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Diabetic retinopathy is a devastating and frequent complication of poorly controlled diabetes, whose pathogenesis is still only partially understood. Advances in basic research over the last two decades have led to the discovery of angiopoietins, proteins that strongly influence the growth and integrity of blood vessels in many vascular beds, with particular importance in the retina. Angiopoietin 1 (Ang1), produced mostly by pericytes and platelets, and angiopoietin 2 (Ang2), produced mainly by endothelial cells, bind to the same receptor (Tie2), but exert opposing effects on target cells. Ang1 maintains the stability of the mature vasculature, while Ang2 promotes vessel wall destabilization and disruption of the connections between endothelial cells and pericytes. Human retinal endothelial cells exposed to Ang2 show reduced membrane expression of the adhesion molecule VE-cadherin, and patients with proliferative diabetic retinopathy or diabetic macular edema have markedly increased vitreal concentrations of Ang2. Faricimab, a bi-specific antibody simultaneously directed against Ang2 and VEGF, has shown promising results in clinical trials among patients with diabetic retinopathy, and other agents targeting the angiopoietin system are currently in development.

Introduction: Calories from sugar-sweetened beverages (SSBs) contribute to the development of noncommunicable diseases. There is limited knowledge of the intake of SSBs and their correlates in developing countries. Thus, this study aimed to estimate the consumption of multiple SSBs and their sociodemographic correlates in an urban adult population from Colombia, South America. Methods: This was a probabilistic, population-level study of adults aged 18 to 75 from five cities representing different regions of Colombia. Dietary intake was assessed employing a 157-item semiquantitative food frequency questionnaire that inquired about intake over the last year. The consumption of regular soda, low-calorie soda, homemade and industrialized fruit juices, energy drinks, sport drinks, malt drinks and traditional sugar cane infusion (“agua de panela”) was analyzed for the total sample and subgroups defined by sociodemographic and clinical factors of interest. Results: The study included 1491 individuals (female: 54.2%, mean age: 45.3, overweight: 38.0%, obese: 23.3%). Sugary beverages contributed, on average, 287 Cal/d among women and 334 Cal/d among men, representing 8.9% of total daily calories (TDC). Women in the lowest SEL consumed 10.6% of their TDC from sugary drinks, as opposed to 6.6% for those in a high SEL. For men, this difference was not present (p-value for interaction = 0.039). Interestingly, a higher educational level correlated with a lower consumption of calories from sugary drinks only among men. Fruit juices were by far the main source of sugary drinks, and their consumption did not change sizably by sex and socioeconomic or educational level. Among women, there was a negative association between socioeconomic level (SEL) and consumption of regular soda, a 50% difference between extreme levels. The intake of low-calorie soda was much higher among men than women, and it more than tripled in the highest vs. lowest SEL among men. The consumption of energy drinks was heavily concentrated in men of low SEL. Conclusion: Colombian urban adults obtain a considerable proportion of their calories from sugary drinks, especially vulnerable groups such as women with lower education. Given the recent acceleration of the obesity epidemic in Latin America, strategies to limit the intake of such liquid calories may provide important public health benefits.

Objective:To explore the influence of socio-economic position (SEP) on habitual dietary intake in Colombian cities.Design:We conducted a cross-sectional, population-based study in five Colombian cities. Dietary intake was assessed with a 157-item semi-quantitative FFQ previously developed for the Colombian population. Nutrient analysis was performed using national and international food composition tables. SEP was assessed with two indicators: a government-defined, asset-based, household-level index called socio-economic stratum (SES) and, among adults, highest educational level attained.Setting:The five main urban centers of Colombia: Bogotá, Medellin, Barranquilla, Cali and Bucaramanga.Participants:Probabilistic, multi-stage sample of 1865 participants (n 1491 for analyses on education).Results:For both sexes, increasing SES was associated with a lower consumption of energy (P-trend P-trend P-trend = 0·005 in males, P-trend P-trend = 0·002). More educated men consumed significantly less energy and carbohydrates (P-trend = 0·036 and P-trend = 0·023). Among women, higher educational level was associated with higher MUFA intake (P-trend = 0·027).Conclusions:SES and educational level are strong correlates of the usual diet of urban Colombians. Economically deprived and less educated segments of society display dietary habits that make them vulnerable to chronic diseases and should be the primary target of public health nutrition policies.

