Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity

The aim of our study was to evaluate rapid insulin pulses and insulin secretion regularity in fasting state in lean women with polycystic ovary syndrome (PCOS) in comparison to lean healthy women. PCOS (n=8) and controls (n=7) underwent every minute blood sampling for 60 min. Insulin pulsatility was assessed by deconvolution and insulin secretion regularity by approximate entropy methodology. PCOS had higher testosterone (p<0.02), prolactin (p<0.05) and lower sex hormone binding globulin (SHBG) (p<0.0006) levels than controls. Approximate entropy, insulin pulse frequency, mass, amplitude and interpulse interval did not differ between PCOS and controls. PCOS had broader insulin peaks determined by a common half-duration (p<0.07). Burst mass correlated positively with testosterone (p<0.05) and negatively with SHBG (p 0.0004) and common half-duration correlated positively with prolactin (p<0.008) and cortisol levels (p<0.03). Approximate entropy positively correlated with BMI (p<0.04) and prolactin (p<0.03). Lean PCOS patients tended to have broader insulin peaks in comparison to healthy controls. Prolactin, androgens and cortisol might participate in alteration of insulin secretion in PCOS-affected women. Body weight and prolactin levels could influence insulin secretion regularity.

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Predictors of abnormal glucose metabolism in women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.1.02095 ◽

2006 ◽

Vol 154 (2) ◽

pp. 295-301 ◽

Cited By ~ 17

Author(s):

Matthias Möhlig ◽

Joachim Spranger ◽

Michael Ristow ◽

Andreas F H Pfeiffer ◽

Thilo Schill ◽

...

Keyword(s):

Glucose Metabolism ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Receiver Operating Curve ◽

Oral Glucose ◽

Model Assessment ◽

Fasting Insulin ◽

Ovary Syndrome ◽

Easy Method ◽

Abnormal Glucose Metabolism

Objective: Polycystic ovary syndrome (PCOS) is a risk factor for type 2 diabetes mellitus and screening for abnormal glucose metabolism has been recommended by an oral glucose tolerance test (OGTT). This procedure is time-consuming and inconvenient, limiting its general use. Therefore, an easy method is wanted to separate PCOS women with normal from those with potentially abnormal glucose metabolism. Design: Simple parameters obtained from 101 consecutive PCOS patients were assessed by receiver operating curve analysis for their ability to predict abnormal glucose metabolism. Results: Comparing discriminating parameters at defined sensitivities revealed that, assessed by homeostasis model assessment (HOMA), insulin resistance (HOMA%S) had the highest specificitiy. At a cut-off point of 73.1%, HOMA%S had a sensitivity of 95.5% and a specificity of 51.9%. Applying this cut-off separated 59 women who had a high probability of abnormal glucose metabolism from 42 women who were at low risk (less than 2.5%). Fasting insulin was the second-best parameter and had a similar specificity. A screening strategy which applies HOMA%S or fasting insulin could almost halve the number of OGTTs by directing them to those PCOS women most likely to be suffering from abnormal glucose metabolism. The negative predictive value of this strategy was 97%. The strategy was tested and confirmed in a second and independent cohort of 264 PCOS women. Conclusions: HOMA%S, or to a lesser extent fasting insulin, appears to allow for stratified metabolic screening of PCOS women with OGTT.

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Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance

Acta Endocrinologica ◽

10.1530/eje-07-0294 ◽

2007 ◽

Vol 157 (5) ◽

pp. 669-676 ◽

Cited By ~ 59

Author(s):

Susanne Tan ◽

Susanne Hahn ◽

Sven Benson ◽

Tiina Dietz ◽

Harald Lahner ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Fasting Glucose ◽

