Impaired beta-cell compensation to dexamethasone-induced hyperglycemia in women with polycystic ovary syndrome.
Deterioration in glucose tolerance occurs rapidly in women with polycystic ovary syndrone (PCOS), suggesting that pancreatic beta-cell dysfunction may supervene early. To determine whether the compensatory insulin secretory response to an increase in insulin resistance induced by the glucocorticoid dexamethasone differs in women with PCOS and control subjects, we studied 10 PCOS and 6 control subjects with normal glucose tolerance. An oral glucose tolerance test (OGTT) and a graded glucose infusion protocol were performed at baseline and after subjects took 2.0 mg of dexamethasone orally. Basal (Phi(b)), static (Phi(s)), dynamic (Phi(d)), and global (Phi) indexes of beta-cell sensitivity to glucose were derived. Insulin sensitivity (S(i)) was calculated using the minimal model; a disposition index (DI) was calculated as the product of S(i) and Phi. PCOS and control subjects had nearly identical fasting and 2-h glucose levels at baseline. Phi(b) was higher, although not significantly so, in the PCOS subjects. The Phi(d), Phi(s), and Phi indexes were 28, 19, and 20% higher, respectively, in PCOS subjects. The DI was significantly lower in PCOS (30.01 +/- 5.33 vs. 59.24 +/- 7.59) at baseline. After dexamethasone, control subjects averaged a 9% increase (to 131 +/- 12 mg/dl) in 2-h glucose levels; women with PCOS had a significantly greater 26% increase to 155 +/- 6 mg/dl. The C-peptide-to-glucose ratios on OGTT increased by 44% in control subjects and by only 15% in PCOS subjects. The accelerated deterioration in glucose tolerance in PCOS may result, in part, from a relative attenuation in the response of the beta-cell to the demand placed on it by factors exacerbating insulin resistance.
Ehrmann
David A
DA
Department of Medicine, Section of Endocrinology, The University of Chicago Pritzker School of Medicine, 5841 South Maryland Ave., MC 1027, Chicago, IL 60637, USA. dehrmann@medicine.bsd.uchicago.edu
Breda
Elena
E
Corcoran
Matthew C
MC
Cavaghan
Melissa K
MK
Imperial
Jacqueline
J
Toffolo
Gianna
G
Cobelli
Claudio
C
Polonsky
Kenneth S
KS
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000139:chemically induced; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000503:physiopathology; D016555:Matched-Pair Analysis; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000503:physiopathology; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D003907:Dexamethasone