Adiponectin is a key regulator of insulin resistance. Recent studies on multimer formation in human blood have demonstrated that high–molecular weight (HMW) adiponectin is the active form of the protein (1–3). Recently, Hara et al. (3) demonstrated that the ratio of HMW adiponectin to total adiponetin (HMWR) in systemic circulation is useful for the prediction of insulin resistance and metabolic syndrome.
Metabolically obese, normal-weight (MONW) subjects (BMI <25 kg/m2) are characterized by excess visceral fat area (VFA; ≥100 cm2 by abdominal computed tomography scanning) and insulin resistance (4–6). In addition, we previously demonstrated that the plasma level of total adiponectin is significantly associated with insulin resistance and hyperinsulinemia in Japanese MONW men with normal glucose tolerance (NGT) (6). However, the relationship of HMWR with insulin resistance has not yet been evaluated in Japanese MONW men with NGT.
The present study comprised 24 Japanese MONW (mean [±SE] age 35.7 ± 1.5 years, BMI 23.5 ± 0.2 kg/m2, and VFA 130.1 ± 4.3 cm2) and 28 age-matched normal (BMI <25 kg/m2 and VFA <100 cm2) men (aged 31.6 ± 1.5 years, BMI 21.2 ± 0.3 kg/m2, and VFA 61.5 ± 4.2 cm2) with NGT.
The serum levels of HMW and total adiponectin were measured using a commercially available enzyme-linked immunosorbent assay kit (Daiichi Pure Chemicals, Ibaraki, Japan) (7).
The serum levels of HMW (1.260 ± 0.152 vs. 1.791 ± 0.172 μg/ml, P < 0.05) and total (4.593 ± 0.307 vs. 5.680 ± 0.395 μg/ml, P < 0.05) in MONW men were significantly decreased compared with normal men. HMWR was significantly decreased in MONW subjects (0.261 ± 0.018, P < 0.05) compared with normal subjects (0.321 ± 0.023). The glucose infusion rate (GIR; index of insulin resistance during the euglycemic-hyperinsulinemic clamp study) in MONW subjects (50.2 ± 2.1 μmol · kg−1 · min−1, P < 0.01) was significantly decreased compared with normal subjects (62.8 ± 0.3 μmol · kg−1 · min−1). The serum levels of HMW (r = 0.491, P < 0.05) and total (r = 0.414, P < 0.05) adiponectin were significantly correlated with GIR in MONW subjects. Significant correlation was observed between HMWR and GIR (r = 0.454, P < 0.05) in MONW men.
This is the first report that demonstrates the relationship of HMWR with insulin resistance in Japanese MONW men with NGT. In our present study, three of the MONW subjects had hypertriglyceridemia (≥1.7 mmol/l) and nine men had arterial hypertension (blood pressure ≥130/85 mmHg), but the remaining subjects showed no low HDL cholesterol (<1.0 mmol/l). Based on these findings, these subjects are considered to have premetabolic syndrome (8). This clinical condition should be diagnosed at early stages to prevent the progression of oxidative stress and the occurrence of obesity-related complications (9). The results of this study showed that in addition to total serum levels of adiponectin, HMWR should also be evaluated for screening and early diagnosis of insulin resistance in Japanese MONW subjects with NGT.