Resting energy expenditure in women with polycystic ovary syndrome.

STUDY QUESTION: Is resting energy expenditure (REE) altered in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Women with PCOS have a reduction in REE, when corrected for fat-free mass, independent of PCOS clinical phenotypes and BMI categories. WHAT IS KNOWN ALREADY: Obesity is an important issue in women with PCOS, in terms of frequency and pathophysiological implications. It has been hypothesized that obesity may be favoured by alterations in REE, but the studies have been limited and conflicting. STUDY DESIGN, SIZE, DURATION: This case-control study was a comparison of 266 women with PCOS and 51 healthy controls, recruited in the Verona 3P study from 2010 to 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS diagnosed by the Rotterdam criteria, with normal thyroid function and no interfering medications, were referred to the outpatient clinic of a tertiary care centre of endocrinology and metabolism for a measurement of REE. Healthy controls were recruited in the same period and submitted to the same procedure. In all subjects, REE was measured by indirect calorimetry and serum androgens were measured by LC-MS/MS. In women with PCOS, insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp. MAIN RESULTS AND THE ROLE OF CHANCE: REE was similar in women with PCOS and controls. However, REE corrected for fat-free mass (REE/FFM) was significantly lower in women with PCOS than in controls (31.8 ± 4.0 vs 35.4 ± 3.9 kcal/kgFFM·day, P < 0.001). REE/FFM did not differ between normal-weight, overweight, or obese women with PCOS, and each of these subgroups showed lower REE/FFM values than controls. Reduced REE/FFM values were found in each phenotype of the syndrome. In multiple regression analysis, REE/FFM was independently associated with age and PCOS status, but not with fat mass. In PCOS women, REE/FFM was independently and directly associated with ovarian follicle number. LIMITATIONS, REASONS FOR CAUTION: Limitations of the study are the cross-sectional design, which limits the causal inference of the results, and the unavailability of precise information about lifestyle factors, which may be potential confounders. Further prospective studies are needed to establish the importance of this phenomenon in contributing to the weight excess of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: A reduction of REE could potentially favour weight gain in women with PCOS and possibly contribute to the altered metabolic profile typical of this condition, even counteracting the therapeutic strategies aimed to reduce excess body fat in these women. Nevertheless, the presence of this abnormality in both obese/overweight and normal-weight patients suggests that other factors must play a role in this phenomenon. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by academic grants to PM from the University of Verona (FUR 2010-2022). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Circadian and sex differences in post-ischemic vasodilation and reactive hyperemia in young individuals and elderly with and without type 2 diabetes.

OBJECTIVE: Cardiovascular events show morning preference and sex differences, and are related to aging and type 2 diabetes. We assessed circadian variations and sex differences in vascular conductance (VC) and blood flow (BF) regulations following a brief bout of forearm ischemia. METHODS: Young healthy individuals (H18-30) and elderly without (H50-80) and with type 2 diabetes (T2DM50-80) of both sexes were included. Forearm VC and BF, and mean arterial pressure (MAP) at baseline and following circulatory reperfusion were measured at 6 a.m. and 9 p.m. RESULTS: In the morning compared to evening, following reperfusion, the VC and BF increments were similar in H18-30 (p>.71), but lower in H50-80 (p<.001) and T2DM50-80 (p<.01). VC and BF following circulatory reperfusion were higher in men than women in H18-30 (p<.001), but similar between sexes in the older groups (p>.23). CONCLUSIONS: Forearm vasodilation following reperfusion is attenuated in the morning in the elderly, impairing BF towards an ischemic area. Diabetes does not affect the circadian regulation of VC and BF, but that of MAP. There are sex differences in VC and BF at baseline and after circulatory reperfusion at a young age, being greater in men, which disappear with aging without being affected by diabetes.

The Multiple Functions of Insulin Put into Perspective: From Growth to Metabolism, and from Well-Being to Disease.

Insulin has pleiotropic effects, and is of importance both as a key regulator of glucose metabolism and as a growth factor [...].

