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


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.
Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, DK-2900 Copenhagen, Denmark.
Jonatan I
JI
Bagger
Filip K
FK
Knop
Asger
A
Lund
Henrik
H
Vestergaard
Jens J
JJ
Holst
Tina
T
Vilsbøll
D000082:Acetaminophen / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D008875:Middle Aged
D000082:Acetaminophen; D018712:Analgesics, Non-Narcotic; D001786:Blood Glucose; D002096:C-Peptide; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D006442:Glycated Hemoglobin; D054795:Incretins; D007328:Insulin