Dataset Information

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study.

ABSTRACT:

Aims/hypothesis

Genotype does not change over the life course and may thus facilitate earlier identification of individuals at high risk for type 2 diabetes. We hypothesised that a genotype score predicts incident type 2 diabetes from young adulthood and improves diabetes prediction models based on clinical risk factors alone.

Methods

The Coronary Artery Risk Development in Young Adults (CARDIA) study followed young adults (aged 18-30 years, mean age 25) serially into middle adulthood. We used Cox regression to build nested prediction models for incident type 2 diabetes based on clinical risk factors assessed in young adulthood (age, sex, race, parental history of diabetes, BMI, mean arterial pressure, fasting glucose, HDL-cholesterol and triacylglyercol), without and with a 38-variant genotype score. Models were compared with C statistics and continuous net reclassification improvement indices (NRI).

Results

Of 2,439 participants, 830 (34%) were black and 249 (10%) had a BMI ≥ 30 kg/m(2) at baseline. Over a mean 23.9 years of follow-up, 215 (8.8%) participants developed type 2 diabetes. The genotype score significantly predicted incident diabetes in all models, with an HR of 1.08 per risk allele (95% CI 1.04, 1.13) in the full model. The addition of the score to the full model modestly improved reclassification (continuous NRI 0.285; 95% CI 0.126, 0.433) but not discrimination (C statistics 0.824 and 0.829 in full models with and without score). Race-stratified analyses were similar.

Conclusions/interpretation

Knowledge of genotype predicts type 2 diabetes over 25 years in white and black young adults but may not improve prediction over routine clinical measurements.

SUBMITTER: Vassy JL

PROVIDER: S-EPMC3434294 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study.

Vassy J L JL Durant N H NH Kabagambe E K EK Carnethon M R MR Rasmussen-Torvik L J LJ Fornage M M Lewis C E CE Siscovick D S DS Meigs J B JB

Diabetologia 20120711 10

<h4>Aims/hypothesis</h4>Genotype does not change over the life course and may thus facilitate earlier identification of individuals at high risk for type 2 diabetes. We hypothesised that a genotype score predicts incident type 2 diabetes from young adulthood and improves diabetes prediction models based on clinical risk factors alone.<h4>Methods</h4>The Coronary Artery Risk Development in Young Adults (CARDIA) study followed young adults (aged 18-30 years, mean age 25) serially into middle adult ...[more]

PMID: 22782289

Similar Datasets

Project description:Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear.To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD).Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up.The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated.Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P?<?.001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P?=?.002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (??=?-0.24; 95% CI, -0.45 to -0.03; P?=?.02) and significantly better lobal longitudinal strain (??=?-0.09; 95% CI, -0.14 to -0.05; P?<?.001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P?=?.002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P?=?.006), respectively, along with a more impaired strain (??=?0.15; 95% CI, 0.08-0.23; P?<?.001). No association between change in fitness and CAC was found.Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.

Dataset Information

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study.

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets