Waist circumference cut-off points to identify major cardiovascular events and incident diabetes in Latin America: findings from the prospective Urban rural epidemiology study Colombia.

Background: Abdominal obesity (AO) indirectly represents visceral adiposity and can be assessed by waist circumference (WC) measurement. In Latin America, cut-off points for the diagnosis of AO are based on Asian population data. We aim to establish the WC cut-off points to predict major cardiovascular events (MACE) and incident diabetes. Methods: We analyzed data from the cohort PURE study in Colombia. WC cut-off points were defined according to the maximum Youden index. Multivariate logistic regression was used to obtain associations between WC and MACE, diabetes, and cumulative incidence of outcomes visualized using Kaplan-Meier curves. Results: After a mean follow-up of 12 years, 6,580 individuals with a mean age of 50.7 ± 9.7 years were included; 64.2% were women, and 53.5% were from rural areas. The mean WC was 85.2 ± 11.6 cm and 88.3 ± 11.1 cm in women and men, respectively. There were 635 cases of the MACE composite plus incident diabetes (5.25 events per 1,000 person-years). Using a cut-off value of 88.85 cm in men (sensitivity = 0.565) and 85.65 cm in women (sensitivity = 0.558) resulted in the highest value for the prediction of the main outcome. These values were associated with a 1.76 and 1.41-fold increased risk of presenting the composite outcome in men and women, respectively. Conclusions: We defined WC cut-off points of 89 cm in men and 86 cm in women to identify the elevated risk of MACE and incident diabetes. Therefore, we suggest using these values in cardiovascular risk assessment in Latin America.

Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development. METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality. INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Insulin Resistance Markers to Detect Nonalcoholic Fatty Liver Disease in a Male Hispanic Population.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease and is closely associated with cardiometabolic disorders, being insulin resistance (IR) the common pathogenic mechanism. The triglycerides/glucose (TyG) index and triglycerides/HDL-c (TG/HDL) ratio are markers correlated with IR. We compared the capacity of these two indexes, alongside IR, to detect NAFLD. Methods: In a cross-sectional cohort study, we examined 263 active military personnel from the Colombian Air Force, aged between 29 and 54 years. Anthropometric measurements and biochemical determinations (glycemia, lipid profile, and insulin) were obtained, and ultrasound studies were performed to evaluate the presence of NAFLD. HOMA-IR index was calculated as (fasting insulin (µIU/mL) × fasting glucose (mmol/L)/22.5), the TyG index as Ln (triglycerides (mg/dL) × fasting glucose (mg/dL)/2), and the TG/HDL ratio as (triglycerides (mg/dL)/HDL-c (mg/dL)). Results: NAFLD ultrasound criteria were met in 70 individuals (26.6%). Subjects with NAFLD had significantly higher values of HOMA-IR (2.55 ± 1.36 vs. 1.51 ± 0.91), TyG (9.17 ± 0.53 vs. 8.7 ± 0.51), and TG/HDL (6.6 ± 4.54 vs. 3.52 ± 2.32) compared to those without NAFLD (p < 0.001). A TyG cutoff point of 8.92 showed an AUC of 0.731, while cutoff points of 3.83 for TG/HDL and 1.68 for HOMA-IR showed an AUC of 0.766 and 0.781, respectively. Conclusion: Our study shows that novel and lower-cost markers of IR are useful for detecting NALFD, with a performance comparable to the HOMA-IR index. These markers should be used as the first step when screening patients for NAFLD.

Immunomodulatory effect of a very-low-calorie ketogenic diet compared with bariatric surgery and a low-calorie diet in patients with excessive body weight.

