Discrimination Between Obesity and Insulin Resistance in the Relationship With Adiponectin

Fahim Abbasi; James W. Chu; Cindy Lamendola; Tracey McLaughlin; John Hayden; Gerald M. Reaven; Peter D. Reaven

Disclosures

Diabetes. 2004;53(3) 

In This Article

Research Design and Methods

Subjects included 20 men and 40 women volunteers from the San Francisco Bay Area who had participated in studies conducted at Stanford University within the past 3 years to investigate relationships of insulin resistance and weight. The Stanford Human Subjects Committee had approved all studies, and written informed consent had been obtained from all subjects. In each study, blood was drawn after an overnight fast, plasma was separated, and aliquots prepared for determination of glucose, free fatty acid (FFA), insulin, lipid, and lipoprotein concentrations as previously described[13,14] or frozen for additional assays. In each of the studies, insulin-mediated glucose disposal was also quantified by a modification[19] of the insulin suppression test as originally described and validated.[20] Briefly, subjects were infused for 180 min with octreotide acetate (0.27 µg · m-2 · min-1), insulin (32 mU · m-2 · min-1), and glucose (267 mg · m-2 · min-1). Blood was drawn at 10-min intervals from 150-180 min of the infusion to measure plasma glucose and insulin concentrations, and the mean of these four values was used as the steady-state plasma insulin and glucose (SSPG) concentration for each individual. As steady-state plasma insulin concentrations were similar in all subjects during these tests, the SSPG concentration provided a direct measure of the ability of insulin to mediate disposal of an infused glucose load; the higher the SSPG concentration, the more insulin resistant the individual.

From the cohort of subjects studied during the past 3 years, we selected a subset of individuals who both met the criteria described below and had plasma that had been carefully frozen at -80°C for <3 years and was available for measurement of adiponectin. Participants were required to be in good general health as determined by a complete medical history and physical examination and a normal blood count and chemistry screening battery. Four equal groups of volunteers meeting these general criteria were then created on the basis of both BMI and SSPG concentration. Subjects were classified as being either obese or nonobese on the basis of BMI. The BMI cut points chosen to make this distinction were values of ≥30.0 or <27.0 kg/m2, respectively, to correspond to suggested criteria for classifying individuals as being either obese or not heavy enough to merit the use of U.S. Food and Drug Administration-approved weight loss drugs.[21] Subjects were classified as insulin resistant or insulin sensitive on the basis of having an SSPG concentration in the upper (>190 mg/dl) or lower (<100 mg/dl) tertile, respectively, of measurements of insulin-mediated glucose disposal in 490 healthy volunteers.[22] Tertiles of SSPG concentrations were used to make this distinction on the basis of results of prospective studies[23,24] showing that individuals in the upper tertile of SSPG concentration developed a variety of adverse outcomes, none of which occurred in those in the lowest SSPG tertile. In additional analyses, the Adult Treatment Panel III waist circumference criteria[25] were also used to classify subjects with measurements of waist circumference (n = 33) into those with and without visceral obesity.

Plasma adiponectin was measured with a radioimmunoassay established by Linco Research (St. Charles, MO). This assay has a sensitivity of 0.01 mg/dl and intra- and interassay coefficients of variation (CVs) of <8%.

Summary statistics are expressed as mean ± SD. Adiponectin, HDL cholesterol, triglyceride, insulin, and FFA concentrations were log transformed to obtain a more normal distribution for statistical tests. Demographic and metabolic characteristics of the four study groups were compared by one-way ANOVA, except for sex distribution, which was compared by χ2 test. Post hoc Bonferroni pairwise comparisons were performed for variables that were significantly different (P < 0.05) by one-way ANOVA. Variation of adiponectin levels in both the insulin-sensitive and the insulin-resistant groups was assessed by calculating each group's variance and 95% CIs. Spearman correlation coefficients (r s) were calculated to evaluate the relationship of adiponectin levels with BMI and SSPG concentrations in the whole study group. Pearson (r) correlation coefficients were calculated to explore the relationships between plasma adiponectin concentrations and the demographic and metabolic characteristics of the study subjects. As several of these parameters, including adiponectin, vary between the sexes, the Pearson correlation coefficients were sex adjusted. Standardized regression coefficients (β) were calculated using multiple regression analysis to further quantify the strengths of associations between plasma adiponectin and the variables of interest, specifically, age, sex, BMI, blood pressure, lipids, glucose, FFA, insulin, and SSPG concentrations.

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