Improvement of ß-cell function ameliorated glycemic variability in patients with newly diagnosed type 2 diabetes after short-term continuous subcutaneous insulin infusion or in combination with sitagliptin treatment: a randomized control trial.

Glycemic variability (GV) has been proposed as contributor to diabetes-related macrovascular complications. This randomized control trial evaluated a new combination therapy with continuous subcutaneous insulin infusion (CSII) plus sitagliptin (CSII + sitagliptin) vs. CSII only in terms of metabolic control, GV and ß-cell function in patients with newly diagnosed type 2 diabetes (T2DM). 217 patients were randomized to two weeks of CSII (n = 108) or CSII + sitagliptin (n = 109) therapy. As a measure of GV, the coefficient of variation (CV) was computed from capillary blood glucose during the first and second week, respectively. ß-cell function before and after treatment was determined with the Insulin Secretion-Sensitivity Index-2 (ISSI-2). Good metabolic controls were established with both therapies. CSII + sitagliptin therapy resulted in greater improvements in CV and ISSI-2 than CSII alone (all P = 0.000). For each group, change in CV was inversely correlated with change in ISSI-2 (r = -0.529, P = 0.000 and r = -0.433, P = 0.000, respectively). The multivariate regression analysis demonstrated that improved ISSI-2 was the only independent contributor to reduced CV in both groups (standardized ß = -0.388, P = 0.004 and standardized ß = -0.472, P = 0.000, respectively). Correction of ß-cell function in newly diagnosed T2DM patients via use of either CSII or CSII + sitagliptin therapy was feasible in controlling GV to prevent secondary complications of T2DM. Moreover, CSII + sitagliptin therapy was superior to CSII monotherapy in terms of GV.

Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients.

OBJECTIVE: Betatrophin, a newly identified hormone, has been recently characterized as a potent stimulator that increases the production and expansion of insulin-secreting ß-cells in mice, but the physiological role of betatrophin remains poorly understood. This study measured for the first time serum betatrophin levels in newly diagnosed patients with type 2 diabetes (T2DM) and explored the correlations between its serum levels and various metabolic parameters in T2DM. RESEARCH DESIGN AND METHODS: We analyzed the concentrations of betatrophin by ELISA in blood samples of 166 well-characterized individuals in whom anthropometric parameters, oral glucose tolerance test (OGTT), glycosylated hemoglobin, blood lipids, insulin sensitivity (1/homeostasis model assesment of insulin resistance [1/HOMA-IR] and Matsuda index [ISIM]), and insulin secretion were measured. The participants were divided into newly diagnosed T2DM patients (n = 83) and age-, sex- and BMI-matched healthy control subjects (n = 83). RESULTS: Serum betatrophin levels were significantly higher in T2DM patients than in healthy control subjects (613.08 [422.19-813.08] vs. 296.57 [196.53-509.46] pg/mL; P < 0.01). Serum betatrophin positively correlated with age, 2-h post-OGTT glucose (2hPG), and postprandial serum insulin (PSI), but negatively with 1/HOMA-IR and ISIM in T2DM patients. In the control group, betatrophin was only positively associated with age. In T2DM subjects, multivariate regression analyses showed that age, 2hPG, and PSI were independent factors influencing serum betatrophin levels. CONCLUSIONS: Circulating concentrations of betatrophin are significantly increased in T2DM patients. Our results suggest that betatrophin may play a role in the pathogenesis of T2DM.