John P. Foreyt

Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes

BACKGROUND Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).

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.

Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: Four-year results of the look AHEAD trial

BACKGROUND Lifestyle interventions produce short-term improvements in glycemia and cardiovascular disease (CVD) risk factors in individuals with type 2 diabetes mellitus, but no long-term data are available. We examined the effects of lifestyle intervention on changes in weight, fitness, and CVD risk factors during a 4-year study. METHODS The Look AHEAD (Action for Health in Diabetes) trial is a multicenter randomized clinical trial comparing the effects of an intensive lifestyle intervention (ILI) and diabetes support and education (DSE; the control group) on the incidence of major CVD events in 5145 overweight or obese individuals (59.5% female; mean age, 58.7 years) with type 2 diabetes mellitus. More than 93% of participants provided outcomes data at each annual assessment. RESULTS Averaged across 4 years, ILI participants had a greater percentage of weight loss than DSE participants (-6.15% vs -0.88%; P < .001) and greater improvements in treadmill fitness (12.74% vs 1.96%; P < .001), hemoglobin A(1c) level (-0.36% vs -0.09%; P < .001), systolic (-5.33 vs -2.97 mm Hg; P < .001) and diastolic (-2.92 vs -2.48 mm Hg; P = .01) blood pressure, and levels of high-density lipoprotein cholesterol (3.67 vs 1.97 mg/dL; P < .001) and triglycerides (-25.56 vs -19.75 mg/dL; P < .001). Reductions in low-density lipoprotein cholesterol levels were greater in DSE than ILI participants (-11.27 vs -12.84 mg/dL; P = .009) owing to greater use of medications to lower lipid levels in the DSE group. At 4 years, ILI participants maintained greater improvements than DSE participants in weight, fitness, hemoglobin A(1c) levels, systolic blood pressure, and high-density lipoprotein cholesterol levels. CONCLUSIONS Intensive lifestyle intervention can produce sustained weight loss and improvements in fitness, glycemic control, and CVD risk factors in individuals with type 2 diabetes. Whether these differences in risk factors translate to reduction in CVD events will ultimately be addressed by the Look AHEAD trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00017953.

Appropriate Intervention Strategies for Weight Loss and Prevention of Weight Regain for Adults

In excess of 55% of adults in the United States are classified as either overweight (body mass index = 25-29.9 kg.m(-2)) or obese (body mass index > or = 30 kg.m(-2)). To address this significant public health problem, the American College of Sports Medicine recommends that the combination of reductions in energy intake and increases in energy expenditure, through structured exercise and other forms of physical activity, be a component of weight loss intervention programs. An energy deficit of 500-1000 kcal.d-1 achieved through reductions in total energy intake is recommended. Moreover, it appears that reducing dietary fat intake to <30% of total energy intake may facilitate weight loss by reducing total energy intake. Although there may be advantages to modifying protein and carbohydrate intake, the optimal doses of these macronutritents for weight loss have not been determined. Significant health benefits can be recognized with participation in a minimum of 150 min (2.5 h) of moderate intensity exercise per week, and overweight and obese adults should progressively increase to this initial exercise goal. However, there may be advantages to progressively increasing exercise to 200-300 min (3.3-5 h) of exercise per week, as recent scientific evidence indicates that this level of exercise facilitates the long-term maintenance of weight loss. The addition of resistance exercise to a weight loss intervention will increase strength and function but may not attenuate the loss of fat-free mass typically observed with reductions in total energy intake and loss of body weight. When medically indicated, pharmacotherapy may be used for weight loss, but pharmacotherapy appears to be most effective when used in combination with modifications of both eating and exercise behaviors. The American College of Sports Medicine recommends that the strategies outlined in this position paper be incorporated into interventions targeting weight loss and the prevention of weight regain for adults.

One-year weight losses in the Look AHEAD study: factors associated with success.

This report provides a further analysis of the first year weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with success. Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and randomly assigned to an intensive lifestyle intervention (ILI) or a control condition, Diabetes Support and Education (DSE). During year 1, participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions, compared with three educational sessions for DSE participants. As reported previously, at the end of the year, ILI participants lost 8.6% of initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all racial/ethnic groups achieved clinically significant weight losses (>5.5%), although there were significant differences among groups. For the year, ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products. Greater self‐reported physical activity was the strongest correlate of weight loss, followed by treatment attendance and consumption of meal replacements. The use of orlistat, during the second half of the year, increased weight loss only marginally in those ILI participants who had lost <5% of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option. The lifestyle intervention was clinically effective in all subsets of an ethnically and demographically diverse population.

