The role of adiponectin in endothelial dysfunction and hypertension.

It has been two decades since the discovery of adiponectin, and today its role in insulin resistance, inflammation, and atherosclerosis are areas of major interest. Production of adiponectin is reduced in all inflammatory processes and states of insulin resistance such as obesity, type 2 diabetes mellitus, and coronary artery disease. Adiponectin regulates carbohydrate metabolism, and may also regulate vascular homeostasis by affecting important signaling pathways in endothelial cells and modulating inflammatory responses in the subendothelial space. Clinical studies have demonstrated a relationship between serum adiponectin concentrations and the activity of the renin-angiotensin-aldosterone system (RAAS), causing changes in blood pressure. Antihypertensive therapy with angiotensin II receptor blockers (ARBs) has been demonstrated to increase adiponectin levels in 3-6 months. Adiponectin has also been shown to play a role in cardiac injury in modulation of pro-survival reactions, cardiac energy metabolism, and inhibition of hypertrophic remodeling. The effects of adiponectin on the cardiovascular system are believed to be partially mediated by the activation of 5' adenosine monophosphate-activated protein kinase (AMPK) and cyclooxygenase-2 (COX-2) pathways, reducing endothelial cell apoptosis, promoting nitric oxide production, decreasing tumor necrosis factor-alpha (TNF-α) activity, and preventing atherosclerotic proliferation and smooth muscle cell migration. Further evaluation of biologically active forms of adiponectin and its receptor should help to clarify how obesity affects the cardiovascular system.

Evaluation of Resting Energy Expenditure in Subjects with Severe Obesity and Its Evolution After Bariatric Surgery.

PURPOSE: One major determinant of weight loss is resting energy expenditure (REE). However, data regarding REE is scarce in patients with severe obesity (SO)-BMI>50kg/m2. Most studies used equation in order to estimate REE and not indirect calorimetry (IC) (gold standard). Additionally, there is no reliable data on the impact of bariatric surgery (BS) on REE. OBJECTIVES: (a) To evaluate the REE in patients with SO; (b) to compare REE measured by IC (mREE) to that calculated by Mifflin St-Jeor equation (eREE); (c) to evaluate the impact of BS on REE and the relationship with evolution post-BS. MATERIAL AND METHODS: Single-center observational study including consecutive patients with SO between January 2010 and December 2015, candidates for BS. mREE was determined at baseline, and 1 and 12 months post-BS by IC, using a Vmax metabolic monitor. RESULTS: Thirty-nine patients were included: mean age 46.5±11.77 years, 64.1%women. Preoperative mREE was 2320.38±750.81 kcal/day. One month post-BS, the mREE significantly decreased (1537.6 ± 117.46 kcal/day, p = 0.023) and remained unchanged at 12 months (1526.00 ± 123.35 kcal/day; p =0.682). Reduction in mREE after the BS was a predictor of reaching successful weight loss (nadir) and weight regain (5 years follow-up) (AUCROC of 0.841 (95%CI [0.655-0.909], p=0.032) and AUCROC of 0.855 (95% CI [0.639-0.901]), p= 0.027, respectively). eREE was not valid to identify these changes. CONCLUSION: In patients with SO, a significant reduction of mREE occurs 1 month post-BS, unchanged at 12 months, representing the major conditioning of successful weight loss and maintenance post-BS.

Thyroid disorders associated with immune control point inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICPI) have improved progression-free survival in several solid tumors. Side effects are related to overstimulation of the immune system. Thyroid dysfunction (TD) is the most common endocrine immune-related adverse event of ICPI. OBJECTIVE: To describe the clinical presentation and the course of TD in cancer patients treated with ICPI referred to an endocrinology outpatient clinic. MATERIAL AND METHODS: This was a descriptive, retrospective and multicenter study of patients with TD associated with ICPI in six Spanish hospitals. RESULTS: 120 patients (50.8% women), mean age 60 ±â€¯12 years were included. The initial TD was hypothyroidism in 49% of patients and hyperthyroidism in 51%, with an average of 76 (41-140) and 43 (26-82) days respectively between the onset of ICPI and the analytical alteration. Significantly, the earlier the first analytical determination was, the greater the prevalence of hyperthyroidism. A turnover was observed in 80% of subjects during follow-up, mostly from hyperthyroidism to hypothyroidism. Twenty-one percent received double ICPI therapy. The most frequent form of presentation in monotherapy was hypothyroidism (57%), and in double therapy it was hyperthyroidism (77%) (p = 0.002). Patients under double therapy showed thyroid alterations earlier than those in the monotherapy group (p = 0.001). After a follow-up of 205 (112-360) days, half of the patients continued under levothyroxine treatment. CONCLUSIONS: Hypothyroidism and hyperthyroidism present in a similar proportion in cancer patients undergoing ICPI therapy. Our results suggest that transitory hyperthyroidism may not be detected in a relevant number of cases. In addition, TD in double therapy presents earlier. This should be taken into account in the follow-up protocols of these patients.

