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

Y1 - 2011

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 be crucial 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 be crucial 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

VL - 96

SP - 737

EP - 745

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -