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

Gerlies Bock, Chiara Dalla Man, Francesco Micheletto, Rita Basu, Paula D. Giesler, Jeanette Laugen, Carolyn F. Deacon, Jens J. Holst, Gianna Toffolo, Claudio Cobelli, Robert A. Rizza, Adrian Vella

Research output: Contribution to journalArticle

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Abstract

Objective Low glucagon-like peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether 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-blinded, placebo-controlled, parallel-group design. At the time of enrolment, subjects ate a standardized meal labelled with [1- 13C]-glucose. Infused [6- 3H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6- 2H 2] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to 100 mg 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 molkg per min, P = 0·53), Rd (55·6 ± 4·3 vs 58·9 ± 3·3 molkg per min, P = 0·47) and MRa (6639 ± 377 vs 6581 ± 316 molkg per 6 h, 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.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalClinical Endocrinology
Volume73
Issue number2
DOIs
StatePublished - Aug 2010

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Dipeptidyl Peptidase 4
Incretins
Fasting
Glucose
Glucagon-Like Peptide 1
Meals
Sitagliptin Phosphate
Inhibition (Psychology)
Placebos
Dipeptidyl-Peptidase IV Inhibitors
Glucose Intolerance
C-Peptide

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. / Bock, Gerlies; Man, Chiara Dalla; Micheletto, Francesco; Basu, Rita; Giesler, Paula D.; Laugen, Jeanette; Deacon, Carolyn F.; Holst, Jens J.; Toffolo, Gianna; Cobelli, Claudio; Rizza, Robert A.; Vella, Adrian.

In: Clinical Endocrinology, Vol. 73, No. 2, 08.2010, p. 189-196.

Research output: Contribution to journalArticle

Bock, G, Man, CD, Micheletto, F, Basu, R, Giesler, PD, Laugen, J, Deacon, CF, Holst, JJ, Toffolo, G, Cobelli, C, Rizza, RA & Vella, A 2010, 'The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose', Clinical Endocrinology, vol. 73, no. 2, pp. 189-196. https://doi.org/10.1111/j.1365-2265.2009.03764.x
Bock, Gerlies ; Man, Chiara Dalla ; Micheletto, Francesco ; Basu, Rita ; Giesler, Paula D. ; Laugen, Jeanette ; Deacon, Carolyn F. ; Holst, Jens J. ; Toffolo, Gianna ; Cobelli, Claudio ; Rizza, Robert A. ; Vella, Adrian. / The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. In: Clinical Endocrinology. 2010 ; Vol. 73, No. 2. pp. 189-196.
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abstract = "Objective Low glucagon-like peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether 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-blinded, placebo-controlled, parallel-group design. At the time of enrolment, subjects ate a standardized meal labelled with [1- 13C]-glucose. Infused [6- 3H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6- 2H 2] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to 100 mg 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 molkg per min, P = 0·53), Rd (55·6 ± 4·3 vs 58·9 ± 3·3 molkg per min, P = 0·47) and MRa (6639 ± 377 vs 6581 ± 316 molkg per 6 h, 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.",
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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 - Giesler, Paula D.

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 - 2010/8

Y1 - 2010/8

N2 - Objective Low glucagon-like peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether 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-blinded, placebo-controlled, parallel-group design. At the time of enrolment, subjects ate a standardized meal labelled with [1- 13C]-glucose. Infused [6- 3H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6- 2H 2] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to 100 mg 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 molkg per min, P = 0·53), Rd (55·6 ± 4·3 vs 58·9 ± 3·3 molkg per min, P = 0·47) and MRa (6639 ± 377 vs 6581 ± 316 molkg per 6 h, 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 - Objective Low glucagon-like peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether 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-blinded, placebo-controlled, parallel-group design. At the time of enrolment, subjects ate a standardized meal labelled with [1- 13C]-glucose. Infused [6- 3H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6- 2H 2] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to 100 mg 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 molkg per min, P = 0·53), Rd (55·6 ± 4·3 vs 58·9 ± 3·3 molkg per min, P = 0·47) and MRa (6639 ± 377 vs 6581 ± 316 molkg per 6 h, 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.

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