Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance.
Recent evidence suggests that the postprandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (delta 0-10 min insulin area divided by delta 0-10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2-19.4] vs 9.1 [2.6-14.5] mU.mmol-1; p < 0.01). During the clamp, circulating insulin (93 +/- 8 [mean +/- SEM] and 81 +/- 10 mU.l-1) and glucagon (54 +/- 4 and 44 +/- 6 ng.l-1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 +/- 0.27 vs 4.47 +/- 0.53 mg.kg-1.min-1; p < 0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38 +/- 0.10 and 0.30 +/- 0.18 mg.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Berrish
T S
TS
Human Diabetes and Metabolism Research Centre, University of Newcastle upon Tyne, UK.
Hetherington
C S
CS
Alberti
K G
KG
Walker
M
M
D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D003903:Deuterium; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D000078790:Insulin Secretion; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D003903:Deuterium; D005947:Glucose