Investigation On Serum Sfrp5Levels And Correlation With Insulin Resistance In Obese Young Adults With Type2Diabetes Mellitus

Aims: Secreted frizzled-related protein5(Sfrp5), whose well-knownfunction as Wnt5α (wingless-type MMTV integration site family member5α) inhibitor, has been described as an anti-inflammatory andinsulin-sensitizing adipokine in animal models of obesity and type2diabetes mellitus (T2DM). We aimed to investigate (1) whether circulatingSfrp5level is altered in obese young adults with T2DM and correlates withinsulin resistance and inflammation; and (2) whether Sfrp5serumconcentration can be regulated by Roux-en-Y gastric bypass surgery(RYGB).Materials and Methods: We conducted a cross-sectional andinterventional study of136Chinese young adults:34obese patients withnormal glucose tolerance (OB-NGT),48obese patients with T2DM(OB-T2DM) and54subjects with normal weight-normal glucose tolerance(NW-NGT) as controls.12patients of OB-T2DM group underwent RYGBand were followed up at12months. Serum Sfrp5concentration wasmeasured by ELISA at baseline and after surgery. Circulating levels ofhs-CRP, FPG, HbA1c, and Fins were measured. Insulin resistance (IR) was assessed by the homeostasis model assessment-IR index (HOMA-IR).Demographic characteristics, and regulation of metabolic and inflammatoryvariables after RYGB were analyzed.Results: Serum Sfrp5levels were elevated in the OB-NGT andOB-T2DM groups compared with controls (8.63±3.58vs10.84±4.28vs7.04±2.61ng/mL, p<0.05or p<0.001). Sfrp5directly correlated withbody fat parameter (BMI; r=0.343, p=0.000), with a surrogate of insulinresistance (HOMA-IR; r=0.417, p=0.000), and with a marker ofinflammation (hs-CRP; r=0.280, p=0.001). In multiple stepwise regressionanalysis, only HOMA-IR was positively associated with serum Sfrp5level(β=0.417, p=0.000). After RYGB, Sfrp5levels decreased significantlycompared to preoperatively (6.29±2.32vs13.41±4.10ng/mL, p<0.001)at12months. In fact, Sfrp5concentrations reached levels of normalweight-normal glucose tolerance subjects(p＞0.05). Additionally,HOMA-IR, hs-CRP, and Sfrp5levels decreased significantly (84.2%,81.5%, and52.9%, respectively).Conclusions: Serum Sfrp5levels were elevated in young Chineseadults with OB-T2DM. Sfrp5was directly related to insulin resistance andwas regulated by Roux-en-Y gastric bypass surgery. Therefore, Sfrp5mayplay an important role in the pathogenesis of obesity and T2DM.