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Taurbekova B, Sarsenov R, Yaqoob MM, Atageldiyeva K, Semenova Y, Fazli S, Starodubov A, Angalieva A, Sarria-Santamera A. Cluster Analysis in Diabetes Research: A Systematic Review Enhanced by a Cross-Sectional Study. J Clin Med 2025; 14:3588. [PMID: 40429583 PMCID: PMC12112067 DOI: 10.3390/jcm14103588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 05/03/2025] [Accepted: 05/16/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Diabetes mellitus is a heterogeneous metabolic disorder that poses substantial challenges in the management of patients with diabetes. Emerging research underscores the potential of unsupervised cluster analysis as a promising methodological approach for unraveling the complex heterogeneity of diabetes mellitus. This systematic review evaluated the effectiveness of unsupervised cluster analysis in identifying diabetes phenotypes, elucidating the risks of diabetes-related complications, and distinguishing treatment responses. Methods: We searched MEDLINE Complete, PubMed, and Web of Science and reviewed forty-one relevant studies. Additionally, we conducted a cross-sectional study using K-means cluster analysis of real-world clinical data from 558 patients with diabetes. Results: A key finding was the consistent reproducibility of the five clusters across diverse populations, encompassing various patient origins and ethnic backgrounds. MOD and MARD were the most prevalent clusters, while SAID was the least prevalent. Subgroup analysis stratified by ethnic group indicated a higher prevalence of SIDD among individuals of Asian descent than among other ethnic groups. These clusters shared similar phenotypic traits and risk profiles for complications, with some variations in their distribution and key clinical variables. Notably, the SIRD subtype was associated with a wide spectrum of kidney-related clinical presentations. Alternative clustering techniques may reveal additional clinically relevant diabetes subtypes. Our cross-sectional study identified five subgroups, each with distinct profiles of glycemic control, lipid metabolism, blood pressure, and renal function. Conclusions: Overall, the results suggest that unsupervised cluster analysis holds promise for revealing clinically meaningful subgroups with distinct characteristics, complication risks, and treatment responses that may remain undetected using conventional approaches.
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Affiliation(s)
- Binura Taurbekova
- Department of Biomedical Sciences, School of Medicine, Nazarbayev University, 5/1 Kerey and Zhanibek Khandar Str., Astana 010000, Kazakhstan;
| | - Radmir Sarsenov
- Department of Biology, School of Sciences and Humanities, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan;
| | - Muhammad M. Yaqoob
- Department of Renal Medicine and Transplantation, The Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London E1 1BB, UK;
- William Harvey Research Institute, Faculty of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
| | - Kuralay Atageldiyeva
- Department of Medicine, School of Medicine, Nazarbayev University, 5/1 Kerey and Zhanibek Khandar Str., Astana 010000, Kazakhstan;
| | - Yuliya Semenova
- Department of Surgery, School of Medicine, Nazarbayev University, 5/1 Kerey and Zhanibek Khandar Str., Astana 010000, Kazakhstan;
| | - Siamac Fazli
- Department of Computer Science, School of Engineering and Digital Sciences, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan;
| | - Andrey Starodubov
- «B.B.NURA» Hospitals Group, Office 815, 33/1 Mangilik El Str., Astana 010000, Kazakhstan;
| | - Akmaral Angalieva
- Women’s Health Department, City Multidisciplinary Hospital No. 2, 6 Turar Ryskulov Str., Astana 010000, Kazakhstan;
| | - Antonio Sarria-Santamera
- Department of Biomedical Sciences, School of Medicine, Nazarbayev University, 5/1 Kerey and Zhanibek Khandar Str., Astana 010000, Kazakhstan;
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Papatheodorou K, Shubrook JH. Beta-cell preservation in T2DM using a pathophysiologic approach. Postgrad Med 2025; 137:235-242. [PMID: 40247637 DOI: 10.1080/00325481.2025.2494502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 04/11/2025] [Accepted: 04/14/2025] [Indexed: 04/19/2025]
Abstract
Type 2 diabetes and obesity rates continue to rise. Type 2 diabetes affects 1-2 million new individuals annually. Despite a wide range of treatment options for type 2 diabetes, many people still fail to achieve therapeutic goals. Treating type 2 diabetes more proactively with a pathophysiologic approach can ensure higher rates of success and reduce complications. This article summarizes the progressive understanding of the pathophysiology of diabetes, draws a connection between illness and beta-cell health, and introduces the pathophysiologic approach to type 2 diabetes and its focus on beta-cell preservation. This article compiled clinical data, evidence-based medicine, and experimental results to create a comprehensive narrative review.
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Affiliation(s)
| | - Jay H Shubrook
- Department of Clinical Sciences and Community Health, Touro University, California, College of Osteopathic Medicine, Vallejo, CA, USA
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Golubic R, Car J, Nicolaides K. Enhancing postpartum cardiometabolic health for women with previous gestational diabetes: Next steps and unanswered questions for pharmacological and lifestyle strategies. Diabetes Obes Metab 2025; 27:447-449. [PMID: 39552532 DOI: 10.1111/dom.16070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/21/2024] [Accepted: 11/01/2024] [Indexed: 11/19/2024]
Affiliation(s)
- Rajna Golubic
- Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Josip Car
- School of Life Course and Population Sciences, King's College London, London, UK
| | - Kypros Nicolaides
- School of Life Course and Population Sciences, King's College London, London, UK
- The Fetal Medicine Research Institute, London, UK
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Gómez Fernández C, Golubic R, Mitsigiorgi R, Mansukhani T, Car J, Nicolaides KH. Predictors of Cardiometabolic Health a Few Months Postpartum in Women Who Had Developed Gestational Diabetes. Nutrients 2025; 17:390. [PMID: 39940248 PMCID: PMC11820877 DOI: 10.3390/nu17030390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 01/18/2025] [Accepted: 01/20/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND To assess the incidence of dysglycaemia and metabolic syndrome and factors associated with them 5 months postpartum in women with gestational diabetes mellitus (GDM) in their last pregnancy. METHODS We conducted an observational prospective cohort study in 558 women with previous GDM who attended a 5-month postpartum follow-up clinic. Backward elimination was performed to select significant factors for the multivariable logistic regression model. Dysglycaemia (prediabetes and type 2 diabetes (T2D)) and metabolic syndrome were used as outcomes in separate models. RESULTS Dysglycaemia was diagnosed in 202 (36.2%) women, including 174 (31.2%) with prediabetes and 28 (5.0%) with T2D. Women with dysglycaemia, compared with those with normoglycaemia, were more likely to be of black ethnicity (33.2 vs. 20.5%) and have severe GDM (31.7 vs. 16%), a higher postpartum BMI (29.5 vs. 27.6 kg/m2), and metabolic syndrome (20 vs. 7%). Multivariable logistic regression analysis showed that significant predictors of dysglycaemia were black (OR 2.09; 95% CI: 1.27-3.46) and mixed ethnicity (OR 3.05; 95% CI: 1.26-7.42), diagnosis of GDM before 24 weeks gestation (OR 3.05, 95% CI: 1.90-4.91), and treatment of GDM with metformin (OR 1.63; 95% CI: 1.05-2.55) or insulin (OR 2.08; 95% CI: 1.14-3.79) rather than diet alone. Significant predictors of metabolic syndrome were postpartum maternal BMI (OR 5.49; 95% CI: 2.60-11.59) and absence of breastfeeding (OR 2.14; 95% CI: 1.21-3.77). CONCLUSIONS At 5 months postpartum, a high proportion of women who developed GDM showed evidence of dysglycaemia. Future studies should investigate interventions that could reduce the risk of short- and long-term consequences of suboptimal cardiometabolic health in such women.
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Affiliation(s)
- Cristina Gómez Fernández
- Harris Birthright Research Centre for Fetal Medicine, King’s College, London SE5 8BB, UK; (C.G.F.); (R.M.); (T.M.)
- Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
| | - Rajna Golubic
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford OX3 9DU, UK;
| | - Rea Mitsigiorgi
- Harris Birthright Research Centre for Fetal Medicine, King’s College, London SE5 8BB, UK; (C.G.F.); (R.M.); (T.M.)
| | - Tanvi Mansukhani
- Harris Birthright Research Centre for Fetal Medicine, King’s College, London SE5 8BB, UK; (C.G.F.); (R.M.); (T.M.)
| | - Josip Car
- Department of Women and Children’s Health, School of Life Course and Population Sciences, King’s College London, London SE5 8BB, UK;
| | - Kypros H. Nicolaides
- Harris Birthright Research Centre for Fetal Medicine, King’s College, London SE5 8BB, UK; (C.G.F.); (R.M.); (T.M.)
- Department of Women and Children’s Health, School of Life Course and Population Sciences, King’s College London, London SE5 8BB, UK;
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Manchi RK, Chenchula S, Haritha M. Effectiveness and Safety of Metformin, Teneligliptin, and Glimepiride Combination Therapy in Type 2 Diabetes: A Quasi Experimental Clinical Trial. Curr Diabetes Rev 2025; 21:102-111. [PMID: 39620331 DOI: 10.2174/0115733998292943240730115310] [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: 04/23/2024] [Revised: 06/22/2024] [Accepted: 07/02/2024] [Indexed: 02/26/2025]
Abstract
INTRODUCTION Type 2 Diabetes Mellitus (T2DM) accounts for more than 95% of all diabetes cases and is a leading cause of disability and death. This study aimed to evaluate the effectiveness and safety of a combination therapy involving metformin, teneligliptin, and glimepiride in patients diagnosed with T2DM. METHODS The present quasi-experimental clinical trial involved 300 adult T2DM patients. They were divided into three groups: Group 1 (Metformin; n=100), Group 2 (Metformin + Teneligliptin; n=100), and Group 3 (Metformin + Teneligliptin +; n=100). Along with demographic data, we collected information on HbA1c, FBS, and PPBS levels, as well as fasting insulin, CPeptide, HOMA-IR, QUICKI-IR, and lipid, renal, and hepatic profiles at baseline and after 3, 6, and 12 months. Data analysis was performed using SPSS 21.0 software. RESULTS A total of 300 patients participated in the study. At the end of 12 months, triple-drug therapy achieved significant glycemic control (HbA1c: 6.56±0.50%; P<0.0001) and reduced FBS (7.6±1.41 mg/dl; P<0.0001), PPBS (9.39±2.14 mg/dl; P<0.0001), and fasting insulin (11.26±2.5 IU; P<0.0001), C-peptide (2.01±2.29 ng/ml; P<0.0001), and insulin resistance by HOMA-IR (3.74±0.7; P<0.0001). Favorable lipid profiles (P<0.0001) were noted versus other groups. Despite renal and hepatic profile variations, values remained within the normal range. CONCLUSION The combination of teneligliptin with metformin and glimepiride in T2DM patients demonstrated significant improvements in glycaemic control, reduced insulin resistance, and positive effects on lipid, renal, and hepatic profiles. Importantly, the therapy did not result in serious adverse drug reactions, such as hypoglycemia. We need more RCTs to substantiate these findings.