BACKGROUND & AIM: Inflammation and oxidative stress are the most probable mechanistic link between obesity and its co-diseases with cancer among them. The aim of this study was to evaluate whether the nutritional ketosis and weight loss induced by a very-low-calorie ketogenic diet (VLCKD) modulates the inflammatory and oxidative stress profile, compared with a standard, balanced hypocaloric diet (LCD) or bariatric surgery (BS) in patients with obesity. METHODS: The study was performed in 79 patients with overweight or obesity and 32 normal-weight volunteers as the control group. Patients with obesity underwent a weight reduction therapy based on VLCKD, LCD or BS. The quantification of the circulating levels of a multiplexing test of cytokines and carcinogenesis/aging biomarkers, as well as of lipid peroxides and total antioxidant power, was carried out. RESULTS: First, we observed that pro-inflammatory cytokines increase, while anti-inflammatory cytokines decrease under excessive body weight. Relevantly, when patients underwent weight loss strategies, it was shown that energy-restricted and surgical strategies of weight loss induced changes in circulating cytokine and lipid peroxides. This effect was more notable in patients following the VLCKD than the LCD or BS and it was observed mainly in the ketosis phase of the intervention. Particularly, IL-11, IL-12, IL-2, INF-γ, INF-ß, Pentraxin-3 or MMP1 changed after VLCKD. Whereas, APRIL, TWEAK, osteocalcin and IL-28A increased after BS. CONCLUSION: As far as we know, this is the first study that evaluate the time-course of cytokines and oxidative stress markers after a VLCKD as compared with a standard LCD and BS. The observed results support the immunomodulatory effect of nutritional ketosis induced by a VLCKD synergistically with weight loss as a strategy to improve innate-immunity and to prevent infections and carcinogenesis in patients with obesity.

Unilateral Proptosis (Exophthalmos) Caused by Axillary-Subclavian Venous Thrombosis in a Patient with Upper Extremity Arteriovenous Dialysis Fistula.

Arterialization of orbital veins is most often due to dural arteriovenous malformations of the cavernous sinus area. We report an unusual case of unilateral proptosis (exophthalmos) caused by arterialized retrograde venous flow in the external jugular vein and cavernous sinus in a patient with an upper extremity hemodialysis fistula and ipsilateral acute central venous thrombosis. The patient's symptoms improved after surgical closure of the hemodialysis fistula.

The prediction of Metabolic Syndrome alterations is improved by combining waist circumference and handgrip strength measurements compared to either alone.

BACKGROUND: Adiposity is a major component of the metabolic syndrome (MetS), low muscle strength has also been identified as a risk factor for MetS and for cardiovascular disease. We describe the prevalence of MetS and evaluate the relationship between muscle strength, anthropometric measures of adiposity, and associations with the cluster of the components of MetS, in a middle-income country. METHODS: MetS was defined by the International Diabetes Federation criteria. To assess the association between anthropometric variables (waist circumference (WC), waist-to-hip ratio (W/H), body mass index (BMI)), strength (handgrip/kg bodyweight (HGS/BW)) and the cluster of MetS, we created a MetS score. For each alteration (high triglycerides, low HDLc, dysglycemia, or high blood pressure) one point was conferred. To evaluate the association an index of fat:muscle and MetS score, participants were divided into 9 groups based on combinations of sex-specific tertiles of WC and HGS/BW. RESULTS: The overall prevalence of MetS in the 5,026 participants (64% women; mean age 51.2 years) was 42%. Lower HGS/BW, and higher WC, BMI, and W/H were associated with a higher MetS score. Amongst the 9 HGS/BW:WC groups, participants in the lowest tertile of HGS/BW and the highest tertile of WC had a higher MetS score (OR = 4.69 in women and OR = 8.25 in men;p < 0.01) compared to those in the highest tertile of HGS/BW and in the lowest tertile of WC. CONCLUSION: WC was the principal risk factor for a high MetS score and an inverse association between HGS/BW and MetS score was found. Combining these anthropometric measures improved the prediction of metabolic alterations over either alone.

Mortality of COVID-19 patients with vascular thrombotic complications.

