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

Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome

Context/Objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women. Patients/Design: A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique. Results: Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030). Conclusions: There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group

Comparison of plasma lipids changes after middle-distance running in euglycemic and diabetic subjects

Background: Although regular performance of aerobic physical exercise is pivotal for preserving or improving health and fitness, scarce information is available on plasma lipids changes after middle-distance running in euglycemic and diabetic subjects. Methods: Eleven male euglycemic amateur runners (mean age 41\ub16 years) and 9 male diabetic amateur runners (4 with type 1 and 5 with type 2 diabetes; mean age 55\ub114 years) participated to a 21.1-km running trial. All subjects belonged to an amateur running team, regularly engaged in amateur running. Blood was collected before the start of the trial and immediately after. The lipid profile, encompassing measurement of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), was assayed with Roche Cobas 6000. Results: All athletes successfully completed the 21.1-km running trial, with running pace comprised between 9.6\u201312.8 km/h. In both categories of subjects the values of LDL-C significantly decreased by approximately 6% after the run, whilst HDL-C and triglycerides significantly increased by 6\u20139% and 30\u201336%, respectively. The post-run variations of all lipoprotein fractions after the running trial were virtually identical in diabetic and euglycemic subjects. Conclusions: The results of this study show for the first time that middle-distance running elicits acute favorable changes of lipid profile both in euglycemic and diabetic subjects. This form of endurance exercise shall hence be further fostered for purposes of public health promotion and improvement

Comparison between dual-energy X-ray absorptiometry and skinfold thickness in assessing body fat in overweigh/obese adult patients with type-2 diabetes

Percentage of body fat (%BF) is estimated in clinical practice using anthropometric equations, but little is known about their reliability in overweight/obese patients with type-2 diabetes. The aim of this study was to compare, in overweight/obese adults with type-2 diabetes, %BF estimated with several commonly used anthropometric equations and %BF measured with dual-energy X-ray absorptiometry (DXA, Hologic). The %BF was measured with DXA in 40 patients aged 40-68 years with type-2 diabetes (mean HbA1c, 7.3\u2009\ub1\u20090.9%). Body density was estimated in the same patients by means of four anthropometric equations and converted to %BF using the Siri and Brozek equations. Paired-sample t-test and the mean signed difference procedure were used to compare anthropometric equation-derived %BF and DXA measurements. The coefficient of determination was computed. Bland-Altman analysis was used to test the agreement between methods. Among the four anthropometric equations, the Durnin-Womersley equation only showed close agreement with DXA in both female and male patients; the other equations significantly underestimated or overestimated %BF. Two new predictive equations were developed using DXA as the reference to predict total body and trunk %BF. Further comparative studies are required to confirm and refine the accuracy of practical, non-invasive methods for monitoring %BF in this population

Association of free-living physical activity measures with metabolic phenotypes in type 2 diabetes at the time of diagnosis. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)

Objective: Lifestyle is considered a major determinant of risk of type 2 diabetes (T2D). We investigated whether daily physical activity (DPA) is associated with beta-cell function (BF) and/or insulin sensitivity (IS) in patients with T2D at the time of diagnosis. Methods: In 41 subjects enrolled in the Verona Newly-Diagnosed Type 2 Diabetes Study we assessed: (1) IS, by euglycaemic insulin clamp; (2) BF, estimated by prolonged-OGTT minimal modeling and expressed as derivative and proportional control; (3) DPA and energy expenditure (EE), assessed over 48-hours monitoring by a validated wearable armband system. Results: Study participants (median[IQR]; age: 62 [53-67] years, BMI: 30.8 [26.5-34.3] Kg c5m-2, HbA1c: 6.7 [6.3-7.3]%; 49.7 [45.4-56.3] mmol/mol) were moderately active (footsteps/day: 7,773 [5,748-10,927]; DPA 653MET: 70 [38-125] min/day), but none of them exercised above 6 metabolic equivalents (MET). EE, expressed as EETOT (total daily-EE) and EE 653MET (EE due to DPA 653MET) were 2,398 [2,226-2,801] and 364 [238-617] Kcal/day, respectively. IS (M-clamp 630 [371-878] \u3bcmol/min/m2) was positively associated with DPA and EE, independent of age, sex and BMI (p&lt;0.05). Among the DPA and EE parameters assessed, DPA 653MET and EETOT were independent predictors of IS in multivariable regression analyses, adjusted for age, sex, BMI (R2=16%, R2=19%, respectively; p&lt;0.01). None of model-derived components of BF was significantly associated with DPA or accompanying EE. Conclusions Our study highlighted moderate levels of DPA and total EE as potential determinants of IS, but not BF, in T2D at the time of diagnosis. Intervention studies are needed to conclusively elucidate the effect of DPA on these features

Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism

Context: Metabolic inflexibility, ie, the impaired ability of the body to switch from fat to carbohydrate oxidation under insulin-stimulated conditions, is associated with insulin resistance. This alteration in metabolic plasticity can lead to organ dysfunction and is considered a key issue among the abnormalities of the metabolic syndrome. It is still unknown whether this phenomenon occurs in women with polycystic ovary syndrome (PCOS). Objective: Our objective was to examine whether metabolic inflexibility is a feature of PCOS women and whether hyperandrogenism may contribute to this phenomenon. Design and Patients: Eighty-nine Caucasian women with PCOS were submitted to hyperinsulinemic-euglycemic clamp. Respiratory exchange ratios were evaluated at baseline and during hyperinsulinemia by indirect calorimetry to quantify substrate oxidative metabolism. Total testosterone was measured by liquid chromatography mass spectrometry and free testosterone by equilibrium dialysis. Setting: Outpatients were seen in a tertiary care academic center. Main Outcome Measure: Metabolic flexibility was assessed by the change in respiratory quotient upon insulin stimulation. Results: Sixty-five of the 89 PCOS women(73%) had increased serum free testosterone, 68 (76%) were insulin resistant, and 62 (70%) had an impaired metabolic flexibility. Comparison of hyperandrogenemic and normoandrogenemic women showed that the 2 subgroups were of similar age but differed in terms of several anthropometric and metabolic features. In particular, hyperandrogenemic women had greater body mass index (32.9 +/- 1.0 vs 24.7 +/- 0.9 kg/m(2), P < .001) and lower glucose utilization during the clamp (9.2 +/- 0.4 vs 10.9 +/- 0.7 mg/kg fat-free mass . min, P < .023) and metabolic flexibility (0.09 +/- 0.06 vs 0.12 +/- 0.01, P < .014). In univariate analysis, metabolic flexibility was associated with several anthropometric, endocrine, and metabolic features. In multivariate analysis, this feature was directly associated with baseline respiratory quotient and insulin sensitivity and inversely with free testosterone and free fatty acids concentrations under insulin suppression (R-2 = 0.634, P < .001). Conclusions: Metabolic inflexibility is a feature of PCOS women. Both insulin resistance and androgen excess might contribute to this abnormality

Insulin Resistance and Polycystic Ovary Syndrome

Background: Insulin resistance and the associated compensatory hyperinsulinemia are common findings in women with PCOS, and may play a key role in this condition. Methods: In this article, we focused on the significance of insulin resistance in PCOS, reviewing the available literature on epidemiology, pathogenesis, pathophysiology and treatment of this condition. Results: It has been estimated that approximately 70% of these women are insulin resistant, but this figure is affected by frequent referral bias. In addition, there is metabolic heterogeneity between clinical phenotypes of PCOS. A fundamental issue is the role that hyperinsulinemia plays in androgen overproduction, which is enhanced by bidirectional links between insulin resistance and hyperandrogenism. Available data suggest that women with PCOS may have insulin action alterations of heterogeneous origins, which induce specific abnormalities in these subjects due to the presence of intrinsic defects. Obesity is a common finding in these patients and contributes to the association between PCOS and insulin resistance, combining with the effect of PCOS per se. Insulin sensitization shows several beneficial effects in the treatment of this condition. However, clinical response is heterogeneous. Conclusion: Insulin resistance is a common feature of women with PCOS, although it is not universal and differ between clinical phenotypes of PCOS. Insulin resistance and hyperandrogenism appear to be interrelated key factors in the pathogenesis of PCOS. We hypothesize that PCOS might represent a common end-stage clinical phenotype of different processes, in which there are impaired insulin action and hyperandrogenism, probably favoured by specific, intrinsic abnormalities of these women

