Effects of a high-fat meal on inflammatory and endothelial injury biomarkers in accordance with adiposity status: a cross-sectional study.

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/m2) and 18 eutrophic ones (BMI 20.0-24.9 kg/m2) 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.

Changes in appetite, taste, smell, and food aversion in post-bariatric patients and their relations with surgery time, weight loss and regain.

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/m2, 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).

Constitutive DPP4 activity, inflammation, and microvascular reactivity in subjects with excess body weight and without diabetes.

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/m2 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 activityAUC was inversely correlated with the myogenic componentAUC 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.

Dynamic nailfold videocapillaroscopy may be used for early detection of microvascular dysfunction in obesity.

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.

Nonobese Young Females with Polycystic Ovary Syndrome have Nutritive Microvascular Dysfunction: A Pilot Study.

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.

Long-term dietary intake of selenium, calcium, and dairy products is associated with improved capillary recruitment in healthy young men.

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.

Microvascular Function, Inflammatory Status, and Oxidative Stress in Post-Bariatric Patients with Weight Regain.

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/m2, 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.

Screening Risks of Alcohol Abuse, Depressive Symptoms, and Decreased Health-Related Quality of Life in Post-Bariatric Patients and Their Relations to Weight Regain.

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/m2) 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.

Ghrelin and glucagon-like peptide-1 according to body adiposity and glucose homeostasis.

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/m2) 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.

Muscle endothelial-dependent microvascular dysfunction in adulthood due to early postnatal overnutrition.

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.

Effects of physical training on physical and functional fitness, physical activity level, endothelial function, hemodynamic variables, bone metabolism, and quality of life of post-bariatric patients: study protocol for a randomized controlled trial.

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.

Metabolic and Inflammatory Profiles of Post-Bariatric Patients with Weight Recidivism.

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-1ß (IL-1 ß), 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.

Physical Activity Level, Sedentary Time, and Weight Regain After Bariatric Surgery in Patients Without Regular Medical Follow-up: a Cross-Sectional Study.

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/m2, 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.

Peripheral microvascular dysfunction is also present in patients with ischemia and no obstructive coronary artery disease (INOCA).

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.

Dipeptidyl peptidase-4 activity, lipopolysaccharide, C-reactive protein, glucose metabolism, and gut peptides 3 months after bariatric surgery.

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.

Obesity blunts cephalic-phase microvascular responses to food.

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 (RBCVmax), and time taken to reach RBCVmax (TRBCVmax) 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.

Acute Effects of Metformin and Vildagliptin after a Lipid-Rich Meal on Postprandial Microvascular Reactivity in Patients with Type 2 Diabetes and Obesity: A Randomized Trial.

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/m2. 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.

Evaluation of Heart Rate Variability and Endothelial Function 3 Months After Bariatric Surgery.

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.

Dipeptidyl Peptidase 4 Activity Is Related to Body Composition, Measures of Adiposity, and Insulin Resistance in Subjects with Excessive Adiposity and Different Degrees of Glucose Tolerance.

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/m2 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.