William C. Knowler

Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

OBJECTIVE—The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-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—This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45–74 years, with BMI >25 kg/m2 (>27 kg/m2 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 with a diabetes support and education (DSE) condition. RESULTS—Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). CONCLUSIONS—At 1 year, ILI resulted in clinically significant weight loss in people 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.

The diabetes prevention program: Recruitment methods and results

The Diabetes Prevention Program (DPP) is a multicenter randomized controlled trial designed to test whether diet and exercise or medication can prevent or delay the onset of type 2 diabetes in persons with impaired glucose tolerance, who are at increased risk of the disease. This paper describes DPP recruitment methods, strategies, performance, and costs. The DPP developed an organizational structure for comprehensive management and continuous monitoring of recruitment efforts. The DPP utilized a variety of recruitment strategies, alone or in combination, and a stepped informed consent procedure leading to randomization. Studywide and clinic-specific recruitment data were monitored, analyzed, and used to modify recruitment approaches. DPP recruitment was completed slightly ahead of schedule, meeting goals for the proportion of women enrolled and nearly meeting goals for the proportion of racial/ethnic minorities. Clinics varied widely in the recruitment strategies they used, and these strategies also varied by participant age, gender, and race/ethnicity. Staff time devoted to recruitment averaged 86.8 hours per week per clinic, with the majority of effort by staff specifically assigned to recruitment. The number of staff hours required to recruit a participant varied by recruitment strategy. Recruitment cost (excluding staff cost) was about 1075 US dollars per randomized participant. The DPP experience offers lessons for those planning similar efforts: (1) a method for ongoing assessment and revision of recruitment strategies is valuable; (2) a range of recruitment strategies may be useful; (3) the most effective methods for recruiting potential subjects may vary according to the gender, age, and race/ethnicity of those individuals; (4) recruitment strategies vary in the amount of staff time required to randomize a participant; and (5) a stepped screening may make it easier to identify and recruit volunteers who understand the requirements of the study.

The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long‐term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long‐term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow‐up continued for a median of 11.3 years at 16 academic centers. A total of 5145 persons aged 45 to 76 years with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self‐report and confirmed with central adjudication of medical records. The baseline mean age of participants was 59 years, 60% were women, 63% were white, and the mean BMI was 36u2009kg/m2. Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. A total of 731 participants had a confirmed incident fracture (358 in DSE versus 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR 1.39; 95% CI, 1.02 to 1.89). An intensive lifestyle intervention resulting in long‐term weight loss in overweight/obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted.

Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes

Exercise has been prescribed for diabetes treatment since at least 600 B.C. The early East Indian text, the Shushruta, described a reduction in the sweetness of urine from diabetic patients after exercise. One might think that very little could be left to discover in the field of exercise and diabetes, yet surprisingly this is far from the truth. Ongoing research is refining the exercise prescription for patients of all ages, with the main types of diabetes (gestational, type 1, and type 2) and discovering new ways in which exercise has benefits. Alterations in metabolism caused by diabetes and new types of exercise modalities are also actively being researched. A search of several hundred articles on exercise published between July 1, 2012, to June 30, 2013, uncovered the following 9 articles we felt had the most relevance to patients with diabetes or prediabetes.