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/m2 ; FPG=9.9±0.2 mmol/l; HbA1c=7.7±0.1 %) were studied: 29 pateients 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 AUC0-240 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.
Key words
proinsulin to C-peptide ratio - beta-cell function - DPP-4 inhibitor - incretins -
GLP-1 - mathematical modeling
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Correspondence
B. AhrénMD
Department of Medicine
B11 BMC
221 84 Lund
Sweden
Phone: +46/46/222 07 58
Fax: +46/46/222 07 57
Email: Bo.Ahren@med.lu.se