PURPOSE: To analyze the survival of patients hospitalized with COVID-19 and who presented some vascular thrombotic complication. MATERIAL AND METHODS: All consecutive patients with COVID-19 who were treated during the months of March and April 2020 at our institution were included. All patients were symptomatic and the thrombotic event objectively confirmed. Patients with deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and peripheral arterial thrombosis (PAT) were included. Survival curves for all groups were analyzed using Kaplan-Meier with Log Rank test, and Cox regression. RESULTS: During the pandemic period from March-1 to April-30, 2943 patients were treated with confirmed COVID-19 in our center. 106 patients showed some symptomatic vascular thrombosis: 13 patients had PAT, 15 ischemic stroke, 20 DVT and 58 PE. 11 patients presented multiple vascular thrombosis. Although the mean age was 65 years, there were differences between groups being older those patients with arterial thrombosis. A 67.92% were men. In total, 25 patients died during their hospital admission (23.58%), with differences between groups, being more common in patients with PAT (9 patients out of 13) and ischemic stroke (8 patients out of 15), than in those with DVT (1 patient out of 20) or PE (7 patients out of 58). CONCLUSIONS: The venous thromboembolic risk in these patients is greater than the arterial, but arterial thrombosis when it occurs was associated with high mortality rates. Survival was better in patients with DVT and PE than in patients with ischemic stroke or PAT.

OBJETIVO: Presentar nuestra experiencia y analizar la supervivencia de los pacientes hospitalizados con COVID-19 y que presentaron algún proceso trombótico vascular. MATERIAL Y MÉTODOS: Se incluyeron todos los pacientes consecutivos COVID-19 que fueron atendidos durante los meses de marzo-abril 2020 en nuestra institución. Se incluyeron pacientes sintomáticos con trombosis venosa profunda (TVP), tromboembolia pulmonar (TEP), ictus isquémico y trombosis arterial periférica (TAP) confirmados objetivamente. Se analizaron las curvas de supervivencia de todos los grupos mediante Kaplan-Meier, test de Log Rank, y regresión de Cox. RESULTADOS: Durante el periodo pandémico del 1-marzo al 30-abril, se atendieron 2943 pacientes COVID-19 en nuestro centro. 106 pacientes presentaron algún proceso trombótico vascular sintomático: 13 pacientes tuvieron TAP, 15 ictus, 20 TVP y 58 TEP. 11 pacientes mostraron trombosis vasculares múltiples. Aunque la edad media fue de 65 años, fueron de edad más avanzada los que mostraron trombosis arteriales que procesos tromboembólicos venosos. El 67.92% fueron hombres. En total, 25 pacientes murieron durante su ingreso hospitalario (23.58%), existiendo diferencias entre grupos siendo más común en pacientes con TAP (9 pacientes de 13), e ictus isquémico (8 pacientes de 15), que en los de TVP (1 paciente de 20) o TEP (7 pacientes de 58). CONCLUSIONES: El riesgo tromboembólico venoso en estos pacientes es mayor que el arterial, pero la trombosis arterial cuando acontece estuvo asociada a altas tasas de mortalidad. La supervivencia fue mejor en los pacientes con TVP y TEP que en los pacientes con ictus isquémico o trombosis arterial periférica.

[Mortality of covid-19 patients with vascular thrombotic complications]. / Mortalidad de los pacientes covid-19 con complicaciones trombóticas.

OBJECTIVE: To analyze the survival of patients hospitalized with covid-19 and who presented some vascular thrombotic complication. MATERIAL AND METHODS: All consecutive patients with covid-19 who were treated during the months of March and April 2020 at our institution were included. All patients were symptomatic and the thrombotic event objectively confirmed. Patients with deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and peripheral arterial thrombosis (PAT) were included. Survival curves for all groups were analyzed using Kaplan-Meier with log rank test, and Cox regression. RESULTS: During the pandemic period from March-1 to April-30, 2943 patients were treated with confirmed covid-19 in our center. Of them, 106 patients showed some symptomatic vascular thrombosis: 13 patients had PAT, 15 ischemic stroke, 20 DVT and 58 PE. Another 11 patients presented multiple vascular thrombosis. Although the mean age was 65 years, there were differences between groups being older those patients with arterial thrombosis. A 67.92% were men. In total, 25 patients died during their hospital admission (23.58%), with differences between groups, being more common in patients with PAT (9 patients out of 13) and ischemic stroke (8 patients out of 15), than in those with DVT (1 patient out of 20) or PE (7 patients out of 58). CONCLUSIONS: The venous thromboembolic risk in these patients is greater than the arterial, but arterial thrombosis when it occurs was associated with high mortality rates. Survival was better in patients with DVT and PE than in patients with ischemic stroke or PAT.

