Insulin Resistance In Obese Women Research Articles

PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women

Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism, contributes to metabolic disorders related to insulin action and body weight regulation, and is influenced by inflammation. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)γ2 gene seems to influence LPL functioning, but its role in obesity and insulin resistance status, which usually coexist in the clinical setting, has not been explored. Our aim was to analyze the association of obesity and insulin resistance with adipose LPL activity and expression, and the influence of the PPARγ2 Pro12Ala polymorphism. A cross-sectional study was conducted in 58 reproductive-age women who underwent elective abdominal surgery. Free-fatty acids, glucose, insulin, and selected adipokines were measured in fasting blood samples. DNA was isolated and the polymorphism genotyped. Biopsies of abdominal subcutaneous adipose tissue obtained during surgery were used to determine enzymatic LPL activity and expression; and expression of selected cytokines. Overweight/obese women presented lower LPL activity (P=0.022) and higher circulating TNF-α (P=0.020) than controls. Insulin resistant women also showed borderline lower LPL activity than non-resistant (P=0.052), but adiposity and inflammatory molecules were comparable. Nevertheless, LPL activity was higher in Pro12Ala carriers than in non-carriers after adjusting for obesity, insulin resistance and inflammation. Likewise, adipose LPL expression was increased in carriers while expression of cytokines was decreased. Our data suggest that insulin resistance is associated with low adipose LPL activity independently of obesity, but the PPARγ2 Pro12Ala polymorphism seems to protect the LPL functioning of obese insulin resistant women, likely through regulating inflammation in adipose tissue.

Phase I trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor–positive metastatic breast cancer

Obese women with breast cancer have worse prognosis than women with normal body mass index. Endocrine therapy resistance is in part mediated by insulin resistance in obese women with breast cancer. We investigated the tolerability and pharmacokinetics of exemestane in combination with metformin and rosiglitazone in nondiabetic overweight and obese postmenopausal women with hormone receptor-positive metastatic breast cancer. Patients had previously received chemotherapy and endocrine therapy for breast cancer. Exemestane was given as 25 mg orally per day. Metformin (M) and rosiglitazone (R) were given twice daily. Dose level 1 consisted of M 1,500 mg/day and R 6 mg/day. Dose level 2 consisted of M 2,000 mg/day and R 8 mg/day. Plasma concentrations of exemestane were measured on days 1, 8, and 15. Twenty patients were enrolled. Fourteen patients received exemestane, metformin, and rosiglitazone. Six patients received exemestane with metformin only (2,000 mg/day). Both regimens were well tolerated at the highest doses tested, and there were no notable changes in plasma exemestane levels. Six patients (30%) had stable disease for 6 months or longer. Oral daily administration of exemestane (25 mg) and metformin (2,000 mg) with and without rosiglitazone (8 mg) daily was well tolerated. Exemestane pharmacokinetics were not altered by metformin and rosiglitazone.

Short-term topiramate treatment does not improve insulin sensitivity or secretion in obese insulin-resistant women