Data on dietary calcium and vitamin D intake from Latin America are scarce. We explored the main correlates and dietary sources of calcium and vitamin D in a probabilistic, population-based sample from Colombia. We studied 1554 participants aged 18–75 from five different geographical regions. Dietary intake was assessed by employing a 157-item semi-quantitative food frequency questionnaire and national and international food composition tables. Daily vitamin D intake decreased with increasing age, from 230 IU/day in the 18–39 age group to 184 IU/day in the 60–75 age group (P -trend < 0.001). Vitamin D intake was positively associated with socioeconomic status (SES) (196 IU/day in lowest vs 234 in highest SES, P-trend < 0.001), and with educational level (176 IU/day in lowest vs 226 in highest education level, P-trend < 0.001). Daily calcium intake also decreased with age, from 1376 mg/day in the 18–39 age group to 1120 mg/day in the 60–75 age group (P -trend < 0.001). Calcium intake was lowest among participants with only elementary education, but the absolute difference in calcium intake between extreme education categories was smaller than for vitamin D (1107 vs 1274 mg/day, P-trend = 0.023). Daily calcium intake did not correlate with SES (P -trend = 0.74). Eggs were the main source of overall vitamin D, albeit their contribution decreased with increasing age. Dairy products contributed at least 48% of dietary calcium in all subgroups, mostly from cheese-containing traditional foods. SES and education were the key correlates of vitamin D and calcium intake. These findings may contribute to shape public health interventions in Latin American countries.

Data on dietary calcium and vitamin D intake from Latin America are scarce. We explored the main correlates and dietary sources of calcium and vitamin D in a probabilistic, population-based sample from Colombia. We studied 1554 participants aged 18–75 from five different geographical regions. Dietary intake was assessed by employing a 157-item semi-quantitative food frequency questionnaire and national and international food composition tables. Daily vitamin D intake decreased with increasing age, from 230 IU/day in the 18–39 age group to 184 IU/day in the 60–75 age group (P -trend < 0.001). Vitamin D intake was positively associated with socioeconomic status (SES ) (196 IU/day in lowest vs 234 in highest SES, P-trend < 0.001), and with educational level (176 IU/day in lowe st vs 226 in highest education level, P-trend < 0.001). Daily calcium intake also decreased with age, from 1376 mg/day in the 18–39 age group to 1120 mg/day in the 60–75 age group (P -trend < 0.001). Calcium intake was lowest among participants with onl y elementary education, but the absolute difference in calcium intake between extreme ed ucation categories was smaller than for vitamin D (1107 vs 1274 mg/day, P-trend = 0.023). Daily calcium intake did not correlate with SES (P -trend = 0.74). Eggs were the main source of overall vitamin D, albeit their contribution decreased with increasing age. Dairy products contributed at least 48% of dietary calcium in all subgroups, mostly from cheese-containing traditional foods. SES and education were the key correlates of vitamin D and calc ium intake. These findings may contribute to shape public health interventions in Latin American countries.

Context The relative importance of the control of different metabolic risk factors for the prevention of chronic kidney disease among patients with diabetes in real life conditions is insufficiently understood. Objective We evaluated the effect of the achievement of glycated hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDLc) or non–high-density lipoprotein cholesterol (non-HDLc) goals (ABC goals) on the development of incident chronic kidney disease (iCKD) among patients with diabetes. Methods In a nationwide registry of all individuals diagnosed with diabetes assisted by the health system in Colombia, we analyzed the association between baseline or sustained goal achievement and development of iCKD over a 4-year follow-up. iCKD was defined as a new occurrence of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2, hemodialysis, peritoneal dialysis, or kidney transplant. Results The study included 998 790 adults with diabetes (56% female, mean age 59). There were 125 626 cases of iCKD. After adjustment for multiple confounders, a baseline SBP less than 130 mm Hg (odds ratio [OR] 0.79 [0.78-0.80]) and a baseline HbA1c less than 7.0% (OR 0.86 [0.85-0.87]) were negatively associated with iCKD. Sustained achievement showed stronger negative associations with iCKD than just baseline achievement. Considering each goal separately, sustained non-HDLc less than 130 mg/dL had the strongest negative association with iCKD (OR 0.67 [0.65-0.69]). Patients who maintained the triple ABC goal over the entire follow-up had 32% (29-34) lower odds of developing CKD, 38% (34-42) if they additionally kept a normal body mass index (BMI). Sustained ABC control including a normal BMI was more strongly associated with a lower incidence of CKD in patients of Black race (OR 0.72 vs 0.89; P for interaction = .002). Conclusion At the country level, sustained achievement of ABC goals and most especially non-HDLc were associated with substantial reductions in iCKD.

Background Primary biliary cholangitis (PBC) is a serious disease that causes significant morbidity. PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis. The performance of autoantibodies for the diagnosis of PBC seems to vary widely across populations. Aim To assess the diagnostic performance of several autoantibodies for the diagnosis of PBC in Latin American individuals. Methods We studied 85 female adult Colombians, 43 cases with biopsy-confirmed PBC and 42 controls in whom a liver biopsy ruled out PBC. Plasma anti-mitochondrial antibodies (AMAs), anti-smooth muscle antibodies (ASMAs) and anti-nuclear antibodies (ANAs), as well as total immunoglobulin (Ig) M and IgG were determined using immunofluorescence or enzyme-linked immunosorbent assay in all study participants within 1 year of the biopsy. For all variables, values analyzed were those closest to the date of the biopsy. Patients with viral or alcoholic hepatitis were excluded. Results Mean age at diagnosis was 58.7 years for cases and 56.9 years for controls, and the body mass index was lower among cases. Most cases received ursodeoxycholic acid, while most controls received vitamin E. Sjogren syndrome and Hashimoto's thyroiditis were the most frequent autoimmune comorbidities of PBC. The prevalence of AMA positivity among PBC cases was unexpectedly low. The sensitivity and specificity values were respectively 44.2% and 76.2% for AMA, 74.4% and 38.1% for ANA, 14.0% and 73.8% for ASMA, 26.7% and 80.0% for IgG, and 57.1% and 85.7% for IgM. The combination of positive AMA plus positive IgM had 91% positive predictive value for PBC. Among AMA-negative cases, the most prevalent antibodies were ANA (87.5%). In all, 62% of AMA-positive and 84.6% of IgM-positive individuals had fibrosis in their biopsy. Conclusion AMA positivity was very low among female Latin American patients with PBC. The performance of all antibodies was quite limited. These results highlight the urgent need for better PBC biomarkers.

Diabetes is a highly prevalent disease with complications that impact most bodily systems. However, the impact of diabetes on bone health is frequently ignored or underestimated. Both type 1 (T1D) and type 2 diabetes (T2D) are associated with a higher risk of fractures, albeit through different mechanisms. T1D is characterized by near total insulinopenia, which affects the anabolic tone of bone and results in reduced bone mineral density (BMD). Meanwhile, patients with T2D have normal or high BMD, but carry an increased risk of fractures due to alterations of bone microarchitecture and a local humoral environment that stimulates osteoclast activity. Chronic hyperglycemia induces non-enzymatic glycation of collagen in both types of diabetes. Epidemiological evidence confirms a largely increased fracture risk in T1D and T2D, but also that it can be substantially reduced by opportune monitoring of fracture risk and appropriate treatment of both diabetes itself and osteopenia or osteoporosis if they are present. In this review, we summarize the mechanistic, epidemiological, and clinical evidence that links diabetes and bone fragility, and describe the impact of available diabetes treatments on bone health.

Objective To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis. Patients and methods Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration ( Results Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (P < 0.001) to 35.1 mg/dL for chlormadinone (P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (–7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration. Conclusion Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

Familial chylomicronemia is a disease in which a genetic mutation affects the ability of the organism to metabolize triglycerides bound to lipoproteins, causing extremely high plasma triglycerides and associated consequences. The most frequent complication is acute pancreatitis, which may lead to multiorganic failure or pancreatic insufficiency. Familial chylomicronemia also exerts a profound negative impact on quality of life, social relationships and professional development. The gene most frequently affected is lipoprotein lipase-1 gene (LPL), the enzyme in charge of hydrolyzing circulating triglycerides for tissue uptake. Mutations in other genes regulating maturation, transport or polymerization (eg. APOC2, APOAV, LMF-1, GPIHBP-1) of lipoprotein lipase-1, may also be involved. However, in about 30% of patients the causal variant is not identified. Familial chylomicronemia should be suspected in patients with severe hypertriglyceridemia with poor response to conventional treatment, or accompanied by eruptive xanthomas, lipemia retinalis or abdominal pain. The availability of risk scores and genetic tests should facilitate its opportune detection and management. Nutritional therapy is based on a very-low-fat diet with adequate supply of lipid-soluble vitamins and essential fatty acids, plus avoidance of alcohol consumption. Current pharmacological treatment may include fibrates and omega-3 fatty acids but prioritizes biotechnological agents targeting the molecular disturbances of the disease. These include an antisense oligonucleotide against apoC-III (volanesorsen), a monoclonal antibody against angiopoietin-like protein-3 (evinacumab), and other agents currently in development.

Objective Latin American countries are experiencing a nutritional and demographic transition that predisposes to the spread of the obesity epidemic, especially among the socially and economically disadvantaged. We aimed to describe the prevalence of obesity, overweight and abdominal obesity and their association with household socioeconomic status (SES) and personal educational level in the five major cities of Colombia (Bogota, Medellin, Cali, Barranquilla and Bucaramanga). Materials and methods We collected demographic and anthropometric measurements from a population-based, stratified, multi-stage probability sample of individuals aged 2-75 years. Study surveys and anthropometric measurements were administered by highly trained staff. All reported prevalences are expanded to the target population, taking into account the sampling design. Results The study sample included 1922 participants. In children and adolescents, the prevalence of overweight and obesity were respectively 23% and 8.8%. Overweight was most prevalent in the 2-4 (30.9%), followed by the 5-11 (23.8%) and the 12-17 age group (17.8%). The combined prevalence of childhood overweight and obesity increased with SES (16.8% in the lowest vs 42.8% in the highest stratum). In adults (18-75 years), the prevalence of excess body weight was 57.5% (36.2% overweight, 21.3% obesity), the prevalence of abdominal obesity was 34.4%, all prevalences increased with age. Obesity was far more prevalent among adult women (29.4%) than men (12.6%) (p˂0.001). Adult obesity and abdominal obesity decreased significantly and monotonically with SES and were most prevalent in individuals with the lowest educational level (35.3% and 50.7%, respectively). Almost 40% of overweight adults had abdominal obesity. Conclusion Obesity and abdominal obesity are highly prevalent in the urban population of Colombia, and much more frequent among adults of lower SES and educational level. Excess body weight affected more often children of higher SES. Public health measures are urgently needed to tackle the spread of the obesity epidemic in Colombia and other Latin American countries, with a focus on low-income and low-educational level segments of society.

Aim: To study the criterion validity of three indirect maximal oxygen uptake (V˙O2max) assessment equations at altitude. Methods: We studied 64 young adults (53% men) at Bogota, Colombia (2600 m al...

Background The functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. Methods Eighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E + C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E + C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using non-denaturing electrophoresis and anti-apoA-I western blotting. Results HDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6% of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8, 12.2 and 8.37% of plasma LCAT respectively for E + C-, E-C+ and E + C+). LCAT mass was lower in E + C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r = − 0.55, P = 0.017) and E-C- alpha 1 HDL (r = − 0.49, P = 0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r = 0.52, P = 0.025). Conclusions The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.

Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of aging-associated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype—SASP) that plays a physiological role in embryonic development and healing processes. However, DNA damage and oxidative stress that occur during aging cause the accumulation of senescent cells, which through their SASP bring about deleterious effects on multiple organ and systemic functions. Ablation of senescent cells through genetic or pharmacological means leads to improved life span and health span in animal models, and preliminary evidence suggests it may also have a positive impact on human health. Thus, strategies to reduce or eliminate the burden of senescent cells or their products have the potential to impact multiple clinical outcomes with a single intervention. In this review, we touch upon the basics of cell senescence and summarize the current state of development of therapies against cell senescence for human use.

To assess the achievement of essential treatment goals among patients with diabetes in Colombia.We analyzed data from a nationwide registry of all individuals with diagnosed diabetes, hypertension or CKD assisted by the health system. We explored the prevalence of treatment goals (HbA1c 7% [53 mmol/mol], systolic blood pressure (SBP) 130 mmHg and LDLc 100 mg/dL), and their variations by race and type of health insurance, between July 1, 2015, and June 30, 2019.We studied 1 352 846 patients with diagnosed diabetes. The prevalence of HbA1c 7% (53 mmol/mol) remained steady at 52%, systolic blood pressure (SBP) 130 mmHg was also stable at 80-82%. Meanwhile, the prevalence of both LDLc 100 mg/dL and non-HDLc 130 mg/dL increased by 6 percentage points. Achievement of the triple HbA1c + SBP + LDLc goal was only 21.4% in 2015, increasing to 24.4% by 2019. Goal achievement was consistently lower among patients of black race, especially for HbA1c (5% lower than other races), but also for the SBP, LDLc and joint goals. Patients under third-party insurance reached better HbA1c, SBP, and LDLc control.Achievement of treatment goals of patients with diabetes in Colombia remains substantially low, despite improvements in LDLc control.

Rare pathogenic variants in the LMF1 gene, which encodes lipase maturation factor 1, are a minor cause of familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia. In this report we present three adult patients, all of them born and raised in Quito, Ecuador, with severe hypertriglyceridemia secondary to biallelic LMF1 variants. In two of the three cases (patients 1 and 3), the presentation was acute pancreatitis secondary to plasma triglycerides well above 10 mmol/L. The other case (patient 2) was a sibling of one of the initial patients, who was asymptomatic but markedly hypertriglyceridemic. Next-generation sequencing revealed a homozygous splice-site variant in exon 6 of LMF1 in patients 1 and 2 (c.897GA, p.Gln299=), and a homozygous missense variant in exon 2 of LMF1 in patient 3 (c.233TC, p.Leu78Pro). The finding of two disease-causing variants in three patients from the same location raises the question of whether LMF1 may be a more prevalent cause of severe hypertriglyceridemia among Latin-American patients.

ObjectivesDiabetes is increasing rapidly in low-income and middle-income countries. We aimed to estimate the prevalence of diabetes, describe its correlates and its associated dietary intake in urban adults from Colombia.SettingThe Colombian Study of Nutritional Profiles was a population-based, cross-sectional, multi-stage probabilistic sampling survey designed to represent the five main Colombian cities.ParticipantsBetween June and November 2018, we studied 736 non-pregnant participants aged 18 or older. Diabetes was defined as a random plasma glucose ≥200 mg/dL, self-reported prior diagnosis of diabetes or use of any oral or injectable antidiabetic medication(s). Participants also fulfilled a detailed 157-item food-frequency questionnaire.Primary and secondary outcome measuresPrevalence of diabetes, dietary intake of key nutrients, achievement of dietary goals among individuals with diabetes.ResultsThe overall estimated prevalence of diabetes was 10.1%, with no difference by sex (9.6% in women, 10.8% in men, p=0.43). The association between diabetes and education level depended on sex, diabetes was more prevalent among more educated men and less educated women. Abdominal obesity was associated with a 65% increase in diabetes prevalence among men, and a 163% increase in women. Individuals with diabetes reported lower mean consumption of all nutrients, but after adjustment by sex, age, socioeconomic level (SEL) and body mass index, only their lower sodium consumption remained significant (p=0.013). The proportion of non-achievement of dietary intake goals among participants with diabetes was 94.4% for saturated fats, 86.7% for sodium, 84.4% for fibre and 80% for trans fats. In multivariate logistic regression models, age was the strongest independent correlate of diabetes.ConclusionsDiabetes by self-report, random plasma glucose or medication use was highly prevalent among Colombian adults. There were large differences by abdominal obesity status, region of residence, SEL and educational level. The proportion of individuals with diabetes meeting dietary recommendations was alarmingly low.

