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Lin Z, He J, Yuan S, Song C, Bian X, Yang M, Dou K. Hemoglobin glycation index and cardiovascular outcomes in patients with diabetes and coronary artery disease: insights from a large cohort study. Nutr Diabetes 2024; 14:69. [PMID: 39191777 DOI: 10.1038/s41387-024-00318-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 07/11/2024] [Accepted: 07/16/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND/OBJECTIVES The hemoglobin glycation index (HGI) has been demonstrated to serve as a substitute for the individual bias in glycosylated hemoglobin A1c (HbA1c). Our objective was to assess the correlation between HGI and cardiovascular (CV) outcomes in patients with diabetes and coronary artery disease (CAD). SUBJECTS/METHODS We sequentially recruited 11921 patients with diabetes and CAD at Fuwai Hospital. The patients were categorized into five groups based on their HGI quintiles, ranging from Q1 to Q5. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), which included CV death and nonfatal myocardial infarction. RESULTS During the median 3-year follow-up, 327 (2.7%) MACEs were observed. A U-shaped relationship between HGI and 3-year MACEs was demonstrated by restricted cubic spline (RCS) after multivariable adjustment (nonlinear P = 0.014). The Kaplan-Meier curves demonstrated that the Q2 group had the lowest risk of MACE (P = 0.006). When comparing the HGI Q2 group, multivariable Cox regression models showed that both low (Q1) and high (Q4 or Q5) HGI were linked to a higher risk of MACEs (all P < 0.05). Patients with a low HGI (Q1) had a significantly increased risk of all-cause and CV death, with a 1.70-fold increase in both cases (both P < 0.05). CONCLUSIONS In individuals with diabetes and established CAD, HGI levels were found to have a U-shaped relationship with the occurrence of MACEs over a period of three years. Significantly, those with low HGI had an increased risk of CV death.
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Affiliation(s)
- Zhangyu Lin
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jining He
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sheng Yuan
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenxi Song
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohui Bian
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min Yang
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Kefei Dou
- State Key Laboratory of Cardiovascular Disease, Beijing, China.
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- National Clinical Research Center for Cardiovascular Diseases, Beijing, China.
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Le TQ, Thanh KM, Tran TV, Nguyen DTB, Nguyen LT, Pham DT, Dam LTP, Hoang MT, Huynh TQ. The Correlation Between Glycation Gap and Renal Complications in Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2024; 17:333-341. [PMID: 38283633 PMCID: PMC10821664 DOI: 10.2147/dmso.s439800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 01/16/2024] [Indexed: 01/30/2024] Open
Abstract
Purpose The aim of this study was to investigate the correlations between the glycation gap (GG) and renal complications such as urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus patients. Materials and Methods A cross-sectional study was conducted on 104 individuals (52 males and 52 females), aged 36-93 years old. Fasting blood glucose (FBG), HbA1c, and serum fructosamine were measured simultaneously. GG was calculated as the difference between the measured and fructosamine-based predicted HbA1c levels (FHbA1c). Results There was a moderately positive correlation between HbA1c and fructosamine concentration (r = 0.488; p < 0.001). GG was positively correlated with UACR (r = 0.3275; p = 0.0007), negatively correlated with eGFR (r = -0.3400; p = 0.0004). HbA1c was positively correlated with UACR (r = 0.2437; p = 0.0127) but not correlated with eGFR (r = -0.444; p = 0.6542). Fructosamine has a positive correlation with eGFR (r = 0.2426; p = 0.0131) but not with UACR (r = -0.1021; p = 0.3025). Conclusion GG was positively correlated with UACR and inversely correlated with eGFR in type 2 Diabetes mellitus patients. This suggests that GG is a valuable index for predicting kidney complications due to diabetes.
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Affiliation(s)
- Tuan Quoc Le
- Department of Physiology-Pathophysiology-Immunology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Khanh Minh Thanh
- Department of Physiology-Pathophysiology-Immunology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Tien Van Tran
- Department of Nephrology, Ho Chi Minh City Hospital for Rehabilitation - Professional Diseases, Ho Chi Minh City, Vietnam
| | | | - Le Thi Nguyen
- Nephrology Department, University Medical Center, Ho Chi Minh City, Vietnam
| | - Diep Thao Pham
- Biochemistry Department, Viet Duc Hospital, Ha Noi, Vietnam
| | - Lan Thi Phuong Dam
- Biochemistry Department, 103 Military Medical Hospital, Vietnam Military Medical University (VMMU), Ha Noi City, Vietnam
| | - Minh Thị Hoang
- Biochemistry Department, 103 Military Medical Hospital, Vietnam Military Medical University (VMMU), Ha Noi City, Vietnam
| | - Thuan Quang Huynh
- Biochemistry Department, 103 Military Medical Hospital, Vietnam Military Medical University (VMMU), Ha Noi City, Vietnam
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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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Lin L, Wang A, Jia X, Wang H, He Y, Mu Y, Dou J. High hemoglobin glycation index is associated with increased risk of diabetes: A population-based cohort study in China. Front Endocrinol (Lausanne) 2023; 14:1081520. [PMID: 36909319 PMCID: PMC9999023 DOI: 10.3389/fendo.2023.1081520] [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: 10/27/2022] [Accepted: 02/08/2023] [Indexed: 02/26/2023] Open
Abstract
PURPOSE The hemoglobin glycation index (HGI) quantifies the mismatch between glycated hemoglobin A1c and average glycemia among individuals. Currently, it is unknown the potential role of HGI in exhaustively evaluating the progression of glucose metabolism/the risk of developing diabetes mellitus. Therefore, this study aimed to investigate the association between HGI and the risk of incident diabetes. METHODS A total of 7,345 participants aged at least 40 years and without diabetes were divided into three groups according to the tertile of their baseline HGI level and followed for a median of 3.24 years to track new-onset diabetes. Using multivariate Cox regression analyses, we explored the association between the HGI, both categorized and continuous, and incident diabetes. RESULTS During follow-up, 742 subjects (263 males and 479 females) developed diabetes mellitus. Higher HGI was associated with an increased risk of diabetes, even when adjusted for confounding factors, and every standard deviation increase in HGI was associated with a significant risk increase of 30.6% for diabetes (hazard ratio 1.306, 95% confidence interval 1.232-1.384). CONCLUSIONS Participants with a higher HGI were at a higher risk of future diabetes, irrespective of their glycemic conditions. Consequently, HGI may be employed to identify individuals at high risk for diabetes.
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Affiliation(s)
- Lu Lin
- Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- Department of Endocrinology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Anping Wang
- Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Xiaomeng Jia
- Center for Endocrine Metabolism and Immune Disease, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Haibin Wang
- Department of endocrinology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yan He
- Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China
- Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Yiming Mu
- Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Jingtao Dou
- Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- *Correspondence: Jingtao Dou,
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Marks BE, Wolfsdorf JI. Monitoring of paediatric type 1 diabetes. Curr Opin Pediatr 2022; 34:391-399. [PMID: 35836398 DOI: 10.1097/mop.0000000000001136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW This article reviews recent developments in methods used to monitor paediatric type 1 diabetes (T1D), including an examination of the role of glycated haemoglobin (haemoglobin A1c) and its limitations for long-term assessment of glycaemia in individual patients, self-monitoring of blood glucose, continuous glucose monitoring (CGM) systems and ketone monitoring. RECENT FINDINGS Monitoring of glycemia and ketones, when indicated, is a cornerstone of paediatric T1D management and is essential to optimize glycaemic control. Ongoing technological advancements have led to rapid changes and considerable improvement in the methods used to monitor glucose concentrations in people with T1D. As a result of recent innovations that have enhanced accuracy and usability, CGM is now considered the optimal method for monitoring glucose concentrations and should be introduced soon after diagnosis of T1D. SUMMARY Patients/families and healthcare providers must receive comprehensive education and proper training in the use of CGM and interpretation of the vast amounts of data. Future challenges include ensuring equal access to and optimizing clinical use of CGM to further improve T1D care and outcomes.
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Affiliation(s)
- Brynn E Marks
- Children's National Hospital, Division of Endocrinology, Washington, District of Columbia
| | - Joseph I Wolfsdorf
- Boston Children's Hospital, Division of Endocrinology, Boston, Massachusetts, USA
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Wang S, Gu L, Chen J, Jiang Q, Sun J, Wang H, Wang L. Association of hemoglobin glycation index and glycation gap with cardiovascular disease among US adults. Diabetes Res Clin Pract 2022; 190:109990. [PMID: 35820564 DOI: 10.1016/j.diabres.2022.109990] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/16/2022] [Accepted: 07/06/2022] [Indexed: 01/01/2023]
Abstract
AIMS To investigate the association of hemoglobin glycation index (HGI) and glycation gap (GGap), reflecting mismatches between HbA1c and other measures of glycemia, with cardiovascular disease (CVD) in the general population. METHODS 5966 US adult (age ≥ 20 years) participants were included from the National Health and Nutrition Examination Survey (NHANES) (1999-2004). In this cross-sectional study, predicted HbA1c was calculated based on fasting plasma glucose (FPG) and glycated albumin (GA), respectively. Multivariable binary logistic regression analysis was performed to explore the association of HGI and GGap with CVD prevalence. RESULTS Compared to the lowest tertile, the ORs with 95% CIs for CVD across the tertiles were 1.41 (1.01, 1.96) and 0.87 (0.58, 1.31) for HGI (P for trend = 0.535) and 1.06 (0.77, 1.47) and 1.60 (1.18, 2.17) for GGap (P for trend = 0.002) in the fully-adjusted model. Besides, the discordantly high GGap/low HbA1c group was associated with higher CVD prevalence compared with the low GGap/high HbA1c group (OR = 1.50, 95% CI, 1.04-2.16, P = 0.030). CONCLUSIONS GGap derived from GA is associated with CVD independent of traditional risk factors, even HbA1c, in US general adults. Considering the potential limitations of HbA1c, the introduction of GGap is warranted.
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Affiliation(s)
- Sibo Wang
- Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China
| | - Lingfeng Gu
- Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China
| | - Jiawen Chen
- Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China
| | - Qiqi Jiang
- Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China
| | - Jiateng Sun
- Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China
| | - Hao Wang
- Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China
| | - Liansheng Wang
- Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China.
