Obesity Epidemiology

METABOLIC AND HORMONAL PREDICTORS OF OBESITY 387While several studies reported no association between insulin resistance and weightgain, 39,42 others found a positive relationship. Hodge et al. 34 observed that in Chinesemen, insulin resistance predicted greater weight gain during follow-up. However, therewere no associations between insulin resistance and changes in weight and waist-hipratio (WHR) in Asian Indian and Creole men and women. Gould et al. 40 found that inmiddle-aged women, fasting insulin was associated with increased WHR during 4.4 yearsof follow-up. In addition, there was an association between reduced first-phase insulinsecretion and greater weight gain. The Normative Aging Study 38 showed that increasedfasting insulin predicted future weight gain. During a 3-year follow-up in the Women’sHealth Initiative observational cohort, Howard et al. 43 reported an independent associationbetween higher insulin resistance and weight gain, especially among women witha lower BMI at baseline. In Japanese Americans, Boyko et al. 35 examined the relationshipbetween insulin resistance and changes in intra-abdominal fat (IAF) measured byCT scan during 5.5 years of follow-up. After adjusting for baseline IAF, they found thatbaseline fasting insulin and C-peptide were significantly associated with increased IAFover time. Schwartz et al. 32 observed that reduced insulin secretion rather than insulinresistance was an independent predictor of weight gain in Pima Indian adults. In addition,Sigal et al. 36 found that insulin resistance measured by Bergman’s minimal modelpredicted a lower risk of weight gain only among those with higher insulin secretion.Studies conducted among children have also produced contradictory results. Odeleyeet al. 44 examined the association between fasting insulin concentration measured in 328Pima Indian children 5 to 9 years old and the rate of weight gain during 9.3 years offollow-up. After adjusting for initial relative weight, sex, and changes in height and ageover time, there was a significant association between higher fasting plasma insulin concentrationand weight gain per year in both boys and girls. The authors concluded thatincreased insulin resistance may predict greater weight gain in Pima Indian children. Onthe other hand, Travers et al. 45 found that lower insulin resistance was associated withincreased body fat among 111 healthy children aged 9.7 to 14.5 years. The authors suggestedthat during puberty, increased insulin resistance may prevent fat accumulation.Whether insulin sensitivity predicts weight regain after weight loss remains controversial.Yost et al. 46 followed 10 obese women who had undergone a 3-month weightloss program followed by 3 months of weight maintenance. Improved insulin sensitivity,measured by a euglycemic clamp before weight loss and at the end of the weightmaintenance phase, significantly predicted the amount of weight regain at both 12 and18 months. Wing et al., 47 however, found no significant association between changes infasting insulin from baseline to 6 months and weight regain in either nondiabetic ordiabetic subjects who had been through a weight loss program.On the whole, the literature does not provide clear evidence supporting the hypothesisthat insulin resistance is an adaptive mechanism that prevents further weight gain amongthe obese. In other words, an increase in insulin sensitivity does not necessarily lead toweight gain. In contrast, there appears to be more evidence that insulin resistance maylead to subsequent weight gain in some populations. The interpretation of the literature,however, is complicated by a number of factors. First, population characteristics (e.g.,ethnicity, sex, and age groups) differ across and within studies. Because insulin sensitivityis affected by these variables, the relationship between insulin sensitivity andweight change trajectories may differ across different age, sex, and ethnic groups. Second,some studies have focused on obese subjects, while others have evaluated weightchanges among relatively lean subjects. Initially obese subjects who already have highinsulin resistance at baseline tend to not gain weight or even lose weight during follow-up.Therefore, the observation that baseline insulin resistance promotes subsequent