Dietary habits are a major determinant of the risk of chronic disease, particularly metabolic and endocrine disorders. Fish as a food group are a unique source of nutrients with metabolic and hormonal importance including omega-3 fatty acids, iodine, selenium, vitamin D, taurine and carnitine. Fish are also a source of high quality protein and have in general low caloric density. The impact of these nutrients on cardiovascular risk has been extensively reviewed, but the impact of fish on the broader field of endocrine and metabolic health is sometimes not sufficiently appreciated. This article aimed to summarize the impact the effect of regular fish consumption on conditions like the metabolic syndrome, obesity, diabetes, hypothyroidism, polycystic ovary syndrome and the menopausal transition, which are in and of themselves significant causes of morbidity and mortality worldwide. The review revealed that scientific evidence from food science, translational research, epidemiologic studies and interventional trials shows that regular fish consumption has a positive impact on thyroid homeostasis, facilitates maintenance of a healthy body weight, reduces the magnitude of age-associated increases in blood pressure, improves glucose homeostasis helping prevent diabetes and the metabolic syndrome, and has a positive impact on muscle mass preservation among the elderly. These effects are mediated by multiple mechanisms, only some of which have been identified. For most of these effects it holds true that the potential benefits are more substantial when baseline fish consumption is low.

Dietary habits have a major impact on the development and function of the immune system. This impact is mediated both by the intrinsic nutritional and biochemical qualities of the diet, and by its influence on the intestinal microbiota. Fish as a food is rich in compounds with immunoregulatory properties, among them omega-3 fatty acids, melatonin, tryptophan, taurine and polyamines. In addition, regular fish consumption favors the proliferation of beneficial members of the intestinal microbiota, like short-chain fatty acid-producing bacteria. By substituting arachidonic acid in the eicosanoid biosynthesis pathway, long-chain omega-3 fatty acids from fish change the type of prostaglandins, leukotrienes and thromboxanes being produced, resulting in anti-inflammatory properties. Further, they also are substrates for the production of specialized pro-resolving mediators (SPMs) (resolvins, protectins, and maresins), lipid compounds that constitute the physiological feedback signal to stop inflammation and give way to tissue reparation. Evidence from human observational and interventional studies shows that regular fish consumption is associated with reduced incidence of chronic inflammatory conditions like rheumatoid arthritis, and that continuous infusion of fish oil to tube-fed, critically ill patients may improve important outcomes in the ICU. There is also evidence from animal models showing that larger systemic concentrations of omega-3 fatty acids may counter the pathophysiological cascade that leads to psoriasis. The knowledge gained over the last few decades merits future exploration of the potential role of fish and its components in other conditions characterized by deregulated activation of immune cells and a cytokine storm like viral sepsis or COVID-19.

Background High-density lipoproteins (HDL) in plasma are strongly and negatively associated with cardiovascular risk, yet interventions to raise HDL have not improved cardiovascular outcomes. HDL functionality and heterogeneity may hold the clue to this paradox. The apolipoprotein composition of HDL may be an important determinant of their functionality. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are key enzymes for HDL-mediated reverse cholesterol transport. We assessed the distribution and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. Methods We isolated in adult humans of both sexes (mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%), four subspecies of HDL containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E+C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E+C+). In each HDL subspecies, we measured LCAT and CETP concentration and activity using immunoenzymatic and fluorometric methods. Additionally, we determined the size distribution of HDL in each apolipoprotein-defined fraction using non-denaturing electrophoresis and anti-ApoA-I western blot. Results Similar to previous studies, HDL in the E-C- fraction was the predominant subtype. The size distribution of HDL was very similar across all four apolipoprotein-defined fractions. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6 % of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8%, 12.2% and 8.37% of plasma LCAT respectively for E+C-, E-C+ and E+C+). Despite a much lower LCAT mass, LCAT activity in E+C- HDL was comparable to that in E-C- HDL. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and both E-C+ pre-beta HDL (r=-0.55, p=0.017) and E-C- alpha 1 HDL (r=-0.49, p=0.041). Conversely, there was a direct correlation between E-C+ alpha 1 HDL and CETP activity in plasma (r=0.52, p=0.025). Conclusions Our results suggest that LCAT activity in humans is influenced by the presence of small interchangeable apolipoproteins. The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol.

