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

Department of Obstetrics and Gynaecology (OBSTGYN), University of Oslo, Kristiania (historical), Oslo, Norway
Metabolism (Impact Factor: 3.89). 06/1995; 44(5):611-6. DOI: 10.1016/0026-0495(95)90118-3
Source: PubMed


In overweight women with polycystic ovary syndrome (PCOS), increased insulin resistance has been observed. Since abdominal obesity is associated with impaired fibrinolytic capacity and elevated levels of plasminogen activator inhibitor (PAI-1) and since PAI-1 seems to be related to insulin resistance, we investigated the possible effects of dietary intervention on lipids, fibrinolysis, coagulation, and insulin sensitivity in obese PCOS women. Nine women aged 22 to 39 years (median weight, 97 kg) ate a protein-rich very-low-calorie diet (VLCD) (Nutrilett, Nycomed Pharma, Oslo, Norway; 421 kcal/d) for 4 weeks (part 1). After significant reductions of body fat (13%, P < .01), two of nine women achieved regular menstruation and became pregnant. Six of the remaining women continued on a conventional low-calorie diet (1,000 to 1,500 kcal/d) for the next 20 weeks (part 2), during which time they were generally able to preserve the body fat loss obtained in part 1 of the study. During part 1, significant reductions of total serum cholesterol (29%, P = .001) and fasting triglyceride ([TG] 31%, P < .05) levels were observed, as well as significant reductions of fasting glucose (6%, P < .05) and insulin (20%, P < .05). Insulin sensitivity (glucose disposal rate [GDR]) was increased by 93% (P < .05). After finishing part 2, insulin sensitivity was still significantly increased (86%, P < .05) and PAI-1 activity was significantly reduced (54%, P < .05). Moreover, overall fibrinolytic activity was significantly improved (serum D-dimer concentration increased by 75%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

