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Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).

ABSTRACT: OBJECTIVE:Glycated hemoglobin (HbA1c) is a stable index of chronic glycemic status and hyperglycemia associated with progressive development of insulin resistance and frank diabetes. It is also associated with premature aging and increased mortality. To uncover novel loci for HbA1c that are associated with healthy aging, we conducted a genome-wide association study (GWAS) using non-diabetic participants in the Long Life Family Study (LLFS), a study with familial clustering of exceptional longevity in the US and Denmark. METHODS:A total of 4088 non-diabetic subjects from the LLFS were used for GWAS discoveries, and a total of 8231 non-diabetic subjects from the Atherosclerosis Risk in Communities Study (ARIC, in the MAGIC Consortium) and the Health, Aging, and Body Composition Study (HABC) were used for GWAS replications. HbA1c was adjusted for age, sex, centers, 20 principal components, without and with BMI. A linear mixed effects model was used for association testing. RESULTS:Two known loci at GCK rs730497 (or rs2908282) and HK1 rs17476364 were confirmed (p<5e-8). Of 25 suggestive (5e-8

SUBMITTER: An P

PROVIDER: S-EPMC3965585 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).

An Ping P Miljkovic Iva I Thyagarajan Bharat B Kraja Aldi T AT Daw E Warwick EW Pankow James S JS Selvin Elizabeth E Kao W H Linda WH Maruthur Nisa M NM Nalls Micahel A MA Liu Yongmei Y Harris Tamara B TB Lee Joseph H JH Borecki Ingrid B IB Christensen Kaare K Eckfeldt John H JH Mayeux Richard R Perls Thomas T TT Newman Anne B AB Province Michael A MA

Metabolism: clinical and experimental 20131204 4

<h4>Objective</h4>Glycated hemoglobin (HbA1c) is a stable index of chronic glycemic status and hyperglycemia associated with progressive development of insulin resistance and frank diabetes. It is also associated with premature aging and increased mortality. To uncover novel loci for HbA1c that are associated with healthy aging, we conducted a genome-wide association study (GWAS) using non-diabetic participants in the Long Life Family Study (LLFS), a study with familial clustering of exceptional ...[more]

PMID: 24405752

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Project description:BackgroundPrevious studies have shown increased risk of fracture in older patients with poor or strict glycemic control (glycated hemoglobin, HbA1c, ≥ 8% or < 6-7% respectively); however, these reports did not investigate the oldest-old population. Comprehensive geriatric assessment (CGA) and a patient-centered approach have been proven to improve the quality of care in the management of Type 2 Diabetes Mellitus (T2DM) in the older patients, but data regarding T2DM in patients with fragility fractures are still lacking.AimTo investigate the prognostic role of HbA1c and frailty level in older diabetic patients admitted for hip fracture.MethodsProspective observational cohort study conducted on diabetic geriatric patients consecutively hospitalized for hip fracture in the orthogeriatric unit of a tertiary care hospital. Preoperative comprehensive geriatric assessment (CGA) was performed. Using the Clinical Frailty Scale (CFS), diabetic patients were categorized in robust (CFS < 5) and frail (CFS ≥ 5), and further stratified according to HbA1c values [Tertile 1 (T1) HbA1c < 48 mmol/mol, Tertile 2 (T2) 48-58 mmol/mol and Tertile 3 (T3) > 58 mmol/mol). Comparisons between continuous variables were performed with analysis of non-parametric test for independent samples, while relationships between categorical variables were assessed by chi-square test. Using logistic multivariate regression, we evaluated the determinants of 1-year all-cause mortality in diabetic older patients with hip fracture.ResultsAmong the 1319 older patients (mean age 82.8 ± 7.5 years, 75.9% females) hospitalized for hip fracture, 204 (15.5%) had a previous diagnosis of T2DM. T2DM patients showed an increased proportion of multiple concurrent fractures occurred during the accidental fall or syncope (12.7% vs 11.2%, p=0.02). One-year mortality after hip fracture surgery was significantly higher in T2DM as compared to not diabetic patients (21.2% vs 12.5%, p<0.001). No significant difference in mortality was found across HbA1c tertiles; however, frail diabetic patients in the second and third HbA1c tertiles showed higher mortality risk compared to the robust counterparts (26.9% vs 5%, p=0.001 for T2 and 43.5% vs 13.3%, p=<0.05 for T3), while no difference was observed among those in T1.ConclusionsFrail patients with HbA1c ≥ 48 mmol/L showed an increased mortality risk as compared to robust counterparts. CFS represents an important tool to select diabetic subjects with higher likelihood of adverse outcome.

Dataset Information

Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).

Publications

Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).

Similar Datasets

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