Long-term treatment with topiramate reduces body weight and improves insulin sensitivity in obese humans. Our aim was to evaluate the effect of topiramate treatment for 4 weeks on insulin sensitivity and secretion, independent of weight loss. Randomized, double-blind, crossover, placebo-controlled study. Thirteen obese (BMI 36.6 ± 1.3 kg/m(2) (mean ± s.e.m.)), insulin-resistant (homeostasis model of assessment-insulin resistance 2.0 ± 0.2) women received topiramate (T, maximum dose of 75 mg) and placebo (P) for 4 weeks, separated by a 4-week washout period. Insulin sensitivity and β-cell function were assessed using a two-step hyperinsulinemic euglycemic clamp with stable isotopes and a hyperglycemic clamp. Hepatic and peripheral insulin sensitivities were not affected by topiramate treatment (glucose disposal rate (step 1 (insulin infusion rate 10 MU/M(2) per min) T: 17.5 ± 0.8 vs P: 18.5 ± 1.0 μmol/kg(LBM) per min, t=1.016, P=0.33; step 2 (insulin infusion rate 40 mU/m(2) per min) T: 27.9 ± 3.2 vs P: 28.8 ± 1.9 μmol/kg(LBM) per min, t=0.418, P=0.68)). Subjects lost a small amount of weight during the topiramate period (T: -1.0 ± 0.2 vs P: -0.1 ± 0.2 kg, t=2842, P=0.15). There were no changes in body fat mass, blood pressure, and fasting glucose. β-Cell function was not affected by topiramate as evidenced by an unaltered area under the curve of early (0-10 min; T: 1929.6 ± 265.7 vs P: 2024.7 ± 333.6 pmol/l, t=-0.357, P=0.73) and late (80-120 min; T: 28,017.7 ± 5029.9 vs P: 31,567.7 ± 5376.2 pmol/l, t=-1.481, P=0.16) phase insulin levels during hyperglycemia. The use of topiramate was associated with significant side effects such as paresthesia, nausea, dizziness, and concentration problems. Low-dose topiramate treatment for 4 weeks, relative to placebo, had no significant effect on insulin sensitivity in overweight/obese adult females without established diabetes.

Regional Adiposity, Adipokines, and Insulin Resistance in Type 2 Diabetes

The prevalence of obesity is rapidly increasing worldwide, and obesity is a well-known risk factor for type 2 diabetes involving insulin resistance. In recent decades, marked environmental and lifestyle changes have occurred and led to increased obesity and obesity-related cardiovascular diseases in Korea. Obesity is a heterogeneous condition, and body fat location may have a more important impact on the development of cardiovascular risk factors and related diseases than total excess adiposity [1]. Excessive accumulation of visceral adipose tissue causes low-grade chronic inflammation, dyslipidemia, insulin resistance, type 2 diabetes, and cardiovascular diseases. Recently, regional distribution of fat mass seems to correlate with risk level; fat mass in the lower extremities has a protective effect against insulin resistance and dyslipidemia [2,3]. Gluteofemoral fat, as measured by thigh circumference, hip circumference or leg adipose tissue mass, is independently associated with low total- and low-density lipoprotein triglyceride levels and high high-density lipoprotein cholesterol levels. A small amount of adiposity in the lower extremities is associated with higher insulin resistance and unfavorable glucose level [4]. Increased leg adipose tissue mass is associated with lower aortic calcification and arterial stiffness as well as with a decreased progression of aortic calcification [5,6]. Hip circumference was positively associated with plasma ascorbic acid level, an anti-oxidant marker, and might contribute to endothelial protection [7]. There are a few possible mechanisms to explain the protective role of lower extremity fat deposition. First, subcutaneous adipose tissue acts as a buffer for the daily influx of dietary lipids, protecting other tissues from a lipid overflow associated with lipotoxicity [8]. Second, there is differential secretion of adipose tissue-related proteins, called adipokines. Gluteofemoral adipose tissue could contribute to a protective adipokine profile by secreting more beneficial adipokines and fewer inflammatory molecules compared with abdominal fat. However, even though the negative association between lower extremity fat mass and insulin resistance is established, it is still unclear whether the lower extremity fat mass per se exerts beneficial effects on glucose metabolism independent of the mere absence of trunk fat. Several metabolic characteristics of adipocyte size and location might influence their metabolic consequences. Adipocytes in the lower extremities are larger, less sensitive to lipolytic stimuli, and more sensitive to insulin compared with those in the abdomen [9,10]. Although increases in adipocyte number and size can occur with increasing obesity level, larger adipocytes are also associated with higher secretion of adipokines which favorably influence insulin resistance [11]. The large adipocytes in the femoral region can result in higher insulin sensitivity and increased secretion of metabolically beneficial adipokines. This combination of factors may partially offset the detrimental influence of abdominal adiposity and offer metabolic defense against additional glucose dysregulation [12]. Trunk to leg fat ratio may have a different impact according to age and gender. With aging, this ratio increased more markedly in women than men, because the women's lower extremity fat mass remained much the same at all ages. According to the literature, the relationship between leg and trunk fat mass is associated with the risk of insulin resistance and dyslipidemia in obese women, both before and after menopause [2]. Adipokines are biomarkers for fat mass, fat distribution, adipose tissue function, liver fat content, insulin sensitivity, and subclinical chronic inflammation associated with metabolic diseases. Circulating biomarkers for abdominal fat accumulation include adiponectin, retinol binding protein-4 (RBP4), vaspin, chemerin, progranulin, and fetuin-A and others [13]. RBP4 is predominantly secreted from the liver, but is also expressed in adipocytes. Increased RBP4 expression in visceral adipose induces the increased serum RBP4 levels in tissues of patients with insulin resistance [14]. Adiponectin and letptin are more likely to be associated with impaired insulin sensitivity or insulin secretion, while RBP4 is associated with adverse fat distribution and insulin resistance. In a recent issue of Diabetes & Metabolism Journal, Kim et al. [15] presented an article regarding the relationship of absolute or relative adiposity to insulin resistance in obese women with type 2 diabetes. They measured the trunk fat mass and lower extremities fat mass and found that relative adiposity (defined by peripheral fat mass/trunk fat mass) was correlated with insulin resistance. They also observed the positive association of total, central, and peripheral fat mass with adiponectin and leptin levels, but not with RBP4 level. The regional adiposity was positively associated with serum adiponectin level and negatively associated with RBP4 level, suggesting the favorable effect of regional adiposity. However, regional adiposity was also positively associated with insulin resistance. Although the authors did not discuss these conflicting results, they may be due to the age distribution of the study subject's considering that peripheral fat mass does not change with age, while visceral adiposity is markedly increased after menopause. Additional studies in various conditions such as age, gender, obesity degree, and underlying disease condition will be helpful for understanding the metabolic effects of regional adiposity.

Serum Ferritin Is Differentially Associated with Anti-oxidative Status and Insulin Resistance in Healthy Obese and Non-obese Women

BackgroundFerritin is known to be associated with insulin resistance (IR) and oxidative stress; however, recent studies have shown that there is an association between ferritin and anti-oxidative status. To date, the biphasic response of ferritin to oxidative stress has not been fully evaluated. Thus, we investigated the association between ferritin and IR and anti-oxidative status in obese and non-obese women.MethodsWe evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) and total anti-oxidant status (TAS) in a total of 111 healthy women between the ages of 32 and 68 years.ResultsIn all of the study subjects, ferritin levels were positively correlated with age (r = 0.38, P < 0.001), body mass index (r = 0.24, P = 0.01), TAS (r = 0.38, P < 0.001) and HOMA-IR (r = 0.20, P = 0.04). In the subgroup analysis, ferritin levels were correlated with age (r = 0.39, P < 0.001) and TAS (r = 0.43, P < 0.001) in the non-obese group and with insulin (r = 0.50, P = 0.02) and HOMA-IR (r = 0.52, P = 0.01) levels in the obese group. On stepwise multiple linear regression analysis, ferritin was found to be independently associated with TAS (B = 177.16, P < 0.0001) in the non-obese group and independently associated with HOMA-IR (B = 30.36, P = 0.01) in the obese group.ConclusionOur findings suggest ferritin is associated with IR in obese women and with anti-oxidative status in non-obese women. Further studies are warranted to elucidate the precise role of ferritin in obesity.

PS8 - 43. Short-term Topiramate treatment in obese insulin resistant women does not improve insulin secretion and sensitivity

Long-term treatment with Topiramate reduces body weight and improves serum lipids and insulin sensitivity in obese humans. The aim of this study was to evaluate the effect of short-term, low-dose Topiramate treatment on insulin secretion and sensitivity, independent of weight loss, in obese insulin resistant women.