Canagliflozin: A New Therapeutic Option in Patients That Present Postprandial Hyperinsulinemic Hypoglycemia after Roux-en-Y Gastric Bypass: A Pilot Study.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) is the most common surgical procedure for morbid obesity. However, it can present serious late complications, like postprandial hyperinsulinemic hypoglycemia (PHH). Recent data suggested an increase in intestinal SGLT-1 after RYGB. However, there is no data on the inhibition of SGLT-1 to prevent PHH in patients with prior RYBG. On this basis, we aimed to evaluate (a) the effect of canagliflozin 300 mg on the response to 100 g glucose overload (oral glucose tolerance test [OGTT]); (b) the pancreatic response after intra-arterial calcium stimulation in the context of PHH after RYGB. MATERIALS AND METHODS: This is a prospective pilot study including patients (n = 21) with PHH after RYGB, matched by age and gender with healthy controls (n = 5). Basal OGTT and after 2 weeks of daily 300 mg of canagliflozin was performed in all cases. In addition, venous sampling after intra-arterial calcium stimulation of the pancreas was performed in 10 cases. RESULTS: OGTT after canagliflozin showed a significant reduction of plasma glucose levels (minute 30: 161.5 ± 36.22 vs. 215.9 ± 58.11 mg/dL; minute 60: 187.46 ± 65.88 vs. 225.9 ± 85.60 mg/dL, p < 0.01) and insulinemia (minute 30: 95.6 ± 27.31 vs. 216.35 ± 94.86 mg/dL, p = 0.03; minute 60: 120.85 ± 94.86 vs. 342.64 ± 113.32 mIU/L, p < 0.001). At minute 180, a significant reduction (85.7%) of the rate of hypoglycemia was observed after treatment with canagliflozin (p < 0.00001). All cases presented normal pancreatic response after intra-arterial calcium administration. CONCLUSION: Canagliflozin (300 mg) significantly decreased glucose absorption and prevented PHH after 100 g OGTT in patients with RYGB. Our results suggest that canagliflozin could be a new therapeutic option for patients that present PHH after RYGB.

A Clinical-Genetic Score for Predicting Weight Loss after Bariatric Surgery: The OBEGEN Study.

Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805-0.880), p < 0.001; sensitivity 90.1%, specificity 65.5%] was obtained by combining three clinical variables (age, type of surgery, presence diabetes) and nine SNPs located in ADIPOQ, MC4R, IL6, PPARG, INSIG2, CNR1, ELOVL6, PLIN1 and BDNF genes. This predictive model showed a significant higher area under ROC than the clinical score (p = 0.0186). The OBEGEN study shows the key role of combining clinical variables with genetic testing to increase the predictability of the weight loss response after BS. This finding will permit us to implement a personalized medicine which will be associated with a more cost-effective clinical practice.

New Metrics to Assess Type 2 Diabetes After Bariatric Surgery: The "Time-Within-Remission Range".

Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the "time-within-remission range" as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 ± 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, "time-within-remission range" and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 ± 9.2 years old, body mass index (BMI) 46.3 ± 6.9 kg/m2) underwent primary bariatric procedures. "Time-within-remission range" were 83.3% (33.3-91.6) after gastric bypass, 68.7% (7.1-87.5) after sleeve gastrectomy and 90% (83.3-92.8) after malabsorptive techniques (p < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the "time-within-remission range". The association of bariatric techniques with "time-within-remission range", using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34-5.84), p < 0.001 for malabsorptive techniques and OR 0.55 (0.40-0.75), p < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The "time-within-remission range" unveils a superiority of gastric bypass compared to sleeve gastrectomy.

