Look AHEAD is the first study to examine the effects of an intensive lifestyle intervention through 4 years of follow-up in a large cohort of overweight and obese individuals with type 2 diabetes. This study shows that lifestyle interventions can produce long term weight loss and improvement in fitness and sustained beneficial effects on CVD risk factors. Across the four years, the intensive lifestyle group experienced significantly greater average improvements in all risk factors, except LDL-cholesterol. Although the differences between the two groups was greatest initially and decreased over time for several measures, the differences between the groups averaged over the four years were substantial () and indicate that the intervention group spent a considerable time at lower CVD risk.
The average weight losses achieved in the intensive lifestyle intervention at one year (8.6%) were greater than those seen in other multi-center lifestyle trials.5, 12, 13
Although few studies report weight loss data for two or more years of follow-up, the Look AHEAD results at year 2 (6.4%), 3 (5.1%) and year 4 (4.7%) appear comparable or better than those reported previously.5, 14–16
The weight losses in Look AHEAD are impressive in light of the perception that individuals with diabetes have more difficulty losing weight than do their non-diabetic counterparts.17
Maintenance of weight loss has always been a major problem in behavioral treatments of obesity.18, 19
Thus it is interesting to note that weight regain may be slowing over time in Look AHEAD. Whereas participants regained approximately 25% of their weight losses between years 1 and 2 and 20% between years 2 and 3, they regained only 8% of their weight loss between years 3 and 4. The positive effects of the Look AHEAD intervention on weight loss may reflect the ongoing intensive contact,20
combination of group and individual contact, use of meal replacement products, and higher goals prescribed for weight loss.6
Since there have been no intervention studies reporting fitness changes beyond one year for participants with diabetes,21
Look AHEAD provides unique data on long-term changes in fitness. At year 4 the ILI group had maintained a 5% improvement in fitness whereas the control group was below their baseline. The improvements in fitness seen in the ILI group exceed those reported previously for patients with type 2 diabetes in response to a 52 week diet plus exercise intervention.22
The sustained improvements in fitness are important in light of the large number of studies showing that fitness levels are associated with CVD and all-cause mortality.23–26
Averaged across the 4 years, the intervention had significant effects relative to the control group for every cardiovascular risk factor, except LDL-cholesterol. Whereas medications typically address only one risk factor, the lifestyle intervention produced positive changes in glycemic control, blood pressure, and lipids simultaneously. Thus across this time period, participants in the ILI group had lower exposure to a number of potentially negative effects of elevated CVD risk factors.
The improvements in risk factors can also be viewed at each annual visit separately to determine the duration of the effect. Compared with the DSE group, the intervention produced sustained positive effects for four years on glycemic control, systolic blood pressure and HDL-C. The effects on DBP and triglycerides were maintained for only 2–3 years, respectively. We have found no prior intervention studies with individuals with diabetes followed for as long as four years. Based on studies with non-diabetic subjects, the long-term effects of the lifestyle intervention in Look AHEAD are consistent with or greater than those reported previously in other randomized trials with 2 to 3 year follow-up periods or in meta-analyses for blood pressure,13, 27, 28
triglycerides,14, 15, 28
and HDL-C.14, 15, 29
The impact of the intervention on several of the risk factors (HbA1c and SBP) was greatest at year 1, followed by recidivism toward baseline levels. This pattern is likely due in part to the regain of weight and decreases in changes in fitness from years 1 to 4. It may also relate to the stronger effect of weight loss on CVD risk factors immediately after weight loss than at longer time intervals even in those who maintain their weight loss in full.30, 31
In the Swedish Obesity Study (SOS) much larger weight losses achieved through gastric surgery led to short-term improvements in CVD risk factors, which were not necessarily sustained long-term;32
despite this, there were marked benefits of weight loss on cardiovascular mortality.33
The decrease in the beneficial effects of lifestyle, relative to DSE, over the four years for measures such as DBP was also due to the improvements that occurred in the DSE group. These improvements may reflect secular trends in the treatment of CVD risk factors or the effects of diabetes on body weight,34
joining a clinical trial, and/or the beneficial effects of the educational classes.
In addition to the significant differences between groups in the levels of the CVD risk factors, the intervention also resulted in fewer participants in the lifestyle group starting on medications to achieve this control. This was particularly apparent for diabetes medications, especially insulin. Thus, in addition to health benefits, the intervention may result in both health benefits and cost-savings due to decreased medication use.
Of particular note is the sustained effect of lifestyle intervention on HDL-cholesterol. In contrast to several other risk factors, the effect for HDL-cholesterol of the intensive lifestyle intervention relative to the control group was as great at year 4 as it had been at year 1. At each of the 4 years, HDL-C in the lifestyle group was approximately 8–9% higher than baseline levels, whereas the control group was 3–6% above baseline. Early randomized controlled trials35, 36
showed that the combination of weight loss and increased physical activity had the greatest impact on HDL-cholesterol levels and parallel the type of approach used in Look AHEAD. Given the evidence from the Helsinki Heart Study of a strong association between increases in HDL-C and reduced heart disease,37
the effects of lifestyle intervention on HDL-C may provide important long-term cardiovascular benefit.
The finding from Look AHEAD of greater benefits of lifestyle intervention for HDL-C than for LDL-C is consistent with prior studies.2
Levels of LDL-cholesterol decreased consistently over the four years of follow-up in both groups in Look AHEAD, likely due to the large number of participants in both groups who were started on lipid lowering medications, typically statins and reflecting the increasing emphasis given to treating LDL-cholesterol in individuals with diabetes.38
After adjusting for the use of lipid lowering medications, no significant differences in LDL-cholesterol were observed either initially or at follow-up.
In conclusion, the intensive lifestyle intervention was successful in producing sustained weight losses and improvements in cardiovascular fitness through 4 years of follow-up. The intervention group also experienced significantly greater improvements than the usual care group in all CVD risk factors averaged across this time period, with the exception of LDL-C, where after adjusting for medication use, improvements were similar in the two groups. The lifestyle group in Look AHEAD is being offered ongoing intervention activities in an effort to sustain the improvements in risk factors. The critical question is whether these differences between groups in risk factors will translate into differences in the development of cardiovascular disease. These results will not be available for several additional years. However, we note that the magnitude of the effects we have observed for fitness, HDL-C, HbA1c and blood pressure have been associated with decreased cardiovascular events and mortality in prior medication trials and observational studies.24, 25, 39–41
Moreover, there may be long-term beneficial effects from the four year period in which lifestyle participants have been exposed to lower CVD risk factors as seen in other clinical trials.42, 43
Longer follow-up will allow us to determine whether the differences between groups in cardiovascular risk factors can be maintained and whether lifestyle intervention has positive effects on cardiovascular morbidity and mortality.