Relation Between Soluble Adhesion Molecules and Insulin Sensitivity in Type 2 Diabetic Individuals

Abstract

OBJECTIVE -The purpose of this study was to explore the relation between insulin resistance and plasma levels of soluble adhesion molecules and to examine the effects of acute hyperinsulinemia on these molecules in type 2 diabetic individuals.RESEARCH DESIGN AND METHODS -Intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-and P-selectin plasma concentrations were measured in 36 nonobese type 2 diabetic patients without cardiovascular disease and in 7 healthy subjects. Insulin sensitivity was assessed by a 4-h euglycemic (ϳ5 mmol/l)-hyperinsulinemic (ϳ300 pmol/l) clamp performed in combination with [ RESULTS -Diabetic subjects were insulin resistant but did not show plasma concentrations of adhesion molecules that were significantly higher than control subjects. In diabetic subjects, plasma ICAM-1 and E-selectin were negatively correlated with total glucose disposal during the insulin clamp (r ϭ Ϫ0.432, P Ͻ 0.01; and r ϭ Ϫ0.375, P Ͻ 0.05, respectively), whereas plasma VCAM-1 and P-selectin were not. Plasma ICAM-1 as well as E-and P-selectin were positively correlated with BMI, total body fat (TBF), and waist girth (P Ͻ 0.05-0.001). In multiple regression analyses, the relation of plasma ICAM-1 and E-selectin with insulin sensitivity was lost after adjustment for potential confounders, including HbA 1c , blood pressure, and/or LDL cholesterol. In these analyses, BMI was the only independent predictor of plasma ICAM-1 (R 2 ϭ 0.244, P Ͻ 0.002), whereas TBF was the only independent predictor of plasma E-selectin (R 2 ϭ 0.202, P ϭ 0.01). The 4-h insulin infusion during the glucose clamp did not significantly change plasma levels of adhesion molecules.CONCLUSIONS -Overall adiposity, rather than insulin resistance, may be a determinant of plasma levels of ICAM-1 and E-selectin in type 2 diabetic individuals. In these patients, acute hyperinsulinemia does not exert any significant effect on plasma adhesion molecules. These findings support the possibility that adipose tissue releases one or more factors that may adversely affect endothelial function on one hand and insulin sensitivity on the other. Diabetes Care

Insulin Resistance

“…However, unlike the previous report (30) demonstrating significant sex differences in soluble adhesion molecules in a large sample of middle-aged men and women (aged 40 -59 years), we observed a sex difference in VCAM-1 levels in blacks only (boys: 378.9 Ϯ 20.0 vs. girls: 450.7 Ϯ 22.7, P ϭ 0.028). In addition, the observation that in whites the relationship between insulin sensitivity, ICAM-1, and E-selectin levels disappears after controlling for VAT is consistent with Targher et al (31), who reported a similar finding in Caucasian adults with type 2 diabetes. These findings suggest that excess adiposity may contribute to increased circulating levels of adhesion molecules.…”

Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women

“…There is substantial evidence indicating that inflammatory cytokines act through paracrine and autocrine mechanisms to induce insulin resistance [33,34]. Nevertheless, there are conflicting reports on the usefulness of their circulating concentrations to detect this process, and several studies have failed to identify relationships between serum markers of inflammation and measures of insulin resistance [35], especially when the correlations were controlled for the influence of obesity [36,37,38].…”

Hemostatic abnormalities in endocrine and metabolic disorders

“…intercellular adhesion molecule-1, P-selectin, and E-selectin) than those without the syndrome (142)(143)(144)(145). Moreover, increased endothelial cell microparticles (EMP) release, platelet and leukocyte hyperactivation, increased binding of both EMPs and platelets to leukocytes are also shown in patients with the metabolic syndrome (133,146).…”