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Affiliation(s)
- Rajesh Kumar Manchi
- Department of Pharmacology, Saraswati Medical College, Unnao, Uttar Pradesh, India
- Department of Pharmacology, T S Misra Medical College, Lucknow, India
| | - Santenna Chenchula
- Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, India
| | - Manchi Haritha
- Department of Pharmacology, Narayana Medical College, Nellore, Andhra Pradesh, India
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Page KA. Neurodevelopmental Pathways to Obesity and Type 2 Diabetes: Insights From Prenatal Exposure to Maternal Obesity and Gestational Diabetes Mellitus: A Report on Research Supported by Pathway to Stop Diabetes. Diabetes 2024; 73:1937-1941. [PMID: 39432818 PMCID: PMC11583106 DOI: 10.2337/dbi24-0012] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 09/08/2024] [Indexed: 10/23/2024]
Abstract
Incidences of childhood obesity and type 2 diabetes (T2D) are climbing at alarming rates. Evidence points to prenatal exposures to maternal obesity and gestational diabetes mellitus (GDM) as key contributors to these upward trends. Children born to mothers with these conditions face higher risks of obesity and T2D, beyond genetic or shared environmental factors. The underpinnings of this maternal-fetal programming are complex. However, animal studies have shown that such prenatal exposures can lead to changes in brain pathways, particularly in the hypothalamus, leading to obesity and T2D later in life. This article highlights significant findings stemming from research funded by my American Diabetes Association Pathway Accelerator Award and is part of a series of Perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program. This critical support, received more than a decade ago, paved the way for groundbreaking discoveries, translating the neural programming findings from animal models into human studies and exploring new avenues in maternal-fetal programming. Our BrainChild cohort includes >225 children, one-half of whom were exposed in utero to maternal GDM and one-half born to mothers without GDM. Detailed studies in this cohort, including neuroimaging and metabolic profiling, reveal that early fetal exposure to maternal GDM is linked to alterations in brain regions, including the hypothalamus. These neural changes correlate with increased energy intake and predict greater increases in BMI, indicating that early neural changes may underlie and predict later obesity and T2D, as observed in animal models. Ongoing longitudinal studies in this cohort will provide critical insights toward breaking the vicious cycle of maternal-child obesity and T2D. ARTICLE HIGHLIGHTS
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Affiliation(s)
- Kathleen A. Page
- Division of Endocrinology and Diabetes, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, Diabetes and Obesity Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA
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Chen L, Zhu Y. Gestational Diabetes Mellitus and Subsequent Risks of Diabetes and Cardiovascular Diseases: the Life Course Perspective and Implications of Racial Disparities. Curr Diab Rep 2024; 24:244-255. [PMID: 39230861 PMCID: PMC11985260 DOI: 10.1007/s11892-024-01552-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/19/2024] [Indexed: 09/05/2024]
Abstract
PURPOSE OF REVIEW Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide and the prevalence is continuously rising globally. Importantly, GDM is not an isolated complication of pregnancy. Growing evidence suggests that individuals with GDM, compared to those without GDM, have an increased risk of subsequent type 2 diabetes (T2D) and cardiovascular diseases (CVD). Substantial racial and ethnic disparities exist in the risk of GDM. However, the role of race and ethnicity in the progression from GDM to T2D and CVD remains unclear. The purpose of the current review is to summarize recent research about GDM and its life-course impacts on cardiometabolic health, including 1) the peak time of developing T2D and CVD risks after GDM, 2) the racial and ethnic disparities in the risk cardiometabolic diseases after GDM, 3) the biological plausibility and underlying mechanisms, and 4) recommendations for screening and prevention of cardiometabolic diseases among individuals with GDM, collectively to provide an updated review to guide future research. RECENT FINDINGS Growing evidence has indicated that individuals with GDM had greater risks of T2D (7.4 to 9.6 times), hypertension (78% higher), and CDV events (74% higher) after GDM than their non-GDM counterparts. More recently, a few studies also suggested that GDM could slightly increase the risk of mortality. Available evidence suggests that key CVD risk factors such as blood pressure, plasma glucose, and lipids levels are all elevated as early as < 1 year postpartum in individuals with GDM. The risk of T2D and hypertension is likely to reach a peak between 3-6 years after the index pregnancy with GDM compared to normal glycemia pregnancy. Cumulative evidence also suggests that the risk of cardiometabolic diseases including T2D, hypertension, and CVD events after GDM varies by race and ethnicity. However, whether the risk is higher in certain racial and ethnic groups and whether the pattern may vary by the postpartum cardiometabolic outcome of interest remain unclear. The underlying mechanisms linking GDM and subsequent T2D and CVD are complex, often involving multiple pathways and their interactions, with the specific mechanisms varying by individuals of different racial and ethnic backgrounds. Diabetes and CVD risk screening among individuals with GDM should be initiated early during postpartum and continue, if possible, frequently. Unfortunately, adherence to postpartum glucose testing with either obstetrician or primary care providers remained poor among individuals with GDM. A life-course perspective may provide critical information to address clinical and public health gaps in postpartum screening and interventions for preventing T2D and CVD risks in individuals with GDM. Future research investigating the racial- and ethnic-specific risk of progression from GDM to cardiometabolic diseases and the role of multi-domain factors including lifestyle, biological, and socio-contextual factors are warranted to inform tailored and culture-appropriate interventions for high-risk subpopulations. Further, examining the barriers to postpartum glucose testing among individuals with GDM is crucial for the effective prevention of cardiometabolic diseases and for enhancing life-long health.
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Affiliation(s)
- Liwei Chen
- Department of Epidemiology, University of California Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
| | - Yeyi Zhu
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
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Gurlo T, Liu R, Wang Z, Hoang J, Ryazantsev S, Daval M, Butler AE, Yang X, Blencowe M, Butler PC. Dysregulation of cholesterol homeostasis is an early signal of β-cell proteotoxicity characteristic of type 2 diabetes. Physiol Genomics 2024; 56:621-633. [PMID: 38949617 DOI: 10.1152/physiolgenomics.00029.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/26/2024] [Accepted: 06/27/2024] [Indexed: 07/02/2024] Open
Abstract
Type 2 diabetes (T2D) is a common metabolic disease due to insufficient insulin secretion by pancreatic β-cells in the context of insulin resistance. Islet molecular pathology reveals a role for protein misfolding in β-cell dysfunction and loss with islet amyloid derived from islet amyloid polypeptide (IAPP), a protein coexpressed and cosecreted with insulin. The most toxic form of misfolded IAPP is intracellular membrane disruptive toxic oligomers present in β-cells in T2D and in β-cells of mice transgenic for human IAPP (hIAPP). Prior work revealed a high degree of overlap of transcriptional changes in islets from T2D and prediabetic 9- to 10-wk-old mice transgenic for hIAPP with most changes being pro-survival adaptations and therefore of limited therapeutic guidance. Here, we investigated islets from hIAPP transgenic mice at an earlier age (6 wk) to screen for potential mediators of hIAPP toxicity that precede predominance of pro-survival signaling. We identified early suppression of cholesterol synthesis and trafficking along with aberrant intra-β-cell cholesterol and lipid deposits and impaired cholesterol trafficking to cell membranes. These findings align with comparable lipid deposits present in β-cells in T2D and increased vulnerability to develop T2D in individuals taking medications that suppress cholesterol synthesis.NEW & NOTEWORTHY β-Cell failure in type 2 diabetes (T2D) is characterized by β-cell misfolded protein stress due to the formation of toxic oligomers of islet amyloid polypeptide (IAPP). Most transcriptional changes in islets in T2D are pro-survival adaptations consistent with the slow progression of β-cell loss. In the present study, investigation of the islet transcriptional signatures in a mouse model of T2D expressing human IAPP revealed decreased cholesterol synthesis and trafficking as a plausible early mediator of IAPP toxicity.
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Affiliation(s)
- Tatyana Gurlo
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
| | - Ruoshui Liu
- Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California, United States
| | - Zhongying Wang
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
| | - Jonathan Hoang
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
| | - Sergey Ryazantsev
- Electron Imaging Center, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, California, United States
| | - Marie Daval
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
| | - Alexandra E Butler
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
| | - Xia Yang
- Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California, United States
- Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, California, United States
| | - Montgomery Blencowe
- Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California, United States
- Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, California, United States
| | - Peter C Butler
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
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Moon JH, Choe HJ, Lim S. Pancreatic beta-cell mass and function and therapeutic implications of using antidiabetic medications in type 2 diabetes. J Diabetes Investig 2024; 15:669-683. [PMID: 38676410 PMCID: PMC11143426 DOI: 10.1111/jdi.14221] [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: 01/21/2024] [Revised: 03/23/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Nowadays, the focus of diabetes treatment has switched from lowering the glucose level to preserving glycemic homeostasis and slowing the disease progression. The main pathophysiology of both type 1 diabetes and long-standing type 2 diabetes is pancreatic β-cell mass loss and dysfunction. According to recent research, human pancreatic β-cells possess the ability to proliferate in response to elevated insulin demands. It has been demonstrated that in insulin-resistant conditions in humans, such as obesity or pregnancy, the β-cell mass increases. This ability could be helpful in developing novel treatment approaches to restore a functional β-cell mass. Treatment strategies aimed at boosting β-cell function and mass may be a useful tool for managing diabetes mellitus and stopping its progression. This review outlines the processes of β-cell failure and detail the many β-cell abnormalities that manifest in people with diabetes mellitus. We also go over standard techniques for determining the mass and function of β-cells. Lastly, we provide the therapeutic implications of utilizing antidiabetic drugs in controlling the mass and function of pancreatic β-cells.
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Affiliation(s)
- Joon Ho Moon
- Department of Internal MedicineSeoul National University College of MedicineSeongnamSouth Korea
- Department of Internal MedicineSeoul National University Bundang HospitalSeongnamSouth Korea
| | - Hun Jee Choe
- Department of Internal MedicineHallym University Dongtan Sacred Heart HospitalHwaseongSouth Korea
| | - Soo Lim
- Department of Internal MedicineSeoul National University College of MedicineSeongnamSouth Korea
- Department of Internal MedicineSeoul National University Bundang HospitalSeongnamSouth Korea
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Razavi SM, Arab ZN, Niknejad A, Hosseini Y, Fouladi A, Khales SD, Shahali M, Momtaz S, Butler AE, Sukhorukov VN, Jamialahmadi T, Abdolghaffari AH, Sahebkar A. Therapeutic effects of anti-diabetic drugs on traumatic brain injury. Diabetes Metab Syndr 2024; 18:102949. [PMID: 38308863 DOI: 10.1016/j.dsx.2024.102949] [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: 08/21/2023] [Revised: 01/15/2024] [Accepted: 01/16/2024] [Indexed: 02/05/2024]
Abstract
AIMS In this narrative review, we have analyzed and synthesized current studies relating to the effects of anti-diabetic drugs on traumatic brain injury (TBI) complications. METHODS Eligible studies were collected from Scopus, Google Scholar, PubMed, and Cochrane Library for clinical, in-vivo, and in-vitro studies published on the impact of anti-diabetic drugs on TBI. RESULTS Traumatic brain injury (TBI) is a serious brain disease that is caused by any type of trauma. The pathophysiology of TBI is not yet fully understood, though physical injury and inflammatory events have been implicated in TBI progression. Several signaling pathways are known to play pivotal roles in TBI injuries, including Nuclear factor erythroid 2-related factor 2 (Nrf2), High mobility group box 1 protein/Nuclear factor kappa B (HMGB1/NF-κB), Adiponectin, Mammalian Target of Rapamycin (mTOR), Toll-Like Receptor (TLR), Wnt/β-catenin, Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Nod-like receptor protein3 (NLRP3) inflammasome, Phosphoglycerate kinase 1/Kelch-like ECH-associated protein 1 (PGK1/KEAP1)/Nrf2, and Mitogen-activated protein kinase (MAPK) . Recent studies suggest that oral anti-diabetic drugs such as biguanides, thiazolidinediones (TZDs), sulfonylureas (SUs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPPIs), meglitinides, and alpha-glucosidase inhibitors (AGIs) could have beneficial effects in the management of TBI complications. These drugs may downregulate the inflammatory pathways and induce antioxidant signaling pathways, thus alleviating complications of TBI. CONCLUSION Based on this comprehensive literature review, antidiabetic medications might be considered in the TBI treatment protocol. However, evidence from clinical trials in patients with TBI is still warranted.
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Affiliation(s)
- Seyed Mehrad Razavi
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Zahra Najafi Arab
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Amirhossein Niknejad
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Yasamin Hosseini
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Abtin Fouladi
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saba Darban Khales
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mostafa Shahali
- School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeideh Momtaz
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran; Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Alexandra E Butler
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Vasily N Sukhorukov
- Institute of General Pathology and Pathophysiology, Moscow, Russia; Institute of Experimental Cardiology Named after Academician V.N. Smirnov, Federal State Budgetary Institution National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Moscow, Russia
| | - Tannaz Jamialahmadi
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Hossein Abdolghaffari
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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11
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Van JAD, Luo Y, Danska JS, Dai F, Alexeeff SE, Gunderson EP, Rost H, Wheeler MB. Postpartum defects in inflammatory response after gestational diabetes precede progression to type 2 diabetes: a nested case-control study within the SWIFT study. Metabolism 2023; 149:155695. [PMID: 37802200 DOI: 10.1016/j.metabol.2023.155695] [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: 05/03/2023] [Revised: 09/27/2023] [Accepted: 09/30/2023] [Indexed: 10/08/2023]
Abstract
BACKGROUND Gestational diabetes (GDM) is a distinctive form of diabetes that first presents in pregnancy. While most women return to normoglycemia after delivery, they are nearly ten times more likely to develop type 2 diabetes than women with uncomplicated pregnancies. Current prevention strategies remain limited due to our incomplete understanding of the early underpinnings of progression. AIM To comprehensively characterize the postpartum profiles of women shortly after a GDM pregnancy and identify key mechanisms responsible for the progression to overt type 2 diabetes using multi-dimensional approaches. METHODS We conducted a nested case-control study of 200 women from the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT) to examine biochemical, proteomic, metabolomic, and lipidomic profiles at 6-9 weeks postpartum (baseline) after a GDM pregnancy. At baseline and annually up to two years, SWIFT administered research 2-hour 75-gram oral glucose tolerance tests. Women who developed incident type 2 diabetes within four years of delivery (incident case group, n = 100) were pair-matched by age, race, and pre-pregnancy body mass index to those who remained free of diabetes for at least 8 years (control group, n = 100). Correlation analyses were used to assess and integrate relationships across profiling platforms. RESULTS At baseline, all 200 women were free of diabetes. The case group was more likely to present with dysglycemia (e.g., impaired fasting glucose levels, glucose tolerance, or both). We also detected differences between groups across all omic platforms. Notably, protein profiles revealed an underlying inflammatory response with perturbations in protease inhibitors, coagulation components, extracellular matrix components, and lipoproteins, whereas metabolite and lipid profiles implicated disturbances in amino acids and triglycerides at individual and class levels with future progression. We identified significant correlations between profile features and fasting plasma insulin levels, but not with fasting glucose levels. Additionally, specific cross-omic relationships, particularly among proteins and lipids, were accentuated or activated in the case group but not the control group. CONCLUSIONS Overall, we applied orthogonal, complementary profiling techniques to uncover an inflammatory response linked to elevated triglyceride levels shortly after a GDM pregnancy, which is more pronounced in women who progress to overt diabetes.
