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Ku KC, Zhong J, Song E, Fong CHY, Lam KSL, Xu A, Lee CH, Cheung CYY. Clinical utility of glycated albumin and 1,5-anhydroglucitol in the screening and prediction of diabetes: A multi-center study. World J Diabetes 2025; 16:102867. [PMID: 40236844 PMCID: PMC11947923 DOI: 10.4239/wjd.v16.i4.102867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/24/2024] [Accepted: 02/12/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Despite being the gold standard, the use of glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) for diagnosing dysglycemia is imperfect. In particular, a low level of agreement between HbA1c and FPG in detecting prediabetes and diabetes has led to difficulties in clinical interpretation. Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) may potentially serve as biomarkers for the detection and prediction of diabetes, as well as glycemic monitoring. AIM To explore the diagnostic performance of GA and 1,5-AG for screening dysglycemia; assess whether they can be used for glycemic monitoring in Chinese morbidly-obese patients; and examine their predictive ability for incident diabetes in a Chinese community-based cohort. METHODS GA and 1,5-AG concentrations were measured in 462 morbidly-obese patients from the Obese Chinese Cohort (OCC). A sub-group of diabetes subjects (n = 24) was prospectively followed-up after bariatric surgery. Differences between baseline and post-surgery biomarker values were converted to percentage change from baseline to assess the response to glycemic control. Predictive ability of the biomarkers was assessed in 132 incident diabetes cases and 132 matched non-diabetes controls in the community-based Cardiovascular Risk Factor Prevalence Study (CRISPS). A prediction model was developed and compared with clinical models based on conventional risk factors. RESULTS GA exhibited an excellent diagnostic value with an area under the receiver operating characteristic curve (AUC) of 0.919 (95%CI: 0.884-0.955) for identifying diabetes and a high agreement in the classification of diabetes with both FPG and HbA1c in the OCC. GA demonstrated the fastest response to glycemic control. In CRISPS, the 'B3A' prediction model, which consisted of body mass index (BMI) and 3 biomarkers (HbA1c, GA and 1,5-AG), achieved a comparable predictive value [AUC (95%CI): 0.793 (0.744-0.843)] to that of a clinical model comprising BMI, HbA1c, FPG and 2-hour glucose (2hG) [AUC (95%CI): 0.783 (0.733-0.834); DeLong P value = 0.736]. The 'B3A' was significantly superior to a clinical model including BMI, HbA1c, FPG and triglycerides [AUC (95%CI): 0.729 (0.673-0.784); DeLong P value = 0.027]. CONCLUSION GA and 1,5-AG have the potential to act as robust biomarkers for the screening and risk prediction of diabetes. FPG and 2hG may be replaced by GA and 1,5-AG in future diabetes predictions.
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Affiliation(s)
- Kam-Ching Ku
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Junda Zhong
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Erfei Song
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Carol Ho-Yi Fong
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Karen Siu-Ling Lam
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Aimin Xu
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Chi-Ho Lee
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
| | - Chloe Yu-Yan Cheung
- Department of Medicine, University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong 999077, China
- Guangdong-Hong Kong Joint Institute of Metabolic Medicine, University of Hong Kong, Hong Kong 999077, China
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Mir MM, Alghamdi M, BinAfif WF, Alharthi MH, Alshahrani AM, Alamri MMS, Alfaifi J, Ameer AYA, Mir R. Emerging biomarkers in type 2 diabetes mellitus. Adv Clin Chem 2025; 126:155-198. [PMID: 40185534 DOI: 10.1016/bs.acc.2025.01.002] [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] [Indexed: 04/07/2025]
Abstract
Diabetes mellitus is a chronic condition caused by high blood glucose resulting from insufficient insulin production or cellular resistance to insulin action or both. It is one of the fastest-growing public health concerns worldwide. Development of long-term nephropathy, retinopathy, neuropathy, and cardiovascular disease are some of the complications commonly associated with poor blood glycemic control. Type 2 diabetes mellitus (T2DM), the most prevalent type of diabetes, accounts for around 95 % of all cases globally. Although middle-aged or older adults are more likely to develop T2DM, its prevalence has grown in children and young people due to increased obesity, sedentary lifestyle and poor nutrition. Furthermore, it is believed that more than 50 % of cases go undiagnosed annually. Routine screening is essential to ensure early detection and reduce risk of life-threatening complications. Herein, we review traditional biomarkers and highlight the ongoing pursuit of novel and efficacious biomarkers driven by the objective of achieving early, precise and prompt diagnoses. It is widely acknowledged that individual biomarkers will inevitably have certain limitations necessitating the need for integrating multiple markers in screening.
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Affiliation(s)
- Mohammad Muzaffar Mir
- Departments of Clinical Biochemistry, College of Medicine, University of Bisha, Bisha, Saudi Arabia.
| | - Mushabab Alghamdi
- Internal Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Waad Fuad BinAfif
- Internal Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Muffarah Hamid Alharthi
- Family and Community Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Abdullah M Alshahrani
- Family and Community Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | | | - Jaber Alfaifi
- Child Health, College of Medicine, University of Bisha, Bisha, Saudi Arabia
| | | | - Rashid Mir
- Prince Fahd Bin Sultan Research Chair, Department of MLT, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
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Agarwal S, Mader JK, Arevalo G, Avula S, Chavez E, Sloan LA, Galindo RJ. Diabetes and Glucose Management in People on Hemodialysis. Diabetes Spectr 2025; 38:7-18. [PMID: 39959530 PMCID: PMC11825408 DOI: 10.2337/dsi24-0015] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/18/2025]
Abstract
Diabetes is a major cause of end-stage kidney disease (ESKD). Glycemic management is challenging in this population, and A1C, commonly used for monitoring glycemic control, is unreliable. Continuous glucose monitoring indices can be used for glycemic monitoring in people with ESKD. Dipeptidyl peptidase 4 inhibitors, incretin mimetic agents (glucagon-like peptide 1 and glucose-dependent insulinotropic peptide receptor agonists), and insulin using an automated insulin delivery system are preferred to manage diabetes in people with ESKD on hemodialysis.
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Affiliation(s)
- Shubham Agarwal
- Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE
| | - Julia K. Mader
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Giuliana Arevalo
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Sreekant Avula
- Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Minnesota, Minneapolis, MN
| | - Efren Chavez
- Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL
| | - Lance A. Sloan
- Department of Clinical Metabolism, Texas Institute for Kidney and Endocrine Disorders, Lufkin, TX
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX
- College of Osteopathic Medicine, Sam Houston State University, Conroe, TX
| | - Rodolfo J. Galindo
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
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Klein KR, Lingvay I, Tuttle KR, Flythe JE. Glycemic Management and Individualized Diabetes Care in Dialysis-Dependent Kidney Failure. Diabetes Care 2025; 48:164-176. [PMID: 39693267 PMCID: PMC11770169 DOI: 10.2337/dci24-0081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 11/22/2024] [Indexed: 12/20/2024]
Abstract
Of the nearly 600,000 people in the U.S. who receive dialysis for chronic kidney failure, >60% have diabetes. People receiving dialysis who have diabetes have worse overall and cardiovascular survival rates than those without diabetes. Diabetes care in the dialysis setting is complicated by kidney failure-related factors that render extrapolation of glycated hemoglobin (HbA1c) targets to the dialysis population unreliable and may change the risk-benefit profiles of glucose-lowering and disease-modifying therapies. No prospective studies have established the optimal glycemic targets in the dialysis population, and few randomized clinical trials of glucose-lowering medications included individuals receiving dialysis. Observational data suggest that both lower and higher HbA1c are associated with mortality in the dialysis population. Existing data suggest the potential for safety and effectiveness of some glucose-lowering medications in the dialysis population, but firm conclusions are hindered by limitations in study design and sample size. While population-specific knowledge gaps about optimal glycemic targets and diabetes medication safety and effectiveness preclude the extension of all general population diabetes guidelines to the dialysis-dependent diabetes population, these uncertainties should not detract from the importance of providing person-centered diabetes care to people receiving dialysis. Diabetes care for individuals with and without dialysis-dependent kidney failure should be holistic, based on individual preferences and prognoses, and tailored to integrate established treatment approaches with proven benefits for glycemic control and cardiovascular risk reduction. Additional research is needed to inform how recent pharmacologic and technological advances can be applied to support such individualized care for people receiving maintenance dialysis.
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Affiliation(s)
- Klara R. Klein
- Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Ildiko Lingvay
- Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
- Peter O’Donnel Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX
| | - Katherine R. Tuttle
- Division of Nephrology, University of Washington School of Medicine, Seattle, WA
- Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA
| | - Jennifer E. Flythe
- Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC
- Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, NC
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Al-Lahham Y, Volanski W, Signorini L, do Prado AL, Valdameri G, Moure VR, Welter M, Alves AC, Sari MHM, Rego FGDM, Picheth G. Reference Interval for Glycated Albumin, 1,5-AG/GA, and GA/HbA1c Ratios and Cut-Off Values for Type 1, Type 2, and Gestational Diabetes: A Cross-Sectional Study. Biomedicines 2024; 12:2651. [PMID: 39767558 PMCID: PMC11673511 DOI: 10.3390/biomedicines12122651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/16/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025] Open
Abstract
Background/Objectives: Glycated albumin (GA) serves as a biomarker for short-term glycemic control (2-3 weeks), playing a role in diabetes management. Our goal was to establish reference intervals (RIs) for serum GA, and the ratios of 1,5-anhydroglucitol to GA (AGI) and GA to HbA1c in a Euro-Brazilian pediatric population (10 y, n = 299), adults (43.5 y; n = 290), and pregnant women (26 y, n = 406; 26.5 ± 3.1 gestation weeks). Methods: Receiver operating characteristic curve analysis was employed to determine RIs for type 1 diabetes (T1D) in children (n = 148) and adults (n = 81), type 2 diabetes (T2D, n = 283), and gestational diabetes mellitus (GDM, n = 177). Results: Both non-pregnant and pregnant women exhibited GA RIs of 10.0-13.3% and 10.6-14.7%, respectively. The AGI ratio varied from 1.2-4.3 in children, 0.9-3.6 in adults, and 0.8-3.1 in pregnant women. Meanwhile, the GA/HbA1c ratio ranged from 1.8-2.6 in children and adults to 2.3-3.6 in pregnant women. GA and AGI ratios accurately differentiated between T1D and T2D, demonstrating high sensitivity (>84%) and specificity (>97%), with AGI showing superior performance (AUC > 0.99). The GA/HbA1c ratio exhibited moderate discriminatory power (AUC > 0.733) but was less effective in distinguishing adult-onset T1D and T2D, suggesting its limited utility in certain groups. Conclusions: The proposed RIs are consistent with those of other Caucasian populations, affirming their relevance for Euro-Brazilian patients. The GA and AGI ratios emerge as valuable diagnostic tools for T1D and T2D, though their reduced sensitivity in diagnosing GDM warrants further investigation. Clinicians might leverage GA and AGI ratios for more tailored diabetes management, especially when HbA1c results are not optimal.
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Affiliation(s)
- Yusra Al-Lahham
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
| | - Waldemar Volanski
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
- Laboratory Division, Curitiba City Hall, Curitiba 80530-908, Brazil
| | - Liana Signorini
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
- Laboratory Division, Curitiba City Hall, Curitiba 80530-908, Brazil
| | - Ademir Luiz do Prado
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
- Federal Institute of Parana, Colombo 83403-515, Brazil
| | - Glaucio Valdameri
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
| | - Vivian Rotuno Moure
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
| | - Marciane Welter
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
| | - Alexessander C. Alves
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK;
| | - Marcel Henrique Marcondes Sari
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
| | - Fabiane Gomes de Moraes Rego
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
| | - Geraldo Picheth
- Graduate Program in Pharmaceutical Sciences, Federal University of Paraná, Curitiba 80210-170, Brazil (W.V.); (L.S.); (G.V.); (V.R.M.); (M.H.M.S.); (F.G.d.M.R.)
