OBJECTIVE -Autonomic nervous system dysfunction, a correlate of obesity and poor cardiorespiratory fitness, is associated with the development of diabetes. We tested whether estimates of autonomic nervous system function improved in the intensive lifestyle versus metformin or placebo arms of the Diabetes Prevention Program (DPP) and whether baseline or a change in autonomic nervous system function was associated with the development of diabetes over 3.2 years.RESEARCH DESIGN AND METHODS -In 2,980 DPP participants, 12-lead electrocardiograms were measured at baseline and annually. Heart rate, heart rate variability (HRV), and QT duration were used to estimate fitness and autonomic nervous system function.RESULTS -In the lifestyle arm, heart rate and QT indexes decreased, and HRV increased over time. The magnitude of decline in heart rate and QT duration was substantially smaller in the other arms, whereas HRV did not increase. Baseline heart rate was the only index significantly (P Ͻ 0.05) associated with incident diabetes after adjustment for demographics and weight change (hazard ratio for lifestyle and metformin arms ϭ 1.19 and 1.17 per 10.6 beats/min, respectively). Decreases in heart rate and QT indexes and increases in HRV over time were associated with a lower risk of developing diabetes. The protective association between decreased heart rate and incident diabetes in the lifestyle arm remained significant after accounting for change in weight and physical activity.CONCLUSIONS -Indexes that reflect autonomic function and fitness improved (i.e., heart rate decreased and HRV increased) in the lifestyle modification arm of the DPP. Improvements in these indexes are inversely associated with the development of diabetes independent of weight change. Diabetes Care 29:914 -919, 2006A utonomic impairment has been identified at the time of diabetes diagnosis, which suggests that impairment may be present after a relatively brief exposure to hyperglycemia or develop in conjunction with obesity or insulin resistance (1,2). Cross-sectional studies in adults without diabetes provide evidence that markers of autonomic functioning are inversely associated with obesity, insulin resistance, and fasting glucose (3-6). Recent research suggesting that autonomic dysfunction predicts the development of diabetes (7,8) supports the long-held clinical suspicion that autonomic dysfunction is associated with the development of diabetes in healthy adults (9).Adults were identified as eligible to participate in the Diabetes Prevention Program (DPP) because they were at risk for developing diabetes, most commonly because of existing hyperglycemia and obesity. Thus, it is plausible that many had existing autonomic impairment at baseline in the study. At the conclusion of the trial, there was a significantly lower incidence of diabetes in the intensive lifestyle modification arm compared with that in the metformin or placebo arms (10). Lifestyle modification involved increasing physical activity and lowering dietary fat intake with a goa...

Background It has recently been reported that atrial fibrillation [AF] is associated with an increased risk of myocardial infarction [MI]. However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with type of MI [ST elevation MI (STEMI) vs. non-ST elevation MI [NSTEMI] might shed light on the potential mechanisms. Methods and Results We examined the association between AF and incident MI in 14,462 participants [mean age 54 years, 56% women, 26% African Americans] from the Atherosclerosis Risk in Communities study who were free of coronary heart disease at baseline [1987–1989] with follow-up through December 31, 2010. AF cases were identified from study visits electrocardiogram and by review of hospital discharge records. Incident MI and its types were ascertained by an independent adjudication committee. Over a median follow up of 21.6 years, 1374 MI events occurred [829 NSTEMI, 249 STEMI, 296 unclassifiable]. In a multivariable adjusted model, AF [n=1545] as a time-varying variable was associated with a 63% increased risk of MI [HR (95% CI):1.63(1.32–2.02)]. However, AF was associated with NSTEMI [HR (95% CI): 1.80(1.39–2.31)] but not STEMI [HR (95% CI): 0.49(0.18–1.34)]; p-value for hazard ratios comparison=0.004. Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men [interaction p-value<0.01 for both]. Conclusions AF is associated with an increased risk of incident MI, especially in women. However, this association is limited to NSTEMI.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74

Among 35,192 postmenopausal, predominantly white women in Iowa age 55-69 years and free of cancer, we collected baseline history, dietary information, and anthropometric data by mail in 1986. We ascertained the 8-year incidence (62 new cases) of renal cell carcinoma using the Iowa Surveillance, Epidemiology, and End Results (SEER) register, the National Death Index, and mail follow-up. Risk factors for renal cell carcinoma included increasing age, increasing weight (either current, maximum adult weight, or weight at ages 18, 30, or 50 years), greater waist-to-hip ratio, and a history of blood transfusion. Total dietary calcium was associated independently with a reduced risk of renal cell carcinoma. No other dietary micro- or macronutrients or food groups were predictive of the development of renal cell carcinoma. Other previously identified risk factors were not confirmed: most notably, there was no increased risk from a history of hypertension, after adjustment for diuretic use. History of ever-use of diuretics was associated with a twofold increased risk of renal cancer, although the strength of association was markedly reduced after adjustment for age, weight, waist-to-hip ratio, and calcium intake.

Although advanced inter-atrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age=54±5.8 years; 26% black; 55% female) participants from the Atherosclerosis Risk In Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987–1989, 1990–1992, 1993–1995, and 1996–1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 (0.5%) participants had aIAB at baseline and 193 (1.3%) developed aIAB during follow-up. The incidence rate for aIAB was 2.27 (95%CI=1.97, 2.61) per 1000 person-years. Risk factors for aIAB development included age, male sex, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (HR=3.09, 95%CI=2.51, 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF and the presence of aIAB is associated with an increased risk for AF.