Increased serum cystatin C levels and responses of pancreatic α- and β-cells in type 2 diabetes

Abstract

Background: Increased serum cystatin C (CysC) can predict the onset of typ e 2 diabetes (T2D). Meanwhile, impaired pancreatic α- and β-cell functions get involved in the pathophysiological processes of T2D. So this study was to explo re the relationships between serum CysC levels and pancreatic α- and β-cell functions in T2D. Methods: In this cross-sectional observational study, a total of 2634 p atients with T2D were consecutively recruited. Each recruited patient received a serum CysC test and oral glucose tolerance test for synchronous detection of serum C-peptide and plasma glucagon. As components of pancreatic β-cell function, insulin secretion and sensitivity indices were evaluated by C-peptide area under the curve (AUC-C P) and C-peptide-substituted Matsuda’s index (Matsuda-CP), respectively. Fasting glucagon (F-GLA) and post-challenge glucagon calculated by glucagon area under the c urve (AUC-GLA) were used to assess pancreatic α-cell function. These skewed indices and were further natural log-transformed (ln). Results: With quartiles of serum CysC levels ascending, AUC-CP, F-GLA a nd AUC-GLA were increased, while Matsuda-CP was decreased (P for trend <0.001). Moreover, serum CysC levels were positively related to lnAUC-CP, lnF-GLA and lnAUC-G LA (r = 0.241, 0.131 and 0.208, respectively, P < 0.001), and inversely related to lnMatsuda-CP (r = –0.195, P < 0.001). Furthermore, after controlling for other relevant v ariables via multivariable linear regression analysis, serum CysC levels were identified to account for lnAUC-CP (β = 0.178, t = 10.518, P < 0.001), lnMatsuda-CP (β = –0.137, t = –7.118, P < 0.001), lnF-GLA (β = 0.049, t = 2.263, P = 0.024) and lnAUC-GLA (β = 0.121, t = 5.730, P < 0.001). Conclusions: Increased serum CysC levels may be partly responsible for incr eased insulin secretion from β-cells, decreased systemic insulin sensitivity, and elevated fa sting and postprandial glucagon secretion from α-cells in T2D.