Ge. Krassas et al., LEPTIN LEVELS IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME BEFORE AND AFTER TREATMENT WITH DIAZOXIDE, European journal of endocrinology, 139(2), 1998, pp. 184-189
Leptin, a product of the ob gene, is a 16 kDa protein which is produce
d by adipocytes. In humans, obesity is a common finding in women with
polycystic ovary syndrome (PCOS). The role, however, of leptin in PCOS
is not clear Some studies have reported increased levels of leptin in
PCOS, while others report that they are normal. Also, insulin resista
nce is a common finding in PCOS. The aim of this study was to investig
ate further the role of insulin in leptin secretion in patients with P
COS by treating them for 10 days with diazoxide, an insulin-reducing c
ompound. Eight women with PCOS, mean age 22.1 +/- 2.7 years, with mean
body mass index (BMI) 28.4 +/- 5.7 kg/m(2), were studied, An oral glu
cose tolerance test (OGTT) was performed in all women and blood sample
s were taken before and at 30, 60, 90, 120 and 150 min after the admin
istration of glucose. Glucose, insulin, leptin, free testosterone, Del
ta 4 androstenedione, sex hormone binding globulin (SHBG), LH, FSH, IG
F-I and insulin-like growth factor-binding protein-3 (IGFBP-3) were me
asured in the sera taken before the administration of glucose, while g
lucose and insulin levels were measured in all samples which were coll
ected after the administration of glucose. Diazoxide 300 mg daily was
given to all women starting after the end of the OGTT for 10 days. A s
econd OGTT was performed the day after the discontinuation of the diaz
oxide treatment. The same hormonal and biochemical parameters were als
o measured in all patients during the second OGTT. After the administr
ation of diazoxide a reduction in sum insulin (262 +/- 147 vs 679 +/-
341 mu U/ml, P < 0.01), leptin (18.5 +/- 10.6 vs 24.2 +/- 10.2 ng/ml,
P < 0.01), free testosterone (3.0 +/- 1.9 vs 5.1 +/- 1.3 pg/ml, P < 0.
01), Delta 4 androstenedione (3.8 +/- 1.9 vs 5.7 +/- 2.0 ng/ml, P < 0.
01) and IGF-I (219.5 +/- 69.2 vs 314.5 +/- 82.3 ng/ml, P < 0.01) level
s was observed. Serum SHBG (38.8 +/- 16.8 vs 27.8 +/- 12.1 nmol/l, P <
0.01) and sum glucose leuels (994.1 +/- 252.7 vs 711.1 +/- 166.1 mg/d
l, P < 0.05) were increased while IGFBP-3 (3.96 +/- 2.49 vs 3.75 +/- 2
.24 mg/l), FSH (6.2 +/- 1.8 vs 6.0 +/- 2.5 mU/l) and LH (18.9 +/- 6.7
vs 21.4 +/- 6.7 mU/l) concentrations did not change significantly. A s
ignificant positive correlation was found between serum leptin and BMI
values before and after administration of diazoxide as well as betwee
n leptin, insulin and IGFBP-3 values. Also, sum insulin values correla
ted significantly with BMI. However, when multiple regression analysis
was used this correlation was eliminated except that between leptin a
nd BMI. This was most probably due to the small number of cases, The m
echanism of the reduction of leptin levels is unclear, However, it is
suggested that the concomitant decrease of insulin levels may play a r
ole.