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Affiliation(s)
- Julie A D Van
- Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Metabolism Research Group, Division of Advanced Diagnostics, Toronto General Research Institute, Toronto, Ontario, Canada.
| | - Yihan Luo
- Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Metabolism Research Group, Division of Advanced Diagnostics, Toronto General Research Institute, Toronto, Ontario, Canada
| | - Jayne S Danska
- Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
| | - Feihan Dai
- Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Stacey E Alexeeff
- Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America
| | - Erica P Gunderson
- Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, United States of America
| | - Hannes Rost
- Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
| | - Michael B Wheeler
- Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Metabolism Research Group, Division of Advanced Diagnostics, Toronto General Research Institute, Toronto, Ontario, Canada.
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12
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Bell DSH, Jerkins T. In praise of pioglitazone: An economically efficacious therapy for type 2 diabetes and other manifestations of the metabolic syndrome. Diabetes Obes Metab 2023; 25:3093-3102. [PMID: 37534526 DOI: 10.1111/dom.15222] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/26/2023] [Accepted: 07/06/2023] [Indexed: 08/04/2023]
Abstract
Pioglitazone improves glycaemic control, not only by lowering insulin resistance, but also by improving beta cell function. Because of the improved beta cell function the glycaemic control that occurs with pioglitazone is prolonged. Pioglitazone has positive effects not only on cardiac risk factors and surrogate measures of cardiovascular disease, it also lowers the incidence of cardiac events in patients with diabetes. The recurrence of transient ischaemic attack and ischaemic stroke is also reduced in non-diabetic, insulin-resistant subjects. Utilized at preclinical stages (but not later) of heart failure, pioglitazone improves diastolic function and avoids progression to heart failure. Pioglitazone, through suppression of atrial remodelling, also decreases the incidence of atrial fibrillation. The manifestations of diseases associated with insulin resistance (non-alcoholic steatohepatitis and polycystic ovary disease) are also improved with pioglitazone. Pioglitazone may possibly improve psoriasis and other dermopathies. Pioglitazone is therefore an inexpensive and efficacious drug for the insulin-resistant subject with diabetes that is underutilized because of biases that have evolved from the toxicities of other thiazolidinediones.
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Affiliation(s)
- David S H Bell
- Department of Endocrinology, Southside Endocrinology, Irondale, Alabama, USA
| | - Terri Jerkins
- Department of Endocrinology, Lipscomb University, Nashville, Tennessee, USA
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13
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Lowe WL. Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes. Int J Mol Sci 2023; 24:6047. [PMID: 37047019 PMCID: PMC10094577 DOI: 10.3390/ijms24076047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/19/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Gestational diabetes (GDM) is one of the most common complications of pregnancy, affecting as many as one in six pregnancies. It is associated with both short- and long-term adverse outcomes for the mother and fetus and has important implications for the life course of affected women. Advances in genetics and epigenetics have not only provided new insight into the pathophysiology of GDM but have also provided new approaches to identify women at high risk for progression to postpartum cardiometabolic disease. GDM and type 2 diabetes share similarities in their pathophysiology, suggesting that they also share similarities in their genetic architecture. Candidate gene and genome-wide association studies have identified susceptibility genes that are shared between GDM and type 2 diabetes. Despite these similarities, a much greater effect size for MTNR1B in GDM compared to type 2 diabetes and association of HKDC1, which encodes a hexokinase, with GDM but not type 2 diabetes suggest some differences in the genetic architecture of GDM. Genetic risk scores have shown some efficacy in identifying women with a history of GDM who will progress to type 2 diabetes. The association of epigenetic changes, including DNA methylation and circulating microRNAs, with GDM has also been examined. Targeted and epigenome-wide approaches have been used to identify DNA methylation in circulating blood cells collected during early, mid-, and late pregnancy that is associated with GDM. DNA methylation in early pregnancy had some ability to identify women who progressed to GDM, while DNA methylation in blood collected at 26-30 weeks gestation improved upon the ability of clinical factors alone to identify women at risk for progression to abnormal glucose tolerance post-partum. Finally, circulating microRNAs and long non-coding RNAs that are present in early or mid-pregnancy and associated with GDM have been identified. MicroRNAs have also proven efficacious in predicting both the development of GDM as well as its long-term cardiometabolic complications. Studies performed to date have demonstrated the potential for genetic and epigenetic technologies to impact clinical care, although much remains to be done.
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Affiliation(s)
- William L Lowe
- Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Rubloff 12, 420 E. Superior Street, Chicago, IL 60611, USA
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14
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Majety P, Lozada Orquera FA, Edem D, Hamdy O. Pharmacological approaches to the prevention of type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1118848. [PMID: 36967777 PMCID: PMC10033948 DOI: 10.3389/fendo.2023.1118848] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/13/2023] [Indexed: 03/11/2023] Open
Abstract
About 1 in 10 adults worldwide are estimated to have diabetes mellitus. They are at risk of developing life-threatening complications resulting in reduced quality of life, increased mortality and higher healthcare costs. The ability to prevent or delay type 2 diabetes mellitus (T2DM) by modifying some of its risk factors has been hypothesized for decades. The long and often gradual time-course of increasing dysglycemia prior to diabetes diagnosis suggests that interventions during that period could be effective in preventing T2DM. In addition to lifestyle modifications, certain drugs prevent or slow development of hyperglycemia. Recently, drugs used for obesity management were shown to prevent T2DM. In this review, we discuss various pharmacotherapeutic options for preventing T2DM.
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Affiliation(s)
- Priyanka Majety
- Division of Endocrinology, Diabetes and Metabolism, Virginia Commonwealth University Health System, Richmond, VA, United States
| | | | - Dinesh Edem
- Division of Endocrinology, Diabetes and Metabolism, University of Arkansas Medical Center, Little Rock, AR, United States
| | - Osama Hamdy
- Joslin Diabetes Center, Harvard Medical School, Boston, MA, United States
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15
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Xiang AH. Diabetes in Pregnancy for Mothers and Offspring: Reflection on 30 Years of Clinical and Translational Research: The 2022 Norbert Freinkel Award Lecture. Diabetes Care 2023; 46:482-489. [PMID: 37594959 PMCID: PMC10020015 DOI: 10.2337/dci22-0055] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 12/02/2022] [Indexed: 02/24/2023]
Abstract
Hyperglycemia during pregnancy is a double-edged sword, affecting both mothers and their offspring and creating a vicious cycle that can affect multiple generations. Research in this field over the past 30 years has greatly improved our understanding of this disease and formed the basis of improved strategies to improve the health of mothers and their babies. Despite this progress, gestational and preexisting diabetes continue to have significant effects on both short- and long-term health of mothers and their offspring. In this article, I provide an overview of the work that my colleagues and I have done to advance the knowledge base around diabetes and pregnancy in four areas: 1) diabetes risk after gestational diabetes mellitus (GDM), including racial and ethnic disparities; 2) the pathophysiology of GDM and subsequent diabetes in Hispanic women; 3) diabetes prevention and β-cell preservation following GDM; and 4) evidence for multiple potential developmental effects in offspring that vary according to the timing of exposure and severity of maternal diabetes during pregnancy. This research continues the legacy of Norbert Freinkel and the concepts that he contributed to the field of diabetes and pregnancy. With the epidemic of obesity, increasing rates of type 1 and type 2 diabetes in youth, and rising prevalence of GDM across all racial and ethnic groups, we have a lot more work to do to combat this disease to break the vicious cycle.
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Affiliation(s)
- Anny H. Xiang
- Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA
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16
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Adam S, McIntyre HD, Tsoi KY, Kapur A, Ma RC, Dias S, Okong P, Hod M, Poon LC, Smith GN, Bergman L, Algurjia E, O'Brien P, Medina VP, Maxwell CV, Regan L, Rosser ML, Jacobsson B, Hanson MA, O'Reilly SL, McAuliffe FM. Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice. Int J Gynaecol Obstet 2023; 160 Suppl 1:56-67. [PMID: 36635082 PMCID: PMC10107137 DOI: 10.1002/ijgo.14537] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Gestational diabetes (GDM) impacts approximately 17 million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.
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Affiliation(s)
- Sumaiya Adam
- Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.,Diabetes Research Centre, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Harold David McIntyre
- Mater Health, University of Queensland, Mater Health Campus, South Brisbane, Queensland, Australia
| | - Kit Ying Tsoi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | | | - Ronald C Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China
| | - Stephanie Dias
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Cape Town, South Africa
| | - Pius Okong
- Department of Obstetrics and Gynecology, St Francis Hospital Nsambya, Kampala City, Uganda
| | - Moshe Hod
- Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Liona C Poon
- Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Graeme N Smith
- Department of Obstetrics and Gynecology, Kingston Health Sciences Centre, Queen's University, Kingston, Ontario, Canada
| | - Lina Bergman
- Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa.,Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Esraa Algurjia
- The World Association of Trainees in Obstetrics and Gynecology (WATOG), Paris, France.,Elwya Maternity Hospital, Baghdad, Iraq
| | - Patrick O'Brien
- Institute for Women's Health, University College London, London, UK
| | - Virna P Medina
- Department of Obstetrics and Gynecology, Faculty of Health, Universidad del Valle, Clínica Imbanaco Quirón Salud, Universidad Libre, Cali, Colombia
| | - Cynthia V Maxwell
- Maternal Fetal Medicine, Sinai Health and Women's College Hospital University of Toronto, Ontario, Canada
| | | | - Mary L Rosser
- Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, New York, USA
| | - Bo Jacobsson
- Department of Obstetrics and Gynecology, Sahlgrenska University Hospital/Ostra, Gothenburg, Sweden.,Department of Genetics and Bioinformatics, Domain of Health Data and Digitalisation, Institute of Public Health, Oslo, Norway
| | - Mark A Hanson
- Institute of Developmental Sciences, University Hospital Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK
| | - Sharleen L O'Reilly
- UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland.,School of Agriculture and Food Science, University College Dublin, Dublin, Ireland
| | - Fionnuala M McAuliffe
- UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
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17
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Kim BY, Kwon HS, Kim SK, Noh JH, Park CY, Park HK, Song KH, Won JC, Yu JM, Lee MY, Lee JH, Lim S, Chun SW, Jeong IK, Chung CH, Han SJ, Kim HS, Min JY, Kim S. A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus. Diabetes Metab J 2022; 46:855-865. [PMID: 35255547 PMCID: PMC9723193 DOI: 10.4093/dmj.2021.0264] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 12/07/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. METHODS In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. RESULTS Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42. CONCLUSION Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.
