Glucose intolerance in obese adolescents with polycystic ovary syndrome: Roles of insulin resistance and beta-cell dysfunction and risk of cardiovascular disease
Sa. Arslanian et al., Glucose intolerance in obese adolescents with polycystic ovary syndrome: Roles of insulin resistance and beta-cell dysfunction and risk of cardiovascular disease, J CLIN END, 86(1), 2001, pp. 66-71
The roles of insulin resistance and insulin secretion in the pathogenesis o
f glucose intolerance in polycystic ovary syndrome (PCOS) were evaluated in
11 adolescents with impaired glucose tolerance (IGT) and 10 with normal gl
ucose tolerance (NGT). Hepatic glucose production and insulin-stimulated gl
ucose disposal were measured using [6,6-H-2(2)]glucose and a 3-h hyperinsul
inemic (80 mu/m(2).min)-euglycemic clamp. First and second phase insulin se
cretions were evaluated during a hyperglycemic clamp. Automated blood press
ure measurements were made to assess the nocturnal change in blood pressure
.
Hepatic glucose production was significantly higher in IGT vs. NGT. Insulin
-stimulated glucose disposal was not different between the two groups. The
first phase insulin level was lower in IGT (207.9 +/- 21.0 vs. 357.0 +/- 62
.9 muu/mL; P = 0.025; 1247 +/- 126 vs. 2142 +/- 377 pmol/L) without a diffe
rence in second phase insulin. The glucose disposition index (product of in
sulin sensitivity x first phase insulin) was lower in IGT vs. NGT (278 +/-
40 vs. 567 +/- 119 mg/kg.min; P = 0.023; 1546 +/- 223 vs. 3249 +/- 663 mu m
ol/kg.min). The glucose disposition index correlated inversely with OGTT gl
ucose concentrations at 30, 60, and 120 min. Adolescents with PCOS-IGT lack
ed the normal nocturnal decline in blood pressure.
We conclude that in obese adolescents with PCOS, glucose intolerance is ass
ociated with 1) decreased first phase insulin secretion, 2) decreased gluco
se disposition index, and 3) increased hepatic glucose production. These me
tabolic abnormalities are precursors of type 2 diabetes and are present ear
ly in the course of PCOS. Furthermore, the absence of nocturnal dipping in
blood pressure may herald the early expression of cardiovascular disease ri
sk in these adolescents.