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The high cardiometabolic risk associated with polycystic ovary syndrome (PCOS) may be linked to central fat accumulation. This study compared fat distribution between women with PCOS and controls matched by body mass index. It also sought to determine if insulin resistance (IR), androgens, or inflammatory markers correlate with body composition parameters in PCOS patients. In total, thirty-five women with PCOS and 37 controls, aged 18-40 years, were included. Hormonal/metabolic profiles, inflammatory biomarkers [tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6)], anthropometry (waist circumference, waist-to-hip ratio, lipid accumulation product [LAP], visceral adiposity index [VAI]), and body composition assessed through dual-energy X-ray absorptiometry were assessed. The PCOS group exhibited significantly higher androgen levels and markers of IR. However, levels of TNF-α and IL-6 were comparable between the groups. Despite having similar total body fat mass (FM), the PCOS group had excessive central fat, including increased truncal FM and visceral adipose tissue (VAT). In PCOS, androgens were not associated with body fat or its distribution. IL-6 was positively correlated with total and truncal FM, while insulinemia and the homeostatic model assessment for IR were positively associated with VAT, as well as with total and truncal FM. Although anthropometric measurements and indices were positively associated with DXA-derived central FM parameters, our data suggest that LAP is the most effective tool for assessing central fat deposition and metabolic dysfunction in the PCOS patients studied herein. Furthermore, in this population, IR, rather than androgens or proinflammatory cytokines, is more closely associated with abdominal obesity., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Obesity poses a significant global health challenge, given its association with the excessive accumulation of adipose tissue (AT) and various systemic disruptions. Within the adipose microenvironment, expansion and enrichment with immune cells trigger the release of inflammatory mediators and growth factors, which can disrupt tissues, including bones. While obesity's contribution to bone loss is well established, the direct impact of obese AT on osteoblast maturation remains uncertain. This study aimed to explore the influence of the secretomes from obese and lean AT on osteoblast differentiation and activity., Methods: SAOS-2 cells were exposed to the secretomes obtained by culturing human subcutaneous AT from individuals with obesity (OATS) or lean patients, and their effects on osteoblasts were evaluated., Results: In the presence of the OATS, mature osteoblasts underwent dedifferentiation, showing an increased proliferation accompanied by a morphological shift towards a mesenchymal phenotype, with detrimental effects on osteogenic markers and the calcification capacity. Concurrently, the OATS promoted the expression of mesenchymal and adipogenic markers, inducing the formation of cytoplasmic lipid droplets in SAOS-2 cells exposed to an adipogenic differentiation medium. Additionally, TGF-β1 emerged as a key mediator of these effects, as the OATS was enriched with this growth factor., Conclusions: Our findings demonstrate that obese subcutaneous AT promotes the dedifferentiation of osteoblasts and increases the adipogenic profile in these cells.

Competing Interests: The authors have no multiplicity of interest to disclose.

Purpose: Not all patients who underwent bariatric surgery keep their regular medical follow-up. We screened alcohol use, depressive symptoms, and health-related quality of life (HRQoL) in post-bariatric patients who have lost medical follow-up at their first appointment in our healthcare unit. These screened disorders were compared between low vs. high ratios of weight regain (RWR) and correlated with surgical outcomes., Material and Methods: Ninety-four post-bariatric patients without medical follow-up (87.2% female, aged 42 ± 9 years, BMI = 32.9 ± 6.5kg/m 2 ) were included. They underwent Roux-en-Y gastric bypass (n = 80) or sleeve gastrectomy (n = 14). They were divided into high RWR (≥ 20%) and low RWR (< 20%) groups. We used Alcohol Use Disorders Inventory Test, Beck Depression Inventory, and 36-Item Short-Form Health Survey., Results: Neck and waist circumferences, diastolic blood pressure, and time since surgery were higher in the high than low RWR group (P≤ 0.05). No differences between groups for alcohol use and depressive symptoms were detected (P≥ 0.07), but those who regained more weight exhibited poorer health scores in physical functioning, physical role limitations, bodily pain, and vitality (P≤ 0.05). In the low RWR group, the RWR was inversely correlated to physical/social functioning and vitality. Positive associations were present between RWR vs. depressive symptoms, while negative ones were noted to physical functioning and general health perception in the high RWR group., Conclusions: HRQoL has deteriorated in those post-bariatric patients without medical follow-up who regained more weight, possibly indicating the need for regular long-term health care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We investigated the biological behavior of ghrelin and glucagon-like peptide-1 (GLP-1) after a standard liquid meal according to body adiposity and glucose homeostasis., Subjects and Methods: This cross-sectional study included 41 individuals (92.7% women; aged 38.3 ± 7.8 years; BMI 32.2 ± 5.5 kg/m 2 ) allocated into three groups according to body adiposity and glucose homeostasis, as follows: normoglycemic eutrophic controls (CON, n = 11), normoglycemic with obesity (NOB, n = 15), and dysglycemic with obesity (DOB, n = 15). They were tested at fasting and 30 and 60 min after the ingestion of a standard liquid meal in which we measured active ghrelin, active GLP-1, insulin, and plasma glucose levels., Results: As expected, DOB exhibited the worst metabolic status (glucose, insulin, HOMA-IR, HbA1c) and an inflammatory status (TNF-α) at fasting, besides a more significant increase in glucose than postprandial NOB ( p ≤ 0.05). At fasting, no differences between groups were detected in lipid profile, ghrelin, and GLP-1 ( p ≥ 0.06). After the standard meal, all groups exhibited a reduction in ghrelin levels between fasting vs. 60 min ( p ≤ 0.02). Additionally, we noticed that GLP-1 and insulin increased equally in all groups after the standard meal (fasting vs. 30 and 60 min). Although glucose levels increased in all groups after meal intake, these changes were significantly more significant in DOB vs. CON and NOB at 30 and 60 min post-meal ( p ≤ 0.05)., Conclusion: Time course of ghrelin and GLP-1 levels during the postprandial period was not influenced by body adiposity or glucose homeostasis. Similar behaviors occurred in controls and patients with obesity, independently of glucose homeostasis.

Weight loss after bariatric surgery in obesity improves vascular function and metabolic/inflammatory profiles and reduces cardiovascular mortality but there are limited data on the effects of weight regain on vascular health. We compared the metabolic/inflammatory profiles, oxidative status, and vascular function of post-bariatric patients with a high ratio of weight regain (RWR) vs. non-surgical controls. Thirty-two post-bariatric patients [Roux-en-Y gastric bypass; aged = 44 ± 8 years, BMI = 40.1 ± 7.7 kg/m 2 , and RWR = 58.7 ± 24.3%] and thirty controls that were BMI-, age-, and gender-matched entered the study. We collected clinical data, metabolic/inflammatory/oxidative stress circulating biomarkers, and endothelial/microvascular reactivity through Venous occlusion plethysmography and Laser speckle contrast imaging. The bariatric group exhibited lower neck circumference, fasting glucose, and triglycerides than the non-surgical group, while HDL-cholesterol was higher in the bariatric group ( p < 0.001). There was no significant difference between groups for endothelial/microvascular reactivities ( p ≥ 0.06). Resistin, leptin, endothelin-1, soluble forms of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, tumor necrosis factor-α, and thiobarbituric acid reactive substances did not differ significantly between groups ( p ≥ 0.09) either. The adiponectin level was higher in the bariatric compared to the non-surgical group, while interleukin-6 was lower in the bariatric group ( p < 0.001). Despite the fact that endothelial/microvascular functions were not significantly different between groups, post-bariatric patients present partially preserved metabolic/inflammatory benefits even with high RWR.

Background: It is known that consuming a high-fat meal (HFM) induces microvascular dysfunction (MD) in eutrophic women and aggravates it in those with obesity. Our purpose was to investigate if the MD observed after a single HFM intake is caused by endothelial damage or increased inflammatory state, both determined by blood biomarkers., Methods: Nineteen women with obesity (BMI 30-34.9 kg/m 2 ) and 18 eutrophic ones (BMI 20.0-24.9 kg/m 2 ) were enrolled into two groups: Obese (OBG) and Control (CG), respectively. Blood samples were collected at five-time points: before (fasting state) and 30, 60, 120, and 180 min after HFM intake to determine levels of adipokines (adiponectin, leptin), non-esterified fatty acid (NEFA), inflammatory [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] and endothelium damage [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1)] biomarkers., Results: Levels of soluble E-selectin, leptin, and PAI-1 were higher in OBG at all-time points (P < 0.05) compared to CG. In the fasting state, OBG had higher levels of NEFA compared to CG (P < 0.05). In intra-group analysis, no significant change in the levels of circulating inflammatory and endothelial injury biomarkers was observed after HFM intake, independently of the group., Conclusion: Our findings suggest that women with obesity have an increased pro-inflammatory state and more significant endothelial injury compared to eutrophic ones. However, the consumption of a HFM was not sufficient to change circulating levels of inflammatory and endothelial injury biomarkers in either group., Registration Number for Clinical Trials: NCT01692327., (© 2022. The Author(s).)

