Background: Irisin is a novel myokine secreted in response to peroxisome proliferator-activated receptor ?\ncoactivator-1? (PGC-1?) activation through exercise. The first-degree relatives (FDRs) of type 2 diabetes mellitus\n(T2DM) patients bear a lifetime risk for developing T2DM, especially after 40 years old. However, the circulating irisin\nlevels in middle-aged FDRs of T2DM is unclear. We therefore investigated the association between circulating irisin\nand pancreatic ?-cell function in normal-glucose-tolerance (NGT) subjects.\nMethods: In this cross-sectional study, we recruited 412 supposed healthy subjects aged 40-60 who were FDRs of\nT2DM patients but without previous diagnosis of T2DM. Of the 412 individuals, 254 had NGT and 60 were newly\ndiagnosed T2DM based on the results of a 75 g oral glucose tolerance test (OGTT- World Health Organization\ndiagnostic criteria). We measured irisin in the newly diagnosed T2DM group (n = 60) and in an age- and\nsex-matched NGT subgroups (n = 62). Serum irisin was quantified by ELISA, and its association with metabolic\nparameters was analysed by Pearson�s correlation and multiple linear regression analyses.\nResults: There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients\nand the NGT control group. Circulating irisin was correlated with haemoglobin A1c (r = 0.202, p = 0.026) and\nestimated glomerular filtration rate (r = 0.239, p = 0.010). Multiple linear regression revealed that only homeostasis model\nassessment-? (HOMA-?) was associated with irisin in NGT subjects after adjusting for confounding factors. However,\nsimilar analysis in T2DM did not reveal a significant association between circulating irisin and metabolic parameters.\nConclusions: There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients\nand the NGT controls. Serum irisin level was closely related to HOMA-? in NGT, suggesting that irisin may play a crucial\nrole in pancreatic ?-cell function.
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