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The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes

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@article{c3cf2999f15848a0bd2ff1e67ed3b5db,
title = "The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes",
abstract = "Aims: The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes.Methods: In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57-85 years, HbA1c: 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed.Results: Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163).Conclusions: We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.",
keywords = "Acarbose/pharmacology, Aged, Aged, 80 and over, Blood Glucose/drug effects, Cross-Over Studies, Denmark, Diabetes Mellitus, Type 2/drug therapy, Double-Blind Method, Female, Gastric Emptying/drug effects, Glucagon-Like Peptide 1/physiology, Humans, Insulin Resistance, Insulin-Secreting Cells/drug effects, Male, Metformin/therapeutic use, Middle Aged, Placebos, Postprandial Period/drug effects",
author = "Dalsgaard, {Niels B} and Gasbjerg, {L{\ae}rke S} and Hansen, {Laura S} and Hansen, {Nina L} and Signe Stensen and Bolette Hartmann and Rehfeld, {Jens F} and Holst, {Jens J} and TIna Vilsb{\o}ll and Knop, {Filip K}",
year = "2021",
month = mar,
doi = "10.1530/EJE-20-1121",
language = "English",
volume = "184",
pages = "383--394",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes

AU - Dalsgaard, Niels B

AU - Gasbjerg, Lærke S

AU - Hansen, Laura S

AU - Hansen, Nina L

AU - Stensen, Signe

AU - Hartmann, Bolette

AU - Rehfeld, Jens F

AU - Holst, Jens J

AU - Vilsbøll, TIna

AU - Knop, Filip K

PY - 2021/3

Y1 - 2021/3

N2 - Aims: The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes.Methods: In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57-85 years, HbA1c: 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed.Results: Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163).Conclusions: We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.

AB - Aims: The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes.Methods: In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57-85 years, HbA1c: 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed.Results: Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163).Conclusions: We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.

KW - Acarbose/pharmacology

KW - Aged

KW - Aged, 80 and over

KW - Blood Glucose/drug effects

KW - Cross-Over Studies

KW - Denmark

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Double-Blind Method

KW - Female

KW - Gastric Emptying/drug effects

KW - Glucagon-Like Peptide 1/physiology

KW - Humans

KW - Insulin Resistance

KW - Insulin-Secreting Cells/drug effects

KW - Male

KW - Metformin/therapeutic use

KW - Middle Aged

KW - Placebos

KW - Postprandial Period/drug effects

U2 - 10.1530/EJE-20-1121

DO - 10.1530/EJE-20-1121

M3 - Journal article

C2 - 33449919

VL - 184

SP - 383

EP - 394

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 3

ER -

ID: 61868796