BACKGROUND Weight loss is recommended for overweight and obese individuals with type 2 diabetes based on short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether intensive lifestyle intervention for weight loss decreased cardiovascular morbidity and mortality in overweight or obese adults with type 2 diabetes. METHODS We randomly assigned 5,145 overweight or obese individuals with type 2 diabetes recruited at 16 US centers to intensive lifestyle intervention (the intervention group), which promoted weight loss through decreased calorie intake and increased physical activity, or diabetes support and education (the control group). The primary outcome was the first post-randomization occurrence of a composite cardiovascular outcome (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalized angina) over a planned maximum follow-up of 13.5 years. RESULTS The trial was stopped early based on a futility analysis when median follow-up was 9.6 years. Weight loss was greater in the intervention group than the control group throughout (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). Intensive lifestyle intervention also produced greater reductions in hemoglobin A1c and greater initial improvements in fitness and all cardiovascular risk factors, except LDL cholesterol. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83/100 person-years and 1.92/100 person-years, respectively; hazard ratio 0.95; 95% CI 0.83 to 1.09, p=0.505). CONCLUSION In our study, intensive lifestyle intervention focused on weight loss did not reduce cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT00017953.)

Objective-The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes one-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events.Research Design and Methods-A multi-centered randomized controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with body mass index ≥25 kg/m 2 (≥27 kg/m 2 if taking insulin). An Intensive Lifestyle Intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared to a Diabetes Support and Education (DSE) condition.Results-Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (p<0.001). Mean fitness increased in ILI by 20.9% versus 5.8% in DSE (p<0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean HbA 1 c dropped from 7.3% to 6.6% in ILI (p<0.001) versus from 7.3% to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL-cholesterol, and urine albumin/creatinine improved significantly more in ILI than DSE participants (all p<0.01).Conclusions-At 1 year, ILI resulted in clinically significant weight loss in persons with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.

More than half of adult Americans are overweight or obese, and public health recommendations call for weight loss in those who are overweight with associated medical conditions or who are obese. However, some controversy exists in the lay press and in the medical literature about the health risks of obesity. We review briefly the large body of evidence indicating that higher levels of body weight and body fat are associated with an increased risk for the development of numerous adverse health consequences. Efforts to prevent further weight gain in adults at risk for overweight and obesity are essential. For those whose present or future health is at risk because of their obesity and who are motivated to make lifestyle changes, a recommendation for weight loss is appropriate.

Macromolecular crowding extends the range of ionic conditions supporting high DNA polymerase reaction rates. Reactions tested were nick-translation and gap-filing by DNA polymerase I ofEscherichia coli, nuclease and polymerase activities of the large fragment of that polymerase, and polymerization by the T4 DNA polymerase. For all of these reactions, high concentrations of nonspecific polymers increased enzymatic activity under otherwise inhibitory conditions resulting from relatively high ionic strength. The primary mechanism of the polymer effect seems to be to increase the binding of polymerase to DNA. We suggest that this effect on protein-DNA complexes is only one example of a general "metabolic buffering" action of crowded solutions on a variety of macromolecular interactions. Reactions were terminated by chilling and adding 0.20 ml of 10 mM Na4P207, 0.4 mg of bovine plasma albumin per ml, and 2 mM EDTA followed by addition of 0.20 ml of 10% trichloroacetic acid. After 5 min at 0C, the mixtures were centrifuged. For nuclease assays, aliquots of the supernatant fluids were neutralized and plated. For polymerase assays, the supernatant fluids were discarded and the pellets were washed twice by redissolving in 0.1 ml of 0.1 M NaOH and precipitation with 0.4 ml of5% trichloroacetic acid before finally redissolving in 0.4 ml of 2 M NH40H and plating. 32P was measured with a low background (0.5 cpm) end-window gas-flow counter (Tracerlab, Waltham, MA

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