Disturbances in beta-cell function in impaired fasting glycemia.
In a cross-sectional study, we assessed beta-cell function and insulin sensitivity index (ISI) with hyperglycemic clamps (10 mmol/l) in 24 subjects with impaired fasting glycemia (IFG, fasting plasma glucose [FPG] between 6.1 and 7.0 mmol/l), 15 type 2 diabetic subjects (FPG >7.0 mmol/l), and 280 subjects with normal fasting glycemia (NFG, FPG <6.1 mmol/l). First-phase insulin release (0-10 min) was lower in IFG (geometric mean 541 pmol/l.10 min; 95% confidence interval [CI] 416-702 pmol/l.10 min) and in type 2 diabetes (geometric mean 376 pmol/l.10 min; 95% CI 247-572 pmol/l.10 min) than NFG (geometric mean 814 pmol/l.10 min; 95% CI 759-873 pmol/l.10 min) (P < 0.001). Second-phase insulin secretion (140-180 min) was also lower in IFG (geometric mean 251 pmol/l; 95% CI 198-318 pmol/l; P = 0.026) and type 2 diabetes (geometric mean 157 pmol/l; 95% CI 105-235 pmol/l; P < 0.001) than NFG (geometric mean 295 pmol/l; 95% CI 276-315 pmol/l). IFG and type 2 diabetic subjects had a lower ISI (0.15 plus minus 0.02 and 0.16 plus minus 0.02 micromol/kg fat-free mass [FFM]/min/pmol/l, respectively) than NFG (0.24 plus minus 0.01 micromol/kg FFM/min/pmol/l, P < 0.05). We found a stepwise decline in first-phase (and second-phase) secretion in NFG subjects with progressive decline in oral glucose tolerance (P < 0.05). IFG subjects with impaired glucose tolerance (IGT) had lower first-phase secretion than NFG subjects with IGT (P < 0.02), with comparable second-phase secretion and ISI. NFG and IFG subjects with a diabetic glucose tolerance (2-h glucose >11.1 mmol/l) had a lower ISI than their respective IGT counterparts (P < 0.05). We conclude that the early stages of glucose intolerance are associated with disturbances in beta-cell function, while insulin resistance is seen more markedly in later stages.
van Haeften
Timon W
TW
Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. t.w.vanhaeften@azu.nl
Pimenta
Walkyria
W
Mitrakou
Asimina
A
Korytkowski
Mary
M
Jenssen
Trond
T
Yki-Jarvinen
Hannele
H
Gerich
John E
JE
D000328:Adult; D001786:Blood Glucose; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005215:Fasting / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose