Failure of Mathematical Indices to Accurately Assess Insulin Resistance in Lean, Overweight, or Obese Women with Polycystic Ovary Syndrome

Abstract Insulin resistance is a common metabolic feature of polycystic ovary syndrome (PCOS). In this study, we examined the validity of the mathematical indices [the quantitative insulin sensitivity check index (QUICKI) and the homeostasis model of assessment (HOMA)] that calculate insulin sensitivity and their correlation to glucose utilization with the insulin infusion rate in 40 mU/m2·min by the euglycemic clamp (M) in women with PCOS. We studied 59 women with PCOS (20 lean, 16 overweight, and 23 obese subjects). Euglycemic clamp testing was performed, and QUICKI, HOMA, total testosterone, fasting insulin, fasting glucose, and glucose-to-insulin ratio were estimated. No difference was found in testosterone and glucose levels among the three groups. Lean or overweight women compared with obese women differed in insulin levels, glucose-to-insulin ratio, QUICKI, and HOMA (P < 0.01). No statistical difference was found between lean and overweight women in the above parameters. M differed when lean women were compared with overweight (P < 0.002) or obese women (P < 0.0001); however, no statistical difference was observed between overweight and obese women. No significant correlation was found between M and QUICKI or HOMA. We conclude that mathematical indices should be applied with caution in different insulin-resistant populations and should not be considered a priori equivalent to the euglycemic clamp technique.

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Lower insulin sensitivity differentiates hirsute from non-hirsute Sicilian women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.1.02290 ◽

2006 ◽

Vol 155 (6) ◽

pp. 859-865 ◽

Cited By ~ 18

Author(s):

Marco C Amato ◽

Aldo Galluzzo ◽

Simona Merlino ◽

Antonina Mattina ◽

Pierina Richiusa ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Free Testosterone ◽

Total Testosterone ◽

Obese Women ◽

Ovary Syndrome ◽

The Metabolic Syndrome ◽

Matsuda Index

Objective: It is well known that hyperandrogenism and insulin-resistance with or without compensatory hyperinsulinism are closely associated, but the Rotterdam Consensus has concluded that principally obese women with polycystic ovary syndrome (PCOS) should be evaluated for the metabolic syndrome. Our aim was to study insulin sensitivity in PCOS women with hirsutism regardless of obesity. Methods: Clinical characteristics, sex hormones and fasting- and after OGTT-glycemia and insulinemia, homeostatic model of insulin resistance (HOMA IR), and Matsuda index of insulin sensitivity were analyzed in 130 women with PCOS. Hirsutism has been evaluated through the Ferriman–Gallwey (FG) map scoring system. Results: PCOS women with hirsutism (57.7% of participants) showed significant higher values of total testosterone levels (P = 0.016), free testosterone (P = 0.027), DHEA sulfate (P = 0.017), and Δ4androstenedione (P = 0.018). They had similar body mass index (BMI) (P = 0.073) and were significantly less insulin sensitive (P = 0.002) than those without hirsutism (42.3% of participants). In women with PCOS and hirsutism, there was a significant correlation between FG score and insulin-sensitivity indexes (HOMA IR, ρ = 0.33, P = 0.005; Matsuda index, ρ = −0.34, P = 0.003) but not with the androgen levels. Moreover, women with hirsutism showed a significantly greater insulin (P = 0.019), C-peptide (P = 0.002), and glucose (P = 0.024) areas under the curve (auc2h). Conclusions: Our study suggests that the increased responsiveness of the pilo-sebaceous unit to androgens seems to be influenced by insulin sensitivity and that insulin resistance should be assessed in all hirsute women with PCOS regardless of their BMI, as insulin resistance was found in hirsute women irrespective of whether they were overweight or obese.

