within 5 years after diagnosis, the rate of GADAb positivity was 47.9% using RIA and 69.4% using ELISA. The participants were divided into four groups according to their RIA and ELISA results for GADAb as follows: group I (RIA+/ELISA+), group II (RIA+/ELISA-), group III (RIA-/ELISA+) and group IV (RIA-/ELISA-). The clinical and genetic characteristics of group I and group III were quite similar in terms of age at diagnosis, male/female ratio, relatively high positive rates for both autoantibody to protein tyrosine phosphatase IA-2 and autoantibody to the cation efflux transporter zinc transporter 8, and human leukocyte antigen genotype. Group II contained just five patients, and was characterized by a younger age at diagnosis, low positive rates for both autoantibody to protein tyrosine phosphatase IA-2 and autoantibody to the cation efflux transporter zinc transporter 8, and a unique human leukocyte antigen genotype. If the positive rates of either autoantibody to protein tyrosine phosphatase IA-2 or autoantibody to the cation efflux transporter zinc transporter 8 or both were added to the GADAb results using RIA, the percentage of autoimmune type 1 diabetes increased from 47.9% to 78.5%. CONCLUSIONS The diagnosis of autoimmune childhood-onset Japanese type 1 diabetes increased when GADAb results were obtained using a new ELISA method, compared with a previously utilized RIA method.
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Affiliation(s)
- Shigetaka Sugihara
- Department of PediatricsTokyo Women’s Medical University Medical Center EastTokyoJapan
| | - Ichiro Yokota
- Department of Pediatric Endocrinology and MetabolismShikoku Medical Center for Children and AdultsKagawaJapan
| | - Tokuo Mukai
- Department of PediatricsAsahikawa‐Kosei General HospitalAsahikawaJapan
| | | | | | - Emiko Tachikawa
- Department of PediatricsTokyo Women's Medical University HospitalTokyoJapan
| | - Yasumasa Kawada
- Department of PediatricsKyushu Rousai HospitalKitakyushuJapan
| | - Kinship Minamitani
- Department of PediatricsTeikyo University Chiba Medical CenterChibaJapan
| | - Nobuyuki Kikuchi
- Department of PediatricsYokohama City Minato Red Cross HospitalYokohamaJapan
| | - Tatsuhiko Urakami
- Department of PediatricsNihon University School of MedicineTokyoJapan
| | - Tomoyuki Kawamura
- Department of PediatricsOsaka City University School of MedicineOsakaJapan
| | - Eiji Kawasaki
- Department of Diabetes and EndocrinologyShin‐Koga HospitalKurumeJapan
| | - Toru Kikuchi
- Department of PediatricsSaitama Medical UniversityIrumaSaitamaJapan
| | - Shin Amemiya
- Department of PediatricsSaitama Medical UniversityIrumaSaitamaJapan
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Takagi S, Miura J, Hoshina S, Uchigata Y, Babazono T. Clinical and genetic characteristics of people with type 1 diabetes who have discrepancies in titers of anti-glutamic acid decarboxylase antibody measured by radioimmunoassay and enzyme-linked immunosorbent assay. J Diabetes Investig 2020; 11:356-362. [PMID: 31267698 PMCID: PMC7078079 DOI: 10.1111/jdi.13111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 06/12/2019] [Accepted: 07/01/2019] [Indexed: 11/03/2022] Open
Abstract
AIMS/INTRODUCTION The aim of the present study was to compare the clinical and genetic characteristics between people with type 1 diabetes who were positive and negative for autoantibodies against glutamic acid decarboxylase (GADA) measured by enzyme-linked immunosorbent assay (ELISA) with low-titer GADA measured by radioimmunoassay. MATERIALS AND METHODS Among Japanese people with type 1 diabetes in whom GADA were measured by both ELISA and radioimmunoassay, those who had low titers of GADA measured by radioimmunoassay (1.5-10 U/mL), regardless of positivity for GADA measured by ELISA, were studied. There were 65 participants with acute-onset type 1 diabetes and 30 participants with slowly progressive insulin-dependent diabetes mellitus. Clinical characteristics and human leukocyte antigen types were compared in ELISA-positive (≥5 U/mL) and ELISA-negative participants. Endogenous insulin secretion was evaluated by C-peptide index. RESULTS Among participants with slowly progressive insulin-dependent diabetes mellitus, postprandial C-peptide index was significantly higher in ELISA-negative participants than in ELISA-positive participants (r = 0.619, P = 0.002). Among 52 participants whose human leukocyte antigen typing was carried out, all of the participants with slowly progressive insulin-dependent diabetes mellitus who had DRB1*09:01 were positive by GADA-ELISA (P = 0.021). In acute-onset type 1 diabetes participants, there were no significant differences for the C-peptide index and human leukocyte antigen genotypes. CONCLUSIONS The difference in the positivity for GADA-ELISA might reflect cytotoxicity toward pancreatic β-cells and preservation of endogenous insulin secretion in people with slowly progressive insulin-dependent diabetes mellitus. We also suggest that the difference in the GADA-ELISA-specific epitope depends on the human leukocyte antigen genotype.
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Affiliation(s)
- Satoshi Takagi
- Diabetes CenterTokyo Women's Medical University School of MedicineTokyoJapan
| | - Junnosuke Miura
- Diabetes CenterTokyo Women's Medical University School of MedicineTokyoJapan
| | - Sari Hoshina
- Diabetes CenterTokyo Women's Medical University School of MedicineTokyoJapan
| | - Yasuko Uchigata
- Diabetes CenterTokyo Women's Medical University School of MedicineTokyoJapan
- Tokyo Women's Medical University Medical Center EastTokyoJapan
| | - Tetsuya Babazono
- Diabetes CenterTokyo Women's Medical University School of MedicineTokyoJapan
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Wacher NH, Gómez-Díaz RA, Ascencio-Montiel IDJ, Rascón-Pacheco RA, Aguilar-Salinas CA, Borja-Aburto VH. Type 1 diabetes incidence in children and adolescents in Mexico: Data from a nation-wide institutional register during 2000-2018. Diabetes Res Clin Pract 2020; 159:107949. [PMID: 31794808 DOI: 10.1016/j.diabres.2019.107949] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 10/25/2019] [Accepted: 11/22/2019] [Indexed: 12/11/2022]
Abstract
AIMS To describe the annual incidence of type 1 diabetes in children and adolescents insured by the Mexican Institute of Social Security, the main health provider in Mexico, during 2000-2018. METHODS We conducted a secondary data analyses using the incidence registers from the Epidemiological Surveillance Coordination of the Mexican Institute of Social Security collected during 2000-2018. Incident type 1 diabetes cases (age 19 years old and below) were identified using ICD-10-CM E10 diagnostic codes. Age, sex, and geographical region and seasonal-specific incidence were calculated with their corresponding annual percentage change (APC) as well. RESULTS In the period 2000-2018, the number of incident cases with type 1 diabetes decreased from 3.4 to 2.8 per 100,000 in insured for subjects below 20 years old. We observed an increase in the 2000-2006, followed by a decrease for the 2006-2018 period (APC +16.1 and -8.7 respectively). Females and children <5 years old had a significant decrease in the incidence rate, while inhabitants in Central Mexico showed a significant increase. No difference was found in incidence between seasons. CONCLUSIONS Our study describes significant fluctuations of the incidence of type 1 diabetes during the period 2000-2018, which appeared to correspond to influenza outbreaks, among Mexican children and adolescents.