Polycystic Ovary ◽

Model Assessment ◽

Fasting Insulin ◽

Ovary Syndrome ◽

Insulin Levels ◽

Outcome Parameters ◽

Pre Treatment

AbstractObjectiveInsulin resistance (IR) and obesity are common features of the polycystic ovary syndrome (PCOS). Insulin-sensitizing agents have been shown to improve both reproductive and metabolic aspects of PCOS, but it remains unclear whether it is also beneficial in lean patients without pre-treatment IR. The aim of this study was to determine the influence of metformin on the clinical and biochemical parameters of PCOS irrespective of the presence of basal obesity and IR.DesignThe effect of 6 months of metformin treatment was prospectively assessed in 188 PCOS patients, divided into three groups according to body mass index (BMI; lean: BMI<25 kg/m2, overweight: BMI 25–29 kg/m2, and obese: BMI≥30 kg/m2). Outcome parameters, which were also assessed in 102 healthy controls, included body weight, homeostasis model assessment for IR (HOMA-IR), fasting glucose and insulin levels, area under the curve of insulin response (AUCI), hyperandrogenism, and menstrual irregularities.ResultsIn comparison with the respective BMI-appropriate control groups, only obese but not lean and overweight PCOS patients showed differences in fasting insulin and HOMA-IR. Metformin therapy significantly improved all outcome parameters except fasting glucose levels. Subgroup analyses revealed that in the group of lean PCOS patients without pre-treatment IR, metformin significantly improved HOMA-IR (1.7±1.0 vs 1.1±0.7 μmol/l×mmol/l2) and fasting insulin levels (7.7±4.2 vs 5.4±3.9 mU/l), in addition to testosterone levels (2.6±0.9 vs 1.8±0.7 nmol/l), anovulation rate (2.3 vs 59.5%), and acne (31.8 vs 11.6%; all P<0.017). In the overweight and obese PCOS groups, metformin also showed the expected beneficial effects.ConclusionMetformin improves parameters of IR, hyperandrogenemia, anovulation, and acne in PCOS irrespective of pre-treatment IR or obesity.

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Increased Endothelin-1 Levels in Women with Polycystic Ovary Syndrome and the Beneficial Effect of Metformin Therapy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.10.7904 ◽

2001 ◽

Vol 86 (10) ◽

pp. 4666-4673 ◽

Cited By ~ 104

Author(s):

Evanthia Diamanti-Kandarakis ◽

Giovanna Spina ◽

Chryssa Kouli ◽

Ilias Migdalis

Keyword(s):