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Metformin Decreases the Adipokine Vaspin in Overweight Women With Polycystic Ovary Syndrome Concomitant With Improvement in Insulin Sensitivity and a Decrease in Insulin Resistance

Diabetes ◽

10.2337/db08-0127 ◽

2008 ◽

Vol 57 (6) ◽

pp. 1501-1507 ◽

Cited By ~ 98

Author(s):

B. K. Tan ◽

D. Heutling ◽

J. Chen ◽

S. Farhatullah ◽

R. Adya ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Overweight Women

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1965 ◽

2005 ◽

Vol 90 (3) ◽

pp. 1360-1365 ◽

Cited By ~ 140

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 < 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P < 0.002) or metformin (P < 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 < 0.05) and serum concentrations of free testosterone (P < 0.02) and androstenedione (P < 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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No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide

Acta Endocrinologica ◽

10.1530/eje.0.1330718 ◽

1995 ◽

Vol 133 (6) ◽

pp. 718-722 ◽

Cited By ~ 7

Author(s):

Antonino Lasco ◽

Domenico Cucinotta ◽

Alfonso Gigante ◽

Giulia Denuzzo ◽

Marilena Pedulla ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Obese Women ◽

Ovary Syndrome ◽

Control Subjects ◽

Peripheral Insulin Resistance ◽

Androgen Levels

Lasco A, Cucinotta D, Gigante A, Denuzzo G, Pedulla M, Trifiletti A, Frisina N. No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide. Eur J Endocrinol 1995;133:718–22. ISSN 0804–4643 The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic–hyperinsulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome. A Lasco, Via Faustina e Tertullo 19, 98100 Messina, Italy

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Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

International Journal of Endocrinology ◽

10.1155/2016/7631804 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Kai I. Cheang ◽

Sakita N. Sistrun ◽

Kelley S. Morel ◽

John E. Nestler

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Obese Women ◽

Ovary Syndrome ◽

Matsuda Index ◽

Normal Women ◽

The Relationship

Background.A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS.Methods.Obese PCOS (n=16) and normal (n=15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUCDCI-IPG),AUCinsulin, andAUCDCI-IPG/AUCinsulinwere measured during a 2 hr OGTT at baseline and 8 weeks.Results.PCOS women had lowerAUCDCI-IPG/AUCinsulinat baseline and a significant relationship betweenAUCDCI-IPG/AUCinsulinand Matsuda index (p=0.0003), which was not present in controls. Weight loss was similar between PCOS (−4.08 kg) and normal women (−4.29 kg,p=0.6281). Weight loss in PCOS women did not change the relationship betweenAUCDCI-IPG/AUCinsulinand Matsuda index (p=0.0100), and this relationship remained absent in control women.Conclusion.The association betweenAUCDCI-IPG/AUCinsulinand insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

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Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with the polycystic ovary syndrome

Fibrinolysis and Proteolysis ◽

10.1016/0268-9499(94)90690-4 ◽

1994 ◽

Vol 8 ◽

pp. 144

Author(s):

P. Andersen ◽

I. Seljeflot ◽

M. Abdelnoor ◽

H. Arnesen ◽

P.O. Dale ◽

...

Keyword(s):

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Dietary Intervention ◽

Polycystic Ovary ◽

Obese Women ◽

Ovary Syndrome ◽

Fibrinolytic Capacity

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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 ◽

10.1210/en.2015-1159 ◽

2015 ◽

Vol 156 (11) ◽

pp. 4071-4080 ◽

Cited By ~ 17

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.

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Endotrophin as a novel marker in PCOS and its relation with other adipokines and metabolic parameters: a pilot study

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/20420188211049607 ◽

2021 ◽

Vol 12 ◽

pp. 204201882110496

Author(s):

Gurhan Guney ◽

Mine Islimye Taskin ◽

Ozgur Baykan ◽

Ertan Adali ◽

Selin Gul Tezcan ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Density Lipoprotein ◽

Resistance Index ◽

Total Testosterone ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Ovary Syndrome ◽

Significant Difference

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.

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