Circulating Adiponectin Levels Are Reduced in Nonobese but Insulin-Resistant First-Degree Relatives of Type 2 Diabetic Patients

Abstract

Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity (S i ) was studied with the minimal model, and measurements of adiponectin, metabolic variables, inflammatory markers, and endothelial injury markers, as well as lipoprotein concentrations, were performed. FDR were insulin resistant (3.3 ؎ 2.4 vs. 4.5 ؎ 2.6 ؋ 10 ؊4 ؋ min ؊1per U/ml [mean ؎ SD], P < 0.01), and their circulating plasma adiponectin levels (6.6 ؎ 1.8 vs. 8.1 ؎ 3.0 g/ml, P < 0.03) were decreased. After adjustments for age in FDR, adiponectin levels were negatively correlated with fasting proinsulin (r ؊0.64, P < 0.001), plasminogen activator inhibitor (PAI)-1 activity (r ؊0.56, P < 0.001), fasting insulin (r ؊0.55, P < 0.001), and acute insulin response (r ؊0.40, P < 0.05); they were positively related to HDL cholesterol (r 0.48, P < 0.01) and S i (r 0.41, P < 0.01). Furthermore, when adjusted for age, waist, and S i , adiponectin was associated with HDL cholesterol and proinsulin, which explained 51% of the variation in adiponectin in multiple regression analyses in that group. In conclusion, circulating plasma adiponectin levels were decreased in nonobese but insulinresistant FDR and, in addition, related to several facets of the insulin resistance syndrome (IRS). Thus, hypoadiponectinemia may be an important component of the association between cardiovascular disease and IRS.

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 ).…”

Serum adiponectin is associated with family history of diabetes independently of obesity and insulin resistance in healthy Korean men and women

“…Our study demonstrates that FHD is associated with hypoadiponectinemia that supports findings of previous studies (9,10). In a recent study, in 64-year-old women in Sweden, mean ADIPOQ levels were lower (11.4 vs 13.9) in those with FHD than those without FHD (10).…”

“…In a recent study, in 64-year-old women in Sweden, mean ADIPOQ levels were lower (11.4 vs 13.9) in those with FHD than those without FHD (10). In another study in male subjects in Sweden, firstdegree relatives of type 2 diabetic patients also had significantly lower ADIPOQ levels (9). The present study showed an inverse relationship between FHD and ADIPOQ levels in Korean men and women.…”

Role of resistin in cardiac contractility and hypertrophy

“…Further differences in the action of both peptides have also been reported. In contract to resistin, adiponectin levels correlated negatively with obesity [46], dyslipidemia [47], coronary artery disease [48], insulin resistance [49], [50] and inflammation. Since hypertrophy is one of the earliest manifestations of cardiac dysfunction, such effects further support a role of adipokines in the development of cardiomyopathy.…”