Association of Interleukin-6, C-reactive Protein, Interleukin-10 and Adiponectin Plasma Concentrations with Measures of Obesity, Insulin Sensitivity and Glucose Metabolism

Abstract

Abnormal glucose tolerance is associated with subclinical chronic inflammation in patients with type 2 diabetes. The aim of this study was to investigate whether plasma concentrations of inflammatory markers are associated with measures of obesity, insulin sensitivity, and hyperglycemia. IL-6, adiponectin, CRP, and IL-10 plasma concentrations were evaluated in 142 patients with a wide range of obesity, insulin sensitivity and glucose tolerance. In parallel with the impairment of glucose tolerance, there was a significant increase in IL-6, and CRP, and a significant decrease in adiponectin and IL-10 plasma concentrations. There were significant correlations between the plasma concentrations of all inflammatory markers and % body fat, insulin sensitivity, and fasting plasma glucose. However, multivariate linear regression analysis identified insulin sensitivity as determined by glucose infusion rate during the steady state of an euglycemic-hyperinsulinemic clamp as the strongest predictor of adiponectin, CRP, IL-6, and IL-10 plasma concentrations. In addition, fasting plasma glucose was a significant determinant of adiponectin, CRP, and IL-6 plasma concentrations, whereas body fat content was only a significant predictor of CRP plasma concentration. In conclusion, our data suggest that abnormal inflammatory markers in patients with type 2 diabetes are primarily related to decreased insulin sensitivity.

Key words

IL-6 - IL-10 - CRP - adiponectin - insulin resistance

References

• 1 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.  Biochem Biophys Res Commun. 1999;  257 79-83
• 2 Blüher M, Unger R, Rassoul F, Richter V, Paschke R. Relation between glycaemic control, hyperinsulinaemia and plasma concentrations of soluble adhesion molecules in patients with impaired glucose tolerance or Type II diabetes.  Diabetologia. 2002;  45 210-216
• 3 Colwell J A. Vascular thrombosis in type II diabetes mellitus.  Diabetes. 1993;  42 8-11
• 4 Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Mohlig M, Pfeiffer A F, Luft F C, Sharma A M. Association between adiponectin and mediators of inflammation in obese women.  Diabetes. 2003;  52 942-947
• 5 Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial.  JAMA. 2003;  289 1799-1804
• 6 Esposito K, Pontillo A, Giugliano F, Di Palo C, Grella E, Nicoletti G, Giugliano D. Association of low interleukin-10 levels with the metabolic syndrome in obese women.  J Clin Endocrinol Metab. 2003;  88 1055-1058
• 7 Fernandez-Real J M, Broch M, Vendrell J, Gutierrez C, Casamitjana R, Pugeat M, Richart C, Ricart W. Interleukin-6 gene polymorphism and insulin sensitivity.  Diabetes. 2000;  49 517-520
• 8 Festa A, D′Agostino Jr R, Howard G, Mykkanen L, Tracy R P, Haffner S M. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS).  Circulation. 2000;  102 42-47
• 9 Haffner S M, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.  N Engl J Med. 1998;  339 229-234
• 10 Leinonen E, Hurt-Camejo E, Wiklund O, Hulten L M, Hiukka A, Taskinen M R. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes.  Atherosclerosis. 2003;  166 387-394
• 11 McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P, Reaven P. Differentiation between obesity and insulin resistance in the association with C-reactive protein.  Circulation. 2002;  106 2908-2912
• 12 [no author listed] . Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. 2000;  23 (Suppl 1) S4-S19
• 13 van Exel E, Gussekloo J, de Craen A J, Frolich M, Bootsma-Van Der Wiel A, Westendorp R G. Leiden 85 Plus Study: Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study.  Diabetes. 2002;  51 1088-1092
• 14 Visser M, Bouter L M, McQuillan G M, Wener M H, Harris T B. Elevated C-reactive protein levels in overweight and obese adults.  JAMA. 1999;  282 2131-2135
• 15 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.  J Clin Endocrinol Metab. 2001;  86 1930-1935