Body Mass Index ◽

Polycystic Ovary Syndrome ◽

Body Mass ◽

Glucose Utilization ◽

Polycystic Ovary ◽

Analysis Of Covariance ◽

Fasting Insulin ◽

Ovary Syndrome ◽

Metformin Therapy ◽

Endothelin 1

Women with polycystic ovary syndrome who present with hyperandrogenemia, hyperinsulinemia, and insulin resistance appear to be at high risk of cardiovascular disease. Elevated levels of endothelin-1, a marker of vasculopathy, have been reported in insulin-resistant subjects with endothelial dysfunction. Male gender also seems to be an aggravating factor for cardiovascular disease. In this study we investigated endothelin-1 levels in women with polycystic ovary syndrome, and we evaluated the effect of an insulin sensitizer, metformin, on endothelin-1 levels. Plasma endothelin-1 levels were measured in 23 obese (mean age, 24.3 ± 4.6 yr; body mass index, 35 ± 5.6 kg/m2) and 20 nonobese women with polycystic ovary syndrome (24.1 ± 3.6 yr; body mass index, 21.8 ± 2.5 kg/m2) as well as in 7 obese and 10 nonobese healthy, normal cycling, age-matched women. Additionally, endothelin-1 levels were evaluated in a subgroup of women with polycystic ovary syndrome (10 obese and 10 nonobese) 6 months postmetformin administration (1700 mg daily). Our results showed that obese and nonobese women with polycystic ovary syndrome had higher levels of endothelin-1 compared with the controls[ obese, 2.52 ± 1.87 vs. 0.44 ± 0.23 pmol/liter (by analysis of covariance, P < 0.02); nonobese, 1.95 ± 1.6 vs. 0.43 ± 0.65 pmol/liter (P < 0.009)]. All of the participating women with polycystic ovary syndrome (n = 43) when compared with the total group of controls (n = 17) demonstrated hyperinsulinemia (polycystic ovary syndrome, 24.5 ± 19.6; controls, 11.2 ± 3.4 U/liter; P < 0.03), lower glucose utilization (M40) during the hyperinsulinemic euglycemic clamps (3.4 ± 2.4 vs. 5.6 ± 1.75 mg/kg·min; P< 0.045, by one-tailed test), and higher levels of endothelin-1 (polycystic ovary syndrome, 2.52 ± 1.87; controls, 0.44 ± 0.23 pmol/liter; P < 0.02, analysis of covariance covariate for body mass index). A positive correlation of endothelin-1 with free T levels was also shown (r = 0.4, P= 0.002) as well as a negative correlation of endothelin-1 with glucose utilization (r = −0.3; P = 0.033) in the total studied population. Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 ± 2.2; endothelin-1 after, 1.1 ± 0.9 pmol/liter; P< 0.003) and nonobese (endothelin-1 before, 2.7 ± 2; endothelin-1 after, 0.7 ± 0.4 pmol/liter; P< 0.01) women with polycystic ovary syndrome, with no change in body mass index. Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved[ obese before: total T, 0.9 ± 0.15 ng/ml; fasting insulin, 22.2 ± 12.1 U/liter; glucose utilization, 2.15 ± 0.5 mg/kg·min; obese after: total T, 0.5 ± 0.2 ng/ml; fasting insulin, 11.6 ± 6 U/liter; glucose utilization, 4.7 ± 1.4 mg/kg·min 9P < 0.003, P < 0.006, and P < 0.002, respectively); nonobese before: total T, 1 ± 0.5 ng/ml; fasting insulin, 15.5 ± 7.6 U/liter; glucose utilization, 3.4 ± 0.7 mg/kg·min; nonobese after: total T, 0.8 ± 0.5 ng/ml; fasting insulin, 9 ± 3.8 U/liter; glucose utilization, 6 ± 1.7 mg/kg·min (P < 0.04, P < 0.02, and P < 0.0008, respectively)]. In conclusion, our data clearly demonstrate that women with polycystic ovary syndrome, obese and nonobese, have elevated endothelin-1 levels compared with the age-matched control group. In addition, 6 months of metformin therapy reduces endothelin-1 levels and improves their hormonal and metabolic profile.

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Dietary and Physical Activity Habits in Adolescent Girls with Polycystic Ovary Syndrome (PCOS)-HAstudy

Journal of Clinical Medicine ◽

10.3390/jcm10163469 ◽

2021 ◽

Vol 10 (16) ◽

pp. 3469

Author(s):

Małgorzata Mizgier ◽

Grażyna Jarząbek-Bielecka ◽

Dorota Formanowicz ◽

Elżbieta Jodłowska-Siewert ◽

Kinga Mruczyk ◽

...

Keyword(s):