Current treatment for polycystic ovary syndrome: focus on adolescence.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women and it is associated with an increased rate of infertility. Its etiology remains largely unknown, although both genetic and environmental factors play a role. PCOS is characterized by insulin resistance, metabolic disorders and low-grade chronic inflammation. To date, the treatment of PCOS is mainly symptomatic and aimed at reducing clinical signs of hyperandrogenism (hirsutism and acne), at improving menstrual cyclicity and at favoring ovulation. Since PCOS pathophysiology is still largely unknown, the therapeutic interventions currently in place are rarely cause-specific. In such cases, the therapy is mainly directed at improving hormonal and metabolic dysregulations typical of this condition. Diet and exercise represent the main environmental factors influencing PCOS. Thus, therapeutic lifestyle changes represent the first line of intervention, which, in combination with oral contraceptives, represent the customary treatment. Insulin resistance is becoming an increasingly studied target for therapy, most evidence stemming from the time-honored metformin use. Relatively novel strategies also include the use of thiazolidinediones and GLP1-receptor agonists. In recent years, a nutraceutical approach has been added to the therapeutic toolkit targeting insulin resistance. Indeed, emerging data support inositol and alpha-lipoic acid as alternative compounds, alone or in combination with the aforementioned strategies, with favorable effects on ovulation, insulin resistance and inflammation. Nevertheless, additional studies are required in adolescents, in order to assess the effectiveness of diet supplements in preventing negative impacts of PCOS on fertility in adult age. This review focuses on the main therapeutic options for PCOS to date.

The free androgen index is inaccurate in women when the SHBG concentration is low.

OBJECTIVE/CONTEXT: The free androgen index (FAI) is known to give erroneous results in men, but it is still a commonly used test for the investigation of hyperandrogenism in women. This study aimed to compare the results of the FAI with the gold standard equilibrium dialysis method for free testosterone in women. DESIGN/PATIENTS: Free serum testosterone T (ED-T) and total serum T (T) were measured by equilibrium dialysis and LC-MS/MS in patients with polycystic ovarian syndrome (n = 130), normal female controls (n = 53) and normal males (n = 120). Calculated free T (cFT) and free androgen index (FAI) were also measured in these patients. In addition, cFT was retrospectively calculated in 4223 female patients with a normal T (<1.6 nmol/L) routinely investigated for hyperandrogenism. RESULTS: The cFT showed good agreement with measured ED-T, and the ratio cFT/ED-T was stable across all SHBG concentrations. In contrast, the FAI/ED-T ratio and the FAI/cFT ratio increased when the concentration of SHBG fell below 30 nmol/L. CONCLUSIONS: The FAI is not a reliable indicator of free T when the SHBG concentration is low and would give misleading information in a large number of women being investigated for hyperandrogenism.

Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes.

STUDY QUESTION: Could surrogate indexes identify insulin resistant individuals among women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Surrogate indexes may be able to rule in, but not rule out, insulin resistance in women with PCOS. WHAT IS KNOWN ALREADY: Insulin resistance is a typical finding of women with PCOS and most clinical information on this issue is based upon surrogate indexes of insulin resistance. However, data on the performance of these indexes in PCOS women are very limited. STUDY DESIGN SIZE, DURATION: A retrospective analysis of 406 women referred to our outpatient clinic for hyperandrogenism and/or menstrual dysfunction and submitted to hyperinsulinemic euglycaemic clamp between 1998 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 375 of these women had PCOS by the Rotterdam criteria and were included in the study. Six surrogate indexes of insulin sensitivity were calculated from glucose and insulin levels, either at fasting (homeostasis model assessment (HOMA), glucose/insulin (G/I) ratio and quantitative insulin sensitivity check index (QUICKI)) or after oral glucose load (Gutt, Stumvoll0-120 and Matsuda). MAIN RESULTS AND THE ROLE OF CHANCE: Overall, insulin resistance, as identified by the M-clamp value, was found in 74.9% of these women. The percentage was 59.3% in normal-weight vs 77.5% in overweight and 93.9% in obese subjects. All surrogate indexes were highly correlated with the M-clamp values. However, their ability to identify insulin resistant individuals was limited, in terms of sensitivity and especially in normal-weight subjects. ROC analysis showed similar performances of these indexes (AUC values 0.782-0.817). LIMITATIONS REASONS FOR CAUTION: Potential referral bias of PCOS patients may have caused overestimation of the prevalence of insulin resistance in these women. WIDER IMPLICATIONS OF THE FINDINGS: By using surrogate indexes many subjects with PCOS may be erroneously diagnosed as insulin sensitive, especially among normal-weight women. These indexes can be used to rule in, but not rule out, insulin resistance in PCOS. STUDY FUNDING/COMPETING INTEREST(S): Academic grants to P. Moghetti from the University of Verona. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Serum testosterone predicts cardiorespiratory fitness impairment in normal-weight women with polycystic ovary syndrome.

