"It is also possible that lifestyle interventions may have a real but modest effect on cardiovascular outcomes akin to that of glucose lowering (e.g., a 10%-15% reduction) that requires more than 10 years to become apparent. If so, this trial was clearly too small to detect such an effect," wrote Dr. Gerstein, an endocrinologist and professor at McMaster University and Hamilton Health Sciences, Hamilton, Ont.
A look at the data
The patients in the intervention group (2,570) and control group (2,575) had similar characteristics at baseline. They were between 45 and 75 years old, were mostly female (60%) and white (63%), and had a mean body mass index of 36.0. Fourteen percent had a history of cardiovascular disease, and the median duration of diabetes was 5 years. Less than 30% were on insulin.
Close to 96% of the patients stayed in the trial.
During months 1 and 6, the intervention group had weekly contact with staff members. The contact was gradually reduced in the following months to one on-site individual session per month, and one phone call or e-mail per month from 2 years onward. The patients’ medications were adjusted by their own physicians.
Patients in the control group had 3-4 meetings per year during years 1 through 4, and after that, they had one meeting per year. They received education on diet, exercise, and social support.
Weight loss was greater in the intervention group compared with the control group, with the greatest difference at 1 year (8.6% vs. 0.7%), but it remained significant through the end of the study (6.0% vs. 3.5%).
Specifically, the intervention group had an initial weight loss of 8.6%, followed by weight regain in the first 5 years, and then gradual weight loss, leading to average weight loss of 6%. The control group had a gradual but consistent weight loss, for an average of 3.5% at the end of the trial.
One audience member suggested that some of the weight loss might have been due to aging. The authors said they are looking at those factors in their ongoing data analysis, which they’re planning to publish in the near future.
Meanwhile, the intervention group had significantly greater weight loss than did the control group throughout the trial. They had significantly greater improvements in fitness, hemoglobin A1c levels, systolic blood pressure, and HDL cholesterol (P less than .05 for all). The control group had significantly greater reductions in LDL cholesterol (P less than .05), although they also had a significantly greater use of medications, including insulin, statins, and antihypertensives, compared with the intervention group, the authors noted.
In the short-term (1-4 years), the intervention group saw improvements in cardiovascular risk factors, preservation of mobility, and improvements in fitness, obstructive sleep apnea, fatty liver disease, urinary incontinence, sexual function, and markers of inflammation.
The intervention also reduced the incidence of high-risk chronic kidney disease by 31%, and reduced the total costs and service utilization, especially related to hospitalization ($2,500 per participant), and medication ($2,500 per participant), the authors reported. Although the intervention didn’t affect neuropathy symptoms, it reduced the incidence of reported retinopathy by 14%, reduced the incidence of symptoms of mild or greater depression by 20%, and slowed age-related decline in reported physical function.
Program reduced burden of diabetes
"Even with no clear evidence of cardiovascular benefit, the Look AHEAD investigators have shown that attention to activity and diet can safely reduce the burden of diabetes and have reaffirmed the importance of lifestyle approach as one of the foundations of modern diabetes care," Dr. Gerstein wrote in his editorial, adding that the data show "intensive lifestyle interventions are unlikely to cause harm and may provide a modest benefit."
Interactions among subgroups – history of cardiovascular disease at baseline, and gender, race/ethnicity – showed nonsignificant interaction with cardiovascular disease history (P = .06).
Summarizing the study’s limitations, the authors said that it’s not clear whether changing the intervention groups’ dietary composition might have yielded different results. Their diet during the intervention was 1,200 to 1,800 kcal/day, with less than 30% of calories from fat, and less than 15% from protein. Authors added that the patients recruited successfully competed the fitness test at baseline, so the results can’t be generalized to all patients with type 2 diabetes.
Although the intervention has stopped, the trial continues as an observational study, said Dr. Wing. And some wonder if longer-term results would reveal new information.
"My prediction is that even after stopping the trial, as long as follow-up is carried on for several more years, you’ll see differences in total mortality," said Dr. Bennett, citing the results of UK Prospective Diabetes Study (UKPDS), which showed no difference in cardiovascular disease at 12 years, but a significant difference at 20 years. "So it does appear that intervention does have a lasting but delayed effect on that endpoint."