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Gomez-Peralta F, Choudhary P, Cosson E, Irace C, Rami-Merhar B, Seibold A. Understanding the clinical implications of differences between glucose management indicator and glycated haemoglobin. Diabetes Obes Metab 2022; 24:599-608. [PMID: 34984825 DOI: 10.1111/dom.14638] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 12/20/2021] [Accepted: 01/01/2022] [Indexed: 12/18/2022]
Abstract
Laboratory measured glycated haemoglobin (HbA1c) is the gold standard for assessing glycaemic control in people with diabetes and correlates with their risk of long-term complications. The emergence of continuous glucose monitoring (CGM) has highlighted limitations of HbA1c testing. HbA1c can only be reviewed infrequently and can mask the risk of hypoglycaemia or extreme glucose fluctuations. While CGM provides insights in to the risk of hypoglycaemia as well as daily fluctuations of glucose, it can also be used to calculate an estimated HbA1c that has been used as a substitute for laboratory HbA1c. However, it is evident that estimated HbA1c and HbA1c values can differ widely. The glucose management indicator (GMI), calculated exclusively from CGM data, has been proposed. It uses the same scale (% or mmol/mol) as HbA1c, but is based on short-term average glucose values, rather than long-term glucose exposure. HbA1c and GMI values differ in up to 81% of individuals by more than ±0.1% and by more than ±0.3% in 51% of cases. Here, we review the factors that define these differences, such as the time period being assessed, the variation in glycation rates and factors such as anaemia and haemoglobinopathies. Recognizing and understanding the factors that cause differences between HbA1c and GMI is an important clinical skill. In circumstances when HbA1c is elevated above GMI, further attempts at intensification of therapy based solely on the HbA1c value may increase the risk of hypoglycaemia. The observed difference between GMI and HbA1c also informs the important question about the predictive ability of GMI regarding long-term complications.
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Affiliation(s)
| | - Pratik Choudhary
- Leicester Diabetes Centre - Bloom, University of Leicester, Leicester General Hospital, Leicester, UK
| | - Emmanuel Cosson
- Department of Endocrinology-Diabetology-Nutrition, AP-HP, Avicenne Hospital, Université Paris 13, Bobigny, France
- Paris 13 University, Sorbonne Paris Cité, UMR U557 INSERM/U11125 INRAE/CNAM/Université Paris13, Unité de Recherche Epidémiologique Nutritionnelle, Bobigny, France
| | - Concetta Irace
- Department of Health Science, University Magna Graecia, Catanzaro, Italy
| | - Birgit Rami-Merhar
- Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria
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Delanghe JR, Lambrecht S, Fiers T, Speeckaert MM. Labile glycated hemoglobin: an underestimated laboratory marker of short term glycemia. Clin Chem Lab Med 2022; 60:451-455. [PMID: 35041778 DOI: 10.1515/cclm-2021-1321] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 01/10/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Diabetes mellitus is a major public health problem. Hemoglobin A1c (HbA1c) is a key laboratory parameter in the management of diabetes patients. However, in diabetes monitoring, interpretation of HbA1c results is hampered by the important interindividual variation in red blood cell (RBC) life span. Furthermore, HbA1c only slowly responds to changes in glucose metabolism. Besides HbA1c, there exists a labile HbA1c fraction (l-HbA1c), exhibiting much faster kinetics. As both HbA1c and l-HbA1c are measured by modern standard chromatography, we explored the possibilities of using the l-HbA1c fraction for monitoring glycemia. METHODS l-HbA1c and HbA1c fractions were simultaneously assayed on a Tosoh G8 analyzer and expressed as %. l-HbA1c results were compared with serum glucose and HbA1c. Concomitantly, RBC distribution width (RDW) was determined on a Sysmex SN analyzer as a marker for erythrocyte life span. RESULTS l-HbA1c could be measured with between-run coefficient of variations (CVs) between 2.2 and 2.3%. l-HbA1c correlated with both glycemia (r=0.80) and HbA1c results (r=0.73). In a multiple regression model (r2=0.752), glycemia and HbA1c were the most determining factors. To a lesser extent, RDW correlated with l-HbA1c (r=0.158). Furthermore, the l-HbA1c/HbA1c ratio weakly positively correlated with RDW (r=0.247). CONCLUSIONS L-HBA1c represents an additional marker for monitoring the rapid occurrence of glycemic disorders that escape detection when using only HbA1c and blood glucose. RDW can be used as an indicator of atypical RBCs life span, in which the l-HbA1c fraction may be helpful.
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Affiliation(s)
- Joris R Delanghe
- Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium
| | - Stijn Lambrecht
- Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium
| | - Tom Fiers
- Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium
| | - Marijn M Speeckaert
- Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.,Research Foundation-Flanders (FWO), Brussels, Belgium
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Toschi E, Michals A, Adam A, Davis D, Atakov-Castillo A, Slyne C, Munshi M. Usefulness of CGM-Derived Metric, the Glucose Management Indicator, to Assess Glycemic Control in Non-White Individuals With Diabetes. Diabetes Care 2021; 44:2787-2789. [PMID: 34635503 PMCID: PMC8669533 DOI: 10.2337/dc21-1373] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/14/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess the relationship between the glucose management indicator (GMI) and HbA1c in non-White individuals with diabetes. RESEARCH DESIGN AND METHODS We performed a retrospective analysis of continuous glucose monitoring metrics in individuals with diabetes divided by race into non-White and White cohorts. RESULTS We evaluated 316 individuals (non-White n = 68; White n = 248). Although GMI was not different (7.6 vs. 7.7; P = not significant) between the cohorts, HbA1c was higher in the non-White cohort (8.7% vs. 8.1%; P = 0.004). HbA1c higher than GMI by ≥0.5% was more frequently observed in the non-White cohort (90% vs. 75%; P = 0.02). In the non-White cohort only, duration of hypoglycemia was longer among those with HbA1c higher than GMI by ≥0.5% compared with those with HbA1c and GMI within 0.5%. CONCLUSIONS A differential relationship between HbA1c and GMI in non-White versus White individuals with diabetes was observed. In non-White individuals, a greater difference between HbA1c and GMI was associated with higher risk of hypoglycemia.
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Affiliation(s)
- Elena Toschi
- Joslin Diabetes Center, Boston, MA .,Beth Israel Deaconess Medical Center, Boston, MA.,Harvard Medical School, Boston, MA
| | | | | | | | | | | | - Medha Munshi
- Joslin Diabetes Center, Boston, MA.,Beth Israel Deaconess Medical Center, Boston, MA.,Harvard Medical School, Boston, MA
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10
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Doumatey AP, Feron H, Ekoru K, Zhou J, Adeyemo A, Rotimi CN. Serum fructosamine and glycemic status in the presence of the sickle cell mutation. Diabetes Res Clin Pract 2021; 177:108918. [PMID: 34126128 PMCID: PMC8447861 DOI: 10.1016/j.diabres.2021.108918] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/18/2021] [Accepted: 06/09/2021] [Indexed: 11/29/2022]
Abstract
AIMS The glycated hemoglobin (HbA1c) test can be unreliable in the presence of hemoglobinopathies. The co-existence of type 2 diabetes (T2D) with sickle cell anemia calls for alternative tests. Therefore, we established a reference interval for serum fructosamine and evaluated its utility as a potential glycemic biomarker that is not affected by abnormal hemoglobin. METHODS The accuracies of serum fructosamine in monitoring and diagnosing T2D were evaluated using the Area under the Receiver Operating Characteristics and other measures in 618 Nigerians with or without sickle cell trait. The estimated diagnostic cut-off for serum fructosamine was then validated in an independent multi-ethnic cohort of 634 West Africans. RESULTS Serum fructosamine was similar between individuals with or without sickle cell trait (median: 287 vs 275 umol/L, p = 0·11, respectively) despite statistically different HbA1c. Fructosamine was highly correlated with both HbA1c and fasting glucose independently of sickle cell trait. The areas under the curve (AUC) of serum fructosamine in identifying individuals with uncontrolled glycemia and individuals with T2D were similar and independent of sickle cell trait: 0·92 (95% confidence interval [95% CI ], 0·88-0·95 and 0.92 (95% CI, (0.89-0.95) respectively. CONCLUSIONS Serum fructosamine is a good alternative to HbA1c for monitoring and diagnosing T2D in the presence of sickle cell trait.
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Affiliation(s)
- Ayo P Doumatey
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, MD 20892, United States.
| | - Hermon Feron
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, MD 20892, United States
| | - Kenneth Ekoru
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, MD 20892, United States
| | - Jie Zhou
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, MD 20892, United States
| | - Adebowale Adeyemo
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, MD 20892, United States
| | - Charles N Rotimi
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, MD 20892, United States.
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11
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Predicted HbA1c and fructosaminated HbA1c: evaluating their role as an indicator of glycemic status in diabetes mellitus: a hospital based cross-sectional study. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00942-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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12
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Mi J, Song J, Zhao Y, Wu X. Association of hemoglobin glycation index and its interaction with obesity/family history of hypertension on hypertension risk: a community-based cross-sectional survey. BMC Cardiovasc Disord 2020; 20:477. [PMID: 33148181 PMCID: PMC7640660 DOI: 10.1186/s12872-020-01762-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 10/29/2020] [Indexed: 01/12/2023] Open
Abstract
Background Hemoglobin glycation index (HGI) is considered to be a convenient measurable indicator to assess the inter-individual variation of HbA1c. In the present study, we tested the relationship between HGI and risk of hypertension, and further explored the possible interacting influences of HGI with other such factors on hypertension risk among Chinese individuals. Methods The eligible subjects were chosen from a community-based cross-sectional survey in China. We collected relevant data and clinical indicators for each participant. HGI was calculated as “measured HbA1c-predicted HbA1c” and divided into four categories according to quartile. The following indicators were used to assess interactive effects: (1) relative excess risk due to interaction (RERI); (2) attributable proportion due to interaction (AP); and (3) synergy index (SI). Statistical analysis was performed using R software. Results Specifically, 1777 eligible participants were selected in this cross-sectional survey. There were 433 subjects who were identified to have hypertension (24.4%). A significant increase in the prevalence of hypertension from Q1 to Q4 of HGI was observed (p < 0.001). Multivariable logistic model demonstrated that subjects at the highest HGI group had a substantially increased risk of being hypertensive than subjects in the first quartile of HGI, as indicated by the OR value of 1.87 (95% CI 1.26–2.78). Moreover, a significant interaction between family history of hypertension and HGI on hypertension risk was detected (RERI: 1.36, 95% CI 0.11–2.63; AP: 0.43, 95% CI 0.17–0.69; and SI:2.68, 95% CI 1.10–6.48). The interactive effect between HGI and abdominal obesity was also found to be significant, as estimated by the value of RERI (1.04, 95% CI 0.24–1.85), AP (0.33, 95% CI 0.11–0.56) and SI (1.96, 95% CI 1.01–3.79). However, in the analysis of the interaction between HGI and general obesity, only the AP value (0.28, 95% CI 0.01–0.54) was observed to be significant. Conclusion High HGI was independently associated with the risk of hypertension. Moreover, HGI significantly shared interactions with obesity and family history of hypertension that influenced the risk of hypertension.