Physical Activity ◽

Polycystic Ovary Syndrome ◽

Inflammatory Markers ◽

Leisure Time ◽

Polycystic Ovary ◽

Inverse Correlation ◽

Control Group ◽

Fasting Insulin ◽

Ovary Syndrome ◽

Total Fat

The role of inappropriate lifestyle in the etiology of polycystic ovary syndrome (PCOS) and its metabolic and reproductive complications has attracted much attention in recent years; however, most studies involve adult patients. Thus, the study aimed to compare dietary patterns, physical activity, metabolic, anthropometric and inflammatory markers of 14–18-year-old girls with and without PCOS (n = 61 and n = 35, respectively) as well as to assess correlations between concentrations of metabolic and inflammatory markers and macronutrient intake and to identify the independent predictors of PCOS, related to diet and physical activity (PA). Compared to the control group, PCOS girls consumed significantly more total fat (p = 0.0005), including both saturated (SFA) (p = 0.03), monounsaturated (MUFA) (p = 0.0003) and polyunsaturated fatty acids (PUFA) (p = 0.01). A significantly higher percentage of PCOS patients consumed high and medium glycemic index (GI) foods (p = 0.03) and represented a low level of PA, both during school and in leisure time (41.67 vs. 6.06%; p = 0.0001 and 32.79 vs. 5.71%; p = 0.003, respectively). The PCOS group had also significantly higher waist circumference (WC), C-reactive protein (CRP) (p = 0.01), LDL cholesterol (p = 0.01), fasting insulin (p = 0.002) and HOMA-IR (p = 0.006) levels. There was an inverse correlation between fiber intake and fasting insulin, (p = 0.0002, r = −0.37), HOMA-IR (p = 0.0004, r = −0.35), WC (p = 0.029; r = −0.222) and a positive relationship between high and medium GI diet and insulin concentration (p = 0.003; r = 0.3). An increase of 10 g/day in total fat intake per day increases the probability of PCOS by 1.4 times. If the SFA or MUFA intakes increase by 10 g, the probability of PCOS increase 1.7-fold and 2.5-fold, respectively. The consumption of foods with a medium GI raises the probability of PCOS by more than 3 times, after adjusting for age. The odds ratio decreased for the moderate and high PA at school/work and in leisure time. Further research in girls with PCOS is needed to test whether low GI and dietary fatty acid reduction combined with increased PA is effective in the nonpharmacological treatment and prevention of PCOS complications. ClinicalTrial.gov Identifier: NCT04738409.

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Lack of relationship between 17-hydroxyprogesterone response to buserelin testing and hyperinsulinemia in polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.0.1360410 ◽

1997 ◽

Vol 136 (4) ◽

pp. 410-415 ◽

Cited By ~ 12

Author(s):

Yilmaz Şahin ◽

Demet Ayata ◽

Fahrettin Keleştimur

Keyword(s):

Polycystic Ovary Syndrome ◽

Gnrh Agonist ◽

Polycystic Ovary ◽

Insulin Response ◽

Prospective Clinical Study ◽

Oral Glucose ◽

Fasting Insulin ◽

Ovary Syndrome ◽

C Peptide ◽

17 Hydroxyprogesterone

Abstract Objective: To determine whether hyperinsulinism affects cytochrome P450c 17α activity by investigating the correlation between 17–hydroxyprogesterone (17–OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS). Design: Ultrasound, clinical and hormonal parameters were used to define PCOS in this prospective clinical study. We investigated the correlation between the 17–OHP response to buserelin testing and the insulin response to oral glucose in PCOS. Methods: Twenty-eight women with PCOS and eighteen normal women were included in the study. 17–OHP response to buserelin, and insulin and C–peptide responses to oral glucose were measured. Results: Twenty–live women with PCOS had an increased 17–OHP response. The PCOS patients showed significantly higher mean post–glucose load insulin and C–peptide levels than controls (P<0·05). No significant correlations were found between basal 17–OHP and fasting insulin or fasting C–peptide, between peak 17–OHP and fasting insulin, peak insulin or peak C–peptide, between 17–OHP area under the curve (AUC) and insulin AUC or C–peptide AUC, and between percent increment in 17–OHP and insulin AUC or C–peptide AUC (P >0·05). Conclusions: Lack of a relationship between the 17–OHP response to the GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not play a role in the dysregulation of the cytochrome P450c17α enzyme seen in PCOS. European Journal of Endocrinology 136 410–415

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Association between the serum estrone-to-estradiol ratio and parameters related to glucose metabolism and insulin resistance in women with polycystic ovary syndrome