Myocardial steatosis, cardiac remodelling and fitness in insulin-sensitive and insulin-resistant obese women

BackgroundObesity predisposes to heart failure and premature cardiovascular death, particularly in sedentary women. In animal models and in men with type 2 diabetes mellitus, impaired cardiac function is associated with...

Deterioration in cardiometabolic risk markers in obese women during depot medroxyprogesterone acetate use

Background Highly effective contraception is essential in obese women, but it should not increase their risk of developing or worsening obesity-related cardiometabolic illness. The purpose of this 18-week prospective experimental study was to compare the impact of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on cardiometabolic markers in obese and normal-weight women. Methods Normal-weight [body mass index (BMI) 18.5–24.9 kg/m 2] and obese (BMI≥30 kg/m 2) women received injections of 104 mg DMPA-SC at baseline and 12 weeks later. Markers of cardiometabolic risk measured at baseline and 18 weeks after the first injection included body morphometry, fasting blood tests, and oral and frequently sampled intravenous glucose tolerance tests (FSIGT). Results At baseline, median gravidity, BMI, abdominal circumference, and acute insulin response to intravenous glucose were higher and high-density lipoprotein (HDL) cholesterol and insulin sensitivity ( S I from FSIGTs) were lower in the 10 obese participants than the five normal-weight women (p≤.05 for each). While there was no significant difference between median baseline and follow-up values among normal-weight women, the difference between median baseline and follow-up among the obese cohort was significantly higher for BMI and lower for HDL cholesterol and insulin sensitivity ( S I) (p≤.05 for each). The absolute changes for routinely measured clinical laboratory values of metabolic decline were no different among the normal-weight vs. obese women. The difference in absolute change in β-cell compensation for insulin resistance [disposition index (DI)] was significant between the two groups at follow-up, with the normal-weight group experiencing an increase in DI while the obese group experienced a decline in DI (188.5 vs. −286, p=.04). Conclusions Obese women have an increased baseline cardiometabolic risk when compared with normal-weight women at baseline. There was a significantly greater decline in β-cell compensation for insulin resistance in obese women on DMPA. Our data suggest potential deleterious effects of DMPA on glucose regulation in obese women. Further studies should elucidate the long-term cardiometabolic consequences of DMPA use in obese women.

Retinol-binding protein 4 and insulin resistance in preeclampsia

Preeclampsia is characterized by the onset of high blood pressure and proteinuria during pregnancy, which results in substantial maternal and neonatal morbidity and mortality. Insulin resistance has been observed before the onset of preeclampsia, and is implicated in its pathophysiology. Recently, retinol-binding protein 4 (RBP4), which carries retinol in circulation, has been shown to be a potential regulator of insulin resistance originating from adipose tissue. Here we measured insulin resistance and RBP-4 levels in patients with preeclampsia and in women with normal pregnancies matched for gestational age and body mass index at Okayama University Hospital. Our aim was to examine the potential role of RBP4 in the pathophysiology of this disorder. There were no significant differences in RBP4 levels between all patients with preeclampsia and controls. However, the RBP4 level and homeostasis model assessment as an index of insulin resistance (HOMA-IR) in overweight patients with late-onset preeclampsia were significantly higher than in overweight controls carrying normal pregnancies and in normal weight women with late-onset preeclampsia. In contrast, there were no significant differences between the overweight and normal weight groups among patients with early-onset preeclampsia and in healthy pregnant women. These data suggest that RBP4 might act in the pathophysiology of late-onset preeclampsia via increased insulin resistance in obese women.