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Affiliation(s)
- Jing Mi
- School of Public Health, Bengbu Medical College, 2600 Donghai road, Bengbu, 233000, Anhui Province, China
| | - Jian Song
- School of Public Health, Bengbu Medical College, 2600 Donghai road, Bengbu, 233000, Anhui Province, China
| | - Yingying Zhao
- Bengbu Health Board, 568 Nanhu road, Bengbu, 233000, Anhui Province, China
| | - Xuesen Wu
- School of Public Health, Bengbu Medical College, 2600 Donghai road, Bengbu, 233000, Anhui Province, China.
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13
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Urakami T, Yoshida K, Kuwabara R, Mine Y, Aoki M, Suzuki J, Morioka I. Individualization of recommendations from the international consensus on continuous glucose monitoring-derived metrics in Japanese children and adolescents with type 1 diabetes. Endocr J 2020; 67:1055-1062. [PMID: 32565500 DOI: 10.1507/endocrj.ej20-0193] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
We assessed the significance of recommendations from the international consensus on continuous glucose monitoring (CGM)-derived metrics in Japanese children and adolescents with type 1 diabetes. Eighty-five patients (age, 13.5 ± 4.7 years) who wore the FreeStyle® Libre for a 28-day period were enrolled in this study. Seventy-three patients were treated with multiple daily injections of insulin and 12 with insulin pump therapy without using a sensor-augmented pump or a predictive low-glucose suspend-function pump. We evaluated the relationship between CGM-derived metrics: time in range (TIR: 70-180 mg/dL), time below range (TBR: <70 mg/dL), and time above range (TAR: >180 mg/dL), and laboratory-measured HbA1c and estimated HbA1c (eA1c) levels calculated from the mean glucose values. The TIR was 50.7 ± 12.2% (23-75%), TBR was 11.8 ± 5.8% (2-27%), and TAR was 37.5 ± 13.5% (9-69%). The TIR was highly correlated with HbA1c level, eA1c level, and TAR, but not with TBR. An HbA1c level of 7.0% corresponded to a TIR of 55.1% (95% CI: 53.7-56.5%), whereas a TIR of 70% corresponded to an HbA1c level of 6.1% (95% CI: 5.9-6.3%). The results of eA1c levels were similar to those observed for HbA1c levels. From these findings, we conclude that low rates of a recommended TIR of 70% may be due to less use of advanced technology and insufficient comprehensive diabetes care. Ethnic characteristics including lifestyle and eating customs may have contributed to the result. CGM-derived targets must be individualized based on ethnic characteristics, insulin treatment and diabetes care, and needs of individuals with diabetes.
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Affiliation(s)
- Tatsuhiko Urakami
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Kei Yoshida
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Remi Kuwabara
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Yusuke Mine
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Masako Aoki
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Junichi Suzuki
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Ichiro Morioka
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
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14
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Jagannathan R, Neves JS, Dorcely B, Chung ST, Tamura K, Rhee M, Bergman M. The Oral Glucose Tolerance Test: 100 Years Later. Diabetes Metab Syndr Obes 2020; 13:3787-3805. [PMID: 33116727 PMCID: PMC7585270 DOI: 10.2147/dmso.s246062] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 09/24/2020] [Indexed: 12/15/2022] Open
Abstract
For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1-h PG. Measurement of the 1-h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic ß-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2-h OGTT making it more acceptable in the clinical setting.
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Affiliation(s)
- Ram Jagannathan
- Division of Hospital Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - João Sérgio Neves
- Department of Surgery and Physiology, Cardiovascular Research and Development Center, Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Endocrinology, Diabetes and Metabolism, Sa˜o Joa˜ o University Hospital Center, Porto, Portugal
| | - Brenda Dorcely
- NYU Grossman School of Medicine, Division of Endocrinology, Diabetes, Metabolism, New York, NY10016, USA
| | - Stephanie T Chung
- Diabetes, Obesity, and Endocrinology Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Kosuke Tamura
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, Cardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD20892, USA
| | - Mary Rhee
- Emory University School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipids, Atlanta VA Health Care System, Atlanta, GA30322, USA
| | - Michael Bergman
- NYU Grossman School of Medicine, NYU Diabetes Prevention Program, Endocrinology, Diabetes, Metabolism, VA New York Harbor Healthcare System, Manhattan Campus, New York, NY10010, USA
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15
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Vergès B, Rouland A, Baillot-Rudoni S, Brindisi MC, Duvillard L, Simoneau I, Legris P, Petit JM, Bouillet B. Increased body fat mass reduces the association between fructosamine and glycated hemoglobin in obese type 2 diabetes patients. J Diabetes Investig 2020; 12:619-624. [PMID: 32767822 PMCID: PMC8015815 DOI: 10.1111/jdi.13383] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/21/2020] [Accepted: 08/02/2020] [Indexed: 01/23/2023] Open
Abstract
Obesity is increasing in patients with type 2 diabetes. A possible reduced association between fructosamine and glycated hemoglobin (HbA1c) in obese individuals has been previously discussed, but this has never been specifically evaluated in type 2 diabetes, and the potential influence of body fat mass and fat distribution has never been studied. We studied 112 type 2 diabetes patients with assessment of fat mass, liver fat and fat distribution. Patients with body mass index (BMI) above the median (34.9 kg/m2 ), versus BMI below the median, had a correlation coefficient between fructosamine and HbA1c significantly reduced (r = 0.358 vs r = 0.765). In the whole population, fructosamine was correlated negatively with BMI and fat mass. In multivariate analysis, fructosamine was associated with HbA1c (positively) and fat mass (negatively), but not with BMI, liver fat or fat distribution. The association between fructosamine and HbA1c is significantly reduced in the most obese type 2 diabetes patients, and this is mostly driven by increased fat mass.
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Affiliation(s)
- Bruno Vergès
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France.,INSERM LNC-UMR1231, University of Burgundy, Dijon, France
| | - Alexia Rouland
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France
| | - Sabine Baillot-Rudoni
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France
| | - Marie-Claude Brindisi
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France
| | - Laurence Duvillard
- INSERM LNC-UMR1231, University of Burgundy, Dijon, France.,Department of Biochemistry, CHU Dijon, Dijon, France
| | - Isabelle Simoneau
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France.,INSERM LNC-UMR1231, University of Burgundy, Dijon, France
| | - Pauline Legris
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France
| | - Jean-Michel Petit
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France.,INSERM LNC-UMR1231, University of Burgundy, Dijon, France
| | - Benjamin Bouillet
- Department of Endocrinology, Diabetology and Metabolic Diseases, CHU Dijon, Dijon, France.,INSERM LNC-UMR1231, University of Burgundy, Dijon, France
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16
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Gordon DK, Hussain M, Kumar P, Khan S, Khan S. The Sickle Effect: The Silent Titan Affecting Glycated Hemoglobin Reliability. Cureus 2020; 12:e9685. [PMID: 32923278 PMCID: PMC7486097 DOI: 10.7759/cureus.9685] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 08/12/2020] [Indexed: 12/18/2022] Open
Abstract
Hemoglobin A1c (HbA1c) is a popular invaluable tool in the diagnosis of Type 2 diabetes for red blood cells (RBCs) with a lifespan of 120 days; however, many factors, including hemoglobinopathies, affect its accuracy. Sickle cell trait, primarily a benign medical condition, is a point mutation in only one of two beta-globin genes on chromosome 11. We performed a traditional review to identify how the sickle cell trait (SCT) affects the interpretation of HbA1c and the further implications it may have on the diagnosis and management of Type 2 diabetes. A literature search was performed using PubMed®/MEDLINE® and Google Scholar with formulated keywords (sickle cell trait, HbAS, HbA1c, glycosylated hemoglobin, diabetes, RBC lifespan, race, and genetics), with the majority of results being mainly observational studies. The National Glycohemoglobin Standardization Program (NGSP) is responsible for standardizing HbA1c results and also highlights factors that can interfere with HbA1c, including hemoglobin variants. Studies that utilize only an NGSP-certified method with no clinically significant interference by HbS in patients with and without SCT showed contrasting results. Additional studies showed that persons of African ancestry, the group to which the majority of SCT patients belong, have a higher HbA1c than non-Hispanic whites (NHWs), just based on race, and a greater probability of having glucose-6-phosphate dehydrogenase (G6PD) deficiency, which lowers HbA1c. The most extensive study investigating the RBC lifespan in SCT patients showed a reduction in the cell lifespan compared to normal patients; however, other smaller studies were contradictory. Our study highlights the need for hemoglobinopathy detection before or during HbA1c measurement in populations with a high degree of African ancestry and the importance of patient notification. It also shows that SCT affects the accuracy of HbA1c, through its likely reduction of RBC lifespan and its increased association with African ancestry and G6PD deficiency. This review recommends that for SCT patients with potential Type 2 diabetes, HbA1c should be used in combination with another diagnostic tool such as fasting blood glucose, fructosamine, or glycated albumin to decrease the chances of a missed diagnosis.
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Affiliation(s)
- Domonick K Gordon
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Scarborough General Hospital, Scarborough, TTO
| | - Madiha Hussain
- Neuropsychiatry, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Prabhat Kumar
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, USA
- Medicine and Surgery, Bangalore Medical College & Research Institute, Bangalore, IND
| | - Sara Khan
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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17
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Sartore G, Ragazzi E, Burlina S, Paleari R, Chilelli NC, Mosca A, Avemaria F, Lapolla A. Role of fructosamine-3-kinase in protecting against the onset of microvascular and macrovascular complications in patients with T2DM. BMJ Open Diabetes Res Care 2020; 8:8/1/e001256. [PMID: 32467223 PMCID: PMC7259852 DOI: 10.1136/bmjdrc-2020-001256] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 04/02/2020] [Accepted: 04/30/2020] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION Microangiopathic and macroangiopathic complications are the main cause of morbidity and mortality in the diabetic population. Numerous publications have highlighted the role of glycation in the onset of complications of diabetes. In this context, the detection of fructosamine-3-kinase (FN3K)-an enzyme capable of counteracting the effect of hyperglycemia by intervening in protein glycation-has attracted great interest. Several studies have linked FN3K genetic variability to its enzymatic activity and glycated hemoglobin (HbA1c) levels. Here, we investigated the role of FN3K polymorphisms in the development of microvascular and macrovascular complications of diabetes. RESEARCH DESIGN AND METHODS The anthropometric and biochemical parameters, and any medical history of microangiopathic and macroangiopathic complications, were documented in a sample of 80 subjects with type 2 diabetes. All subjects were screened for FN3K gene and analyzed for the combination of three polymorphisms known to be associated with its enzymatic activity (rs3859206 and rs2256339 in the promoter region and rs1056534 in exon 6). RESULTS The combination of allelic variants of FN3K polymorphisms resulted in 13 distinct genotypic variants within the cohort. Comparison between genotypes showed no significant differences in terms of demographic, anthropometric and biochemical parameters, risk markers and long-term complications, except for a higher age and vitamin E levels associated with the genotype presenting GG at position -385, TT at position -232, and CC at c.900 A. Evaluating the microangiopathic and macroangiopathic complications as a whole, we found that they appeared significantly less present in this genotype compared with all other genotypes (p=0.0306). CONCLUSIONS The group of patients carrying the favorable allele for the three polymorphisms of the FN3K gene revealed less severe microangiopathy and macroangiopathy, suggesting a protective role of this genotype against the onset of the complications of diabetes.