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Affiliation(s)
- Niels H Wacher
- Clinic Epidemiology Research Unit, National Medical Center "Siglo XXI", Mexican Institute of Social Security, Mexico
| | - Rita A Gómez-Díaz
- Clinic Epidemiology Research Unit, National Medical Center "Siglo XXI", Mexican Institute of Social Security, Mexico.
| | - Iván de Jesús Ascencio-Montiel
- Non Communicable Diseases Surveillance Division, Epidemiological Surveillance Coordination, Mexican Institute of Social Security, Mexico City, Mexico
| | - Ramón Alberto Rascón-Pacheco
- Epidemiological Information Division, Epidemiological Surveillance Coordination, Mexican Institute of Social Security, Mexico City, Mexico
| | - Carlos A Aguilar-Salinas
- Research Unit for Metabolic Diseases and Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran", Mexico City, Mexico
| | - Victor H Borja-Aburto
- Dirección de Prestaciones Médicas, Mexican Institute of Social Security, Mexico City, Mexico
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Kaku K, Araki E, Tanizawa Y, Ross Agner B, Nishida T, Ranthe M, Inagaki N. Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naïve Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial. Diabetes Obes Metab 2019; 21:2674-2683. [PMID: 31407845 PMCID: PMC6899795 DOI: 10.1111/dom.13856] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 08/05/2019] [Accepted: 08/06/2019] [Indexed: 01/09/2023]
Abstract
AIMS To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with its individual components in Japanese people with type 2 diabetes (T2D) uncontrolled on an oral antidiabetic drug (OAD). MATERIALS AND METHODS This 52-week, open-label, multicentre, treat-to-target trial randomized participants (n = 819) 1:1:1 to IDegLira, liraglutide 1.8 mg or degludec, as add-on to their pre-trial OAD. The maximum IDegLira dose was 50 dose steps (50 U degludec/1.8 mg liraglutide), there was no maximum dose for degludec, and both were titrated based on individual blood glucose measurements. RESULTS After 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were -6.91 mmol/mol (95% confidence interval [CI] -8.18; -5.64) and -5.30 mmol/mol (95% CI -6.58; -4.03), confirming non-inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]). Mean body weight changes were 2.9 kg, 4.1 kg and -1.0 kg with IDegLira, degludec and liraglutide, respectively, showing superiority of IDegLira versus degludec (P = .0001), but a significant difference in favour of liraglutide (P < .0001). Rates of severe or blood glucose-confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001). Mean daily total insulin dose was lower with IDegLira (27.7 U) versus degludec (34.8 U; P < .0001). Overall adverse event (AE) rates were similar. In total, 34.9%, 22.9% and 41.8% of IDegLira-, degludec- and liraglutide-treated participants experienced gastrointestinal AEs. CONCLUSION IDegLira was superior to degludec and liraglutide in terms of HbA1c reduction and superior to degludec in terms of body weight change and rates of hypoglycaemia in Japanese people with T2D.
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Affiliation(s)
- Kohei Kaku
- Department of Internal MedicineKawasaki Medical SchoolKurashikiJapan
| | - Eiichi Araki
- Department of Metabolic MedicineKumamoto UniversityKumamotoJapan
| | | | | | | | | | - Nobuya Inagaki
- Department of Diabetes, Endocrinology and NutritionKyoto University Graduate School of MedicineKyotoJapan
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Watada H, Kaneko S, Komatsu M, Agner BR, Nishida T, Ranthe M, Nakamura J. Superior HbA1c control with the fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with a maximum dose of 50 units of insulin degludec in Japanese individuals with type 2 diabetes in a phase 3, double-blind, randomized trial. Diabetes Obes Metab 2019; 21:2694-2703. [PMID: 31423685 PMCID: PMC6900157 DOI: 10.1111/dom.13859] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 07/25/2019] [Accepted: 08/11/2019] [Indexed: 12/24/2022]
Abstract
AIMS To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with 50 U insulin degludec (degludec) or less in Japanese individuals with type 2 diabetes (T2D). MATERIALS AND METHODS In this 26-week, double-blind, multicentre, treat-to-target trial, Japanese individuals with T2D that was uncontrolled with basal or pre-mix insulin (20-50 units) were randomized (1:1) to receive IDegLira or degludec, both with metformin. The maximum dose was 50 dose steps (IDegLira) or 50 units (degludec). The primary endpoint was change from baseline in HbA1c with IDegLira vs degludec after 26 weeks of treatment. RESULTS In total, 210 Japanese individuals were randomized to IDegLira or degludec and completion rates were 100% and 93%, respectively. IDegLira was superior to degludec with respect to change from baseline in HbA1c: estimated treatment difference (ETD) (95% confidence interval), -13.98 mmol/Mol (-16.41; -11.55); P < 0.0001. The change in mean HbA1c was from 70.6 by -21.3 mmol/Mol with IDegLira and from 70.1 by -7.1 mmol/Mol with degludec. Mean change in body weight was -0.7 kg with IDegLira and 0.7 kg with degludec: ETD (95% CI) -1.41 kg (-2.26; -0.56); P = 0.0012. Mean daily total insulin dose was significantly lower with IDegLira (37.6 U) as compared to that with degludec (41.2 U) at Week 26. Overall rates of severe or blood glucose-confirmed hypoglycaemia and adverse events were comparable between treatment groups. CONCLUSIONS IDegLira provided superior reductions in HbA1c compared with ≤50 U degludec, with weight loss and similar hypoglycaemia rates and no unexpected safety or tolerability issues. These results suggest that this treatment could be an attractive intensification option for Japanese subjects with T2D that was uncontrolled with basal or pre-mixed insulin.
