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

Clinical Diabetes and Nutrition Section (C.W., R.E.P., P.A.T.), National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016; and Department of Internal Medicine and Molecular Science (T.F., S.T., K.H., Y.M.), Graduate School of Medicine, Osaka University, Osaka, Japan

Address all correspondence and requests for reprints to: Christian Weyer, M.D., Clinical Diabetes and Nutrition Section, National Institutes of Health, 4212 North 16th Street, Room 5-41, Phoenix, Arizona 85016. E-mail: cweyer{at}phx.niddk.nih.gov

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 (r² = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 ± 2.6 vs. 10.2 ± 4.3 µg/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 µg/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.

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				Y.-F. Tian, C.-H. Chu, M.-H. Wu, C.-L. Chang, T. Yang, Y.-C. Chou, G.-C. Hsu, C.-P. Yu, J.-C. Yu, and C.-A. Sun Anthropometric measures, plasma adiponectin, and breast cancer risk Endocr. Relat. Cancer, September 1, 2007; 14(3): 669 - 677. [Abstract] [Full Text] [PDF]

				L. Cong, J. Gasser, J. Zhao, B. Yang, F. Li, and A. Z Zhao Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2 Endocr. Relat. Cancer, September 1, 2007; 14(3): 713 - 720. [Abstract] [Full Text] [PDF]

				M. Bullo, M. R Peeraully, P. Trayhurn, J Folch, and J. Salas-Salvado Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women Eur. J. Endocrinol., September 1, 2007; 157(3): 303 - 310. [Abstract] [Full Text] [PDF]

				D. Barb, C. J Williams, A. K Neuwirth, and C. S Mantzoros Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence Am. J. Clinical Nutrition, September 1, 2007; 86(3): 858S - 866S. [Abstract] [Full Text] [PDF]

				W.-S. Yang, Y.-C. Yang, C.-L. Chen, I-L. Wu, J.-Y. Lu, F.-H. Lu, T.-Y. Tai, and C.-J. Chang Adiponectin SNP276 is associated with obesity, the metabolic syndrome, and diabetes in the elderly Am. J. Clinical Nutrition, August 1, 2007; 86(2): 509 - 513. [Abstract] [Full Text] [PDF]

				A. E Schutte, H. W Huisman, R. Schutte, L. Malan, J. M van Rooyen, N. T Malan, and P. E H Schwarz Differences and similarities regarding adiponectin investigated in African and Caucasian women Eur. J. Endocrinol., August 1, 2007; 157(2): 181 - 188. [Abstract] [Full Text] [PDF]

				A Klamer, K Skogstrand, D M Hougaard, B Norgaard-Petersen, A Juul, and G Greisen Adiponectin levels measured in dried blood spot samples from neonates born small and appropriate for gestational age Eur. J. Endocrinol., August 1, 2007; 157(2): 189 - 194. [Abstract] [Full Text] [PDF]

				G. Yuan, X. Chen, Q. Ma, J. Qiao, R. Li, X. Li, S. Li, J. Tang, L. Zhou, H. Song, et al. C-reactive protein inhibits adiponectin gene expression and secretion in 3T3-L1 adipocytes J. Endocrinol., August 1, 2007; 194(2): 275 - 281. [Abstract] [Full Text] [PDF]

				T. Josephs, H. Waugh, I. Kokay, D. Grattan, and M. Thompson Fasting-induced adipose factor identified as a key adipokine that is up-regulated in white adipose tissue during pregnancy and lactation in the rat J. Endocrinol., August 1, 2007; 194(2): 305 - 312. [Abstract] [Full Text] [PDF]

				L. J. Moran, M. Noakes, P. M. Clifton, G. A. Wittert, D. P. Belobrajdic, and R. J. Norman C-Reactive Protein before and after Weight Loss in Overweight Women with and without Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2944 - 2951. [Abstract] [Full Text] [PDF]

				M. Cesari, K. Narkiewicz, R. De Toni, E. Aldighieri, C. J. Williams, and G. P. Rossi Heritability of Plasma Adiponectin Levels and Body Mass Index in Twins J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3082 - 3088. [Abstract] [Full Text] [PDF]