Ketogenic diets as treatment of obesity and type 2 diabetes mellitus.

During the last decades, several interventions for the management of overweight and obesity have been proposed. Among diets, the first studies focused on the effect of water only and total fasting diets with or without proteins. Unfortunately, they were found to be associated with adverse events which lead to the abandon of these strategies. Interestingly, despite the radical approach, total fasting was effective and generally well tolerated. A strict connection between protein-calorie malnutrition and increased in morbidity and mortality in hospitalized patients was found at that time. Then, the seminal works of Blackburn and his collaborators lead to the introduction of the protein-sparing modified fast. Encouraged by the early results using this intervention, diets evolved to the current very-low-calorie ketogenic diets (VLCKD). In the present review, results of studies on the VLCKDs are presented and discussed, with a particular reference to the protocolled VLCKD. Also, a recent proposal on the nomenclature on the ketogenic diets is reported. Available evidence suggests VLCKDs to be effective in achieving a rapid and significant weight loss by means of an easily reversible intervention which could be repeated, if needed. Muscle mass and strength are preserved, resting metabolic rate is not impaired, hunger, appetite and mood are not worsened. Symptoms and abnormal laboratory findings can be there, but they have generally been reported as of mild intensity and transient. Preliminary studies suggest VLCKDs to be a potential game-changer in the management of type 2 diabetes too. Therefore, VLCKDs should be considered as an excellent initial step in properly selected and motivated patients with obesity or type 2 diabetes, to be delivered as a part of a multicomponent strategy and under strict medical supervision.

COVID-19-Related Aortic Thrombosis: A Report of Four Cases.

COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe 4 cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.

Self-Reported Prevalence of Chronic Non-Communicable Diseases in Relation to Socioeconomic and Educational Factors in Colombia: A Community-Based Study in 11 Departments.

Background: Chronic non-communicable diseases are prevalent conditions in developing countries, such as Colombia. Several socioeconomic and educational factors have been associated with these pathologies. However, there is little country-specific information regarding the self-reported prevalence of chronic diseases and their association with the aforementioned factors in Colombia. Objectives: To evaluate the current situation of chronic non-transmissible diseases in Colombia by self-report and to analyze its potential relationship with sociodemographic, economic and educational factors. Methods: This is a cross-sectional baseline sub-analysis from the prospective, standardized collaborative PURE study in Colombia. Participants were recruited between 2005 to 2009, in 11 departments of the country, and included 7,485 subjects of 35 to 70 years old. Questionnaires of self-reported chronic non-communicable diseases, and demographic, socioeconomic and educational variables were applied. Results: Hypertension was the most prevalent chronic condition reported with a prevalence of 22.2% (21.2%-23.1%, 95% CI), followed by diabetes with a prevalence of 5.7% (5.1%-6.2%, 95% CI), asthma 2.7% (2.2%-3.0%, 95% CI), coronary heart disease 2.4% (2.0%-2.7%, 95% CI), stroke and heart failure 1.5% (1.2%-1.8%, 95% CI) each, chronic obstructive pulmonary disease 1.2% (0.6%-1.5%, 95% CI), and cancer 1.2% (1.0%-1.5%, 95% CI). Among the study sample, 23.3% (22.4%-24.3%, 95% CI) reported having one chronic NCDs, and 6.4% (5.9%-7.0%, 95% CI) reported having multiple chronic NCDs. The prevalence of multiple NCDs increased significantly with age, was more common in those from households with higher income, whereas it was significantly lower in persons with high education.The central and central-east regions of the country are those with the higher prevalence of self-reported NCDs. Conclusion: The results of the current study indicate the presence of socioeconomic and educational inequalities in the distribution of chronic NCDs in the Colombian population.