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Affiliation(s)
- Hirotaka Watada
- Department of Metabolism and EndocrinologyJuntendo University Graduate School of MedicineTokyoJapan
| | - Shizuka Kaneko
- Division of Diabetes/Endocrinology/Lifestyle‐related DiseaseTakatsuki Red Cross HospitalTakatsukiJapan
| | - Mitsuhisa Komatsu
- Department of Diabetes, Endocrinology and Metabolism, Division of Internal MedicineShinshu University School of MedicineMatsumotoJapan
| | | | | | | | - Jiro Nakamura
- Division of Diabetes, Department of Internal MedicineAichi Medical University School of MedicineNagakuteJapan
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Oikawa Y, Sakamoto K, Satomura A, Haisa A, Katsuki T, Hattori Y, Inoue I, Noda M, Shimada A. Significance of peripheral mononuclear cells producing interferon-γ in response to insulin B:9-23-related peptides in subtypes of type 1 diabetes. Clin Immunol 2019; 208:108260. [PMID: 31525445 DOI: 10.1016/j.clim.2019.108260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 09/09/2019] [Accepted: 09/12/2019] [Indexed: 10/26/2022]
Abstract
Type 1 diabetes is largely caused by β-cell destruction through anti-islet autoimmunity. Reportedly, interferon (IFN)-γ-secreting peripheral blood mononuclear cells (PBMCs) specific to four insulin B-chain amino acid 9-23-related peptides (B:9-23rPep) were increased in type 1 diabetes participants. This study aimed to investigate the PBMC frequencies in subtypes of type 1 diabetes using enzyme-linked immunospot assay. In this cross-sectional study, peripheral blood samples were obtained from 148 participants including 72 with acute-onset type 1 diabetes (AT1D), 51 with slowly progressive insulin-dependent diabetes mellitus (SPIDDM), and 25 with type 2 diabetes. The frequency of B:9-23rPep-specific IFN-γ-producing PBMCs was significantly higher in AT1D participants than in SPIDDM and type 2 diabetes participants. Meanwhile, a significant inverse correlation was observed between the PMBC frequencies and insulin secretion capacity in SPIDDM participants. These findings suggest that the increased peripheral B:9-23rPep-specific IFN-γ immunoreactivity reflects decreased functional β-cell mass and greater disease activity of type 1 diabetes.
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Affiliation(s)
- Yoichi Oikawa
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan.
| | - Kumiko Sakamoto
- Cellular Immunology Analysis Section, Genetic and Chromosome Analysis Department, SRL Inc., Tokyo, Japan
| | - Atsushi Satomura
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan
| | - Akifumi Haisa
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan
| | - Takeshi Katsuki
- Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan
| | - Yutaka Hattori
- Division of Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Ikuo Inoue
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan
| | - Mitsuhiko Noda
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan; Department of Diabetes, Metabolism and Endocrinology, Ichikawa Hospital, International University of Health and Welfare, Chiba, Japan
| | - Akira Shimada
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan
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de Filette JMK, Pen JJ, Decoster L, Vissers T, Bravenboer B, Van der Auwera BJ, Gorus FK, Roep BO, Aspeslagh S, Neyns B, Velkeniers B, Kharagjitsingh AV. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol 2019; 181:363-374. [PMID: 31330498 PMCID: PMC6709545 DOI: 10.1530/eje-19-0291] [Citation(s) in RCA: 166] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 07/19/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs). DESIGN AND METHODS We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy. RESULTS Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population. CONCLUSION ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.
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Affiliation(s)
| | - Joeri J Pen
- Diabetes Clinic, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Lore Decoster
- Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Thomas Vissers
- Medical Library, Haaglanden Medical Center, Hague, The Netherlands
| | - Bert Bravenboer
- Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | | | - Frans K Gorus
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
| | - Bart O Roep
- Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
- Department of Diabetes Immunology, Diabetes & Metabolism Research Institute, City of Hope, Duarte, California, USA
| | - Sandrine Aspeslagh
- Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Bart Neyns
- Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Brigitte Velkeniers
- Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Aan V Kharagjitsingh
- Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium
- Diabetes Clinic, Universitair Ziekenhuis Brussel, Brussels, Belgium
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
- Section Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Bao YK, Weide LG, Ganesan VC, Jakhar I, McGill JB, Sahil S, Cheng AL, Gaddis M, Drees BM. High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes from the HealthFacts database. J Diabetes 2019; 11:273-279. [PMID: 30226016 DOI: 10.1111/1753-0407.12856] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 08/07/2018] [Accepted: 09/11/2018] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Patients with type 1 diabetes (T1D) are at risk for other autoimmune diseases (ie, polyautoimmunity). The prevalence and risk factors of this phenomenon have been underreported in adults and ethnic minorities, and data are lacking regarding non-endocrine autoimmune diseases. METHODS Study population data were gathered from HealthFacts, a deidentified patient database compiled from electronic medical records systems in the US. Patients with an International Classification of Diseases diagnosis code specifying T1D were included in the study, whereas those with a diagnosis of type 2 diabetes were excluded. RESULTS The cross-sectional study cohort comprised 158 865 adults with T1D (mean [±SD] age 51.4 ± 18.9 years, 52.5% female). The most common autoimmune diseases were thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the autoimmune diseases were more common in women (eg hypothyroidism, hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjögren syndrome). Caucasians were more likely than other ethnicities to have an additional autoimmune disease. The prevalence of autoimmune diseases increased with increasing age, significantly in women, such that 38.5% of women over 80 years of age had an additional autoimmune disease, compared with 17.9% of women aged ≤29 years. CONCLUSIONS Additional autoimmunity represents a significant comorbidity in patients with T1D. Autoimmune diseases are more common in Caucasians and in women, and increase with age. Clinicians treating patients with T1D should be aware of the risk factors for additional autoimmune diseases.
