Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state?
We aimed to investigate whether the reduced incretin effect observed in patients with type 2 diabetes is a primary event in the pathogenesis of type 2 diabetes or a consequence of the diabetic state. Eight patients with chronic pancreatitis and secondary diabetes (A1C mean [range] of 6.9% [6.2-8.0]), eight patients with chronic pancreatitis and normal glucose tolerance (NGT; 5.3 [4.9-5.7]), eight patients with type 2 diabetes (6.9 [6.2-8.0]); and eight healthy subjects (5.5 [5.1-5.8]) were studied. Blood was sampled over 4 h on 2 separate days after a 50-g oral glucose load and an isoglycemic intravenous glucose infusion, respectively. The incretin effect (100% x [beta-cell secretory response to oral glucose tolerance test - intravenous beta-cell secretory response]/beta-cell secretory response to oral glucose tolerance test) was significantly (P < 0.05) reduced (means +/- SE) in patients with chronic pancreatitis and secondary diabetes (31 +/- 4%) compared with patients with chronic pancreatitis and NGT (68 +/- 3) and healthy subjects (60 +/- 4), respectively. In the type 2 diabetes group, the incretin effect amounted to 36 +/- 6%, significantly (P < 0.05) lower than in chronic pancreatitis patients with NGT and in healthy subjects, respectively. These results suggest that the reduced incretin effect is not a primary event in the development of type 2 diabetes, but rather a consequence of the diabetic state.
Knop
Filip K
FK
Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. filipknop@dadlnet.dk
Vilsbøll
Tina
T
Højberg
Patricia V
PV
Larsen
Steen
S
Madsbad
Sten
S
Vølund
Aage
A
Holst
Jens J
JJ
Krarup
Thure
T
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000627:therapeutic use*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000627:therapeutic use*; D005972:Glutaminase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C421249:TAX1BP3 protein, human; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005972:Glutaminase