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ABSTRACT: Polycystic ovary syndrome (PCOS) and menopausal subjects are characterized by an increased cardiovascular and type 2 diabetes mellitus risk, at least partially related to insulin disturbances. The evaluation of insulin resistance in these patients could be useful as primary prevention. The aim of the study was to verify the validity of several indexes of insulin sensitivity in PCOS and menopausal subjects by comparing the data obtained by these indexes to those of euglycemic-hyperinsulinemic clamp studies.
One hundred PCOS and 110 menopausal subjects were analyzed; all subjects underwent an oral glucose tolerance test (75 g) and euglycemic-hyperinsulinemic clamp study. Seven PCOS patients and 13 menopausal subjects had impaired glucose tolerance or type 2 diabetes mellitus and were excluded from the study. After analysis of correlation coefficients between the evaluated indexes and the clamp studies, the sensitivity and specificity of different cut-off values for each parameter were analyzed by receiver operating characteristic (ROC) curves.
The best correlation coefficients with clamp studies were obtained with the Avignon insulin sensitivity index (SiM) (R(s) = 0.7812) in PCOS patients and the Matsuda and De Fronzo index (R(s) = 0.6178) in menopausal patients. The best predictive index of insulin resistance in PCOS was a Avignon insulin sensitivity basal index (SibB) value of 62 or less (78% sensitivity, 95% specificity) and an insulin area under the curve (AUC) of 7,000 microIU/ml or more (>/=50,225 pmol/liter) x 120 min (83% sensitivity, 90% specificity). In the menopausal population, the best predictive performance was obtained by an insulin AUC of 10,000 microIU/ml or more (>/=71,750 pmol/liter) x 240 min (70% sensitivity, 88% specificity).
The presence of high correlation coefficients does not necessarily mean that the indexes of insulin resistance have an optimal predictive performance; this is probably due to the presence of many borderline values. The simple evaluation of insulin AUC seems to effectively replace the euglycemic-hyperinsulinemic clamp in routine clinical practice, allowing results superimposable to those obtained by minimal model analysis.
Journal of Clinical Endocrinology & Metabolism 03/2005; 90(3):1398-406. · 6.50 Impact Factor
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ABSTRACT: The aim was to study the effectiveness of subjective color Doppler evaluation and spectral Doppler parameters in preoperative characterization of endometrial carcinomas.
Seventy-six patients with endometrial carcinoma were preoperatively analyzed by color Doppler ultrasound in order to subjectively evaluate the amount of intratumoral blood flow (color score) and to analyze the lowest resistance index (RI), the highest peak systolic velocity (PV), and the highest time averaged maximum velocity (TAMVX). These parameters were analyzed according to clinico-pathological characteristics.
In 13 patients no intratumoral arterial vessels were detected by color Doppler examination. No lymph node metastases were found in this group of patients. Positive nodes were found in 24% of patients with detectable arterial vessels, although the difference did not reach the statistical significance. No differences were found in spectral Doppler parameters (RI, PV, TAMVX) according to tumor characteristics or nodal involvement. A higher percentage of cases with a color score of 3 was found in stage >I than in stage I patients (69 vs 42%, P < 0.05), and in patients with myometrial invasion greater than 50% than in those with less than 50% invasion (72 vs 38%; P = 0.05).
Nodal metastases were found in 24% of patients with detectable vessels at color Doppler examination. Subjective analysis of vessel density correlated >50%, myometrial invasion, but spectral Doppler analysis was not predictive of surgical stage, tumor grade, myometrial invasion, or lymph node metastases. These results do not support the use of preoperative intratumoral blood flow analysis as a clinical test in evaluating tumor characteristics or in predicting lymph node metastases.
Gynecologic Oncology 03/2003; 88(3):298-303. · 3.89 Impact Factor
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ABSTRACT: To evaluate the effect of N-acetyl-cysteine (NAC) on insulin secretion and peripheral insulin resistance in subjects with polycystic ovary syndrome (PCOS).
Prospective data analysis.
Volunteer women in an academic research environment.
Six lean and 31 obese subjects, aged 19-33 years.
Patients were treated for 5-6 weeks with NAC at a dose of 1.8 g/day orally. A dose of 3 g/day was arbitrarily chosen for massively obese subjects. Six of 31 obese patients with PCOS were treated with placebo and served as controls.
Before and after the treatment period, the hormonal and lipid blood profile and insulin sensitivity, assessed by an hyperinsulinemic euglycemic clamp, were evaluated and an oral glucose tolerance test (OGTT) was performed.
Fasting glucose, fasting insulin, and glucose area under curve (AUC) were unchanged after treatment. Insulin AUC after OGTT was significantly reduced, and the peripheral insulin sensitivity increased after NAC administration, whereas the hepatic insulin extraction was unaffected. The NAC treatment induced a significant fall in T levels and in free androgen index values (P<.05). In analyzing patients according to their insulinemic response to OGTT, normoinsulinemic subjects and placebo-treated patients did not show any modification of the above parameters, whereas a significant improvement was observed in hyperinsulinemic subjects.
NAC may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.
Fertility and Sterility 07/2002; 77(6):1128-35. · 3.56 Impact Factor
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ABSTRACT: SummaryDESIGN There are conflicting data on hypothalamic-pituitary-adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects.PATIENTS Twenty PCOS patients and 10 control women participated in the study.MEASUREMENTS On days 5–6 Of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2-mg naloxone infusion In 100 ml of 0.9% saline over one hour. Samples were collected at −30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples.RESULTS PCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261 vs 172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher In PCOS patients (P < 0.05 and P < 0.04 respectively).The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production.CONCLUSIONS Polycystic ovary syndrome patients showed a hypothalamic-pituitary-adrenal axis hyper-responsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be central in origin.
Clinical Endocrinology 06/1996; 45(1):73 - 77. · 3.17 Impact Factor
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ABSTRACT: To investigate the effect of a chronic anti-opioid treatment on the adrenal steroid production in polycystic ovarian syndrome (PCOS), 20 women affected by PCOS were studied before and after 6 weeks of treatment with an opioid antagonist. All women had an oral glucose tolerance test (OGTT) (75 g) on day 5 of the cycle. At 11.00 p.m. 2 mg of dexamethasone was orally administered and blood samples collected the following day at 7.00 a.m. Then 250 μgof adrenocortkotrophin hormone (ACTH) was injected i.v. and samples collected 60 min later. At this time a 6 week course of naltrexone treatment (50 mg/day orally) was started, following which the protocol was repeated on day 6–7 of the menstrual cycle. According to OGTT responses, 10 patients were classified as hyperinsulinaemic and 10 as normoinsulin-aemic. No difference in baseline hormone concentrations was found, except for sex hormone-binding globulin, which was significantly greater in normoinsulinaemic patients (P < 0.02). The plasma concentration of all steroids after dexamethasone and ACTH administration was similar in both groups, except for androstenedione (P < 0.02) and 17α-hydroxyprogesterone (17-OHP) (P < 0.05), which were significantly greater after ACTH injection in hyperinsulinaemic compared with normoinsulinaemic PCOS patients. Naltrexone treatment significantly (P < 0.001) reduced insulin response to OGTT in the hyperinsulinaemic group, while it did not affect the response in the normoinsulinaemic group; thus at the end of the treatment the two groups had the same insulin concentrations. Similarly, naltrexone abolished the difference between normoinsulinaemic and hyperinsulinaemic patients regarding androstenedione and 17-OHP response to ACTH. These data confirm that insulin may in part affect the responsiveness of the adrenal glands to ACTH, so that modifications of its plasma concentrations can in turn modify adrenal steroid production.
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ABSTRACT: To assess the differential impact of the insulin secretory pattern and obesity on the endocrinometabolic features of the polycystic ovary syndrome (PCOS), we studied 110 PCOS women. Patients underwent a gonadotropin-releasing hormone (GnRH) test, an oral glucose tolerance test (OGTT), and basal evaluation of hormonal and biochemical parameters. Basal androgens and lipids, basal and stimulated gonadotropins, insulin, and glucose levels were measured. Patients were classified into four groups according to the body mass index (BMI) and insulin secretion: normoinsulinemic-lean ([NL] n = 24), normoinsulinemic obese ([NO] n = 24), hyperinsulinemic lean ([HL] n = 17), hyperinsulinemic obese ([HO] n = 45). HL patients showed a higher luteinizing hormone (LH) area under curve (AUC) after GnRH stimulus compared with NL patients (HL v NL, 4,285 ± 348 v 3,377 ± 314 IU/L · 120 min, P < .05), whereas we failed to find a statistically significant difference in a similar comparison among obese subjects (HO v NO, 3,606 ± 302 v 3,129 ± 602 IU/L · 120 min). A trend toward increased plasma testosterone and decreased sex hormone—binding globulin (SHBG) was found in relation to hyperinsulinemia and obesity, thus resulting in a higher free androgen index (FAI) in groups HL and NO versus NL (HL, 5.54 ± 0.51; NO, 5.64 ± 0.49; NL, 4.13 ± 0.33; P < .05 and P < .01, respectively). The presence of both exaggerated insulin secretion and obesity resulted in a synergistic additive effect on the FAI in the HO group (6.81 ± 0.34). Concerning the lipoprotein lipid profile, the NL group showed lower plasma triglyceride levels compared with the other three groups, whereas no significant differences were found for nonesterified fatty acid (NEFA) concentrations. Higher low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol (VLDL-C) and lower high-density lipoprotein cholesterol (HDL-C) levels were found in the obese groups compared with the lean counterparts, whereas the same parameters did not significantly differ in a comparison between normoinsulinemic and hyperinsulinemic groups. In conclusion, our data suggest an important role of hyperinsulinemia in the LH response to a GnRH stimulus and an independent and synergistic additive effect of obesity and hyperinsulinemia on the FAI in PCOS.
Metabolism.
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ABSTRACT: Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of polycystic ovarian disease (PCOD). On the other hand, being generally admitted that opioids may play a role in glycoregulation and that opioid tone is altered in PCOD, an involvement of the opioids in determining the hyperinsulinemia of PCOD patients could be suggested. The aim of this study was to evaluate the effect of a chronic opioid blockade on insulin metabolism and peripheral insulin sensitivity in PCOD hyperinsulinemic patients. Twenty-three women with PCOD were studied. An oral glucose tolerance test (OGTT) and a clamp study were performed at baseline (during the follicular phase) and after 6 weeks of naltrexone administration (50 mg/d orally). Based on the insulinemic response to the OGTT, 16 women were classified as hyperinsulinemic and seven as normoinsulinemic. Naltrexone treatment significantly reduced fasting (P < .05) and area under the curve (AUC) (P < .02) plasma insulin levels only in the hyperinsulinemic group. Moreover, hyperinsulinemic patients showed similar C-peptide incremental areas after naltrexone treatment, whereas in the same patients the fractional hepatic insulin extraction calculated from the incremental areas of insulin and C-peptide was found to be increased after chronic opioid blockade by naltrexone. For peripheral insulin sensitivity, the hyperinsulinemic group showed significantly lower (P < .01) total-body glucose utilization (M) compared with the normoinsulinemic group. No change in the M value was found after treatment in both groups. These data suggest that the insulin sensitivity and hyperinsulinemia after an OGTT are two distinct deranged features of the insulin disorder of PCOD patients.
Metabolism.
