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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.)

Abbreviations: AaO 2 , alveolar-to-arteriolar oxygen; AKA, alcoholic ketoacidosis; ARDS, adult respiratory distress syndrome; BUN, blood urea nitrogen; CPT, carnitine palmitoyl-transferase; CSF, cerebrospinal fluid; DKA, diabetic ketoacidosis; FFA, free fatty acid; HHS, hyperosmolar hyperglycemic state; IRI, immunoreactive insulin; PaO 2 , arteriolar partial pressure of oxygen; RDKA, recurrent DKA.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Management of Hyperglycemic Crises in Patients With Diabetes T E C H N I C A L R E V I E R e v i e w s / C o m m e n t a r i e s / P o s i t i o n S t a t e m e n t s 132DIABETES CARE, VOLUME 24, NUMBER 1, JANUARY 2001Technical Review noted in newly diagnosed obese type 2 diabetic patients (5,26,31). Therefore, the concept that the presence of DKA in type 2 diabetes is a rare occurrence is incorrect.The most common types of infections are pneumonia and urinary tract infection, accounting for 30-50% of cases (Table 4). Other acute medical illnesses as precipitating causes include alcohol abuse, trauma, pulmonary embolism, and myocardial infarction, which can occur both in type 1 and 2 diabetes (6). Various drugs that alter carbohydrate metabolism, such as corticosteroids, pentamidine, sympathomimetic agents, and ␣-and ␤-adrenergic blockers, and excessive use of diuretics in the elderly may also precipitate the development of DKA and HHS.The recent increased use of continuous subcutaneous insulin infusion pumps that use small amounts of short-acting insulin has been associated with an incidence of DKA that is significantly increased over the incidence seen with conventional methods of multiple daily insulin injections, in spite of the fact that most of the mechanical problems with insulin pumps have been resolved (6,(32)(33)(34). In the Diabetes Control and Complications Trial, the incidence of DKA in patients on insulin pumps was about twofold higher than that in the multipleinjection group over a comparable time period (35). This may be due to the exclusive use of short-acting insulin in the pump, which if interrupted leaves no reservoir of insulin for blood glucose control.Psychological factors and poor compliance, leading to omission of insulin therapy, are important precipitating factors for recurrent ketoacidosis. In young female patients with type 1 diabetes, psychological problems complicated by eating disorders may be contributing factors in up to 20% of cases of recurrent ketoacidosis (36,37). Factors that may lead to insulin omission in younger patients include fear of weight gain with good metabolic control, fear of hypoglycemia, rebellion against authority, and stress related to chronic disease (36). Noncompliance with insulin therapy has been found to be the leading precipitating cause for DKA in urban African-Americans and medically indigent patients (5,26). In addition, a recent study showed that diabetic patients without health insurance or with Medicaid alone had hospitali...