Background: Evidence of the benefits induced from resistance exercise on health markers of post-bariatric patients is limited. The study will investigate the effects of a resistance training (RT) program on muscle mass and strength, bone metabolism biomarkers, bone mineral density (BMD), bone microarchitecture, and endothelial function of patients subjected to Roux-en-Y gastric bypass., Methods/design: This randomized controlled trial will include 60 post-bariatric patients, physically inactive, aging 18 to 50 years, with a post-surgery period ≥ 12 months. They will be randomly assigned into two groups: (i) the non-exercised control group, which will receive the standard clinical follow-up, or (ii) the intervention group which will consist of RT (60 min/session; 3 times/week, for 6 months). The primary outcomes will include muscle mass and strength, bone metabolism biomarkers, BMD, and bone microarchitecture. The secondary outcomes will be anthropometry, hemodynamic measurements, cardiovascular risk factors, health-related quality of life (QoL), and endothelial function. Outcomes will be assessed by blood biomarkers of bone formation and reabsorption, dual X-ray absorptiometry, repetition maximum and handgrip strength tests, high-resolution peripheral quantitative computed tomography, 36-Item Short-Form Health Survey, venous occlusion plethysmography, and nailfold videocapillaroscopy., Discussion: It is expected that there are greater benefits from the RT program, possibly improving muscle mass and strength, bone metabolism, density and microarchitecture, QoL, and cardiovascular risk., Trial Registration: ClinicalTrials.gov NCT04193397. Registered on 7 December 2019., (© 2022. The Author(s).)

Purpose: We aimed to study the occurrence of long-term changes in appetite, taste, smell perceptions, and food aversion in patients following bariatric surgery. Additionally, we compared two surgery types, excess weight loss, rate of weight regain, and time since surgery., Methods: This cross-sectional study included 146 post-bariatric patients who were without regular medical follow-up (126 post-Roux-en-Y gastric bypass [RYGB] and 20 post-sleeve gastrectomy [SG]), aged 42 ± 8 years, BMI of 32.6 ± 6.3 kg/m 2 , with excess weight loss of 87.5 ± 20.2%, rate of weight regain (RWR) of 15.4 [3.9-30.9]% and time since surgery of 5.0 ± 4.0 years. They answered a questionnaire about sensory and food perceptions at their first medical appointment at our unit., Results: Changes in appetite (76%), taste (48.6%), and an increased sensation for sweet taste (60.2%) frequently occurred in our sample. Sensory and food aversion perceptions, taste changes to specific foods, and loss level of taste and smell were similar between RYGB and SG. No differences between patients with or without changes in appetite, taste, smell, and food aversion perceptions concerning excess weight loss were observed. The RWR in post-RYGB was lower in those with changes in taste and smell (P = 0.05). Sensory changes were noted in those with shorter time since surgery for both surgeries (P ≤ 0.05)., Conclusion: Changes in appetite and taste occurred frequently in our patients even in the long term. Post-RYGB patients with lower RWR had more changes in taste and smell while a shorter time since surgery showed more frequent changes in appetite, taste, and smell., Level of Evidence: Level V, cross-sectional study., Trial Registration Number: ClinicalTrials.gov (NCT04193384)., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Bariatric surgery promotes expressive weight loss, improving the metabolic and inflammatory profiles. The behavior of these indicators in bariatric patients with weight recidivism is unknown. We aimed to investigate both profiles in bariatric patients with high ratio of weight regain (RWR), comparing them with nonsurgical patients with obesity., Methods: Forty patients with obesity subjected to Roux-en-Y gastric bypass (RYGB) with high RWR composed the bariatric group, and 40 controls matched for BMI, age, and gender were recruited as nonsurgical group. Between-group comparisons were performed for clinical history, physical examination, biochemical, metabolic, and inflammatory profiles., Results: Bariatric group was composed of a group with an excess weight loss of 85.9 ± 16.8%, a RWR of 56.5 ± 19.7%, and a time since surgery of 10.7 ± 4.3 years. We noticed a lower proportion of patients with type 2 diabetes mellitus and dyslipidemia (P ≤ 0.05) and lower neck and waist circumferences (P ≤ 0.05) in this group. No differences between groups were observed concerning hip circumference, blood pressure, heart rate, total cholesterol, LDL-c, acid uric, creatinine, ALT, ASP, interferon-γ (INF-γ), interferon gamma-induced protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), TNF-α, interleukin-1β (IL-1 β), interleukin-17 (IL-17), and interleukin-10 (IL-10). Of note, fasting glucose; HbA1c; triglycerides; and, surprisingly, IL-6 levels were lower (P ≤ 0.05) in the bariatric group than nonsurgical one while HDL-c level was higher (P < 0.001)., Conclusion: Expressive post-bariatric weight loss, even in patients with high RWR, suggests a possible metabolic benefit/protection in the long term. Probably decreased circulating levels of IL-6 are involved in it., Trial Registration: NCT04193397., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The impact of regular exercises or physical activity (PA) on weight of bariatric patients need to be elucidated. We investigated PA levels, sedentary time (ST), and weight regain on these patients who were without regular medical follow-up before recruitment. Moreover, we investigated correlation and concordance between self-reported and objective measures in moderate-to-vigorous PA (MVPA) and ST., Materials and Methods: We invited 132 patients previously subjected to a bariatric procedure to a medical appointment in our unit and proposed them to be volunteers. Ninety patients, aged 42 ± 8 years and BMI 32.9 ± 6.6 kg/m 2 , entered the study and were allocated into groups according to time since surgery < or ≥5 years (G5- or G5+, respectively). They were further assigned into low or high rates of weight regain (RWR; cutoff 20%). PA and ST were measured by International PA Questionnaire (IPAQ) and ActiGraph GT3X+ accelerometer., Results: In G5- group, PA and ST were similar between low and high RWR. In G5+ group, MVPA time, number of steps/day, percent of patients somewhat active, and 30-60 min/day of MVPA were statistically higher in those with low RWR. Of note, measures of MVPA < 30 min/day occurred more frequently in those with high RWR. MVPA and ST self-reported vs. objective measures were correlated (P < 0.001). Nevertheless, there was no concordance between these measures (P > 0.05)., Conclusions: Low level of PA and longer ST occurred more frequently in those with high RWR and longer time since surgery. Although well-correlated, any concordance between IPAQ and accelerometer measures was noted.

Purpose: Data on endothelial derangements in patients with non-functioning adrenal incidentaloma (NFAI) are scarce., Methods: We investigated if NFAI patients present clinical, biochemical and endothelial alterations compared to individuals without an adrenal lesion and also the associations among these variables. Forty-two NFAI and 40 controls were evaluated. NFAI diagnosis and controls were defined according to the current guidelines and based on a normal adrenal imaging exam, respectively. Body composition was evaluated by dual emission X-ray absorptiometry. Endothelial reactivity was assessed by two methods: tonometry (Endo-PAT ® ) and laser speckle contrast imaging (LSCI)., Results: There were no differences between groups regarding age, gender, ethnicity, smoking status, and statin use. The frequency of metabolic syndrome according to the International Diabetes Federation criteria was 69% and 57.9%, respectively in NFAI and controls (p = 0.36), whereas the atherosclerotic cardiovascular disease (ASCVD) risk was 63.4% and 66.7% (p = 0.81). The clinical, laboratory, and anthropometric characteristics, as well as body composition, were similar between the groups. Additionally, any differences between groups were observed on endothelial reactivity tests. Nevertheless, we noted an association between cortisol levels after 1 mg-dexamethosone suppression test (1 mg-DST) and the duration of post-occlusive reactive hyperemia tested on microcirculation (r = 0.30; p = 0.03). NFAI patients require more antihypertensive drugs to achieve blood pressure control (p = 0.04). The number of antihypertensive drugs used to control blood pressure correlated with cortisol levels after 1 mg-DST (r = 0.29; p = 0.03)., Conclusions: Since both groups herein investigated had a high frequency of metabolic syndrome and ASCVD risk, it might explain similarities observed on endothelial reactivity. Nevertheless, prolonged reactive hyperemia response on microcirculation was correlated with cortisol levels under suppression.