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Affiliation(s)
- Yicheng K Bao
- Department of Medicine, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
| | - Lamont G Weide
- Department of Medicine, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
| | - Vishwanath C Ganesan
- Department of Medicine, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
| | - Ishaan Jakhar
- Department of Medicine, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
| | - Janet B McGill
- Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri
| | - Suman Sahil
- Department of Biomedical and Health Informatics, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
| | - An-Lin Cheng
- Department of Biomedical and Health Informatics, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
| | - Monica Gaddis
- Department of Biomedical and Health Informatics, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
| | - Betty M Drees
- Department of Medicine, University of Missouri, Kansas City School of Medicine, Kansas City, Missouri
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Kobayashi M, Ohara N, Ikeda Y, Nagano O, Takada T, Kodama M, Sone H. Glutamic Acid Decarboxylase Autoantibody-negative Slowly Progressive Type 1 Diabetes Mellitus: A Case Report and Literature Review. Intern Med 2018; 57:3581-3587. [PMID: 30101912 PMCID: PMC6355411 DOI: 10.2169/internalmedicine.1008-18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
A 59-year-old non-obese Japanese woman developed diabetes mellitus with a negative glutamic acid decarboxylase autoantibody (GADA) test result. Her hyperglycemia was initially well controlled by oral hypoglycemic agents; however, despite continued treatment the hyperglycemia gradually worsened. As she had endogenous insulin deficiency and tested positive for insulin autoantibody (IAA), insulin therapy was initiated. Few studies have investigated GADA-negative patients with slowly progressive type 1 diabetes mellitus (SPT1D). Our IAA-positive SPT1D patient progressed from the clinical onset of diabetes mellitus to starting insulin therapy relatively quickly (1.5 years), similarly to other previously reported non-obese patients with GADA-positive SPT1D.
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Affiliation(s)
- Michi Kobayashi
- Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Nobumasa Ohara
- Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Yohei Ikeda
- Department of Radiology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Ouki Nagano
- Department of Hematology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Toshinori Takada
- Department of Respiratory Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | | | - Hirohito Sone
- Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Japan
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40
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Tung YC, Fann CSJ, Chang CC, Chu CC, Yang WS, Hwu WL, Chen PL, Tsai WY. Comprehensive human leukocyte antigen genotyping of patients with type 1 diabetes mellitus in Taiwan. Pediatr Diabetes 2018; 19:699-706. [PMID: 29383806 DOI: 10.1111/pedi.12645] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 12/11/2017] [Accepted: 12/27/2017] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) mellitus is an autoimmune disorder involving both complex genetic and environmental factors. The incidence rates are low in Asian countries, and the specific, explanatory genetic factors underlying this have been investigated. The aim of this study was to elucidate the association of human leukocyte antigen (HLA) alleles/haplotypes with T1D in Taiwan. METHODS We performed direct comprehensive genotyping of 6 classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) to 4-digit resolution in 104 unrelated T1D patients and 504 controls. Twenty-four of the 104 patients also exhibited thyroid autoimmunity. RESULTS Three major susceptibility haplotypes were identified: DRB1*03:01-DQB1*02:01 (odds ratio [OR] = 5.39 under the dominant model, P = 2.3 × 10-13 ), DRB1*04:05-DQB1*04:01 (OR = 2.44, P = 5.0 × 10-4 ), and DRB1*09:01-DQB1*03:03 (OR = 2.02, P = 1.4 × 10-3 ); one protective haplotype was identified: DRB1*08:03-DQB1*06:01 (OR = 0.10, P = 1.6 × 10-3 ). DRB1*03:01-DQB1*02:01, the major T1D susceptibility haplotype, was found at a lower frequency in T1D patients with thyroid autoimmunity. The T1D protective allele DRB1*12:02 was shown to be protective against Graves' disease in our previous report. CONCLUSION In addition to clarifying the roles of several known T1D HLA alleles and haplotypes, we discovered that the DRB1*08:03-DQB1*06:01 haplotype is protective against T1D. The DRB1*12:02 allele protected against both T1D and Graves' disease.
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Affiliation(s)
- Yi-Ching Tung
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cathy S-J Fann
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | | | - Chen-Chung Chu
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
| | - Wei-Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wuh-Liang Hwu
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Lung Chen
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Yu Tsai
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
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Katahira M, Ogata H, Ito T, Miwata T, Goto M, Nakamura S, Takashima H. Association of Autoimmune Thyroid Disease with Anti-GAD Antibody ELISA Test Positivity and Risk for Insulin Deficiency in Slowly Progressive Type 1 Diabetes. J Diabetes Res 2018; 2018:1847430. [PMID: 30116734 PMCID: PMC6079579 DOI: 10.1155/2018/1847430] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 05/23/2018] [Accepted: 05/28/2018] [Indexed: 12/28/2022] Open
Abstract
The presence of antiglutamic acid decarboxylase antibody (GADA) is required for the diagnosis of slowly progressive type 1 diabetes (SPT1D). We examined the factors influencing GADA determination by radioimmunoassay (GADA-RIA) and by enzyme-linked immunosorbent assay (GADA-ELISA). Sixty patients with SPT1D and 154 patients with type 2 diabetes were examined by both GADA-RIA and GADA-ELISA and for the presence of autoimmune thyroid disease (AITD). We compared the clinical characteristics of these patients based on the positivity or negativity of GADA-RIA and GADA-ELISA, and the existence or nonexistence of AITD. Thirty of 60 (50.0%) GADA-RIA-positive patients were GADA-ELISA negative, whereas none of the 154 GADA-RIA-negative patients were GADA-ELISA positive. Concomitant AITD was significantly less in patients with GADA-RIA and without GADA-ELISA and was significantly more in patients with GADA-RIA and GADA-ELISA. In GADA-RIA-positive patients, there was no significant difference in the GADA-RIA titer among the GADA-ELISA-negative patients with and without AITD, and the GADA-ELISA-positive patients without AITD; whereas the frequency of insulin deficiency was significantly higher in the patients with AITD and/or GADA-ELISA than in those without AITD and GADA-ELISA. Examination of GADA-ELISA and AITD in GADA-RIA-positive patients might be useful in predicting insulin deficiency in these patients.