Clinical and Experimental Reproductive Medicine ◽

10.5653/cerm.2021.04553 ◽

2021 ◽

Vol 48 (4) ◽

pp. 374-379

Author(s):

Nayoung Kim ◽

Sungwook Chun

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Postprandial Glucose ◽

Serum Glucose ◽

Clinical Variable ◽

Fasting Insulin ◽

Ovary Syndrome ◽

Glucose Levels

Objective: We aimed to evaluate associations between the ratio of serum estrone (E1) to estradiol (E2) and parameters related to serum glucose metabolism and insulin resistance in women with polycystic ovary syndrome (PCOS). Methods: In total, 133 women between the ages of 18 and 33 diagnosed with PCOS were enrolled in this study. All participants with PCOS underwent blood tests to determine hormonal and biochemical metabolic parameters and a standard 2-hour 75-g oral glucose tolerance test. They were divided into two groups according to the serum E1-to-E2 ratio: group 1 (E1/E2 ratio <2.0) and group 2 (E1/E2 ratio ≥2.0). Results: In the comparative analysis, the waist-to-hip ratio (WHR) was the only clinical variable that was significantly different between the two groups. Patients with a higher E1/E2 ratio showed higher fasting insulin levels, homeostasis model for insulin resistance, and postprandial glucose levels at 2 hours (PPG2). In a correlation analysis, only PPG2 was significantly related to the serum E1/E2 ratio. However, after controlling for the confounding effects of body mass index (BMI) and WHR, fasting glucose was also significantly correlated with the serum E1/E2 ratio. Conclusion: Women with PCOS with a higher serum E1/E2 ratio were found to be more likely to show higher fasting insulin and postprandial glucose levels. Significant correlations were found between the serum E1/E2 ratio and both fasting and postprandial serum glucose levels after adjusting for BMI and WHR in women with PCOS.

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ROLE FAILURE CORRECTION OF 25(OH)D IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2015-5-47-53 ◽

2015 ◽

Vol 14 (5) ◽

pp. 47-53

Author(s):

M. V. Matveyeva ◽

Yu. G. Samoylova ◽

O. A. Oleynik ◽

M. V. Koshmeleva ◽

M. A. Rotkank

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovarian Syndrome ◽

Comparison Group ◽

Polycystic Ovary ◽

Enzyme Linked Immunosorbent Assay ◽

Fasting Insulin ◽

Ovary Syndrome ◽

Combined Oral Contraceptive ◽

25 Oh Vitamin D ◽

Ovarian Syndrome

Objective. To estimate the correction failure 25 (OH) D in patients with polycystic ovary syndrome.Material and Methods. The study involved 44 patients with polycystic ovary syndrome, aged 31.32 ± 5.05, who were randomly assigned to 2 groups: 1st – obtained coca biguanides and Kolekaltsiferol, second – combined oral contraceptive (combined hormonal ) and biguanides. The comparison group consisted of 22 healthy women matched for age and sex. Polycystic Ovarian Syndrome (PCOS) was verified on theОригинальные статьиБюллетень сибирской медицины, 2015, том 14, № 5, с. 47–53 53basis of diagnostic criteria ESHRE / ASRM (2012). 25 (OH) vitamin D was determined by enzyme-linked immunosorbent assay (ELISA ng/ml). Examined glucose and fasting insulin, HOMA index of insulin re-sistance. Depression was assessed using the Beck test. Statistical analysis – R-system.Results. The patients with PCOS defined by the expression deficit of 25 (OH) D, which is associated with hyperandrogenism, hyperglycemia, hyperinsulinemia, insulin resistance, as well as depression. Ad-mission kolekaltsiferola leads to improved glucose metabolism and manifestations of PCOS, and also significantly reduces the parameters of OT, OT / OB, depression.Conclusion. Failure correction of 25 (OH) D contributes to the improvement of metabolic and psycho-logical parameters of fertility.

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