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Tang M, Berg AH, Zheng H, Rhee EP, Allegretti AS, Nigwekar SU, Karumanchi SA, Lash JP, Kalim S. Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study. Am J Kidney Dis 2024; 84:329-338. [PMID: 38518919 PMCID: PMC11344690 DOI: 10.1053/j.ajkd.2024.02.006] [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: 12/18/2023] [Revised: 01/24/2024] [Accepted: 02/02/2024] [Indexed: 03/24/2024]
Abstract
RATIONALE & OBJECTIVE Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 3,110 participants with CKD from the Chronic Renal Insufficiency Cohort study. EXPOSURE Baseline GA levels. OUTCOME Incident end-stage kidney disease (ESKD), cardiovascular disease (CVD) events, and all-cause mortality. ANALYTICAL APPROACH Cox proportional hazards regression. RESULTS Participant characteristics included mean age 59.0±10.8 SD years; 1,357 (43.6%) female; and 1,550 (49.8%) with diabetes. The median GA was 18.7% (IQR, 15.8%-23.3%). During an average 7.9-year follow-up, there were 980 ESKD events, 968 CVD events, and 1,084 deaths. Higher GA levels were associated with greater risks of all outcomes, regardless of diabetes status: hazard ratios for ESKD, CVD, and death among participants with the highest quartile compared with quartile 2 (reference) were 1.42 (95% CI, 1.19-1.69), 1.67 (95% CI, 1.39-2.01), and 1.63 (95% CI, 1.37-1.94), respectively. The associations with CVD and death appeared J-shaped, with increased risk also seen at the lowest GA levels. Among patients with coexisting CKD and diabetes, the associations of GA with outcomes remained significant even after adjusting for HbA1c. For each outcome, we observed a significant increase in the fraction of new prognostic information when both GA and HbA1c were added to models. LIMITATIONS Lack of longitudinal GA measurements; and HbA1c measurements were largely unavailable in participants without diabetes. CONCLUSIONS Among patients with CKD, GA levels were independently associated with risks of ESKD, CVD, and mortality, regardless of diabetes status. GA added prognostic value to HbA1c among patients with coexisting CKD and diabetes. PLAIN-LANGUAGE SUMMARY Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. In this cohort study of 3,110 individuals with non-dialysis-dependent CKD, GA levels were independently associated with risks of end-stage kidney disease, cardiovascular disease (CVD), and mortality. The associations with CVD and mortality appeared to be J-shaped. Among patients with coexisting CKD and diabetes, GA added prognostic value to HbA1c. Thus, GA may be a valuable complementary test to HbA1c in patients with CKD.
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Affiliation(s)
- Mengyao Tang
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
| | - Anders H Berg
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Hui Zheng
- Center for Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Eugene P Rhee
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Sagar U Nigwekar
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - S Ananth Karumanchi
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - James P Lash
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Sahir Kalim
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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Suzuki R, Kazumori K, Usui T, Shinohara M. Medical database analysis of the association between kidney function and achievement of glycemic control in older Japanese adults with type 2 diabetes who started with oral antidiabetic drugs. J Diabetes Investig 2024; 15:1057-1067. [PMID: 38634412 PMCID: PMC11292379 DOI: 10.1111/jdi.14214] [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: 07/07/2023] [Revised: 03/12/2024] [Accepted: 03/29/2024] [Indexed: 04/19/2024] Open
Abstract
AIMS/INTRODUCTION Despite the emergence of new drugs with novel mechanisms of action, treatment options for older people and those with chronic kidney disease are still limited. MATERIALS AND METHODS Using a medical database compiled from Diagnostic Procedure Combination hospitals, we retrospectively analyzed treatment status, glycemic control and kidney function over 3 years after the first oral antidiabetic drugs in Japanese adults with type 2 diabetes who were aged ≥65 years. RESULTS Among 5,434 study participants, 3,246 (59.7%) were men, the median age was 72.0 years, the baseline median hemoglobin A1c was 7.1% and the baseline median estimated glomerular filtration rate was 66.6 mL/min/1.73 m2. Treatment was intensified in 40.0% of people during the 3-year observation period, and the median time to the first treatment intensification was 198 days. Insulin was the most commonly used agent for treatment intensification (36.9%, 802/2,175). Hemoglobin A1c of <7.0% was achieved in 3,571 (65.7%) at 360 ± 90 days. Multivariable logistic regression analysis found that baseline age, hemoglobin A1c and estimated glomerular filtration rate were negatively associated with achieving hemoglobin A1c of <7.0% at 360 ± 90 days. CONCLUSIONS In older Japanese adults with type 2 diabetes, those with a lower estimated glomerular filtration rate were more likely to achieve hemoglobin A1c of <7.0%. To safely manage blood glucose levels in older adults with chronic kidney disease, physicians should remain vigilant about the risk of iatrogenic hypoglycemia.
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Affiliation(s)
- Ryo Suzuki
- Department of Diabetes, Metabolism and EndocrinologyTokyo Medical UniversityTokyoJapan
| | | | - Tatsuya Usui
- Medical Science, Sumitomo Pharma Co., Ltd.TokyoJapan
| | - Masahiko Shinohara
- Data Science Division Real‐World Evidence DepartmentINTAGE Healthcare Inc.TokyoJapan
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Kaizu Y, Nagata M, Kaizu S, Qie Y, Kaizu K, Tanaka S, Nakano T, Kitazono T. Association between glycated albumin and sudden death in patients undergoing hemodialysis. Clin Exp Nephrol 2024; 28:656-663. [PMID: 38436900 PMCID: PMC11190002 DOI: 10.1007/s10157-024-02475-w] [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: 12/17/2023] [Accepted: 02/09/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND The frequency of sudden death and its risk factors in patients undergoing hemodialysis are unknown. This study was performed to examine the association between glycated albumin (GA) and sudden death in Japanese patients undergoing hemodialysis. METHODS In total, 260 patients undergoing hemodialysis aged ≥18 years were retrospectively followed for a mean of 4.6 years. The patients' serum GA levels were divided into tertiles, and the patients' sex, age, albumin level, C-reactive protein (CRP) level, and cardiothoracic ratio (CTR) were selected as adjustment factors. A logistic regression model was used to calculate the odds ratio (OR) for the occurrence of sudden death by GA level. RESULTS Ninety-one patients died during follow-up. Of the 91 deaths, 23 (25.2%) were defined as sudden deaths. Compared with non-sudden death cases, sudden death cases were significantly younger (p = 0.002) and had a higher proportion of men (p = 0.03), a higher proportion of diabetes (p = 0.008), and higher GA levels (p = 0.023). Compared with patients with the lowest GA levels (<15.2%), those with the highest GA levels (≥18.5%) had a sex- and age-adjusted OR for sudden death of 5.40 [95% confidence interval (CI): 1.35-21.85]. After adjusting for the albumin level, CRP level, and CTR in addition to sex and age, the OR for sudden death of patients with the highest GA levels increased to 6.80 (95%CI: 1.64-28.08); the relationship did not change. CONCLUSION Serum GA levels were significantly associated with sudden death in patients undergoing hemodialysis.
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Affiliation(s)
| | - Masaharu Nagata
- Shin-Eikai Hospital, 14-11 Benten-Cho, Kokurakita-Ku, Kitakyushu-City, Fukuoka, 803-0856, Japan.
| | | | | | - Kazo Kaizu
- Shinkitakyusyujinzo Clinic, Fukuoka, Japan
| | - Shigeru Tanaka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Chen GY, Chai TQ, Zhang H, Yang FQ. Applications of mild-condition synthesized metal complexes with enzyme-like activity in the colorimetric and fluorescence analysis. Coord Chem Rev 2024; 508:215761. [DOI: 10.1016/j.ccr.2024.215761] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
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10
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Kaminski CY, Galindo RJ, Navarrete JE, Zabala Z, Moazzami B, Gerges A, McCoy RG, Fayfman M, Vellanki P, Idrees T, Peng L, Umpierrez GE. Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes. Diabetes Care 2024; 47:267-271. [PMID: 38085705 PMCID: PMC11148628 DOI: 10.2337/dc23-1276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 11/13/2023] [Indexed: 01/21/2024]
Abstract
OBJECTIVE Patients with diabetes and end-stage kidney disease (ESKD) may experience "burnt-out diabetes," defined as having an HbA1c value <6.5% without antidiabetic therapy for >6 months. We aim to assess glycemic control by continuous glucose monitoring (Dexcom G6 CGM) metrics and glycemic markers in ESKD patients on hemodialysis with burnt-out diabetes. RESEARCH DESIGN AND METHODS In this pilot prospective study, glycemic control was assessed by continuous glucose monitoring (CGM), HbA1c measures, and glycated albumin and fructosamine measurements in patients with burnt-out diabetes (n = 20) and without a history of diabetes (n = 20). RESULTS Patients with burnt-out diabetes had higher CGM-measured daily glucose levels, lower percent time in the range 70-180 mg/dL, higher percent time above range (>250 mg/dL), and longer duration of hyperglycemia >180 mg/dL (hours/day) compared with patients without diabetes (all P < 0.01). HbA1c and fructosamine levels were similar; however, patients with burnt-out diabetes had higher levels of glycated albumin than did patients without diabetes. CONCLUSIONS The use of CGM demonstrated that patients with burnt-out diabetes have significant undiagnosed hyperglycemia. CGM and glycated albumin provide better assessment of glycemic control than do values of HbA1c and fructosamine in patients with ESKD.
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Affiliation(s)
| | - Rodolfo J. Galindo
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Jose E. Navarrete
- Division of Nephrology, Department of Medicine, Emory University, Atlanta, GA
| | - Zohyra Zabala
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Bobak Moazzami
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Amany Gerges
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Rozalina G. McCoy
- Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
- University of Maryland Institute for Health Computing, Bethesda, MD
| | - Maya Fayfman
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Priyathama Vellanki
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Thaer Idrees
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Limin Peng
- Emory University Rollins School of Public Health, Atlanta, GA
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11
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Mukherjee S, Yadav P, Ray SK, Jadhav AA, Wakode SL. Clinical Risk Assessment and Comparison of Bias between Laboratory Methods for Estimation of HbA1c for Glycated Hemoglobin in Hyperglycemic Patients. Curr Diabetes Rev 2024; 20:e261023222764. [PMID: 37921160 DOI: 10.2174/0115733998257140231011102518] [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: 04/24/2023] [Revised: 07/28/2023] [Accepted: 08/25/2023] [Indexed: 11/04/2023]
Abstract
INTRODUCTION Hemoglobin A1c (HbA1c), also known as glycated hemoglobin, is a blood test used to evaluate and track a patient's blood sugar levels over the previous 2-3 months. We have compared the analytical performance of the D10 hemoglobin (HPLC) testing system to that of the immunoturbidimetric technique, which is a light-scattering immunoassay. OBJECTIVES To assess the clinical risk assessment between two methods (Compare the two Immunoturbidometric methods (AU680) vs. HPLC method (D10)) in hyperglycemic patients and assess the acceptability of the respective methods in the Clinical biochemistry laboratory. METHODS The charge of the globins in Hb was used as the basis for the HPLC method used to measure HbA1c. HPLC detects and quantifies even the tiniest Hb fractions and the full spectrum of Hb variants. HbA1c was measured using the immunoturbidimetric (AU 680 Beckmann coulter analyzer) and high-performance liquid chromatography (HPLC) techniques. Experiments also made use of immunoturbidimetric techniques (using an AU 680 Beckmann coulter analyzer equipment). RESULTS There is no statistically significant difference in HbA1c readings between male and female patients, as measured by either the Immunoturbidimetric or HPLC techniques. CONCLUSION The immunoturbidimetric and high-performance liquid chromatography techniques for estimating HbA1c yielded identical results. From the results of this study, we may deduce that both techniques are valid for estimating HbA1c. As a result, it may be suggested that both approaches can be used to estimate HbA1c in diabetic individuals.
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Affiliation(s)
- Sukhes Mukherjee
- Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, 462020, India
| | - Prasant Yadav
- Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, 462020, India
| | - Suman Kumar Ray
- Independent Researcher, Bhopal, Madhya Pradesh, 462020, India
| | - Ashish A Jadhav
- Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, 462020, India
| | - Santosh L Wakode
- Department of Physiology. All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, 462020, India
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12
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Sittiwanichai S, Japrung D, Mori T, Pongprayoon P. Structural and Dynamic Alteration of Glycated Human Serum Albumin in Schiff Base and Amadori Adducts: A Molecular Simulation Study. J Phys Chem B 2023. [PMID: 37267456 DOI: 10.1021/acs.jpcb.3c02048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Human serum albumin (HSA) is a protein carrier in blood transporting metabolites and drugs. Glycated HSA (GHSA) acts as a potential biomarker for diabetes. Thus, many attempts have been made to detect GHSA. Glycation was reported to damage the structure and ligand binding capability, where no molecular detail is available. Recently, the crystal structure of GHSA has been solved, where two glucose isomers (pyranose/GLC and open-chain/GLO) are located at Sudlow's site I. GLO was found to covalently bind to K195, while GLC is trapped by noncontact interactions. GHSA exists in two forms (Schiff base (SCH) and Amadori (AMA) adducts), but how both disrupt albumin activity microscopically remains unknown. To this end, molecular dynamics simulations were performed here to explore the nature of SCH and AMA. Both forms are found to alter the main protein dynamics, resulting in (i) the widening of Sudlow's site I entrance, (ii) the size reduction of nine fatty acid-binding pockets, (iii) the enlargement of Sudlow's site I and the shrinking of Sudlow's site II, (iv) the enhancement of C34 reactivity, and (v) the change in the W214 microenvironment. These unique characteristics found here can be useful for understanding the effect of glycation on the albumin function in more detail and designing specific and selective GHSA detection strategies.
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Affiliation(s)
- Sirin Sittiwanichai
- Faculty of Science, Department of Chemistry, Kasetsart University, Chatuchak, Bangkok 10900, Thailand
| | - Deanpen Japrung
- National Science and Technology Development Agency, National Nanotechnology Center, Thailand Science Park, Pathum Thani 12120, Thailand
| | - Toshifumi Mori
- Intitute for Materials Chemistry and Engineering, Kyushu University, Kasuga, Fukuoka 816-8580, Japan
- Interdisciplinary Graduate School of Engineering Science, Kyushu University, Kasuga, Fukuoka 816-8580, Japan
| | - Prapasiri Pongprayoon
- Faculty of Science, Department of Chemistry, Kasetsart University, Chatuchak, Bangkok 10900, Thailand
- Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok 10900, Thailand
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13
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Bomholt T, Rix M, Almdal T, Knop FK, Rosthøj S, Jørgensen MB, Feldt-Rasmussen B, Hornum M. Glucose variability in maintenance hemodialysis patients with type 2 diabetes: Comparison of dialysis and nondialysis days. Hemodial Int 2023; 27:126-133. [PMID: 36760179 DOI: 10.1111/hdi.13073] [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: 02/09/2022] [Revised: 12/09/2022] [Accepted: 01/19/2023] [Indexed: 02/11/2023]
Abstract
INTRODUCTION Hemodialysis (HD) induces several physiological changes that can affect plasma glucose levels in patients with diabetes and in turn their glycemic control. Studies using continuous glucose monitoring (CGM) to assess glucose variations on dialysis days compared with nondialysis days report conflicting results. Here, we used CGM to examine glucose variations induced by HD in patients with type 2 diabetes. METHODS Patients with type 2 diabetes undergoing maintenance HD were included. CGM (Ipro2®, Medtronic) was performed at baseline and Week 4, 8, 12, and 16 for up to 7 days at each visit. CGM profiles on days where participants received HD were compared with days without HD using a linear mixed model. FINDINGS Twenty-seven patients were included. The median number of CGM days performed was 8 (interquartile range [IQR] 6-10) for dialysis days and 16 (IQR 12-17) for nondialysis days. The median sensor glucose was 9.4 (95% confidence interval [CI] 8.8-10.2) mmol/L on dialysis days compared with 9.5 (95% CI 8.9-10.2) mmol/L on nondialysis days (p = 0.58). Nocturnal mean sensor glucose was higher on dialysis days compared with nondialysis days: 8.8 (95% CI 8.0-9.6) mmol/L versus 8.4 (95% CI 7.7-9.2) mmol/L (p = 0.029). DISCUSSION Similar median sensor glucose values were found for days on and off HD. Nocturnal glucose levels were modestly increased on dialysis days. Our findings indicate that antidiabetic treatment does not need to be differentiated on dialysis versus nondialysis days in patients with type 2 diabetes undergoing maintenance HD.
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Affiliation(s)
- Tobias Bomholt
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Marianne Rix
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Almdal
- Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Filip K Knop
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Susanne Rosthøj
- Section of Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Morten B Jørgensen
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Bo Feldt-Rasmussen
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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14
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Avari P, Tang W, Jugnee N, Hersi I, Al-Balah A, Tan T, Frankel A, Oliver N, Reddy M. The Accuracy of Continuous Glucose Sensors in People with Diabetes Undergoing Haemodialysis (ALPHA Study). Diabetes Technol Ther 2023. [PMID: 36961385 DOI: 10.1089/dia.2023.0013] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/25/2023]
Abstract
OBJECTIVES Real-time and intermittently scanned continuous glucose monitoring are increasingly used for glucose monitoring in people with diabetes requiring renal replacement therapy, with limited data reporting their accuracy in this cohort. We evaluated the accuracy of Dexcom G6 and Abbott Freestyle Libre 1 glucose monitoring systems in people with diabetes undergoing haemodialysis. METHODS Participants on haemodialysis with diabetes (on insulin or sulfonylureas) were recruited. Paired sensor glucose from Dexcom G6 and Freestyle Libre 1 were recorded with plasma glucose analysed using the YSI (Yellow Springs Instrument) method at frequent intervals during haemodialysis. Analysis of accuracy metrics included mean absolute relative difference (MARD), Clarke Error Grid (CEG) analysis and proportion of CGM values within 15 and 20% or 15 and 20mg/dL of YSI reference values for blood glucose >100 mg/dL or ≤100 mg/dL, respectively (% 15/15, % 20/20). RESULTS Forty adults (median age 64.7 (60.2-74.4) years) were recruited. Overall MARD for Dexcom G6 was 22.7% (2,656 matched glucose pairs), and 11.3% for Libre 1 (n=2,785). The proportions of readings meeting %15/15 and %20/20 were 29.1% and 45.4% for Dexcom G6, respectively, and 73.5% and 85.6% for Libre 1. CEG analysis showed 98.9% of all values in zones A and B for Dexcom G6 and 99.8% for Libre 1. CONCLUSIONS Our results indicate Freestyle Libre 1 is a reliable tool for glucose monitoring in adults on haemodialysis. Further studies are required to evaluate Dexcom G6 accuracy in people on haemodialysis. Small molecule interferents may affect electrochemical glucose sensors in end-stage kidney disease.
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Affiliation(s)
- Parizad Avari
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
| | - Wenxi Tang
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
| | - Narvada Jugnee
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, London, United Kingdom of Great Britain and Northern Ireland;
| | - Ibrahim Hersi
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
| | - Amer Al-Balah
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
| | - Tricia Tan
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
| | - Andrew Frankel
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
| | - Nick Oliver
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
| | - Monika Reddy
- Imperial College London, 4615, Department of Metabolism, Digestion and Reproduction, London, United Kingdom of Great Britain and Northern Ireland;
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15
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Abstract
Diabetes mellitus is the ninth leading cause of mortality worldwide. It is a complex disease that manifests as chronic hyperglycemia. Glucose exposure causes biochemical changes at the proteome level as reflected in accumulation of glycated proteins. A prominent example is hemoglobin A1c (HbA1c), a glycated protein widely accepted as a diabetic indicator. Another emerging biomarker is glycated albumin which has demonstrated utility in situations where HbA1c cannot be used. Other proteins undergo glycation as well thus impacting cellular function, transport and immune response. Accordingly, these glycated counterparts may serve as predictors for diabetic complications and thus warrant further inquiry. Fortunately, modern proteomics has provided unique analytic capability to enable improved and more comprehensive exploration of glycating agents and glycated proteins. This review broadly covers topics from epidemiology of diabetes to modern analytical tools such as mass spectrometry to facilitate a better understanding of diabetes pathophysiology. This serves as an attempt to connect clinically relevant questions with findings of recent proteomic studies to suggest future avenues of diabetes research.
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Affiliation(s)
- Aleks Shin
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States
| | - Shawn Connolly
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States
| | - Kuanysh Kabytaev
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States.
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16
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Bleskestad IH, Skadberg Ø, Åsberg A, Gøransson LG. Glycated albumin and post-transplant diabetes mellitus in kidney transplant recipients. Ann Clin Biochem 2023; 60:109-116. [PMID: 36604778 DOI: 10.1177/00045632231152074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Post-transplant diabetes mellitus is one of the most important cardiovascular risk factors after solid organ transplantation. Factors other than hyperglycaemia found in patients post-transplant, affect the level of haemoglobin A1c (HbA1c), and new markers of hyperglycaemia are needed. Our aim was to establish a 95% reference interval for glycated albumin in kidney transplant recipients, and to compare glycated albumin concentrations to the diagnostic criteria for diabetes mellitus post-transplant using oral glucose tolerance test and HbA1c. METHODS A total of 341 non-diabetic kidney transplant recipients aged ≥18 years who underwent an oral glucose tolerance test at 8 weeks and 1 year after transplantation were included. Glycated albumin was determined by liquid chromatography coupled with tandem mass spectrometry. RESULTS The 95% reference interval for glycated albumin was 8.2 (90% CI: 7.2-8.5) to 12.8% (90% CI: 12.2-13.5) which is not significantly different from our laboratory's 95% reference interval for persons without diabetes. At both 8 weeks and 1 year after transplantation, 35 patients (10.3%) fulfilled one, two or all three diagnostic criteria for diabetes mellitus. One year after transplantation, eight additional patients had glycated albumin concentration >12.8%. CONCLUSION Our findings are in accordance with the notion that kidney transplant recipients form glycation end products like normal controls as estimated by glycated albumin and HbA1c. Further studies should address glycated albumin as a supplemental tool for the diagnosis of post-transplant diabetes mellitus in kidney transplant recipients.
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Affiliation(s)
- Inger H Bleskestad
- Department of Medicine, 60496Stavanger University Hospital, Stavanger, Norway
| | - Øyvind Skadberg
- Department of Medicine, 60496Stavanger University Hospital, Stavanger, Norway
| | - Anders Åsberg
- Department of Organ Transplantation, The Norwegian Renal Registry, 155272Oslo University Hospital, Oslo, Norway.,Department of Pharmacy, University of Oslo, Oslo, Norway
| | - Lasse G Gøransson
- Department of Medicine, 60496Stavanger University Hospital, Stavanger, Norway.,Faculty of Medicine, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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17
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Folgueras García A, Corte Arboleya Z, Venta Obaya R. [Alternative strategies to the use of glycosylated hemoglobin in monitoring the glycemic status of diabetic patients with end-stage renal disease]. Med Clin (Barc) 2023; 160:145-150. [PMID: 35945057 DOI: 10.1016/j.medcli.2022.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 05/11/2022] [Accepted: 05/13/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) is one of the leading causes of end-stage renal disease. Glycosylated hemoglobin (HbA1c) is the recommended glycemic marker to achieve an optimal glycemic control that is essential to prevent comorbidities associated with the disease. However, in patients on haemodialysis (HD) this marker has important limitations, this reason has led us to search alternative markers such as glycosylated albumin (AG), labile fraction of glycosylated hemoglobin (LHbA1c) or glycation indices. PATIENTS AND METHODS We enrolled 47 patients in HD, 23 with DM, obtaining samples for the determination of de AG, HbA1c y LHbA1c. Glycation indices, which allow estimated the HbA1c using glucose, AG or LHbA1c, were calculated including a control group composed of 75 diabetic patients without kidney disease. RESULTS Diabetic patients in HD had significantly higher mean values than patients without DM for glucose [160 (44) vs 96 (12)mg/dL], HbA1c [6,4 (1,0) vs 4,9 (0,3)%], AG [16,0 (5,1) vs 12,9 (1,6)%] and LHbA1c [2,0 (0,3) vs 1,7 (0,2)%]. HbA1c calculated using glycation indices was significantly higher than measured in all HD patients, regardless of the marker used for the estimation. CONCLUSIONS The glycemic markers evaluated (glucose, AG and LHbA1c), could reflect a possible underestimation of the real glycemic state by HbA1c because of the limitations of this marker in HD patients. The use of alternative markers, knowing their limitations, could improve the monitoring of patients on HD and, therefore, reduce the risk of developing DM2 complications.
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Affiliation(s)
- Andrés Folgueras García
- Servicio de Análisis Clínicos, Hospital Universitario San Agustín, Avilés. Asturias, España.
| | - Zoraida Corte Arboleya
- Servicio de Análisis Clínicos, Hospital Universitario San Agustín, Avilés. Asturias, España
| | - Rafael Venta Obaya
- Servicio de Análisis Clínicos, Hospital Universitario San Agustín, Avilés. Asturias, España; Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Oviedo, Asturias, España
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18
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Mimura K, Nishide T, Naganuma T, Katsube Y, Ishitani S, Nakahara K, Hirasaka N, Mizobata R, Yamagata Y, Nishikawa O, Yukawa S. Inverse correlation of free triiodothyronine with glycated albumin and the glycated albumin/glycated hemoglobin ratio in hemodialysis patients: a cross-sectional study. RENAL REPLACEMENT THERAPY 2023. [DOI: 10.1186/s41100-023-00461-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
Abstract
Background
That the prevalence of low triiodothyronine (T3) syndrome is high among hemodialysis (HD) patients has been previously established. Herein, we examined the association of glycated albumin (GA) and the GA to glycated hemoglobin (HbA1c) ratio (GA/HbA1c) with free triiodothyronine (FT3) in HD patients.
Methods
We conducted a cross-sectional study on 134 patients (68 patients with diabetes mellitus [DM group] and 66 patients without diabetes mellitus [non-DM group]) who received maintenance HD at our dialysis clinic between 2014 and 2018. Univariate linear regression analyses of GA, GA/HbA1c, or HbA1c with several clinical variables were primarily conducted. Multiple regression analyses with GA (or GA/HbA1c) as the objective variable were conducted with explanatory variable FT3 adjusted for age, sex, Hb, Alb, and average plasma glucose (Av-PG) (or HbA1c).
Results
In the DM and non-DM groups, GA tended to be inversely correlated with FT3, although significantly so only in the non-DM group. GA/HbA1c also showed a strong significant inverse correlation with FT3 in the DM group and the non-DM group. FT3 and GA/HbA1c were also significantly correlated with the Geriatric Nutritional Risk Index in the DM group and non-DM group. In the multivariate analysis, which was adjusted for age, sex, Hb, Alb, and HbA1c, FT3 was a significant and independent factor associated with GA in the DM group (β = − 0.334, p < 0.001) and in the non-DM group (β = − 0.412, p < 0.001). The regression equations obtained by stepwise multiple regression analyses using all of these variables as independent variables were GA = 3.3HbA1c − 4.4FT3 + 1.9sex + 8.8 for the DM group and GA = − 2.4FT3 + 0.04Age − 0.5Hb + 25.2 for the non-DM group. These contribution rates (i.e., coefficient of determination) were R2 = 0.708 in the DM group and R2 = 0.347 in the non-DM group, In the DM group, the estimation formulas, based on the regression equation [GA (men) = 3.3HbA1c − 4.4FT3 + 10.7 and GA (women) = 3.3HbA1c − 4.4FT3 + 8.8], showed very high contribution rates (i.e., coefficient of determination R2 = 0.674 for men and 0.761 for women) for the GA measured values.
Conclusions
GA and GA/HbA1c have a close relationship with FT3 in HD patients. The estimation formulas of GA could be obtained. In particular, the estimation formulas in the DM group are believed to be useful in considering HbA1c and FT3 simultaneously when evaluating GA.
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Mohammadinejad A, Heydari M, Kazemi Oskuee R, Rezayi M. A Critical Systematic Review of Developing Aptasensors for Diagnosis and Detection of Diabetes Biomarkers. Crit Rev Anal Chem 2022; 52:1795-1817. [DOI: 10.1080/10408347.2021.1919986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Arash Mohammadinejad
- Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Heydari
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Kazemi Oskuee
- Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Rezayi
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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20
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Abe M, Matsuoka T, Kawamoto S, Miyasato K, Kobayashi H. Toward Revision of the ‘Best Practice for Diabetic Patients on Hemodialysis 2012’. KIDNEY AND DIALYSIS 2022; 2:495-511. [DOI: 10.3390/kidneydial2040045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Diabetic nephropathy is the leading cause of dialysis therapy worldwide. The number of diabetes patients on dialysis in clinical settings has been increasing in Japan. In 2013, the Japanese Society for Dialysis Therapy (JSDT) published the “Best Practice for Diabetic Patients on Hemodialysis 2012”. While glycated hemoglobin (HbA1c) is used mainly as a glycemic control index for dialysis patients overseas, Japan is the first country in the world to use glycated albumin (GA) for assessment. According to a survey conducted by the JSDT in 2018, the number of facilities measuring only HbA1c has decreased compared with 2013, while the number of facilities measuring GA or both has significantly increased. Ten years have passed since the publication of the first edition of the guidelines, and several clinical studies regarding the GA value and mortality of dialysis patients have been reported. In addition, novel antidiabetic agents have appeared, and continuous glucose monitoring of dialysis patients has been adopted. On the other hand, Japanese dialysis patients are rapidly aging, and the proportion of patients with malnutrition is increasing. Therefore, there is great variation among diabetes patients on dialysis with respect to their backgrounds and characteristics. This review covers the indices and targets of glycemic control, the treatment of hyperglycemia, and diet recommendations for dialysis patients with diabetes.
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Affiliation(s)
- Masanori Abe
- Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Tomomi Matsuoka
- Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Shunsuke Kawamoto
- Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Kota Miyasato
- Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Hiroki Kobayashi
- Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan
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21
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Wallam S, Abusamaan MS, Clarke W, Mathioudakis N. Factors Associated With Discordant A1C-Estimated and Measured Average Glucose Among Hospitalized Patients With Diabetes. Clin Diabetes 2022; 41:208-219. [PMID: 37092143 PMCID: PMC10115769 DOI: 10.2337/cd22-0047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
In this retrospective analysis, we explored the correlation between measured average glucose (mAG) and A1C-estimated average glucose (eAG) in hospitalized patients with diabetes and identified factors associated with discordant mAG and eAG at the transition from home to hospital. Having mAG lower than eAG was associated with Black race, other race, increasing length of stay, community hospital setting, surgery, fever, metformin use, certain inpatient diets, home antihyperglycemic treatment, and coded type 1 or type 2 diabetes. Having mAG higher than eAG was associated with certain discharge services (e.g., intensive care unit), higher BMI, hypertension, tachycardia, higher albumin, higher potassium, anemia, inpatient glucocorticoid use, and treatment with home insulin, secretagogues, and glucocorticoids. These factors should be considered when using patients' A1C as an indicator of outpatient glycemic control to determine the inpatient antihyperglycemic regimens.
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Affiliation(s)
- Sara Wallam
- Division of Endocrinology, Diabetes, & Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Mohammed S. Abusamaan
- Division of Endocrinology, Diabetes, & Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD
| | - William Clarke
- Division of Clinical Chemistry, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Nestoras Mathioudakis
- Division of Endocrinology, Diabetes, & Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD
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22
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Afghahi H, Nasic S, Rydell H, Svensson J, Peters B. The association between long-term glycemic control and all-cause mortality is different among older versus younger patients with diabetes mellitus and maintenance hemodialysis treatment. Diabetes Res Clin Pract 2022; 191:110033. [PMID: 35940301 DOI: 10.1016/j.diabres.2022.110033] [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: 03/19/2022] [Revised: 08/01/2022] [Accepted: 08/03/2022] [Indexed: 11/17/2022]
Abstract
AIMS Knowledge about association between glycated hemoglobin (HbA1c) and risk of all-cause mortality in patients with diabetes mellitus on maintenance hemodialysis (HD)-treatment is sparse. The study aims to investigate association between HbA1c and all-cause mortality in patients with diabetes and maintenance HD-treatment, separately for two age groups- above and below 75 years. METHODS 2487 patients (mean age 66 years, 66 % men) were separated in two age groups: ≤75 years (n = 1810) and > 75 years (n = 677) and followed up between 2008 and 2018. Hazard ratios (HR) and 95 % confidence intervals (CI) for associations between HbA1c and all-cause mortality were calculated using Cox-regression-models. RESULTS 1295 (52 %) patients died and 473 (70 %) among the patients above 75 years old. In the multivariate analysis, HbA1c5-6 % was used as reference. In patients ≤ 75 years old, only increased HbA1c > 9.7 %, HR2.03(CI1.43-2.89) was associated with increased risk of all-cause mortality. In patients > 75 years, HbA1c ≤ 5 %, HR1.67(CI1.16-2.40); HbA1c6.9-7.8 %, HR1.41(CI1.03-1.93) and HbA1c8.7-9.7 %, HR1.79 (CI1.08-2.96) were associated with increased risk of all-cause mortality. CONCLUSIONS We found a J-shaped association between HbA1c and mortality only in diabetic HD-patients > 75 years. This probably indicates that in an old population of diabetic HD-patients, both intensive glucose control and hyperglycemia could be harmful and associated with higher risk of death.
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Affiliation(s)
- Hanri Afghahi
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Salmir Nasic
- Research and Development Centre at Skaraborg Hospital, Skövde, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Helena Rydell
- Karolinska University Hospital, Stockholm Division of Renal Medicine, CLINTEC, Karolinska Institutet, Sweden
| | - Johan Svensson
- Research and Development Centre at Skaraborg Hospital, Skövde, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Björn Peters
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
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23
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Rescalli A, Varoni EM, Cellesi F, Cerveri P. Analytical Challenges in Diabetes Management: Towards Glycated Albumin Point-of-Care Detection. BIOSENSORS 2022; 12:bios12090687. [PMID: 36140073 PMCID: PMC9496022 DOI: 10.3390/bios12090687] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/20/2022] [Accepted: 08/23/2022] [Indexed: 11/16/2022]
Abstract
Diabetes mellitus is a worldwide-spread chronic metabolic disease that occurs when the pancreas fails to produce enough insulin levels or when the body fails to effectively use the secreted pancreatic insulin, eventually resulting in hyperglycemia. Systematic glycemic control is the only procedure at our disposal to prevent diabetes long-term complications such as cardiovascular disorders, kidney diseases, nephropathy, neuropathy, and retinopathy. Glycated albumin (GA) has recently gained more and more attention as a control biomarker thanks to its shorter lifespan and wider reliability compared to glycated hemoglobin (HbA1c), currently the “gold standard” for diabetes screening and monitoring in clinics. Various techniques such as ion exchange, liquid or affinity-based chromatography and immunoassay can be employed to accurately measure GA levels in serum samples; nevertheless, due to the cost of the lab equipment and complexity of the procedures, these methods are not commonly available at clinical sites and are not suitable to home monitoring. The present review describes the most up-to-date advances in the field of glycemic control biomarkers, exploring in particular the GA with a special focus on the recent experimental analysis techniques, using enzymatic and affinity methods. Finally, analysis steps and fundamental reading technologies are integrated into a processing pipeline, paving the way for future point-of-care testing (POCT). In this view, we highlight how this setup might be employed outside a laboratory environment to reduce the time from measurement to clinical decision, and to provide diabetic patients with a brand-new set of tools for glycemic self-monitoring.
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Affiliation(s)
- Andrea Rescalli
- Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy
- Correspondence: (A.R.); (E.M.V.)
| | - Elena Maria Varoni
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, 20122 Milan, Italy
- Correspondence: (A.R.); (E.M.V.)
| | - Francesco Cellesi
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, 20133 Milan, Italy
| | - Pietro Cerveri
- Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy
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24
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Shimizu N, Ogawa A, Hayashi A, Shichiri M. Discordance in the reduction rate between glycated albumin and glycated hemoglobin levels in type 2 diabetes patients receiving SGLT2 inhibitors. J Diabetes Complications 2022; 36:108225. [PMID: 35690574 DOI: 10.1016/j.jdiacomp.2022.108225] [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: 11/07/2021] [Revised: 05/23/2022] [Accepted: 05/30/2022] [Indexed: 10/18/2022]
Abstract
AIMS Although the difference in HbA1c reduction between sodium-glucose cotransporter 2 (SGLT2) inhibitors and other oral glucose-lowering agents is relatively small, SGLT2 inhibitors exhibit beneficial cardiorenal protection. This study was based on the hypothesis that changes of HbA1c in patients treated with SGLT2 inhibitors may not accurately reflect an improved glycemic profile. METHODS Two studies were conducted: 1) a retrospective cohort study of 3039 patients administered with either an SGLT2 or a dipeptidyl peptidase-4 (DPP4) inhibitor for 12 months comparing the changes in glycated albumin (GA) and HbA1c levels and 2) a pilot study of 10 patients whose glycemic dynamics were evaluated using flash glucose monitoring at baseline and 2 months after treatment with an SGLT2 inhibitor. RESULTS SGLT2 inhibitors reduced GA more markedly than HbA1c in both studies. DPP4 inhibitors decreased both GA and HbA1c to a comparable degree. The mean glucose levels and glycemic standard deviation were significantly reduced after treatment with an SGLT2 inhibitor, in concordance with GA decline, although the lowering of HbA1c was marginal. CONCLUSIONS Changes in HbA1c levels underestimated the glucose-lowering effect and the diminished glycemic fluctuation induced by SGLT2 inhibitors. Thus, the distinct biomarker roles of GA and HbA1c should be reevaluated.
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Affiliation(s)
- Naoya Shimizu
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan
| | - Akifumi Ogawa
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan
| | - Akinori Hayashi
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan
| | - Masayoshi Shichiri
- Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan; Tokyo Kyosai Hospital, 2-3-8 Nakameguro, Meguro-ku, Tokyo 153-8934, Japan.
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25
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Resistance to glycation in the zebra finch: Mass spectrometry-based analysis and its perspectives for evolutionary studies of aging. Exp Gerontol 2022; 164:111811. [PMID: 35472570 DOI: 10.1016/j.exger.2022.111811] [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] [Received: 11/30/2021] [Revised: 03/15/2022] [Accepted: 04/18/2022] [Indexed: 12/30/2022]
Abstract
In humans, hyperglycemia is associated with protein glycation, which may contribute to aging. Strikingly, birds usually outlive mammals of the same body mass, while exhibiting high plasma glucose levels. However, how birds succeed in escaping pro-aging effects of glycation remains unknown. Using a specific mass spectrometry-based approach in captive zebra finches of known age, we recorded high glycaemia values but no glycated hemoglobin form was found. Still, we showed that zebra finch hemoglobin can be glycated in vitro, albeit only to a limited extent compared to its human homologue. This may be due to peculiar structural features, as supported by the unusual presence of three different tetramer populations with balanced proportions and a still bound cofactor that could be inositol pentaphosphate. High levels of the glycated forms of zebra finch plasma serotransferrin, carbonic anhydrase 2, and albumin were measured. Glucose, age or body mass correlations with either plasma glycated proteins or hemoglobin isoforms suggest that those variables may be future molecular tools of choice to monitor glycation and its link with individual fitness. Our molecular advance may help determine how evolution succeeded in associating flying ability, high blood glucose and long lifespan in birds.
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26
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Abstract
Reliable assessment of glycemia is central to the management of diabetes. The kidneys play a vital role in maintaining glucose homeostasis through glucose filtration, reabsorption, consumption, and generation. This review article highlights the role of the kidneys in glucose metabolism and discusses the benefits, pitfalls, and evidence behind the glycemic markers in patients with chronic kidney disease. We specifically highlight the role of continuous glucose monitoring as an emerging minimally invasive technique for glycemic assessment.
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Affiliation(s)
- Mohamed Hassanein
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA
| | - Tariq Shafi
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA. .,Department of Population Health, John D. Bower School of Population Health, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA. .,Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
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27
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Kijewska M, Zawadzka M, Włodarczyk K, Stefanowicz P. HPLC-free method of synthesis of isotopically labeled deoxyfructosylated peptides. Anal Bioanal Chem 2022; 414:3803-3811. [PMID: 35316349 DOI: 10.1007/s00216-022-04022-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/28/2022] [Accepted: 03/15/2022] [Indexed: 12/01/2022]
Abstract
The biomarker strategy, based on multiple specific glycation sites in plasma proteins, could essentially increase the efficiency of glycemic control and disease prediction. Besides glycated albumin being a potential biomarker of early states of diabetes mellitus and control of short-term, it has been shown that the glycation of fibrinogen may also impact the formation of the fibrin network, while quantification of glycation of the CD59 protein allows for early detection of glucose intolerance in pregnant women. A different level of glycation of individual lysine residues in proteins has a crucial influence on the stages of the disease. The quantification of new biomarkers of different stages of diabetes requires appropriate isotope-labeled analogs that may improve biomarker search by providing more accurate quantitative data and by more robust detection/quantitation of low-abundance biomarkers. In the presented work, we proposed a fast and simple protocol for the synthesis of isotopically labeled and bi-labeled deoxyfructosylated peptide based on a combination of microwave-assisted synthesis and boronic affinity chromatography using functionalized resin (PhB-Lys(PhB)-ChemMatrix® Rink resin) developed by us. Our method is focused on the synthesis of glycated peptides identified in glycated albumin (GA) after enzymatic hydrolysis catalyzed by trypsin after arginine residues. Thereby, the standard peptides comprised [13C6]-deoxyfructose attached to lysine residue side chain, a dabcyl moiety for determination of standard amounts, and a cleavable linker. Moreover, we applied bi-labeled deoxyfructosylated peptide to determine the concentration of appropriate analog in a sample of human serum albumin glycated in vitro.
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Affiliation(s)
- Monika Kijewska
- Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland.
| | - Michalina Zawadzka
- Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland
| | - Karolina Włodarczyk
- Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland
| | - Piotr Stefanowicz
- Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland
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28
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Yeh KH, Hsu LA, Teng MS, Wu S, Chou HH, Ko YL. Pleiotropic Effects of Common and Rare GCKR Exonic Mutations on Cardiometabolic Traits. Genes (Basel) 2022; 13:genes13030491. [PMID: 35328045 PMCID: PMC8951277 DOI: 10.3390/genes13030491] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/04/2022] [Accepted: 03/06/2022] [Indexed: 02/05/2023] Open
Abstract
Background: The common non-synonymous mutation of the glucokinase regulator (GCKR) gene, namely rs1260326, is widely reported to have pleiotropic effects on cardio-metabolic traits and hematological parameters. Objective: This study aimed to identify whether other GCKR variants may have pleiotropic effects independent of the rs1260326 genotypes. Methods: In total, 81,097 Taiwan Biobank participants were enrolled for the regional plot association studies and candidate variant analysis of the region around the GCKR gene. Results: The initial candidate variant approach showed the significant association of the rs1260326 genotypes with multiple phenotypes. Regional plot association analysis of the GCKR gene region further revealed genome-wide significant associations between GCKR variants and serum total and low-density lipoprotein cholesterol; triglyceride, uric acid, creatinine, aspartate aminotransferase, γ-Glutamyl transferase, albumin, and fasting plasma glucose levels; estimated glomerular filtration rate; leukocyte and platelet counts; microalbuminuria, and metabolic syndrome, with rs1260326 being the most common lead polymorphism. Serial conditional analysis identified genome-wide significant associations of two low-frequency exonic mutations, rs143881585 and rs8179206, with high serum triglyceride and albumin levels. In five rare GCKR exonic non-synonymous or nonsense mutations available for analysis, GCKR rs146175795 showed an independent association with serum triglyceride and albumin levels and rs150673460 showed an independent association with serum triglyceride levels. Weighted genetic risk scores from the combination of GCKR rs143881585 and rs146175795 revealed a significant association with metabolic syndrome. Conclusion: In addition to the rs1260326 variant, low-frequency and rare GCKR exonic mutations exhibit pleiotropic effects on serum triglyceride and albumin levels and the risk of metabolic syndrome. These results provide evidence that both common and rare GCKR variants may play a critical role in predicting the risk of cardiometabolic disorders.
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Affiliation(s)
- Kuan-Hung Yeh
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; (K.-H.Y.); (H.-H.C.)
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
| | - Lung-An Hsu
- The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan;
| | - Ming-Sheng Teng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan;
| | - Semon Wu
- Department of Life Science, Chinese Culture University, Taipei 11114, Taiwan;
| | - Hsin-Hua Chou
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; (K.-H.Y.); (H.-H.C.)
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
| | - Yu-Lin Ko
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; (K.-H.Y.); (H.-H.C.)
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan;
- Correspondence: ; Tel.: +886-2-6628-9779 (ext. 5355); Fax: +886-2-6628-9009
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29
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Cavallari G, Mancini E. The Nephrologist's Role in the Collaborative Multi-Specialist Network Taking Care of Patients with Diabetes on Maintenance Hemodialysis: An Overview. J Clin Med 2022; 11:jcm11061521. [PMID: 35329847 PMCID: PMC8949004 DOI: 10.3390/jcm11061521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 02/28/2022] [Accepted: 03/02/2022] [Indexed: 12/22/2022] Open
Abstract
Diabetes mellitus is the leading cause of renal failure in incident dialysis patients in several countries around the world. The quality of life for patients with diabetes in maintenance hemodialysis (HD) treatment is in general poor due to disease complications. Nephrologists have to cope with all these problems because of the “total care model” and strive to improve their patients’ outcome. In this review, an updated overview of the aspects the nephrologist must face in the management of these patients is reported. The conventional marker of glycemic control, hemoglobin A1c (HbA1c), is unreliable. HD itself may be responsible for dangerous hypoglycemic events. New methods of glucose control could be used even during dialysis, such as a continuous glucose monitoring (CGM) device. The pharmacological control of diabetes is another complex topic. Because of the risk of hypoglycemia, insulin and other medications used to treat diabetes may need dose adjustment. The new class of antidiabetic drugs dipeptidyl peptidase 4 (DPP-4) inhibitors can safely be used in non-insulin-dependent end-stage renal disease (ESRD) patients. Nephrologists should take care to improve the hemodynamic tolerance to HD treatment, frequently compromised by the high level of ultrafiltration needed to counter high interdialytic weight gain. Kidney and pancreas transplantation, in selected patients with diabetes, is the best therapy and is the only approach able to free patients from both dialysis and insulin therapy.
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30
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Ortiz-Martínez M, González-González M, Martagón AJ, Hlavinka V, Willson RC, Rito-Palomares M. Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus. Curr Diab Rep 2022; 22:95-115. [PMID: 35267140 PMCID: PMC8907395 DOI: 10.1007/s11892-022-01453-4] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/27/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE OF REVIEW Diabetes mellitus is a complex, chronic illness characterized by elevated blood glucose levels that occurs when there is cellular resistance to insulin action, pancreatic β-cells do not produce sufficient insulin, or both. Diabetes prevalence has greatly increased in recent decades; consequently, it is considered one of the fastest-growing public health emergencies globally. Poor blood glucose control can result in long-term micro- and macrovascular complications such as nephropathy, retinopathy, neuropathy, and cardiovascular disease. Individuals with diabetes require continuous medical care, including pharmacological intervention as well as lifestyle and dietary changes. RECENT FINDINGS The most common form of diabetes mellitus, type 2 diabetes (T2DM), represents approximately 90% of all cases worldwide. T2DM occurs more often in middle-aged and elderly adults, and its cause is multifactorial. However, its incidence has increased in children and young adults due to obesity, sedentary lifestyle, and inadequate nutrition. This high incidence is also accompanied by an estimated underdiagnosis prevalence of more than 50% worldwide. Implementing successful and cost-effective strategies for systematic screening of diabetes mellitus is imperative to ensure early detection, lowering patients' risk of developing life-threatening disease complications. Therefore, identifying new biomarkers and assay methods for diabetes mellitus to develop robust, non-invasive, painless, highly-sensitive, and precise screening techniques is essential. This review focuses on the recent development of new clinically validated and novel biomarkers as well as the methods for their determination that represent cost-effective alternatives for screening and early diagnosis of T2DM.
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Affiliation(s)
- Margarita Ortiz-Martínez
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, México
| | - Mirna González-González
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, México.
- Tecnologico de Monterrey, The Institute for Obesity Research, Monterrey, Nuevo León, México.
| | - Alexandro J Martagón
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, México
- Tecnologico de Monterrey, The Institute for Obesity Research, Monterrey, Nuevo León, México
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Victoria Hlavinka
- Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, USA
| | - Richard C Willson
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, México
- Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, USA
| | - Marco Rito-Palomares
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, México
- Tecnologico de Monterrey, The Institute for Obesity Research, Monterrey, Nuevo León, México
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31
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Afghahi H, Nasic S, Peters B, Rydell H, Hadimeri H, Svensson J. Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis. PLoS One 2022; 17:e0262880. [PMID: 35077471 PMCID: PMC8789125 DOI: 10.1371/journal.pone.0262880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 01/10/2022] [Indexed: 11/18/2022] Open
Abstract
Background
The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD.
Methods
325 patients with diabetes and ESRD were followed (2008–2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses.
Results
During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83–4.60 (HR 3.15, 95% CI 1.78–5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21–5.11; p = 0.014) were associated with increased risk of death.
Conclusion
The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
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Affiliation(s)
- Hanri Afghahi
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Salmir Nasic
- Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Research and Development Center at Skaraborg Hospital, Skövde, Sweden
| | - Björn Peters
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- * E-mail:
| | - Helena Rydell
- Division of Renal Medicine, Department of Clinical Sciences Intervention and Technology, Karolinska Institute, Stockholm, Sweden
- Department of Internal Medicine, Swedish Renal Registry, Ryhov Regional Hospital, Jönköping, Sweden
| | - Henrik Hadimeri
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Johan Svensson
- Research and Development Center at Skaraborg Hospital, Skövde, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
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Sittiwanichai S, Japrung D, Pongprayoon P. The binding of apo and glucose-bound human serum albumins to a free graphene sheet in aqueous environment: Simulation studies. J Mol Graph Model 2021; 110:108073. [PMID: 34768229 DOI: 10.1016/j.jmgm.2021.108073] [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] [Received: 05/06/2021] [Revised: 10/14/2021] [Accepted: 11/02/2021] [Indexed: 12/24/2022]
Abstract
Human serum albumin (HSA) is a blood protein serving as a carrier for a wide range of drugs and nutrients. A level of glycated HSA (GHSA) is used as a diabetes biomarker. A graphene-based aptasensor is one of potential techniques to detect GHSA. Not only the interactions of albumin and aptamer, but the albumin-graphene (GRA) binding mechanism are also crucial for developing a diabetes aptasensor. In this work, Molecular Dynamics simulations (MD) were employed to explore the binding of GRA to both GHSA and HSA. The GRA binding from the back and front sides of an albumin are fast and spontaneous. The multiple GRA binding sites are identified. GRA causes more denaturation of helical characteristics in GHSA (∼12% reduction of helical structure). Both back and front GRA adhesions generate comparable degrees of helical unfolding. Importantly, the presence of bound GRA induces the release of glucose from drug sites implying the loss of ligand-binding affinity. This loss of drug site activity is independent on the GRA binding positions because all bound positions lead to the exit of sugars. The GRA binding deconstructs not only secondary structure, but also albumin function. Apparently, GRA is a non-biocompatible material for albumin. To construct a potential graphene-based aptasensor to detect GHSA, it is necessary to be certain that no free GRA surface is available because a bare GRA can bind and denature both HSA and GHSA which can cause misleading data.
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Affiliation(s)
- Sirin Sittiwanichai
- Faculty of Science, Department of Chemistry, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand
| | - Deanpen Japrung
- National Nanotechnology Center, National Science and Technology Development Agency, Thailand Science Park, Pathumthani, 12120, Thailand
| | - Prapasiri Pongprayoon
- Faculty of Science, Department of Chemistry, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand; Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok, 10900, Thailand.
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Ceccarelli Ceccarelli D, Paleari R, Solerte B, Mosca A. Re-thinking diabetic nephropathy: Microalbuminuria is just a piece of the diagnostic puzzle. Clin Chim Acta 2021; 524:146-153. [PMID: 34767792 DOI: 10.1016/j.cca.2021.11.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 10/29/2021] [Accepted: 11/07/2021] [Indexed: 12/13/2022]
Abstract
The decline of the estimated glomerular filtration rate (eGFR) and the presence of albuminuria are the typical hallmarks of kidney disease arising as one of the most frequent diabetic complications over a long period of time, generally known as diabetic nephropathy or diabetes kidney disease (DKD). However, a decline in the renal function may occur in diabetic patients for other reasons unrelated to glycemic control, and this condition is known as non-diabetic kidney disease (NDKD). In this opinion paper we will review these conditions, and we outline the importance of other investigations, such as kidney biopsy and the measurement of novel biomarkers, in order to identify the disease progression early, and to allow a timely intervention. We will also focus on the actual limits of the quantitative measurements of albumin in urine, especially with regards to potential interferences due to the treatment of patients with statins.