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Affiliation(s)
- Masahito Katahira
- Aichi Prefectural University School of Nursing and Health, Nagoya 463-8502, Japan
- Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
| | - Hidetada Ogata
- Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
| | - Takahiro Ito
- Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
| | - Tsutomu Miwata
- Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
| | - Megumi Goto
- Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
| | - Shizuka Nakamura
- Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
- Department of General Internal Medicine, Matsunami General Hospital, Gifu 501-6062, Japan
| | - Hiromi Takashima
- Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
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Oikawa Y, Shimada A, Awata T, Fukui T, Ikegami H, Imagawa A, Kajio H, Kawabata Y, Kawasaki E, Miura J, Osawa H, Takahashi K, Tanaka S, Uchigata Y, Yasuda H, Yasuda K, Hanafusa T, Kobayashi T. Clinical features of cases of seroconversion of anti-glutamic acid decarboxylase antibody during the clinical course of type 2 diabetes: a nationwide survey in Japan. Diabetol Int 2017; 8:306-315. [PMID: 30603336 PMCID: PMC6224891 DOI: 10.1007/s13340-017-0312-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2016] [Accepted: 02/03/2017] [Indexed: 10/20/2022]
Abstract
The pathogenesis of type 1 diabetes is different from that of type 2 diabetes, and anti-glutamic acid decarboxylase antibody (GADA) helps to diagnose autoimmune type 1 diabetes. Some studies reported that GADA seroconversion occurs during the clinical course of type 2 diabetes, leading to development of "type 1 on type 2 diabetes". To clarify the clinical characteristics and triggers of GADA seroconversion, we performed a nationwide questionnaire survey for clinical cases identified by literature search, and obtained information on 38 cases (24 with insulin therapy and 14 without it). The diabetes duration up to determination of GADA seroconversion was significantly longer in the group with insulin therapy than that without it. This finding was particularly noted in insulin-treated non-obese patients with lower serum C-peptide levels. In these patients, insulin therapy could have masked sudden increases in plasma glucose and HbA1c levels, possibly leading to delayed determination of GADA seroconversion. In non-obese patients without insulin therapy, an abrupt rise in the plasma glucose and HbA1c levels was observed at immediately before the determination, a finding which may help to predict GADA seroconversion. From the results of the present survey, we could not determine apparent triggers of GADA seroconversion. Thus, physicians may need to consider the possibility of concurrent type 1 diabetes during the therapeutic course of type 2 diabetes; GADA measurement should be considered when non-obese type 2 diabetic patients not receiving insulin therapy experience unexpected abrupt hyperglycemia and when those receiving insulin therapy show low serum C-peptide levels.
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Affiliation(s)
- Yoichi Oikawa
- Department of Internal Medicine, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato, Tokyo, 108-0073 Japan
| | - Akira Shimada
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, 350-0495 Japan
| | - Takuya Awata
- Division of Diabetes and Endocrine, Internal Medicine, International University of Health and Welfare Hospital, Tochigi, 324-8501 Japan
| | - Tomoyasu Fukui
- Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, 142-8666 Japan
| | - Hiroshi Ikegami
- Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka, 589-8511 Japan
| | - Akihisa Imagawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, 565-0871 Japan
| | - Hiroshi Kajio
- Department of Endocrinology, Diabetes, and Metabolism, Center Hospital, National Center for Global Health and Medicine, Tokyo, 162-8655 Japan
| | - Yumiko Kawabata
- Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka, 589-8511 Japan
| | - Eiji Kawasaki
- Department of Diabetes and Endocrinology, Shin Koga Hospital, Fukuoka, 830-8577 Japan
| | - Junnosuke Miura
- Diabetes Center, Tokyo Women’s Medical University School of Medicine, Tokyo, 162-8666 Japan
| | - Haruhiko Osawa
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, 791-0295 Japan
| | - Kazuma Takahashi
- Faculty of Nursing and Graduate School of Nursing, Iwate Prefectural University, Iwate, 020-0693 Japan
| | | | - Yasuko Uchigata
- Diabetes Center, Tokyo Women’s Medical University School of Medicine, Tokyo, 162-8666 Japan
| | - Hisafumi Yasuda
- Division of Health Sciences, Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Hyogo, 654-0142 Japan
| | - Kazuki Yasuda
- Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655 Japan
| | - Toshiaki Hanafusa
- Department of Internal Medicine (I), Osaka Medical College, Osaka, 569-8686 Japan
| | - Tetsuro Kobayashi
- Department of Health Management Center, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, 105-8470 Japan
| | - Research Committee on Type 1 Diabetes of the Japan Diabetes Society
- Department of Internal Medicine, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato, Tokyo, 108-0073 Japan
- Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, 350-0495 Japan
- Division of Diabetes and Endocrine, Internal Medicine, International University of Health and Welfare Hospital, Tochigi, 324-8501 Japan
- Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, 142-8666 Japan
- Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka, 589-8511 Japan
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, 565-0871 Japan
- Department of Endocrinology, Diabetes, and Metabolism, Center Hospital, National Center for Global Health and Medicine, Tokyo, 162-8655 Japan
- Department of Diabetes and Endocrinology, Shin Koga Hospital, Fukuoka, 830-8577 Japan
- Diabetes Center, Tokyo Women’s Medical University School of Medicine, Tokyo, 162-8666 Japan
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, 791-0295 Japan
- Faculty of Nursing and Graduate School of Nursing, Iwate Prefectural University, Iwate, 020-0693 Japan
- Ai Home Clinic, Tokyo, 170-0005 Japan
- Division of Health Sciences, Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Hyogo, 654-0142 Japan
- Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655 Japan
- Department of Internal Medicine (I), Osaka Medical College, Osaka, 569-8686 Japan
- Department of Health Management Center, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, 105-8470 Japan
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Onda Y, Sugihara S, Ogata T, Yokoya S, Yokoyama T, Tajima N. Incidence and prevalence of childhood-onset Type 1 diabetes in Japan: the T1D study. Diabet Med 2017; 34:909-915. [PMID: 27925270 DOI: 10.1111/dme.13295] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 10/24/2016] [Accepted: 11/28/2016] [Indexed: 12/11/2022]
Abstract
AIMS A majority of children with Type 1 diabetes in Japan are registered with the government-subsidized Specified Pediatric Chronic Disease Treatment Research Projects (SPCDTRP). In this study, the incidence and prevalence of childhood-onset (< 15 years) Type 1 diabetes in Japan were estimated by drawing on SPCDTRP data. METHODS Data available for 2005-2012 from the SPCDTRP and Statistics Bureau, Ministry of Internal Affairs and Communications were used to estimate the incidence of Type 1 diabetes for 2005-2010, adjusted to cover those registered within 3 years of disease onset and stratified by sex, age at onset and period of onset. RESULTS The incidence of Type 1 diabetes for 2005-2010 was 2.25/100,000 persons [95% confidence intervals (95% CI), 2.14-2.36] (boys: 1.91, 95% CI, 1.83-1.98; girls: 2.52, 95% CI, 2.34-2.69), with that for the age brackets 0-4, 5-9 and 10-14 years being 1.48 (95% CI, 1.29-1.66), 2.27 (95% CI, 2.08-2.47) and 3.00 (95% CI, 2.74-3.25), respectively. The onset of disease was shown to peak at age 13 among boys (3.28, 95% CI, 3.02-3.55) and at age 10 among girls (3.28, 95% CI, 3.02-3.55). The peak periods of disease onset were April/May and December. The number of children aged < 15 years with Type 1 diabetes for 2005-2012 was estimated to be 2326 (95% CI, 2202-2450) with the prevalence estimated as 13.53/100,000 persons (95% CI, 12.63-14.43). CONCLUSIONS Study findings demonstrated no increase in the incidence of Type 1 diabetes, although suggesting, in agreement with earlier reports, that the onset of disease peaks in adolescence with a female predominance. In addition, the incidence of childhood-onset diabetes exhibited an annual bimodal pattern in this study.
