Disassociated relation between plasma tumor necrosis factor-alpha, interleukin-6 and increased body weight in Amerindian women: A long-term prospective study of natural body weight variation and impaired glucose tolerance

Background: Inflammatory cytokines are linked to obesity-related insulin resistance and may predict type 2 diabetes independently of obesity. We previously reported that a majority of a cohort of 73 non-diabetic women with normal plasma (p-) glucose with Amerindian heritage in Lima, Peru, during a 5-year period increased both body weight and p-glucose levels, yet p-insulin was unaltered. A high proportion of palmitoleic acid (16: 1n-7) in serum (s) and systolic blood pressure (SBP) were independent predictors of high p-glucose. Whether cytokines also contributed is, however, not known. Methods: During 5 years we prospectively investigated the relation between changed concentrations of p-tumor necrosis factor (TNF)-alpha, p-interleukin (IL)-6 and circulating insulin and glucose in relation to the natural variation of body weight. Study variables included anthropometric measurements, p-insulin, TNF-alpha, IL-6, SBP and the proportion of 16: 1n-7 in s-fatty acid composition. Results: Weight and waist differences correlated negatively to the difference in p-TNF-alpha but positively to differences in p-IL-6 and p-insulin, whereas the increase of p-glucose from baseline to follow-up did not correlate with changes in levels of the two cytokines. In multiple regression analysis changes of TNF-alpha and insulin contributed independently to the variance in weight. P-insulin at baseline and weight change were determinants of fasting p-insulin at follow-up. Multiple regression analysis revealed that weight change (t-value = -2.42; P = 0.018) and waist change (t-value = 2.41; P = 0.019) together with S-16: 1n-7 (p < 0.0001) and SBP (p = 0.0005) at baseline were significant predictors of p-glucose at follow-up. Conclusion: Our prospective study of Amerindian women revealed disassociations between changes in p-TNF-alpha and p-IL-6 in relation to variation in body weight. A high proportion of s-16: 1n-7, SBP at baseline together with weight and waist changes were independent predictors of p-glucose at follow-up. The exact role of the opposite effects and clinical impact of p-TNF-alpha and p-IL-6 on loss and gain of body weight and indirectly on the development of glucose intolerance is not known.