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Affiliation(s)
- Giovanni Sartore
- Department of Medicine (DIMED), University of Padova School of Medicine and Surgery, Padova, Italy
| | - Eugenio Ragazzi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova School of Medicine and Surgery, Padova, Italy
| | - Silvia Burlina
- Department of Medicine (DIMED), University of Padova School of Medicine and Surgery, Padova, Italy
| | - Renata Paleari
- Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
- Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche (ITB-CNR), Milan, Italy
| | - Nino Cristiano Chilelli
- Department of Medicine (DIMED), University of Padova School of Medicine and Surgery, Padova, Italy
| | - Andrea Mosca
- Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
- Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche (ITB-CNR), Milan, Italy
| | - Francesca Avemaria
- Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
| | - Annunziata Lapolla
- Department of Medicine (DIMED), University of Padova School of Medicine and Surgery, Padova, Italy
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18
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Nayak AU, Singh BM, Dunmore SJ. Potential Clinical Error Arising From Use of HbA1c in Diabetes: Effects of the Glycation Gap. Endocr Rev 2019; 40:988-999. [PMID: 31074800 DOI: 10.1210/er.2018-00284] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 04/05/2019] [Indexed: 01/17/2023]
Abstract
The glycation gap (GGap) and the similar hemoglobin glycation index (HGI) define consistent differences between glycated hemoglobin and actual glycemia derived from fructosamine or mean blood glucose, respectively. Such a disparity may be found in a substantial proportion of people with diabetes, being >1 U of glycated HbA1c% or 7.2 mmol/mol in almost 40% of estimations. In this review we define these indices and explain how they can be calculated and that they are not spurious, being consistent in individuals over time. We evaluate the evidence that GGap and HGI are associated with variation in risk of complications and mortality and demonstrate the potential for clinical error in the unquestioning use of HbA1c. We explore the underlying etiology of the variation of HbA1c from mean glucose in blood plasma, including the potential role of enzymatic deglycation of hemoglobin by fructosamine-3-kinase. We conclude that measurement of GGap and HGI are important to diabetes clinicians and their patients in individualization of therapy and the avoidance of harm arising from consequent inappropriate assessment of glycemia and use of therapies.
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Affiliation(s)
- Ananth U Nayak
- Department of Endocrinology and Diabetes, University Hospital of North Midlands NHS Trust, Stoke on Trent, United Kingdom
| | - Baldev M Singh
- Diabetes Research Group, School of Medicine and Clinical Practice, University of Wolverhampton, Wolverhampton, United Kingdom.,Wolverhampton Diabetes Centre, New Cross Hospital, Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
| | - Simon J Dunmore
- Diabetes Research Group, School of Medicine and Clinical Practice, University of Wolverhampton, Wolverhampton, United Kingdom
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19
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Beck RW, Bergenstal RM, Cheng P, Kollman C, Carlson AL, Johnson ML, Rodbard D. The Relationships Between Time in Range, Hyperglycemia Metrics, and HbA1c. J Diabetes Sci Technol 2019; 13:614-626. [PMID: 30636519 PMCID: PMC6610606 DOI: 10.1177/1932296818822496] [Citation(s) in RCA: 316] [Impact Index Per Article: 52.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND As the use of continuous glucose monitoring (CGM) increases, there is a need to better understand key metrics of time in range 70-180 mg/dL (TIR70-180) and hyperglycemia and how they relate to hemoglobin A1c (A1C). METHODS Analyses were conducted utilizing datasets from four randomized trials encompassing 545 adults with type 1 diabetes (T1D) who had central-laboratory measurements of A1C. CGM metrics were calculated and compared with each other and A1C cross-sectionally and longitudinally. RESULTS Correlations among CGM metrics (TIR70-180, time >180 mg/dL, time >250 mg/dL, mean glucose, area under the curve above 180 mg/dL, high blood glucose index, and time in range 70-140 mg/dL) were typically 0.90 or greater. Correlations of each metric with A1C were lower (absolute values 0.66-0.71 at baseline and 0.73-0.78 at month 6). For a given TIR70-180 percentage, there was a wide range of possible A1C levels that could be associated with that TIR70-180 level. On average, a TIR70-180 of 70% and 50% corresponded with an A1C of approximately 7% and 8%, respectively. There also was considerable spread of change in A1C for a given change in TIR70-180, and vice versa. An increase in TIR70-180 of 10% (2.4 hours per day) corresponded to a decrease in A1C of 0.6%, on average. CONCLUSIONS In T1D, CGM measures reflecting hyperglycemia (including TIR and mean glucose) are highly correlated with each other but only moderately correlated with A1C. For a given TIR or change in TIR there is a wide range of possible corresponding A1C values.
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Affiliation(s)
- Roy W. Beck
- Jaeb Center for Health Research, Tampa,
FL, USA
- Roy W. Beck, MD, PhD, Jaeb Center for Health
Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647, USA.
| | - Richard M. Bergenstal
- International Diabetes Center, Park
Nicollet and HealthPartners, St. Louis Park, MN, USA
| | | | | | - Anders L. Carlson
- International Diabetes Center, Park
Nicollet and HealthPartners, St. Louis Park, MN, USA
| | - Mary L. Johnson
- International Diabetes Center, Park
Nicollet and HealthPartners, St. Louis Park, MN, USA
| | - David Rodbard
- Biomedical Informatics Consultants, LLC,
Potomac, MD, USA
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20
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Evaluation of agreement between hemoglobin A1c, fasting glucose, and fructosamine in Senegalese individuals with and without sickle-cell trait. PLoS One 2019; 14:e0212552. [PMID: 30768636 PMCID: PMC6377192 DOI: 10.1371/journal.pone.0212552] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 02/05/2019] [Indexed: 12/26/2022] Open
Abstract
Fasting glucose (FG) and glycated hemoglobin A1c (HbA1c) perform sub-optimally in people of African origin, especially in individuals with sickle-cell trait (SCT). The purpose of this study was to compare the relationships between HbA1c, FG, and fructosamine in individuals from Senegal with and without SCT. HbA1c, FG, and fructosamine were measured in 203 adults from Senegal (100 control: 45 with type 2 diabetes (T2D); 103 SCT: 51 with T2D). Significant, positive correlations were observed between HbA1c and FG, fructosamine and FG, and fructosamine and HbA1c in both groups. The limits of agreement were inappropriately large in both groups for the Bland-Altman plots of HbA1c and FG (control: -95.97 to 83.97%; SCT: -115.9 to 91.52%), fructosamine and FG (control: -100.6 to 99.89%; SCT: -105.6 to 100.6%), and fructosamine and HbA1c (control: -52.03 to 38.98%; SCT: -88.04 to 71.41%). In both groups, the greatest proportion of subjects were considered above the clinical cut-point for hyperglycemia when fructosamine was used as the criterion (control: 33%; SCT: 44.6%), and the lowest percentage of subjects were classified as over the clinical cut-point when HbA1c was used as the criterion (control: 21%; SCT: 27.7%).Substantial disparities between HbA1c, FG, and fructosamine were observed in both groups, and these differences were exaggerated in the SCT group. Therefore, these three biomarkers should not be considered to be interchangeable measures of glycemic control. These biomarkers should be used thoughtfully, and special care should be taken when using them in individuals with SCT.
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21
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Musha I, Mochizuki M, Kikuchi T, Akatsuka J, Ohtake A, Kobayashi K, Kikuchi N, Kawamura T, Yokota I, Urakami T, Sugihara S, Amemiya S. Estimation of glycaemic control in the past month using ratio of glycated albumin to HbA 1c. Diabet Med 2018; 35:855-861. [PMID: 29653463 DOI: 10.1111/dme.13640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/03/2018] [Indexed: 12/28/2022]
Abstract
AIMS To evaluate comprehensively the use of the glycated albumin to HbA1c ratio for estimation of glycaemic control in the previous month. METHODS A total of 306 children with Type 1 diabetes mellitus underwent ≥10 simultaneous measurements of glycated albumin and HbA1c . Correlation and concordance rates were examined between HbA1c measurements taken 1 month apart (ΔHbA1c ) and glycated albumin/HbA1c ratio fluctuations were calculated as Z-scores from the cohort value at enrolment of this study cohort (method A) or the percent difference from the individual mean over time (method B). RESULTS Fluctuations in glycated albumin/HbA1c ratio (using both methods) were weakly but significantly correlated with ΔHbA1c , whereas concordance rates were significant for glycaemic deterioration but not for glycaemic improvement. Concordance rates were higher using method B than method A. CONCLUSIONS The glycated albumin/HbA1c ratio was able to estimate glycaemic deterioration in the previous month, while estimation of glycaemic improvement in the preceding month was limited. Because method B provided a better estimate of recent glycaemic control than method A, the individual mean of several measurements of the glycated albumin/HbA1c ratio over time may also identify individuals with high or low haemoglobin glycation phenotypes in a given population, such as Japanese children with Type 1 diabetes, thereby allowing more effective diabetes management.