OBJECTIVE: Limited literature has shown that maximal oxygen consumption (V'O2max), that is the maximal capacity of an individual to perform aerobic work, may be lowered in overweight/obese women with polycystic ovary syndrome (PCOS). However, it remains unclear whether this impairment is associated with PCOS per se or is entirely due to body fat excess. Our objective was to assess whether cardiorespiratory fitness is altered in normal-weight PCOS women and to investigate which factors are associated with this phenomenon. SUBJECTS: Fifteen normal-weight PCOS women and 15 age- and BMI-matched healthy controls. Fourteen subjects in each group completed the protocol. MEASUREMENTS: V'O2max and ventilatory thresholds (maximal incremental cycle ergometer test with breath-by-breath analysis of gas exchange), insulin sensitivity (hyperinsulinaemic euglycaemic clamp) and androgenaemia (serum total and free testosterone, measured by liquid chromatography mass spectrometry and equilibrium dialysis) were accurately assessed. RESULTS: Maximal V'O2 and power were strikingly impaired in normal-weight PCOS individuals, as compared with healthy controls (29·4 ± 1·5 vs 35·8 ± 1·6 ml O2/kg/min, P = 0·008; 138 ± 6 vs 170 ± 10 W, P = 0·011, respectively). Similarly, oxygen consumption and power at both the first and second ventilatory thresholds were significantly lower in PCOS subjects than in healthy women. In multiple regression analysis, V'O2max was negatively predicted by serum-free testosterone levels, but not by body fat mass and glucose disposal rate (R(2) = 0·45 P = 0·013). CONCLUSIONS: Cardiorespiratory fitness is impaired in normal-weight PCOS women. Androgen excess but not insulin sensitivity is associated with this alteration.

Hemostatic and fibrinolytic abnormalities in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common form of anovulatory infertility, affecting up to 10% of women of reproductive age. This syndrome was first described in 1935 when American gynecologists Stein and Leventhal associated the presence of ovarian cysts with anovulation, obesity, and hirsutism. For many years, the effects of PCOS on coagulation and fibrinolysis have remained largely unexplored. This review summarizes current knowledge of the effects of PCOS on coagulation and fibrinolysis, and the putative mechanisms by which PCOS may contribute to the development of coagulation and fibrinolytic disorders. To date, there is relatively strong evidence suggesting that PCOS is associated with increased platelet aggregation and decreased plasma fibrinolytic activity. However, whether these hemostatic disorders are linked to the abnormal hormonal system in PCOS remains to be elucidated. Moreover, it should be emphasized that PCOS is a heterogeneous endocrine condition, and that the number of published studies is limited, the sample size of most of these studies is relatively small, and the selection of control subjects has not been always appropriate. Furthermore, well-designed studies on larger cohorts of carefully characterized PCOS patients are needed to provide more comprehensive information on this issue.

Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial).