Atrial Fibrillation and Surgical Patients with Peripheral Arterial Disease.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice and its prevalence rate significantly increases with age. The prognostic implication of AF in surgical patients with peripheral arterial disease (PAD) has not been analyzed. The aims of this study were to analyze the prevalence of AF among patients operated on with symptomatic PAD, and to determine whether these patients are at a higher risk of death or amputation. METHODS: We designed a retrospective cohort study, from January 2013 to December 2017, in which we analyzed the medical records of all consecutive patients with symptomatic PAD admitted to our hospital and underwent a vascular procedure. We compared the outcomes of patients with and without AF. All statistically significant demographic variables that underwent a univariate analysis were inserted in the stepwise multivariate model along with AF. A survival analysis was performed to evaluate the factors associated with mortality through a Cox regression model. P-value of 0.05 was considered statistically significant. RESULTS: Four hundred three patients were admitted in-hospital with symptomatic PAD and they underwent a vascular intervention. The mean follow-up was 2 years. Seventy-six patients (18.8%) had AF. These patients were older (78 ± 9.1 years) than the 327 patients without AF (68 ± 12.37 years) (P < 0.0001), and more likely to undergo emergency surgery (18.42% vs. 7.34%, P = 0.0029). Age and emergency admission were dependent associates of AF. The patients with AF were frequently men (69.7%) with previous hypertension (96% %). The presence of AF was associated with higher rate of all-cause mortality (55.26%, P < 0.0001, hazard ratio 2.24, confidence interval 1.55-3.25), but the multivariate analysis adjusted for risk factors showed that the mortality was only associated with age because these patients were older and with many comorbidities. The majority of this population with AF showed some tissue lesion when they were admitted in-hospital (Rutherford V-VI, AF 80.2%, P = 0.0004), and this fact justified that a 22.36% underwent a major amputation affecting the ischemic lower limb in admission (P = 0.018). During the follow-up the free amputation rate was similar between groups (60.5% AF vs. 78.3% non-AF). CONCLUSIONS: This study showed the high prevalence of AF in patients with symptomatic PAD that required surgical admission in-hospital. The presence of AF was related with a greater and serious risk of mortality, but this was independently associated to age, because patients with AF were older and frailer. Clearly, this group of patients had a high risk of amputation when they arrived to the hospital and they needed emergency surgery.

Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity.

: The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet.

Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese Patients.

Psychological well-being and hunger and food control are two relevant factors involved in the success of weight-loss therapy in treating obesity. Thus, this study aims to evaluate food and alcohol cravings, physical and sexual activity, sleep, and life quality (QoL) in obese patients following a very low-calorie ketogenic (VLCK) diet, as well as the role of weight lost and ketosis on these parameters. A battery of psychological test was performed in twenty obese patients (12 females, 47.2 ± 10.2 year and BMI of 35.5 ± 4.4) through the course of a 4-month VLCK diet on four subsequent visits: baseline, maximum ketosis, reduced ketosis, and endpoint. Each subject acted as their own control. Relevantly, the dietary-induced changes in body composition (7.7 units of BMI lost, 18 kg of fat mass (1.2 kg of visceral fat mass)) were associated with a statistically significant improvement in food craving scores, physical activity, sleepiness, and female sexual function. Overall, these results also translated in a notable enhancement in QoL of the treated obese patients. Therefore, the rapid and sustained weight and fat mass (FM) loss induced by the VLCK diet is associated with good food control and improvements in the psychological well-being parameters in obese subjects, which could contribute to the long-term success of this therapy.

Resting metabolic rate of obese patients under very low calorie ketogenic diet.