Weight Loss With Naltrexone SR/Bupropion SR Combination Therapy as an Adjunct to Behavior Modification: The COR-BMOD Trial

This 56‐week, randomized, placebo‐controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 ± 4.2 kg/m2) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained‐release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy‐reduced diet and 28 group BMOD sessions. Co‐primary end points were percentage change in weight and the proportion of participants who lost ≥5% weight at week 56. Efficacy analyses were performed on a modified intent‐to‐treat population (ITT; i.e., participants with ≥1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 ± 0.6% with placebo + BMOD vs. 9.3 ± 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 ± 0.9% (N = 106) vs. 11.5 ± 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD‐ vs. placebo + BMOD‐treated participants lost ≥5 and ≥10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.

Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials

AIM: This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity.METHOD: Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another.RESULT: Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research.

Relation of diet to high-density-lipoprotein cholesterol in middle-aged marathon runners, joggers, and inactive men.

We investigated the effect of diet on high-density-lipoprotein (HDL) cholesterol in 59 healthy middle-aged marathon runners, 85 joggers, and 74 inactive men. Marathon runners and joggers reported eating less red meat (P less than 0.0001), bacon (P less than 0.05), and sausage (P less than 0.01) than did the inactive men, although meat consumption was not significantly correlated with HDL. Results suggest that HDL differences (marathon runners, 65 mg per deciliter; joggers, 58 mg per deciliter; inactive men, 43 mg per deciliter) among the three groups were primarily the result of distance run, not dietary factors. Distance run was also the best predictor of the HDL:total cholesterol ratio and of total cholesterol (a negative correlation), and it was second only to weight in predicting triglyceride levels.

Physical activity, genetic, and nutritional considerations in childhood weight management

Almost one-quarter of U.S. children are now obese, a dramatic increase of over 20% in the past decade. It is intriguing that the increase in prevalence has been occurring while overall fat consumption has been declining. Body mass and composition are influenced by genetic factors, but the actual heritability of juvenile obesity is not known. A low physical activity (PA) is characteristic of obese children and adolescents, and it may be one cause of juvenile obesity. There is little evidence, however, that overall energy expenditure is low among the obese. There is a strong association between the prevalence of obesity and the extent of TV viewing. Enhanced PA can reduce body fat and blood pressure and improve lipoprotein profile in obese individuals. Its effect on body composition, however, is slower than with low-calorie diets. The three main dietary approaches are: protein sparing modified fast, balanced hypocaloric diets, and comprehensive behavioral lifestyle programs. To achieve long-standing control of overweight, one should combine changes in eating and activity patterns, using behavior modification techniques. However, the onus is also on society to reduce incentives for a sedentary lifestyle and over-consumption of food. To address the key issues related to childhood weight management, the American College of Sports Medicine convened a Scientific Roundtable in Indianapolis.

Comparison of 2-Year Weight Loss Trends in Behavioral Treatments of Obesity: Diet, Exercise, and Combination Interventions

OBJECTIVE The effects of three cognitive-behavioral weight control interventions for adults were compared: diet only, exercise only, and a combination of diet and exercise. This article reports 2-year follow-up data. DESIGN The three interventions were compared in a randomized, experimental design. SUBJECTS A total of 127 men and women who were at least 14 kg overweight (according to height-weight tables) were recruited from an urban community and assigned randomly to the experimental conditions. INTERVENTION The dietary intervention was a low-energy eating plan adjusted to produce a 1 kg/week loss of weight. The exercise component involved training in walking and a home-based program of up to five exercise periods per week. There were 12 weekly instructional sessions, followed by 3 biweekly and 8 monthly meetings. All sessions were led by registered dietitians. OUTCOME MEASURES Changes in body weight. STATISTICAL ANALYSES Analysis of variance for weight changes and repeated measures analysis of variance for weight change trends. RESULTS At 1 year, no significant differences were noted among the three groups. The diet-only group lost 6.8 kg, the exercise-only group lost 2.9 kg, and the combination group lost 8.9 kg (P=.09). During the second year, the diet-only group regained weight--reaching 0.9 kg above baseline; the combination group regained to 2.2 kg below baseline; and the exercise-only group regained slightly to 2.7 kg below baseline (P=.36). Repeated measures analysis of variance showed a group-by-time interaction (P=.001); data for the dieting groups best fit a U-shaped regain curve (P=.001). APPLICATIONS The results suggest that dieting is associated with weight loss followed by regain after treatment ends, whereas exercise alone produced smaller weight losses but better maintenance. The large outcome variability and unequal difficulty of the regimens across groups limit the generalizability of the findings.