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Affiliation(s)
- I Musha
- Department of Paediatrics, Saitama Medical University, Saitama, Japan
| | - M Mochizuki
- Department of Paediatrics, University of Yamanashi, Yamanashi, Japan
| | - T Kikuchi
- Department of Paediatrics, Saitama Medical University, Saitama, Japan
| | - J Akatsuka
- Department of Paediatrics, Saitama Medical University, Saitama, Japan
| | - A Ohtake
- Department of Paediatrics, Saitama Medical University, Saitama, Japan
| | - K Kobayashi
- Department of Paediatrics, University of Yamanashi, Yamanashi, Japan
| | - N Kikuchi
- Department of Paediatrics, Yokohama City Minato Red Cross Hospital, Kanagawa, Japan
| | - T Kawamura
- Department of Paediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - I Yokota
- Division of Paediatrics Endocrinology and Metabolism, Shikoku Medical Centre for Children and Adults, Kagawa, Japan
| | - T Urakami
- Department of Paediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - S Sugihara
- Department of Paediatrics, Tokyo Women's Medical University Medical Centre East, Tokyo, Japan
| | - S Amemiya
- Department of Paediatrics, Saitama Medical University, Saitama, Japan
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Huang Z, Liu Y, Mao Y, Chen W, Xiao Z, Yu Y. Relationship between glycated haemoglobin concentration and erythrocyte survival in type 2 diabetes mellitus determined by a modified carbon monoxide breath test. J Breath Res 2018; 12:026004. [DOI: 10.1088/1752-7163/aa9081] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Dunmore SJ, Al-Derawi AS, Nayak AU, Narshi A, Nevill AM, Hellwig A, Majebi A, Kirkham P, Brown JE, Singh BM. Evidence That Differences in Fructosamine-3-Kinase Activity May Be Associated With the Glycation Gap in Human Diabetes. Diabetes 2018; 67:131-136. [PMID: 29066600 DOI: 10.2337/db17-0441] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023]
Abstract
The phenomenon of a discrepancy between glycated hemoglobin levels and other indicators of average glycemia may be due to many factors but can be measured as the glycation gap (GGap). This GGap is associated with differences in complications in patients with diabetes and may possibly be explained by dissimilarities in deglycation in turn leading to altered production of advanced glycation end products (AGEs). We hypothesized that variations in the level of the deglycating enzyme fructosamine-3-kinase (FN3K) might be associated with the GGap. We measured erythrocyte FN3K concentrations and enzyme activity in a population dichotomized for a large positive or negative GGap. FN3K protein was higher and we found a striking threefold greater activity (323%) at any given FN3K protein level in the erythrocytes of the negative-GGap group compared with the positive-GGap group. This was associated with lower AGE levels in the negative-GGap group (79%), lower proinflammatory adipokines (leptin-to-adiponectin ratio) (73%), and much lower prothrombotic PAI-1 levels (19%). We conclude that FN3K may play a key role in the GGap and thus diabetes complications such that FN3K may be a potential predictor of the risk of diabetes complications. Pharmacological modifications of its activity may provide a novel approach to their prevention.
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Affiliation(s)
- Simon J Dunmore
- Diabetes Research Group, Academic Institute of Medicine, University of Wolverhampton, Wolverhampton, U.K.
| | - Amr S Al-Derawi
- Diabetes Research Group, Academic Institute of Medicine, University of Wolverhampton, Wolverhampton, U.K
| | - Ananth U Nayak
- Department of Endocrinology and Diabetes, University Hospital of North Midlands NHS Trust, Stoke-on-Trent, U.K
| | - Aruna Narshi
- Diabetes Research Group, Academic Institute of Medicine, University of Wolverhampton, Wolverhampton, U.K
| | - Alan M Nevill
- Faculty of Health, Education and Wellbeing, Institute of Sport, University of Wolverhampton, Walsall, U.K
| | - Anne Hellwig
- Food Chemistry, Technische Universität Dresden, Dresden, Germany
| | - Andrew Majebi
- Diabetes Research Group, Academic Institute of Medicine, University of Wolverhampton, Wolverhampton, U.K
| | - Paul Kirkham
- Faculty of Science and Engineering, Department of Biomedical Science and Physiology, University of Wolverhampton, Wolverhampton, U.K
| | - James E Brown
- Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, U.K
| | - Baldev M Singh
- Diabetes Research Group, Academic Institute of Medicine, University of Wolverhampton, Wolverhampton, U.K
- Wolverhampton Diabetes Centre, New Cross Hospital, Royal Wolverhampton NHS Trust, Wolverhampton, U.K
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Hirsch IB. Professional flash continuous glucose monitoring as a supplement to A1C in primary care. Postgrad Med 2017; 129:781-790. [DOI: 10.1080/00325481.2017.1383137] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Irl B. Hirsch
- University of Washington School of Medicine, Seattle, WA, USA
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25
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Cheng PC, Hsu SR, Cheng YC, Liu YH. Relationship between hemoglobin glycation index and extent of coronary heart disease in individuals with type 2 diabetes mellitus: a cross-sectional study. PeerJ 2017; 5:e3875. [PMID: 29018613 PMCID: PMC5632534 DOI: 10.7717/peerj.3875] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 09/09/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Individuals with type 2 diabetes (T2D) are at an increased risk of coronary heart disease (CHD). Diabetic complications have recently been associated with a measure of glucose metabolism known as the hemoglobin glycation index (HGI). Currently there is insufficient information regarding a potential link between HGI and cardiovascular disease. This study aimed to investigate the relationship between HGI and extent of CHD in individuals with T2D. METHODS This cross-sectional study screened individuals visiting the endocrinology clinic between June 2012 and May 2016 for eligibility. Enrollment criteria included individuals above 21 years of age with T2D diagnosed in the preceding ten years. Candidates with hemoglobin disorders, pregnancy, and existing coronary artery disease were excluded. Fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) were sampled three months prior to angiography. The regression equation of predicted HbA1c = 0.008 × FPG + 6.28 described the linear relationship between these variables. HGI was calculated as the difference between the measured HbA1c and predicted HbA1c. Participants were classified into two groups according to the presence of supranormal (≥0) or subnormal HGI (<0). RESULTS Among 423 participants, people with supranormal HGI harbored an increased prevalence of multiple vessel disease relative to those with subnormal HGI (Odds ratio (OR): 3.9, 95% CI [2.64-5.98], P < 0.001). Moreover, individuals with supranormal HGI more frequently demonstrated lesions involving the left anterior descending artery (OR: 3.0, 95% CI [1.97-4.66], P < 0.001). The intergroup difference in mean HbA1c was statistically nonsignificant (7.5 ± 1.0% versus 7.4 ± 1.1%, P = 0.80). DISCUSSION This study demonstrated that HGI correlated with the extent of CHD in individuals with T2D. People with supranormal HGI harbored a higher prevalence of extensive cardiovascular disease compared to those with subnormal HGI. The relationship between HGI and extent of CHD enables cardiovascular risk stratification in at risk individuals. Overall, HGI provides useful information concerning cardiovascular risk in clinical practice.
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Affiliation(s)
- Po Chung Cheng
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan
| | - Shang Ren Hsu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan
| | - Yun Chung Cheng
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yu Hsiu Liu
- Department of Accounting and Information Systems, National Taichung University of Science and Technology, Taichung, Taiwan
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26
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Beck RW, Connor CG, Mullen DM, Wesley DM, Bergenstal RM. The Fallacy of Average: How Using HbA 1c Alone to Assess Glycemic Control Can Be Misleading. Diabetes Care 2017; 40:994-999. [PMID: 28733374 PMCID: PMC5521971 DOI: 10.2337/dc17-0636] [Citation(s) in RCA: 341] [Impact Index Per Article: 42.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 05/11/2017] [Indexed: 02/03/2023]
Abstract
HbA1c is a valuable metric for comparing treatment groups in a randomized trial, for assessing glycemic trends in a population over time, or for cross-sectional comparisons of glycemic control in different populations. However, what is not widely appreciated is that HbA1c may not be a good indicator of an individual patient's glycemic control because of the wide range of mean glucose concentrations and glucose profiles that can be associated with a given HbA1c level. To illustrate this point, we plotted mean glucose measured with continuous glucose monitoring (CGM) versus central laboratory-measured HbA1c in 387 participants in three randomized trials, showing that not infrequently HbA1c may underestimate or overestimate mean glucose, sometimes substantially. Thus, if HbA1c is to be used to assess glycemic control, it is imperative to know the patient's actual mean glucose to understand how well HbA1c is an indicator of the patient's glycemic control. With knowledge of the mean glucose, an estimated HbA1c (eA1C) can be calculated with the formula provided in this article to compare with the measured HbA1c. Estimating glycemic control from HbA1c alone is in essence applying a population average to an individual, which can be misleading. Thus, a patient's CGM glucose profile has considerable value for optimizing his or her diabetes management. In this era of personalized, precision medicine, there are few better examples with respect to the fallacy of applying a population average to a specific patient rather than using specific information about the patient to determine the optimal approach to treatment.
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Affiliation(s)
- Roy W Beck
- Jaeb Center for Health Research, Tampa, FL
| | | | | | - David M Wesley
- International Diabetes Center Park Nicollet, Minneapolis, MN
- Sursumcorda Resource Group, LLC, Minneapolis, MN
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Neelofar K, Ahmad J. Glycosylation Gap in Patients with Diabetes with Chronic Kidney Disease and Healthy Participants: A Comparative Study. Indian J Endocrinol Metab 2017; 21:410-414. [PMID: 28553596 PMCID: PMC5434724 DOI: 10.4103/ijem.ijem_2_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
AIM The aim of this study it to determine the level of glycosylation gap in patients with type 2 diabetes and its relation with kidney dysfunction. MATERIALS AND METHODS In this study, 150 individuals were enrolled (aged 20-75 year) and divided into three groups. Group 1 included 50 nondiabetic individuals who served as control. Group 2 included 50 patients with type 2 diabetes without chronic kidney disease (CKD), and in Group 3, there were 50 patients with type 2 diabetes with CKD. Glycated hemoglobin (HbA1c) and fructosamine (FA) were measured in all groups to determine the glycosylation gap (GG), predicted HbA1c, and mean blood glucose (MBG). GG is defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA. The variables were compared by correlation analysis. RESULTS Serum creatinine level was significantly high in patients with CKD (1.93 ± 0.99) as compared to patients with diabetes and control (0.891 ± 0.16; 0.912 ± 0.1), respectively. The study demonstrated a significant elevation in serum FA, measured HbA1c and predicted HbA1c, MBG in patients with diabetes with CKD as compared with those of without CKD, and controls. GG was found in healthy control (0.51 ± 0.78), patients with type 2 diabetes without CKD (0.62 ± 0.45), and patients with diabetes with CKD (1.0 ± 0.91), respectively. CONCLUSION It is concluded that GG may be a useful clinical research tool for evaluating pathological source of variation in diabetes complications such as kidney disease.
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Affiliation(s)
- Km Neelofar
- Faculty of Medicine, Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Jamal Ahmad
- Faculty of Medicine, Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
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Cikomola JC, Kishabongo AS, Vandepoele K, Mulder MD, Katchunga PB, Laukens B, Schie LV, Grootaert H, Callewaert N, Speeckaert MM, Delanghe JR. A simple colorimetric assay for measuring fructosamine 3 kinase activity. Clin Chem Lab Med 2017; 55:154-159. [PMID: 27394048 DOI: 10.1515/cclm-2016-0441] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 06/13/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fructosamine 3 kinase (FN3K) is a deglycating enzyme, which may play a key role in reducing diabetes-induced organ damage by removing bound glucose from glycated proteins. We wanted to develop a simple colorimetric method for assaying FN3K activity in human body fluids. METHODS Glycated bovine serum albumin (BSA) was obtained by glycation with a 10% glucose solution at 37 °C. After 72 h, glycated BSA was dialyzed against phosphate buffered saline (0.1 mol/L, pH 7.4). The dialyzed solution (containing ±1000 µmol/L fructosamine) was used as an FN3K substrate. In the assay, 300 µL of substrate was incubated with 50 µL of serum and 100 µL of MgCl2 (0.7 mmol/L)/ATP (3.2 mmol/L). The fructosamine concentration was determined at the start and after incubation (120 min, 25 °C). The decrease in fructosamine concentration over time is a measure for the FN3K activity (1 U corresponding to 1 µmol/min). Concomitantly, the FN3K SNP rs1056534 and the ferroportin SNP rs1156350 were genotyped. RESULTS Within-assay CV was 6.0%. Reference values for FN3K activity in serum were 14.2±1.6 U/L (n=143). Reference values for FN3K were neither age- nor sex-dependent. The various FN3K SNP rs1056534 genotypes showed no significant differences in serum FN3K activity. In diabetics (n=191), values (14.0±2.2 U/L) were comparable to those of the controls. FN3K activity in erythrocytes was significantly higher (170.3±7.6 U/L). The intra-erythrocytic FN3K activity makes the results prone to hemolysis. FN3K activity depended on the ferroportin Q248H genotypes, with the highest value for the wild type genotype. Neither transferrin saturation nor ferritin were confounders for the FN3K activity. FN3K activity was significantly (p<0.0001) correlated with HbA1c values, although the correlation between FN3K and HbA1c was weak. CONCLUSIONS The simple colorimetric method allows determining FN3K activity in human serum. The assay may be useful for studying the impact of deglycation processes in diabetes mellitus.
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Argento NB, Nakamura K, Sala RD, Simpson P. Hemoglobin A1C, mean glucose, and persistence of glycation ratios in insulin-treated diabetes. Endocr Pract 2016; 20:252-60. [PMID: 24246336 DOI: 10.4158/ep13079.or] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Determine the relationship between mean glucose (MG), as assessed by continuous glucose monitoring (CGM), and hemoglobin A1c (A1C) in insulin-requiring adults in a clinical practice setting and examine the persistence of this relationship over time. METHODS In this retrospective record review in a diabetes practice, a linear regression model was developed using data sets from all patients with ≥1 available download of a Dexcom SevenPlus CGM device in which there was >50% utilization in the 60 days prior to a laboratory A1C. Persistence of the MG to A1C relationship was examined in patients with ≥2 data sets available. RESULTS A total of 139 patients had ≥1 data set available for evaluation, and 101 patients had ≥2 data sets (range, 2 to 6; total, 279). The slope of the MG versus A1C curve was 19.5 mg/dL for each 1% change in A1C, with an intercept of 17.7 mg/dL. Although 88% of the measured MG values were within 15% of the A1C-predicted MG, there was substantial variation in individuals, with differences as large as ±26%. The MG to A1C (MG:A1C) ratio, which is a measure of glycation, was normally distributed, with a median of 21.6. Spearman correlation coefficients for the MG:A1C ratio on repeated measures ranged from 0.52 to 0.73, demonstrating persistence. CONCLUSION The relationship between MG and A1C is linear in a population but can vary between individuals. The MG:A1C ratio was normally distributed, tended to persist in individuals over time, and thus could be useful to identify apparent high and low glycators. Glycemic goals may need to be modified in such patients.
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Shi D, Lv L. Associations of glycemic markers: Dose the non-linear fitting is better? Clin Chim Acta 2016; 458:103-5. [DOI: 10.1016/j.cca.2016.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 05/05/2016] [Accepted: 05/06/2016] [Indexed: 12/16/2022]
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Argento NB, Nakamura K. GLYCEMIC EFFECTS OF SGLT-2 INHIBITOR CANAGLIFLOZIN IN TYPE 1 DIABETES PATIENTS USING THE DEXCOM G4 PLATINUM CGM. Endocr Pract 2015; 22:315-22. [PMID: 26523624 DOI: 10.4158/ep151016.or] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Limited information is available on chronic use of sodium glucose cotransporter 2 inhibitors in type 1 diabetes (T1D). We conducted a retrospective review of T1D patients on Dexcom G4Platinum continuous glucose monitors (DCGMs) >1 year (mean, 4.6 years) who were prescribed canagliflozin (CANA) 100 mg daily and had a baseline DCGM 30-day download prior to and a second download after at least 1 month (mean, 3.7 months) taking CANA 100 mg daily. The glycemic, weight, and systolic blood pressure (SBP) effects are reported. METHODS We identified 27 patients meeting the selection criteria: 14 men; 25 white; 22 on pump; average T1D duration, 34 years (range, 12 to 48 years); average hemoglobin A1C (A1C), 7.6% (range, 6.1 to 9.8%); 22 with baseline A1C 7.0% or higher. All patients had an estimated glomerular filtration rate (eGFR) at baseline of 60 mL/min/1.73 m(2) or higher and were normotensive or on stable therapy. On average, 29 days of CGM data was reviewed. Total daily insulin dose (TDD) was available in 21 patients. We identified 27 patients who were judged to be candidates for CANA but did not have any change in glycemic therapy other than insulin adjustment as controls. RESULTS CANA resulted in significant reductions in mean blood glucose, CGM standard deviation, time in hyperglycemia, A1C, weight, SBP, and TDD, with increased time in target, with minimal increase in hypoglycemia and no significant change in eGFR. Three females developed genital mycotic infections but continued therapy, 2 developed ketoacidosis from insulin interruption. CONCLUSION CANA offers promise as adjunct therapy in T1D, though caution is advised.
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Finamore F, Priego-Capote F, Nolli S, Fontana P, Sanchez JC. Aspirin-mediated acetylation of haemoglobin increases in presence of high glucose concentration and decreases protein glycation. EUPA OPEN PROTEOMICS 2015. [DOI: 10.1016/j.euprot.2015.04.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Rodriguez-Segade S, Rodriguez J, García-López JM, Casanueva FF, Coleman IC, Alonso de la Peña C, Camiña F. Influence of the glycation gap on the diagnosis of type 2 diabetes. Acta Diabetol 2015; 52:453-9. [PMID: 25344767 DOI: 10.1007/s00592-014-0666-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 10/14/2014] [Indexed: 12/16/2022]
Abstract
AIMS The results of using HbA1C-based criteria for diagnosis of type 2 diabetes and prediabetes have been reported to differ from those obtained using fasting plasma glucose (FPG) or an oral glucose tolerance test (OGTT). We aimed to determine whether these discrepancies might be due to the influence of the glycation gap. METHODS For 430 patients without previously diagnosed diabetes for whom an OGTT had been requested in normal clinical practice, FPG, fructosamine and HbA1C were measured at the time of the test and again 1 month later. Glycaemia/diabetes status was classified as normoglycaemia, prediabetes or diabetes using both HbA1C-based and FPG/OGTT-based criteria, and their glycation gaps GG were calculated. RESULTS The specificity of an HbA1C level of 6.5 % (48 mmol/mol) for diagnosis of FPG/OGTT-defined type 2 diabetes was 99 %, but its sensitivity was less than 37 %. HbA1C-diabetic patients had higher average blood glucose levels than FPG/OGTT-diabetic patients. With either set of criteria, high-GG patients were disproportionately numerous among those classified as diabetic and were disproportionately infrequent among those classified as normoglycaemic, but the effect was greater for the HbA1C criteria. CONCLUSIONS The differences between HbA1C-based and FPG/OGTT-based diagnoses are largely due to the influence of the glycation gap, which may also influence the early stages of FPG/OGTT-defined diabetes.
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Affiliation(s)
- Santiago Rodriguez-Segade
- Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Santiago de Compostela, Spain,
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Zaccardi F, Kurl S, Pitocco D, Ronkainen K, Laukkanen JA. Serum fructosamine and risk of cardiovascular and all-cause mortality: a 24-year prospective population-based study. Nutr Metab Cardiovasc Dis 2015; 25:236-241. [PMID: 25445881 DOI: 10.1016/j.numecd.2014.09.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Revised: 09/01/2014] [Accepted: 09/23/2014] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND AIMS The association between fructosamine and cardiovascular complications is not well established. We sought to evaluate whether serum fructosamine may be a risk factor for cardiovascular and all-cause mortality in nondiabetic subjects. METHODS AND RESULTS Fructosamine and other cardiovascular risk factors were measured in a sample of 1909 nondiabetic middle-aged men without a known history of coronary heart disease (CHD) at baseline. Associations between baseline fructosamine levels and fatal CHD and cardiovascular disease (CVD) events, and all-cause mortality were estimated using a Cox regression analysis, progressively adjusted for potential confounders. Mean baseline age was 52 years and 30% were smokers. During a median follow-up of 24 years (interquartile range: 18-26 years), 177 (9%) fatal CHD, 289 (15%) fatal CVD, and 728 (38%) all-cause mortality events occurred. In analyses adjusted for several conventional risk factors (i.e., age, systolic blood pressure, smoking, LDL- and HDL-cholesterol), the hazard ratios (HRs) comparing top vs bottom quartile of serum fructosamine levels resulted: 1.33 (95% CI: 0.97, 1.82; p = 0.078) for CHD death and 0.93 (0.72, 1.19; p = 0.567) for CVD death, and 1.04 (0.89, 1.22; p = 0.617) for all-cause mortality. In similar comparisons, further adjustments for body mass index, alcohol consumption, C-reactive protein, and fasting plasma glucose did not materially change these estimates. The exclusion of participants with prevalent CVD at baseline yielded similar results. CONCLUSION In our cohort of nondiabetic men without known CHD, baseline fructosamine levels were not independently associated with cardiovascular and all-cause mortality. Further studies are warranted to confirm these results in other populations.
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Affiliation(s)
- F Zaccardi
- Internal Medicine and Diabetes Care Unit, Catholic University, Rome, Italy.
| | - S Kurl
- Institute of Public Health, School of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - D Pitocco
- Internal Medicine and Diabetes Care Unit, Catholic University, Rome, Italy
| | - K Ronkainen
- Institute of Public Health, School of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - J A Laukkanen
- Institute of Public Health, School of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Lapland Central Hospital, Department of Internal Medicine, Rovaniemi, Finland
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Akatsuka J, Mochizuki M, Musha I, Ohtake A, Kobayashi K, Kikuchi T, Kikuchi N, Kawamura T, Urakami T, Sugihara S, Hoshino T, Amemiya S. The ratio of glycated albumin to hemoglobin A1c measured in IFCC units accurately represents the glycation gap. Endocr J 2015; 62:161-72. [PMID: 25367400 DOI: 10.1507/endocrj.ej14-0066] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The glycation gap (G-gap: difference between measured hemoglobin A1c [A1C] and the value predicted by its regression on the fructosamine level) is stable and associated with diabetic complications. Measuring A1C level in International Federation of Clinical Chemistry (IFCC) units (A1C-SI; mmol/mol) and National Glycohemoglobin Standardization Program units (A1C-NGSP; %) and using glycated albumin (GA) level instead of fructosamine level for calculating the G-gap, we investigated whether the G-gap is better represented by GA/A1C ratio if expressed in SI units (GA/A1C-SI ratio) rather than in NGSP units (GA/A1C-% ratio). We examined 749 Japanese children with type 1 diabetes using simultaneous GA and A1C measurements. Of these, 369 patients were examined more than five times to assess the consistency of the G-gap and the GA/A1C ratio within individuals. The relationship of GA/A1C-% ratio to the corresponding A1C-NGSP was stronger than that of GA/A1C-SI ratio to A1C-IFCC. At enrollment, the inverse relationship between the GA/A1C-SI ratio and G-gap was highly significant (R(2) = 0.95) compared with that between the GA/A1C-% ratio and G-gap (R(2) = 0.69). A highly significant inverse relationship was also observed between the mean GA/A1C-SI ratio and the mean G-gaps obtained individually over time (R(2) = 0.95) compared with that using the corresponding A1C-NGSP (R(2) = 0.67). We conclude that the G-gap is better represented by the GA/A1C-SI ratio. We propose the use of mean GA/A1C-SI ratios easily obtained individually over time as reference values in Japanese children with type 1 diabetes (6.75 ± 0.60 [means ± SD]).
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Affiliation(s)
- Junya Akatsuka
- Department of Pediatrics, Saitama Medial University, Saitama 350-0495, Japan
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Brar PC, Mengwall L, Franklin BH, Fierman AH. Screening obese children and adolescents for prediabetes and/or type 2 diabetes in pediatric practices: a validation study. Clin Pediatr (Phila) 2014; 53:771-6. [PMID: 24671874 DOI: 10.1177/0009922814528571] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Increased prevalence of type 2 diabetes mellitus (T2DM) makes it important for pediatricians to use effective screening tools for risk assessment of prediabetes/T2DM in children. METHODS Children (n = 149) who had an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) were studied. American Diabetes Association recommended screening criteria-HbA1c ≥5.7% and fasting plasma glucose (FPG) ≥100 mg/dL-were compared against OGTT. The homeostatic model assessment of insulin resistance (HOMA-IR), a mathematical index derived from fasting insulin and glucose, was compared with OGTT. We studied whether combining screening tests (HbA1c and fasting glucose or HbA1c and HOMA-IR) improved accuracy of prediction of the OGTT. RESULTS HbA1c of ≥5.7% had a sensitivity of 75% and specificity of 57% when compared with the OGTT. Combining screening tests (HbA1c ≥5.7% and FPG ≥100 mg/dL; HbA1c ≥5.7% and HOMA-IR ≥3.4) resulted in improved sensitivity (95.5% for each), with the HbA1c-FPG doing better than the HbA1c-HOMA-IR combination in terms of ability to rule out prediabetes (likelihood ratio [LR]) negative. 0.07 vs 0.14). CONCLUSIONS HbA1c of ≥5.7% provided fair discrimination of glucose tolerance compared with the OGTT. The combination of HbA1c and FPG is a useful method for identifying children who require an OGTT.
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Affiliation(s)
- Preneet C Brar
- New York University School of Medicine, New York, NY, USA
| | - Lisa Mengwall
- New York University School of Medicine, New York, NY, USA
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Dalan R, Earnest A, Leow MKS. Ethnic variation in the correlation between fasting glucose concentration and glycated hemoglobin (HbA1c). Endocr Pract 2014; 19:812-7. [PMID: 23757612 DOI: 10.4158/ep12417.or] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE We aimed to determine the relationship between fasting serum glucose (FSG) concentration and glycated hemoglobin-A1c (HbA1c) in the 3 ethnicities in Singapore after adjustment for demographic and therapeutic variables. METHODS Fasting serum glucose (FSG), HbA1c, and serum creatinine levels were simultaneously sampled from 575 patients with diabetes (389 Chinese, 97 Indians, 89 Malays) in this cross-sectional study between January and May 2008, and the results were subjected to multivariate linear regression analysis. RESULTS We found a significant interaction between FSG and ethnicity on HbA1c. The correlation between FSG and HbA1c among Chinese subjects was 0.25 (95% confidence interval [CI]:0.2-0.3) relative to the Malays (0.38, 95% CI: 0.30-0.45) after adjustment for age; gender; serum creatinine concentrations; body mass index (BMI); duration of diabetes; use of sulfonylureas, metformin, and insulin; and hemoglobin (Hb) and red cell indices (P = .005). Hence, for a given FSG, the predicted HbA1c will be higher in Malays compared to Chinese subjects. We did not observe a statistically significant difference between Indians and Malays with respect to the correlation between FSG and HbA1c. CONCLUSION We showed a higher correlation between HbA1c and FSG in Malay subjects relative to the Chinese in this cohort. The ethnic variation in the HbA1c-FSG relationship may be related to differences in percentage contribution by the FSG to overall HbA1c among ethnic groups. Future studies using continuous glucose monitoring (CGM) to elucidate the relative contributions by FSG and postprandial glucose (PPG) to the daily blood glucose profile and the overall HbA1c by ethnicity are required.
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Affiliation(s)
- Rinkoo Dalan
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore Yong Loo Lin School of Medicine, Singapore Duke-NUS Graduate Medical School, Singapore
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Kishabongo AS, Katchunga P, Van Aken EH, Speeckaert MM, Lagniau S, Husein D, Taes YE, Delanghe JR. Glycated nail proteins: a new approach for detecting diabetes in developing countries. Trop Med Int Health 2013; 19:58-64. [DOI: 10.1111/tmi.12218] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- Antoine Sadiki Kishabongo
- Department of Laboratory Medicine; Catholic University of Bukavu; Bukavu Democratic Republic of the Congo
| | - Philippe Katchunga
- Department of Internal Medicine; Catholic University of Bukavu; Bukavu Democratic Republic of the Congo
| | | | | | - Sabrina Lagniau
- Department of Clinical Chemistry; Ghent University Hospital; Gent Belgium
| | - Dashty Husein
- Department of Endocrinology; Ghent University Hospital; Gent Belgium
| | - Youri E. Taes
- Department of Endocrinology; Ghent University Hospital; Gent Belgium
| | - Joris R. Delanghe
- Department of Clinical Chemistry; Ghent University Hospital; Gent Belgium
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Nayak AU, Nevill AM, Bassett P, Singh BM. Association of glycation gap with mortality and vascular complications in diabetes. Diabetes Care 2013; 36:3247-53. [PMID: 23835697 PMCID: PMC3781552 DOI: 10.2337/dc12-1040] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The "glycation gap" (G-gap), an essentially unproven concept, is an empiric measure of disagreement between HbA1c and fructosamine, the two indirect estimates of glycemic control. Its association with demographic features and key clinical outcomes in individuals with diabetes is uncertain. RESEARCH DESIGN AND METHODS The G-gap was calculated as the difference between measured HbA1c and a fructosamine-derived standardized predicted HbA1c in 3,182 individuals with diabetes. The G-gap's associations with demographics and clinical outcomes (retinopathy, nephropathy, macrovascular disease, and mortality) were determined. RESULTS Demographics varied significantly with G-gap for age, sex, ethnic status, smoking status, type and duration of diabetes, insulin use, and obesity. A positive G-gap was associated with retinopathy (odds ratio 1.24 [95% CI 1.01-1.52], P=0.039), nephropathy (1.55 [1.23-1.95], P<0.001), and, in a subset, macrovascular disease (1.91 [1.18-3.09], P=0.008). In Cox regression analysis, the G-gap had a "U"-shaped quadratic relationship with mortality, with both negative G-gap (1.96 [1.50-2.55], P<0.001) and positive G-gap (2.02 [1.57-2.60], P<0.001) being associated with a significantly higher mortality. CONCLUSIONS We confirm published associations of G-gap with retinopathy and nephropathy. We newly demonstrate a relationship with macrovascular and mortality outcomes and potential links to distinct subpopulations of diabetes.
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40
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Chalew SA, McCarter RJ, Hempe JM. Biological variation and hemoglobin A1c: relevance to diabetes management and complications. Pediatr Diabetes 2013; 14:391-8. [PMID: 23952704 DOI: 10.1111/pedi.12055] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2013] [Revised: 05/08/2013] [Accepted: 05/14/2013] [Indexed: 01/10/2023] Open
Affiliation(s)
- Stuart A Chalew
- Division of Pediatric Endocrinology and Diabetes, Louisiana State University Health Sciences Center, Children's Hospital of New Orleans and the Research Institute for Children, New Orleans, LA 70118, USA.
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Cosson E, Banu I, Cussac-Pillegand C, Chen Q, Chiheb S, Jaber Y, Nguyen MT, Charnaux N, Valensi P. Glycation gap is associated with macroproteinuria but not with other complications in patients with type 2 diabetes. Diabetes Care 2013; 36:2070-6. [PMID: 23378625 PMCID: PMC3687281 DOI: 10.2337/dc12-1780] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We investigated whether glycation gap (G-Gap), an index of intracellular glycation of proteins, was associated with diabetes complications. RESEARCH DESIGN AND METHODS We measured concomitantly HbA1c and fructosamine in 925 patients with type 2 diabetes to calculate the G-Gap, defined as the difference between measured HbA1c, and fructosamine-based predicted HbA1c. Patients were explored for retinopathy, nephropathy, peripheral neuropathy, cardiac autonomic neuropathy (n = 512), and silent myocardial ischemia (n = 506). RESULTS Macroproteinuria was the only complication that was associated with G-Gap (prevalence in the first, second, and third tertile of G-Gap: 2.9, 6.2, and 11.0%, respectively; P < 0.001). The G-Gap was higher in patients with macroproteinuria than in those without (1.06 ± 1.62 vs. 0.03 ± 1.30%; P < 0.0001). Because HbA1c was associated with both G-Gap (HbA1c 7.0 ± 1.4, 7.9 ± 1.4, and 10.1 ± 1.8% in the first, second, and third G-Gap tertile, respectively; P < 0.0001) and macroproteinuria (HbA1c 8.8 ± 2.2% if macroproteinuria, 8.3 ± 2.0% if none; P < 0.05), and because it could have been a confounder, we matched 54 patients with macroproteinuria and 200 patients without for HbA1c. Because macroproteinuria was associated with lower serum albumin and fructosamine levels, which might account for higher G-Gap, we calculated in this subpopulation albumin-indexed fructosamine and G-Gap; macroproteinuria was independently associated with male sex (odds ratio [OR] 3.2 [95% CI 1.5-6.7]; P < 0.01), hypertension (2.9 [1.1-7.5]; P < 0.05), and the third tertile of albumin-indexed G-Gap (2.3 [1.1-4.4]; P < 0.05) in multivariate analysis. CONCLUSIONS In type 2 diabetic patients, G-Gap was associated with macroproteinuria, independently of HbA1c, albumin levels, and confounding factors, suggesting a specific role of intracellular glycation susceptibility on kidney glomerular changes.
