Study Design. This is a prospective study on the effect of a subcutaneously injected single 60mg dose of denosumab in 14 postmenopausal severe osteoporotic nondiabetic women evaluated at baseline and 4 and 12 weeks after their first injection by an oral glucose

tolerance test. Results. A single 60mg dose of denosumab efficiently inhibited serum alkaline phosphatase while it did not exert any significant variation in fasting glucose, insulin, or HOMA-IR at both 4 and 12 weeks. No changes could be detected in glucose response to the glucose load, Matsuda Index, or insulinogenic index. Nonetheless, 60mg denosumab induced a significant SB202190 in vitro reduction in the hepatic insulin resistance index at 4 weeks and in HbA1c levels at 12 weeks. Conclusions. A single 60mg dose of denosumab might positively affect hepatic insulin sensitivity though it does not induce clinical evident glucose metabolic disruption in nondiabetic patients.”
“Aims: Insulin resistance is characterized by impaired biological

response of peripheral tissues to the metabolic effects of insulin. Organic cation transporter 2 (OCT2) is responsible for 80% metformin clearance. Limited information is available on the potential relationship between genetic variants of OCT2 and insulin resistance. In this study, we examined the role of OCT2-T201M (602 C bigger than T) variant in insulin resistance in patients BKM120 order with type 2 diabetes (T2D) who were treated with metformin. Methods: Serum concentrations of insulin and C-peptide were assessed using ELISA. Homeostasis model assessment for insulin resistance (HOMA-IR) and HOMA for beta cell function (HOMA-BCF) were determined. PCR-based restriction fragment length

polymorphism was used to genotype the OCT2-T201M variant. Results: Patients with minor alleles had higher HbA1c concentrations (p = 0.019), fasting glucose levels (p = 0.023), HOMA-IR (p = 0.03), and selleck screening library HOMA-BCF (p = 0.26) than patients with common alleles. Multivariate analysis identified a significant association between the variables OCT2-T201M and gender, with HOMA-IR and HOMA-BCF (Wilks’ lambda = 0.549, F = 12.71, p smaller than 0.001 for OCT2-T201M and Wilks’ lambda = 0.369, F = 26.46, p smaller than 0.001 for gender. Changes in HOMA-BCF were inversely correlated with changes in fasting glucose levels (r = -0.412, p = 0.008) and HbA1c (r = -0.257, p = 0.114). Conclusions: Our findings suggest that the loss-of-function variant OCT2-T201M (rs145450955) contribute to changes in insulin resistance and beta cell activity in patients with T2D treated with metformin. Moreover, gender as an independent variable has a significant relationship with HOMA-BCF. (C) 2015 Elsevier Ireland Ltd. All rights reserved.