Background: In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events., Objective: To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation., Methods: 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP)., Results: Red blood cell velocity (RBCV) before and after ischemia (RBCVmax) were significantly lower in patients with INOCA (p = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax) was significantly longer in INOCA group (p = 0.0004). Concerning VOP, maximal blood flow (p = 0.004) and its relative increment were significantly lower in patients with INOCA (p = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r = -0.38, p < 0.05), ET-1 (r = -0.73, p < 0.05) and CRP (r = -0.33, p < 0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r = -0.42, p < 0.05) and ET-1 (r = -0.48, p < 0.05)., Conclusions: The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation.

Background: Bariatric surgery induces weight loss, but changes in glucose metabolism, gut peptides, and inflammatory biomarkers still have conflicting results., Settings: University hospital., Objectives: We investigated glucose metabolism, gut hormones, and inflammatory profile after bariatric surgery and medical treatment., Methods: Forty patients with obesity were recruited and were subjected to Roux-en-Y gastric bypass (n = 15; Bariatric Surgery Group - BSG) or received medical care (n = 20; MG). Sleeve gastrectomy was performed in five patients who were excluded from analysis. Glucose, insulin, homeostatic model for the assessment of insulin resistance (HOMA-IR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon, ghrelin, dipeptidyl peptidase-4 (DPP-4) activity, circulating lipopolysaccharide (LPS), LPS-binding protein (LPB) and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and three months after each treatment. Except for HOMA-IR, hs-CRP, and LBP, all variables were assessed at fasting and 30- and 60-minutes after a standard meal., Results: After 3 months, both groups lost weight. However, BSG had a more extensive reduction than MG (respectively, 17.6% vs. 4.25%; P < 0.01). Except for LPS levels, higher on BSG than MG (1.38 ± 0.96 vs. 0.83 ± 0.60 EU/ml, P < 0.01), groups were similar before treatment. In respect to metabolic/hormonal changes, the BSG showed higher glucose, insulin, GLP-1, and GIP levels at 30-min and also GLP-1 at 30- and 60-minutes. DPP-4 activity, HOMA-IR, and fasting LBP did not change. LPS levels at 60-minutes decreased after surgery in the BSG. hs-CRP decreased on BSG compared to MG., Conclusions: Bariatric surgery resulted in more extensive effects on glucose metabolism, gut hormones, and inflammation., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Neurally mediated anticipatory responses, also named cephalic-phase responses, and microcirculatory regulation are two important mechanisms to maintain metabolic homeostasis. Altered cephalic-phase responses in obesity and its metabolic consequences have been proposed. There is, however, a lack of studies focusing on in vivo assessment of the microcirculation during this phase in patients with obesity. In this randomized controlled trial, we selected patients with obesity and healthy subjects after clinical and laboratory assessments. Those with obesity were randomized into two groups: experimental (cephalic-phase microvascular response stimulation - CP group, n = 13) and controls (n = 14). Healthy subjects (n = 17) were also included to form a CP control group. Skin microvascular assessment was used as a model of systemic microcirculation. Resting functional capillary density (FCD) and peak FCD during post-occlusive reactive hyperemia (PORH) were measured by dorsal finger videocapillaroscopy and expressed mainly capillary recruitment capacity. Resting red blood cell velocity (RBCV), peak RBCV during PORH (RBCV max ), and time taken to reach RBCV max (TRBCV max ) were assessed by dynamic nailfold videocapillaroscopy and expressed the microhemodynamics. Patients with obesity (with or without stimulus) failed to show an increase on FCD during PORH post-stimulus (p = 0.221 and p = 0.307, respectively) depicting lack of capillary recruitment. In contrast, healthy subjects presented an increase in this microvascular outcome (p = 0.004). Changes in all variables of microhemodynamics occurred in both CP groups (healthy and those with obesity). During CP, we originally demonstrated an absence of capillary recruitment in subjects with obesity. These findings might contribute to the literature of microvascular impairment and metabolic conditions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes mellitus and obesity are both related to endothelial dysfunction. Postprandial lipemia is a cardiovascular risk. Notably, it is known that a high-fat diet may elicit microvascular dysfunction, even in healthy subjects. Since anti-diabetic drugs have different mechanisms of action and also distinct vascular benefits, we aimed to compare the results of two anti-diabetic drugs after the intake of a lipid-rich meal on microcirculation in patients with type 2 diabetes and obesity. In parallel, we also investigated the metabolic profile, oxidative stress, inflammation, plasma viscosity, and some gastrointestinal peptides., Subjects/methods: We included 38 drug-naïve patients, all women aged between 19 and 50 years, with BMI ≥ 30 kg/m 2 . We performed endothelial measurements and collected samples before (fasting) and after the intake of a lipid-rich meal at 30, 60, 120, and 180 min. Patients were randomized to metformin or vildagliptin, given orally just before the meal. Endothelial function was assessed by videocapillaroscopy and laser-Doppler flowmetry to investigate microvascular reactivity. Besides, we also investigated plasma viscosity, inflammatory and oxidative stress biomarkers, gastrointestinal peptides, and metabolic profile in all time points., Results: No differences at baseline were noted between groups. Vildagliptin increased glucagon-like peptide-1 compared to metformin. Paired comparisons showed that, during the postprandial period, vildagliptin significantly changed levels of insulin and glucagon-like peptide-1, and also the dipeptidyl peptidase-4 activity, while metformin had effects on plasma glucose solely. Metformin use during the test meal promoted an increase in functional capillary density, while vildagliptin kept non-nutritive microvascular blood flow and vasomotion unchanged., Conclusions: After the intake of a lipid-rich meal, the use of vildagliptin preserved postprandial non-nutritive microflow and vasomotion, while metformin increased capillary recruitment, suggesting protective and different mechanisms of action on microcirculation.

We investigated endothelial and autonomic nervous functions after bariatric surgery. For this, we prospectively recruited 40 patients for bariatric surgery or medical treatment (20 in each group). Heart rate variability (HRV) and endothelial function were evaluated before and 3 months after treatments. Glucagon-like peptide 1 (GLP-1), insulin, and glucose at fasting and 30 and 60 min after a standard 300-kcal meal were also analyzed. Surgery but not medical care increased HRV in all time-domain variables, while frequency-domain variables, vascular elasticity, and endothelial reactivity did not change. Changes in GLP-1 and insulin resistance markers did not correlate with HRV. After 3 months, bariatric surgery improved the parasympathetic activity of cardiac autonomic function. Trial registration: NCT03911479.

Background: Obesity is the main risk factor for diabetes and excessive visceral fat triggers low-grade inflammatory process, mediated by activation and release of cytokines and high flow of free fatty acids that contribute to insulin resistance, increased oxidative stress, and impaired endothelial function. Metformin and vildagliptin have known vasculoprotective actions, but the value of these drugs on drug-naïve diabetic patients during 30 days use warrants investigation. Our purpose was to observe their effects on endothelial function, oxidative stress, inflammatory biomarkers, and plasma viscosity., Methods: 38 women with obesity and type 2 diabetes drug-naïve, aged between 19 and 50 years, BMI ≥ 30 kg/m 2 , were recruited and subjected to measurements of endothelial function, nutritive skin microvascular reactivity, plasma viscosity, inflammatory and oxidative stress biomarkers at baseline and randomized 1:1 to ingest metformin (850 mg twice/day) or vildagliptin (50 mg twice/day) during 30 days, and then, re-evaluated., Results: No differences between groups were noticed at baseline. After treatment, vildagliptin promoted an improvement on endothelial-dependent and -independent vasodilatations, at arteriole level, while metformin resulted in improved nutritive microvascular reactivity, at the capillary level. Intragroup analysis showed that vildagliptin reduced insulin, C-peptide and oxidized LDL, and increased adiponectin and glucagon-like peptide-1 while metformin reduced weight, plasma glucose, total cholesterol, HDL-c, LDL-c, and dipeptidyl peptidase-4 activity, with an unexpected increase on tumor necrosis factor-α. No significant difference in plasma viscosity was noted., Conclusions: In the vascular beds investigated, both drugs used for only 30 days improved endothelial function, through distinct, and possibly, complementary mechanisms on drug-naïve diabetic women. Trial Registration ClinicalTrials.gov: NCT01827280., Competing Interests: Competing interestsThe authors declare that they have no competing interests. LGK-A received funds from Novartis S.A. that partially supported this study.