UNLABELLED: Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease (NAFLD), which is extremely common in people with type 2 diabetes, no intervention studies have compared the effects of aerobic (AER) or resistance (RES) training on hepatic fat content in type 2 diabetic subjects with NAFLD. In this randomized controlled trial, we compared the 4-month effects of either AER or RES training on insulin sensitivity (by hyperinsulinemic euglycemic clamp), body composition (by dual-energy X-ray absorptiometry), as well as hepatic fat content and visceral (VAT), superficial (SSAT), and deep (DSAT) subcutaneous abdominal adipose tissue (all quantified by an in-opposed-phase magnetic resonance imaging technique) in 31 sedentary adults with type 2 diabetes and NAFLD. After training, hepatic fat content was markedly reduced (P < 0.001), to a similar extent, in both the AER and the RES training groups (mean relative reduction from baseline [95% confidence interval] -32.8% [-58.20 to -7.52] versus -25.9% [-50.92 to -0.94], respectively). Additionally, hepatic steatosis (defined as hepatic fat content >5.56%) disappeared in about one-quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group). Insulin sensitivity during euglycemic clamp was increased, whereas total body fat mass, VAT, SSAT, and hemoglobin A1c were reduced comparably in both intervention groups. CONCLUSION: This is the first randomized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD.

Ten-week whole-body vibration training improves body composition and muscle strength in obese women.

This work explored the short-term effect of whole body vibration (WBV) training on anthropometry, body composition and muscular strength in obese women. Fifty obese women (age = 46.8 ± 7.81[SD]y; BMI = 35.1 ± 3.55 kg/m(2)) were assigned to a ten-week WBV training period, two times a week (in each session, 14 min vibration training, 5 min rest; vibration amplitude 2.0-5.0mm, frequency 40-60 Hz), with (n = 18) or without (n = 17) radiofrequency, or to a non-exercise control group (n = 15). Subjects were instructed not to change their habitual lifestyle. Before and after the ten-week experimental period, anthropometric measurements, dual-energy X-ray absorptiometry (DXA), and the leg press, leg curl and leg extension strength tests were carried out. All changes in the two groups of WBV training, with or without radiofrequency, were similar and these groups were combined in a single WBV intervention group. As compared to controls, subjects submitted to WBV training had significantly lower BMI, total body and trunk fat, sum of skinfolds and body circumferences. On the other hand, lower limb strength tests were increased in the WBV group. These preliminary results suggest that WBV training may improve body composition and muscular strength in obese women and may be a useful adjuvant to lifestyle prescriptions.

Circadian Variations in Sympathetic Vasoconstriction in Older Adults with and Without Type 2 Diabetes.

INTRODUCTION: An impact of the sympathetic nervous system in the higher rate of cardiovascular events in the early morning compared to the evening has been claimed. Augmented sympathetic vasoconstriction increases cardiovascular risk by augmenting pulse pressure and cardiac afterload. Type 2 diabetes (T2DM) further increases sympathetic neurovascular transduction and cardiovascular risk. AIM: We assessed whether peripheral vasoconstriction triggered by a standardized sympathetic stressor is augmented at 6am vs 9pm in adults between 50-80 years with type 2 diabetes (T2DM50-80) vs healthy ones (H50-80). METHODS: Mean values of sympathetic vasoconstrictor responsiveness (SVR), vascular conductance (VC), brachial artery blood flow, and mean arterial pressure were measured on the contralateral forearm over two 5-minute bouts of rest and handgrip-mediated sympathetic stimulation, respectively. RESULTS: Although baseline VC values were lower (p < 0.01) in the morning vs evening in both groups, SVR values in response to sympathoexcitation were similar in H50-80 (- 0.43 ± 12.44 vs - 2.57 ± 11.63 %, p = 0.73) and T2DM50-80 (+6.64 ± 10.67 vs +5.21 ± 7.64 %, p = 0.90), but higher (p < 0.01) in T2DM50-80 vs H50-80 at both day hours. Individuals with T2DM reported positive SVR values and VC change-scores, while healthy individuals reported statistically different (p < 0.02) negative SVR values and VC change-scores. CONCLUSION: Peripheral vasoconstriction triggered by a standardized sympathetic stressor is similar between morning and evening, regardless of T2DM and different baseline VC values. However, peripheral vasoconstriction responsiveness is blunted in individuals with T2DM as handgrip-mediated sympathoexcitation induces vasodilation in the contralateral forearm in adults with T2DM and vasoconstriction in healthy age-matched controls, highlighting a neurovascular response altered by T2DM.

