Objective: To identify variables associated with leptin change in subjects with type 2 diabetes after 3 weeks and 20 weeks of weight loss.
Research methods and procedures: Subjects with type 2 diabetes treated with diet or sulfonylureas (n = 54) were enrolled in a 20-week behavioral weight control program. Sulfonylureas were stopped > or =2 weeks before study entry. Seven subjects who restarted sulfonylureas after week 3 had their data analyzed separately after this point.
Results: Leptin, fasting plasma glucose, and insulin levels were measured at baseline and at 3, 10, and 20 weeks. After 3 weeks, subjects lost 2.7+/-2.0 kg (p<0.001), and had significant decreases in leptin (5.2+/-7.0 ng/mL, p<0.001), fasting plasma glucose (1.8+/-1.8 mmol/L, p<0.001), and insulin (23+/-60 pmol/L, p<0.03). Between week 3 and week 20, subjects lost an additional 6.3+/-4.4 kg (p<0.001), but had no further changes in leptin. The primary determinants of leptin change at all time-points were weight loss and initial leptin level. Changes in insulin were not related to changes in leptin after controlling for the effects of weight loss. At week 20, more recent weight loss (week 10 to week 20) was as strong a predictor of overall change in leptin as overall weight loss (baseline to 20 week). Subjects who restarted sulfonylureas had an increase in both leptin levels (+1.9+/-9.0 ng/mL, p<0.05) and insulin levels (+23+/-65 pmol/L, p<0.05), despite significant overall weight loss (-7.4+/-4.0 kg, p<0.01). Initial changes in leptin (0 weeks to 3 weeks) did not affect subsequent ability to lose weight.
Discussion: Both short- and long-term changes in weight had an effect on leptin changes in individuals with type 2 diabetes. Although physiological insulin changes did not independently influence changes in leptin concentration with weight loss, increases in insulin levels with sulfonylurea therapy were associated with increases in leptin levels despite weight loss.