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Genetic determinants of variability in glycated hemoglobin (HbA(1c)) in humans: review of recent progress and prospects for use in diabetes care.

ABSTRACT: Glycated hemoglobin A(1c) (HbA(1c)) indicates the percentage of total hemoglobin that is bound by glucose, produced from the nonenzymatic chemical modification by glucose of hemoglobin molecules carried in erythrocytes. HbA(1c) represents a surrogate marker of average blood glucose concentration over the previous 8 to 12 weeks, or the average lifespan of the erythrocyte, and thus represents a more stable indicator of glycemic status compared with fasting glucose. HbA(1c) levels are genetically determined, with heritability of 47% to 59%. Over the past few years, inroads into understanding genetic predisposition by glycemic and nonglycemic factors have been achieved through genomewide analyses. Here I review current research aimed at discovering genetic determinants of HbA(1c) levels, discussing insights into biologic factors influencing variability in the general and diabetic population, and across different ethnicities. Furthermore, I discuss briefly the relevance of findings for diabetes monitoring and diagnosis.

SUBMITTER: Soranzo N

PROVIDER: S-EPMC3207128 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Genetic determinants of variability in glycated hemoglobin (HbA(1c)) in humans: review of recent progress and prospects for use in diabetes care.

Soranzo Nicole N

Current diabetes reports 20111201 6

Glycated hemoglobin A(1c) (HbA(1c)) indicates the percentage of total hemoglobin that is bound by glucose, produced from the nonenzymatic chemical modification by glucose of hemoglobin molecules carried in erythrocytes. HbA(1c) represents a surrogate marker of average blood glucose concentration over the previous 8 to 12 weeks, or the average lifespan of the erythrocyte, and thus represents a more stable indicator of glycemic status compared with fasting glucose. HbA(1c) levels are genetically d ...[more]

PMID: 21975967

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Project description:IntroductionObesity is associated with compromised glucose metabolism. Hence, it is of interest to investigate if the lifestyle interventions used in the LIBRA-cohort, which aimed at not only weight loss, but also patient well-being, could also help obese patients improve glucose metabolism by evidence of reduced HbA1c. The aim of the study was to retrospectively investigate if patients who were referred to a lifestyle intervention for obesity, were able to alter HbA1c.Research design and methodsPatients with a BMI≥30 undergoing a 6-month lifestyle intervention, who also completed physical and mental health surveys and whose baseline and 6-month blood samples were available, were included in the analysis. For changes in HbA1c and body weight a clinically relevant change of 5≥mmom/mol and 5%≥, respectively, was chosen. Participants were divided into groups according to their baseline HbA1c level: "Diabetes": HbA1c of ≥6.5% (≥48 mmol/mol), "Prediabetes": HbA1c of 5.7% to 6.4% (39-47.99 mmol/mol) or "Normal" HbA1c <5.7% (<39 mmol/mol).Results180 patients met the stated inclusion criteria and these patients were divided into groups (median age (25th;75th quartile): Diabetes: n=47, age 54 (43;60), 51% women, Prediabetes: n=68, age 60 (50;66), 71% women and Normal: n=65, median age 61 (50;66), 85% women. Significant reductions were found in all three groups and specifically in the diabetes group HbA1c was reduced (mean [95%CI]) -5[-8;-2] mmol/mol from baseline to the end of the intervention. Furthermore, 35% of patients with prediabetes normalized their HbA1c (<39) and 30% patients with diabetes reduced their HbA1c <48. All groups had clinically relevant (≥5%) reductions in body weight (p<0.01). There was an association between body weight reduction and HbA1c reduction in the diabetes group (p<0.01). All groups reported improvements in physical health (p<0.01).ConclusionIn this retrospective cohort study, all patients achieved clinically relevant weight loss after participation in the lifestyle intervention and obese patients with diabetes achieved clinically relevant reductions in HbA1c after 6-months. More than 1/3 of patients with prediabetes normalized their HbA1c.

Project description:BackgroundCombining HbA1c with glycated albumin (GA) may improve detection of dysglycaemia. As BMI correlates positively with HbA1c and negatively with GA, HbA1c may be more effective in obese and GA in nonobese individuals.MethodsTo relate these findings to Africans, we assessed in 1274 South Africans living in CapeTown (male 26%; age 48±16y; BMI 28.7 kg/m2 (range 15.6-73.8); obesity 39.9% and no prior diabetes history) the: (1) correlation of BMI with HbA1c and GA, (2) ability of HbA1c and GA separately and jointly, to detect OGTT-diagnosed dysglycaemia (diabetes plus prediabetes). Data collection took place between 2014 and 2016 in the City of Cape Town. Dysglycaemia was diagnosed by glucose criteria for the OGTT. Youden index was used to optimize diagnostic thresholds for HbA1c and GA.FindingsNormal glucose tolerance, prediabetes and diabetes occurred in 76%, 17% and 7%, respectively. BMI positively correlated with HbA1c [r = 0·34 [95%CI: 0·29,0·39)] and negatively with GA [-0·08 (0·13,0·03)]. For HbA1c the optimal threshold by Youden-index for dysglycaemia diagnosis was: 6·0% (95%CI: 5·8,6·2) and for GA: 13·44% (12·72,14·71). In the nonobese, obese and total cohort, HbA1c-alone detected: 51% (42-60), 72% (65,78), 63% (57,68), respectively; GA-alone detected 55% (52% (46,63), 52% (44, 59) and 53% (47,53), respectively; whereas: HbA1c+GA detected: 69% (60,76), 82% (75,87) and 76% (71, 81). Therefore, for the total cohort detection of dysglycaemia HbA1c-alone vs HbA1c+GA detected 63% (57,68) vs 76% (71,81).InterpretationThe opposite correlations of HbA1c and GA with BMI have now been demonstrated in an African-based population. Improving detection of dysglycaemia by combining HbA1c and GA has important implications for diabetes risk screening.FundingAES is supported by the intramural programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Minority Health and Health Disparities of the National Institutes of Health (NIH, Bethesda, Maryland, USA). DBS is supported by the intramural program of the Clinical Center of NIH. The South African Medical Research Council (SAMRC) funded the VMH study with funds from the National Treasury under its Economic Competitiveness and Support Package (MRC-RFA-UFSP-01-2013/VMH Study).

Dataset Information

Genetic determinants of variability in glycated hemoglobin (HbA(1c)) in humans: review of recent progress and prospects for use in diabetes care.

Publications

Genetic determinants of variability in glycated hemoglobin (HbA(1c)) in humans: review of recent progress and prospects for use in diabetes care.

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