Sympathetic-mediated blunting of forearm vasodilation is similar between young men and women.

BACKGROUND: The in-vivo regulation of vascular conductance (VC) is a continuous balance between endothelial vasodilation and sympathetic vasoconstriction. Although women may report blunted sympathetic vasoconstriction along with higher endothelial vasodilation than men, it is currently unknown whether the interaction between vasoconstriction and vasodilation leads to different regulation of VC between sexes. This study assessed sex differences in sympathetic-mediated blunting of endothelial vasodilation after a brief period of ischemia and whether any restriction of vasodilation blunts tissue blood flow (BF) and re-oxygenation. METHODS: 13 young women and 12 young men underwent two 5-min forearm circulatory occlusions followed by reperfusion, one in basal conditions and the other during cold pressor test-induced sympathetic activation (SYMP). Brachial artery diameter and BF, mean arterial pressure, total peripheral resistance (TPR), and thenar eminence oxygenation were collected. Percent changes normalized to baseline values of forearm VC, brachial artery BF and flow-mediated dilation (FMD), TPR, and hand oxygenation after circulatory reperfusion were calculated. RESULTS: TPR increased during SYMP in men (p = 0.019) but not in women (p = 0.967). Women showed a greater brachial artery FMD than men (p = 0.004) at rest, but sex differences disappeared after normalization to shear rate and baseline diameter (p > 0.11). The percent increases from baseline of peak and average forearm VC after circulatory reperfusion did not differ between sexes in basal conditions (p > 0.98) or during SYMP (p > 0.97), and were restrained by SYMP similarly in both sexes (p < 0.003) without impairing the hand re-oxygenation (p > 0.08) or average hyperemic response (p > 0.09). CONCLUSIONS: Although women may report blunted sympathetic vasoconstriction than men when assessed separately, the similar sympathetic-mediated restriction of vasodilation suggests a similar dynamic regulation of VC between sexes. SYMP-mediated restrictions of the normal forearm vasodilation do not impair the average hyperemic response and hand re-oxygenation in both sexes.

Circadian and sex differences in carotid-femoral pulse wave velocity in young individuals and elderly with and without type 2 diabetes.

The incidence of cardiovascular events is higher in the morning than in the evening and differs between sexes. We tested the hypothesis that aortic stiffness, a compelling cardiovascular risk factor, increases in the morning than in the evening in young, healthy individuals between 18 and 30 years (H18-30) or in older individuals between 50 and 80 years, either healthy (H50-80) or with type 2 diabetes (T2DM50-80). Sex differences were also investigated. Carotid-femoral pulse wave velocity (cf-PWV) recorded via Doppler Ultrasound, blood pressure and heart rate were checked at 6 a.m. and 9 p.m., at rest and during acute sympathetic activation triggered by handgrip exercise. Cf-PWV values were lower in the morning compared to the evening in all groups (p < 0.01) at rest and lower (p = 0.008) in H18-30 but similar (p > 0.267) in the older groups during sympathetic activation. At rest, cf-PWV values were lower in young women compared to young men (p = 0.001); however, this trend was reversed in the older groups (p < 0.04). During sympathetic activation, the cf-PWV was lower in women in H18-30 (p = 0.001), similar between sexes in H50-80 (p = 0.122), and higher in women in T2DM50-80 (p = 0.004). These data do not support the hypothesis that aortic stiffness increases in the morning compared to the evening within any of the considered groups in both rest and sympathetic activation conditions. There are differences between the sexes, which vary according to age and diabetes status. In particular, aortic stiffness is higher in older women than in men with diabetes during acute stress.

