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Changes in Inflammatory Cytokines Are Related to Impaired Glucose Tolerance in Offspring of Type 2 Diabetic Subjects

¹ Department of Medicine, University of Kuopio, Kuopio, Finland
² Department of Clinical Chemistry, University of Kuopio, Kuopio, Finland
³ Department of Clinical Radiology, University of Kuopio, Kuopio, Finland

Address correspondence and reprint requests to Markku Laakso, MD, Academy Professor, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi

OBJECTIVE—We sought to determine whether levels of inflammatory markers and different cytokines are abnormal in nondiabetic offspring of type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS—Cytokine levels were measured in 19 healthy control subjects and 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance [NGT] and 20 with impaired glucose tolerance [IGT]). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography.

RESULTS—Levels of C-reactive protein and inflammatory cytokines were elevated in nondiabetic offspring of type 2 diabetic subjects. Interleukin (IL)-1ß was increased in the NGT group and decreased in the IGT group. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) were increased in both groups. IL-1ß and -Ra levels correlated inversely (P < 0.05) with rates of whole-body glucose uptake and IL-1ß positively with visceral fat mass (P < 0.05) in normoglycemic offspring.

CONCLUSIONS—Nondiabetic offspring of type 2 diabetic subjects have changes in the levels of inflammatory cytokines. The level of IL-1Ra seems to be the most sensitive marker of cytokine response in the pre-diabetic state.

Abbreviations: CRP, C-reactive protein • IGT, impaired glucose tolerance • IL, interleukin • IL-1Ra, IL-1 receptor antagonist • NGT, normal glucose tolerance • TNF, tumor necrosis factor • WBGU, whole-body glucose uptake

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