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Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

ABSTRACT: INTRODUCTION:Mitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes. RESEARCH DESIGN AND METHODS:We assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016. RESULTS:Mean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants. CONCLUSIONS:Lower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.

SUBMITTER: DeBarmore B

PROVIDER: S-EPMC7430458 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

DeBarmore Bailey B Longchamps Ryan J RJ Zhang Yiyi Y Kalyani Rita R RR Guallar Eliseo E Arking Dan E DE Selvin Elizabeth E Young J Hunter JH

BMJ open diabetes research & care 20200801 1

<h4>Introduction</h4>Mitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes.<h4>Research design and methods</h4>We assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black part ...[more]

PMID: 32801120

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Project description:ObjectiveTo examine the magnitude and types of hospitalizations among persons with prediabetes, undiagnosed diabetes, and diagnosed diabetes.Research design and methodsThis study included 13,522 participants in the Atherosclerosis Risk in Communities (ARIC) study (mean age 57 years, 56% female, 24% black, 18% with prediabetes, 4% with undiagnosed diabetes, 9% with diagnosed diabetes) with follow-up in 1990-2011 for hospitalizations. Participants were categorized by diabetes/HbA1c status: without diagnosed diabetes, HbA1c <5.7% (reference); prediabetes, 5.7 to <6.5%; undiagnosed diabetes, ≥6.5%; and diagnosed diabetes, <7.0 and ≥7.0%.ResultsDemographic adjusted rates per 1,000 person-years of all-cause hospitalizations were higher with increasing diabetes/HbA1c category (Ptrend < 0.001). Persons with diagnosed diabetes and HbA1c ≥7.0% had the highest rates of hospitalization (3.1 times higher than those without a history of diagnosed diabetes, HbA1c <5.7%, and 1.5 times higher than those with diagnosed diabetes, HbA1c <7.0%, P < 0.001 for both comparisons). Persons with undiagnosed diabetes had 1.6 times higher rates of hospitalization and those with prediabetes had 1.3 times higher rates of hospitalization than those without diabetes and HbA1c <5.7% (P < 0.001 for both comparisons). Rates of hospitalization by diabetes/HbA1c category were different by race (Pinteraction = 0.011) and by sex (Pinteraction = 0.020). There were significantly excess rates of hospitalizations due to cardiovascular, endocrine, respiratory, gastrointestinal, iatrogenic/injury, neoplasm, genitourinary, neurologic, and infection causes among those with diagnosed diabetes compared with those without a history of diagnosed diabetes (all P < 0.05).ConclusionsPersons with diagnosed diabetes, undiagnosed diabetes, and prediabetes are at a significantly elevated risk of hospitalization compared with those without diabetes. Substantial excess rates of hospitalizations in persons with diagnosed diabetes were for endocrine, infection, and iatrogenic/injury causes, which may be preventable with improved diabetes care.

Project description:<p>The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date.</p> <p>ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort.</p> <p>In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005.</p> <p>ARIC is currently funded through January 31, 2012.</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>

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Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

Publications

Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

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