Background: The enzyme dipeptidyl peptidase 4 (DPP4) has been recently recognized as an adipo-myokine. However, studies that associate its constitutive activity with body composition, anthropometry, and insulin resistance (IR) are very scarce and included only healthy people., Methods: First, we investigated the relationships of constitutive DPP4 activity, body composition (assessed by bioelectrical impedance analysis), and measures of adiposity and IR in fifty-two subjects of both sexes, 18-50 years, and BMI ≥25.0 kg/m 2 who comprised three groups according to glucose tolerance. Additionally, we evaluated associations among DPP4 activity and adipokines, gut peptides, and biochemical variables at fasting and 30 and 60 min after a standardized meal intake., Results: DPP4 activity was no different among the three groups. At fasting, pooled analysis showed it was positively correlated with measures of central adiposity, such as WC ( P = 0.011) and WHR ( P = 0.009), and with all measures of IR, but inversely related to indexes of general adiposity, such as fat mass percentage ( P = 0.014) and BAI ( P = 0.0003). DPP4 activity was also associated with lean mass ( r = 0.57, P < 0.0001). After meal intake, DPP4 activity remained significantly associated with insulin, leptin, and resistin. In multiple regression analysis, BAI, WHR, percent lean mass, HOMA-IR, and leptin influenced DPP4 activity and explained approximately 26% of the variance on it., Conclusions: Constitutive DPP4 activity is positively associated with lean mass, central adiposity, and IR and negatively to general adiposity. Furthermore, it seems to be influenced by body composition and IR and could also be viewed as an adipo-myokine in subjects with excessive adiposity and different stages of glucose tolerance.

Prediabetes is the subclinical impairment in fasting plasma glucose, impaired glucose tolerance or both. The degree of impairment is between euglycemia and the hyperglycemia of type 2 diabetes (T2DM). Prediabetes is not considered benign, because it is a risk factor for T2DM but is also associated with micro and macrovascular complications. Lifestyle interventions including diet and exercise are first-line treatments. Medications can also play a role, as randomized controlled trials of biguanides (metformin) alpha-glucosidase inhibitors (Acarbose), inhibitors of pancreatic lipase (Orlistat), PPAR-gamma agonists (Rosiglitazone, Pioglitazone), meglitinides (Nateglinide) and GLP-1 receptor agonists (Liraglutide) have all shown benefits. Bariatric surgery is another efficacious means of preventing T2DM in patients with prediabetes and obesity. Prediabetes in its various guises is a risk factor for the future development T2DM and diabetic complications. Importantly the prediabetic state is amenable to interventions that prevent/delay transition to overt T2DM. Knowledge gaps exist regarding how best to make prognostication highly sensitive and specific as to which patient will develop T2DM. Moreover, understanding of phenotype specific pathophysiology may add value to funding appropriate interventions for patients with prediabetes. Management of patients with prediabetes should be individualized based on the algorithms that predict phenotype specific risk and allow for the use of phenotype tailored interventions.

Background: Frequently, ingestion of lipids exceeds our daily requirements and constantly exposes humans to circulating lipid overload which may lead to endothelial dysfunction (ED), the earliest marker of atherosclerosis. Nailfold videocapillaroscopy (NVC) technique can detect ED on microcirculation. Using NVC, we aimed to demonstrate if metabolic alterations evoked by high-fat meals can act differently on microvascular endothelial reactivity in lean and women with obesity., Methods: Women, aged between 19 and 40 years, were allocated to control group (CG) and with obesity group (OBG) and were subjected to blood analysis for determination of glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) and NVC evaluation at fasting and 30, 60, 120, and 180-min after high-fat meal ingestion. NVC technique evaluated microvascular reactivity through the following variables: red blood cell velocity (RBCV) at rest and after 1-min ischemia (maximal red blood cell velocity, RBCV max ) and time taken to reach it (TRBCV max ). A P value ≤0.05 was considered significant., Results: High-fat meal promoted a two-phase response in both groups: one until 60-min, associated with glucose and insulin levels, and the other after 120-min, associated with TG levels. Significant differences between groups were observed concerning insulin and HDL-c concentrations only at fasting and TC, TG, and LDL-c levels in all-time points. Regarding microvascular reactivity, RBCV, RBCV max , and TRBCV max were significantly different in OBG at 30-min compared to baseline. RBCV max and TRBCV max were significantly different in CG at 30-min and 60-min comparing to fasting. In all-time points, OBG presented RBCV, RBCV max  , and TRBCV max significantly different in comparison to CG., Conclusion: High-fat meal worsened ED on microcirculation in women with obesity and induced impairment of endothelial function in lean ones, reinforcing the association between high-fat meal and atherosclerosis.

Objective: In patients with diabetes, dipeptidyl peptidase 4 (DPP4) inhibition is associated with attenuation of inflammation and endothelial dysfunction. Here, we investigated the associations between constitutive DPP4 activity, inflammatory biomarkers, and microvascular reactivity in subjects with excess body weight without diabetes., Methods: Forty subjects of BMI ≥ 25.0 kg/m 2 and without diabetes were cross-sectionally evaluated. We assessed microvascular blood flow and vasomotion by laser Doppler flowmetry, and measured at baseline, 30, and 60 min after a standardized meal: DPP4 activity, glucose, insulin, hs-CRP, TNF-α, IL-6, PAI-1, ICAM-1, and VCAM-1. HOMA-IR and HOMA-AD were used to assess insulin resistance. Linear correlations of DPP4 activity with the biomarkers of inflammation and components of microvascular function were conducted. In step further, multiple regression analyses were performed to test whether some of these variables could influence, or be influenced by, the plasma DPP4 activity., Results: DPP4 activity was inversely associated with VCAM-1 at baseline (P < 0.05), and DPP4 activity AUC was inversely correlated with the myogenic component AUC of vasomotion (P < 0.05). In multiple regression analysis, HOMA-AD, IL-6, VCAM-1, PAI-1, blood flow, and vasomotion influenced DPP4 activity and explained almost 40% of the variance on it. When HOMA-AD, VCAM-1, and blood flow were placed respectively as dependent variables, DPP4 activity exerted a significant effect in all of them., Conclusions: Constitutive DPP4 activity was associated with early markers of endothelial proinflammatory activation and microvascular function, and may have an influence and even be influenced by inflammation and microvascular blood flow in subjects with excess body weight without diabetes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Previous studies have shown that microvascular dysfunction (MD) is associated with a number of cardiovascular risk factors, including obesity. Few studies have assessed microvascular reactivity in children, and in most of these, results were confounded by the effects of puberty. Our aim was to establish whether MD is already present in obese prepubertal children., Methods: This cross-sectional study included 52 obese, 18 overweight, and 28 eutrophic children, with a mean ± standard deviation age of 7.44 ± 1.22 years. We evaluated cardiovascular risk factors and nutritive microvascular function by using nailfold dynamic videocapillaroscopy and determined functional capillary density (FCD), red blood cell velocity at resting conditions (RBCV) and at peak (RBCV max ), and time to reach peak velocity during the post-occlusive reactive hyperemic response following 1 minute ischemia., Results: On univariate analysis, differences in microvascular reactivity were not observed among the groups. Obese and overweight children had significantly higher scores than eutrophic children for the following parameters: body mass index, waist circumference, waist-to-height ratio, mean arterial pressure, homeostasis model assessment for insulin resistance, levels of insulin, leptin, glucose, triglycerides, total cholesterol, uric acid, and C-reactive protein. Multivariate analysis demonstrated the association between metabolic, anthropometric, and microvascular variables, stratified according to the degree of adiposity and body fat distribution., Conclusions: Univariate analysis did not show any difference in microvascular reactivity between groups but, by testing these variables by multivariate means, we noticed a common and direct variation between cardiovascular/metabolic risk factors and microvascular reactivity occurring early in life.