Retinal Microperimetry: A Useful Tool for Detecting Insulin Resistance-Related Cognitive Impairment in Morbid Obesity.

BACKGROUND: There is clear association between type 2 diabetes (T2D) and cognitive decline. Retinal microperimetry is a useful tool for detecting cognitive impairment in T2D. Morbid obesity (MO) has been associated with cognitive impairment. Insulin resistance (IR) seems a major determinant, but the data are unclear. The aim of this study was to evaluate the cognitive impairment in MO as well as the utility of retinal microperimetry in identifying these alterations. METHODS: In total, 50 consecutive patients with MO were matched by age and gender with 30 healthy controls. All patients underwent cognitive evaluation (Montreal Cognitive Assessment Test-MoCA) and retinal microperimetry, using MAIA microperimeter 3rd generation. Retinal sensitivity and gaze fixation parameters were used for the evaluation of the analysis. RESULTS: MO patients showed a significantly lower neurocognitive performance than the controls: MoCA score 24.94 ± 2.74 vs. 28.95 ± 1.05, p < 0.001. Cognitive function inversely correlated with the HOMA-IR (r = -0.402, p = 0.007). The AUROC for cognitive impairment using microperimetry was 0.807, CI 95% (0.592-0.947), p = 0.017. CONCLUSIONS: (1) Systemic insulin resistance is a major underlying mechanism accounting for the higher prevalence of cognitive impairment detected in young MO subjects. (2) Retinal microperimetry is a useful tool for identifying MO patients with cognitive impairment.

Genetic Testing to Predict Weight Loss and Diabetes Remission and Long-Term Sustainability after Bariatric Surgery: A Pilot Study.

INTRODUCTION: The aim of this pilot study was to assess genetic predisposition risk scores (GPS) in type 2 diabetic and non-diabetic patients in order to predict the better response to bariatric surgery (BS) in terms of either weight loss or diabetes remission. RESEARCH DESIGN AND METHODS: A case-control study in which 96 females (47 with type 2 diabetes) underwent Roux-en-Y gastric by-pass were included. The DNA was extracted from saliva samples and SNPs were examined and grouped into 3 GPS. ROC curves were used to calculate sensitivity and specificity. RESULTS: A highly sensitive and specific predictive model of response to BS was obtained by combining the GPS in non-diabetic subjects. This combination was different in diabetic subjects and highly predictive of diabetes remission. Additionally, the model was able to predict the weight regain and type 2 diabetes relapse after 5 years' follow-up. CONCLUSIONS: Genetic testing is a simple, reliable and useful tool for implementing personalized medicine in type 2 diabetic patients requiring BS.

Stevia rebaudiana Bertoni and Its Effects in Human Disease: Emphasizing Its Role in Inflammation, Atherosclerosis and Metabolic Syndrome.

PURPOSE OF REVIEW: Stevia rebaudiana Bertoni is a perennial shrub with zero calorie content that has been increasing in popularity for its potential use as an adjuvant in the treatment of obesity. The level of evidence supporting general benefits to human health is insufficient. We conducted a review of the literature summarizing the current knowledge and role in human disease. RECENT FINDINGS: Despite stevia's minimal systemic absorption, studies have been promising regarding its potential benefits against inflammation, carcinogenesis, atherosclerosis glucose control, and hypertension. On the other hand, the growing popularity of artificial sweeteners does not correlate with improved trends in obesity. An increased intake of artificial non-caloric sweeteners may not be associated with decreased intake of traditional sugar-sweetened beverages and foods. The effects of Stevia on weight change have been linked to bacteria in the intestinal microbiome, mainly by affecting Clostridium and Bacteroides sp. POPULATIONS: A growing body of evidence indicates that Stevia rebaudiana Bertoni is protective against malignant conversion by inhibition of DNA replication in human cancer cell growth in vitro. Consumption of Stevia has demonstrated to be generally safe in most reports. Further clinical studies are warranted to determine if regular consumption brings sustained benefits for human health.