Glucose intolerance is predicted by low insulin secretion and high glucagon secretion: outcome of a prospective study in postmenopausal Caucasian women.
OBJECTIVE
To study the pathophysiological importance of changes in insulin sensitivity and islet function over time for alterations in glucose tolerance in a randomly selected large group of non-diabetic women aged 57-59 years over a 3-year period.


METHODS
At baseline and at the 3-year follow-up, glucose tolerance (WHO 75 g oral glucose), insulin sensitivity (euglycaemic, hyperinsulinaemic clamp) and insulin and glucagon secretion (2 to 5-min responses to 5 g i.v. arginine at fasting, 14 and > 25 mmol/l glucose) were measured.


RESULTS
At baseline, women with impaired glucose tolerance (IGT, n = 28) had lower insulin sensitivity (p = 0.048) than normal women (NGT, n = 58). The arginine-induced insulin responses (AIR) were inversely associated with insulin sensitivity (r > or = -0.55, p < 0.001). When related to the 3-year follow-up, the baseline product of AIR at 14 mmol/l glucose times insulin sensitivity, insulin effect index (IE) (r = -0.40, p < 0.001) and the arginine-induced glucagon response at 14 mmol/l glucose (AGR, r = 0.28, p = 0.009) both correlated with follow-up 2-h glucose. In a multiple regression model, baseline 2-h glucose, insulin effect index and arginine-induced glucagon response independently predicted 2-h glucose at follow-up (total r = 0.668, p < 0.001). Furthermore, delta insulin sensitivity (i. e. follow-up minus baseline) correlated with delta insulin secretion (r = -0.30, p = 0.006), whereas delta glucagon secretion correlated with delta2-h glucose (r = 0.30, p = 0.006) over the 3 years. In a multiple regression, alterations in 2-h glucose over the 3 years were independently determined by changes in fasting insulin and glucagon secretion (r = 0.424, p < 0.001).


CONCLUSIONS
Low insulin secretion, when judged in relation to insulin sensitivity, and high glucagon secretion, determine glucose tolerance over time in the individual subject. These processes are therefore potential targets for prevention of deterioration in glucose tolerance.
Larsson
H
H
Department of Medicine, Lund University, Malmö, Sweden.
Ahrén
B
B
D000704:Analysis of Variance; D001120:Arginine; D001824:Body Constitution; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D018149:Glucose Intolerance / Q000453:epidemiology* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008875:Middle Aged; D017698:Postmenopause; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis; D013548:Sweden; D013997:Time Factors; D044465:White People
D007328:Insulin; D005934:Glucagon; D001120:Arginine