Leprosy is a chronic granulomatous infection of skin and peripheral nerves caused by Mycobacterium leprae and is considered the main infectious cause of disability worldwide. Despite the several studies regarding leprosy, little is known about its effects on microvascular structure and function in vivo. Thus, we have aimed to compare skin capillary structure and functional density, cutaneous vasomotion (spontaneous oscillations of arteriolar diameter), which ensures optimal blood flow distribution to skin capillaries) and cutaneous microvascular blood flow and reactivity between ten men with lepromatous leprosy (without any other comorbidity) and ten age- and gender-matched healthy controls. Orthogonal polarization spectral imaging was used to evaluate skin capillary morphology and functional density and laser Doppler flowmetry to evaluate blood flow, vasomotion and spectral analysis of flowmotion (oscillations of blood flow generated by vasomotion) and microvascular reactivity, in response to iontophoresis of acetylcholine and sodium nitroprusside. The contribution of different frequency components of flowmotion (endothelial, neurogenic, myogenic, respiratory and cardiac) was not statistically different between groups. However, endothelial-dependent and -independent vasodilatations elicited by acetylcholine and sodium nitroprusside iontophoresis, respectively, were significantly reduced in lepromatous leprosy patients compared to controls, characterizing the existence of microvascular dysfunction. These patients also presented a significant increase in the number of capillaries with morphological abnormalities and in the diameters of the dermal papilla and capillary bulk when compared to controls. Our results suggest that lepromatous leprosy causes severe microvascular dysfunction and significant alterations in capillary structure. These structural and functional changes are probably induced by exposure of the microvascular bed to chronic inflammation evoked by the Mycobacterium leprae.

Objective: The beneficial effects of estrogen on endothelial function depend on its integrity. This study evaluates the short-term effects of low-dose transdermal estradiol on endothelial function, insulin sensitivity, and blood viscosity in nondiabetic overweight/obese women., Methods: Forty-four nondiabetic overweight/obese women with a history of recent menopause were randomly allocated, in a double-blind fashion, to receive transdermal estradiol (1 mg/d, n = 22) or placebo (n = 22). The following parameters were assessed: endothelial reactivity (venous occlusion plethysmography and nailfold videocapillaroscopy), plasma levels of soluble adhesion molecules, insulin sensitivity (homeostasis model assessment of insulin resistance and areas under the curve of insulin and glucose during an oral glucose tolerance test), and blood and plasma viscosity. Data were expressed as means ± SD or medians [first to third quartiles]., Results: Participants were aged 51.8 ± 2.3 years with a body mass index of 31.5 ± 2.5 kg/m and time since menopause was 3 [2-5] years. At baseline, no differences between the groups were observed; however, after 3 months of treatment, the following changes were observed in the estradiol group compared with the placebo group: a decrease in the forearm vascular resistance at baseline (36.37 [24.9-51.27] vs 51.3 [40.88-70.03] mm Hg/mL per min 100 mL tissue, P < 0.01) and during the postocclusive reactive hyperemia response (15.93 [11.32-22.29] vs 22.13 [16.46-29.7] mm Hg/mL per min 100 mL tissue, P < 0.01), and an increase in red blood cell velocity at rest (0.316 [0.309-0.326] vs 0.303 [0.293-0.308] mm/s, P < 0.001) and during postocclusive reactive hyperemia response (0.374 [0.353-0.376] vs 0.341 [0.333-0.355] mm/s, P < 0.001). Furthermore, blood viscosity was lower in the estradiol group than in the placebo group (3.57 ± 0.12 vs 3.76 ± 0.22 mPa.s; P < 0.01)., Conclusions: Short-term use of low-dose transdermal estradiol in nondiabetic overweight/obese women with a history of recent menopause improved endothelial function and decreased blood viscosity compared with placebo.

Purpose: Cardiac autonomic dysfunction (CADysf) in children is often associated to obesity and may be attenuated by physical activity. In this study, we investigated the effects of resistance training (RT) upon CADysf assessed by heart rate variability (HRV) in obese adolescents., Method: Volunteers were assigned into groups according to standard deviation scores for body mass index (z-BMI) and percentile for age and sex: obese (OB; z-BMI from 2 to 3 and ≥ 95th percentile, n = 24) and normal weight controls (CG; z-BMI from -2-1 and < 85th percentile, n = 20). OB performed isolated RT during 12 weeks [3 sets of 6-10reps with 70-85% 10RM]. Waist circumference, systolic/diastolic blood pressures (SBP/DBP), lipids, and HRV were assessed at baseline. Only OB underwent postintervention assessments., Results: At baseline, SBP (122.4 ± 9.1 vs. 109.7 ± 11.5 mmHg, p < .001) and DBP (76.1 ± 7.1 vs. 65.3 ± 5.9 mmHg, p < .001) were higher, while parasympathetic HRV indexes were lower (p < .05) in OB compared with CG. After RT, waist circumference (3%, p < .001) and SBP (10%, p < .001) reduced in OB. Parasympathetic indexes of HRV increased in OB (SDNN: 25%, p = .03; rMSSD: 48%, p = .0006; pNN50: 67%, p = .001; total power: 54%, p = .01; HF: 101%, p = .001) and baseline differences between groups for sympathetic and parasympathetic activities were no longer observed after RT., Conclusion: RT attenuated CAdyfs and BP in obese adolescents, by increasing parasympathetic activity and decreasing sympatho-vagal balance.

Objective: We aimed to investigate the effects of low-dose transdermal estrogen on endothelial and inflammatory biomarkers in menopausal overweight/obese women., Methods: We recruited 44 menopausal women (47-55 years; body mass index 27.5-34.9 kg/m(2)) and divided them into estradiol (1 mg/day; n = 22) or placebo groups (n = 22). They were double-blinded, followed and treated for 3 months. At baseline and post-intervention, inflammatory biomarkers (hs-CRP, IL-1β, IL-6, MCP-1 and TNF-α) and of vascular injury (activated circulating endothelial cells, CEC-a) and repair (endothelial progenitor cells, EPC) were quantified. Resting CECs (CEC-r) were also assessed. Microvascular reactivity and vasomotion were analyzed by laser-Doppler flowmetry., Results: Volunteers (51.8 ± 2.3 years; mean body mass index 31.5 ± 2.5 kg/m(2)) had been menopausal for 3 (range 2-5) years. After treatment, no changes were observed in the placebo group, while levels of CEC-r and EPC increased in the estradiol group. In this group, no changes in inflammatory biomarkers were observed but it required a lower cumulative dose of acetylcholine to achieve peak velocity during endothelial-dependent vasodilatation and there was increased endothelial-independent vasodilatation., Conclusions: The short-term use of low-dose transdermal estradiol therapy in overweight/obese menopausal women increased markers of vascular repair and improved microvascular reactivity without changing the inflammatory biomarkers., Clinical Trial Registration: NCT01295892 at www.clinicaltrials.gov .

Objectives: It has been hypothesized that obesity is the primary cause of microvascular dysfunction (MD), which could be a pathway to increase blood pressure and decrease insulin sensitivity. Due to the high prevalence of this metabolic disorder in the world today, the aim of this study was to investigate which is the most appropriate videocapillaroscopic method, between nailfold and dorsal finger, to assess microvascular function in obese patients since both techniques are non-invasive and could be used for early detection as well as for follow-up., Methods: Eighteen lean [27.8±6.2years, body mass index (BMI) 21.8±1.8kg/m(2)] and nineteen obese (30.8±4.6years; BMI 32.3±1.5kg/m(2)) women participated in the study. Dynamic nailfold videocapillaroscopy assessed morphological (capillary diameters) and functional [functional capillary density (FCD); red blood cell velocity (RBCV) at baseline and peak and time (TRBCVmax) taken to reach it during the post-occlusive reactive hyperemia (PORH) response, after 1-min ischemia] parameters; while dorsal finger videocapillaroscopy assessed FCD at rest and capillary recruitment during PORH and post-venous occlusion., Results: RBCV (0.32±0.01 vs. 0.30±0.01mm/s; p<0.0001) and RBCVmax (0.32±0.01 vs. 0.30±0.015mm/s; p=0.0020) were significantly higher in control subjects compared to the obese group. Moreover, TRBCVmax was prolonged in the obese group compared to control one (3.5±1.4 vs. 5.5±1.3s; p=0.0001). Multiple regression analysis showed that these variables were influenced by some others, especially those related to adiposity and metabolic disease. On the other hand, dorsal finger videocapillaroscopy did not show any significant differences between groups., Conclusion: Our results strongly suggest that microvascular dysfunction consequent to obesity could be better detected by dynamic nailfold videocapillaroscopy than by dorsal finger videocapillaroscopy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Obesity is a crescent epidemic in the world, affecting more than half a billion of adults worldwide. Obesity is associated to main cardiovascular risk factors, such as insulin resistance, type 2 diabetes mellitus, high blood pressure and dyslipidemia. The excessive adiposity causes a dysregulation of adipokines secretion by adipose tissue, upregulating the expression of pro-inflammatory adipokines and downregulating the anti-inflammatory ones. This scenario contributes for the appearance of atherosclerosis. Since endothelium dysfunction is considered the earliest known marker of the atherosclerotic process, several methods to assess precociously the manifestations of endothelial dysfunction in microvessels, such as venous occlusion plethysmography, laser Doppler flowmetry and nailfold videocapillaroscopy, have been developed. Clinical and experimental studies have shown an impairment of microvascular function, capillary rarefaction and increase in inflammatory status in obesity and the introduction of lifestyle modifications, mainly physical activity and diet, constitute effective interventions to restore microvascular function in obesity.