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Affiliation(s)
| | - Renata Paleari
- Dip. di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, Italy
| | - Bruno Solerte
- Dip. di Medicina Interna e Terapia Medica, Università degli Studi di Pavia, Pavia, Italy
| | - Andrea Mosca
- Dip. di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, Italy.
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Ben-David E, Hull R, Banerjee D. Diabetes mellitus in dialysis and renal transplantation. Ther Adv Endocrinol Metab 2021; 12:20420188211048663. [PMID: 34631007 PMCID: PMC8495524 DOI: 10.1177/20420188211048663] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/29/2021] [Indexed: 12/31/2022] Open
Abstract
Diabetes mellitus is the commonest cause of end-stage kidney failure worldwide and is a proven and significant risk factor for the development of cardiovascular disease. Renal impairment has a significant impact on the physiology of glucose homeostasis as it reduces tissue sensitivity to insulin and reduces insulin clearance. Renal replacement therapy itself affects glucose control: peritoneal dialysis may induce hyperglycaemia due to glucose-rich dialysate and haemodialysis often causes hypoglycaemia due to the relatively low concentration of glucose in the dialysate. Autonomic neuropathy which is common in chronic kidney disease (CKD) and diabetes increases the risk for asymptomatic hypoglycaemia. Pharmacological options for improving glycaemic control are limited due to alterations to drug metabolism. Impaired glucose tolerance and diabetes are also common in the post-kidney-transplant setting and increase the risk of graft failure and mortality. This review seeks to summarise the literature and tackle the intricacies of glycaemic management in patients with CKD who are either on maintenance haemodialysis or have received a kidney transplant. It outlines changes to glycaemic targets, monitoring of glycaemic control, the use of oral hypoglycaemic agents, the management of severe hyperglycaemia in dialysis and kidney transplantation patients.
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Affiliation(s)
- Eyal Ben-David
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Richard Hull
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Debasish Banerjee
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, Room G2.113, Second Floor, Grosvenor Wing, Blackshaw Road, Tooting, London SW17 0QT, UK
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Williams J, Gilchrist M, Strain WD, Fraser D, Shore A. 24-h Glycaemic profiles in peritoneal dialysis patients and non-dialysis controls with advanced kidney disease. Perit Dial Int 2021; 42:497-504. [PMID: 34579595 DOI: 10.1177/08968608211047787] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND For patients on peritoneal dialysis (PD), the deleterious effects of high concentrations of dialysate glucose on the peritoneal membrane are well-documented. Systemic effects of peritoneally absorbed glucose are more poorly defined. Using continuous glucose monitoring (CGM), we aimed to describe 24-h glycaemic profiles of PD patients without diabetes and compare with non-dialysis controls with stage 5 chronic kidney disease (CKD-5). METHODS In this cross-sectional, case-control study, 15 patients on PD (9 automated PD (APD) and 6 continuous ambulatory PD (CAPD)) and 16 CKD-5 controls underwent 72 h of CGM and metabolic profiling. CGM was used to derive average glucose concentrations and within-participant standard deviation (SD) of glucose. Data were analysed for the whole 72-h monitoring period and as daytime (09.00 to 21.00) and night-time (21.00 to 09.00). RESULTS Average glucose concentrations and within-participant SD of glucose for the whole monitoring period were not different between the three groups (p ≥ 0.5). Daytime average glucose concentrations were also similar across the three groups (p = 0.729). APD was associated with a significantly higher nocturnal glucose than CAPD (5.25 mmol/L ± 0.65 vs. 4.28 ± 0.5, p = 0.026). A significant drop in nocturnal glucose compared with daytime average seen in both CAPD patients and controls was absent in APD patients. CONCLUSIONS Systematically different glycaemic patterns were observed in non-diabetic APD and CAPD patients, including an absence of physiological nocturnal glucose dipping in patients on APD. Comprehensive CGM data sets highlight subtleties not appreciated by traditional metabolic biomarkers; this has implications when choosing the most appropriate outcome measures in future research addressing the metabolic impact of PD.
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Affiliation(s)
- Jennifer Williams
- Diabetes and Vascular Medicine Research Centre, NIHR Exeter Clinical Research Facility, University of Exeter College of Medicine and Health, UK
| | - Mark Gilchrist
- Diabetes and Vascular Medicine Research Centre, NIHR Exeter Clinical Research Facility, University of Exeter College of Medicine and Health, UK
| | - William David Strain
- Diabetes and Vascular Medicine Research Centre, NIHR Exeter Clinical Research Facility, University of Exeter College of Medicine and Health, UK
| | | | - Angela Shore
- Diabetes and Vascular Medicine Research Centre, NIHR Exeter Clinical Research Facility, University of Exeter College of Medicine and Health, UK
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Divani M, Georgianos PI, Didangelos T, Liakopoulos V, Makedou K, Iliadis F, Savopoulos C, Grekas DM. Assessment of Hyperglycemia, Hypoglycemia and Inter-Day Glucose Variability Using Continuous Glucose Monitoring among Diabetic Patients on Chronic Hemodialysis. J Clin Med 2021; 10:jcm10184116. [PMID: 34575228 PMCID: PMC8465363 DOI: 10.3390/jcm10184116] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/08/2021] [Accepted: 09/09/2021] [Indexed: 12/21/2022] Open
Abstract
Continuous glucose monitoring (CGM) facilitates the assessment of short-term glucose variability and identification of acute excursions of hyper- and hypo-glycemia. Among 37 diabetic hemodialysis patients who underwent 7-day CGM with the iPRO2 device (Medtronic Diabetes, Northridge, CA, USA), we explored the accuracy of glycated albumin (GA) and hemoglobin A1c (HbA1c) in assessing glycemic control, using CGM-derived metrics as the reference standard. In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) in diagnosing a time in the target glucose range of 70–180 mg/dL (TIR70–180) in <50% of readings was higher for GA (AUC: 0.878; 95% confidence interval (CI): 0.728–0.962) as compared to HbA1c (AUC: 0.682; 95% CI: 0.508–0.825) (p < 0.01). The accuracy of GA (AUC: 0.939; 95% CI: 0.808–0.991) in detecting a time above the target glucose range > 250 mg/dL (TAR>250) in >10% of readings did not differ from that of HbA1c (AUC: 0.854; 95% CI: 0.699–0.948) (p = 0.16). GA (AUC: 0.712; 95% CI: 0.539–0.848) and HbA1c (AUC: 0.740; 95% CI: 0.570–0.870) had a similarly lower efficiency in detecting a time below target glucose range < 70 mg/dL (TBR<70) in >1% of readings (p = 0.71). Although the mean glucose levels were similar, the coefficient of variation of glucose recordings (39.2 ± 17.3% vs. 32.0 ± 7.8%, p < 0.001) and TBR<70 (median (range): 5.6% (0, 25.8) vs. 2.8% (0, 17.9)) were higher during the dialysis-on than during the dialysis-off day. In conclusion, the present study shows that among diabetic hemodialysis patients, GA had higher accuracy than HbA1c in detecting a 7-day CGM-derived TIR70–180 < 50%. However, both biomarkers provided an imprecise reflection of acute excursions of hypoglycemia and inter-day glucose variability.
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Affiliation(s)
- Maria Divani
- 1st Propedeutic Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (M.D.); (T.D.); (F.I.); (C.S.); (D.M.G.)
| | - Panagiotis I. Georgianos
- Hemodialysis Unit, 1st Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, 54626 Thessaloniki, Greece;
- Correspondence: ; Tel./Fax: +30-2313-303-844
| | - Triantafyllos Didangelos
- 1st Propedeutic Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (M.D.); (T.D.); (F.I.); (C.S.); (D.M.G.)
| | - Vassilios Liakopoulos
- Hemodialysis Unit, 1st Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, 54626 Thessaloniki, Greece;
| | - Kali Makedou
- Laboratory of Biochemistry, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece;
| | - Fotios Iliadis
- 1st Propedeutic Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (M.D.); (T.D.); (F.I.); (C.S.); (D.M.G.)
| | - Christos Savopoulos
- 1st Propedeutic Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (M.D.); (T.D.); (F.I.); (C.S.); (D.M.G.)
| | - Dimitrios M. Grekas
- 1st Propedeutic Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (M.D.); (T.D.); (F.I.); (C.S.); (D.M.G.)
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Jacobs MJ, Pinger CW, Castiaux AD, Maloney KJ, Spence DM. A novel 3D-printed centrifugal ultrafiltration method reveals in vivo glycation of human serum albumin decreases its binding affinity for zinc. Metallomics 2021; 12:1036-1043. [PMID: 32626857 DOI: 10.1039/d0mt00123f] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Plasma proteins are covalently modified in vivo by the high-glucose conditions in the bloodstreams of people with diabetes, resulting in changes to both structure and function. Human Serum Albumin (HSA) functions as a carrier-protein in the bloodstream, binding various ligands and tightly regulating their bioavailability. HSA is known to react with glucose via the Maillard reaction, causing adverse effects on its ability to bind and deliver certain ligands, such as metals. Here, the binding between in vivo glycated HSA and zinc (Zn2+) was determined using a novel centrifugal ultrafiltration method that was developed using a 3D-printed device. This method is rapid (90 minutes), capable of high-throughput measurements (24 samples), low-cost (<$1.00 USD per device) and requires lower sample volumes (200 μL) compared to other binding techniques. This device was used to determine an equilibrium dissociation constant between Zn2+ and a commercially obtained normal HSA (nHSA) with a glycation level of 11.5% (Kd = 2.1 (±0.5) × 10-7 M). A glycated fraction of the nHSA sample was enriched (gHSA, 65.5%) and isolated using boronate-affinity chromatography, and found to have a 2.3-fold decrease in Zn2+ binding-affinity (Kd = 4.8 (±0.8) × 10-7 M) when compared to the nHSA sample. The level of glycation of HSA in control plasma (13.0% ± 0.8, n = 3 donors) and plasma from people with diabetes (26.9% ± 6.6, n = 5 donors) was assessed using mass spectrometry. Furthermore, HSA was isolated from plasma obtained in-house from a person with type 1 diabetes and found to have a glycation level of 24.1% and Kd = 3.3 (± 0.5) × 10-7 M for Zn2+, revealing a 1.5-fold decrease in binding affinity compared to nHSA. These findings suggest that increased levels of glycated HSA result in reduced binding to Zn2+, which may have implications in complications associated with diabetes.
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Affiliation(s)
- Monica J Jacobs
- Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI 48824, USA. and Comparative Medicine and Integrative Biology, Michigan State University, East Lansing, MI 48824, USA
| | - Cody W Pinger
- Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI 48824, USA. and Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA
| | - Andre D Castiaux
- Department of Chemistry, Saint Louis University, East Lansing, MI 48824, USA
| | - Konnor J Maloney
- Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA
| | - Dana M Spence
- Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI 48824, USA. and Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA
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Nishad R, Tahaseen V, Kavvuri R, Motrapu M, Singh AK, Peddi K, Pasupulati AK. Advanced-Glycation End-Products Induce Podocyte Injury and Contribute to Proteinuria. Front Med (Lausanne) 2021; 8:685447. [PMID: 34277660 PMCID: PMC8280521 DOI: 10.3389/fmed.2021.685447] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/26/2021] [Indexed: 01/02/2023] Open
Abstract
The prevalence of diabetes reaches epidemic proportions. Diabetes is the leading cause of end-stage kidney disease (ESKD) since 30-40% of diabetic patients develop diabetic nephropathy. Albuminuria and glomerular filtration rate used to assess kidney function are considered surrogate outcomes of chronic kidney disease. The search for a biomarker that predicts progression to diabetic kidney disease is intense. We analyzed the association of serum advanced glycation end-products (AGEs) index (AGI) with impaired kidney function in poorly controlled type II diabetic patients. We observed an association between AGI and impaired kidney function in microalbuminuria patients with hyperglycemia. A significant association between AGEs, particularly carboxymethyl lysine (CML), and impaired kidney function were observed. Administration of AGEs to mice showed heavy proteinuria and glomerular abnormalities. Reduced podocyte number in mice administered with AGEs could be attributed to the epithelial-mesenchymal transition of podocytes. Our study suggests CML could be independently related to the podocyte injury and the risk of DN progression to ESKD in patients with microalbuminuria. AGEs in general or CML could be considered a prognostic marker to assess diabetic kidney disease.