Food Fried in Extra-Virgin Olive Oil Improves Postprandial Insulin Response in Obese, Insulin-Resistant Women

The benefits of low glycemic load (GL) diets on clinical outcome in several metabolic and cardiovascular diseases have extensively been demonstrated. The GL of a meal can be affected by modulating the bioavailability of carbohydrates or by changing food preparation. We investigated the effect on plasma glucose and insulin response in lean and obese women of adding raw or fried extra-virgin olive oil to a carbohydrate-containing meal. After an overnight fast, 12 obese insulin-resistant women (body mass index [BMI], 32.8 ± 2.2 kg/m(2)) and five lean subjects (BMI, 22.2 ± 1.2 kg/m(2)) were randomly assigned to receive two different meals (designated A and B). Meal A was composed of 60 g of pasta made from wheat flour and 150 g of grilled courgettes with 25 g of uncooked oil. Meal B included 15 g of oil in the 150 g of deep-fried courgettes and 10 g of oil in the 60 g of stir-fried pasta. Both meals included 150 g of apple. Blood samples were collected at baseline and every 30 minutes over a 3-hour post-meal period and were tested for levels of glucose, insulin, C-peptide, and triglycerides. The area under the curve (AUC) values were calculated. In obese women the AUCs for C-peptide were significantly higher after meal A than after meal B at 120 minutes (W [Wilcoxon sign rank test] = 27.5, P = .0020), 150 minutes (W = 26.5, P = .0039), and 180 minutes (W = 26.5, P = .0039). No differences were found in lean subjects. This study demonstrated that in obese, insulin-resistant women, food fried in extra-virgin olive oil significantly reduced both insulin and C-peptide responses after a meal.

The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome

Insulin resistance (IR) is one of the common features of the polycystic ovary syndrome (PCOS), and recent studies indicate the possible role of vitamin D in the pathogenesis of IR and glucose metabolism. Aim of this study was aimed to determine the effect of vitamin D replacement therapy on glucose metabolism, insulin, and androgen levels in obese, insulin-resistant women with PCOS. Eleven women with PCOS were included in the study. Mean age of the patients was 23.6+/-5.7 yr, body mass index 33.9+/-5.1 kg/m(2). Six patients (54.5%) had acantosis nigricans and 10 (90.9%) oligoamenorrhea. The mean Ferriman Gallwey score was 14.1+/-4.6. Only 2 women were within the normal limits of vitamin D levels as >20 ng/ml. Three weeks after the administration of the single dose of 300,000 units of vitamin D3 orally, 25-hydroxyvitamin D3 significantly increased from 16.9+/-16 ng/ml to 37.1+/-14.6 ng/ml (p: 0.027) and only 2 women were detected to have vitamin D3 levels <20 ng/ml. Although glucose and insulin levels were decreased non-significantly, homeostasis model assessment (HOMA)-IR significantly decreased from 4.41+/-1.38 to 3.67+/-1.48 (p: 0.043). No significant alterations were witnessed at the levels of DHEAS, total and free testosterone, androstenedione. No correlation was found between vitamin D with HOMA and other hormonal parameters. In conclusion, women with PCOS have mostly insufficient vitamin D levels, and vitamin D replacement therapy may have a beneficial effect on IR in obese women with PCOS.

Evaluation of insulin resistance in obese women with and without acanthosis nigricans

Acanthosis nigricans is characterized by hyperpigmented velvety plaques of body folds and neck. Insulin could be a responsible factor in the pathogenesis of this condition and hyperinsulinemia: a consequence of insulin resistance stimulates the formation of these characteristic plaques. In this study, insulin resistance was compared in obese women with and without acanthosis nigricans. This was a cross-sectional study. Sixty-six obese women (32 patients with acanthosis nigricans and 34 patients without acanthosis nigricans) were selected randomly. Levels of fasting serum insulin and fasting blood glucose were measured in both groups and insulin resistance was determined using homeostasis model assessment. Glucose tolerance test also was performed for all of participants. Five (15.6%) patients with acanthosis nigricans and no (0%) patient without acanthosis nigricans had insulin resistance (P < 0.05). Six (18.7%) patients with acanthosis nigricans and one (2.9%) patient without acanthosis nigricans had impaired glucose tolerance test (P < 0.05). The mean levels of fasting serum insulin were 15.7 +/- 8.7 and 12.2 +/- 4.1 microm/mL (P < 0.05) and the mean values of insulin resistance index were 3.5 +/- 1.9 and 2.6 +/- 0.9 microm/mL between patients with and without acanthosis nigricans, respectively (P < 0.05). In Iranian obese women, acanthosis nigricans is a marker of insulin resistance.

