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

ABSTRACT: 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.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).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.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

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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

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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.

Project description:ObjectivesThis study sought to evaluate the association between early-life cardiorespiratory fitness (CRF) and measures of left ventricular (LV) structure and function in midlife.BackgroundLow CRF in midlife is associated with a higher risk of heart failure. However, the unique contributions of early-life CRF toward measures of LV structure and function in middle age are not known.MethodsCARDIA (Coronary Artery Risk Development in Young Adults) study participants with a baseline maximal treadmill test and an echocardiogram at year 25 were included. Associations among baseline CRF, CRF change, and echocardiographic LV parameters (global longitudinal strain [GLS] and global circumferential strain, E/e') were assessed using multivariable linear regression.ResultsThe study included 3,433 participants. After adjustment for baseline demographic and clinical characteristics, lower baseline CRF was significantly associated with higher LV strain (standardized parameter estimate [Std β] = -0.06; p = 0.03 for GLS) and ratio of early transmitral flow velocity to early peak diastolic mitral annular velocity (E/e') (Std β = -0.10; p = 0.0001 for lateral E/e'), findings suggesting impaired contractility and elevated diastolic filling pressure in midlife. After additional adjustment for cumulative cardiovascular risk factor burden observed over the follow-up period, the association of CRF with LV strain attenuated substantially (p = 0.36), whereas the association with diastolic filling pressure remained significant (Std β = -0.05; p = 0.02 for lateral E/e'). In a subgroup of participants with repeat CRF tests at year 20, greater decline in CRF was significantly associated with increased abnormalities in GLS (Std β = -0.05; p = 0.02) and higher diastolic filling pressure (Std β = -0.06; p = 0.006 for lateral E/e') in middle age.ConclusionsCRF in young adulthood and CRF change were associated with measures of LV systolic function and diastolic filling pressure in middle age. Low CRF-associated abnormalities in systolic function were related to the associated higher cardiovascular risk factor burden. In contrast, the inverse association between CRF and LV diastolic filling pressure was independent of cardiovascular risk factor burden.

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

Publications

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

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