				A. J. G. Hanley, D. Bowden, L. E. Wagenknecht, A. Balasubramanyam, C. Langfeld, M. F. Saad, J. I. Rotter, X. Guo, Y.-D. I. Chen, M. Bryer-Ash, et al. Associations of Adiponectin with Body Fat Distribution and Insulin Sensitivity in Nondiabetic Hispanics and African-Americans J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2665 - 2671. [Abstract] [Full Text] [PDF]

				T. Sir-Petermann, B. Echiburu, M M. Maliqueo, N. Crisosto, F. Sanchez, C. Hitschfeld, M. Carcamo, P. Amigo, and F. Perez-Bravo Serum adiponectin and lipid concentrations in pregnant women with polycystic ovary syndrome Hum. Reprod., July 1, 2007; 22(7): 1830 - 1836. [Abstract] [Full Text] [PDF]

				J. Jurimae and T. Jurimae Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E42 - E47. [Abstract] [Full Text] [PDF]

				J.A. Paniagua, A. G. de la Sacristana, I. Romero, A. Vidal-Puig, J.M. Latre, E. Sanchez, P. Perez-Martinez, J. Lopez-Miranda, and F. Perez-Jimenez Monounsaturated Fat-Rich Diet Prevents Central Body Fat Distribution and Decreases Postprandial Adiponectin Expression Induced by a Carbohydrate-Rich Diet in Insulin-Resistant Subjects Diabetes Care, July 1, 2007; 30(7): 1717 - 1723. [Abstract] [Full Text] [PDF]

				L. A. Barbour, C. E. McCurdy, T. L. Hernandez, J. P. Kirwan, P. M. Catalano, and J. E. Friedman Cellular Mechanisms for Insulin Resistance in Normal Pregnancy and Gestational Diabetes Diabetes Care, July 1, 2007; 30(Supplement_2): S112 - S119. [Full Text] [PDF]

				S. Santosa, I. Demonty, A. H. Lichtenstein, K. Cianflone, and P. J.H. Jones An Investigation of Hormone and Lipid Associations after Weight Loss in Women J. Am. Coll. Nutr., June 1, 2007; 26(3): 250 - 258. [Abstract] [Full Text] [PDF]

				R. K. Stoving, J.-W. Chen, D. Glintborg, K. Brixen, A. Flyvbjerg, K. Horder, and J. Frystyk Bioactive Insulin-Like Growth Factor (IGF) I and IGF-Binding Protein-1 in Anorexia Nervosa J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2323 - 2329. [Abstract] [Full Text] [PDF]

				N. R. Poa and P. F. Edgar Insulin Resistance Is Associated With Hypercortisolemia in Polynesian Patients Treated With Antipsychotic Medication Diabetes Care, June 1, 2007; 30(6): 1425 - 1429. [Abstract] [Full Text] [PDF]

				C. M. de Souza Batista, R.-Z. Yang, M.-J. Lee, N. M. Glynn, D.-Z. Yu, J. Pray, K. Ndubuizu, S. Patil, A. Schwartz, M. Kligman, et al. Omentin Plasma Levels and Gene Expression Are Decreased in Obesity Diabetes, June 1, 2007; 56(6): 1655 - 1661. [Abstract] [Full Text] [PDF]

				L. Qi, A. Doria, E. Giorgi, and F. B. Hu Variations in Adiponectin Receptor Genes and Susceptibility to Type 2 Diabetes in Women: A Tagging-Single Nucleotide Polymorphism Haplotype Analysis Diabetes, June 1, 2007; 56(6): 1586 - 1591. [Abstract] [Full Text] [PDF]

				W.-S. Chow, B. M.Y. Cheung, A. W.K. Tso, A. Xu, N. M.S. Wat, C. H.Y. Fong, L. H.Y. Ong, S. Tam, K. C.B. Tan, E. D. Janus, et al. Hypoadiponectinemia as a Predictor for the Development of Hypertension: A 5-Year Prospective Study Hypertension, June 1, 2007; 49(6): 1455 - 1461. [Abstract] [Full Text] [PDF]