Relationship between serum secreted frizzled-related protein 4 levels and the first-phase of glucose-stimulated insulin secretion in individuals with different glucose tolerance.

Recent evidence suggests that serum secreted frizzled-related protein (SFRP) 4 may affect β-cell function. In a cross-sectional clinical study, 56 subjects with type 2 diabetes mellitus (T2DM), 52 subjects with impaired glucose tolerance (IGT) and 42 normal glucose tolerance (NGT) subjects were enrolled to investigate the relationship between SFRP4 levels and the first-phase of glucose-stimulated insulin secretion, glucose metabolism and inflammation. Intravenous glucose tolerance tests were conducted, and acute insulin response (AIR), the area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and the glucose disposition index (GDI) were calculated. The serum levels of SFRP4, IL-1β, plasma glucose, serum lipid, and glycated hemoglobin (HbA1c) were measured. Levels of serum SFRP4 and IL-1β in the T2DM group and IGT group were significantly higher than those in the NGT group (P < 0.01). The AIR, AUC and GDI between the three groups showed a progressive decrease from the NGT to IGT groups with the lowest value in the T2DM groups (P < 0.01). The serum SFRP4 levels were negatively correlated with AIR, AUC, GDI and HOMA-β (P < 0.01) and were positively correlated with fasting plasma glucose, HbA1c, hs-CRP, and IL-1β (P < 0.01). Our study provides evidence that the concentrations of serum SFRP4 in T2DM and IGT subjects were increased and were correlated closely with glycose metabolic disorder, the first-phase of glucose-stimulated insulin secretion and chronic low-grade inflammation. SFRP4 may participate in the development of type 2 diabetes mellitus.