Body Weight, Not Insulin Sensitivity or Secretion, May Predict Spontaneous Weight Changes in Nondiabetic and Prediabetic Subjects

OBJECTIVE Previous studies have found that high insulin sensitivity predicts weight gain; this association has not been confirmed. Our aim was to systematically analyze metabolic predictors of spontaneous weight changes. RESEARCH DESIGN AND METHODS In 561 women and 467 men from the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort (mean age 44 years, BMI range 19-44 kg/m(2), 9% impaired glucose tolerance) followed up for 3 years, we measured insulin sensitivity (by a euglycemic clamp) and β-cell function (by modeling of the C-peptide response to oral glucose and by acute insulin response to intravenous glucose). RESULTS Insulin sensitivity was similar in weight gainers (top 20% of the distribution of BMI changes), weight losers (bottom 20%), and weight stable subjects across quartiles of baseline BMI. By multiple logistic or linear regression analyses controlling for center, age, sex, and baseline BMI, neither insulin sensitivity nor any β-cell function parameter showed an independent association with weight gain; this was true in normal glucose tolerance, impaired glucose tolerance, and whether subjects progressed to dysglycemia or not. Baseline BMI was significantly higher in gainers (26.1 ± 4.1 kg/m(2)) and losers (26.6 ± 3.7 kg/m(2)) than in weight stable subjects (24.8 ± 3.8 kg/m(2), P<0.0001 for both gainers and losers). Baseline waist circumference (or equivalently, BMI or weight) was a positive, independent predictor of both weight gain and weight loss (odds ratio 1.48 [95% CI 1.12-1.97]) in men and (1.67 [1.28-2.12]) in women. In men only, better insulin sensitivity was an additional independent predictor of weight loss. CONCLUSIONS Neither insulin sensitivity nor insulin secretion predicts spontaneous weight gain. Individuals who have attained a higher weight are prone to either gaining or losing weight regardless of their glucose tolerance.