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Affiliation(s)
- Bo-Yeon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon,
Korea
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Suk Kyeong Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University School of Medicine, Seoul,
Korea
| | - Jung-Hyun Noh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, College of Medicine, Inje University, Goyang,
Korea
| | - Cheol-Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Hyeong-Kyu Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul,
Korea
| | - Kee-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University School of Medicine, Seoul,
Korea
| | - Jong Chul Won
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Sanggye Paik Hospital, College of Medicine, Inje University, Seoul,
Korea
| | - Jae Myung Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul,
Korea
| | - Mi Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju,
Korea
| | - Jae Hyuk Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang,
Korea
| | - Soo Lim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam,
Korea
| | - Sung Wan Chun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - In-Kyung Jeong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul,
Korea
| | - Choon Hee Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju,
Korea
| | - Seung Jin Han
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon,
Korea
| | - Hee-Seok Kim
- Department of Drug Safety Research, Chong Kun Dang Pharmaceutical Corporation, Seoul,
Korea
| | - Ju-Young Min
- Department of Drug Safety Research, Chong Kun Dang Pharmaceutical Corporation, Seoul,
Korea
| | - Sungrae Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul,
Korea
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18
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Giglio RV, Papanas N, Rizvi AA, Ciaccio M, Patti AM, Ilias I, Pantea Stoian A, Sahebkar A, Janez A, Rizzo M. An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1475. [PMID: 36295635 PMCID: PMC9609741 DOI: 10.3390/medicina58101475] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/09/2022] [Accepted: 10/14/2022] [Indexed: 11/06/2022]
Abstract
Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists ("glitazones") are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that point to their usefulness. The use of glitazones has always been controversial both for the type of patients who must take these drugs and for the side effects associated with them. Unfortunately, the recent guidelines do not include them among the preferred drugs for the treatment of hyperglycemia and rosiglitazone is out of the market in many countries due to an adverse cardiovascular risk profile. Even though real-life studies have proven otherwise, and their pleiotropic effects have been highlighted, they have been unable to achieve primacy in the choice of antihyperglycemic drugs. It would be appropriate to demonstrate the usefulness of pioglitazone and its therapeutic benefit with further cardiovascular safety studies.
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Affiliation(s)
- Rosaria Vincenza Giglio
- Department of Biomedicine, Neuroscience, and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital “Paolo Giaccone”, 90127 Palermo, Italy
| | - Nikolaos Papanas
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, 68132 Alexandroupoli, Greece
| | - Ali Abbas Rizvi
- Department of Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USA
| | - Marcello Ciaccio
- Department of Biomedicine, Neuroscience, and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
- Department of Laboratory Medicine, University Hospital “Paolo Giaccone”, 90127 Palermo, Italy
| | - Angelo Maria Patti
- Promise Department, School of Medicine, University of Palermo, 90133 Palermo, Italy
| | - Ioannis Ilias
- Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou Hospital, 11521 Athens, Greece
| | - Anca Pantea Stoian
- Faculty of Medicine, Diabetes, Nutrition and Metabolic Diseases, Carol Davila University, 050474 Bucharest, Romania
| | - Amirhossein Sahebkar
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 1696700, Iran
| | - Andrej Janez
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Manfredi Rizzo
- Promise Department, School of Medicine, University of Palermo, 90133 Palermo, Italy
- Faculty of Medicine, Diabetes, Nutrition and Metabolic Diseases, Carol Davila University, 050474 Bucharest, Romania
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19
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Abdul-Ghani T, Puckett C, Migahid O, Abdelgani S, Migahed A, Adams J, Triplitt C, DeFronzo R, Jayyousi A, Abdul-Ghani M. Type 2 diabetes subgroups and response to glucose-lowering therapy: Results from the EDICT and Qatar studies. Diabetes Obes Metab 2022; 24:1810-1818. [PMID: 35581905 DOI: 10.1111/dom.14767] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/20/2022] [Accepted: 05/08/2022] [Indexed: 11/29/2022]
Abstract
AIM To examine the efficacy of glucose-lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose-lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years. RESULTS Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta-cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance. CONCLUSION Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose-lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta-cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.
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Affiliation(s)
- Tamam Abdul-Ghani
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - Curtiss Puckett
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | | | - Siham Abdelgani
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | | | - John Adams
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - Curtis Triplitt
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - Ralph DeFronzo
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | | | - Muhammad Abdul-Ghani
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
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20
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Li LJ, Huang L, Tobias DK, Zhang C. Gestational Diabetes Mellitus Among Asians - A Systematic Review From a Population Health Perspective. Front Endocrinol (Lausanne) 2022; 13:840331. [PMID: 35784581 PMCID: PMC9245567 DOI: 10.3389/fendo.2022.840331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 04/11/2022] [Indexed: 11/23/2022] Open
Abstract
Objective Since Asians are particularly vulnerable to the risk of gestational diabetes mellitus (GDM), the lifecourse health implications of which are far beyond pregnancy, we aimed to summarize the literature to understand the research gaps on current GDM research among Asians. Methods We systematically searched the articles in PubMed, Web of Science, Embase, and Scopus by 30 June 2021 with keywords applied on three topics, namely "GDM prevalence in Asians", "GDM and maternal health outcomes in Asians", and "GDM and offspring health outcomes in Asians". Results We observed that Asian women (natives and immigrants) are at the highest risk of developing GDM and subsequent progression to type 2 diabetes among all populations. Children born to GDM-complicated pregnancies had a higher risk of macrosomia and congenital anomalies (i.e. heart, kidney and urinary tract) at birth and greater adiposity later in life. Conclusion This review summarized various determinants underlying the conversion between GDM and long-term health outcomes in Asian women, and it might shed light on efforts to prevent GDM and improve the lifecourse health in Asians from a public health perspective. Systematic Review Registration Prospero, CRD42021286075.
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Affiliation(s)
- Ling-Jun Li
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Lihua Huang
- Department of Medical Statistics and Epidemiology, Sun Yat-sen University, Guangzhou, China
| | - Deirdre K. Tobias
- School of Public Health, Harvard University, Boston, MA, United States
| | - Cuilin Zhang
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH), Bethesda, MD, United States
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21
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Fu J, Retnakaran R. The life course perspective of gestational diabetes: An opportunity for the prevention of diabetes and heart disease in women. EClinicalMedicine 2022; 45:101294. [PMID: 35198924 PMCID: PMC8850315 DOI: 10.1016/j.eclinm.2022.101294] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/10/2022] [Accepted: 01/20/2022] [Indexed: 02/07/2023] Open
Abstract
Gestational diabetes mellitus (GDM), which has traditionally been defined as glucose intolerance of varying severity with first onset in pregnancy, is rising in prevalence with maternal hyperglycemia currently affecting one in every six pregnancies worldwide. Although often perceived as a medical complication of pregnancy, GDM is actually a chronic cardiometabolic disorder that identifies women who have an elevated lifetime risk of ultimately developing type 2 diabetes and cardiovascular disease. In identifying high-risk women early in the natural history of these conditions, the diagnosis of GDM raises the tantalizing possibility of early intervention and risk modification. However, before such promise can be realized in practice, a series of clinical challenges/obstacles (reviewed herein) must be overcome. Ultimately, the coupling of this life course perspective of GDM with concerted efforts to overcome these challenges may enable fulfilment of this unique opportunity for the primary prevention of diabetes and heart disease in women.
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Affiliation(s)
- Jennifer Fu
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, University of Toronto, 60 Murray Street, Suite L5-025, Mailbox-21, Toronto, Ontario M5T 3L9, Canada
- Division of Endocrinology, University of Toronto, Toronto, Canada
| | - Ravi Retnakaran
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, University of Toronto, 60 Murray Street, Suite L5-025, Mailbox-21, Toronto, Ontario M5T 3L9, Canada
- Division of Endocrinology, University of Toronto, Toronto, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
- Corresponding author at: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, University of Toronto, 60 Murray Street, Suite L5-025, Mailbox-21, Toronto, Ontario M5T 3L9, Canada.
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22
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Montaigne D, Butruille L, Staels B. PPAR control of metabolism and cardiovascular functions. Nat Rev Cardiol 2021; 18:809-823. [PMID: 34127848 DOI: 10.1038/s41569-021-00569-6] [Citation(s) in RCA: 507] [Impact Index Per Article: 126.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/10/2021] [Indexed: 12/22/2022]
Abstract
Peroxisome proliferator-activated receptor-α (PPARα), PPARδ and PPARγ are transcription factors that regulate gene expression following ligand activation. PPARα increases cellular fatty acid uptake, esterification and trafficking, and regulates lipoprotein metabolism genes. PPARδ stimulates lipid and glucose utilization by increasing mitochondrial function and fatty acid desaturation pathways. By contrast, PPARγ promotes fatty acid uptake, triglyceride formation and storage in lipid droplets, thereby increasing insulin sensitivity and glucose metabolism. PPARs also exert antiatherogenic and anti-inflammatory effects on the vascular wall and immune cells. Clinically, PPARγ activation by glitazones and PPARα activation by fibrates reduce insulin resistance and dyslipidaemia, respectively. PPARs are also physiological master switches in the heart, steering cardiac energy metabolism in cardiomyocytes, thereby affecting pathological heart failure and diabetic cardiomyopathy. Novel PPAR agonists in clinical development are providing new opportunities in the management of metabolic and cardiovascular diseases.
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Affiliation(s)
- David Montaigne
- University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - Laura Butruille
- University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - Bart Staels
- University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.
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23
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Abdul-Ghani M, DeFronzo RA. Personalized approach for type 2 diabetes pharmacotherapy: where are we and where do we need to be? Expert Opin Pharmacother 2021; 22:2113-2125. [PMID: 34435523 DOI: 10.1080/14656566.2021.1967319] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Cluster analysis has identified distinct groups of type 2 diabetes (T2D) subjects with distinct metabolic characteristics. Thus, personalizing pharmacologic therapy to individual phenotypic and pathophysiologic characteristics has potential to improve metabolic control and reduce risk of microvascular and macrovascular complications. AREAS COVERED The authors review the classification of T2D, genetic markers, pathophysiology and natural history of T2D, the ABCDE approach to therapy, the ADA/EASD stepwise approach to therapy, available antidiabetic agents, and provide a more rational therapeutic approach based upon pathophysiology and cardiovascular and renal outcome trials. EXPERT OPINION Although insulin resistance is the earliest detectable abnormality, overt T2D does not occur in the absence of progressive beta cell failure. Because of the complex etiology of T2D (Ominous Octet), initiation of therapy with combined agents that (i) target both insulin resistance and beta cell dysfunction and (ii) prevent macrovascular, as well as microvascular, complications will be required. The ratio of C-peptide at 120 minutes (OGTT) to baseline C-peptide predicts with high sensitivity who will respond to metformin, the response to glucose-lowering agents and provides a useful tool to guide optimal glucose lowering therapy.
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24
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DI Giuseppe G, Ciccarelli G, Cefalo CM, Cinti F, Moffa S, Improta F, Capece U, Pontecorvi A, Giaccari A, Mezza T. Prediabetes: how pathophysiology drives potential intervention on a subclinical disease with feared clinical consequences. Minerva Endocrinol (Torino) 2021; 46:272-292. [PMID: 34218657 DOI: 10.23736/s2724-6507.21.03405-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder whose rising incidence suggests the epidemic proportions of the disease. Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) - alone or combined - represent two intermediate metabolic condition between Normal Glucose Tolerance (NGT) and overt T2DM. Several studies have demonstrated that insulin resistance and beta-cell impairment can be identified even in normoglycemic prediabetic individuals. Worsening of these two conditions may lead to progression of IGT and/or IFG status to overt diabetes. Starting from these assumptions, it seems logical to suppose that interventions aimed at improving metabolic conditions, even in prediabetes, could represent an effective target to halt transition from IGT/IFG to manifest T2DM. Starting from pathophysiological knowledge, in this review we evaluate two possible interventions (lifestyle modifications and pharmacological agents) eligible as prediabetes therapy since they have been demonstrated to improve insulin resistance and beta-cell impairment. Detecting high-risk people and treating them could represent an effective strategy to slow down progression to overt diabetes, normalize glucose tolerance, and even prevent micro- and macrovascular complications.
