Objective To investigate the relationship between serum adipokine expression and insulin resistance in individuals with different degrees of glucose intolerance, and to assess the value of these adipokines in predicting the risk of progression in prediabetes.

Methods A total of 114 participants with oral glucose tolerance test were enrolled and divided into three groups based on diagnostic and classification criteria for diabetes: normal glucose tolerance (NGT, n=32), impaired glucose tolerance (IGT, n=46), and type 2 diabetes mellitus (T2DM, n=36). Serum levels of adiponectin (APN), leptin (LEP) and preadipocyte factor-1 (Pref-1) as well as homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for pancreatic β-cell function (HOMA-β) were compared among the three groups. Pearson correlation analysis was conducted to explore the correlations of serum APN, LEP and Pref-1 levels with HOMA-IR and HOMA-β. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of serum APN, LEP and Pref-1 levels for the progression of prediabetes.

Results Serum APN levels were significantly lower in the T2DM and IGT groups compared to the NGT group, with further significant reduction observed in the T2DM group compared to the IGT group (P < 0.05); conversely, serum LEP, Pref-1, fasting plasma glucose (FPG), 2-hour postprandial glucose (2 hPG), fasting insulin (FINS), glycated hemoglobin (HbA1c), triglycerides (TG) and C-reactive protein (CRP) levels were significantly higher in the T2DM and IGT groups than in the NGT group, with additional significant increases observed in the T2DM group compared to the IGT group (P < 0.05). HOMA-IR was significantly lower in both the T2DM and IGT groups than in the NGT group, with a further significant decrease in the T2DM group compared to the IGT group (P < 0.05). HOMA-β was significantly higher in both the T2DM and IGT groups compared to the NGT group, with a further significant increase in the T2DM group versus the IGT group (P < 0.05). Serum APN level was positively correlated with HOMA-IR (r=0.547, P < 0.05) and negatively correlated with HOMA-β (r=-0.506, P < 0.05); serum LEP and Pref-1 levels were negatively correlated with HOMA-IR (r=-0.325, -0.459, P < 0.05) and positively correlated with HOMA-β (r=0.317, 0.428, P < 0.05). ROC curve analysis revealed optimal cut-off values for serum APN, LEP and Pref-1 levels in predicting the progression of prediabetes were 15.98 mg/L, 4.23 mg/L and 18.85 μg/L, respectively. The combination of these three biomarkers showed a sensitivity of 80.43%, a specificity of 96.87%, and an area under the curve (AUC) of 0.925.

Conclusion Serum levels of APN, LEP and Pref-1 abnormally change in patients with impaired glucose tolerance and are associated with insulin resistance. These adipokines can serve as sensitive indicators for predicting the progression of prediabetes, with higher predictive value when used in combination.