Impaired regulation of the incretin effect in patients with type 2 diabetes

Jonatan I Bagger; Filip K Knop; Asger Lund; Henrik Vestergaard; Jens Juul Holst; Tina Vilsbøll

doi:10.1210/jc.2010-2435

Impaired regulation of the incretin effect in patients with type 2 diabetes

Jonatan I Bagger, Filip K Knop, Asger Lund, Henrik Vestergaard, Jens Juul Holst, Tina Vilsbøll

139 Citations (Scopus)

Abstract

Objective: In healthy subjects, the incretin effect during an oral glucose tolerance test increases with the size of glucose load, resulting in similar glucose excursions independently of the glucose loads. Whether patients with type 2 diabetes mellitus (T2DM) are able to regulate their incretin effect is unknown. Research Design and Methods: Incretin effect was measured over 6 d by means of three 4-h oral glucose tolerance test with increasing glucose loads (25, 75, and 125 g) and three corresponding isoglycemic iv glucose infusions in eight patients with T2DM [fasting plasma glucose, mean 7.7 (range 7.0-8.9) mM; glycosylated hemoglobin, 7.0% (6.2-8.4%)] and eight matched healthy control subjects [fasting plasma glucose, 5.3 (4.8-5.7) mM; glycosylated hemoglobin, 5.4% (5.0-5.7%)]. Results: Patients with T2DM exhibited higher peak plasma glucose in response to increasing oral glucose loads, whereas no differences in peak plasma glucose values among control subjects were observed. The incretin effect was significantly (P < 0.003) lower in patients with T2DM (0 ± 7, 11 ± 9, and 36 ± 5%) as compared with control subjects (36 ± 5, 53 ± 6, and 65 ± 6%). Equal and progressively delayed gastric emptying due to the increasing loads was found in both groups. Incretin hormone responses were similar. Conclusions: Up-regulation of the incretin effect in response to increasing oral glucose loads seems to becrucial for controlling glucose excursions in healthy subjects. Patients with T2DM are characterized by an impaired capability to regulate their incretin effect, which may contribute to the exaggerated glucose excursions after oral ingestion of glucose in these patients.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	96
Issue number	3
Pages (from-to)	737-45
Number of pages	9
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2010-2435
Publication status	Published - Mar 2011

Keywords

Acetaminophen
Adult
Aged
Analgesics, Non-Narcotic
Area Under Curve
Blood Glucose
C-Peptide
Diabetes Mellitus, Type 2
Female
Gastric Emptying
Gastric Inhibitory Polypeptide
Glucagon-Like Peptide 1
Glucose
Glucose Tolerance Test
Hemoglobin A, Glycosylated
Humans
Incretins
Insulin
Insulin-Secreting Cells
Male
Middle Aged

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1210/jc.2010-2435

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@article{d330382f9c4547869de1e5c2980db465,

title = "Impaired regulation of the incretin effect in patients with type 2 diabetes",

abstract = "Objective: In healthy subjects, the incretin effect during an oral glucose tolerance test increases with the size of glucose load, resulting in similar glucose excursions independently of the glucose loads. Whether patients with type 2 diabetes mellitus (T2DM) are able to regulate their incretin effect is unknown. Research Design and Methods: Incretin effect was measured over 6 d by means of three 4-h oral glucose tolerance test with increasing glucose loads (25, 75, and 125 g) and three corresponding isoglycemic iv glucose infusions in eight patients with T2DM [fasting plasma glucose, mean 7.7 (range 7.0-8.9) mM; glycosylated hemoglobin, 7.0% (6.2-8.4%)] and eight matched healthy control subjects [fasting plasma glucose, 5.3 (4.8-5.7) mM; glycosylated hemoglobin, 5.4% (5.0-5.7%)]. Results: Patients with T2DM exhibited higher peak plasma glucose in response to increasing oral glucose loads, whereas no differences in peak plasma glucose values among control subjects were observed. The incretin effect was significantly (P < 0.003) lower in patients with T2DM (0 ± 7, 11 ± 9, and 36 ± 5%) as compared with control subjects (36 ± 5, 53 ± 6, and 65 ± 6%). Equal and progressively delayed gastric emptying due to the increasing loads was found in both groups. Incretin hormone responses were similar. Conclusions: Up-regulation of the incretin effect in response to increasing oral glucose loads seems to becrucial for controlling glucose excursions in healthy subjects. Patients with T2DM are characterized by an impaired capability to regulate their incretin effect, which may contribute to the exaggerated glucose excursions after oral ingestion of glucose in these patients.",

keywords = "Acetaminophen, Adult, Aged, Analgesics, Non-Narcotic, Area Under Curve, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Female, Gastric Emptying, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide 1, Glucose, Glucose Tolerance Test, Hemoglobin A, Glycosylated, Humans, Incretins, Insulin, Insulin-Secreting Cells, Male, Middle Aged",

author = "Bagger, {Jonatan I} and Knop, {Filip K} and Asger Lund and Henrik Vestergaard and Holst, {Jens Juul} and Tina Vilsb{\o}ll",

year = "2011",

month = mar,

doi = "10.1210/jc.2010-2435",

language = "English",

volume = "96",

pages = "737--45",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - Impaired regulation of the incretin effect in patients with type 2 diabetes

