Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes.
In patients with type 2 diabetes, gastric inhibitory polypeptide (GIP) has lost much of its insulinotropic activity. Whether this is similar in first-degree relatives of patients with type 2 diabetes is unknown. A total of 21 first-degree relatives, 10 patients with type 2 diabetes, and 10 control subjects (normal oral glucose tolerance) were examined. During a hyperglycemic "clamp" (140 mg/dl for 120 min), synthetic human GIP (2 pmol. kg(-1). min(-1)) was infused intravenously (30-90 min). With exogenous GIP, patients with type 2 diabetes responded with a lower increment (Delta) in insulin (P = 0.0003) and C-peptide concentrations (P < 0.0001) than control subjects. The GIP effects in first-degree relatives were diminished compared with control subjects (Delta insulin: P = 0.04; Delta C-peptide: P = 0.016) but significantly higher than in patients with type 2 diabetes (P < or = 0.05). The responses over the time course were below the 95% CI derived from control subjects in 7 (insulin) and 11 (C-peptide) of 21 first-degree relatives of patients with type 2 diabetes. In conclusion, a reduced insulinotropic activity of GIP is typical for a substantial subgroup of normoglycemic first-degree relatives of patients with type 2 diabetes, pointing to an early, possibly genetic defect.
Meier
J J
JJ
Medizinische Klinik, Ruhr-Universität Bochum, Knappschafts-Krankenhaus, Bochum (Langendreer), Germany.
Hücking
K
K
Holst
J J
JJ
Deacon
C F
CF
Schmiegel
W H
WH
Nauck
M A
MA
D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D002096:C-Peptide; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide