Plasma Adiponectin Concentrations Predict Insulin Sensitivity of Both Glucose and Lipid Metabolism

Abstract

In animals, the adipocyte-derived hormone adiponectin has been shown to improve insulin sensitivity, a key factor in the pathogenesis of type 2 diabetes. In Pima Indians, high plasma adiponectin levels are associated with increased insulin sensitivity and reduced risk of type 2 diabetes. It is unclear whether this is also the case in white individuals and whether an additional beneficial effect on lipid metabolism exists. We therefore analyzed in nondiabetic individuals the associations between plasma adiponectin concentrations and insulin sensitivity measured by a euglycemic-hyperinsulinemic clamp (n ‫؍‬ 262) and estimated by an oral glucose tolerance test (OGTT; n ‫؍‬ 636) and serum lipid parameters using correlational analysis. Plasma adiponectin concentrations were positively correlated with insulin sensitivity, both measured with the clamp (r ‫؍‬ 0.28, P ‫؍‬ 0.0015 in women; r ‫؍‬ 0.42, P < 0.0001 in men) and estimated from the OGTT (r ‫؍‬ 0.37, P < 0.0001 in women; r ‫؍‬ 0.41, P < 0.0001 in men) before and after adjusting for sex and percentage of body fat (all P < 0.001). Fasting triglycerides and the free fatty acid (FFA) concentrations during the OGTT (area under the curve) and at 120 min were negatively correlated in both women and men, whereas HDL was positively correlated with plasma adiponectin concentrations (all P < 0.004). Most notable, these relationships remained significant after adjusting for insulin sensitivity of glucose disposal in addition to sex and percentage of body fat (all P < 0.05). In conclusion, high adiponectin predicts increased insulin sensitivity. This relationship is independent of low body fat mass and affects not only insulin-stimulated glucose disposal but also lipoprotein metabolism and insulin-mediated suppression of postprandial FFA release. This suggests pleiotropic insulin sensitizing effects of adiponectin in humans. Diabetes 52:239 -243, 2003 A number of hormone-like peptides released from the adipocyte, so-called adipocytokines, have been identified. For some, such as leptin, tumor necrosis factor-␣, resistin, and adiponectin, a number of metabolic effects have been demonstrated, making these molecules candidate links between obesity and insulin resistance (1,2). Adiponectin, however, unlike other adipocytokines, is decreased in adiposity (3,4) and increases after weight reduction (5). In a nested case-control study in Pima Indians, high plasma adiponectin concentrations strongly predicted a lower incidence rate of type 2 diabetes independent of obesity (6). This seemed to be secondary to the association with increased insulin sensitivity in this population (3,7).Despite the strong statistical correlation between circulating adiponectin and measures of adiposity, a high interindividual variability remains. In other words, for a given degree of fatness, adiponectin concentrations can vary considerably among individuals. It remains to be shown whether this remaining (or residual) variability in adiponectin concentrations is an independent predictor of insulin sensiti...

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes

“…On the other hand, there were strong consistent associations between adiponectin and plasma lipids, particularly plasma triglycerides (negative), HDL-C, Apo A1 and NEFA (positive). This strong association of adiponectin with HDL metabolism has been previously noted [40][41][42][43][44][45][46][47] and in fact in a study with 4500 subjects, it was proposed as a useful marker/risk factor in cardiovascular disease assessment. 40 While the physiological nature of this correlation has not been determined, this may be tied to the proposed functions of adiponectin at the vascular wall which include modulation of endothelial function, inhibition of vascular smooth muscle proliferation, suppression of macrophage transformation and modulation of inflammation (for a review, see Ukkola and Santaniem 22 ).…”

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

“…Adiponectin levels are more abundant in plasma of lean human subjects (Coppack, 2005). In contrast, levels of adiponectin are decreased in obese human subjects promoting the onset of metabolic syndrome (Tschritter et al ., 2003; Altinova et al ., 2007). Recent in vivo studies have uncovered beneficial effects of adiponectin treatment on metabolic function.…”

“…Serine phosphorylation of IRS‐1 inhibits association with the insulin receptor stimulating degradation of IRS‐1 (Fasshauer et al ., 2003). Moreover, anti‐inflammatory adipokines such as insulin sensitizer adiponectin are decreased by excess weight gain and this decrease promotes insulin resistance in mice (Yamauchi et al ., 2001) and humans (Tschritter et al ., 2003; Altinova et al ., 2007). …”

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 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. [26][27][28]43 The mechanisms by which adiponectin may affect blood lipids are substantially unknown. There is some evidence that such effects may be mediated via reduced hepatic lipase activity, an enzyme which contributes to a lowering of HDL-C concentrations 26 low adiponectin is associated with increased hepatic lipase activity in vivo independent of insulin resistance.…”