Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.

Look AHEAD Research Group, Wing RR, Bolin P, et al.
N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914

Background

Obese or overweight patients with type 2 diabetes mellitus (T2DM) are recommended to lose weight, since short-term studies show that weight loss comes with several benefits including improvements in glycemic control, risk factors for cardiovascular disease, quality of life, and other obesity-related coexisting illnesses [1]. It is however unknown whether weight loss reduces the risk of cardiovascular morbidity and mortality in patients with type 2 diabetes.
The Look AHEAD (Action for Health in Diabetes) trial therefore investigates whether an intensive lifestyle intervention designed to achieve weight loss through caloric restriction and increased physical activity would decrease cardiovascular morbidity and mortality among overweight and obese adults with T2DM [2,3]. 5145 patients were randomised to participation in an intensive lifestyle intervention or to receive diabetes support and education (control group). The aim of the intervention was to achieve and maintain at least 7% weight loss. Median follow-up was 9.6 years.

Main results

• Patients in the intervention group had significantly greater reductions in weight and waist circumference and greater improvements in fitness than did those in the control group. At the end of the study, mean weight loss from baseline was 6.0% after the intervention and 3.5% in the control group.
• Improvements in all cardiovascular risk factors were greater in the intervention group than in the control group, except for LDL-c levels, which were lower in the control group. Between-group differences diminished over time, with glycated haemoglobin level and systolic BP showing the most sustained differences.
• No difference was seen for the occurrence of the composite primary outcome of incident death from CV causes, nonfatal myocardial infarction, nonfatal stroke or hospitalisation for angina, between patients in the intervention group (n=403 events) and the control group (n=418)(1.83 vs. 1.92 events per 100 person-years, HR: 0.95, 95%CI: 0.83-10.9, P=0.51).

Conclusion

After a median follow-up of about 10 years, an intensive lifestyle intervention did not give an improvement in cardiovascular morbidity and mortality in overweight or obese T2DM patients, as compared to a control group who received diabetes support and education.
This study did show that overweight or obese adults with T2DM can lose weight and maintain modest weight loss over a period of 10 years. Patients in the intervention group also had other clinically meaningful improvements such as in glycated haemoglobin levels.

Editorial comment [4]

The lack of a beneficial effect of an intensive lifestyle intervention on cardiovascular outcomes could mean that lifestyle interventions do not effectively reduce the rate of CV events in patients with T2DM. Or, a possible group difference may have been diminished by the reduced use of reportedly cardioprotective drugs in the intervention group and by the fact that the weight loss effect and the effect on other risk factors diminished after the first few years. Furthermore, the inclusion of hospitalisation for angina in the primary composite outcome may have obscured a possible difference, as the frequency of angina was almost identical in both groups, while the incidence of other components of the primary endpoint were numerically, but not significantly higher in the control group.
Based on these considerations, future trials should use different and novel strategies to maintain initially large effects on weight and other risk factors over several years.
Clinicians can still inform their patients that changes in activity and diet can safely reduce weight, reduce the burden of diabetes and improve well-being. Judging from the confidence intervals, they are unlikely to cause harm, and may provide a modest benefit.

References

1. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults — the evidence report. Obes Res 1998;6:Suppl 2:51S-209S.
[Erratum, Obes Res 1998;6:464.]
2. Knowler WC, Fowler SE, Hamman RF, et al. 10-Year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009;374:1677-86. [Erratum, Lancet 2009;374:2054.]
3. Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in U.S. diabetes care, 1999– 2010. N Engl J Med 2013;368:1613-24.
4. Gerstein HC. Do lifestyle changes reduce serious outcomes in diabetes? N Engl J Med 2013: 369:2 July 11.

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