Is a nutritional therapeutic approach unsuitable for metabolically healthy but obese women?

Metabolically healthy but obese postmenopausal women are a subset of obese individuals who do not show obesityrelated metabolic abnormalities such as insulin resistance, a pro-atherosclerotic lipid profile, a proinflammatory state and hypertension [1, 2]. In longitudinal studies, this phenotype was associated with reduced risks of developing type 2 diabetes and cardiovascular disease [3]. These ‘fit-fat individuals’ are of interest because they constitute a model that may provide insight into the pathogenesis of insulin resistance in humans. In addition, they represent a potential clinical challenge in that they may require a different therapeutic strategy from that used to treat obese and insulin-resistant women. With respect to the pathogenic issue, it is presently unclear why these women are protected. Initially, investigators focused on elucidating the mechanism underlying this protective effect, with the aim of identifying potential therapeutic targets for the treatment of obese and insulinresistant individuals. It was reported that a lower visceral fat content, despite a high body fat content, and a lower accumulation of fat within ectopic sites may contribute to the favourable metabolic profile [2, 4]. These metabolically healthy but obese postmenopausal women had lower circulating levels of high-sensitivity C-reactive protein compared with ‘at-risk’ women [5], suggesting that the lack of a systemic proinflammatory condition, common in obesity, may explain the protection. It is also possible that the higher insulin sensitivity may be due to a primary genetic metabolic event that contributes to a protective metabolic profile but at the same time influences the early onset of obesity. This is consistent with a study on Pima Indians showing that insulin sensitivity is a predictor of future obesity [6]. The importance of these distinctive features is confirmed by the profile of metabolically obese but normal-weight women, who are characterised by a diametrically opposite profile. These women have a higher body fat content in spite of a normal BMI, and show the cluster of phenotypic risk factors associated with the insulin resistance syndrome [7, 8]. With respect to the clinical relevance of metabolically healthy but obese women, in this issue of Diabetologia, Karelis et al. [9] report the original finding that these women may respond differently to an energy-restricted diet than insulin-resistant obese women. From an original population of 121 obese women recruited for a weight loss programme, the authors present data on two selected subgroups of women: those within the upper quartile (the metabolically healthy but obese postmenopausal women) and those within the lower quartile (insulin-resistant and ‘at-risk’ individuals) of insulin sensitivity values as assessed by means of the euglycaemic–hyperinsulinaemic clamp. The clamp was performed before and after the Diabetologia (2008) 51:1567–1569 DOI 10.1007/s00125-008-1077-x

Insulin regulation of MCP-1 in human adipose tissue of obese and lean women

CCL2 (MCP-1, monocyte chemoattractant protein 1) and CCL3 (MIP-1alpha, macrophage inflammatory protein 1alpha) are required for macrophage infiltration in adipose tissue. Insulin increases CCL2 expression in adipose tissue and in serum more in insulin-resistant obese than in insulin-sensitive lean mice, but whether this is true in humans is unknown. We compared basal expression and insulin regulation of CCL2 and CCL3 in adipose tissue and MCP-1 and MIP-1alpha in serum between insulin-resistant and insulin-sensitive human subjects. Subcutaneous adipose tissue biopsies and blood samples were obtained before and at the end of 6 h of in vivo euglycemic hyperinsulinemia (maintained by the insulin clamp technique) in 11 lean insulin-sensitive and 10 obese insulin-resistant women, and before and after a 6-h saline infusion in 8 women. Adipose tissue mRNA concentrations of monocyte/macrophage markers CD68, EMR1, ITGAM, ADAM8, chemokines CCL2 and CCL3, and housekeeping gene ribosomal protein large P0 (RPLP0) were measured by means of real-time PCR at baseline. In addition, mRNA concentrations of CCL2, CCL3, and RPLP0 were measured after insulin infusion. Levels of MCP-1 and MIP-1alpha were determined in serum, and protein concentration of MCP-1 was determined in adipose tissue at baseline and after insulin infusion. Basally, expression of the macrophage markers CD68 and EMR1 were increased in adipose tissue of insulin-resistant subjects. Insulin increased MCP-1 gene and protein expression significantly more in the insulin-resistant than in the insulin-sensitive subjects. Basally expression of CCL2 and CCL3 and expression of macrophage markers CD68 and ITGAM were significantly correlated. In serum, MCP-1 decreased significantly in insulin-sensitive but not insulin-resistant subjects. MIP-1alpha was undetectable in serum. Insulin regulation of CCL2 differs between insulin-sensitive and -resistant subjects in a direction that could exacerbate adipose tissue inflammation.

Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels

To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome. Prospective clinical study. Department of obstetrics and gynecology in a major university in Greece. Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women. Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks. At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured. Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester. Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.

Metabolically Healthy but Obese Women Have an Intermediate Cardiovascular Risk Profile Between Healthy Nonobese Women and Obese Insulin-Resistant Women

Obesity is associated with metabolic and cardiovascular risk factors that include type 2 diabetes, hypertension, and dyslipidemia (1–4). A subset of obese subjects has been identified that appears to be protected from obesity-related metabolic abnormalities (5–11). These subjects, termed metabolically healthy but obese (MHO), are relatively insulin sensitive and have a rather favorable cardiovascular risk profile (5–11). Although the existence of MHO individuals has been recognized, only a few studies have examined in detail the metabolic characteristics associated with their protective profile (5–13). Whereas MHO individuals appear to have a more favorable cardiovascular risk profile than insulin-resistant obese (IRO) individuals, they show early signs of atherosclerosis compared with lean subjects, which could not be explained by alterations in cardiovascular risk factors (12). Among the factors that may account for the early atherosclerosis, insulin-like growth factor (IGF)-1 is a plausible candidate because low plasma IGF-1 concentrations are associated with type 2 diabetes, insulin resistance (14–16), and increased risk of coronary artery disease (17–22). To further characterize the protective profile of MHO individuals, we compared clinical characteristics, including cardiovascular risk factors, plasma IGF-1 levels, and intima-media thickness (IMT) of the common carotid artery, of a group of MHO women from a cohort of nondiabetic Italian Caucasians with those of two age-matched groups comprising healthy nonobese or …

Acute Effect of Exercise on Plasma Leptin Level and Insulin Resistance in Obese Women with Stable Caloric Intake

Obese individuals are frequently hyperleptinemic and insulin resistant. Chronic exercise is associated with improvements in plasma leptin level and insulin sensitivity; however, little is known about the acute effect of exercise on these parameters. The aim of this study was to evaluate the acute effect of aerobic exercise on plasma leptin and insulin sensitivity in obese women with stable caloric intake. Patients and Methods: Twenty-three obese women (age 41.2 ± 10.3 years, body mass index 40.7 ± 6.7 kg/m2) were included to the study. All subjects were admitted to an exercise program (45-minute walking sessions at 60–80% of maximum heart rate) every day except weekends for four weeks (total 20 exercise sessions). Insulin resistance was evaluated by HOMA model. Plasma glucose, insulin and leptin levels were determined at baseline and at the end of the first, seventh, and twentieth exercise session. Results: Baseline and at the end of the first, seventh, and twentieth exercise session plasma leptin levels were 59.1 ± 20.1, 58.5 ± 21.0, 53.4 ± 21.9, and 51.2 ± 20.5 ng/ml and HOMA-r were 2.75 ± 1.47, 1.77 ± 0.71, 1.73 ± 0.89, 1.62 ± 0.70, respectively. Compared to baseline, at the end of the seventh (p=0.021) and twentieth exercise session (p=0.003), plasma leptin levels were significantly low. Plasma leptin level did not change significantly at the end of the first exercise session (p>0.05). At the end of the first exercise session (p=0.005), end of the seventh (p=0.003) and twentieth exercise session (p=0.007) HOMA-r was lower than baseline. There was no correlation between weight loss during exercise period and the change of leptin, and HOMA-r. Fasting plasma glucose, insulin and leptin levels were determined at baseline and at the end of the first, seventh, and twentieth exercise session. Conclusion: Our study suggests that acute exercise decreases insulin resistance at the first exercise session with no effect on leptin levels. Significant leptin decrement was evident at the first week and lasted during the entire four weeks exercise session.

Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women

To study the local tissue lactate production in the normal state and its possible disturbances in insulin resistance, rates of lactate release from adipose tissue (AT) and skeletal muscle (SM) were compared postabsorptively and during a hyperinsulinemic euglycemic clamp in 11 healthy nonobese and 11 insulin-resistant obese women. A combination of microdialysis, to measure interstitial lactate, and the 133Xe clearance technique, to determine local blood flow, were used. In the controls, local blood flow increased by 40% in SM (P<0.05) and remained unchanged in AT, whereas the interstitial-plasma difference in lactate doubled in AT (P<0.005) and was unaffected in SM during hyperinsulinemia. In the obese, blood flow and interstitial-plasma difference in lactate remained unchanged in both tissues during hyperinsulinemia. The lactate release (micromol100 g-1min-1) was 1.17+/-0.22 in SM and 0.43+/-0.11 in AT among the controls (P<0.01) and 0.86+/-0.23 in SM and 0.83+/-0.25 in AT among the obese women in the postabsorptive state. During insulin infusion, lactate release in the controls increased to 1.92+/-0.26 in SM (P<0.005) and to 1.14+/-0.22 in AT (P<0.005) but remained unchanged in the obese women. It is concluded that AT and SM are both significant sources of lactate release postabsorptively, and AT is at least as responsive to insulin as SM. The ability to increase lactate release in response to insulin is impaired in AT and SM in insulin-resistant obese women, involving defective insulin regulation of both tissue lactate metabolism and local blood flow.

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

In a randomized, placebo-controlled study, we studied the effects of 4 months' treatment with rosiglitazone on low-grade inflammation, liver function, lipid levels, and blood pressure in 30 overweight women with polycystic ovary syndrome. Rosiglitazone significantly decreased serum C-reactive protein levels, white blood cell count, and alanine aminotransferase enzyme activity but did not affect lipid or blood pressure levels. Placebo had no effect on any parameters.

Effects of resistance or aerobic exercises on metabolic parameters in obese women who are not on a diet

This longitudinal, controlled clinical study was conducted to compare the effects of resistance exercise (RE) and aerobic exercise (AE) on body mass index (BMI), weight, fat mass (FM), serum lipid profile, and insulin resistance in obese women who cannot adhere to energy-restricted diets. A total of 60 obese women with severe eating disorders were evaluated. Patients were randomly divided into 3 groups: control group with no exercise (n=20), group 1 with AE (n=20), and group 2 with RE (n=20). Demographic and anthropometric measurements were taken. Serum lipid fractions and fasting (FGlc) and postprandial glucose insulin (PGlc) levels were measured. Insulin resistance was calculated with use of homeostasis model assessment (HOMA-IR). Total body FM was measured by bioelectric impedance analysis. After 12 wk of exercise, significant decreases in BMI, waist and weight measurements, and FGlc, PGlc, triglyceride, and total cholesterol levels were noted in each of the study groups. Reduced low-density lipoprotein cholesterol level and FM and HOMA-IR measurements were observed only in group 1 (with AE). This study indicated that AE and RE training induces improvement in body fat composition and has a favorable metabolic effect in obese women with severe eating disorders.