Purpose Numerous prospective studies indicate that improved cardiorespiratory fitness reduces type

Purpose Numerous prospective studies indicate that improved cardiorespiratory fitness reduces type 2 diabetes (T2D) risk and delays disease progression. a level where one in three US adults could be affected (8). Numerous prospective epidemiological studies indicate that regular physical activity is related to a 15-60% reduction in risk of T2D (reviewed in (31)), and that behavioral intervention that promotes physical fitness can reduce progression from pre-diabetes to T2D by up to 58% (22). Cardiorespiratory fitness has been inversely associated with incident T2D (25) and cardiovascular events (23). Exercise programs designed to increase physical fitness are recommended to patients with established T2D. The benefit of exercise can be seen with improved insulin sensitivity, as well as reduced adiposity and adipose tissue inflammation (3). Paragraph Number 2 2 Studies in animal models demonstrate a significant role for genetic background in physical endurance (2). Similarly, cardiorespiratory fitness in humans was found to be heritable, with heritability estimates ranging between 25% and 65% (reviewed in (37)). Genome-wide association studies (GWAS) conducted in the Framingham Heart Study and HERITAGE Family Study using large arrays of single nucleotide polymorphisms (SNPs) identified no variants associated with pre-training levels or changes in heart rate or fitness in response to training at the genome-wide significance level (P-value < 510?8) (7, 39). Suggestive signals, however, were identified in the ryanodine receptor gene (including age, sex, medication use and race/ethnicity were collected via questionnaire at baseline. Weight at baseline and one year post-randomization was measured using the standardized methods as described previously (21). Paragraph Number 8 8 was assessed using a graded exercise test (GXT) on a calibrated motor-driven treadmill as previously described using a standardized protocol (16). A self-selected walking speed of 1 1.5, 2.0, 2.5, MLN9708 3.0, 3.5, or 4.0 mph was used with the velocity held constant throughout the test. Grade of the treadmill was initiated at 0% and increased by 1% each minute until test termination. During the last 10 seconds of each minute and at the point to test termination the heart rate was measured from a 12-lead ECG and rating of perceived exertion (RPE) was measured using the Borg 15-category scale (scale ranges from 6 to 20). Blood pressure was assessed during the last 45 seconds of each even minute and at test termination. A maximal graded exercise to the point of volitional fatigue was conducted at baseline. The baseline GXT was considered valid provided that that subject achieved either 85% of age-predicted maximal heart rate (defined as 220-age) computed as if not taking a medication that would affect the heart rate response to exercise or RPE18 if the subject was taking a medication that would affect the heart rate response to exercise (e.g., beta MLN9708 blocker). This baseline test was used to exclude individuals for whom exercise may have been contraindicated prior to study randomization. Due to cost constraints associated with the need for physicians presence for a maximal test regardless of health status, subjects completed a submaximal GXT at 1 year using the same Rabbit Polyclonal to SLC25A12 walking speed and grade increments as was used for the baseline test; however, the test was terminated at the point with the participant first exceeded 80% of age-predicted maximal heart rate if not on a beta-blocker at either baseline or Year 1, or first exceeded RPE = 16 if on a beta-blocker at either baseline or Year 1. The workload at test termination at 1 year was compared to the workload from baseline where the same heart rate (80% age-predicted maximal heart rate) or RPE (RPE = 16) was met around the baseline GXT. These workloads were converted to estimated METs using the American College of Sports Medicines MLN9708 metabolic calculations for estimating energy expenditure (1), and the change MLN9708 in fitness was computed as the difference in METs at the same submaximal heart rate or RPE between the baseline and 1 year GXT. Genotyping and MLN9708 Candidate Gene selection Paragraph Number 9 9 Genotyping was carried out on leukocyte DNA using the (IBC) chip (19), as previously described (28). Briefly, genomic DNA was extracted from.