The Relationship Between Serum Irisin Level And Obesity And Type 2 Diabetes Mellitus

Objective: Irisin is a novel myokine secreted in response to peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) activation in skeletal muscle through exercise, which can increase total energy expenditure and improve insulin sensitivity in a mouse model. We therefore aimed to investigate the association between serum irisin level in human and overweight/obesity, pancreatic β-cell function, diabetic nephropathy(DN), and various metabolic parameters.Methods: we recruited 460 healthy residents aged 40~60 in Fengxian District of Shanghai. Questionnaire, physical examination, body composition and biochemical index were measured. Serum irisin was quantified by ELISA. The diagnosis of overweight/obesity and diabetes was identified according to the diagnostic standards recommended by the World Health Organization(WHO).Subjects with body mass index(BMI) ≥25 Kg/㎡ and fasting plasma glucose(FPG) ≥7.0mmol/L, and/or oral glucose tolerance test( OGTT) 2h PG≥11.1 mmol/L were respectively diagnosed with overweight/obesity and diabetes. The subjects with urinary albumin/creatinine ratio≥30μg/mg were diagnosed with DN according to the American Diabetes Association(ADA, 2007). We aimed to investigate the serum irisin level in overweight/obesity, newly diagnosed type 2 diabetes mellitus(T2DM) and DN. Multivariate logistic regression analysis was performed to assess the association between irisin levels and overweight/obesity. The association between serum irisin and pancreaticβ-cell function and other metabolic parameters were analysed by Pearson’s correlation and multiple linear regression analyses.Results: Serum irisin levels were significantly decreased in overweight/obesity compared with the control subjects(P<0.05). There was no significant difference in serum irisin between newly diagnosed T2 DM patients and the normal-glucose-tolerance(NGT)group. There was lower irisin level in DN group compared with the control group(P<0.05). Circulating irisin level was positively correlated with FPG, haemoglobin A1 c, serum total cholesterol,high-density lipoprotein cholesterol, systolic pressure, estimated glomerular filtration rate(e GFR)and negatively correlated with low-density lipoprotein cholesterol, and serum creatinin(P<0.05). Importantly, in a multivariable model adjusted for various metabolic parameters, increased irisin levels were associated with reduced odds(OR=0.994, 95%CI=0.989-0.998, P=0.004)of overweight/obesity. Multiple linear regression revealed that homeostasis model assessment-β(HOMA-β) was associated with irisin in NGT subjects after adjusting for confounding factors. However, similar analysis in newly diagnosed T2 DM did not reveal a significant association between circulating irisin and HOMA-β and other metabolic parameters.Conclusions: In the present study, we found that serum irisin levels were decreased in overweight/obesity, which was presumably related to impaired muscle PGC-1α expression or functional disorder among these subjects. Importantly, circulating irisin level was negatively correlated with overweight/obesity, suggesting that irisin may be effective protein drugs with prevention of overweight/obesity and related metabolic diseases. Serum irisin level was closely related to HOMA-βin NGT, suggesting that irisin may play a crucial role in pancreaticβ-cell function. In addition, the lower serum irisin level in DN was positively correlated with e GFR, while negatively correlated with serum creatinine, which could probably be a new target for the prevention and control of DN.