AU - Bagger, Jonatan I

AU - Knop, Filip K

AU - Lund, Asger

AU - Vestergaard, Henrik

AU - Holst, Jens Juul

AU - Vilsbøll, Tina

PY - 2011/3

Y1 - 2011/3

N2 - Objective: In healthy subjects, the incretin effect during an oral glucose tolerance test increases with the size of glucose load, resulting in similar glucose excursions independently of the glucose loads. Whether patients with type 2 diabetes mellitus (T2DM) are able to regulate their incretin effect is unknown. Research Design and Methods: Incretin effect was measured over 6 d by means of three 4-h oral glucose tolerance test with increasing glucose loads (25, 75, and 125 g) and three corresponding isoglycemic iv glucose infusions in eight patients with T2DM [fasting plasma glucose, mean 7.7 (range 7.0-8.9) mM; glycosylated hemoglobin, 7.0% (6.2-8.4%)] and eight matched healthy control subjects [fasting plasma glucose, 5.3 (4.8-5.7) mM; glycosylated hemoglobin, 5.4% (5.0-5.7%)]. Results: Patients with T2DM exhibited higher peak plasma glucose in response to increasing oral glucose loads, whereas no differences in peak plasma glucose values among control subjects were observed. The incretin effect was significantly (P < 0.003) lower in patients with T2DM (0 ± 7, 11 ± 9, and 36 ± 5%) as compared with control subjects (36 ± 5, 53 ± 6, and 65 ± 6%). Equal and progressively delayed gastric emptying due to the increasing loads was found in both groups. Incretin hormone responses were similar. Conclusions: Up-regulation of the incretin effect in response to increasing oral glucose loads seems to becrucial for controlling glucose excursions in healthy subjects. Patients with T2DM are characterized by an impaired capability to regulate their incretin effect, which may contribute to the exaggerated glucose excursions after oral ingestion of glucose in these patients.

AB - Objective: In healthy subjects, the incretin effect during an oral glucose tolerance test increases with the size of glucose load, resulting in similar glucose excursions independently of the glucose loads. Whether patients with type 2 diabetes mellitus (T2DM) are able to regulate their incretin effect is unknown. Research Design and Methods: Incretin effect was measured over 6 d by means of three 4-h oral glucose tolerance test with increasing glucose loads (25, 75, and 125 g) and three corresponding isoglycemic iv glucose infusions in eight patients with T2DM [fasting plasma glucose, mean 7.7 (range 7.0-8.9) mM; glycosylated hemoglobin, 7.0% (6.2-8.4%)] and eight matched healthy control subjects [fasting plasma glucose, 5.3 (4.8-5.7) mM; glycosylated hemoglobin, 5.4% (5.0-5.7%)]. Results: Patients with T2DM exhibited higher peak plasma glucose in response to increasing oral glucose loads, whereas no differences in peak plasma glucose values among control subjects were observed. The incretin effect was significantly (P < 0.003) lower in patients with T2DM (0 ± 7, 11 ± 9, and 36 ± 5%) as compared with control subjects (36 ± 5, 53 ± 6, and 65 ± 6%). Equal and progressively delayed gastric emptying due to the increasing loads was found in both groups. Incretin hormone responses were similar. Conclusions: Up-regulation of the incretin effect in response to increasing oral glucose loads seems to becrucial for controlling glucose excursions in healthy subjects. Patients with T2DM are characterized by an impaired capability to regulate their incretin effect, which may contribute to the exaggerated glucose excursions after oral ingestion of glucose in these patients.

KW - Acetaminophen

KW - Adult

KW - Aged

KW - Analgesics, Non-Narcotic

KW - Area Under Curve

KW - Blood Glucose

KW - C-Peptide

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Gastric Emptying

KW - Gastric Inhibitory Polypeptide

KW - Glucagon-Like Peptide 1

KW - Glucose

KW - Glucose Tolerance Test

KW - Hemoglobin A, Glycosylated

KW - Humans

KW - Incretins

KW - Insulin

KW - Insulin-Secreting Cells

KW - Male

KW - Middle Aged

U2 - 10.1210/jc.2010-2435

DO - 10.1210/jc.2010-2435

M3 - Journal article

C2 - 21252240

SN - 0021-972X

VL - 96

SP - 737

EP - 745

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 3

ER -

Impaired regulation of the incretin effect in patients with type 2 diabetes

Abstract

Keywords

UN SDGs

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