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Affiliation(s)
- Y Onda
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
| | - S Sugihara
- Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo
| | - T Ogata
- Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu
| | - S Yokoya
- Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo
| | - T Yokoyama
- Systematic Review Section, Department of Technology Assessment and Biostatistics, National Institute of Public Health, Saitama
| | - N Tajima
- Jikei University School of Medicine, Tokyo, Japan
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Oikawa Y, Tanaka H, Uchida J, Atsumi Y, Osawa M, Katsuki T, Kawai T, Shimada A. Slowly progressive insulin-dependent (type 1) diabetes positive for anti-GAD antibody ELISA test may be strongly associated with a future insulin-dependent state. Endocr J 2017; 64:163-170. [PMID: 27760891 DOI: 10.1507/endocrj.ej16-0328] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM), believed to be caused by β-cell destruction through islet-cell autoimmunity, gradually progresses to an insulin-dependent state over time. Although the presence of anti-glutamic acid decarboxylase antibody (GADA) is required for the diagnosis of SPIDDM, a recent change in the GADA assay kit from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA) yields mismatched GADA test results between the two kits, leading to confusion in understanding the pathological conditions of SPIDDM in Japan. Thus, this study aimed to clarify the difference in the clinical characteristics of GADA-ELISA-positive and GADA-ELISA-negative patients originally diagnosed as SPIDDM by GADA-RIA test. As a result, 42 of 63 original GADA-RIA-positive SPIDDM patients (66.7%) were found to be GADA-ELISA-positive, whereas the remaining 21 patients (33.3%) were found to be GADA-ELISA-negative. In patients with shorter disease duration, GADA-ELISA-positive patients showed significantly lower serum C-peptide levels than GADA-ELISA-negative patients. Meanwhile, in patients with longer disease duration, serum C-peptide levels were comparably decreased in GADA-ELISA-positive and GADA-ELISA-negative patients. A significant inverse correlation between serum C-peptide level and disease duration was observed in GADA-ELISA-negative patients, but not in GADA-ELISA-positive patients, suggesting that insulin secretory capacity may be gradually impaired over time also in GADA-ELISA-negative SPIDDM patients. In conclusion, physicians should be aware that GADA-ELISA-positive SPIDDM may be strongly associated with a future insulin-dependent state. Meanwhile, physicians should be careful in treating GADA-ELISA-negative SPIDDM patients diagnosed as type 2 DM, and cautiously follow the clinical course, in accordance with SPIDDM.
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Affiliation(s)
- Yoichi Oikawa
- Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo 108-0073, Japan
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Yokomichi H, Nagai A, Hirata M, Kiyohara Y, Muto K, Ninomiya T, Matsuda K, Kamatani Y, Tamakoshi A, Kubo M, Nakamura Y, Yamagata Z. Serum glucose, cholesterol and blood pressure levels in Japanese type 1 and 2 diabetic patients: BioBank Japan. J Epidemiol 2017; 27:S92-S97. [PMID: 28162891 PMCID: PMC5350587 DOI: 10.1016/j.je.2016.12.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Revised: 12/08/2016] [Accepted: 12/11/2016] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Evidence of characteristics of Japanese patients with diabetes from a large-scale population is necessary. Few studies have compared glycaemic controls, complications and comorbidities between type 1 and 2 diabetic patients. This paper focuses on illustrating a clinical picture of Japanese diabetic patients and comparing glycaemic control and prognoses between type 1 and 2 diabetes using multi-institutional data. METHODS The BioBank Japan Project enrolled adult type 1 and 2 diabetic patients between fiscal years 2003 and 2007. We have presented characteristics, controls of serum glucose, cholesterol and blood pressure, prevalence of complications and comorbidities and survival curves. We have also shown glycaemic controls according to various individual profiles of diabetic patients. RESULTS A total of 558 type 1 diabetic patients and 30,834 type 2 diabetic patients participated in this study. The mean glycated haemoglobin A1c was higher in type 1 diabetes than in type 2 diabetes. In the type 1 diabetic patients, the glycated haemoglobin A1c had no consistent trend according to age and body mass index. The Kaplan-Meier estimates represented a longer survival time from baseline with type 1 diabetes than with type 2 diabetes. Compared with type 1 diabetic patients, type 2 diabetic patients had double the prevalence of macrovascular complications. CONCLUSIONS This work has revealed detailed plasma glucose levels of type 1 and 2 diabetic patients according to age, body mass index, blood pressure, serum cholesterol levels and smoking and drinking habits. Our data have also shown that the prognosis is worse for type 2 diabetes than for type 1 diabetes in Japan.
