PLASMA LEPTIN CONCENTRATIONS DO NOT APPEAR TO DECREASE INSULIN-MEDIATED GLUCOSE DISPOSAL OR GLUCOSE-STIMULATED INSULIN-SECRETION IN WOMEN WITH NORMAL GLUCOSE-TOLERANCE
M. Carantoni et al., PLASMA LEPTIN CONCENTRATIONS DO NOT APPEAR TO DECREASE INSULIN-MEDIATED GLUCOSE DISPOSAL OR GLUCOSE-STIMULATED INSULIN-SECRETION IN WOMEN WITH NORMAL GLUCOSE-TOLERANCE, Diabetes, 47(2), 1998, pp. 244-247
The aim of this study was to test the hypothesis that plasma leptin co
ncentrations contributed to the pathophysiology of NIDDM by decreasing
both insulin-mediated glucose disposal and glucose-stimulated insulin
secretion, The study was performed ire 60 women with normal oral gluc
ose tolerance, Differences in insulin-mediated glucose disposal were d
etermined by comparing the steady-state plasma glucose (SSPG) concentr
ations attained at the end of a 180-min constant infusion of somatosta
tin, glucose, and insulin, while comparisons of glucose-stimulated ins
ulin secretion were based on the incremental increase ire insulin conc
entration 30 min after an oral glucose challenge (Delta Ins) as compar
ed with the fasting value, The results showed that the higher the fast
ing plasma leptin concentration, the greater the degree of insulin res
istance (r = 0.47, P < 0.01), Furthermore, multiple regression analysi
s indicated that the relationship between leptin and SSPG was independ
ent of age and degree of obesity as estimated by BMI. However, since t
he total integrated plasma insulin response was highly correlated with
both SSPG (r = 0.80, P < 0.001) and leptin (r = 0.55, P < 0.01), mult
iple regression analysis was repeated, adding total insulin response t
o the model, When this was done, the significant relationship between
leptin and SSPG disappeared, whereas both BMI (P < 0.03) and insulin r
esponse (P < 0.001) were correlated with SSPG. A significant relations
hip between leptin and Delta Ins was seen, but it was a positive one (
r = 0.31, P < 0.02), not a negative one as would be expected if circul
ating levels: of leptin inhibited glucose-stimulated insulin secret-io
n, Furthermore, multiple: regression analysis could only confirm an in
dependent relationship between Delta Ins and SSPG, but not between Del
ta Ins and lep. tin, The results of these studies do not support the v
iew that circulating leptin has a primary effect on either insulin act
ion or secretion in normal female volunteers. It seems more likely tha
t chronic hyperinsulinemia in insulin-resistant individuals acts to in
crease adipose tissue leptin synthesis and secretion, leading to highe
r ambient leptin concentrations.