Effect of Lingliptin and Voglibose on metabolic Profile in patients with Type 2 Diabetes: a randomized, double-blind, placebo-controlled trial
BMC PHARMACOLOGY & TOXICOLOGY
Authors: Parthan, Girish; Bhansali, Shobhit; Kurpad, Anura, V; Walia, Rama; Bhat, Kishor; Bhansali, Anil
Abstract
Background: Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, these patients had uncontrolled blood glucose at inclusion; therefore, the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. This study examines the effect of linagliptin on insulin sensitivity and beta-cell function in patients with well-controlled T2DM. Methods: Thirty patients with T2DM of duration <= 5 years, and having HbA1c < 7.5% were randomized to receive linagliptin, voglibose or placebo (n = 10 each), and were followed up for 6 months. Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp, and insulin secretory response was measured by basal (M-0) and postprandial (M-1) beta-cell function, and area under curve (AUC) for C-peptide during mixed meal tolerance test. Results: The median HbA1c of the study subjects at inclusion was 6.9% and there was no significant difference among the groups in terms of age, duration of diabetes, body mass index (BMI), HbA1c, insulin sensitivity, AUC of C-peptide and M-0 and M, at baseline. At the end of the study, there was a modest reduction in HbA1c (-0.2%) in the linagliptin group, and a significant decrease (-0.8%) in the voglibose group, as compared to placebo (p=0.038). However, there were no significant differences in insulin sensitivity, M-0 and M-1 and AUC of C-peptide, within, or among the groups. Conclusion: Linagliptin modestly improves glycemic profile in patients with well controlled T2DM; however, it may not have an effect on insulin sensitivity in these patients. Trial registration: Retrospectively Registered in Ginicaltrials.gov (ID number, NCT02097342). Registered: March 27, 2014.
Host Determinants of MERS-CoV Transmission and Pathogenesis
VIRUSES-BASEL
Authors: Widagdo, W.; Ayudhya, Syriam Sooksawasdi Na; Hundie, Gadissa B.; Haagmans, Bart L.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. One of these host factors, the MERS-CoV receptor dipeptidyl peptidase-4 (DPP4), may be a critical determinant because it is variably expressed in MERS-CoV-susceptible species as well as in humans. This could partially explain inter- and intraspecies differences in the tropism, pathogenesis, and transmissibility of MERS-CoV. In this review, we explore the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis-such as sialic acids, host proteases, and interferons. Further characterization of these host determinants may potentially offer novel insights to develop intervention strategies to tackle ongoing outbreaks.