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Affiliation(s)
- Hiroshi Yokomichi
- Department of Health Sciences, University of Yamanashi, Yamanashi, Japan.
| | - Akiko Nagai
- Department of Public Policy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Makoto Hirata
- Laboratory of Genome Technology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yutaka Kiyohara
- Hisayama Research Institute for Lifestyle Diseases, Fukuoka, Japan
| | - Kaori Muto
- Department of Public Policy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Toshiharu Ninomiya
- Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Fukuoka, Japan
| | - Koichi Matsuda
- Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yoichiro Kamatani
- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Akiko Tamakoshi
- Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Michiaki Kubo
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Yusuke Nakamura
- Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | | | - Zentaro Yamagata
- Department of Health Sciences, University of Yamanashi, Yamanashi, Japan
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Kamata Y, Takano K, Kishihara E, Watanabe M, Ichikawa R, Shichiri M. Distinct clinical characteristics and therapeutic modalities for diabetic ketoacidosis in type 1 and type 2 diabetes mellitus. J Diabetes Complications 2017; 31:468-472. [PMID: 27499457 DOI: 10.1016/j.jdiacomp.2016.06.023] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2016] [Revised: 05/31/2016] [Accepted: 06/24/2016] [Indexed: 11/20/2022]
Abstract
AIMS Patients with type 1 diabetes often develop diabetic ketoacidosis (DKA). Reportedly, DKA in type 2 diabetes has higher mortality despite its limited occurrence. The exact clinical characteristics and therapeutic modalities yielding successful outcomes in DKA type 2 diabetes remain unknown. METHODS This retrospective study compared the clinical features and detailed treatment of consecutive type 1 and type 2 diabetes patients hospitalized with DKA between January 2001 and December 2014. RESULTS We report on 127 patients with type 1 and 74 patients with type 2 diabetes whose DKA was successfully treated. The most frequent precipitating cause for DKA was infectious disease for patients with type 1 diabetes and consumption of sugar-containing beverages for those with type 2 diabetes. Type 2 diabetes patients showed higher mean plasma glucose levels than those with type 1 diabetes (48.4±21.6, vs. 37.1±16.4mmol/l, P<0.01) and higher serum creatinine, blood urea nitrogen, and hemoglobin levels, which normalized after DKA resolution. Compared with type 1 diabetes patients, those with type 2 diabetes required distinctly higher daily total insulin dosage (35.9±37.0U, vs. 20.2±23.3U, P<0.01), larger replacement fluid volumes (4.17±2.69L, vs. 2.29±1.57L, P<0.01) and greater potassium supplementation (23.9±36.5mEq, vs. 11.2±17.9mEq, P<0.01) to resolve DKA and reduce plasma glucose level to ≤16.7mmol/l. CONCLUSIONS DKA patients with type 2 diabetes required management with a modified treatment protocol to resolve their profound hyperglycemia and dehydration compared with those with type 1 diabetes.
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Affiliation(s)
- Yuji Kamata
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan.
| | - Koji Takano
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan
| | - Eriko Kishihara
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan
| | - Michiko Watanabe
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan
| | - Raishi Ichikawa
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan
| | - Masayoshi Shichiri
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan
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Ohara N, Koda R, Watanabe H, Iino N, Ohashi K, Terajima K, Ozawa T, Ikeda Y, Sekiguchi H, Ohashi H, Yamaguchi S. Generalized Status Epilepticus in a Patient with Acute-onset Type 1 Diabetes Mellitus Associated with Severe Kidney Dysfunction: A Case Report and Literature Review. Intern Med 2017; 56:1993-1999. [PMID: 28768970 PMCID: PMC5577076 DOI: 10.2169/internalmedicine.56.8304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
A 65-year-old Japanese man with advanced chronic kidney disease (CKD) developed acute-onset type 1 diabetes mellitus (T1D) that was associated with severe acute kidney injury and was manifested by generalized tonic-clonic status epilepticus. His seizures resolved without recurrence after correcting the diabetic ketoacidosis. Although hyperglycemia is an important cause of acute symptomatic seizure (ASS), patients with ketotic hyperglycemia develop ASS less frequently. In this T1D case with CKD, severe hyperglycemia in conjunction with other metabolic insults, such as uremia, hyponatremia, and hypocalcemia, probably provoked his seizure despite the severe ketonemia.
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Affiliation(s)
- Nobumasa Ohara
- Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Ryo Koda
- Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Hirofumi Watanabe
- Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Noriaki Iino
- Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Kazumasa Ohashi
- Department of Respiratory Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Kenshi Terajima
- Department of Neurology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Tetsutaro Ozawa
- Department of Neurology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Yohei Ikeda
- Department of Radiology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Hiroshi Sekiguchi
- Department of Emergency and Critical Care Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Hitomi Ohashi
- Department of Emergency and Critical Care Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
| | - Seigo Yamaguchi
- Department of Emergency and Critical Care Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
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Is the incidence of type 1 diabetes in children and adolescents stabilising? The first 6 years of a National Register. Eur J Pediatr 2016; 175:1913-1919. [PMID: 27659662 DOI: 10.1007/s00431-016-2787-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 09/05/2016] [Accepted: 09/12/2016] [Indexed: 02/06/2023]
Abstract
UNLABELLED The Irish Childhood Diabetes National Register (ICDNR) was established in 2008 to define accurately the incidence and monitor the epidemiology of type 1 diabetes (T1D) in the Irish population. Here, we report data from the first 6 years of the National Register and compare with previous national data. Prospective national incident data regarding T1D in those under 15 years resident in Ireland were collected from 2008 to 2013 and national incidence rates (IRs) calculated. Ascertainment completeness was assessed using capture-recapture methodology. The period identified 1566 new cases of T1D, ascertainment reached 96.8 % in 2013. The standardised incidence rate was 27.5 in 2008 stabilising at 28.7 and 28.8 cases /100,000/year in 2012 and 2013. There was no evidence that the incidence changed significantly in the 6-year period either overall or for each age group and gender. There was evidence of a difference in the incidence of T1D across the age groups with the overall incidence highest in the 10-14 year age category. A strong seasonal association was demonstrated. CONCLUSIONS This study confirms Ireland as a high-incidence country for type 1 diabetes whilst demonstrating that the previous marked increase in IR from 16.3 cases/100,000/year in 1997 has not continued. Ongoing monitoring through the robust mechanism of the ICDNR is required to clarify whether this is a fluctuation or if the incidence of T1D diabetes has stopped rising in our population. Alternatively, this apparent stabilisation may reflect a shift to a later age at diagnosis. "What is known :" • The incidence of Type 1 diabetes (T1D) is increasing in most populations worldwide although in certain high-incidence populations, it may be stabilising • There was a marked increase in T1D in Ireland between 1997 and 2008 • T1D incidence increases with affluence "What is New:" • The high incidence of T1D in Ireland has been confirmed at 28.8 cases/100,000/year in 2013 and has been effectively stable in the period 2008-2013 • Incidence is highest in Irish 10-14 year olds • Changes in incidence possibly reflecting life style and economic climate • Marked seasonality of diagnosis confirmed.
