Diabetes Care
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Diabetes Care 29:2327-2328, 2006
DOI: 10.2337/dc06-1239
© 2006 by the American Diabetes Association
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Letters: Observations

Decreased High–Molecular Weight Adiponectin–to–Total Adiponectin Ratio in Sera Is Associated With Insulin Resistance in Japanese Metabolically Obese, Normal-Weight Men With Normal Glucose Tolerance

Akira Katsuki, MD1, Mina Suematsu, MD1, Esteban C. Gabazza, MD2, Shuichi Murashima, MD3, Kaname Nakatani, MD4, Kenji Togashi, PHD5, Yutaka Yano, MD1 and Yashuhiro Sumida, MD1

1 Division of Diabetology and Endocrinology, Department of Internal Medicine, Mie University School of Medicine, Mie, Japan
2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mie University School of Medicine, Mie, Japan
3 Department of Radiology, Mie University School of Medicine, Mie, Japan
4 Department of Laboratory Medicine, Mie University School of Medicine, Mie, Japan
5 Department of Health and Physical Education, Mie University School of Education, Mie, Japan

Address correspondence to Y. Sumida, MD, Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. E-mail: sumidaya{at}clin.medic.mie-u.ac.jp

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.

References

  1. Kadowaki T, Yamauchi T: Adiponectin and adiponectin receptors. Endocr Rev 26:439–451, 2005[Abstract/Free Full Text]
  2. Matsuzawa Y: The metabolic syndrome and adipocytokines. FEBS Lett 580:2917–2921, 2006[Medline]
  3. Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, Imai Y, Nagai R, Kadowaki T: Measurement of the high–molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 29:1357–1362, 2006[Abstract/Free Full Text]
  4. Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S: The metabolically obese, normal-weight individual revisited. Diabetes 47:699–713, 1998[Abstract]
  5. Karelis AD, St-Pierre DH, Conus F, Rabasa-Lhoret R, Poehlman ET: Metabolic and body composition factors in subgroups of obesity: what do we know? J Clin Endocrinol Metab 89:2569–2575, 2004[Abstract/Free Full Text]
  6. Katsuki A, Sumida Y, Urakawa H, Gabazza EC, Murashima S, Matsumoto K, Nakatani K, Yano Y, Adachi Y: Plasma levels of adiponectin are associated with insulin resistance and serum levels of triglyceride in Japanese metabolically obese, normal-weight men with normal glucose tolerance (Letter). Diabetes Care 26:2964–2965, 2003[Free Full Text]
  7. Ebinuma H, Miyazaki O, Yago H, Hara K, Yamauchi T, Kadowaki T: A novel ELISA system for selective measurement of human adiponectin multimers by using proteases. Clin Chim Acta. In press
  8. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497, 2001[Free Full Text]
  9. Katsuki A, Sumida Y, Urakawa H, Gabazza EC, Murashima S, Nakatani K, Yano Y, Adachi Y: Increased oxidative stress is associated with serum levels of triglyceride, insulin resistance, and hyperinsulinemia in Japanese metabolically obese, normal-weight men. Diabetes Care 27:631–632, 2004[Free Full Text]

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