In the present study, we found that the serum irisin level was reduced in Han young males with IGR. Although we ruled out the factor of metabolic abnormalities, serum irisin still plays an important role in impaired glucose regulation. Multiple logistic regression analysis showed that serum irisin and HOMA-IR were significant independent predictors for IGR. Our findings suggest that reduced serum irisin levels may increase the occurrence of glucose disorders and may predict the occurrence of diabetes in Chinese young men.
Many clinical studies have reported lower levels of irisin in patients with T2DM than in controls (17–19). For instance, Ali EY et al, reported irisin was lower in T2DM patients with macrovascular complications as compared to controls (17). Similarly, another study showed a negative association between irisin and FBG in subjects with new-onset T2DM (20). Further, our previous studies also observed a decreased level of circulating irisin in metabolically healthy, obese adults (21). Meanwhile, in animal studies, irisin can positively affect glucose homeostasis, lipid profile and other metabolic parameters related to obesity (22,23). Several underlying mechanisms linking irisin to glucose homeostasis and other metabolic parameters, were suggested as follows. First, it was reported that irisin regulated glucose utilization and improved fatty acid oxidation via adenosine monophosphate-activated protein kinase signaling pathway activation (22). What’s more, irisin functioned as a muscle-derived energy-expenditure signal that induced browning of white adipocytes. At molecular level, irisin upregulated the expression of mitochondrial uncoupling protein-1 and other brown adipose tissue-associated genes by activation of the p38 mitogen-activated protein kinase and extracellular signal-regulated kinase signaling pathway(24).
However, there is some contradictory evidence that described a positive association between irisin and glucose levels, whole-body mass and fat mass in different subpopulations. Patients with anorexia nervosa had significantly lower levels of irisin than normal-weight people or individuals with obesity (25). Serum irisin is also positively associated with fasting insulin and blood glucose levels in individuals who are obesity but not T2DM, and in women with polycystic ovary syndrome (26,27). There is one possible explanation for the association between irisin and fat mass, which is the development of irisin resistance (9). It’s speculated that in order to achieve metabolic balance, the irisin increased secretion in obesity is aimed to maximize energy usage and glucose homeostasis.
In our study, we also evaluated other metabolic parameters. The subjects in the IGR group were found to have significantly higher BMI, WC and HOMA-IR, and lower HDL-C. Although IGR, obesity and dyslipidemia are all risk factors for T2DM and CVD, the combination of these risk factors has been consistently associated with a more adverse risk profile than neither of the isolated categories(28). In a meta-analysis of randomized, subjects with IGR in control group structured changes in lifestyle reduced incident cases of T2DM by almost 50%, as long as a weight loss of at least 5% was achieved(29).
There were some limitations in our study. First, it only included young men of the Han ethnicity in our study and the low number of subjects included on each group that can decrease the power of the statistical analysis performed. So similar studies in a larger population are needed to evaluate the generalizability. Second, a causal relationship is not possible to infer due to the cross-sectional nature of the study design. Future research should focus on the effect of irisin on insulin secretion and signal pathway, and on any possible interactions between the two pathways that might affect glucose homeostasis.
In conclusion, the present study demonstrates that serum irisin levels were reduced in Chinese young men with IGR. In addition, reduced irisin may increase the occurrence of IGR. It suggested that irisin may predict the occurrence of impaired glucose homeostasis and should be examined in future studies.