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Wu HB, Zhong JM, Hu RY, Wang H, Gong WW, Pan J, Fei FR, Wang M, Guo LH, Yang L, Yu M. Rapidly rising incidence of Type 1 diabetes in children and adolescents aged 0-19 years in Zhejiang, China, 2007 to 2013. Diabet Med 2016; 33:1339-46. [PMID: 26499360 DOI: 10.1111/dme.13010] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/21/2015] [Indexed: 12/16/2022]
Abstract
AIMS To investigate the incidence rates and trends in Type 1 diabetes in children and adolescents aged 0-19 years in the registered Zhejiang population over the period 2007-2013 by age, sex and calendar year. METHODS In total, 611 individuals with newly diagnosed Type 1 diabetes were identified from 30 districts in Zhejiang province over the study period. Annual incidence and 95% confidence intervals (CI) by age group and sex were calculated per 100 000 person-years. Trends in diabetes incidence and the associations of age and sex with Type 1 diabetes were assessed using Poisson regression models. RESULTS The mean annual age-standardized incidence of diabetes was 2.02/100 000 person-years (95% CI: 1.92-2.12), with an average annual increase of 12.0% (95% CI: 7.6-16.6%) over the study period. The risk for Type 1 diabetes in girls was estimated to be 1.25 (95% CI: 1.07-1.47) times higher than that in boys. Compared with those aged 0-4 years, the 5-9, 10-14 and 15-19 years age groups were at significantly greater risk, with adjusting incidence rate ratios of 3.54, 6.58 and 5.39, respectively. The mean age at diagnosis decreased significantly from 12.85 years in 2007 to 11.21 years in 2013. A steep rise in diabetes incidence was observed in the under 5 years age group, which showed the greatest increase at 33.61%. CONCLUSIONS The incidence of diabetes in Zhejiang was relatively low, although rapidly rising trends have been found in recent years, particularly in younger children. Further monitoring and research are urgently required to better understand possible environmental risk factors and formulate preventive strategies.
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Affiliation(s)
- H B Wu
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - J M Zhong
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - R Y Hu
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - H Wang
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - W W Gong
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - J Pan
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - F R Fei
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - M Wang
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - L H Guo
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - L Yang
- Zhejiang Provincial Center for Cardio-cerebrovascular Diseases Control and Prevention, Zhejiang Hospital, Hangzhou, China
| | - M Yu
- Department of NCDs Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
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Yasui J, Kawasaki E, Tanaka S, Awata T, Ikegami H, Imagawa A, Uchigata Y, Osawa H, Kajio H, Kawabata Y, Shimada A, Takahashi K, Yasuda K, Yasuda H, Hanafusa T, Kobayashi T. Clinical and Genetic Characteristics of Non-Insulin-Requiring Glutamic Acid Decarboxylase (GAD) Autoantibody-Positive Diabetes: A Nationwide Survey in Japan. PLoS One 2016; 11:e0155643. [PMID: 27177031 PMCID: PMC4866691 DOI: 10.1371/journal.pone.0155643] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Accepted: 05/02/2016] [Indexed: 11/21/2022] Open
Abstract
Aims Glutamic acid decarboxylase autoantibodies (GADAb) differentiate slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) from phenotypic type 2 diabetes, but many GADAb-positive patients with diabetes do not progress to insulin-requiring diabetes. To characterize GADAb-positive patients with adult-onset diabetes who do not require insulin therapy for >5 years (NIR-SPIDDM), we conducted a nationwide cross-sectional survey in Japan. Methods We collected 82 GADAb-positive patients who did not require insulin therapy for >5 years (NIR-SPIDDM) and compared them with 63 patients with insulin-requiring SPIDDM (IR-SPIDDM). Clinical and biochemical characteristics, HLA-DRB1-DQB1 haplotypes, and predictive markers for progression to insulin therapy were investigated. Results Compared with the IR-SPIDDM group, the NIR-SPIDDM patients showed later diabetes onset, higher body mass index, longer duration before diagnosis, and less frequent hyperglycemic symptoms at onset. In addition, C-peptide, LDL-cholesterol, and TG were significantly higher in the NIR-SPIDDM compared to IR-SPIDDM patients. The NIR-SPIDDM group had lower frequency of susceptible HLA-DRB1*04:05-DQB1*04:01 and a higher frequency of resistant HLA-DRB1*15:01-DQB1*06:02 haplotype compared to IR-SPIDDM. A multivariable analysis showed that age at diabetes onset (OR = 0.82), duration before diagnosis of GADAb-positive diabetes (OR = 0.82), higher GADAb level (≥10.0 U/ml) (OR = 20.41), and fasting C-peptide at diagnosis (OR = 0.07) were independent predictive markers for progression to insulin-requiring diabetes. An ROC curve analysis showed that the optimal cut-off points for discriminating two groups was the GADAb level of 13.6 U/ml, age of diabetes onset of 47 years, duration before diagnosis of 5 years, and fasting C-peptide of 0.65 ng/ml. Conclusions Clinical, biochemical and genetic characteristics of patients with NIR-SPIDDM are different from those of IR-SPIDDM patients. Age of diabetes onset, duration before GADAb-positivity, GADAb level, and fasting C-peptide at diagnosis must be carefully considered in planning prevention trials for SPIDDM.
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Affiliation(s)
- Junichi Yasui
- Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki, Japan
| | - Eiji Kawasaki
- Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki, Japan
- Department of Diabetes and Endocrinology, Shin-Koga Hospital, Kurume, Japan
- * E-mail:
| | - Shoichiro Tanaka
- Third Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Takuya Awata
- Department of Diabetes, Endocrinology and Metabolism, International University of Health and Welfare Hospital, Tochigi, Japan
| | - Hiroshi Ikegami
- Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka, Japan
| | - Akihisa Imagawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Yasuko Uchigata
- Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Haruhiko Osawa
- Department of Laboratory Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Hiroshi Kajio
- Department of Diabetes, Endocrinology, and Metabolism, Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yumiko Kawabata
- Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka, Japan
| | - Akira Shimada
- Department of Internal Medicine, Saiseikai Central Hospital, Tokyo, Japan
| | - Kazuma Takahashi
- Department of Diabetes and Metabolism, Iwate Medical University, Iwate, Japan
| | - Kazuki Yasuda
- Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hisafumi Yasuda
- Division of Health Sciences, Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - Toshiaki Hanafusa
- Department of Internal Medicine (I), Osaka Medical College, Takatsuki, Japan
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