Discrimination Between Obesity and Insulin Resistance in the Relationship With Adiponectin

Abstract

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 steadystate 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/m 2 ) or nonobese (<27.0 kg/m 2 ) 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 g/ml) or nonobese (16.3 ؎ 7.5 g/ml) as compared with either obese, insulin-sensitive (34.3 ؎ 13.1 g/ml) or nonobese, insulin-sensitive (29.8 ؎ 15.3 g/ml) subjects. Finally, adiponectin levels in insulinsensitive 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. Diabetes 53: [585][586][587][588][589][590] 2004 A n association between adipokines and insulin resistance has been noted in both diabetic and nondiabetic states (1-3). Of particular interest have been the recent demonstrations that adiponectin may play a direct role in determining insulinmediated glucose uptake (3-7). 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 -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 (12-14). 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 (15-17) have reported that improving insulin resistance and reducing insulin levels with an insulin-sensitizing agent markedly increases adipo...

Effect of moderate alcohol consumption on adipokines and insulin sensitivity in lean and overweight men: a diet intervention study

“…This may relate to lower power for these between-group differences as opposed to withinperson changes. Alternatively, adiponectin may be more related to insulin-mediated glucose disposal than obesity (Abbasi et al, 2004). Since we observed similar glucose concentrations of lean and overweight subjects, this may explain similar adiponectin concentrations.…”

Associations of adiponectin with metabolic and vascular risk parameters in the British Regional Heart Study reveal stronger links to insulin resistance-related than to coronory heart disease risk-related parameters

“…22,25,28,29,43 The associations between adiponectin and insulin sensitivity has been well established in animal and human models. 2,24 The strongest associations, however, were seen between adiponectin and triglycerides and HDL-cholesterol (components of the insulin resistance syndrome) and these relationships were independent of adiposity and insulin resistance as has been reported in other studies.…”

“…2,24 In population-based studies, adiponectin is inversely associated with body mass index (BMI), insulin resistance, triglycerides, and positively associated with high-density lipoprotein (HDL)-cholesterol, components of the metabolic syndrome. [25][26][27][28][29] Although adiponectin has been associated with markers of inflammation in particular, C-reactive protein (CRP) 30,31 associations with other proinflammatory cytokines such as interleukin 6 (IL-6) however have been less consistent 31 and based on small selected populations. Moreover, whether the potential anti-inflammatory properties of adiponectin are mediated by its effect on insulin resistance remains unknown.…”

Negative association between plasma levels of adiponectin and polychlorinated biphenyl 153 in obese women under non-energy-restrictive regime

“…5 In fact, tetrachlorodibenzo-p-dioxin (Agent Orange), one of the POPs, could induce low-grade inflammation of adipose tissue in mice 6 and also downregulation of adiponectin, one of the major secretory products of adipose tissue known to augment the effects of insulin on glucose homeostasis. Adiponectin plasma levels have been shown to be reduced, particularly in obese, 7 insulin-resistant patients 8 and in type 2 diabetics. 9 From three distinct multimeric complexes identified in human plasma, high (HMW), medium (MMW) and low (LMW) molecular weight, only the HMW adiponectin plasma levels are positively associated with insulin sensitivity.…”