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Affiliation(s)
- Gianfranco DI Giuseppe
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gea Ciccarelli
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Chiara M Cefalo
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Cinti
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Simona Moffa
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Flavia Improta
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Umberto Capece
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alfredo Pontecorvi
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Giaccari
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Teresa Mezza
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy - .,Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
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25
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Abdelgani S, Puckett C, Adams J, Triplitt C, DeFronzo RA, Abdul-Ghani M. Insulin secretion is a strong predictor for need of insulin therapy in patients with new-onset diabetes and HbA1c of more than 10%: A post hoc analysis of the EDICT study. Diabetes Obes Metab 2021; 23:1631-1639. [PMID: 33852204 PMCID: PMC8238899 DOI: 10.1111/dom.14383] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 03/08/2021] [Accepted: 03/19/2021] [Indexed: 02/06/2023]
Abstract
AIM To identify predictors of response to glucose-lowering therapy in patients with new-onset diabetes and very high HbA1c (>10%). METHODS The study included EDICT participants with an initial HbA1c of more than 10% (N = 104). All subjects received a 75-g oral glucose tolerance test (OGTT) before initiation of therapy, and then were randomized to receive: (a) initial triple therapy with metformin, pioglitazone and exenatide versus (b) stepwise conventional therapy with metformin followed by glipizide and then glargine insulin to reduce HbA1c to less than 6.5%. Insulin secretion and insulin resistance were calculated with OGTT-derived indices. RESULTS Sixty-one per cent of participants in the conventional therapy group achieved HbA1c of less than 6.5% at 6 months without need of insulin therapy compared with 78% in the triple therapy group (P = NS). Insulin secretion at baseline was the strongest predictor of subjects who did not require insulin therapy; a cut point of CPEP120 /CPEP0 -the ratio between plasma C-peptide concentration at 120 minutes during the OGTT and fasting plasma C-peptide concentration-of more than 1.7 predicted subjects who achieved the treatment target without insulin, irrespective of the fasting plasma glucose (FPG) concentration and whether or not they were started on conventional or triple therapy. Subjects with a CPEP120 /CPEP0 of less than 1.7 plus FPG of 269 mg/dL or less (≤14.9 mmoL/L) also achieved the treatment goal with triple therapy. CONCLUSION Insulin secretion in response to a 75-g OGTT predicts the need for insulin therapy at the time of type 2 diabetes (T2D) diagnosis. A cut point of 1.7 of CPEP120 /CPEP0 provides a useful clinical tool to individualize glucose-lowering therapy in patients with new-onset T2D and HbA1c of more than 10%.
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Affiliation(s)
- Siham Abdelgani
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - Curtiss Puckett
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - John Adams
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - Curtis Triplitt
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - Ralph A DeFronzo
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
| | - Muhammad Abdul-Ghani
- Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas, USA
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26
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Bengtson AM, Ramos SZ, Savitz DA, Werner EF. Risk Factors for Progression From Gestational Diabetes to Postpartum Type 2 Diabetes: A Review. Clin Obstet Gynecol 2021; 64:234-243. [PMID: 33306495 PMCID: PMC7855576 DOI: 10.1097/grf.0000000000000585] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Gestational diabetes mellitus (GDM) complicates 6% to 8% of pregnancies and up to 50% of women with GDM progress to type 2 diabetes mellitus (DM) within 5 years postpartum. Clinicians have little guidance on which women are most at risk for DM progression or when evidence-based prevention strategies should be implemented in a woman's lifecycle. To help address this gap, the authors review identifiable determinants of progression from GDM to DM across the perinatal period, considering prepregnancy, pregnancy, and postpartum periods. The authors categorize evidence by pathways of risk including genetic, metabolic, and behavioral factors that influence progression to DM among women with GDM.
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Affiliation(s)
- Angela M Bengtson
- Department of Epidemiology, Brown University School of Public Health
| | - Sebastian Z Ramos
- Department of Obstetrics and Gynecology, Women & Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - David A Savitz
- Department of Epidemiology, Brown University School of Public Health
- Department of Obstetrics and Gynecology, Women & Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Erika F Werner
- Department of Epidemiology, Brown University School of Public Health
- Department of Obstetrics and Gynecology, Women & Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island
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27
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Egan AM, Enninga EAL, Alrahmani L, Weaver AL, Sarras MP, Ruano R. Recurrent Gestational Diabetes Mellitus: A Narrative Review and Single-Center Experience. J Clin Med 2021; 10:569. [PMID: 33546259 PMCID: PMC7913262 DOI: 10.3390/jcm10040569] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/28/2021] [Accepted: 01/29/2021] [Indexed: 12/16/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is a frequently observed complication of pregnancy and is associated with an elevated risk of adverse maternal and neonatal outcomes. Many women with GDM will go on to have future pregnancies, and these pregnancies may or may not be affected by GDM. We conducted a literature search, and based on data from key studies retrieved during the search, we describe the epidemiology of GDM recurrence. This includes a summary of the observed clinical risk factors of increasing maternal age, weight, ethnicity, and requirement for insulin in the index pregnancy. We then present our data from Mayo Clinic (January 2013-December 2017) which identifies a GDM recurrence rate of 47.6%, and illustrates the relevance of population-based studies to clinical practice. Lastly, we examine the available evidence on strategies to prevent GDM recurrence, and note that more research is needed to evaluate the effect of interventions before, during and after pregnancy.
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Affiliation(s)
- Aoife M. Egan
- Department of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA
| | - Elizabeth Ann L. Enninga
- Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA; (E.A.L.E.); (L.A.); (R.R.)
| | - Layan Alrahmani
- Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA; (E.A.L.E.); (L.A.); (R.R.)
- Department of Obstetrics and Gynecology, Loyola University Medical Center, Maywood, IL 60153, USA
| | - Amy L. Weaver
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA;
| | - Michael P. Sarras
- Department of Cell Biology and Anatomy, Rosalind Franklin University of Medicine and Science, Chicago, IL 60064, USA;
| | - Rodrigo Ruano
- Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA; (E.A.L.E.); (L.A.); (R.R.)
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Abdul-Ghani M, Migahid O, Megahed A, DeFronzo RA, Al-Ozairi E, Jayyousi A. Combination therapy with pioglitazone/exenatide improves beta-cell function and produces superior glycaemic control compared with basal/bolus insulin in poorly controlled type 2 diabetes: A 3-year follow-up of the Qatar study. Diabetes Obes Metab 2020; 22:2287-2294. [PMID: 32729222 DOI: 10.1111/dom.14153] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/15/2020] [Accepted: 07/27/2020] [Indexed: 01/09/2023]
Abstract
AIM To examine the long-term efficacy of thiazolidinedione plus a glucagon-like peptide-1 receptor agonist versus basal-bolus insulin on glycaemic control and beta-cell function in patients with poorly controlled type 2 diabetes (T2D) on metformin plus sulphonylurea. MATERIALS AND METHODS Three hundred and thirty-one patients with poorly controlled T2D were recruited over 3 years and were followed for an additional year. Subjects received a 75 g oral glucose tolerance test (OGTT) at baseline and at study end. After completing the baseline OGTT, subjects were randomized to receive either pioglitazone plus weekly exenatide (combination therapy) or basal/bolus insulin (insulin therapy) to maintain an HbA1c of less than 7.0%. The primary outcome of the study was the difference in HbA1c at study end between the two treatment groups. RESULTS Both therapies caused a robust decrease in HbA1c. However, combination therapy caused a greater decrement (-1.1%, P < .0001) than insulin therapy, and more subjects in the combination therapy group (86%) achieved the American Diabetes Association goal of glycaemic control (HbA1c < 7.0%) than those in the insulin therapy group (44%) (P < .0001). Both therapies improved insulin secretion. However, the improvement in insulin secretion with combination therapy was 2.5-fold greater (P < .001) than with insulin therapy (50%). Insulin therapy caused more weight gain and hypoglycaemia. CONCLUSION Both combination therapy and insulin therapy effectively reduced HbA1c in poorly controlled T2D on multiple oral agents. However, combination therapy produced a greater improvement in insulin secretion and decrease in HbA1c with a lower risk of hypoglycaemia.
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Affiliation(s)
- Muhammad Abdul-Ghani
- Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
- Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Osama Migahid
- Academic Health System, Hamad General Hospital, Doha, Qatar
| | - Ayman Megahed
- Academic Health System, Hamad General Hospital, Doha, Qatar
| | - Ralph A DeFronzo
- Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | | | - Amin Jayyousi
- Academic Health System, Hamad General Hospital, Doha, Qatar
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29
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Daniele G, Tura A, Dardano A, Bertolotto A, Bianchi C, Giusti L, Kurumthodathu JJ, Del Prato S. Effects of treatment with metformin and/or sitagliptin on beta-cell function and insulin resistance in prediabetic women with previous gestational diabetes. Diabetes Obes Metab 2020; 22:648-657. [PMID: 31802616 DOI: 10.1111/dom.13940] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 11/28/2019] [Accepted: 12/03/2019] [Indexed: 12/21/2022]
Abstract
AIM To investigate the effect of sitagliptin (SITA) and metformin (MET) monotherapy as well as in combination (MET+SITA) on beta-cell function and insulin sensitivity in women with recent gestational diabetes (GDM) and impaired glucose regulation (IGR: impaired fasting glucose and/or impaired glucose tolerance). MATERIAL AND METHODS Forty women were randomly assigned to receive SITA (100 mg qd), MET (850 mg bid) or MET+SITA (50 + 850 mg bid) for 16 weeks. A 75 g oral glucose tolerance test (OGTT) and +125 mg/dL hyperglycaemic clamp followed by 5 g i.v. L-arginine were performed at baseline and end of study. The primary outcome of the study was the mean change in arginine-stimulated insulin secretion rate during the hyperglycaemic clamp test from baseline to 16-week therapy. RESULTS At week 16, body mass index declined in all groups (-1.2 ± 0.2 kg/m2 ; P < 0.05). MET+SITA gave a greater increase of first phase(2-10 min) insulin secretion and arginine-stimulated response (720.3 ± 299.0 to 995.5 ± 370.3 pmol/L and 3.2 ± 0.6 to 4.8 ± 1.0 pmoL/min, respectively, both P < 0.05) compared with MET and SITA. Similarly, MET+SITA was more effective in increasing OGTT-based glucose sensitivity (55.7 ± 11.3 to 108 ± 56.2 pmol x min-1 m-2 x mM-1 ; P = 0.04) and insulin-stimulated glucose disposal (M/I: 2.2 ± 0.5 to 4.6 ± 1.3 mg/kg/min÷μIU/min/ml; P = 0.04; Matsuda index [SI]: 3.1 ± 0.4 to 5.7 ± 1.1; P = 0.03) compared with either MET or SITA. Disposition index (ISSI-2) increased with MET+SITA and SITA (both P < 0.05), while no significant change was observed in MET. Among MET+SITA women, 33% reverted to normal glucose tolerance (NGT) compared with 14% with MET and 7% with SITA (P < 0.05). CONCLUSION This study shows that MET+SITA is superior to SITA and MET monotherapy regarding beta-cell function and insulin sensitivity improvement in IGR women with previous GDM, and may offer a potential pharmacologic intervention to reduce the risk of type 2 diabetes in this high-risk population.
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Affiliation(s)
- Giuseppe Daniele
- Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Andrea Tura
- Metabolic Unit, CNR Institute of Neuroscience, Padova, Italy
| | - Angela Dardano
- Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Alessandra Bertolotto
- Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Cristina Bianchi
- Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Laura Giusti
- Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Jancy Joseph Kurumthodathu
- Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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30
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Elkind-Hirsch KE, Shaler D, Harris R. Postpartum treatment with liraglutide in combination with metformin versus metformin monotherapy to improve metabolic status and reduce body weight in overweight/obese women with recent gestational diabetes: A double-blind, randomized, placebo-controlled study. J Diabetes Complications 2020; 34:107548. [PMID: 32046931 DOI: 10.1016/j.jdiacomp.2020.107548] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 01/17/2020] [Accepted: 01/19/2020] [Indexed: 10/25/2022]
Abstract
BACKGROUND Gestational diabetes (GDM) imparts a high risk of developing diabetes postpartum. Insulin resistance appears to be the major contributor. Liraglutide, a glucagon-like peptide-1 analogue, improves peripheral glucose disposal and reduces body weight. We evaluated whether liraglutide in combination with metformin (MET-LIRA) is more effective than metformin monotherapy (MET-P) in improving insulin action and reducing body weight in overweight prior GDM (pGDM) women. METHODS Women (n = 153; body mass index (BMI) ≥25 kg/m2; 18-45 y; GDM within 12 months) with metabolic abnormalities were randomized to MET-LIRA (MET-2000 mg, LIRA 1.8 mg SC QD) or MET-P (MET-2000 mg, Placebo QD). Study visits at baseline, 36-40, 56-60 and 80-84 weeks included body weight (BW), BMI, waist circumference and waist-to-height ratio measures. Oral glucose tolerance tests (OGTTs) were performed to assess glycemia, mean blood glucose (MBG), lipids, and compute insulin sensitivity and secretion measures. FINDINGS Seventy-two (47%) participants completed the study. MET-LIRA therapy was significantly better in improving MBG and insulin sensitivity indices [SIOGTT MET-LIRA from 4.6 (3.2) to 5.9 (2.9) vs. MET-P 5.5 (3.0) to 5.4 (3.2)] and reducing BW and central adiposity [BMI MET-LIRA from 37.2 (8.3) to 33.8 (5.2) vs MET-P 33.8(5.2) to 32.8(6)]. MET-LIRA therapy but not MET-P decreased triglycerides (TRG) and TRG/high density lipoprotein cholesterol (HDL-C) ratios. INTERPRETATION MET-LIRA treatment demonstrated superior efficacy in correcting the metabolic status of pGDM women over 84 weeks of therapy. The addition of liraglutide to metformin therapy resulted in a more dramatic decrease in BW and central adiposity than metformin alone. FUNDATION Supported by an unrestricted investigator initiated grant from Novo Nordisk, Inc. awarded to K.E.H. MEETING PRESENTATION The results from preliminary analyses of this study were presented at 76th meeting of the American Diabetes Association, June 10-14, 2016 New Orleans, LA, and 77th meeting of the American Diabetes Association, June 9-12, 2017San Diego, CA.