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Affiliation(s)
- Rajkishor Nishad
- Department of Biochemistry, University of Hyderabad, Hyderabad, India
| | - Vazeeha Tahaseen
- Department of Biochemistry, Acharya Nagarjuna University, Guntur, India
| | - Rajesh Kavvuri
- Department of Biochemistry, University of Hyderabad, Hyderabad, India
| | - Manga Motrapu
- Department of Biochemistry, University of Hyderabad, Hyderabad, India
| | - Ashish K Singh
- Department of Biochemistry, University of Hyderabad, Hyderabad, India
| | - Kiranmayi Peddi
- Department of Biochemistry, Acharya Nagarjuna University, Guntur, India
| | - Anil K Pasupulati
- Department of Biochemistry, University of Hyderabad, Hyderabad, India
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Putnin T, Waiwinya W, Pimalai D, Chawjiraphan W, Sathirapongsasuti N, Japrung D. Dual sensitive and rapid detection of glycated human serum albumin using a versatile lead/graphene nanocomposite probe as a fluorescence-electrochemical aptasensor. Analyst 2021; 146:4357-4364. [PMID: 34128007 DOI: 10.1039/d1an00556a] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Monitoring of glycated human serum albumin (GHSA) as a glycemic marker for screening and monitoring of diabetes mellitus is widely practiced for patients with conditions that affect red blood cells. In this study, a complex comprising Pb ions adsorbed on graphene oxide (GO-Pb) was fabricated and utilized as a versatile probe in a fluorescence-electrochemical aptasensor for GHSA quantification. To simplify the aptasensor, the GO-Pb complex probe was prepared via an ion adsorption process. After modification with a fluorophore-labeled aptamer, the GO-Pb complex served as an excellent energy acceptor in fluorescence-based analysis, as well as generating a high current in the electrochemical transducer. Additionally, the proposed platform can detect GHSA via the dual technique from a single sample, allowing for precise and accurate results. Under optimal conditions, the fluorescence-electrochemical aptasensor exhibited a linear relationship with GHSA concentrations from 0.001 to 80 μg mL-1 and from 0.005 to 10 μg mL-1 for fluorescence and electrochemical detection, respectively. The corresponding detection limits were 8.80 ng mL-1 and 0.77 ng mL-1, respectively. The proposed aptasensor additionally displayed good selectivity and excellent stability. Moreover, its successful application in the analysis of clinical samples further demonstrated its utility. Therefore, the proposed platform has significant potential as a novel, facile, highly responsive, and low-cost monitoring method for the development of diabetes mellitus diagnostic devices intended for a clinical setting.
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Affiliation(s)
- Thitirat Putnin
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani, Thailand.
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40
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Awang T, Niramitranon J, Japrung D, Saparpakorn P, Pongprayoon P. Investigating the binding affinities of fructose and galactose to human serum albumin: simulation studies. MOLECULAR SIMULATION 2021. [DOI: 10.1080/08927022.2021.1922687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Tadsanee Awang
- Department of Chemistry, Kasetsart University, Bangkok, Thailand
| | - Jitti Niramitranon
- Department of Computer Engineering, Kasetsart University, Bangkok, Thailand
| | - Deanpen Japrung
- National Nanotechnology Center, National Science and Technology Development Agency, Thailand Science Park, Pathumthani, Thailand
| | - Patchreenart Saparpakorn
- Department of Chemistry, Kasetsart University, Bangkok, Thailand
- Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok, Thailand
| | - Prapasiri Pongprayoon
- Department of Chemistry, Kasetsart University, Bangkok, Thailand
- Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok, Thailand
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Ohigashi M, Osugi K, Kusunoki Y, Washio K, Matsutani S, Tsunoda T, Matsuo T, Konishi K, Katsuno T, Namba M, Koyama H. Association of time in range with hemoglobin A1c, glycated albumin and 1,5-anhydro-d-glucitol. J Diabetes Investig 2021; 12:940-949. [PMID: 33058513 PMCID: PMC8169363 DOI: 10.1111/jdi.13437] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 10/03/2020] [Accepted: 10/07/2020] [Indexed: 12/25/2022] Open
Abstract
AIMS/INTRODUCTION Hemoglobin A1c (HbA1c), glycated albumin (GA) and 1,5-anhydro-d-glucitol (1,5-AG) are used as indicators of glycemic control, whereas continuous glucose monitoring (CGM) is used to assess daily glucose profiles. The aim of this study was to investigate the relationships between CGM metrics, such as time in range (TIR), and glycemic control indicators. MATERIALS AND METHODS We carried out retrospective CGM and blood tests on 189 outpatients with impaired glucose tolerance (n = 22), type 1 diabetes mellitus (n = 67) or type 2 diabetes mellitus (n = 100). RESULTS In type 1 diabetes mellitus and type 2 diabetes mellitus patients, HbA1c and GA were negatively correlated with TIR, whereas 1,5-AG was positively correlated with TIR. In type 1 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 6.9% (95% confidence interval [CI] 6.5-7.2%), 20.3% (95% CI 19.0-21.7%) and 6.0 µg/mL (95% CI 5.1-6.9 µg/mL), respectively. In type 2 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 7.1% (95% CI 7.0-7.3%), 19.3% (95% CI 18.7-19.9%) and 10.0 µg/mL (95% CI 9.0-11.0 µg/mL), respectively. TIR values corresponding to HbA1c levels of 7.0% were 56.1% (95% CI 52.3-59.8%) and 74.2% (95% CI 71.3-77.2%) in type 1 diabetes mellitus and type 2 diabetes mellitus patients, respectively. CONCLUSIONS The results of this study showed that the estimated HbA1c corresponding to a TIR of 70% was approximately 7.0% for both type 1 diabetes mellitus and type 2 diabetes mellitus patients, and that the estimated 1,5-AG calculated from the TIR of 70% might be different between type 1 diabetes mellitus and type 2 diabetes mellitus patients.
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Affiliation(s)
- Mana Ohigashi
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Keiko Osugi
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Yoshiki Kusunoki
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Kahori Washio
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Satoshi Matsutani
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Taku Tsunoda
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Toshihiro Matsuo
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Kosuke Konishi
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
| | - Tomoyuki Katsuno
- Department of Occupational TherapySchool of RehabilitationHyogo University of Health SciencesKobeHyogoJapan
| | - Mitsuyoshi Namba
- Department of Diabetes MellitusTakarazuka City HospitalTakarazukaHyogoJapan
| | - Hidenori Koyama
- Department of Diabetes, Endocrinology and Clinical ImmunologyHyogo College of MedicineNishinomiyaHyogoJapan
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Ferrario L, Schettini F, Avogaro A, Bellia C, Bertuzzi F, Bonetti G, Ceriello A, Ciaccio M, Corsi Romanelli M, Dozio E, Falqui L, Girelli A, Nicolucci A, Perseghin G, Plebani M, Valentini U, Zaninotto M, Castaldi S, Foglia E. Glycated Albumin for Glycemic Control in T2DM Population: A Multi-Dimensional Evaluation. CLINICOECONOMICS AND OUTCOMES RESEARCH 2021; 13:453-464. [PMID: 34079308 PMCID: PMC8166313 DOI: 10.2147/ceor.s304868] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/23/2021] [Indexed: 12/16/2022] Open
Abstract
PURPOSE To investigate the glycated albumin (GA) introduction implications, as an add-on strategy to traditional glycemic control (Hb1Ac and fasting plasma glucose - FPG) instruments, considering insulin-naïve individuals with type 2 diabetes mellitus (T2DM), treated with oral therapies. METHODS A Health Technology Assessment was conducted in Italy, as a multi-dimensional approach useful to validate any innovative technology. The HTA dimensions, derived from the EUnetHTA Core Model, were deployed by means of literature evidence, health economics tools and qualitative questionnaires, filled-in by 15 professionals. RESULTS Literature stated that the GA introduction could lead to a higher number of individuals achieving therapeutic success after 3 months of therapy (97.0% vs 71.6% without GA). From an economic point of view, considering a projection of 1,955,447 T2DM insulin-naïve individuals, potentially treated with oral therapy, GA introduction would imply fewer individuals requiring a therapy switch (-89.44%), with a 1.06% in costs reduction, on annual basis, thus being also the preferable solution from a cost-effectiveness perspective (cost-effectiveness value: 237.74 vs 325.53). According to experts opinions, lower perceptions on GA emerged with regard to equity aspects (0.13 vs 0.72, p-value>0.05), whereas it would improve both individuals (2.17 vs 1.33, p-value=0.000) and caregivers quality of life (1.50 vs 0.83, p-value=0.000). Even if in the short term, GA required additional investments in training courses (-0.80 vs 0.10, p-value = 0.036), in the long run, GA could become the preferable technology (0.30 vs 0.01, p-value=0.018) from an organisational perspective. CONCLUSION Adding GA to traditional glycaemic control instruments could improve the clinical pathway of individuals with T2DM, leading to economic and organisational advantages for both hospitals and National Healthcare Systems.
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Affiliation(s)
- Lucrezia Ferrario
- Centre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo - LIUC, Castellanza, Italy
| | - Fabrizio Schettini
- Centre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo - LIUC, Castellanza, Italy
| | - Angelo Avogaro
- Department of Medicine, University-Hospital of Padova, Padova, Italy
| | - Chiara Bellia
- Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
| | - Federico Bertuzzi
- Diabetology Unit, Grande Ospedale Metropolitano Niguarda Hospital, Milan, Italy
| | | | - Antonio Ceriello
- Department of Cardiovascular and Metabolic Diseases, Multimedica Research Institute, Milan, Italy
| | - Marcello Ciaccio
- Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
- Department of Laboratory Medicine, University-Hospital of Palermo, Palermo, Italy
| | - Massimiliano Corsi Romanelli
- Service of Laboratory Medicine 1-Clinical Pathology, Policlinico San Donato, Milan, Italy
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
| | - Elena Dozio
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
| | - Luca Falqui
- Department of Medicine, Diabetes and Endocrinology, Multimedica Research Institute, Milan, Italy
| | - Angela Girelli
- Diabetes Care Unit, Spedali Civili Hospital, Brescia, Italy
| | - Antonio Nicolucci
- Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy
| | - Gianluca Perseghin
- Department of Medicine and Surgery, Università degli Studi di Milano Bicocca, Milan, Italy
- Department of Medicine and Rehabilitation, Unit of Metabolic Medicine, Policlinico di Monza, Monza, Italy
| | - Mario Plebani
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | | | - Martina Zaninotto
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Silvana Castaldi
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
- Fondazione Ca’ Granda Ospedale Maggiore Policlinico Research Institute of Milano, Milano, Italy
| | - Emanuela Foglia
- Centre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo - LIUC, Castellanza, Italy
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Cinacalcet may suppress kidney enlargement in hemodialysis patients with autosomal dominant polycystic kidney disease. Sci Rep 2021; 11:10014. [PMID: 33976330 PMCID: PMC8113347 DOI: 10.1038/s41598-021-89480-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 04/21/2021] [Indexed: 12/24/2022] Open
Abstract
A massively enlarged kidney can impact quality of life of autosomal dominant polycystic kidney disease (ADPKD) patients. A recent in vitro study demonstrated that an allosteric modulator of the calcium sensing receptor decreases adenosine-3′,5′-cyclic monophosphate, an important factor for kidney enlargement in ADPKD. Therefore, the present study was performed to determine whether cinacalcet, a calcium sensing receptor agonist, suppresses kidney enlargement in hemodialysis patients with ADPKD. Alteration of total kidney volume together with clinical parameters was retrospectively examined in 12 hemodialysis patients with ADPKD treated at a single institution in Japan. In the non-cinacalcet group with longer hemodialysis duration (n = 5), total kidney volume had an annual increase of 4.19 ± 1.71% during an overall period of 877 ± 494 days. In contrast, the annual rate of increase in total kidney volume in the cinacalcet group (n = 7) was significantly suppressed after cinacalcet treatment, from 3.26 ± 2.87% during a period of 734 ± 352 days before the start of cinacalcet to − 4.71 ± 6.42% during 918 ± 524 days after initiation of treatment (p = 0.047). The present findings showed that cinacalcet could be a novel therapeutic tool for suppression of kidney enlargement in hemodialysis patients with ADPKD.
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Alalawi F, Bashier A. Management of diabetes mellitus in dialysis patients: Obstacles and challenges. Diabetes Metab Syndr 2021; 15:1025-1036. [PMID: 34000713 DOI: 10.1016/j.dsx.2021.05.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 04/30/2021] [Accepted: 05/02/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS Diabetic kidney disease (DKD) is a major health issue that is associated with an increased risk of morbidity and mortality. The treatment of DKD is challenging given changes in blood glucose homeostasis, unclear accuracy of glucose metrics, and altered kinetics of the blood glucose-lowering medications. There is uncertainty surrounding the optimal glycemic target in this population although recent epidemiologic data suggest that HbA1c ranges of 6-8%, as well as 7-9%, are associated with increased survival rates among diabetic dialysis patients. Furthermore, the treatment of diabetes in patients maintained on dialysis is challenging, and many blood glucose-lowering medications are renally metabolized and excreted hence requiring dose adjustment or avoidance in dialysis patients. METHOD ology: PubMed, Google Scholar, and Medline were searched for all literature discussing the management of diabetes in dialysis patients. RESULTS The literature was discussed under many subheadings providing the latest evidence in the treatment of diabetes in dialysis patients. CONCLUSION The management of diabetes in dialysis is very complex requiring a multi-disciplinary team involving endocrinologists and nephrologists to achieve targets and reduce morbidity and mortality.
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Affiliation(s)
- Fakhriya Alalawi
- Nephrology Department, Dubai Hospital. Dubai Health Authority, United Arab Emirates
| | - Alaaeldin Bashier
- Endocrine Department, Dubai Hospital. Dubai Health Authority, United Arab Emirates.