Aldosterone is a key regulator of water and electrolyte metabolism, but recent evidence from multiple lines of research also identifies it as a major player in other chronic disorders, particularly diabetes and the metabolic syndrome. In this review, we summarize rel- evant aspects of aldosterone production, secretion, action, the way aldosterone and the mineralocorticoid receptor may impact energy metabolism, and useful take-home messages concerning mineralocorticoid antagonism in patients with type 2 diabetes mellitus

Introducción: La folistatina es una proteína capaz de neutralizar varias hormonas de la familia del TGF-?, tales como la activina, las proteínas morfogénicas del hueso y la miostatina. Al inactivar la activina y la folistatina reduce la secreción de FSH. La folistatina se produce además de en el ovario en muchos otros tejidos, por ello se sospecha que tiene otros efectos. En ratones, la deleción genética de la folistatina se acompaña de resistencia a la insulina (RI). Sin embargo, la asociación entre la folistatina plasmática y RI medida directamente no ha sido evaluada en humanos.Métodos: En 81 participantes entre 30 y 69 años (56% mujeres, 54% con sobrepeso, 13% con obesidad), determinamos antropometría, composición corporal, factores de riesgo cardiovascular y múltiples índices de RI: Área incremental bajo la curva de insulina, índice de sensibilidad a la insulina según Gutt, Homeostatic Model Assessment – Insulin Resistance (HOMA-IR) e insulinemia en ayuno. Un subgrupo de 21 participantes se sometió además a un clamp hiperinsulinémico-euglucémico. La folistatina y la miostatina se midieron en plasma de ayuno, empleando técnicas inmunométricas.Resultados: La concentración promedio de folistatina fue 2.517±830 pg/mL, sin diferencia entre sexos (p=0,55). La folistatina tuvo una tendencia a correlación positiva con el porcentaje de masa magra (r=0,19, p=0,088) y negativa con el porcentaje de grasa corporal (r= -0,19, p=0,097). La folistatina no se correlacionó con índices de RI derivados de la PTOG pero sí con la captación corporal de glucosa en el clamp (r=0,42, p=0,031). No se halló asociación entre las concentraciones de folistatina y miostatina plasmáticas.Conclusión: Los niveles de folistatina mostraron una tendencia hacia una correlación positiva con la masa muscular y negativa con adiposidad corporal. Esto concuerda con el efecto inhibitorio de la folistatina sobre la miostatina. Aunque la folistatina no correlacionó con índices indirectos de RI, sí lo hizo con la determinación directa de sensibilidad a la insulina en el clamp hiperinsulinémico-euglucémico.

Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macrovascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with T2DM and compared them with healthy controls. We also analyzed microarrays of DNA methylation and gene expression of other important tissues in the context of diabetes from the GEO database repository and then compared these results with our experimental gene expression data. DNA methylation and, more importantly, DNA hydroxymethylation levels were increased in poorly controlled patients compared to well-controlled and healthy individuals. Both 5mC and 5hmC measurements were correlated with the percentage of glycated hemoglobin, indicating a direct impact of hyperglycemia on changes over the epigenome. The analysis of methylation microarrays was concordant, and 5mC levels were increased in the peripheral blood of T2DM patients. However, the DNA methylation levels were the opposite of those in other tissues, such as the pancreas, adipose tissue and skeletal muscle. We hypothesize that a process of DNA oxidation associated with hyperglycemia may explain the DNA demethylation in which the activity of ten-eleven translocation (TET) proteins is not sufficient to complete the process. High levels of glucose lead to cellular oxidation, which triggers the process of DNA demethylation aided by TET enzymes, resulting in epigenetic dysregulation of the damaged tissues.

Carlos O Mendivil,1,2 Freddy JK Toloza,1 Maria L Ricardo-Silgado,1 Martha C Morales-Álvarez,1 Jose O Mantilla-Rivas,1 Jairo A Pinzón-Cortés,1 Hernán N Lemus1 1School of Medicine, Universidad de los Andes, 2Section of Endocrinology, Fundación Santa Fe de Bogotá, Bogotá, Colombia Background: Autoimmunity against insulin-producing beta cells from pancreatic islets is a common phenomenon in type 1 diabetes and latent autoimmune diabetes in adults. Some reports have also related beta-cell autoimmunity to insulin resistance (IR) in type 2 diabetes. However, the extent to which autoimmunity against components of beta cells is present and relates to IR and insulin secretion in nondiabetic adults is uncertain.Aim: To explore the association between antibodies against glutamic acid decarboxylase (GADA), a major antigen from beta cells, and indices of whole-body IR and beta-cell capacity/insulin secretion in adults who do not have diabetes.Methods: We studied 81 adults of both sexes aged 30–70, without known diabetes or any autoimmune disease. Participants underwent an oral glucose tolerance test (OGTT) with determination of plasma glucose and insulin at 0, 30, 60, 90, and 120 minutes. From these results we calculated indices of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] and incremental area under the insulin curve [iAUCins]) and insulin secretion (corrected insulin response at 30 minutes and HOMA beta-cell%). GADAs were measured in fasting plasma using immunoenzymatic methods.Results: We found an overall prevalence of GADA positivity of 21.3%, without differences by sex and no correlation with age. GADA titers did not change monotonically across quartiles of any of the IR or insulin secretion indices studies. GADA did not correlate linearly with fasting IR expressed as HOMA-IR (Spearman’s r=−0.18, p=0.10) or postabsorptive IR expressed as iAUCins (r=−0.15, p=0.18), but did show a trend toward a negative correlation with insulin secretory capacity expressed by the HOMA-beta cell% index (r=−0.20, p=0.07). Hemoglobin A1c, body mass index, and waist circumference were not associated with GADA titers.Conclusion: GADA positivity is frequent and likely related to impaired beta-cell function among adults without known diabetes. Keywords: insulin resistance, autoimmunity, glutamate decarboxylase, latent autoimmune diabetes in adults, beta cell