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Affiliation(s)
- Karen E Elkind-Hirsch
- Woman's Metabolic Clinic and Research Center, Woman's Hospital, Baton Rouge, LA 70817, USA.
| | - Donna Shaler
- Woman's Metabolic Clinic and Research Center, Woman's Hospital, Baton Rouge, LA 70817, USA
| | - Renee Harris
- Woman's Metabolic Clinic and Research Center, Woman's Hospital, Baton Rouge, LA 70817, USA
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Fernandes G, Matos JE, Jaffe DH, Beyer G, Yang L, Iglay K, Gantz I, Rajpathak S. Factors associated with the discontinuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) after initiation of insulin. Curr Med Res Opin 2020; 36:377-386. [PMID: 31771370 DOI: 10.1080/03007995.2019.1698416] [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: 10/25/2022]
Abstract
Objective: Type 2 diabetes (T2D) is a prevalent health problem. Oral agents, with the exception of metformin, are often discontinued with the initiation of insulin. The objective was to understand the proportion of patients discontinuing dipeptidyl peptidase-4 inhibitors (DPP-4is) and the reasons for the decision to discontinue.Methods: A retrospective study using a health claims database investigated discontinuation of DPP-4i in adult patients on a dual therapy of metformin and DPP-4i who initiated insulin (n = 3391). An online survey administered to 406 physicians in the US examined reasons for discontinuation. Physicians surveyed included endocrinologists (34.5%), general practitioners (32.5%), internal medicine specialists (30.5%), and diabetologists (2.5%), treating a monthly average of 154 patients.Results: Among patients treated with metformin and DPP-4is who were newly prescribed insulin, 33.3 and 57.3% discontinued DPP-4i therapy within 3 and 12 months, respectively. Patients who discontinued DPP-4i therapy had higher out-of-pocket costs and a greater proportion of renal and liver disease. Top 3 responses for discontinuation included adverse events/tolerability issues (58.9%), lack of efficacy/treatment goals not being met (55.4%) and additional cost of DPP-4i with insulin (48.5%). Top 3 responses for continuing DPP-4i included meeting treatment goals (70.7%), using a lower dose of insulin (65.3%) and good tolerability (48.0%). Physician characteristics, such as physician specialty, age, gender and location impacted to some extent the reasons for treatment decisions.Conclusions: A large proportion of patients discontinue DPP-4is in the real world when initiating insulin. The impact of physician characteristics in treatment decisions highlights the need for enhanced physician training and support as new clinical data emerges and therapy options are available.
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Affiliation(s)
| | | | | | | | | | | | - Ira Gantz
- Merck & Co., Inc., Kenilworth, NJ, USA
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Pancer J, Wu N, Mahmoud I, Dasgupta K. Pharmacological intervention for diabetes after pregnancy prevention in women with prior gestational diabetes: A scoping review. Diabetes Res Clin Pract 2020; 160:107998. [PMID: 31911249 DOI: 10.1016/j.diabres.2020.107998] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 12/31/2019] [Indexed: 11/18/2022]
Abstract
Women with previous gestational diabetes mellitus (GDM) are at increased risk of developing diabetes after pregnancy (DAP), especially 5-10 years postpartum. Two well-known diabetes prevention trials demonstrated a significant reduction in DAP incidence using metformin and troglitazone; however, since their publication, several novel classes of anti-hyperglycemic agents have emerged. This review aimed to conduct a systematic literature search for new evidence in support of pharmacotherapy in DAP prevention and to analyze the results based on special considerations for women of reproductive potential. The only studies whose primary outcome was DAP incidence were those examining metformin, the thiazolidinediones troglitazone and pioglitazone, and the dipeptidyl peptidase-4 inhibitor vildagliptin. Metformin was effective in DAP reduction and was well tolerated, but participants were on average 12 years beyond their GDM pregnancy. Troglitazone was also shown to prevent DAP, but was withdrawn from the market due to hepatotoxicity. There was no comparator arm in the pioglitazone study, which limits its interpretability. The vildagliptin study was underpowered. There are ongoing trials with glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, but none with diabetes incidence as a primary outcome. This review highlights the limited evidence base for pharmacological prevention of DAP.
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Affiliation(s)
- Jill Pancer
- Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, Montréal, Québec, Canada; Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada
| | - Nancy Wu
- Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, Montréal, Québec, Canada; Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada
| | - Ibtisam Mahmoud
- Medical Library, McGill University Health Centre, Montréal, Québec, Canada
| | - Kaberi Dasgupta
- Divisions of Internal Medicine, Endocrinology & Metabolism, and Epidemiology, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada; Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, Montréal, Québec, Canada; Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada.
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Wang M, Tan Y, Shi Y, Wang X, Liao Z, Wei P. Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments. Front Endocrinol (Lausanne) 2020; 11:568. [PMID: 32982969 PMCID: PMC7477770 DOI: 10.3389/fendo.2020.00568] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 07/13/2020] [Indexed: 12/11/2022] Open
Abstract
Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging, and general obesity. The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes. Nevertheless, there are two major reasons to cause diabetes: impaired insulin secretion and impaired insulin action. Furthermore, the individual diagnosis of obesity and sarcopenia should be combined to adequately define sarcopenic obesity. Also, the diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms. Healthy diet and physical activity are beneficial to both sarcopenic obesity and diabetes, but there are only recommended drugs for diabetes. This review consolidates and discusses the latest research in pathogenesis, diagnosis, and treatments of diabetes and sarcopenic obesity.
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Affiliation(s)
- Mina Wang
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- Beijing Key Laboratory of Acupuncture Neuromodulation, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Yan Tan
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Yifan Shi
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Xu Wang
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, Stockholm, Sweden
- Zehuan Liao
| | - Peng Wei
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Peng Wei
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Lim S, Ku EJ, Lee SY, Lee JH, Lee JE, Kim KM, Davies MJ. Therapeutic efficacy and safety of initial triple combination of metformin, sitagliptin, and lobeglitazone in drug-naïve patients with type 2 diabetes: initial triple study. BMJ Open Diabetes Res Care 2020; 8:8/1/e000807. [PMID: 31958303 PMCID: PMC7039575 DOI: 10.1136/bmjdrc-2019-000807] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 11/26/2019] [Accepted: 12/15/2019] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE To compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset, drug-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Among drug-naïve patients with 9.0%-12.0% glycated hemoglobin (HbA1c) but no hyperglycemic symptoms, 100 subjects who started triple medications (metformin 1000 mg/day, sitagliptin 100 mg/day, and lobeglitazone 0.5 mg/day) were selected as an initial triple therapy group. Age and body mass index-matched subjects (n=100) who started glimepiride (≥2 mg/day with uptitration) and metformin (≥1000 mg/day with uptitration) were selected as a conventional therapy group. We investigated changes in HbA1c level, dynamic indexes for insulin sensitivity and β-cell function, and hypoglycemia. RESULTS After 12 months of treatment, HbA1c levels decreased significantly in both groups: from 10.7%±1.0% to 6.7%±1.3% in the triple group, and from 10.5%±1.0% to 7.3%±1.2% in the conventional therapy group. At 12 months, achievement of the HbA1c target (<7.0%) was higher in the triple group than in the conventional group (70% vs 52%, p<0.01). Dynamic indexes related to β-cell function and insulin sensitivity improved, and albuminuria reduced significantly only in the triple group. Hypoglycemia was more common in the conventional group. CONCLUSIONS Initial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of β-cell function, and multiple metabolic benefits, implying durable glycemic control. This strategy may be useful for patients presenting with type 2 diabetes and high HbA1c levels.
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Affiliation(s)
- Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Eu Jeong Ku
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea
| | - Seo Young Lee
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, South Korea
| | - Ji Hyun Lee
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine, VHS Hospital, Seoul, South Korea
| | - Jie-Eun Lee
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, South Korea
| | - Kyoung Min Kim
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, UK
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The RISE Consortium. Lack of Durable Improvements in β-Cell Function Following Withdrawal of Pharmacological Interventions in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes. Diabetes Care 2019; 42:1742-1751. [PMID: 31178434 PMCID: PMC6702605 DOI: 10.2337/dc19-0556] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 05/02/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The Restoring Insulin Secretion (RISE) Adult Medication Study compared pharmacological approaches targeted to improve β-cell function in individuals with impaired glucose tolerance (IGT) or treatment-naive type 2 diabetes of <12 months duration. RESEARCH DESIGN AND METHODS A total of 267 adults with IGT (n = 197, 74%) or recently diagnosed type 2 diabetes (n = 70, 26%) were studied. Participants were randomized to receive 12 months of metformin alone, 3 months of insulin glargine with a target fasting glucose <5 mmol/L followed by 9 months of metformin, 12 months of liraglutide combined with metformin, or 12 months of placebo. β-Cell function was assessed using hyperglycemic clamps at baseline, 12 months (on treatment), and 15 months (3 months off treatment). The primary outcome was β-cell function at 15 months compared with baseline. RESULTS All three active treatments produced on-treatment reductions in weight and improvements in HbA1c compared with placebo; the greatest reductions were seen in the liraglutide plus metformin group. At 12 months, glucose-stimulated C-peptide responses improved in the three active treatment groups and were greatest in the liraglutide plus metformin group, but the arginine-stimulated incremental C-peptide response was reduced in the liraglutide plus metformin group. Despite on-treatment benefits, 3 months after treatment withdrawal there were no sustained improvements in β-cell function in any treatment group. CONCLUSIONS In adults with IGT or recently diagnosed type 2 diabetes, interventions that improved β-cell function during active treatment failed to produce persistent benefits after treatment withdrawal. These observations suggest that continued intervention may be required to alter the progressive β-cell dysfunction in IGT or early type 2 diabetes.
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Khan RMM, Chua ZJY, Tan JC, Yang Y, Liao Z, Zhao Y. From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E546. [PMID: 31470636 PMCID: PMC6780236 DOI: 10.3390/medicina55090546] [Citation(s) in RCA: 193] [Impact Index Per Article: 32.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 08/16/2019] [Accepted: 08/23/2019] [Indexed: 12/14/2022]
Abstract
Diabetes, a silent killer, is one of the most widely prevalent conditions of the present time. According to the 2017 International Diabetes Federation (IDF) statistics, the global prevalence of diabetes among the age group of 20-79 years is 8.8%. In addition, 1 in every 2 persons is unaware of the condition. This unawareness and ignorance lead to further complications. Pre-diabetes is the preceding condition of diabetes, and in most of the cases, this ultimately leads to the development of diabetes. Diabetes can be classified into three types, namely type 1 diabetes, type 2 diabetes mellitus (T2DM) and gestational diabetes. The diagnosis of both pre-diabetes and diabetes is based on glucose criteria; the common modalities used are fasting plasma glucose (FPG) test and oral glucose tolerance test (OGTT). A glucometer is commonly used by diabetic patients to measure blood glucose levels with fast and rather accurate measurements. A few of the more advanced and minimally invasive modalities include the glucose-sensing patch, SwEatch, eyeglass biosensor, breath analysis, etc. Despite a considerable amount of data being collected and analyzed regarding diabetes, the actual molecular mechanism of developing type 2 diabetes mellitus (T2DM) is still unknown. Both genetic and epigenetic factors are associated with T2DM. The complications of diabetes can predominantly be classified into two categories: microvascular and macrovascular. Retinopathy, nephropathy, and neuropathy are grouped under microvascular complications, whereas stroke, cardiovascular disease, and peripheral artery disease (PAD) belong to macrovascular complications. Unfortunately, until now, no complete cure for diabetes has been found. However, the treatment of pre-diabetes has shown significant success in preventing the further progression of diabetes. To prevent pre-diabetes from developing into T2DM, lifestyle intervention has been found to be very promising. Various aspects of diabetes, including the aforementioned topics, have been reviewed in this paper.
