Minor long-term changes in weight have beneficial effects on insulin sensitivity and beta-cell function in obese subjects.
OBJECTIVE
To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function.


METHODS
Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet.


METHODS
Twelve obese patients (11 women, 1 man), age 45.8 +/- 10.5 years, body weight (BW) 99.7 +/- 13.3 kg, BMI 35.3 +/- 2.8 kg/m(2).


METHODS
At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning.


RESULTS
The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a19% increase. A significant decrease in both fasting (p = 0.038) and 2 h (p = 0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = - 0.83,p = 0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in S(I) explaining 67% of the variation. First phase insulin response (AIRg)remained unchanged whereas insulin disposition index increased significantly (p = 0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later.


CONCLUSIONS
In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance.
Rosenfalck
A M
AM
Department of Endocrinolgy, Hvidovere University Hospital, Copenhagen, Denmark. amro@dadlnet.dk
Hendel
H
H
Rasmussen
M H
MH
Almdal
T
T
Anderson
T
T
Hilsted
J
J
Madsbad
S
S
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D002096:C-Peptide / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D000077403:Orlistat; D010919:Placebos; D015431:Weight Loss / Q000502:physiology*
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D002096:C-Peptide; D007783:Lactones; D010919:Placebos; D000077403:Orlistat