Purpose: The effects of resistance training (RT) alone upon endothelial function, metabolic and hemodynamic profiles, physical fitness, body composition, and inflammatory biomarkers in nondiabetic obese adolescents were investigated., Methods: Adolescents were assigned into nonobese control (CG, n = 20; 14.7 ± 1.4 yr) and obese (OB, n = 24; 14.1 ± 1.0 yr) groups. Muscle and skin endothelial reactivity, body composition, at-office and 24-h ambulatory blood pressure, metabolic profile, adipocytokines, aerobic and strength fitness were assessed before and after 12 wk of RT (CG, only at admission)., Results: After RT, body mass did not change in OB, but significant reductions in body fat (1.6%; P = 0.01), waist circumference (2.9%; P < 0.001), waist-to-hip ratio (3.3%; P < 0.001), homeostasis model assessment for insulin resistance (15.4%; P = 0.02), endothelin-1 (14.2%; P = 0.04), and fibrinogen (6.9%; P = 0.03) were found. Both at-office and ambulatory blood pressure decreased, whereas skin endothelium-dependent vasodilation (32%; P = 0.02), VO2 (14.3%; P = 0.04), and HR (5.3%; P = 0.04) during submaximal exercise and isokinetic strength (extension, 21.3%; flexion, 29.9%; P < 0.0001) increased. Forearm vascular conductance increased at rest (28.1%; P = 0.03) and during postocclusive reactive hyperemia (25.2%; P = 0.02). After RT differences between CG and OB at admission were no longer detected for most outcomes., Conclusions: RT alone improved endothelial function, hemodynamic and metabolic profiles, body composition, and physical fitness in nondiabetic obese adolescents regardless of changes in body mass.

Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. As obesity is a multiple grade disease, we have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones, creating a window of opportunities for preventive measures. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls (n = 9); Overweight (n = 11); Obese class I (n = 26); Obese class II (n = 15); Obese class III (n = 19). Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Known determinants of endothelial dysfunction, such as inflammatory response, insulin resistance, and diagnosis of metabolic syndrome, did not correlate with forearm blood flow response to vasodilators. Moreover, several risk factors for atherosclerosis were excluded as independent predictors after confounder-adjusted analysis. Our data suggests that obesity per se could be sufficient to promote impairment of vascular reactivity, that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected, and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow.

Background and Objective: Apart from its inotropic property, milrinone has vasodilator, anti-inflammatory and antithrombotic effects that could assist in the reversal of septic microcirculatory changes. This paper investigates the effects of milrinone on endotoxemia-related microcirculatory changes and compares them to those observed with the use of norepinephrine., Materials and Methods: After skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2 mg.kg-1), male golden Syrian hamsters were treated with two regimens of intravenous milrinone (0.25 or 0.5 μg.kg-1.min-1). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables. Macro-hemodynamic, biochemical, and hematological parameters and survival rate were also analyzed. Endotoxemic non-treated animals, endotoxemic animals treated with norepinephrine (0.2 μg.kg-1.min-1), and non-endotoxemic hamsters served as controls., Results: Milrinone (0.5 μg.kg-1.min-1) was effective in reducing lipopolysaccharide-induced arteriolar vasoconstriction, capillary perfusion deficits, and inflammatory response, and in increasing survival. Norepinephrine treated animals showed the best mean arterial pressure levels but the worst functional capillary density values among all endotoxemic groups., Conclusion: Our data suggests that milrinone yielded protective effects on endotoxemic animals' microcirculation, showed anti-inflammatory properties, and improved survival. Norepinephrine did not recruit the microcirculation nor demonstrated anti-inflammatory effects.

Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM.

Objective: To investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables., Methods: Fourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/m2) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCVmax), and time taken to reach RBCVmax (TRBCVmax)., Results: Subjects with PCOS had lower RBCV and higher TRBCVmax compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, P<.01) and (5 [5-6] vs. 4 [3-5] s, P<.05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCVmax (ρ = -0.49, P<.05) and to TRBCVmax (ρ = 0.41, P<.05). SHBG correlated with RBCVmax (ρ = 0.52, P<.01) while estradiol (E2) levels correlated with RBCV (ρ = 0.80, P<.001) and RBCVmax (ρ = 0.46, P<.05)., Conclusion: Microvascular dysfunction characterized by reduced RBCVmax and prolonged TRBCVmax was present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction.

Introduction: In this report, we describe challenges we encountered in the clinical management of a patient with hypoparathyroidism who had previously undergone a bariatric procedure., Case Presentation: We report the case of a 38-year-old Caucasian woman who had undergone a Roux-en-Y gastric bypass procedure for treatment of obesity. She also had a past history of right lobectomy to treat a benign thyroid nodule. Another thyroid nodule was diagnosed after her bariatric surgery, so a new thyroid surgery was performed. Permanent hypoparathyroidism occurred after the second thyroid surgery. A Roux-en-Y gastric bypass resulted in important weight loss, but the preferential site of calcium absorption was bypassed. The lack of endogenous parathyroid hormone secretion due to post-surgical hypoparathyroidism abolished the physiological mechanism that compensates the reduced calcium absorption, which was a challenge for us to overcome. In this report, we describe our clinical therapeutic choices to maintain normocalcemia and normophosphatemia in this patient. Higher doses of exogenous calcium citrate, calcitriol and cholecalciferol were used, but hypocalcemia was still present. To improve vitamin D absorption with resultant improvement of calcium homeostasis, we speculated that adding pancrelipase to meals would increase lipid absorption and possibly fat-soluble vitamins, including vitamin D. Only after the addition of pancrelipase did the patient improve without weight regain according to clinical and laboratory assessments., Conclusion: The use of exogenous pancreatic enzymes improved calcium homeostasis in this bariatric patient. The role of these enzymes on vitamin D absorption and subsequent rise in calcium levels in hypoparathyroid patients who undergo bariatric procedures need further investigation.

Background: The increasing prevalence of obesity in the pediatric age range has become a major concern. Studies have investigated the role of physical activity (PA) to prevent obesity in this population. However, previous reviews did not focus on the effects of PA in overweight/obese adolescents on physical fitness and risk factors for cardiovascular disease altogether., Objective: The present systematic review analyzed trials investigating the effect of PA on aerobic capacity, muscle strength, body composition, hemodynamic variables, biochemical markers, and endothelial function in obese/overweight adolescents., Methods: PubMed, LILACS, Web of Science, Scopus (including Embase), and SPORTDiscus databases were searched for relevant reports without time limits. Inclusion criteria included studies published in English, with overweight and obese adolescents aged 12-17 years. The review was registered (Number CRD42013004632) on PROSPERO, the International Prospective Register of Systematic Reviews., Results: The results indicated that PA is associated with significant and beneficial changes in fat percentage, waist circumference, systolic blood pressure, insulin, low-density lipoprotein cholesterol, and total cholesterol, as well as with small non-significant changes in diastolic blood pressure, glucose, and high-density lipoprotein cholesterol., Conclusion: Although limited, results from controlled trials suggest that PA intervention may improve physical fitness and risk factors for cardiovascular disease in adolescents who are overweight or obese.

Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30) starting on the 21st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change), return to standard chow (HFSC, n = 30), high fat chow associated to an aerobic exercise training program (AET) (HFEX, n = 30) and return to standard chow+AET (HFSCEX, n = 30). Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM) (HF)4.9±1.5 g and (HFEX)4.7±0.9 g vs. (HFSC)*3.0±0.7 g and (HFSCEX)*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10(-8) M (HF)87.9±2.7%; (HFSC)*116.7±5.9%; (HFEX)*109.1±4.6%; (HFSCEX)*105±2.8%; Ach10(-6) M (HF)95.3±3.1%; (HFSC)*126±6.2%; (HFEX)*122.5±2.8%; (HFSCEX)*118.1±4.3% and Ach10(-4) M (HF)109.5±4.8%; (HFSC)*149.6±6.6%; (HFEX)*143.5±5.4% and (HFSCEX)*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF)40.5±4.2; (HFSC)*19.0±1.6; (HFEX)*18.6±2.1 and (HFSCEX)* 21.5±3.7 leaks/cm2), decreased eNOS expression, increased leptin and glycaemic levels. Endothelial-independent microvascular reactivity was similar between groups, suggesting that only endothelial damage had occurred. Our results indicate that an aerobic routine and/or dietary modification may cause significant improvements to high fat fed animals, diminishing visceral depots, increasing eNOS expression and reducing microcirculatory dysfunction.

Objective: We investigated the influence of resistance training on body composition and matrix metalloproteinase 2 activity in skeletal muscles of rats fed a high-fat diet., Methods: Thirty-two Wistar rats were divided into four experimental groups (n = 8/each) according to diet and exercise status: Control (standard diet), Obese Control (high-fat diet), Resistance Training (standard diet) and Obese Resistance Training (high-fat diet) groups. Animals were fed a high-fat diet for 12 weeks to promote excessive weight gain. Resistance Training groups performed 12 weeks of training periods after this period in a vertical ladder three times/week. Fat percentage, fat-free mass and fat mass were assessed using dual-energy X-ray absorptiometry, and matrix metalloproteinase 2 activity in biceps and gastrocnemius muscles was analyzed using zymography., Results: Resistance training significantly reduced body and fat masses and fat percentages in both trained groups (p<0.05). The maximal carrying load between trained groups was not different, but relative force was higher in the Resistance Training group (p<0.05). Of note, increased matrix metalloproteinase 2 activity was noted in the tested muscles of both trained groups (p<0.05)., Conclusion: In conclusion, altered body composition and muscle matrix metalloproteinase 2 activity promoted by excessive weight gain were positively modified by resistance training.

Objectives: Estrogen has been shown to play an important protective role in non-reproductive systems, such as the cardiovascular system. Our aim was to observe gender differences in vivo with regard to the increase in macromolecular permeability and leukocyte-endothelium interaction induced by ischemia/reperfusion as well as in microvascular reactivity to vasoactive substances using the hamster cheek pouch preparation., Methods: Thirty-six male and 36 female hamsters, 21 weeks old, were selected for this study, and their cheek pouches were prepared for intravital microscopy. An increase in the macromolecular permeability of post-capillary venules was quantified as a leakage of intravenously injected fluorescein-labeled dextran, and the leukocyte-endothelium interaction was measured as the number of fluorescent rolling leukocytes or leukocytes adherent to the venular wall, labeled with rhodamin G, during reperfusion after 30 min of local ischemia. For microvascular reactivity, the mean internal diameter of arterioles was evaluated after the topical application of different concentrations of two vasoconstrictors, phenylephrine (α1-agonist) and endothelin-1, and two vasodilators, acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent)., Results: The increase in macromolecular permeability induced by ischemia/reperfusion was significantly lower in females compared with males [19 (17-22) leaks/cm2 vs. 124 (123-128) leaks/cm2, respectively, p<0.001), but the number of rolling or adherent leukocytes was not different between the groups. Phenylephrine-induced arteriolar constriction was significantly lower in females compared with males [77 (73-102)% vs. 64 (55-69)%, p<0.04], but there were no detectable differences in endothelin-1-dependent vasoreactivity. Additionally, arteriolar vasodilatation elicited by acetylcholine or sodium nitroprusside did not differ between the groups., Conclusion: The female gender could have a direct protective role in microvascular reactivity and the increase in macromolecular permeability induced by ischemia/reperfusion.

Objective: The body adiposity index (BAI) has been recently proposed as an alternative index to body mass index (BMI) and waist circumference (WC) to evaluate adiposity in adults, with special focus on its ability to discriminate gender specificities on adiposity. Endothelial dysfunction, circulating endothelial cells (CECs), endothelin-1 and adipocytokines are all related to atherosclerosis and nowadays considered as markers of emerging cardiovascular (CV) risk. This study aimed to determine in normal weight and obese adolescents which measures of body composition (BAI and z-BMI) or distribution (WC) correlate better with emerging CV risk markers., Patients: Forty adolescents were selected according to BMI: normal weight (n = 20; 7 girls/13 boys, 14·7 ± 1·4 years, 53·4 ± 6·0 kg, z-BMI 0·6 ± 0·1) and obese ones (n = 20; 13 girls/7 boys, 14·1± 1·0 years, 86·7 ± 11·5 kg, z-BMI 2·7 ± 0·4)., Measurements: Body fat and fat mass were measured by dual-energy X-ray absorptiometry (DXA). Non-nutritive skin microvascular reactivity was evaluated by laser Doppler flowmetry with iontophoretic release of vasoactive drugs. Activated CECs were assessed by flow cytometric analysis., Results: In adolescents, the measurement of % fat by DXA showed high correlation with BAI (ρ = 0·75, P < 0·0001), z-BMI (r = 0·84, P < 0·0001) and WC (r = 0·83, P < 0·0001). Endothelin-1 and activated CECs did not correlate with any anthropometric measures while adipocytokines expressed variable associations among them. Endothelium-dependent vasodilation showed higher correlation with BAI (r = -0·51, P < 0·0001) compared to z-BMI (r = -0·40, P < 0·001) or WC (r = -0·45, P < 0·001), specially on females., Conclusions: BAI was associated with emerging CV risk markers in adolescents but further research is needed to evaluate its potential in clinical and epidemiological sets., (© 2013 John Wiley & Sons Ltd.)

Objective: The purpose of this study was to evaluate the effect of resistance training (RT) on body composition, systolic and diastolic blood pressures (BP), and activity of muscle MMP-2 in the left ventricle of high-fat fed rats., Materials/methods: We have evaluated 32 male Wistar rats divided into four experimental groups (n=8/each) according to diet and exercise status: sedentary (SED; standard diet), sedentary obese (SED-OB; diet: 30% of fat), RT (RT; standard diet) and RT obese (RT-OB; diet: 30% of fat). After weaning (day 21), animals were subjected to the experimental diet according to their groups during 24 weeks. A 12-week strength-training period was used, during which the rats climbed a 1.1-m vertical ladder with weights attached to their tails. Sessions were performed three times/week (Mondays, Wednesdays and Fridays), with 4-9 climbs/session and 8-12 dynamic movements/climb., Results: RT induced higher muscle MMP-2 activity in the left ventricle in RT and RT-OB groups. Moreover, this study demonstrated that RT promoted lower body and fat masses, fat percentage, systolic and diastolic BPs and higher fat free mass in both trained groups., Conclusion: RT increased muscle MMP-2 activity in the left ventricle, induced positive changes on body composition and lowered BPs in high-fat diet fed rats, suggesting that it may be a useful tool to prevent alterations induced by high-fat diet consumption., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To identify associations between long-term (1 year) food intake and skin nutritive microvascular function in healthy subjects., Methods: This was a cross-sectional study. A validated 88-item food-frequency questionnaire was administered to 39 healthy men aged 23.4 ± 0.5 years and body mass index 23.3 ± 2.3 kg/m², who reported food intake during the last year and underwent videocapillaroscopy exams. The main outcome was the increase in functional capillary recruitment, that is, peak capillary density after post-occlusive reactive hyperemia subtracted from basal capillary density (caps/mm²). Associations between reported food intake and functional capillary recruitment were investigated., Results: Daily average estimates of intake were: total energy (3,745 ± 1,365 kcal), carbohydrates (60.1 ± 5.9 %), lipids (22.1 ± 4.4 %), proteins (17.8 ± 4.1 %), fibers (33.9 ± 18.5 g), and cholesterol (492.8 ± 209.6 mg). Positive significant correlations with capillary recruitment were found for selenium (as μg/day/1,000 kcal; rho = 0.3412, p = 0.038,) calcium (as mg/day/1,000 kcal; rho = 0.3390, p = 0.043), and percentage of total energy from dairy products (rho = 0.3660, p = 0.023)., Conclusions: Long-term intakes of selenium, calcium, and dairy products were positively associated with capillary recruitment in skin nutritive microcirculation in healthy young men. The role of such dietary components is discussed and possible mechanisms for their effects should be further investigated. This evidence adds one more possible functional property of these nutrients and food items.