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Affiliation(s)
- Emmanuel Cosson
- AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology, Diabetology, and Nutrition, CRNH-IdF, Bondy, France
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Katreddy MV, Pappachan JM, Taylor SE, Nevill AM, Indusekhar R, Nayak AU. Hemoglobin A1c in early postpartum screening of women with gestational diabetes. World J Diabetes 2013; 4:76-81. [PMID: 23772276 PMCID: PMC3680627 DOI: 10.4239/wjd.v4.i3.76] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Revised: 03/26/2013] [Accepted: 05/17/2013] [Indexed: 02/05/2023] Open
Abstract
AIM: To assess the utility of hemoglobin A1c (HbA1c) in the early postpartum screening of women with gestational diabetes mellitus (GDM).
METHODS: Over a 3 years period, HbA1c estimations were undertaken in addition to and simultaneously with the traditional oral glucose tolerance test (OGTT), in 203 women with GDM as a part of early postpartum screening for dysglycaemia, at 6 wk post-partum. World Health Organization criteria was used for diagnosing diabetes: fasting blood glucose (FBG) ≥ 7.0 mmol/L and/or 2-h postprandial blood glucose (PPBG) ≥ 11.1 mmol/L and/or HbA1c ≥ 48 mmol/mol; and impaired glycaemiastate: impaired fasting glucose 6.1-6.9 mmol/L and/or impaired glucose tolerance 7.8-11.0 mmol/L and/or HbA1c: 42-47 mmol/mol.
RESULTS: Mean FBG, 2-h PPBG and HbA1c were 4.9 ± 0.7 mmol/L, 5.6 ± 2.0 mmol/L and 38 ± 5 mmol/mol respectively. FBG, 2-h PPBG and HbA1c detected 6 (3%), 7 (3.5%) and 11 (5.4%) cases of diabetes respectively, and 11 (5.4%), 25 (12.3%) and 23 (11.3%) cases of pre-diabetes state respectively. HbA1c values ≥ 48 mmol/mol (≥ 6.5%) showed a diagnostic sensitivity of 71.4% and specificity of 98.5% for diabetes in comparison to OGTT in receiver operating characteristics curve analysis. At HbA1c cut-off 44 mmol/mol, sensitivity and specificity were 100% and 92.3% respectively [area under the curve: 0.98 (95%CI: 0.96-1.00)]. Sensitivity and specificity for detecting high risk “impaired glycaemia” state [HbA1c 42 mmol/mol (6.0%)] were 28% and 80%, respectively.
CONCLUSION: HbA1c level ≥ 48 mmol/mol (≥ 6.5%) has reasonable sensitivity and high specificity in comparison to OGTT for early postpartum screening of diabetes in GDM. At 6th week postpartum screening, if FBG is normal and HbA1c < 44 mmol/mol OGTT is not recommended.
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Zafon C, Ciudin A, Valladares S, Mesa J, Simó R. Variables involved in the discordance between HbA1c and fructosamine: the glycation gap revisited. PLoS One 2013; 8:e66696. [PMID: 23776693 PMCID: PMC3680426 DOI: 10.1371/journal.pone.0066696] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Accepted: 05/13/2013] [Indexed: 01/09/2023] Open
Abstract
AIMS Glycation gap (GG) is defined as the difference between the measured level of HbA1c and the level that would be predicted from its regression on the fructosamine level. The aims of the study were: 1) To determine the reproducibility and consistency of GC; 2) To discover factors related to GG value. Given that metformin might increase glucose transport through the erythrocyte membrane, this treatment was also considered in the analyses of the results. METHODS GG was calculated in two blood samples separated 30.6 (SD 7.3) weeks, obtained in 508 type 2 diabetic patients. The following variables were considered: HbA1c, fructosamine, glucose, creatinine, hematological parameters and treatment with metformin. Multivariate and logistic regression analyses were performed to explore the variables independently related to CG. RESULTS GG was reproducible and consistent over time. Creatinine, mean corpuscular hemoglobin concentration (MCHC), and glycemia (inverse relationship); and HbA1c and treatment with metformin (direct relationship) were independently related to GG. Patients treated with metformin showed higher HbA1c values, despite similar fructosamine concentrations, than patients not treated with the drug. CONCLUSIONS GG is independently related to serum levels of creatinine, MCHC and treatment with metformin. The spurious effect of metformin on Hb glycation could have serious clinical implications and should be considered when interpreting the results of clinical trials.
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Affiliation(s)
- Carles Zafon
- Diabetes and Metabolism Research Unit (VHIR) and Department of Endocrinology, Hospital Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
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Cohen RM, Lindsell CJ. When the blood glucose and the HbA(1c) don't match: turning uncertainty into opportunity. Diabetes Care 2012; 35:2421-3. [PMID: 23173128 PMCID: PMC3507598 DOI: 10.2337/dc12-1479] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Robert M Cohen
- Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
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Rodríguez-Segade S, Rodríguez J, García Lopez JM, Casanueva FF, Camiña F. Estimation of the glycation gap in diabetic patients with stable glycemic control. Diabetes Care 2012; 35:2447-50. [PMID: 22961579 PMCID: PMC3507558 DOI: 10.2337/dc11-2450] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The glycation gap (the difference between measured A1C and the value predicted by regression on fructosamine) is stable and is associated with microvascular complications of diabetes but has not hitherto been estimated within a clinically useful time frame. We investigated whether two determinations 30 days apart suffice for a reasonably reliable estimate if both A1C and fructosamine exhibit stability. RESEARCH DESIGN AND METHODS We studied 311 patients with type 1 or type 2 diabetes for whom simultaneous measurements of A1C and serum fructosamine had been made on at least two occasions separated by 1 month (t(0) and t(1)). Glycemia was deemed stable if A1C(t(1)) - A1C(t(0)) and fructosamine(t(1)) - fructosamine(t(0)) were both less than their reference change values (RCVs). Instantaneous glycation gaps [gg(t(0)) and gg(t(1))] and their mean (GG), were calculated using the data from all stable patients for the required regression. RESULTS Stable glycemia was shown by 144 patients. In 90% of unstable case subjects, a change in medication was identified as the cause of instability. Among 129 stable patients with an average of eight gg determinations prior to t(0), GG correlated closely with the mean of these prior determinations (r(2) = 0.902, slope 1.025, intercept -0.038). CONCLUSIONS The glycation gap can be calculated reliably from pairs of A1C and fructosamine measurements taken 1 month apart if these measurements satisfy the RCV criteria for glycemic control.
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Affiliation(s)
- Santiago Rodríguez-Segade
- Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain.
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Juraschek SP, Steffes MW, Selvin E. Associations of alternative markers of glycemia with hemoglobin A(1c) and fasting glucose. Clin Chem 2012; 58:1648-55. [PMID: 23019309 DOI: 10.1373/clinchem.2012.188367] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND 1,5-Anhydroglucitol (1,5-AG), fructosamine, and glycated albumin are of increasing interest as alternative measures of hyperglycemia. We characterize the associations of these nontraditional glycemic markers with hemoglobin A(1c) (Hb A(1c)) and fasting glucose and assess their ability to identify people with diabetes. METHODS We conducted a cross-sectional comparison of 1,5-AG, fructosamine, and glycated albumin with Hb A(1c) and fasting glucose measurements in 1719 participants from the Atherosclerosis Risk in Communities Study. We evaluated nonlinear relationships using R(2) and F-statistics. Performance for identification of cases of diabetes was determined using the area under the curve (AUC). Diabetes was defined by Hb A(1c) ≥6.5%, fasting glucose ≥126 mg/dL (≥6.99 mmol/L), and/or a self-reported history of diagnosed diabetes. RESULTS Median values of Hb A(1c) and fasting glucose were 5.8% and 109 mg/dL (6.05 mmol/L), respectively; 17.3% of the study population had diagnosed diabetes. Glycated albumin, fructosamine, and 1,5-AG were more strongly correlated with Hb A(1c) compared with fasting glucose (all P values <0.05). Nonlinear models provided the best fit for describing the relationships of the alternative markers to Hb A(1c). When diabetes was defined by an Hb A(1c) ≥6.5%, fructosamine (AUC 0.83; 95% CI, 0.79-0.87) and glycated albumin (AUC 0.87; 95% CI, 0.83-0.90) performed comparably to fasting glucose (AUC 0.83; 95% CI, 0.79-0.87), while 1,5-AG performed worse (AUC 0.74; 95% CI, 0.69-0.78) for identifying cases of undiagnosed diabetes. CONCLUSIONS Fructosamine and glycated albumin may be useful adjuncts to Hb A(1c) and fasting glucose. Future studies should examine these markers in situations in which fasting glucose or Hb A(1c) measurements are invalid or not available.
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Affiliation(s)
- Stephen P Juraschek
- Johns Hopkins School of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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Herman WH, Cohen RM. Racial and ethnic differences in the relationship between HbA1c and blood glucose: implications for the diagnosis of diabetes. J Clin Endocrinol Metab 2012; 97:1067-72. [PMID: 22238408 PMCID: PMC3319188 DOI: 10.1210/jc.2011-1894] [Citation(s) in RCA: 209] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Hemoglobin A1c (HbA1c) is widely used as an index of mean glycemia in diabetes, as a measure of risk for the development of diabetic complications, and as a measure of the quality of diabetes care. In 2010, the American Diabetes Association recommended that HbA1c tests, performed in a laboratory using a method certified by the National Glycohemoglobin Standardization Program, be used for the diagnosis of diabetes. Although HbA1c has a number of advantages compared to traditional glucose criteria, it has a number of disadvantages. Hemoglobinopathies, thalassemia syndromes, factors that impact red blood cell survival and red blood cell age, uremia, hyperbilirubinemia, and iron deficiency may alter HbA1c test results as a measure of average glycemia. Recently, racial and ethnic differences in the relationship between HbA1c and blood glucose have also been described. Although the reasons for racial and ethnic differences remain unknown, factors such as differences in red cell survival, extracellular-intracellular glucose balance, and nonglycemic genetic determinants of hemoglobin glycation are being explored as contributors. Until the reasons for these differences are more clearly defined, reliance on HbA1c as the sole, or even preferred, criterion for the diagnosis of diabetes creates the potential for systematic error and misclassification. HbA1c must be used thoughtfully and in combination with traditional glucose criteria when screening for and diagnosing diabetes.
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Affiliation(s)
- William H Herman
- University of Michigan, 1000 Wall Street, Room 6100/SPC 5714, Ann Arbor, Michigan 48105-1912, USA.
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