Insulin resistance: what is its role in PCOS?

Insulin resistance and associated hyperinsulinemia are common features of polycystic ovary syndrome (PCOS). There is evidence that hyperinsulinemia, in susceptible individuals, may play a major pathogenetic role by increasing free androgen levels. However, it remains unclear whether these alterations are primary or secondary defects. Increased exposure to androgens may contribute to impairing insulin action, generating vicious cycles in which it is difficult to recognize the initial defect. Moreover, distinct genetic and environmental mechanisms may be responsible for insulin resistance in different individuals. These women show several risk factors of cardiovascular disease, typically associated with insulin resistance. Recent data support the hypothesis of increased cardiovascular risk in these women, but there is still no definite proof of this. Large prospective studies should assess whether cardiovascular risk actually increases in these women, focusing on the specific role of insulin resistance and associated features in this phenomenon

Pathophysiology of physical exercise [Fisiopatologia dell’esercizio fisico]

L’esercizio fisico rappresenta un potente fattore di perturbazione dell’equilibrio omeostatico dell’organismo, con numerosi effetti favorevoli e alcuni potenziali inconvenienti sullo stato di salute. Fra gli effetti più rilevanti ci sono quelli sul metabolismo glucidico e lipidico. Una singola sessione di esercizio determina vari effetti insulino-simili, anche se questi derivano in gran parte dall’attivazione di processi che non sono insulino-mediati. Il training cronico induce invece modificazioni che incrementano la sensibilità tessutale all’insulina, attraverso processi che differiscono, almeno in parte, in base alla specifica tipologia di training adottata. L’attività aerobica induce in particolare modifiche nel fenotipo delle fibre muscolari, nella capacità mitocondriale e nella capillarizzazione muscolare. L’attivazione di PGC-1 alfa rappresenta il fenomeno chiave in questo adattamento. L’attività di forza stimola invece la sintesi proteica e l’ipertrofia muscolare e il meccanismo molecolare principale sembra rappresentato dall’attivazione di mTOR. Per i suoi rilevanti effetti metabolici l’attività fisica regolare rappresenta un importante strumento sia nella prevenzione che nella cura del diabete tipo 2. Tuttavia, occorre tenere presente che le alterazioni metaboliche e la terapia farmacologica possono alterare la capacità di adattamento all’esercizio del paziente diabetico.Exercise has a powerful action in perturbing body homeostasis, with a number of favorable effects and some potential adverse effects. Among the main actions of physical activity there are those on glucose and lipid metabolism. A single bout of exercise induces several insulin-like effects, although they are mostly due to insulin-independent mechanisms. However, regular physical exercise induces chronic adaptations that improve tissue insulin action, through molecular mechanisms which are at least in part related to the specific mode of muscle activation. Aerobic training affects fibre phenotype, mitochondrial capacity and muscle capillarity, mainly due to PGC-1 alpha activation. Resistance training induces protein synthesis and muscle hypertrophy, through mTOR activation. Due to its major metabolic effects, regular exercise is a fundamental tool in both prevention and treatment of type 2 diabetes mellitus. However, metabolic abnormalities and anti-diabetic therapy may impair the capacity of adaptation to exercise in diabetic patients