Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance and Hyperinsulinemia

Abstract

Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.

Incidence of Diabetes Mellitus in Insured Swedish Cats in Relation to Age, Breed and Sex

“…In humans, certain ethnic groups with a high propensity for obesity and type 2 diabetes have lower adiponectin concentrations compared to other groups, and this difference was not explained by differences in percent body fat among groups. Instead, the degree of hypoadiponectinemia seemed to be more related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity 24. The dyslipidemia and insulin resistance observed in Burmese cats, thus may be related to the increased risk of DM in the breed.…”

Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

“…While leptin showed significant positive associations with indices of obesity, IR and CRP, adiponectin showed the opposite trend confirming previous observations on its insulin-sensitizing, anti-inflammatory and antiatherogenic properties. 15,16 Several potential mechanisms for adiponectin's unique antidiabetic, antiinflammatory and antiatherogenic effects have been described. Adiponectin enhances insulin sensitivity in the liver and reduces hepatic glucose output, stimulates glucose use and fatty acid oxidation in skeletal muscle, inhibits monocyte adhesion and decreases proliferation of migrating smooth muscle cells in the vascular wall where it also increases nitric oxide production in endothelial cells.…”

Breast Milk Hormones and Their Protective Effect on Obesity

“…Adiponectin circulates in very high concentrations in human serum and its levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity. In fact, plasma adiponectin concentrations are decreased in individuals with obesity and type 2 diabetes [44]. …”