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Affiliation(s)
- Radia Marium Modhumi Khan
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore
| | - Zoey Jia Yu Chua
- School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
| | - Jia Chi Tan
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
| | - Yingying Yang
- Tongji University School of Medicine, Shanghai 201204, China
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65 Solna, Sweden
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
- Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institutet, Biomedicum, Solnavägen 9, SE-17177 Stockholm, Sweden.
| | - Yan Zhao
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
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Lenz A, Lenz G, Ku HT, Ferreri K, Kandeel F. Islets from human donors with higher but not lower hemoglobin A1c levels respond to gastrin treatment in vitro. PLoS One 2019; 14:e0221456. [PMID: 31430329 PMCID: PMC6701795 DOI: 10.1371/journal.pone.0221456] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 08/08/2019] [Indexed: 12/12/2022] Open
Abstract
Gastrin is a peptide hormone, which in combination with other factors such as TGFα, EGF or GLP-1, is capable of increasing beta cell mass and lowering blood glucose levels in adult diabetic mice. In humans, administration of a bolus of gastrin alone induces insulin secretion suggesting that gastrin may target islet cells. However, whether gastrin alone is sufficient to exert an effect on isolated human islets has been controversial and the mechanism remained poorly understood. Therefore, in this study we started to examine the effects of gastrin alone on cultured adult human islets. Treatment of isolated human islets with gastrin I for 48 h resulted in increased expression of insulin, glucagon and somatostatin transcripts. These increases were significantly correlated with the levels of donor hemoglobin A1c (HbA1c) but not BMI or age. In addition, gastrin treatment resulted in increased expression of PDX1, NKX6.1, NKX2.2, MNX1 and HHEX in islets from donors with HbA1c greater than 42 mmol/mol. The addition of YM022, an antagonist of the gastrin receptor cholecystokinin B receptor (CCKBR), together with gastrin eliminated these effects, verifying that the effects of gastrin are mediated through CCKBR.CCKBR is expressed in somatostatin-expressing delta cells in islets from all donors. However, in the islets from donors with higher HbA1c (greater than 42 mmol/mol [6.0%]), cells triple-positive for CCKBR, somatostatin and insulin were detected, suggesting a de-differentiation or trans-differentiation of endocrine cells. Our results demonstrate a direct effect of gastrin on human islets from prediabetic or diabetic individuals that is mediated through CCKBR+ cells. Further, our data imply that gastrin may be a potential treatment for diabetic patients.
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Affiliation(s)
- Ayelet Lenz
- Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California, United States of America
- * E-mail:
| | - Gal Lenz
- Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Hsun Teresa Ku
- Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Kevin Ferreri
- Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Fouad Kandeel
- Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California, United States of America
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Kwon MJ, Lee YJ, Jung HS, Shin HM, Kim TN, Lee SH, Rhee BD, Kim MK, Park JH. The direct effect of lobeglitazone, a new thiazolidinedione, on pancreatic beta cells: A comparison with other thiazolidinediones. Diabetes Res Clin Pract 2019; 151:209-223. [PMID: 30954516 DOI: 10.1016/j.diabres.2019.04.006] [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: 01/08/2019] [Revised: 03/14/2019] [Accepted: 04/01/2019] [Indexed: 12/11/2022]
Abstract
AIMS The direct effects of thiazolidinediones (TZDs) on pancreatic beta cells have been controversial. The aim of this study was to find out whether a novel TZD, lobeglitazone, has beneficial effects on pancreatic beta cells and db/db mice compared to those of other TZDs. METHODS INS-1 cells were incubated at a high-glucose concentration with various concentrations of troglitazone, rosiglitazone, pioglitazone, and lobeglitazone. Apoptosis and proliferation of beta cells, markers for ER stress and glucose-stimulated insulin secretion (GSIS) were assessed. In addition, C57BL/6 db/db mice were treated with pioglitazone or lobeglitazone for 4 weeks, and metabolic parameters and the configuration of pancreatic islets were also examined. RESULTS Lobeglitazone and other TZDs decreased INS-1 cell apoptosis in high-glucose conditions. Lobeglitazone and other TZDs significantly decreased hyperglycemia-induced increases in ER stress markers and increased GSIS. Metabolic parameters showed greater improvement in db/db mice treated with pioglitazone and lobeglitazone than in control mice. Islet size, cell proliferation, and beta cell mass were increased, and collagen surrounding the islets was decreased in treated mice. CONCLUSIONS Lobeglitazone showed beneficial effects on beta cell survival and function against hyperglycemia. The prosurvival and profunction effects of lobeglitazone were comparable to those of other TZDs.
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Affiliation(s)
- Min Jeong Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea
| | - Yong Jae Lee
- CKD Research Institute, Yongin, Gyeonggi-do, Republic of Korea
| | - Hye Sook Jung
- Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea
| | - Hyun Mi Shin
- Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea
| | - Tae Nyun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea
| | - Soon Hee Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea
| | - Byoung Doo Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea
| | - Mi-Kyung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea.
| | - Jeong Hyun Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea.
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Aguayo-Mazzucato C, Diaque P, Hernandez S, Rosas S, Kostic A, Caballero AE. Understanding the growing epidemic of type 2 diabetes in the Hispanic population living in the United States. Diabetes Metab Res Rev 2019; 35:e3097. [PMID: 30445663 PMCID: PMC6953173 DOI: 10.1002/dmrr.3097] [Citation(s) in RCA: 149] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 11/12/2018] [Accepted: 11/13/2018] [Indexed: 12/15/2022]
Abstract
The prevalence and incidence of type 2 diabetes (T2D) among the Hispanic population in the United States are higher than the national average. This is partly due to sociocultural factors, such as lower income and decreased access to education and health care, as well as a genetic susceptibility to obesity and higher insulin resistance. This review focuses on understanding the Hispanic population living in the United States from a multidisciplinary approach and underlines the importance of cultural, social, and biological factors in determining the increased risk of T2D in this population. An overview of the acute and chronic complications of T2D upon this population is included, which is of paramount importance to understand the toll that diabetes has upon this population, the health system, and society as a whole. Specific interventions directed to the Hispanic populations are needed to prevent and alleviate some of the burdens of T2D. Different prevention strategies based on medications, lifestyle modifications, and educational programmes are discussed herein. Diabetes self-management education (DSME) is a critical element of care of all people with diabetes and is considered necessary to improve patient outcomes. To be more effective, programmes should take into consideration cultural factors that influence the development and progression of diabetes. These interventions aim to enhance long-term effects by reducing the incidence, morbidity, and mortality of T2D in the Hispanic population of the United States.
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Affiliation(s)
| | - Paula Diaque
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Sonia Hernandez
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
- Surgery Department, University of Chicago, Chicago, Illinois, USA
| | - Silvia Rosas
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Aleksandar Kostic
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
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Aoki C, Suzuki K, Kuroda H, Sagara M, Shimizu M, Kasai K, Aso Y. Fixed-dose combination of alogliptin/pioglitazone improves glycemic control in Japanese patients with type 2 diabetes mellitus independent of body mass index. NAGOYA JOURNAL OF MEDICAL SCIENCE 2018; 79:9-16. [PMID: 28303056 PMCID: PMC5346615 DOI: 10.18999/nagjms.79.1.9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
This study investigated the effects of switching from combination therapy with either alogliptin (Alo) or pioglitazone (Pio) to fixed-dose combination therapy (FDCT) with alogliptin and pioglitazone (Alo-Pio FDCT). The usefulness and efficacy of Alo-Pio FDCT were investigated. A total of 50 outpatients with type 2 diabetes mellitus (T2DM) treated with Alo and 47 outpatients with T2DM treated with Pio were switched to Alo-Pio FDCT, and its efficacy and usefulness were evaluated. Significant improvements were observed in hemoglobinA1c (HbA1c), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT) levels after switching to Alo-Pio FDCT for 16 weeks in both groups. Only the group switching from Alo to Alo-Pio FDCT showed significant improvements in high-density lipoprotein cholesterol (HDL) levels and triglyceride levels. In a multivariate logistic regression model of the variation in the change of HbA1c at 16 weeks, ALT and GGT were independent predictors of the change of HbA1c at 16 weeks. In addition, the switch to Alo-Pio FDCT improved glycemic control to a certain degree regardless of BMI. Switching from either Alo or Pio to Alo-PIO FDCT may, unlike monotherapy with a DPP-4 inhibitor, be effective for patients with T2DM regardless of whether they are obese or lean.
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Affiliation(s)
- Chie Aoki
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Shimotugagun, Japan
| | - Kunihiro Suzuki
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Shimotugagun, Japan
| | - Hisamoto Kuroda
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Shimotugagun, Japan; Green Clinic, Shimotugagun, Japan
| | - Masaaki Sagara
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Shimotugagun, Japan
| | - Masanori Shimizu
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Shimotugagun, Japan
| | | | - Yoshimasa Aso
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Shimotugagun, Japan
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Di Cianni G, Lacaria E, Lencioni C, Resi V. Preventing type 2 diabetes and cardiovascular disease in women with gestational diabetes - The evidence and potential strategies. Diabetes Res Clin Pract 2018; 145:184-192. [PMID: 29684619 DOI: 10.1016/j.diabres.2018.04.021] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 04/10/2018] [Indexed: 02/01/2023]
Abstract
Gestational Diabetes Mellitus is a condition strongly related to the development of type 2 diabetes later in life, although the risk and the onset have not been fully identified yet. Although glucose tolerance returns to normal levels after delivery in the majority of women with GDM, this condition represents an early stage in the natural history of T2DM. In addition, women with previous GDM exhibit an increased cardiovascular risk profile and a raised incidence of cardiovascular diseases. Lifestyle changes and pharmacological interventions might be able to reduce the incidence of type 2 diabetes in pGDM women, although results are still not conclusive. Long term continuous programs specifically addressed to women with pGDM should be implemented, with the ambitious target to encourage them to regularly check glucose tolerance, lipid profile and other parameters related to cardiovascular diseases, aimed at improving women's health. In this paper, we review the relationship between type 2 diabetes, cardiovascular diseases and a history of GDM.
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Affiliation(s)
- Graziano Di Cianni
- Diabetes and Metabolic Diseases Unit, Health Local Unit Nord-West Tuscany, Livorno Hospital, Livorno, Italy.
| | - Emilia Lacaria
- Diabetes and Metabolic Diseases Unit, Health Local Unit Nord-West Tuscany, Livorno Hospital, Livorno, Italy
| | - Cristina Lencioni
- Diabetes and Metabolic Diseases Unit, Health Local Unit Nord-West Tuscany, Lucca Hospital, Lucca, Italy
| | - Veronica Resi
- Diabetes Service, Unit of Endocrinology, IRCCS Cà Granda-Ospedale Maggiore Policlinico Foundation and Department of Medical Sciences, University of Milan, Milan, Italy
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Mecacci F, Ottanelli S, Petraglia F. Mothers with HIP - The short term and long-term impact, what is new? Diabetes Res Clin Pract 2018; 145:146-154. [PMID: 29730389 DOI: 10.1016/j.diabres.2018.04.039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Accepted: 04/26/2018] [Indexed: 01/13/2023]
Abstract
Hyperglycemia is one of the most common medical conditions that women encounter during pregnancy and it is due to gestational diabetes (GDM) in the majority of cases (International Diabetes Federation, 2015) [1]. GDM is associated with a higher incidence of maternal morbidity in pregnancy in term of hypertensive disorders/preclampsia and higher rate of cesarean delivery but also with long-term risk of type 2 diabetes and cardiovascular disease. Pregnancy can therefore be considered a stress test; diagnosis of HIP can unmask a preexisting susceptibility and consequently a future risk for type 2 diabetes and can be a useful marker of future cardiovascular risk. Postpartum follow up provides an excellent opportunity to implement healthy lifestyle behaviors to prevent or delay the development of diabetes or cardiovascular disease. The aim of the current review is to focus on short and long term maternal morbidity of HIP.
