Benefits of Modest Weight Loss in Improving Cardiovascular Risk Factors in Type 2 Diabetes

We conducted an observational analysis of participants in the Look AHEAD (Action For Health in Diabetes) study (n = 5,145, 40.5% male, 37% from ethnic/racial minorities) and examined the association between the magnitude of weight loss and changes in CVD risk factors at 1 year and the odds of meeting predefined criteria for clinically significant improvements in risk factors in individuals with type 2 diabetes.  

The magnitude of weight loss at 1 year was strongly (P < 0.0001) associated with improvements in glycemia, blood pressure, triglycerides, and HDL cholesterol but not with LDL cholesterol (P = 0.79). Compared with weight-stable participants, those who lost 5 to <10% ([means ± SD] 7.25 ± 2.1 kg) of their body weight had increased odds of achieving a 0.5% point reduction in HbA_1c, a 5-mmHg decrease in diastolic blood pressure, a 5-mmHg decrease in systolic blood pressure, a 5 mg/dL increase in HDL cholesterol, and a 40 mg/dL decrease in triglycerides. The odds of clinically significant improvements in most risk factors were even greater in those who lost 10–15% of their body weight.  

These results provide empirical support for the assertion that modest weight losses of 5–10% of initial weight are sufficient to produce significant, clinically relevant improvements in CVD risk factors in overweight and obese patients with type 2 diabetes. However, greater weight losses were associated with greater improvements in risk factors. The magnitude of weight loss at 1 year was highly related to the improvements in blood pressure, glycemic control, and lipids, with the notable exception of LDL cholesterol. 

Despite the fact that the ILI and the DSE groups differed greatly in their average weight losses, positive associations were seen between weight change and improvements in risk factors within each group separately. This finding suggests that the degree of association between weight change and improved risk factors is relatively constant across a wide range of weight losses. There also was no evidence that a patient's weight at baseline affected the amount of improvement that occurred with a given percentage change in body weight, except for HDL cholesterol, for which the magnitude of weight loss had the greatest effect in the least overweight participants. 

The strongest associations between changes in weight and risk factors were seen for measures of glycemic control, and clinically significant improvements were observed with just a 2 to <5% reduction in initial weight. This finding confirms a large number of previous studies indicating that modest weight losses markedly improve glycemic control. The fact that all participants in this study had type 2 diabetes, whereas only some had hypertension or hyperlipidemia, may be related to this finding. On the other hand, the fact that caloric restriction, independent of weight loss, improves glycemic control may suggest a heightened responsiveness of this risk factor to caloric imbalance and weight changes. 

In contrast, we observed weaker associations between weight loss and LDL cholesterol changes, even among participants not using lipid medications at either baseline or 1 year. Moreover, although the odds of achieving a 10 mg/dL improvement in LDL cholesterol were significantly increased by a 5–10% weight loss relative to remaining weight stable, the effects were not consistent across greater weight loss categories, and even weight losses of 15% of body weight had modest effects on LDL cholesterol. Although a meta-analysis of studies assessing the effect of weight loss on lipids over at least a 2-year follow-up concluded that there was a positive linear relationship between weight loss and improvements in both total and LDL cholesterol. 

In conclusion, Look AHEAD provides empirical support for the benefits of modest weight losses at 1 year. However, greater improvement in risk factors occurred with greater weight losses. Because weight losses of just 5 to <10% of initial body weight significantly increased the odds of achieving clinically meaningful changes in glycemic control, blood pressure, HDL cholesterol, and triglycerides at 1 year, emphasizing modest weight losses seems to be an appropriate clinical message for overweight and obese patients with type 2 diabetes.