TY - JOUR

T1 - The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose

AU - Bock, Gerlies

AU - Man, Chiara Dalla

AU - Micheletto, Francesco

AU - Basu, Rita

AU - Rn, Paula D Giesler

AU - Laugen, Jeanette

AU - Deacon, Carolyn F

AU - Holst, Jens J

AU - Toffolo, Gianna

AU - Cobelli, Claudio

AU - Rizza, Robert A

AU - Vella, Adrian

PY - 2010

Y1 - 2010

N2 - Abstract Objective: Low Glucagon-like Peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain if these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin hormone concentrations enabling an examination of their effects on glucose turnover in IFG. Research Design and Methods: We studied 22 subjects with IFG using a double blind, placebo-controlled parallel group design. At the time of enrollment, subjects ate a standardized meal labeled with [1-(13)C]-glucose. Infused [6-(3)H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6-(2)H(2)] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to100mg of sitagliptin daily or placebo. After an 8-week treatment period, the mixed meal was repeated. Results: As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C-peptide concentrations. Postprandial EGP (18.1+/-0.7 vs. 17.6+/-0.8 mumol/kg/min, p = 0.53), Rd (55.6+/-4.3 vs. 58.9+/-3.3 mumol/kg/min, p = 0.47) and MRa (6639+/-377 vs. 6581+/-316 mumol/kg per 6h, p = 0.85) were unchanged. Sitagliptin was associated with decreased total GLP-1 implying decreased incretin secretion. Conclusions: DPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG.

AB - Abstract Objective: Low Glucagon-like Peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain if these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin hormone concentrations enabling an examination of their effects on glucose turnover in IFG. Research Design and Methods: We studied 22 subjects with IFG using a double blind, placebo-controlled parallel group design. At the time of enrollment, subjects ate a standardized meal labeled with [1-(13)C]-glucose. Infused [6-(3)H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6-(2)H(2)] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to100mg of sitagliptin daily or placebo. After an 8-week treatment period, the mixed meal was repeated. Results: As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C-peptide concentrations. Postprandial EGP (18.1+/-0.7 vs. 17.6+/-0.8 mumol/kg/min, p = 0.53), Rd (55.6+/-4.3 vs. 58.9+/-3.3 mumol/kg/min, p = 0.47) and MRa (6639+/-377 vs. 6581+/-316 mumol/kg per 6h, p = 0.85) were unchanged. Sitagliptin was associated with decreased total GLP-1 implying decreased incretin secretion. Conclusions: DPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG.

U2 - 10.1111/j.1365-2265.2009.03764.x

DO - 10.1111/j.1365-2265.2009.03764.x

M3 - Journal article

C2 - 20039889

VL - 73

SP - 189

EP - 196

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

ER -