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Comparative study on hemoglobin A1c, glycated albumin and glycosylated serum protein in aplastic anemia patients with Type 2 diabetes mellitus. Biosci Rep 2021; 40:223095. [PMID: 32352504 PMCID: PMC7244899 DOI: 10.1042/bsr20192300] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 03/10/2020] [Accepted: 03/18/2020] [Indexed: 12/20/2022] Open
Abstract
Objective: To differentiate the value of hemoglobin A1c (HbA1c), glycated albumin (GA) and glycosylated serum protein (GSP) in monitoring blood glucose of patients with aplastic anemia. Methods: 42 patients with aplastic anemia (AA) and 30 patients with AA and Type 2 diabetes mellitus (T2DM) were enrolled in the study, in comparison with 114 healthy subjects and 88 subjects with T2DM. HbA1c, GA, GSP, fasting plasma glucose (FPG), hemoglobin (Hb) and albumin (ALB) were measured, and group comparison and correlation analysis were carried out. Results: Compared with the non-diabetes patients while ALB were <30 g/l or 30–40 g/l, the HbA1c and GSP values in AA, T2DM and AA+T2DM patients were significantly higher while the GA values were lower. Moreover, no differences in FPG levels. The AA+T2DM patients with ALB >40 g/l had higher HbA1c level, with no difference in GA, GSP and FPG levels. There was a positive correlation between HbA1c and GA in healthy group (ALB ≥ 40 g/l), AA patients (ALB 30–40 g/l and ≥40 g/l), T2DM patients (ALB 30–40 g/l and ≥40 g/l) and AA+T2DM patients (ALB 30–40 g/l and ≥40 g/l) but not in those with ALB < 30 g/l. Conclusion: The HbA1c results were affected by moderate-to-severe anemia, but not mild anemia. HbA1c is not recommended to detect blood glucose levels in AA patients (Hb < 90 g/l) or AA patients (ALB < 30 g/l). FPG and GSP are not suitable for AA patients.
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46
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Waiwinya W, Putnin T, Pimalai D, Chawjiraphan W, Sathirapongsasuti N, Japrung D. Immobilization-Free Electrochemical Sensor Coupled with a Graphene-Oxide-Based Aptasensor for Glycated Albumin Detection. BIOSENSORS-BASEL 2021; 11:bios11030085. [PMID: 33802824 PMCID: PMC8002523 DOI: 10.3390/bios11030085] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/05/2021] [Accepted: 03/10/2021] [Indexed: 01/03/2023]
Abstract
An immobilization-free electrochemical sensor coupled with a graphene oxide (GO)-based aptasensor was developed for glycated human serum albumin (GHSA) detection. The concentration of GHSA was monitored by measuring the electrochemical response of free GO and aptamer-bound GO in the presence of glycated albumin; their currents served as the analytical signals. The electrochemical aptasensor exhibited good performance with a base-10 logarithmic scale. The calibration curve was achieved in the range of 0.01-50 µg/mL. The limit of detection (LOD) was 8.70 ng/mL. The developed method was considered a one-drop measurement process because a fabrication step and the probe-immobilization process were not required. This simple sensor offers a cost-effective, rapid, and sensitive detection method, and could be an alternative approach for determination of GHSA levels.
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Affiliation(s)
- Wassa Waiwinya
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani 12120, Thailand; (W.W.); (T.P.); (D.P.); (W.C.)
| | - Thitirat Putnin
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani 12120, Thailand; (W.W.); (T.P.); (D.P.); (W.C.)
| | - Dechnarong Pimalai
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani 12120, Thailand; (W.W.); (T.P.); (D.P.); (W.C.)
| | - Wireeya Chawjiraphan
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani 12120, Thailand; (W.W.); (T.P.); (D.P.); (W.C.)
| | - Nuankanya Sathirapongsasuti
- Section of Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Deanpen Japrung
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani 12120, Thailand; (W.W.); (T.P.); (D.P.); (W.C.)
- Correspondence: ; Tel.: +66-2564-6665
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47
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Paria D, Convertino A, Mussi V, Maiolo L, Barman I. Silver-Coated Disordered Silicon Nanowires Provide Highly Sensitive Label-Free Glycated Albumin Detection through Molecular Trapping and Plasmonic Hotspot Formation. Adv Healthc Mater 2021; 10:e2001110. [PMID: 33236490 DOI: 10.1002/adhm.202001110] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 11/08/2020] [Indexed: 12/21/2022]
Abstract
Glycated albumin (GA) is rapidly emerging as a robust biomarker for screening and monitoring of diabetes. To facilitate its rapid, point-of-care measurements, a label-free surface-enhanced Raman spectroscopy (SERS) sensing platform is reported that leverages the specificity of molecular vibrations and signal amplification on silver-coated silicon nanowires (Ag/SiNWs) for highly sensitive and reproducible quantification of GA. The simulations and experimental measurements demonstrate that the disordered orientation of the nanowires coupled with the wicking of the analyte molecules during the process of solvent evaporation facilitates molecular trapping at the generated plasmonic hotspots. Highly sensitive detection of glycated albumin is shown with the ability to visually detect spectral features at as low as 500 × 10-9 m, significantly below the physiological range of GA in body fluids. Combined with chemometric regression models, the spectral data recorded on the Ag/SiNWs also allow accurate prediction of glycated concentration in mixtures of glycated and non-glycated albumin in proportions that reflect those in the bloodstream.
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Affiliation(s)
- Debadrita Paria
- Department of Mechanical Engineering Johns Hopkins University Baltimore MD 21218 USA
| | - Annalisa Convertino
- Instituto per la Microelettronica e i Microsistemi Consiglio Nazionale delle Ricerche Roma 00133 Italy
| | - Valentina Mussi
- Instituto per la Microelettronica e i Microsistemi Consiglio Nazionale delle Ricerche Roma 00133 Italy
| | - Luca Maiolo
- Instituto per la Microelettronica e i Microsistemi Consiglio Nazionale delle Ricerche Roma 00133 Italy
| | - Ishan Barman
- Department of Mechanical Engineering Johns Hopkins University Baltimore MD 21218 USA
- Department of Oncology Johns Hopkins University School of Medicine Baltimore MD 21218 USA
- Department of Radiology & Radiological Science Johns Hopkins University School of Medicine Baltimore MD 21218 USA
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Copur S, Siriopol D, Afsar B, Comert MC, Uzunkopru G, Sag AA, Ortiz A, Covic A, van Raalte DH, Cherney DZ, Rossing P, Kanbay M. Serum glycated albumin predicts all-cause mortality in dialysis patients with diabetes mellitus: meta-analysis and systematic review of a predictive biomarker. Acta Diabetol 2021; 58:81-91. [PMID: 32862262 DOI: 10.1007/s00592-020-01581-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 07/16/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM HbA1c, the traditional and current gold standard biomarker guiding diabetic management, has been scrutinized for low predictive value for patients with chronic kidney disease due to variables affecting erythrocyte number and turnover. Glycated albumin, the precursor to advanced glycation end products, reflects glycemic status over the preceding 2-3 week period and already outperforms HbA1c for glycemic monitoring. Our aim was to establish whether serum GA can be further used to predict mortality risk in dialysis patients with diabetes mellitus (DM) METHODS: We did systematic review of the literature in PubMed/Medline, Web of Science, Embase (Elsevier) and the Cochrane Central Register of Controlled Trials (Wiley) up to and including February 2020. RESULTS This meta-analysis included 25,932 dialysis patients across 12 studies with maximum follow-up of 11 years. Higher GA levels were associated with the risk of all-cause mortality in dialysis patients with DM (HR 1.02, 95% CI 1.01 to 1.03, P < 0.001) irrespective of the type of dialysis, whereas higher GA was not associated with cardiovascular mortality (HR 1.03, 95% CI 0.99 to 1.06, P = 0.15) and cardiovascular events (both fatal and non-fatal) (HR 1.03, 95% CI 0.97 to 1.09, P = 0.31) in dialysis patients with DM. CONCLUSION Serum glycated albumin predicts all-cause mortality risk in dialysis patients with DM. The endpoints of cardiovascular mortality and cardiovascular events trended similarly, but did not reach significance at the current sample size.
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Affiliation(s)
- Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Dimitrie Siriopol
- Department of Nephrology, Grigore T. Popa' University of Medicine, Iasi, Romania
| | - Baris Afsar
- Department of Medicine, Division of Nephrology, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Melis C Comert
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Gizem Uzunkopru
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Alan A Sag
- Division of Vascular and Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Alberto Ortiz
- Dialysis Unit, School of Medicine, IIS-Fundacion Jimenez Diaz, Universidad Autónoma de Madrid, Avd. Reyes Católicos 2, 28040, Madrid, Spain
| | - Adrian Covic
- Department of Nephrology, Grigore T. Popa' University of Medicine, Iasi, Romania
| | - Daniel H van Raalte
- Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Loaction VUMC, Amsterdam, The Netherlands
| | - David Z Cherney
- Toronto General Hospital Research Institute, UHN, Toronto, Canada
- Departments of Physiology and Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Copenhagen Denmark and University of Copenhagen, Copenhagen, Denmark
| | - Mehmet Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, 34010, Istanbul, Turkey.
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Bomholt T, Oturai P, Rix M, Almdal T, Knop FK, Rosthøj S, Feldt-Rasmussen B, Hornum M. Reduced erythrocyte lifespan measured by chromium-51 in patients with type 2 diabetes undergoing long-term hemodialysis. Hemodial Int 2020; 25:198-204. [PMID: 33274575 DOI: 10.1111/hdi.12908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 11/10/2020] [Accepted: 11/23/2020] [Indexed: 11/27/2022]
Abstract
INTRODUCTION A reduced erythrocyte lifespan potentially explains the low hemoglobin A1c values found in hemodialysis patients. However, data supporting this notion in patients with type 2 diabetes is unclear. We evaluated the erythrocyte lifespan in patients with type 2 diabetes undergoing long-term hemodialysis and investigated potential predictors of erythrocyte lifespan. METHODS Long-term hemodialysis patients with type 2 diabetes and type 2 diabetes patients without nephropathy (estimated glomerular filtration rate > 60 mL/min/1.73 m2 ) were included. The erythrocyte lifespan was measured using chromium-51 (51 Cr)-labeled erythrocytes. Blood radiotracer activity was measured six to nine times over a period of 3-5 weeks to determine the erythrocyte lifespan of each patient. Biochemical markers were obtained five times over 16 weeks and associated with the erythrocyte lifespan. FINDINGS Type 2 diabetes patients undergoing hemodialysis (N = 13) had a significantly shorter median erythrocyte lifespan of 49.7 (interquartile range [IQR] = 44.1-58.6) days compared with 64.2 (IQR = 62.6-83.5) days in the control group (N = 10) (P ˂ 0.001) with a difference between medians of 14.5 (95% confidence interval = 8.1-38.8) days. In the hemodialysis group, no association could be detected between the erythrocyte lifespan and markers of hemolysis, level of inflammation, or urea. DISCUSSION A reduced erythrocyte lifespan was detected in type 2 diabetes patients undergoing long-term hemodialysis. This may contribute to the reduced hemoglobin A1c values observed in the type 2 diabetic hemodialysis population. An association could not be detected between the erythrocyte lifespan and biochemical markers of hemolysis or inflammation.
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Affiliation(s)
- Tobias Bomholt
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Marianne Rix
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Almdal
- Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Filip K Knop
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Susanne Rosthøj
- Section of Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Bo Feldt-Rasmussen
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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50
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Reading patterns of proteome damage by glycation, oxidation and nitration: quantitation by stable isotopic dilution analysis LC-MS/MS. Essays Biochem 2020; 64:169-183. [PMID: 32065835 DOI: 10.1042/ebc20190047] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 01/08/2020] [Accepted: 01/13/2020] [Indexed: 12/25/2022]
Abstract
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides a high sensitivity, high specificity multiplexed method for concurrent detection of adducts formed by protein glycation, oxidation and nitration, also called AGEomics. Combined with stable isotopic dilution analysis, it provides for robust quantitation of protein glycation, oxidation and nitration adduct analytes. It is the reference method for such measurements. LC-MS/MS has been used to measure glycated, oxidized and nitrated amino acids - also called glycation, oxidation and nitration free adducts, with a concurrent quantitation of the amino acid metabolome in physiological fluids. Similar adduct residues in proteins may be quantitated with prior exhaustive enzymatic hydrolysis. It has also been applied to quantitation of other post-translation modifications, such as citrullination and formation of Nε-(γ-glutamyl)lysine crosslink by transglutaminases. Application to cellular and extracellular proteins gives estimates of the steady-state levels of protein modification by glycation, oxidation and nitration, and measurement of the accumulation of glycation, oxidation and nitration adducts in cell culture medium and urinary excretion gives an indication of flux of adduct formation. Measurement of glycation, oxidation and nitration free adducts in plasma and urine provides for estimates of renal clearance of free adducts. Diagnostic potential in clinical studies has been enhanced by the combination of estimates of multiple adducts in optimized diagnostic algorithms by machine learning. Recent applications have been in early-stage detection of metabolic, vascular and renal disease, and arthritis, metabolic control and risk of developing vascular complication in diabetes, and a blood test for autism.
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