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

Abstract and Introduction

Insulin resistance and obesity are both associated with lower plasma adiponectin concentrations. Since insulin resistance and obesity are related, the extent to which the association of adiponectin with insulin resistance is dependent on its relationship with obesity is unclear. To address this issue, fasting plasma adiponectin concentrations were measured in 60 nondiabetic subjects, stratified into four equal groups on the basis of both their degree of adiposity and insulin resistance. Insulin resistance was quantified by determining the steady-state plasma glucose (SSPG) concentration in response to an infusion of octreotide, glucose, and insulin, and degree of adiposity was assessed by BMI. Subjects were defined as obese (BMI ≥30.0 kg/m2) or nonobese (<27.0 kg/m2) and as either insulin sensitive (SSPG <100 mg/dl) or insulin resistant (>190 mg/dl). Insulin-resistant subjects had significantly (P<0.001) lower (mean ± SD) adiponectin concentrations, whether they were obese (17.1 ± 5.9 µg/ml) or nonobese (16.3 ± 7.5 µg/ml) as compared with either obese, insulin-sensitive (34.3 ± 13.1 µg/ml) or nonobese, insulin-sensitive (29.8 ± 15.3 µg/ml) subjects. Finally, adiponectin levels in insulin-sensitive subjects varied to a significantly greater degree than in insulin-resistant subjects. These results suggest that adiponectin concentrations are more closely related to differences in insulin-mediated glucose disposal than obesity.

An association between adipokines and insulin resistance has been noted in both diabetic and nondiabetic states.[1,2,3] Of particular interest have been the recent demonstrations that adiponectin may play a direct role in determining insulin-mediated glucose uptake.[3,4,5,6,7] However, since adiponectin is the major adipokine secreted by fat cells and is closely linked to obesity,[8,9] it is unclear to what extent the association of adiponectin with insulin resistance is independent of its relationship with obesity. Understanding this association is of importance because it may clarify mechanisms of insulin resistance and influence our understanding and use of therapeutic modalities, such as weight loss or exercise to enhance insulin sensitivity.

Studies have documented that adiponectin concentrations are significantly related to various measures of body fat[8,9,10,11] and that significant weight loss leads to a rise in adiponectin levels.[9,10] However, it is possible that the relationship between obesity and adiponectin is due in part to metabolic changes frequently associated with obesity. For example, insulin resistance and hyperinsulinemia are frequently associated with obesity, and both decline with weight loss.[12,13,14] Importantly, both in vitro and in vivo studies[15,16] have demonstrated that insulin itself may lead to downregulation of adiponectin secretion from fat cells. Moreover, several studies[15,16,17] have reported that improving insulin resistance and reducing insulin levels with an insulin-sensitizing agent markedly increases adiponectin concentrations, even in the absence of or after adjustment of changes in weight. One way to determine whether insulin resistance is associated with adiponectin independently of obesity is to take advantage of the fact that both obese and nonobese individuals can be insulin sensitive as well as insulin resistant.[12,13,14,18] We have used this approach in this study and have compared plasma adiponectin levels in nonobese and obese individuals, stratified at baseline into insulin-sensitive and insulin-resistant groups.

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