Aims: Many patients with type 2 diabetes (DM2) in Latin American countries remain insufficiently controlled. We aimed to identify factors associated with persistent poor metabolic control in Colombian patients with DM2.Methods: Retrospective one-year follow-up cohort study of adult patients with DM2. The primary outcome was persistent poor metabolic control (PPMC): HbA1c level >8% in all measurements during follow-up. Secondary outcomes were intermittent poor metabolic control (IPMC) and good control (GC: simultaneous achievement of HbA1c, blood pressure and LDL cholesterol goals). Multiple demographic, clinical and laboratory variables were predictors in multivariable logistical models. Results: Of 399 patients included, 50 had the primary endpoint during follow-up. Older age was negatively associated with PPMC (OR 0.40, 95%CI 0.17-0.92 for extreme quartiles), even after multivariate adjustment. Depression and the presence of multiple microvascular complications were strongly associated with the secondary endpoint IPMC (multivariate OR respectively 4.2, 95%CI 1.08-16.4 for depression; 5.61, 95%CI 1.03-30.6 for microvascular complications). Being unemployed was associated with significantly less odds of achieving GC (multivariate OR 0.19, 95%CI 0.04-0.95). Conclusions: Age, depression, the presence of microvascular complications and employment status were associated with the success or failure of diabetes management. These factors were better correlates of therapeutic success than the pharmacological agent employed.

Introduction To evaluate the effect of a lipid-based formulation containing unusual polyunsaturated fatty acids, trace elements, polyphenols and plant sterols on insulin resistance and its associated disturbances among adults at risk of diabetes. Methods This was an 8-week, three-arm, open-label randomized clinical trial. We studied individuals aged ≥ 18 years old with diabetes risk given by a body mass index ≥ 25 kg/m2 or a FinnRisc score ≥ 13/20. Participants were randomly assigned to receive: 7 ml sunflower oil (control group), 3.5 ml of the study formulation + 3.5 ml of sunflower oil (low-dose group) or 7 ml of study formulation (high-dose group). Results We randomized 25 individuals. After one withdrawal in the high-dose group, the study sample comprised nine patients in the control, nine in the low-dose and six in the high-dose groups. The insulin sensitivity increased significantly and in a dose-dependent fashion, up to 10% in the high-dose group. At week 8 the low-dose group exhibited lower glycemic excursions during the oral glucose tolerance test (OGTT), especially 1 h after the glucose challenge (32 mg/dl or 23% lower vs. control group). The incremental area under the glucose curve in the OGTT was 17.1% lower in the low-dose group vs. the control group. Waist circumference increased in the control group, remained constant in the low-dose group and decreased in the high-dose group. C-reactive protein decreased in both formulation groups, up to 50% in the high-dose group. Participants in the formulation groups exhibited increased secretion of GLP-1 and plasma irisin at week 8 vs. the control group. Conclusion The formulation induced favorable changes in insulin sensitivity, glucose tolerance, abdominal obesity and inflammation. These effects and their durability will need to be assessed in larger studies. Trial Registration NCT03512665. Funding Team Foods Colombia.

The liver is a key organ in lipid and lipoprotein metabolism, hence hepatic diseases often manifest as lipid disturbances. Cholestatic liver diseases are frequently associated with an important increase in total cholesterol at the expense of lipoprotein X (LpX), an abnormal lipoprotein isolated and characterized in the 1960s to 1970s in patients with obstructive jaundice. Lipoprotein X is rich in phospholipids, albumin, and free cholesterol, has a density similar to low-density lipoprotein (LDL), and a size similar to very low-density lipoprotein (VLDL), which has hampered its detection through routine laboratory tests. Unlike LDL, LpX has no apoB-100, so it is not removed from circulation via the LDL receptor, and it is not clear whether or not it can be atherogenic. Although LpX was initially described in patients with cholestasis, it has also been found in patients with genetic deficiency of lecithin-cholesterol acyltransferase (LCAT), in patients who receive lipid-rich parenteral nutrition and most recently in patients with graft versus host disease of the liver. In the presence of LpX, plasma total cholesterol can rise up to 1000 mg/dL, which may lead to the development of skin xanthomas and hyperviscosity syndrome. Treatment of LpX-dependent hypercholesterolemia with conventional hypolipidemic drugs is frequently ineffective, and definitive treatment relies on correction of the underlying cause of cholestasis. Here, we present the case of a patient with LpX-dependent hypercholesterolemia in the context of primary biliary cholangitis.

Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.

Resumen Introduccion Los viajes urbanos pueden ser una actividad estresante con impacto la capacidad cognitiva, un componente central de la salud de las personas. El proposito de esta investigacion es explorar si el desempeno cognitivo se ve afectado de forma diferencial por el estres producido por el viaje en bicicleta o en transporte publico, en adultos que viajan a estudiar. Metodos Para este estudio, se diseno un experimento en el que se midieron, de forma sistematica el estres y el desempeno cognitivo, en siete participantes, en triplicado, en dias separados, antes y despues de cada viaje, para transporte publico y para bicicleta (6 viajes en total). Todos los participantes completaron una prueba de Stroop y una muestra de saliva antes y despues de cada viaje. Las diferencias de antes y despues de cada viaje en el cortisol salival, en el tiempo de respuesta del Stroop y del porcentaje de exito del Stroop, fueron comparadas entre los modos de transporte por medio de un analisis de varianza de dos vias (ANOVA), usando el modo de transporte y el participante como factores fijos. Resultados El cambio medio en el tiempo ajustado del Stroop fue similar entre los dos modos de transporte (1,392 ms ± 8,379 ms para bicicletas, 889 ms ± 6,675 ms para transporte publico, p = 0.85). Lo mismo ocurrio para el cambio medio en el porcentaje de exito del Stroop (1.39% ±5.16% para bicicletas, −0.59±5.79% para transporte publico, p = 0.83). Para el porcentaje de exito en el Stroop, el valor-p para el termino participante*modo fue p = 0.051. El cambio medio en el cortisol salival fue −0.39±1.69 ng/mL para la bicicleta y −1.02± 1.97 ng/mL para transporte publico (p = 0.11). El termino asociado a la variabilidad inter-individual en el cambio del cortisol fue significativo (p˂0.001). Conclusiones Los viajes urbanos en bicicleta o en transporte publico inducen un efecto comparable tanto en estres biologico como en desempeno cognitivo. Se conoce que la bicicleta otorga beneficios personales y para la sociedad. Nuestros resultados, adicionalmente muestran que a pesar del esfuerzo fisico, la bicicleta no induce un mayor estres biologico que el transporte publico.

Disorders of lipid and lipoprotein metabolism play a central role in the pathogenesis of atherosclerotic cardiovascular diseases (CVDs). Despite the widespread use of efficacious lipid-modifying therapies, the residual risk of CVD remains unacceptably high. The purpose of this manuscript is to review the application of new technologies in the treatment of lipid disorders. New therapies work mostly at the gene expression level and are, therefore, different from traditional small-molecule drugs that work mainly by inhibiting already synthesized proteins. We will briefly lay out the function of the gene products targeted by the new agents. Then, we will organize our review of new biotechnological treatments by the molecular approach, namely: monoclonal antibodies, antisense oligonucleotides, small-interfering RNAs, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9)-based genome editing. The paper concludes with the description of the current clinical studies and the perspectives for the use of these agents. (REV INVEST CLIN. 2018;70:244-54).

BACKGROUND. HDL that contains apolipoprotein E (apoE) is a subspecies especially active in steps in reverse cholesterol transport, a process that brings cholesterol from peripheral cells to the liver. Here, we studied the effect of dietary unsaturated fat compared with carbohydrate on the metabolism of HDL containing apoE. METHODS. We enrolled 9 adults who were overweight or obese and had below-average HDL-cholesterol in a crossover study of a high-fat diet, primarily unsaturated, and a low-fat, high-carbohydrate diet. A metabolic tracer study was performed after each diet period. RESULTS. Dietary fat increased the secretion, metabolism, and clearance of HDL subspecies containing apoE. Dietary fat increased the rate of clearance of large cholesterol-rich HDL containing apoE and increased their conversion to small HDL containing apoE, indicating selective cholesterol ester delivery to the liver. The high-unsaturated-fat diet did not affect the metabolism of HDL lacking apoE. CONCLUSION. HDL containing apoE is a diet-responsive metabolic pathway that renders HDL more biologically active in reverse cholesterol transport. This may be a mechanism by which unsaturated fat protects against coronary heart disease. Protein-based HDL subspecies such as HDL containing apoE may be used to identify additional atheroprotective treatment targets not evident in the total HDL-cholesterol measurement. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01399632","term_id":"NCT01399632"}}NCT01399632. FUNDING. NIH and the National Center for Advancing Translational Science.