Effect of ageing and diabetes on glucose-dependent insulinotropic polypeptide and dipeptidyl peptidase IV responses to oral glucose.
OBJECTIVE
Glucose-dependent insulinotropic polypeptide (GIP) acts on the pancreas to potentiate glucose-induced insulin secretion (enteroinsular axis). GIP is rapidly inactivated in vivo by the enzyme dipeptidyl dipeptidase IV (DPP-IV). The current studies were designed to examine the effect of ageing, obesity and diabetes on GIP and DPP-IV responses to oral glucose.


METHODS
Healthy controls (nine middle-aged, age 42 +/- 2 years, body mass index (BMI) 33 +/- 1 kg/m2; nine elderly, age 71 +/- 1 years, BMI 30 +/- 1 kg/m2) and patients with Type 2 diabetes (12 middle-aged, age 44 +/- 2 years, BMI 34 +/- 2 kg/m2; 19 elderly, age 74 +/- 1 years, BMI 31 +/- 1 kg/m2) underwent a 3-h oral glucose tolerance test (OGTT) (glucose dose 40 g/m2).


RESULTS
Insulin responses were similar in elderly controls and patients with diabetes, but were lower in middle-aged patients with diabetes than in controls (308 +/- 65 vs. 640 +/- 109 pM, P < 0.05). GIP responses were similar in controls and patients with diabetes in each age group, but were higher in elderly controls (middle-aged 45 +/- 13; elderly 112 +/- 13 pM, P < 0.01) and patients with diabetes (middle-aged 55 +/- 10; elderly 99 +/- 10 pM, P < 0.01). DPP-IV levels were lower in patients with diabetes in both middle-aged (control 0.241 +/- 0.015; diabetes 0.179 +/- 0.017 delta OD/20 min, P < 0.05) and elderly groups (control 0.223 +/- 0.019; diabetes 0.173 +/- 0.010 delta OD/20 min, P < 0.05).


CONCLUSIONS
It was concluded that ageing in obese subjects is associated with enhanced GIP responses to oral glucose. In addition, DPP-IV activity is reduced in middle-aged and elderly obese patients with diabetes.
Meneilly
G S
GS
Department of Medicine, The University of British Columbia, Vancouver, Canada. gmeneill@vanhosp.bc.ca
Demuth
H U
HU
McIntosh
C H
CH
Pederson
R A
RA
D000328:Adult; D000368:Aged; D000375:Aging; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male
D001786:Blood Glucose; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D018819:Dipeptidyl Peptidase 4