BACKGROUND: The resting metabolic rate (RMR) decrease, observed after an obesity reduction therapy is a determinant of a short-time weight regain. Thus, the objective of this study was to evaluate changes in RMR, and the associated hormonal alterations in obese patients with a very low-calorie ketogenic (VLCK)-diet induced severe body weight (BW) loss. METHOD: From 20 obese patients who lost 20.2 kg of BW after a 4-months VLCK-diet, blood samples and body composition analysis, determined by DXA and MF-Bioimpedance, and RMR by indirect calorimetry, were obtained on four subsequent visits: visit C-1, basal, initial fat mass (FM) and free fat mass (FFM); visit C-2, - 7.2 kg in FM, - 4.3 kg in FFM, maximal ketosis; visit C-3, - 14.4 kg FM, - 4.5 kg FFM, low ketosis; visit C-4, - 16.5 kg FM, - 3.8 kg FFM, no ketosis. Each subject acted as his own control. RESULTS: Despite the large BW reduction, measured RMR varied from basal visit C-1 to visit C-2, - 1.0%; visit C-3, - 2.4% and visit C-4, - 8.0%, without statistical significance. No metabolic adaptation was observed. The absent reduction in RMR was not due to increased sympathetic tone, as thyroid hormones, catecholamines, and leptin were reduced at any visit from baseline. Under regression analysis FFM, adjusted by levels of ketonic bodies, was the only predictor of the RMR changes (R2 = 0.36; p < 0.001). CONCLUSION: The rapid and sustained weight and FM loss induced by VLCK-diet in obese subjects did not induce the expected reduction in RMR, probably due to the preservation of lean mass. TRIAL REGISTRATION: This is a follow up study on a published clinical trial.

Acid-base safety during the course of a very low-calorie-ketogenic diet.

BACKGROUND AND AIMS: Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet. METHOD: Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (baseline); visit C-2, (1-2 months); maximum ketosis; visit C-3 (2-3 months), ketosis declining; and visit C-4 at 4 months, no ketosis. Results were compared with 51 patients that had an episode of diabetic ketoacidosis as well as with a group that underwent a similar VLCK diet in real life conditions of treatment. RESULTS: Visit C1 blood pH (7.37 ± 0.03); plasma bicarbonate (24.7 ± 2.5 mmol/l); plasma glucose (96.0 ± 11.7 mg/l) as well as anion gap or osmolarity were not statistically modified at four months after a total weight reduction of 20.7 kg in average and were within the normal range throughout the study. Even at the point of maximum ketosis all variables measured were always far from the cut-off points established to diabetic ketoacidosis. CONCLUSION: During the course of a VLCK diet there were no clinically or statistically significant changes in glucose, blood pH, anion gap and plasma bicarbonate. Hence the VLCK diet can be considered as a safe nutritional intervention for the treatment of obesity in terms of acid-base equilibrium.

Mendelian Genes and Risk of Intracerebral Hemorrhage and Small-Vessel Ischemic Stroke in Sporadic Cases.

BACKGROUND AND PURPOSE: Mendelian strokes are rare genetic disorders characterized by early-onset small-vessel stroke. Although extensively studied among families with syndromic features, whether these genes affect risk among sporadic cases is unknown. METHODS: We sequenced 8 genes responsible for Mendelian stroke in a case-control study of sporadic stroke cases (≤70 years). Participants included 1251 primary stroke cases of small-vessel pathology (637 intracerebral hemorrhage and 614 small-vessel ischemic stroke cases) and 1716 controls from the INTERSTROKE study (Study of the Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World). RESULTS: Overall, the prevalence of canonical disease-causing mutations was 0.56% in cases and 0.23% in controls (odds ratio=1.89; 95% confidence interval, 0.54-7.57; P=0.33). CADASIL (Cerebral Autosomal Dominant Arteriopathies with Subcortical Infarcts and Leukoencephalopathies) mutations were more frequent among cases (0.48%) than controls (0.23%) but were not significantly associated with stroke risk (odds ratio=2.03; 95% confidence interval, 0.58-8.02; P=0.27). Next, we included all rare nonsynonymous mutations to investigate whether other types of mutations may contribute to stroke risk. Overall, 13.5% of cases and 14.2% of controls were carriers of at least one rare nonsynonymous mutation among the 8 Mendelian stroke genes. Mutation carriers were not at elevated risk of stroke (odds ratio=0.93; 95% confidence interval, 0.75-1.16; P=0.55). CONCLUSIONS: In the absence of syndromic features and family history of stroke, screening for Mendelian mutations among small-vessel stroke patients is unlikely to have high diagnostic utility.

Body Composition Changes After Very-Low-Calorie Ketogenic Diet in Obesity Evaluated by 3 Standardized Methods.

Context: Common concerns when using low-calorie diets as a treatment for obesity are the reduction in fat-free mass, mostly muscular mass, that occurs together with the fat mass (FM) loss, and determining the best methodologies to evaluate body composition changes. Objective: This study aimed to evaluate the very-low-calorie ketogenic (VLCK) diet-induced changes in body composition of obese patients and to compare 3 different methodologies used to evaluate those changes. Design: Twenty obese patients followed a VLCK diet for 4 months. Body composition assessment was performed by dual-energy X-ray absorptiometry (DXA), multifrequency bioelectrical impedance (MF-BIA), and air displacement plethysmography (ADP) techniques. Muscular strength was also assessed. Measurements were performed at 4 points matched with the ketotic phases (basal, maximum ketosis, ketosis declining, and out of ketosis). Results: After 4 months the VLCK diet induced a -20.2 ± 4.5 kg weight loss, at expenses of reductions in fat mass (FM) of -16.5 ± 5.1 kg (DXA), -18.2 ± 5.8 kg (MF-BIA), and -17.7 ± 9.9 kg (ADP). A substantial decrease was also observed in the visceral FM. The mild but marked reduction in fat-free mass occurred at maximum ketosis, primarily as a result of changes in total body water, and was recovered thereafter. No changes in muscle strength were observed. A strong correlation was evidenced between the 3 methods of assessing body composition. Conclusion: The VLCK diet-induced weight loss was mainly at the expense of FM and visceral mass; muscle mass and strength were preserved. Of the 3 body composition techniques used, the MF-BIA method seems more convenient in the clinical setting.

Social disparities explain differences in hypertension prevalence, detection and control in Colombia.

OBJECTIVE: Hypertension is the principal risk factor for cardiovascular diseases. The global Prospective Urban Rural Epidemiology study showed that the levels of awareness, treatment and control of this condition are very low worldwide and show large regional variations related to a country's income index. The aim of the present analysis was to identify associations between sociodemographic, geographic, anthropometric, behavioral and clinical factors and the awareness, treatment and control of hypertension within Colombia - a high-middle income country which participated in the global Prospective Urban Rural Epidemiology study. METHODS AND RESULTS: The sample comprised 7485 individuals aged 35-70 years (mean age 50.8 years, 64% women). Mean SBP and DBP were 129.12 ±â€Š21.23 and 80.39 ±â€Š11.81 mmHg, respectively. The overall prevalence of hypertension was 37.5% and was substantially higher amongst participants with the lowest educational level, who had a 25% higher prevalence (<0.001). Hypertension awareness, treatment amongst those aware, and control amongst those treated were 51.9, 77.5 and 37.1%, respectively. The prevalence of hypertension was higher amongst those with a higher BMI (<0.001) or larger waist-hip ratio (<0.001). Being male, younger, a rural resident and having a low level of education was associated with significantly lower hypertension awareness, treatment and control. The use of combination therapy was very low (27.5%) and was significantly lower in rural areas and amongst those with a low income. CONCLUSION: Overall Colombia has a high prevalence of hypertension in combination with very low levels of awareness, treatment and control; however, we found large variations within the country that appear to be associated with sociodemographic disparities.