Presence of metabolic risk factors in non-obese PCOS sisters: Evidence of heritability of insulin resistance

Diamanti-Kandarakis, Evanthia; Alexandraki, Krystallenia Ι.; Bergiele, Angeliki; Kandarakis, Helen A.; Mastorakos, George; Aessopos, Athanasios

doi:10.1007/bf03347535

Cited by 27 publications

(7 citation statements)

References 33 publications

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“…In this study, we show that IR can be present in PCOS with normal BMI, confirming that IR is not merely linked to obesity but also to a genetic or epigenetic situation (30,31,32,33).…”

Section: Discussionsupporting

confidence: 71%

“…An increase in the generation of ROS by peripheral blood leucocytes in response to acute hyperglycemia has been previously demonstrated in PCOS patients (11), and the finding that physiological and pharmacological insulin infusions in vivo or in vitro revealed the oxidative effect of insulin (32,33,34,35,36) raised the hypothesis of systemic redox impairment in such patients.…”

Section: Discussionmentioning

confidence: 89%

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Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome

Donà¹,

Sabbadin²,

Fiore³

et al. 2012

European Journal of Endocrinology

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Objective: Possibly due to a deficiency of insulin mediators, polycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR) and hyperinsulinemia, likely responsible for an elevated production of reactive oxygen species. We investigated oxidative-related alterations in erythrocytes and anti-inflammatory effects of inositol in women with PCOS before and after treatment with myo-inositol (MYO). Methods: Twenty-six normal-weight PCOS patients were investigated before and after MYO administration (1200 mg/day for 12 weeks; nZ18) or placebo (nZ8) by evaluating serum testosterone, serum androstenedione, fasting serum insulin, fasting serum glucose, insulin area under the curve (AUC), and glucose AUC after oral glucose tolerance test and homeostasis model of assessment-IR. In erythrocytes, band 3 tyrosine phosphorylation (Tyr-P) level, glutathione (GSH) content, and glutathionylated proteins (GSSP) were also assessed. Results: Data show that PCOS patients' erythrocytes underwent oxidative stress as indicated by band 3 Tyr-P values, reduced cytosolic GSH content, and increased membrane protein glutathionylation. MYO treatment significantly improved metabolic and biochemical parameters. Significant reductions were found in IR and serum values of androstenedione and testosterone. A significant association between band 3 Tyr-P levels and insulin AUC was found at baseline but disappeared after MYO treatment, while a correlation between band 3 Tyr-P and testosterone levels was detected both before and after MYO treatment. Conclusions: PCOS patients suffer from a systemic inflammatory status that induces erythrocyte membrane alterations. Treatment with MYO is effective in reducing hormonal, metabolic, and oxidative abnormalities in PCOS patients by improving IR.

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“…In this study, we show that IR can be present in PCOS with normal BMI, confirming that IR is not merely linked to obesity but also to a genetic or epigenetic situation (30,31,32,33).…”

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 89%

Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome

Donà¹,

Sabbadin²,

Fiore³

et al. 2012

European Journal of Endocrinology

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“…These women had neither clinical nor laboratory evidence of hyperandrogenism, suggesting that insulin resistance is a dominant trait among PCOS families. 88 Govind et al 89 studied 29 probands and 10 control women. Diagnostic criteria consisted of polycystic ovaries on ultrasound with or without clinical or biochemical features of PCOS; 61% of female first-degree relatives were affected and 22% of male first-degree relatives had early onset (before age 30) male-pattern baldness.…”

Section: The Insulin Gene Variable Number Tandem Repeat (Ins-vntr)mentioning

confidence: 99%

Polycystic Ovary Syndrome: The influence of environmental and genetic factors

Diamanti-Kandarakis¹,

Piperi²,

Spina³

et al. 2006

121

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Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. It is the most common endocrine disorder in women of reproductive age with an enigmatic pathophysiologic and molecular basis. The high prevalence of affected individuals and the wide range of phenotypic expression can be explained by the interaction of a number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various population groups (ethnic groups, twins, and PCOS families). Although evidence of familial segregation and clustering of the disease in first-degree relatives of women diagnosed with PCOS has been presented, no particular pattern of inheritance has emerged. Some of the problems in genetic studies have been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features, and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify the propositus and to determine affected status in the kindred, the genetic studies available suggest a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.

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“…Although the genetic component of IR has been well recognized 2 the sharp parallel escalation of obesity and IR‐associated diseases suggests that the pathogenesis of IR is multifactorial and comprises also a lifestyle associated component. In obesity the Randles’ cycle, the Ectopic Fat Storage Hypothesis, the Lipotoxicity theory, the adipose tissue derived bioactive factors that impair glucose metabolism and the obesity‐associated systematic low‐grade inflammation provide the most widely accepted underlying pathogenic mechanisms of IR.…”

Section: Mechanisms Of Insulin Resistance In Womenmentioning

confidence: 99%

The impact of insulin resistance on woman's health and potential treatment options

Lois

Valsamakis

Mastorakos

et al. 2010

Annals of the New York Academy of Sciences

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Insulin resistance (IR) is causatively related to metabolic syndrome and type 2 diabetes, both of which increase the risk of adverse cardiovascular events; in women in particular, severe IR affects the reproductive system causing subfertility and health problems to the mother and the fetus. To date lifestyle modification is the mainstay of treatment, whereas antiobesity drugs and bariatric surgery have been shown to improve insulin sensitivity and many surrogate metabolic defects, real reduction in cardiovascular endpoints has yet to be proved. Increasing attention is being directed to the role of the central nervous system in the modulation of IR, as well as to the use of recombinant adipocytokines for IR management. The scope of this article is to cast light on the detrimental effects of IR on metabolism and the body systems in women as well as to highlight the current therapeutic approach, drugs in progress, and future therapeutic perspectives.

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Presence of metabolic risk factors in non-obese PCOS sisters: Evidence of heritability of insulin resistance

Cited by 27 publications

References 33 publications

Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome

Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome

Polycystic Ovary Syndrome: The influence of environmental and genetic factors

The impact of insulin resistance on woman's health and potential treatment options

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