Insulin-induced capillary recruitment is impaired in both lean and obese women with PCOS.

BACKGROUND: Insulin resistance, i.e. impaired insulin-mediated glucose uptake (IMGU), is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). Insulin-induced capillary recruitment (IICR) is considered a significant determinant of IMGU. We investigated whether IICR is a determinant IMGU in obese and lean women with and without PCOS. METHODS: The study included 36 women with PCOS (20 lean, BMI 21.9 ± 2.3 kg/m(2) and 16 obese, BMI 35.9 ± 6.0 kg/m(2)) and 27 age-matched healthy controls (14 lean, BMI 22.2 ± 1.8 kg/m(2) and 13 obese, BMI 40.5 ± 7.0 kg/m(2)). IICR was evaluated by capillary microscopy during an isoglycemic-hyperinsulinemic clamp. IMGU was expressed as M/I value. RESULTS: The M/I value was significantly lower in obese PCOS women compared with obese controls [0.5 (0.2-1.1) versus 0.8 (0.3-1.4) (mg kg(-1) min(-1) pmol l(-1)) × 100, P < 0.01], whereas the small difference between lean PCOS and lean control women was non-significant [1.5 (0.5-2.6) versus 1.7 (1.0-3.7) (mg kg(-1) min(-1) pmol l(-1)) × 100, P = 0.17]. Hyperinsulinemia increased capillary recruitment in lean controls (53.5 ± 20.3 versus 64.9 ± 27.4 n/mm(2), P < 0.05), but not in either PCOS group nor in obese controls. IICR and androgens were a determinant of M/I value only in lean women with or without PCOS. CONCLUSIONS: PCOS per se is associated with impaired IICR. Obese women with PCOS, in part independent of obesity, demonstrated a profound insulin resistance, whereas the difference between lean PCOS women and healthy controls was small and statistically non-significant. IICR was a determinant of IMGU in lean, but not in obese, women regardless of the presence of PCOS.

Greater arterial stiffness in polycystic ovary syndrome (PCOS) is an obesity--but not a PCOS-associated phenomenon.

CONTEXT: Polycystic ovary syndrome (PCOS) and obesity are associated with cardiovascular disease, but it is unclear to what extent they contribute independently. Arterial stiffness might link obesity and PCOS to cardiovascular diseases. OBJECTIVE: Our objective was to investigate whether PCOS in the presence or absence of obesity is linked with arterial stiffness. DESIGN AND SETTING: We conducted a cross-sectional study, including 31 obese (18 with PCOS) and 39 lean (22 with PCOS) women. INTERVENTIONS AND MAIN OUTCOME MEASURES: Estimates of arterial stiffness were obtained by ultrasonography (distensibility and compliance of carotid, femoral, and brachial arteries; carotid elastic modulus; and intima-media thickness) and pulse wave transit time analyses (carotid-femoral pulse wave velocity and aortic augmentation index). RESULTS: Obese women, with or without PCOS, had stiffer arteries than lean women. After adjustment for 24-h mean arterial pressure and age, obesity was inversely associated with the femoral, brachial, and carotid distensibility coefficients [ß (95% confidence interval), -0.354 (-0.614 to -0.094), -0.354 (-0.547 to -0.161), and -0.248 (-0.370 to -0.126) 10(-3)/kPA, respectively] and with the femoral and carotid compliance coefficients [-0.296 (-0.563 to -0.029) and -0.190 (-0.377 to -0.003) mm(2)/kPA, respectively] but not with the brachial compliance coefficient [-0.018 (-0.052-0.015) mm(2)/kPA], Young's elastic modulus [0.049 (-0.005-0.103) kPA], aortic pulse wave velocity and aortic augmentation index [0.050 msec (-0.959-1.058 msec) and -1.831% (-8.196-4.534%), respectively]. Analyses with waist circumference as key independent variable gave broadly similar results. In contrast, PCOS was not associated with arterial stiffness estimates after adjustment for the presence of obesity. CONCLUSIONS: In young obese women with PCOS, (central) obesity, rather than PCOS itself, is associated with increased arterial stiffness. These data emphasize that, from the perspective of cardiovascular risk reduction, the focus should be on central fat mass reduction in obese women with PCOS.

Clomiphene citrate resistance in relation to follicle-stimulating hormone receptor Ser680Ser-polymorphism in polycystic ovary syndrome.

BACKGROUND: Clomiphene citrate (CC) response in anovulatory women is difficult to predict and patient-tailored treatment would benefit patient care and time-management. The objective of this study was to evaluate the role of the follicle-stimulating hormone receptor (FSHR) Ser680Ser-polymorphism as a predictor for CC response. METHODS: In this retrospective study, 193 patients, diagnosed with polycystic ovary syndrome (PCOS) according to Rotterdam criteria and treated with ovulation induction, were included over a 5-year period in a university hospital in the Netherlands. Data on demographics, BMI, menstrual cycle, laboratory screening (including FSHR genotyping), transvaginal ultrasonography of ovaries and ovulation parameters were collected. Main outcome measures were response to CC and FSHR genotype. RESULTS: The frequency distribution of the 680-polymorphism was 26% (Asn/Asn), 50% (Asn/Ser) and 24% (Ser/Ser). No significant differences in basal characteristics were found. Significantly more patients with Ser/Ser-polymorphism were resistant to CC (28%) compared with Asn/Ser (14%) and Asn/Asn group (15%), with an odds ratio for ovulation of 0.44 (95% CI, 0.21-0.97). Patients with higher FSH levels, higher age and lower BMI were significantly more likely to ovulate in univariate analysis. In a multivariate logistic regression model, corrected for age, BMI, mean ovarian, volume, hyperandrogenism, and amenorrhoea, only FSHR and basal FSH levels were predictive for ovulation. CONCLUSIONS: Chance of resistance to CC is almost double in women with PCOS harbouring the Ser/Ser genotype.

Health related quality of life in disorders of defecation: the Defecation Disorder List.

BACKGROUND: Constipation and encopresis frequently cause problems with respect to emotional wellbeing, and social and family life. Instruments to measure Health Related Quality of Life (HRQoL) in these disorders are not available. METHODS: A disease specific HRQoL instrument, the "Defecation Disorder List" (DDL) for children with constipation or functional non-retentive faecal soiling (FNRFS) was developed using accepted guidelines. For each phase of the process, different samples of patients were used. The final phase of development included 27 children. Reliability was assessed in two ways: internal consistency of domains with Cronbach's alpha, and test-retest reliability with intra-class correlation coefficients (ICC). To assess validity, comparable items and domains were correlated with Tacqol, a generic HRQoL instrument for children (TNO-AZL). RESULTS: In the final phase of the development, 27 children completed the instrument. It consisted of 37 items in four domains. The response rate was 96%. Reliability was good for all domains, with Cronbach's alpha values ranging from 0.61 to 0.76. Measures of test-retest stability were good for all four domains with ICCs ranging from 0.82 to 0.92. Validity based on comparison with the Tacqol instrument was moderate. CONCLUSION: The DDL is promising as a measure of HRQoL in childhood defecation disorders.