Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes

Koichiro Azuma, Zofia Rádiková, Juliet Mancino, Frederico G S Toledo, Ernestine Thomas, Cyrous Kangani, Chiara Dalla Man, Claudio Cobelli, Jens J. Holst, Carolyn F. Deacon, YanLing He, Monica Ligueros-Saylan, Denise Serra, James E. Foley, David E. Kelley

Research output: Contribution to journalArticle

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Abstract

Objective: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research Design and Methods: Participants with T2DM (n = 16) who had a baseline hemoglobin A1c of 7.1 ± 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min·m2 insulin infusions. Results: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 ± 0.3 mmol/liter and 1.6 ± 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P<0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). Conclusions: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.

Original languageEnglish
Pages (from-to)459-464
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number2
DOIs
Publication statusPublished - 2008 Feb
Externally publishedYes

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Dipeptidyl-Peptidase IV Inhibitors
Medical problems
Metabolism
Type 2 Diabetes Mellitus
Glucose
Glucose Clamp Technique
Cross-Over Studies
Clamping devices
Insulin
Incretins
Glucagon-Like Peptide 1
Plasmas
vildagliptin
Glucagon
Insulin Resistance
Fasting
Hemoglobins
Research Design
Placebos
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes. / Azuma, Koichiro; Rádiková, Zofia; Mancino, Juliet; Toledo, Frederico G S; Thomas, Ernestine; Kangani, Cyrous; Dalla Man, Chiara; Cobelli, Claudio; Holst, Jens J.; Deacon, Carolyn F.; He, YanLing; Ligueros-Saylan, Monica; Serra, Denise; Foley, James E.; Kelley, David E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 2, 02.2008, p. 459-464.

Research output: Contribution to journalArticle

Azuma, K, Rádiková, Z, Mancino, J, Toledo, FGS, Thomas, E, Kangani, C, Dalla Man, C, Cobelli, C, Holst, JJ, Deacon, CF, He, Y, Ligueros-Saylan, M, Serra, D, Foley, JE & Kelley, DE 2008, 'Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 2, pp. 459-464. https://doi.org/10.1210/jc.2007-1369
Azuma, Koichiro ; Rádiková, Zofia ; Mancino, Juliet ; Toledo, Frederico G S ; Thomas, Ernestine ; Kangani, Cyrous ; Dalla Man, Chiara ; Cobelli, Claudio ; Holst, Jens J. ; Deacon, Carolyn F. ; He, YanLing ; Ligueros-Saylan, Monica ; Serra, Denise ; Foley, James E. ; Kelley, David E. / Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes. In: Journal of Clinical Endocrinology and Metabolism. 2008 ; Vol. 93, No. 2. pp. 459-464.
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abstract = "Objective: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research Design and Methods: Participants with T2DM (n = 16) who had a baseline hemoglobin A1c of 7.1 ± 0.2{\%} completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min·m2 insulin infusions. Results: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 ± 0.3 mmol/liter and 1.6 ± 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50{\%} (P < 0.01). Vildagliptin lowered postprandial glucagon by 16{\%} (P<0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). Conclusions: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.",
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T1 - Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes

AU - Azuma, Koichiro

AU - Rádiková, Zofia

AU - Mancino, Juliet

AU - Toledo, Frederico G S

AU - Thomas, Ernestine

AU - Kangani, Cyrous

AU - Dalla Man, Chiara

AU - Cobelli, Claudio

AU - Holst, Jens J.

AU - Deacon, Carolyn F.

AU - He, YanLing

AU - Ligueros-Saylan, Monica

AU - Serra, Denise

AU - Foley, James E.

AU - Kelley, David E.

PY - 2008/2

Y1 - 2008/2

N2 - Objective: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research Design and Methods: Participants with T2DM (n = 16) who had a baseline hemoglobin A1c of 7.1 ± 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min·m2 insulin infusions. Results: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 ± 0.3 mmol/liter and 1.6 ± 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P<0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). Conclusions: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.

AB - Objective: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research Design and Methods: Participants with T2DM (n = 16) who had a baseline hemoglobin A1c of 7.1 ± 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min·m2 insulin infusions. Results: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 ± 0.3 mmol/liter and 1.6 ± 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P<0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). Conclusions: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.

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