Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).
Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The Diabetes Prevention ProgramBaseline characteristics of the randomized cohort O R I G I N A L A R T I C L EOBJECTIVE -The Diabetes Prevention Program (DPP) is a 27-center randomized clinical trial designed to evaluate the safety and efficacy of interventions that may delay or prevent development of diabetes in people at increased risk for type 2 diabetes.RESEARCH DESIGN AND METHODS -Eligibility requirements were age Ն25 years, BMI Ն24 kg/m 2 (Ն22 kg/m 2 for Asian-Americans), and impaired glucose tolerance plus a fasting plasma glucose of 5.3-6.9 mmol/l (or Յ6.9 mmol for American Indians). Randomization of participants into the DPP over 2.7 years ended in June 1999. Baseline data for the three treatment groups-intensive lifestyle modification, standard care plus metformin, and standard care plus placebo-are presented for the 3,234 participants who have been randomized.RESULTS -Of all participants, 55% were Caucasian, 20% were African-American, 16% were Hispanic, 5% were American Indian, and 4% were Asian-American. Their average age at entry was 51 ± 10.7 years (mean ± SD), and 67.7% were women. Moreover, 16% were Ͻ40 years of age, and 20% were Ն60 years of age. Of the women, 48% were postmenopausal. Men and women had similar frequencies of history of hypercholesterolemia (37 and 33%, respectively) or hypertension (29 and 26%, respectively). On the basis of fasting lipid determinations, 54% of men and 40% of women fit National Cholesterol Education Program criteria for abnormal lipid profiles. More men than women were current or former cigarette smokers or had a history of coronary heart disease. Furthermore, 66% of men and 71% of women had a firstdegree relative with diabetes. Overall, BMI averaged 34.0 ± 6.7 kg/m 2 at baseline with 57% of the men and 73% of women having a BMI Ն30 kg/m 2 . Average fasting plasma glucose (6.0 ± 0.5 mmol/l) and HbA 1c (5.9 ± 0.5%) in men were comparable with values in women (5.9 ± 0.4 mmol/l and 5.9 ± 0.5%, respectively).CONCLUSIONS -The DPP has successfully randomized a large cohort of participants with a wide distribution of age, obesity, and ethnic and racial backgrounds who are at high risk for developing type 2 diabetes. The study will examine the effects of interventions on the development of diabetes.
Studies of peripheral blood lymphocytes from astronauts indicate that microgravity depresses T-cell responsiveness. However, this effect has not been examined in cells of peripheral lymphatic tissue, where most lymphocytes are located. In this study, inguinal lymph node lymphocytes from rats flown on the COSMOS 2044 mission were tested for proliferation and interleukin-2 (IL-2) production. Cells cultured with mitogenic lectins, phorbol ester, and calcium ionophore, or T-cell mitogen and lymphokine, were assayed for DNA synthesis by [3H]thymidine incorporation. Lymphocytes incubated with a T-cell mitogen alone also were tested for IL-2 production. Proliferation of lymphocytes from flight rats was not significantly different from controls for any of the mitogens tested. Furthermore, lymph node lymphocytes from flight rats was not significantly different from controls for any of the mitogens tested. Furthermore, lymph node lymphocytes from control and flown rats produced similar amounts of IL-2. Thus microgravity may act on lymphocytes in a tissue-specific manner, a new finding that could impact on the evaluation of spaceflight effects on immunocompetence.
Across the Diabetes Prevention Program (DPP) follow-up, cumulative diabetes incidence remained lower in the lifestyle compared with the placebo and metformin randomized groups and could not be explained by weight. Collection of self-reported physical activity (PA) (yearly) with cross-sectional objective PA (in follow-up) allowed for examination of PA and its long-term impact on diabetes prevention. RESEARCH DESIGN AND METHODS Yearly self-reported PA and diabetes assessment and oral glucose tolerance test results (fasting glucose semiannually) were collected for 3,232 participants with one accelerometry assessment 11-13 years after randomization (n 5 1,793). Mixed models determined PA differences across treatment groups. The association between PA and diabetes incidence was examined using Cox proportional hazards models. RESULTS There was a 6% decrease (Cox proportional hazard ratio 0.94 [95% CI 0.92, 0.96]; P < 0.001) in diabetes incidence per 6 MET-h/week increase in time-dependent PA for the entire cohort over an average of 12 years (controlled for age, sex, baseline PA, and weight). The effect of PA was greater (12% decrease) among participants less active at baseline (<7.5 MET-h/week) (n 5 1,338) (0.88 [0.83, 0.93]; P < 0.0001), with stronger findings for lifestyle participants. Lifestyle had higher cumulative PA compared with metformin or placebo (P < 0.0001) and higher accelerometry total minutes per day measured during follow-up (P 5 0.001 and 0.047). All associations remained significant with the addition of weight in the models. CONCLUSIONS PA was inversely related to incident diabetes in the entire cohort across the study, with cross-sectional accelerometry results supporting these findings. This highlights the importance of PA within lifestyle intervention efforts designed to prevent diabetes and urges health care providers to consider both PA and weight when counseling high-risk patients.
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