Clinical Value of Serum Levels of 11-Oxygenated Metabolites of Testosterone in Women With Polycystic Ovary Syndrome.

CONTEXT: Recent data suggested that 11-oxygenated androgens may be the preponderant circulating androgens in women with PCOS. However, the pathophysiological significance of these hormones remains unclear. OBJECTIVE: The aim of this study was to evaluate the relationships between serum 11-OH testosterone (11-OHT) and 11-keto testosterone (11-KetoT) and clinical and biochemical hyperandrogenism, as well as the metabolic parameters, in women with PCOS. METHODS: The main classic and 11-oxygenated androgens were measured by LC-MS/MS and direct equilibrium dialysis in 123 women with PCOS, diagnosed according to the Rotterdam criteria, and 38 healthy controls. Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp. RESULTS: Serum 11-oxygenated androgens were higher in women with PCOS than in controls. Elevated levels of 11-OHT and 11-KetoT were found in 28.5% and 30.1% of PCOS women, respectively, whereas free testosterone (FT) was increased in 61.0% of them. Serum 11-oxygenated androgens showed a limited performance in recognizing women with classically defined hyperandrogenism. Unlike FT, 11-oxygenated androgens did not show significant relationships with anthropometric and metabolic parameters, except for a direct association with insulin sensitivity. In multivariable analysis, 11-OHT and 11-KetoT, directly, and FT, inversely, remained significant independent predictors of insulin sensitivity. CONCLUSIONS: Serum levels of 11-oxygenated androgens are higher in women with PCOS than in controls. However, these hormones show a poor performance in recognizing women with hyperandrogenism, as currently defined. The relationships of these androgens with insulin sensitivity strongly differ from that of FT, suggesting a different role of classic and 11-oxygenated androgens in the pathophysiology of PCOS.

Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report.

Addison Disease is an uncommon, life-threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced.

Insulin-Mediated Substrate Use in Women With Different Phenotypes of PCOS: the Role of Androgens.

CONTEXT: Few studies have explored in vivo insulin action on substrate use in women with PCOS. In particular, no data are available in women with different PCOS phenotypes. OBJECTIVE: The aim of the study was to evaluate insulin action on glucose (Gox) and lipid (Lox) oxidation, nonoxidative glucose metabolism (Gnonox), and serum free fatty acids (FFAs) in different PCOS phenotypes. METHODS: Participants included 187 nondiabetic women with PCOS diagnosed according to the Rotterdam criteria. Data from a historical sample of 20 healthy women were used as reference values. Whole-body substrate use data were obtained by the hyperinsulinemic euglycemic clamp associated with indirect calorimetry. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis. RESULTS: During hyperinsulinemia, the increase of Gox (ΔGox), Gnonox, as well as the suppression of Lox (ΔLox) and serum FFA (Δ% FFA) were altered in each PCOS phenotype. Moreover, Gnonox and Δ% FFA were lower in women with the classic phenotype than in those with the ovulatory or the normoandrogenic phenotypes, and ΔGox was lower in women with the classic than in those with the ovulatory phenotype. In multivariable analysis fat mass and free testosterone were independent predictors of ΔGox, Gnonox, and Δ% FFA, whereas only fat mass predicted ΔLox. CONCLUSION: In women with PCOS, regardless of phenotype, insulin-mediated substrate use is impaired. This phenomenon is greater in individuals with the classic phenotype. Free testosterone plays an independent role in insulin action abnormalities in glucose and lipid metabolism.

Disorders of coagulation and hemostasis in abdominal obesity: emerging role of fatty liver.

Abdominal obesity represents a public health concern because its prevalence is reaching epidemic proportions worldwide, and it is associated with an increased risk of cardiovascular morbidity and mortality and other pathological conditions. A large body of evidence suggests that abdominal obesity is associated with a prothrombotic tendency, which may, at least in part, contribute to the increased risk of atherothrombosis in these individuals. This review briefly summarizes the evidence of direct and indirect effects of the accumulation of excess lipid in visceral adipose tissue on coagulation and fibrinolysis. In addition, this article critically appraises the rapidly expanding body of experimental and clinical data that support a potential direct contribution for the accumulation of excess lipid in the liver (i.e., nonalcoholic fatty liver disease, a very frequent pathological condition in subjects with abdominal obesity) in the pathogenesis of the obesity-induced disorders of coagulation and fibrinolysis.

Serum Androgens Are Independent Predictors of Insulin Clearance but Not of Insulin Secretion in Women With PCOS.

CONTEXT/OBJECTIVE: In insulin-resistant individuals, hyperinsulinemia is a key compensatory mechanism, aimed at maintaining glucose homeostasis. Increased secretion and reduced clearance of insulin may both potentially contribute to this phenomenon. Insulin resistance and hyperinsulinemia are common findings in women with polycystic ovary syndrome (PCOS). While there is some information on insulin secretion, very few studies have investigated metabolic clearance rate of insulin (MCRI) in these women. Moreover, there is paucity of data on the relationships between MCRI and the pathophysiological characteristics of PCOS. The aim of the study was to explore these issues. PATIENTS: One hundred ninety women with PCOS, diagnosed according to the Rotterdam criteria, with normal glucose tolerance. DESIGN: Assessment of MCRI and clinical, hormonal, and metabolic characteristics of subjects. MCRI and insulin sensitivity were measured by the hyperinsulinemic euglycemic clamp. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis. A historical sample of healthy women was used to define the corresponding reference intervals. RESULTS: MCRI was impaired in about two-thirds of women with PCOS. Subjects with low MCRI differed from those with normal MCRI for a number of anthropometric, metabolic, and endocrine features. In multivariate analysis, the degree of adiposity, estimates of insulin secretion, and serum androgen concentrations were independent predictors of MCRI. Conversely, age, adiposity, MCRI, and insulin sensitivity, but not serum androgens, were independent predictors of insulin secretion. CONCLUSIONS: In women with PCOS, metabolic clearance of insulin is reduced, contributing to generating hyperinsulinemia. Serum androgens are independent predictors of this phenomenon.

Effects of Aerobic and Resistance Training on Circulating Micro-RNA Expression Profile in Subjects With Type 2 Diabetes.

CONTEXT: Structured exercise programs are of great benefit for the treatment of type 2 diabetes (T2DM). However, whether aerobic (AER) or resistance (RES) exercise training exerts specific epigenetic changes through the expression profile of circulating miRNAs (c-miRNAs) is still largely unknown. OBJECTIVE: To assess whether the c-miRNAs profile changes after either AER or RES training in subjects with T2DM. DESIGN: Twenty-four patients with T2DM randomized to AER or RES training protocols were randomly selected from the Resistance vs. Aerobic Exercise in Type 2 Diabetes (RAED2) Trial (NAER = 12; NRES = 12). The baseline and post-training levels of 179 c-miRNAs were initially measured by RT-PCR in 6 individuals (NAER = 3; NRES = 3). C-miRNAs exhibiting ≥40% fold change variation and/or nominal significance from baseline were measured in the whole group. RESULTS: Nineteen c-miRNAs were eventually assessed in the whole group. Compared with baseline, the post-training levels of miR-423-3p, miR-451a, and miR-766-3p were significantly up-regulated, irrespective of exercise type (P < 0.0026; 0.05/19), and targeted upstream pathways relevant to fatty acids biosynthesis and metabolic regulation. MiR-451a and miR-423-3p were significantly correlated with fat loss (ρ = 0.45 and 0.43, respectively) and resulted, alone or in combination, in being predictors of fat loss in generalized linear regression models including exercise type as covariate. Only the association with miR-451a eventually retained significance after further correction for age, sex, body mass index, and HbA1c. CONCLUSIONS: Exercise training in T2DM is associated with substantial c-miRNAs profile changes, irrespective of exercise type and other relevant metabolic covariates. The mechanistic significance of the observed relationship between fat loss and the epigenetic modifications induced by exercise warrants further investigation in larger datasets.