scholarly journals The treatment of insulin resistance does not improve adrenal cytochrome P450c17alpha enzyme dysregulation in polycystic ovary syndrome

1999 ◽  
pp. 56-61 ◽  
Author(s):  
K Unluhizarci ◽  
F Kelestimur ◽  
Y Sahin ◽  
F Bayram
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Tolerance Test ◽  
Glucose Disposal ◽  
Ovary Syndrome ◽  
Metformin Therapy ◽  
Insulin Levels ◽  
Healthy Women

OBJECTIVE: To determine whether metformin. when given to non-diabetic women with polycystic ovary syndrome (PCOS), results in a reduction of insulin resistance and hyperinsulinemia while body weight is maintained. Also we aimed to see whether the reduction in insulin levels attenuates the activity of adrenal P450c17alpha enzyme in patients with PCOS. DESIGN: We investigated the 17-hydroxyprogesterone (17-OHP) and androstenedione responses to ACTH, insulin responses to an oral glucose tolerance test (OGTT) and glucose disposal rate in an insulin tolerance test before and after metformin therapy (500 mg, orally, twice daily, for 12 weeks). METHODS: The presence of hyperinsulinemia in 15 women with PCOS was demonstrated by an OGTT and results were compared with those of 10 healthy women. Insulin sensitivity was measured by the rate of endogenous glucose disposal after i.v. bolus injection of insulin. 17-OHP and androstenedione responses to ACTH were measured in all the women with PCOS and the normal women. RESULTS: Women with PCOS were hyperinsulinemic (102.0+/-13.0 (S.E.M.) VS 46.2+/-4.4 pmol/l) and hyperandrogenemic (free testosterone 15.3+/-1.7 vs 7.9+/-0.6 nmol/l; androstenedione 11.8+/-0.8 vs 8.2+/-0.6 nmol/l) and more hirsute (modified Ferriman-Gallwey score, 17.7+/-1.6 vs 3.0+/-0.3) than healthy women. In addition, women with PCOS had higher 17-OHP and androstenedione responses to ACTH when compared with healthy women. Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels. But 17-OHP and androstenedione responses to ACTH were unaltered in response to metformin. CONCLUSIONS: PCOS is characterized by hyperactivity of the adrenal P450c17alpha enzyme and insulin resistance. It seems that there is no direct relationship between insulin resistance and adrenal P450c17alpha enzyme dysregulation.

scholarly journals Incretin levels in polycystic ovary syndrome

2008 ◽  
Vol 159 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Jana Vrbikova ◽  
Martin Hill ◽  
Bela Bendlova ◽  
Tereza Grimmichova ◽  
Katerina Dvorakova ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Repeated Measures ◽  
Polycystic Ovary ◽  
Late Phase ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Ovary Syndrome ◽  
C Peptide ◽  
Healthy Women

ObjectivePolycystic ovary syndrome (PCOS) has been linked to a high risk of type 2 diabetes mellitus. Disturbances in the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been observed in states with impaired glucose regulation. This paper considers the secretion of GIP and GLP-1 after oral glucose load in a group of lean, glucose-tolerant PCOS women in comparison with age- and body mass index (BMI)-matched healthy women.DesignCase control.MethodsPCOS (n=21, 25.8±4.1 years, BMI 21.6±1.7 kg/m2) and control healthy women (CT, n=13, 28.5±7.2 years, BMI 20.3±2.5 kg/m2) underwent oral glucose tolerance test (OGTT) with blood sampling for glucose, insulin, C-peptide, total GIP, and active GLP-1. Insulin sensitivity was determined both at fasting and during the test.StatisticsRepeated measures ANOVA.ResultsGlucose levels and insulin sensitivity did not differ between PCOS and CT. PCOS had significantly higher levels of C-peptide (P<0.05) and tended to have higher insulin levels. The levels of total GIP were significantly higher in PCOS than in CT (P<0.001). Active GLP-1 levels exhibited a significantly different time-dependent pattern in PCOS (P<0.002 for PCOS versus time interaction). GLP-1 concentrations were similar in PCOS and CT in the early phase of OGTT and then reached significantly lower levels in PCOS than in CT at 180 min (P<0.05).ConclusionsIncreased total GIP and lower late phase active GLP-1 concentrations during OGTT characterize PCOS women with higher C-peptide secretion in comparison with healthy controls, and may be the early markers of a pre-diabetic state.

A prospective pilot study of the effect of acupuncture on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance

2020 ◽  
Vol 38 (5) ◽  
pp. 310-318
Author(s):  
Juan Li ◽  
Wanting Wu ◽  
Elisabet Stener-Victorin ◽  
Ernest Hung Yu Ng ◽  
Raymond Hang Wun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Pilot Study ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Secondary Outcome ◽  
Ovary Syndrome ◽  
Insulin Levels ◽  
Prospective Pilot Study

Objective: To test the hypothesis that acupuncture improves insulin sensitivity in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Design: Prospective pilot study. Setting: Guangzhou, China, 2014–2016. Participants: Eighty women with PCOS aged 18–40 years with body mass index (BMI) above 18.5 kg/m2 and with homeostatic model assessment for insulin resistance (HOMA-IR) index ⩾2.14. Interventions: Subjects received acupuncture with combined manual and low-frequency electrical stimulation of the needles three times per week for 6 months. Primary and secondary outcome measures: The primary outcome was the change in HOMA-IR after 6 months of acupuncture relative to baseline. Secondary outcomes included changes after 6 months of acupuncture and at 3 months of follow-up (both relative to baseline) in oral glucose tolerance test (OGTT) parameters (glucose and insulin levels), anthropometric measurements, and circulating metabolic and endocrine variables. Results: HOMA-IR and fasting plasma glucose and insulin levels were significantly decreased after 6 months of acupuncture, and both HOMA-IR and fasting insulin remained significantly decreased at 3 months of follow-up. In a subgroup analysis of normal-weight and overweight/obese women, HOMA-IR was reduced after 6 months of acupuncture in both subgroups, but there was no significant difference between the two groups. Conclusions: Acupuncture treatment in Chinese women with PCOS and IR was associated with an encouraging improvement in insulin sensitivity. Further randomized controlled studies are required to confirm the efficacy of acupuncture for this indication.

scholarly journals Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4071-4080 ◽  
Author(s):  
Amanda Hurliman ◽  
Jennifer Keller Brown ◽  
Nicole Maille ◽  
Maurizio Mandala ◽  
Peter Casson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Phase 1 ◽  
Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

scholarly journals Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Bingjie Zhang ◽  
Jing Wang ◽  
Shanmei Shen ◽  
Jiayi Liu ◽  
Jie Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Glucose Intolerance ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Sensitivity Index ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Family History Of Diabetes

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p<0.001). Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

scholarly journals Responses of Serum Androgen and Insulin Resistance to Metformin and Pioglitazone in Obese, Insulin-Resistant Women with Polycystic Ovary Syndrome

2005 ◽  
Vol 90 (3) ◽  
pp. 1360-1365 ◽  
Author(s):  
C. Ortega-González ◽  
S. Luna ◽  
L. Hernández ◽  
G. Crespo ◽  
P. Aguayo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Body Mass ◽  
Polycystic Ovary ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Waist To Hip Ratio

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P ≤ 0.05) after pioglitazone treatment but not after metformin treatment. Fasting serum insulin concentration (P &lt; 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P &lt; 0.002) or metformin (P &lt; 0.05) treatment. IR (homeostasis model of assessment-IR index) decreased and insulin sensitivity (elevation of the quantitative insulin sensitivity check index and the fasting glucose to insulin ratio) increased (P ≤ 0.008) after treatment with either drug. Hirsutism (P &lt; 0.05) and serum concentrations of free testosterone (P &lt; 0.02) and androstenedione (P &lt; 0.01) declined to a similar extent after treatment with the drugs. Treatment with pioglitazone or metformin was associated with the occurrence of pregnancy (n = 5 and n = 3, respectively). These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyperandrogenism, despite an increase in body weight, body mass index, and the waist to hip ratio associated with pioglitazone.

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