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Affiliation(s)
- Federico Mecacci
- Department of Health Sciences, University of Florence, Obstetrics and Gynecology, Careggi University Hospital, Florence, Italy
| | - Serena Ottanelli
- Department of Health Sciences, University of Florence, Obstetrics and Gynecology, Careggi University Hospital, Florence, Italy.
| | - Felice Petraglia
- Department of Health Sciences, University of Florence, Obstetrics and Gynecology, Careggi University Hospital, Florence, Italy
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Poon LC, McIntyre HD, Hyett JA, da Fonseca EB, Hod M. The first-trimester of pregnancy - A window of opportunity for prediction and prevention of pregnancy complications and future life. Diabetes Res Clin Pract 2018; 145:20-30. [PMID: 29852233 DOI: 10.1016/j.diabres.2018.05.002] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 05/04/2018] [Indexed: 12/26/2022]
Abstract
The International Federation of Gynecology and Obstetrics (FIGO) has identified non communicable maternal diseases (NCDs) as a new focus area. NCDs and exposures as related to pregnancy complications and later impairment of maternal and offspring health will form the basis for action in the forthcoming years. This paper summarizes recent advances, centered on the use of first-trimester testing, as a window of opportunity to predict and prevent many pregnancy complications; and for potential future prevention of NCDs in mother and offspring. Recent results from a large-scale randomized control trial have provided definitive proof that effective screening for preterm preeclampsia (preterm-PE), requiring delivery before 37 weeks' gestation, can be achieved with a combined test of maternal factors and biomarkers at 11-13 weeks and that aspirin, given to high-risk women, is effective in reducing the risk of preterm-PE and the length of stay in neonatal intensive care unit. This is the first successful example to illustrate that pregnancy complications is predictable and preventable in early pregnancy. Similar prediction and prevention strategies are being developed for hyperglycemia in pregnancy and preterm birth, with the intention for longer lasting interventions leading to significant downstream impact in improving long-term health in both mothers and babies.
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Affiliation(s)
- Liona C Poon
- Chinese University of Hong Kong, Hong Kong Special Administrative Region; King's College, London, England, United Kingdom
| | | | | | | | - Moshe Hod
- Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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Khajebishak Y, Payahoo L, Alivand M, Alipour B. Punicic acid: A potential compound of pomegranate seed oil in Type 2 diabetes mellitus management. J Cell Physiol 2018; 234:2112-2120. [PMID: 30317607 DOI: 10.1002/jcp.27556] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 09/13/2018] [Indexed: 12/15/2022]
Abstract
Diabetes is one of the most prevalent diseases in the worldwide. Type 2 diabetes mellitus (T2DM), the most common form of the disease, has become a serious threat to public health and is a growing burden on global economies. Due to the unexpected adverse effects of antidiabetic medicines, the use of nutraceuticals as a complementary therapy has drawn extensive attention by investigators. In this issue, a novel nutraceutical, Punicic acid (PA)-the main ingredient of pomegranate seed oil (PSO) that has potential therapeutic effects in T2DM-has been investigated. PA is a peroxisome proliferator-activated receptor gamma agonist, and unlike synthetic ligands, such as thiazolidinediones, it has no side effects. PA exerts antidiabetic effects via various mechanisms, such as reducing inflammatory cytokines, modulating glucose homeostasis, and antioxidant properties. In this review, we discussed the potential therapeutic effects of PSO and PA and represented the related mechanisms involved in the management of T2DM.
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Affiliation(s)
- Yaser Khajebishak
- Nutrition Research Center, Drug Applied Research Center, Student Research Committee, Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Laleh Payahoo
- Nutrition Research Center, Drug Applied Research Center, Student Research Committee, Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Nutrition, Maraghe University of Medical Sciences, Maraghe, Iran
| | - Mohammadreza Alivand
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Beitollah Alipour
- Department of Community Nutrition, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
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Zuo Gui Wan Alters Expression of Energy Metabolism Genes and Prevents Cell Death in High-Glucose Loaded Mouse Embryos. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:2409471. [PMID: 30046334 PMCID: PMC6036835 DOI: 10.1155/2018/2409471] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 03/15/2018] [Accepted: 04/03/2018] [Indexed: 11/17/2022]
Abstract
Background Zuo Gui Wan (ZGW) is a classic formula in traditional chinese medicine (TCM). Previous studies have shown that it is beneficial for impaired glucose tolerance (IGT) of adults and the offspring as well. This study aimed to understand the molecular mechanisms of the efficacy of ZGW on IGT. Methods We used high-glucose loaded 2-cell stage mouse embryos as a model and took advantage of single-cell RNA sequencing technology to analyze the transcriptome of the model with or without ZGW. Differential gene expression analysis was performed with DESeq2. Results High glucose can downregulate genes in the ribosome pathway, while ZGW can reverse this inhibition and as a result prevent embryo cell death caused by high glucose. Furthermore, high glucose can affect sugar metabolism and influence mitochondrial function, but ZGW can promote sugar metabolism via the tricarboxylic acid cycle mainly through upregulating the genes in the respiratory chain and oxidative phosphorylation. Conclusions ZGW had a protective effect on embryonic cell death caused by glucose loading. The reversion of inhibition of ribosome pathway and regulation of mitochondrial energy metabolism are main effects of ZGW on high-glucose loaded embryos. This research not only revealed the global gene regulation changes of high glucose affecting 2-cell stage embryos but also provided insight into the potential molecular mechanisms of ZGW on the IGT model.
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46
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Feig DS. Type 2 diabetes after gestational diabetes: Can the progression be prevented? Diabetes Metab Res Rev 2018; 34:e2988. [PMID: 29430798 DOI: 10.1002/dmrr.2988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 01/26/2018] [Indexed: 01/11/2023]
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Abstract
With the rising incidence and prevalence rates of type 2 diabetes globally, it is imperative that diabetes prevention strategies are implemented to stem the flow of new cases. Successful interventions include both lifestyle modification and pharmaceutical agents, and large, multicentre, randomised, controlled studies in different populations have identified the benefits of both. However, translating positive trial outcomes to the real world is particularly challenging, as lifestyle interventions require regular reinforcement from healthcare professionals to be maintained. Pharmaceutical therapies may therefore play an adjunctive role in combination with lifestyle to prevent diabetes. Population-based strategies are also necessary to reduce sedentary behaviour and obesity. Well-established glucose-lowering therapies such as metformin, sulphonylureas, thiazolidinediones and insulin and newer agents such as incretin therapies and sodium glucose co-transporter 2 inhibitors have all been investigated in randomised controlled trials for diabetes prevention with varying success. Non-glucose-lowering therapies such as orlistat and renin angiotensin system blockers can prevent diabetes, whereas statins are associated with slightly increased risk. Diabetes prevention strategies should carefully consider the use of these agents according to individual patient circumstances and phenotypic profile.
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Abstract
This chapter reviews both statistical and physiologic issues related to the pathophysiologic effects of genetic variation in the context of type 2 diabetes. The goal is to review current methodologies used to analyze disease-related quantitative traits for those who do not have extensive quantitative and physiologic background, as an attempt to bridge that gap. We leverage mathematical modeling to illustrate the strengths and weaknesses of different approaches and attempt to reinforce with real data analysis. Topics reviewed include phenotype selection, phenotype specificity, multiple variant analysis via the genetic risk score, and consideration of multiple disease-related phenotypes. Type 2 diabetes is used as the example, not only because of the extensive existing knowledge at the genetic, physiologic, clinical, and epidemiologic levels, but also because type 2 diabetes has been at the forefront of complex disease genetics, with many examples to draw from.
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Affiliation(s)
- Richard M Watanabe
- Departments of Preventive Medicine and Physiology & Biophysics, Keck School of Medicine of USC, 2250 Alcazar Street, CSC-204, Los Angeles, CA, 90089-9073, USA.
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Hannon TS, Kahn SE, Utzschneider KM, Buchanan TA, Nadeau KJ, Zeitler PS, Ehrmann DA, Arslanian SA, Caprio S, Edelstein SL, Savage PJ, Mather KJ. Review of methods for measuring β-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes Obes Metab 2018; 20:14-24. [PMID: 28493515 PMCID: PMC6095472 DOI: 10.1111/dom.13005] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 05/04/2017] [Accepted: 05/06/2017] [Indexed: 01/09/2023]
Abstract
The Restoring Insulin Secretion (RISE) study was initiated to evaluate interventions to slow or reverse the progression of β-cell failure in type 2 diabetes (T2D). To design the RISE study, we undertook an evaluation of methods for measurement of β-cell function and changes in β-cell function in response to interventions. In the present paper, we review approaches for measurement of β-cell function, focusing on methodologic and feasibility considerations. Methodologic considerations included: (1) the utility of each technique for evaluating key aspects of β-cell function (first- and second-phase insulin secretion, maximum insulin secretion, glucose sensitivity, incretin effects) and (2) tactics for incorporating a measurement of insulin sensitivity in order to adjust insulin secretion measures for insulin sensitivity appropriately. Of particular concern were the capacity to measure β-cell function accurately in those with poor function, as is seen in established T2D, and the capacity of each method for demonstrating treatment-induced changes in β-cell function. Feasibility considerations included: staff burden, including time and required methodological expertise; participant burden, including time and number of study visits; and ease of standardizing methods across a multicentre consortium. After this evaluation, we selected a 2-day measurement procedure, combining a 3-hour 75-g oral glucose tolerance test and a 2-stage hyperglycaemic clamp procedure, augmented with arginine.
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Affiliation(s)
- Tamara S Hannon
- Departments of Pediatrics (T. S. H.) and Medicine (K. J. M.), Indiana University School of Medicine, Indianapolis, Indiana
| | - Steven E Kahn
- VA Puget Sound Health Care System and Department of Medicine, University of Washington, Seattle, Washington
| | - Kristina M Utzschneider
- VA Puget Sound Health Care System and Department of Medicine, University of Washington, Seattle, Washington
| | - Thomas A Buchanan
- University of Southern California Keck School of Medicine/Kaiser Permanente Southern California, Department of Medicine, Los Angeles, California
| | - Kristen J Nadeau
- University of Colorado Denver/Children's Hospital Colorado, Department of Pediatrics, Denver, Colorado
| | - Philip S Zeitler
- University of Colorado Denver/Children's Hospital Colorado, Department of Pediatrics, Denver, Colorado
| | | | - Silva A Arslanian
- Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Department of Pediatrics, Pittsburgh, Pennsylvania
| | - Sonia Caprio
- Department of Pediatrics, Yale University, New Haven, Connecticut
| | - Sharon L Edelstein
- George Washington University Biostatistics Center (RISE Coordinating Center), Rockville, Maryland
| | - Peter J Savage
- National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland
| | - Kieren J Mather
- Departments of Pediatrics (T. S. H.) and Medicine (K. J. M.), Indiana University School of Medicine, Indianapolis, Indiana
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Wu Y, Li P, Zhang D, Sun Y. Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway. Exp Ther Med 2017; 15:2120-2127. [PMID: 29434814 DOI: 10.3892/etm.2017.5650] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 02/07/2017] [Indexed: 11/06/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogenism and insulin resistance are the basic characteristics of PCOS. To investigate the combined effect of metformin and pioglitazone on POCS and the potential mechanisms, a rat model of PCOS was established by intramuscular injection of estradiol valerate (EV). The effect of metformin and pioglitazone monotherapy or combination therapy in control rats and PCOS rats was evaluated, involving the testosterone level, follicular development and insulin resistance. The potential mechanism for the therapeutic effect of metformin and pioglitazone on POCS was explored through using three inhibitors of the 5'adenosine monophosphate-activated protein kinase (AMPK)/phosphoinositide-3 kinase (PI3K)/c-Jun N-terminal kinase (JNK) pathway (Compound C, Wortmannin and SP600125). The results showed that EV-induced PCOS rats demonstrated hyperandrogenemia, hyperinsulinemia and follicular dysplasia. Metformin or pioglitazone monotherapy significantly suppressed the high level of testosterone, reduced the raised percentage of cystic follicles and primary follicles, promoted the number of early antral follicles, and markedly decreased the high concentration of fasting insulin and homeostatic model assessment for insulin resistance index in PCOS rats. In addition, metformin and pioglitazone combination therapy demonstrated greater efficacy than its individual components. Furthermore, individual or joint treatment with metformin and pioglitazone affected the phosphorylation level of JNK in PCOS rats. Compound C and Wortmannin eliminated the effect of metformin and pioglitazone combination therapy on improving the follicular growth in PCOS rats, whereas SP600125 treatment enhanced this combination therapy effect. These data suggested that metformin and pioglitazone combination therapy demonstrated great efficacy in ameliorating PCOS through regulating the AMPK/PI3K/JNK pathway.
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Affiliation(s)
- Yuanyuan Wu
- Reproductive Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.,Reproductive Medicine Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Pengfen Li
- Reproductive Medicine Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Dan Zhang
- Reproductive Medicine Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Yingpu Sun
- Reproductive Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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