Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.

OBJECTIVEOverweight and obese individuals are encouraged to lose 5–10% of their body weight to improve cardiovascular disease (CVD) risk, but data supporting this recommendation are limited, particularly for individuals with type 2 diabetes.RESEARCH DESIGN AND METHODSWe conducted an observational analysis of participants in the Look AHEAD (Action For Health in Diabetes) study (n = 5,145, 40.5% male, 37% from ethnic/racial minorities) and examined the association between the magnitude of weight loss and changes in CVD risk factors at 1 year and the odds of meeting predefined criteria for clinically significant improvements in risk factors in individuals with type 2 diabetes.RESULTSThe magnitude of weight loss at 1 year was strongly (P < 0.0001) associated with improvements in glycemia, blood pressure, tryiglycerides, and HDL cholesterol but not with LDL cholesterol (P = 0.79). Compared with weight-stable participants, those who lost 5 to <10% ([means ± SD] 7.25 ± 2.1 kg) of their body weight had increased odds of achieving a 0.5% point reduction in HbA1c (odds ratio 3.52 [95% CI 2.81–4.40]), a 5-mmHg decrease in diastolic blood pressure (1.48 [1.20–1.82]), a 5-mmHg decrease in systolic blood pressure (1.56 [1.27–1.91]), a 5 mg/dL increase in HDL cholesterol (1.69 [1.37–2.07]), and a 40 mg/dL decrease in triglycerides (2.20 [1.71–2.83]). The odds of clinically significant improvements in most risk factors were even greater in those who lost 10–15% of their body weight.CONCLUSIONSModest weight losses of 5 to <10% were associated with significant improvements in CVD risk factors at 1 year, but larger weight losses had greater benefits.

Insulin resistance is a major risk factor for the development of NIDDM: A low acute insulin response to glucose is an additional but weaker risk factor.

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.)

Background The effect of childhood risk factors for cardiovascular disease on adult mortality is poorly understood. Methods In a cohort of 4857 American Indian children without diabetes (mean age, 11.3 years; 12,659 examinations) who were born between 1945 and 1984, we assessed whether body-mass index (BMI), glucose tolerance, and blood pressure and cholesterol levels predicted premature death. Risk factors were standardized according to sex and age. Proportional-hazards models were used to assess whether each risk factor was associated with time to death occurring before 55 years of age. Models were adjusted for baseline age, sex, birth cohort, and Pima or Tohono O'odham Indian heritage. Results There were 166 deaths from endogenous causes (3.4% of the cohort) during a median follow-up period of 23.9 years. Rates of death from endogenous causes among children in the highest quartile of BMI were more than double those among children in the lowest BMI quartile (incidence-rate ratio, 2.30; 95% confidence interval [CI], 1.46 to 3.62). Rates of death from endogenous causes among children in the highest quartile of glucose intolerance were 73% higher than those among children in the lowest quartile (incidence-rate ratio, 1.73; 95% CI, 1.09 to 2.74). No significant associations were seen between rates of death from endogenous or external causes and childhood cholesterol levels or systolic or diastolic blood-pressure levels on a continuous scale, although childhood hypertension was significantly associated with premature death from endogenous causes (incidence-rate ratio, 1.57; 95% CI, 1.10 to 2.24). Conclusions Obesity, glucose intolerance, and hypertension in childhood were strongly associated with increased rates of premature death from endogenous causes in this population. In contrast, childhood hypercholesterolemia was not a major predictor of premature death from endogenous causes.

Intrauterine exposure to diabetes is associated with an excess of diabetes and obesity in the offspring, but the effects of intrauterine exposure are confounded by genetic factors. To determine the role of the intrauterine diabetic environment per se, the prevalence of diabetes and the mean BMI were compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born before and one after the mother was diagnosed with type 2 diabetes were selected. Consequently, the siblings born before and after differed in their exposure to diabetes in utero. A total of 58 siblings from 19 families in which at least one sibling had diabetes were examined at similar ages (within 3 years). The risk of diabetes was significantly higher in siblings born after the mother developed diabetes than in those born before the mother's diagnosis of diabetes (odds ratio 3.7, P = 0.02). In 52 families, among 183 siblings without diabetes, the mean BMI was 2.6 kg/m 2 higher in offspring of diabetic than in offspring of nondiabetic pregnancies (P = 0.003). In contrast, there were no significant differences in risk of diabetes or BMI between offspring born before and after the father was diagnosed with diabetes. Intrauterine exposure to diabetes per se conveys a high risk for the development of diabetes and obesity in offspring in excess of risk attributable to genetic factors alone. Diabetes 49:2208-2211, 2000 T ype 2 diabetes has strong genetic and environmental risk factors. Previous studies have shown greater transmission of type 2 diabetes to offspring from mothers than from fathers (1-3), and a significantly higher prevalence of diabetes in offspring of women with diabetes during pregnancy than in offspring of nondiabetic and prediabetic women (2). Intrauterine exposure to diabetes is also associated with a higher prevalence of impaired glucose tolerance in adolescence (4) and with an excess of obesity, especially during the first 20 years of life (5-7). Nevertheless, the effects of intrauterine exposure to diabetes may be confounded by genetic factors. For example, women who develop diabetes at an earlier age might carry more diabetes-susceptibility genes than those who develop diabetes later. Hence, they might transmit greater genetic susceptibility to their offspring.The Pima Indians of Arizona have the world's highest incidence and prevalence of type 2 diabetes (8,9). Both genetic and environmental risk factors contribute to the high rate of diabetes in the Pimas. In Pima Indian children aged 5-19 years, the strongest single risk factor for type 2 diabetes was exposure to diabetes in utero (10). To determine the role of intrauterine diabetic environment, which is in addition to genetic transmission of susceptibility, a sibship study was designed to compare the prevalence of type 2 diabetes and the BMI in Pima Indian siblings born before and after their mother was diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODSData were taken from the longitudinal ...

Background-Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have recently been associated with type 2 diabetes. We examined whether the two most strongly associated variants (rs12255372 and rs7903146) predict the progression to diabetes in persons with impaired glucose tolerance who were enrolled in the Diabetes Prevention Program, in which lifestyle intervention or treatment with metformin was compared with placebo.

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