title: Improved meal-related insulin processing contributes to the enhancement of B-cell function by the DPP-4 inhibitor vildagliptin in patients with type 2 diabetes.
abstract: The aim of this study was to evaluate the contribution of insulin processing to the improved meal-related B-cell function previously shown with the DPP-4 inhibitor vildagliptin. Fifty-five patients with type 2 diabetes (56.5+/-1.5 years; BMI=29.6+/-0.5 kg/m(2); FPG=9.9+/-0.2 mmol/l; HbA1c=7.7+/-0.1 %) were studied: 29 patients were treated with vildagliptin and 26 patients with placebo, both added to an ongoing metformin regimen (1.5-3.0 g/day). A standardized breakfast was given at baseline and after 52 weeks of treatment, and proinsulin related to insulin secretion was measured with C-peptide in the fasting and postprandial (over 4 h post-meal) states to evaluate B-cell function. The between-treatment difference (vildagliptin-placebo) in mean change from baseline in fasting proinsulin to C-peptide ratio (fastP/C) was -0.007+/-0.009 (p=0.052). Following the standard breakfast, 52 weeks of treatment with vildagliptin significantly decreased the dynamic proinsulin to C-peptide ratio (dynP/C) relative to placebo by 0.010+/-0.008 (p=0.037). Importantly, when the P/C was expressed in relation to the glucose stimulus (i.e., the fasting glucose and glucose AUC(0-240 min), respectively), the P/C relative to glucose was significantly reduced with vildagliptin vs. placebo, both in the fasting state (p=0.023) and postprandially (p=0.004). In conclusion, a more efficient B-cell insulin processing provides further evidence that vildagliptin treatment ameliorates abnormal B-cell function in patients with type 2 diabetes.
authors.affiliation: Department of Clinical Sciences, Division of Medicine, Lund University, Lund, Sweden. Bo.Ahren@med.lu.se
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: G
authors.initials: G
authors.lastname: Pacini
authors.forename: A
authors.initials: A
authors.lastname: Tura
authors.forename: J E
authors.initials: JE
authors.lastname: Foley
authors.forename: A
authors.initials: A
authors.lastname: Schweizer
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use; D019518:Postprandial Period / Q000502:physiology; D011384:Proinsulin / Q000097:blood* / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D002096:C-Peptide; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D011384:Proinsulin; D008687:Metformin; D000077597:Vildagliptin; D000218:Adamantane