VOZAROVA, BARBORA, CHRISTIAN WEYER, KRISTIN HANSON, P. ANTONIO TATARANNI, CLIFTON BOGARDUS, AND RICHARD E. PRATLEY. Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obes Res. 2001;9:414 -417. Objective: Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined whether circulating plasma IL-6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes. Research Methods and Procedures: Fasting plasma IL-6 concentrations (enzyme-linked immunosorbent assay), body composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and acute insulin secretory responses to glucose (25 g intravenous glucose tolerance test) were measured in 58 Pima Indians without diabetes (24 women, 34 men). Results: Fasting plasma IL-6 concentrations were positively correlated with percentage of body fat (r ϭ 0.26, p ϭ 0.049) and negatively correlated with M (r ϭ Ϫ0.28, p ϭ 0.031), but were not related to acute insulin response (r ϭ 0.13, p ϭ 0.339). After adjusting for percentage of body fat, plasma IL-6 was not related to M (partial r ϭ Ϫ0.23, p ϭ 0.089). Discussion: Fasting plasma IL-6 concentrations are positively related to adiposity and negatively related to insulin action in Pima Indians. The relationship between IL-6 and insulin action seems to be mediated through adiposity.

Obesity [1±3] and weight gain [3±5] are independent risk factors for the development of Type II (non-insulin-dependent) diabetes mellitus and many obese people are characterized by several prediabetic abnormalities such as impaired glucose tolerance, hyperinsulinaemia and insulin resistance [6±8]. Clinically, it is well-known that glucose tolerance typically improves with weight loss and deteriorates with weight gain and weight reduction is thus commonly recommended to overweight people with normal (NGT) or impaired (IGT) glucose tolerance.Although the beneficial effects of weight loss on glucose tolerance have been well documented in numerous intervention studies [9±21], several aspects relevant to the use of weight reduction as a therapeu- Abstract Aims/hypothesis. We aimed to quantify changes in insulin action and insulin secretion associated with long-term gain, loss, regain, and maintenance of body weight in subjects with normal (NGT) or impaired (IGT) glucose tolerance. Methods. Insulin action (hyperinsulinaemic clamp) and insulin secretion (intravenous glucose challenge) were measured longitudinally in 209 Pima Indians [body weight 94.4 ± 22.8 kg (means ± SD) 89 women/ 120 men, 151 NGT/58 IGT], who either lost (n = 110) or gained (n = 99) weight (±23 % to + 29 %) over 2.6 ± 2.0 years. Insulin action and insulin secretion were reassessed on a third occasion in 33 subjects who lost at least 5 % body weight over 1.5 ± 0.8 years and then either regained or maintained weight over the subsequent 1.8 ± 1.1 years.Results. There was a linear negative relation between changes in body weight and changes in insulin-stimulated glucose disposal in subjects with normal glucose tolerance (r = ± 0.51, p < 0.0001) and impaired glucose tolerance (r = ± 0.54, p < 0.0001). In contrast, changes in the acute insulin response were positively related to weight changes in subjects with normal glucose tolerance (r = + 0.26, p < 0.005) but negatively in those with impaired glucose tolerance (r = ± 0.51, p < 0.0001). Improvements in insulin action after an average of 10 % weight loss were lost with weight regain but largely preserved with weight maintenance. Conclusion/interpretation. Improvements in insulin action are proportional to the amount of weight loss, similar in magnitude to the impairment in insulin action with weight gain, preserved with long-term weight maintenance and similar between subjects with normal and with impaired glucose tolerance. Weight gain could, however, have more detrimental effects in people with impaired glucose tolerance, in whom insulin secretion decreases rather than increases to compensate for the decreased insulin action.

BackgroundSelection of an appropriate patient-reported outcome (PRO) instrument for a clinical trial requires knowledge of the instrument’s responsiveness to detecting treatment effects. The purpose of this study was to examine the responsiveness of two health-related quality of life (HRQL) instruments used in clinical trials involving HIV-infected adults: the HIV-targeted Medical Outcomes Study HIV Health Survey (MOS-HIV), and a generic measure, the EuroQol-5D (EQ-5D).MethodsA systematic review identified clinical trials using the MOS-HIV or EQ-5D to assess outcomes for HIV-infected adults. Data abstracted from each study included study type, treatment regimen(s), PRO results, and effect size (either reported or calculated). Effect size was calculated as the difference between baseline and follow-up mean scores divided by the baseline standard deviation. Magnitude was categorized as small (d=0.20), medium (d=0.50), and large (d=0.80).ResultsBetween 2005 and 2010, the MOS-HIV was administered in 12 trials. Significant differences were observed between groups and over time in physical health summary (PHS) and mental health summary (MHS) scores (P<0.05) in subjects switching therapy after experiencing Grade-2 adverse events. Effect sizes were medium (0.55 and 0.49 for PHS and MHS, respectively) among treatment-naïve adults beginning therapy (two studies), but negligible among treatment-experienced adults (0.04 and 0.13 for PHS and MHS, respectively; three studies). The EQ-5D was used in five trials between 2001 and 2010. It was responsive to occurrences of adverse events and opportunistic infections, with small-to-medium effect sizes (range 0.30–0.50) in each of its five dimensions.ConclusionsA systematic review of PRO study results showed both the MOS-HIV and EQ-5D were responsive to changes between groups and/or over time in treatment-naïve HIV-infected patients. These instruments may be used either individually or together in clinical trials to measure changes in HRQL.