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    • "To date only one small (n ¼ 9) pilot study showed reductions in PAI-1 following 4 weeks of a very low-calorie diet or 20 weeks of a low-calorie diet (Andersen et al., 1995). Previous studies have also shown a favourable effect of exercise training on endothelial function in both healthy and diseased populations, some specifically with reductions in sICAM-1 (Adamopoulos et al., 2001; Zoppini et al., 2006; Saetre et al., 2011) and sVCAM-1 (Adamopoulos et al., 2001; Rankovic et al., 2009), ADMA (Richter et al., 2005; Schlager et al., 2011; Tsarouhas et al., 2011) and PAI-1 (Jahangard et al., 2009). "
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    ABSTRACT: Women with polycystic ovary syndrome (PCOS) present with vascular abnormalities, including elevated markers of endothelial dysfunction. There is limited evidence for the effect of lifestyle modification and weight loss on these markers. The aim of this study was to determine if 20 weeks of a high-protein energy-restricted diet with or without exercise in women with PCOS could improve endothelial function. This is a secondary analysis of a subset of 50 overweight/obese women with PCOS (age: 30.3 ± 6.3 years; BMI: 36.5 ± 5.7 kg/m(2)) from a previous study. Participants were randomly assigned by computer generation to one of three 20-week interventions: diet only (DO; n = 14, ≈ 6000 kJ/day), diet and aerobic exercise (DA; n = 16, ≈ 6000 kJ/day and five walking sessions/week) and diet and combined aerobic-resistance exercise (DC; n = 20, ≈ 6000 kJ/day, three walking and two strength sessions/week). At Weeks 0 and 20, weight, markers of endothelial function [vascular cell adhesion molecule-1 (sVCAM-1), inter-cellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1) and asymmetric dimethylarginine (ADMA)], insulin resistance and hormonal profile were assessed. All three treatments resulted in significant weight loss (DO 7.9 ± 1.2%, DA 11.0 ± 1.6%, DC 8.8 ± 1.1; P < 0.001 for time; P = 0.6 time × treatment). sVCAM-1, sICAM-1 and PAI-1 levels decreased with weight loss (P≤ 0.01), with no differences between treatments (P ≥ 0.4). ADMA levels did not change significantly (P = 0.06). Testosterone, sex hormone-binding globulin and the free androgen index (FAI) and insulin resistance also improved (P < 0.001) with no differences between treatments (P ≥ 0.2). Reductions in sVCAM-1 were correlated to reductions in testosterone (r = 0.32, P = 0.03) and FAI (r = 0.33, P = 0.02) as well as weight loss (r= 0.44, P = 0.002). Weight loss was also associated with reductions in sICAM-1 (r= 0.37, P = 0.008). Exercise training provided no additional benefit to following a high-protein, hypocaloric diet on markers of endothelial function in overweight/obese women with PCOS.
    Full-text · Article · May 2012 · Human Reproduction
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    • "Short-term low calorie diets (4 weeks) with 6.6-9.0% weight loss have been shown to decrease IR (Hamilton-Fairley et al., 1993; Andersen et al., 1995). Studies of moderate caloric restriction for 2-15 months also gave positive outcomes (Pasquali et al., 1989). "
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    ABSTRACT: Insulin resistance (IR) is a consequence of obesity, and in women it is often inextricably linked with ovarian function leading to clinical reproductive manifestations such as early menarche onset, subfertility and polycystic ovary syndrome (PCOS). Likewise, the dramatic fall in oestrogen production after menopause may contribute to weight gain and changes in adipose tissue distribution. Overall, women who are obese, especially those with reproductive complications including PCOS, have been identified as specific high risk subgroups for further progression through to prediabetes, type 2 diabetes mellitus (T2DM) and potentially cardiovascular disease (CVD). This review focuses on the interrelationship between the ovarian function and obesity as well as its treatment strategies.
    Full-text · Article · Mar 2010 · Molecular and Cellular Endocrinology
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    • "Hyperinsulinemia contributes to the prothrombotic state by reducing fibrinolysis and raising the level of plasminogen activator inhibitor (PAI-1) (Potter van Loon et al 1993). In patients with PCOS, the level of PAI-1 was found to be elevated (Atiomo et al 1998; Sampson et al 1996; Yildiz et al 2002), and it decreased with improvement in insulin sensitivity, either through weight loss (Andersen et al 1995) or the use of insulin sensitizing agents (Ehrmann et al 1997; Velazquez et al 1997). The increase in PAI-1 activity in PCOS was thought to be independent of body mass index since elevated levels were also observed in lean PCOS women. "
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    ABSTRACT: It is estimated that 60%-7% of women of reproductive age have polycystic ovarian syndrome (PCOS). Women with this condition exhibit an adverse cardiovascular risk profile, characteristic of the cardiometabolic syndrome and given the high prevalence of PCOS in the female population, this condition may contribute towards the acceleration of cardiovascular disease among young women. This article summarizes the recent development and findings in the cardiometabolic abnormalities in patients with PCOS. Patients with PCOS have the clinical features of oligomenorrhoea, hirsutism and infertility; however, they also exhibit hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased pro-thrombotic state. They have an increased risk of type 2 diabetes and impaired glucose tolerance, and sleep apnea is also found more commonly in this population. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease it is unclear if they have accelerated atherosclerosis. End point studies are currently lacking and the available evidence are conflicting. Adipose tissue has emerged as an important endocrine organ over the last decade and gained recognition in having an important role in the cardiometabolic syndrome. Adiponectin that is secreted exclusively by adipocytes has recently been recognized as an important marker of cardiometabolic syndrome, obesity, type 2 diabetes, and coronary artery disease. Other adipocytokines like leptin and resistin have also recently been recognized. This article will address the current evidence for the adverse cardiovascular risk in PCOS and the other factors that may be implicated. Finally the therapeutic options for treatment will be discussed.
    Full-text · Article · Feb 2007 · Vascular Health and Risk Management
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