Background: We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements., Methods: Data from 189 female subjects (34.0 ± 15.5 years, 30.5 ± 7.1 kg/m2), who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA). PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI), waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), insulin, C-reactive protein (CRP), and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV) at rest and peak after 1 min of arterial occlusion (RBCV(max)), and the time taken to reach RBCV(max) (TRBCV(max))., Results: A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCV(max) varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCV(max), but in the opposite way. Principal component 3 was associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCV(max)). Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity., Conclusions: In non-diabetic female subjects, a multivariate scenario of associations between classic clinical variables strictly related to obesity and metabolic syndrome suggests a significant relationship between these diseases and microvascular reactivity.

The aims of our study were to investigate effects of postnatal overnutrition, obtained by restricting the number of pups per litter, on microcirculatory reactivity, fat depots, its total percentage and lipid profile. Microvascular reactivity was evaluated in the cremaster muscle of 24 hamsters divided into four groups, with 6 animals in each one: normal (NL) and restricted (RL) litter groups, both at 6th and 21st weeks of age. The NL group had 8-9 pups and the RL 3 pups per litter and to avoid the litter effect, only one animal was used per litter. The results have shown that the RL group had higher velocity of weight, body mass and fat gain compared to the NL one at weeks 6 and 21. Significant differences were also observed on urogenital fat depot, total cholesterol and low density lipoprotein between groups. At the lowest concentration of Ach, the RL group showed smaller arteriolar dilatation at the 21st than at the 6th week [5(3-13) vs 19(8-40)%, p<0.01] while the NL one did not show any difference within the group. The highest concentration of Ach at the 21th week pointed to endothelial-dependent microvascular dysfunction in RL compared to NL [3(8-26) vs. 13(8-26)%, p<0.05]. Endothelial-independent microvascular reactivity was similar between groups. Our data suggest that postnatal overnutrition is associated to muscle endothelial-dependent microvascular dysfunction, greater body mass and total percentage of fat and impaired the lipid profile. In conclusion, the imprinting promoted by this experimental model of obesity was able to influence microvascular reactivity later in life., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The cephalic phase of digestion (CPD) has been extensively investigated in terms of digestion and metabolism. Nevertheless, microcirculatory changes required to prepare peripheral tissues in order to dispose nutrients have never been assessed. In this study, microvascular function has been evaluated to determine its behavior and potential association to hormonal secretions during CPD. Thirty-nine healthy male subjects, 23.4 ± 0.5 years (mean ± SD) and BMI of 23.3 ± 2.3 kg/m(2), were randomized into receiving cognitive-sensorial stimuli to elicit CPD (CPD group, n=20) or not (control group, n=19), after a 12-h overnight fast. Main outcomes were differences in resting and peak functional capillary density (FCD, cap/mm(2)); resting red blood cell velocity (RBCV), peak RBCV (RBCV(max)) and time taken to reach it (TRBCV(max)); peak flow and vasomotion, before and after CPD and their associations with insulin and/or pancreatic polypeptide (PP). In the CPD group, basal FCD (24.9 ± 7.6 to 28.3 ± 8.1, p=0.005), peak FCD (27.8 ± 6.3 to 32.6 ± 7.1, p=0.002), RBCV (0.306 ± 0.031 to 0.330 ± 0.027 mm/s, p=0.005), RBCV(max) (0.336 ± 0.029 to 0.398 ± 0.292 mm/s, p=0.005) and peak flow (23.5 ± 14.3 to 26.9 ± 15.8 PU, p<0.01) increased while TRBCV(max) decreased (4.9 ± 1.5 to 3.5 ± 1.2s, p=0.01). No significant changes could be detected in the control group. Groups have not presented differences for insulin, but PP significantly increased in the CPD group and was positively associated to basal FCD increase (rho=0.527, p=0.03). In conclusion, neurally-mediated anticipatory responses of digestion elicited functional capillary recruitment associated to PP in healthy men, suggesting a precocious role for microcirculation in the physiology of digestion and nutrient homeostasis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Obesity is a chronic disease associated to an inflammatory process resulting in oxidative stress that leads to morpho-functional microvascular damage that could be improved by some dietary interventions. In this study, the intake of Brazil nuts (Bertholletia excelsa), composed of bioactive substances like selenium, α- e γ- tocopherol, folate and polyunsaturated fatty acids, have been investigated on antioxidant capacity, lipid and metabolic profiles and nutritive skin microcirculation in obese adolescents., Methods: Obese female adolescents (n = 17), 15.4 ± 2.0 years and BMI of 35.6 ± 3.3 kg/m2, were randomized 1:1 in two groups with the diet supplemented either with Brazil nuts [BNG, n = 08, 15-25 g/day (equivalent to 3 to 5 units/day)] or placebo [PG (lactose), n = 09, one capsule/day] and followed for 16 weeks. Anthropometry, metabolic-lipid profiles, oxidative stress and morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak (RBCVmax) and time (TRBCVmax) to reach it during post-occlusive reactive hyperemia, after 1 min arterial occlusion] microvascular variables were assessed by nailfold videocapillaroscopy at baseline (T0) and after intervention (T1)., Results: T0 characteristics were similar between groups. At T1, BNG (intra-group variation) had increased selenium levels (p = 0.02), RBCV (p = 0.03) and RBCVmax (p = 0.03) and reduced total (TC) (p = 0.02) and LDL-cholesterol (p = 0.02). Compared to PG, Brazil nuts intake reduced TC (p = 0.003), triglycerides (p = 0.05) and LDL-ox (p = 0.02) and increased RBCV (p = 0.03)., Conclusion: Brazil nuts intake improved the lipid profile and microvascular function in obese adolescents, possibly due to its high level of unsaturated fatty acids and bioactive substances., Trial Registration: Clinical Trials.gov NCT00937599.

Objectives: Previous data in our laboratory have shown microvascular dysfunction in normoglycaemic subjects with metabolic syndrome (MS). In a step further, we have investigated which clinical parameters related or not to MS would elicit microvascular dysfunction and the need of diagnosing MS for the establishment of microcirculatory impairment in overweight/obese women., Methods: Nineteen lean [23.6±3.1years, body mass index (BMI) 21.9±1.8kg/m(2)] and 59 overweight/obese [24.6±3.7years; BMI 34.4±5.9kg/m(2)] sedentary non-smoking women, divided in overweight/obese without (MS negative, n=36) and obese with MS (MS positive, n=23) were evaluated. Blood biochemistry, HOMA-IR index and anthropometric variables were determined. Morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak and time (TRBCV(max)) to reach it during post-occlusive reactive hyperemia after 1min ischemia] microcirculatory variables were examined by nailfold videocapillaroscopy., Results: Compared to controls, overweight/obese MS negative and obese MS positive presented longer TRBCV(max); the presence of two MS components was sufficient to prolong it and the MS diagnosis did not add any significant impairment to the microcirculation. Among clinical parameters investigated, a direct relationship between TRBCV(max) and waist circumference and insulin concentrations was found., Conclusion: Our results have shown that microvascular dysfunction is independent of metabolic syndrome diagnosis and could be predicted by the waist circumference on young overweight/obese women, reinforcing the relationship between obesity-related microvascular/metabolic disturbances., (Copyright © 2010 Elsevier Inc. All rights reserved.)

It is speculated that exercise training decreases resting levels of tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP); reduces body mass and leptin (LP); and increases adiponectin (AD) and insulin sensitivity. This systematic review analyzed the effectiveness of resistance training (RT) longitudinal clinical studies on AD, LP, CRP and TNF-alpha. Seventeen studies were included and the majority of randomized controlled trials support that RT produces increases in AD, and decreases in both LP and CRP. Greater responses in AD and LP were evident in overweight and obese individuals; while RT appeared to be effective in reducing CRP in obese individuals, and older adults. Additionally, women may be more responsive to RT effects on AD, LP and CRP. Training duration and intensity may affect the response of AD and CRP with greater responses shown with 16 weeks or more of training and/or with intensities greater than 80% of one repetition maximum. No response to RT of TNF-alpha levels was apparent. Although based on a limited number of studies, some of which are uncontrolled non-randomized in design, our review suggests some positive effects of RT programs on cytokine levels, but specifics of the responses in different populations need further elucidation., (Georg Thieme Verlag KG Stuttgart, New York.)