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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 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.

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.

Rationale: The optimal modality, intensity, duration, frequency, and dose-response of exercise as a therapy for Parkinson's Disease (PD) are insufficiently understood. Objective: To assess the impact of a high-intensity tandem bicycle program on clinical severity, biomarkers, and functional MRI (fMRI) in PD. Methods: A single-center, parallel-group clinical trial was conducted. Thirteen PD patients aged 65 or younger were divided in two groups: a control group and an intervention group that incorporated a cycling program at 80% of each individual's maximum heart rate (HR) (≥80 rpm), three times a week, for 16 weeks. Both groups continued their conventional medications for PD. At baseline and at the end of follow-up, we determined in all participants the Unified Parkinson's Disease Rating Scale, anthropometry, VO2max, PD biomarkers, and fMRI. Results: VO2max improved in the intervention group (IG) (+5.7 ml/kg/min), while it slightly deteriorated in the control group (CG) (-1.6 ml/kg/min) (p = 0.041). Mean Unified Parkinson's Disease Rating Scale (UPDRS) went down by 5.7 points in the IG and showed a small 0.9-point increase in the CG (p = 0.11). fMRI showed activation of the right fusiform gyrus during the motor task and functional connectivity between the cingulum and areas of the frontal cortex, and between the cerebellar vermis and the thalamus and posterior temporal gyrus. Plasma brain-derived neurotrophic factor (BDNF) levels increased more than 10-fold in the IG and decreased in the CG (p = 0.028). Larger increases in plasma BDNF correlated with greater decreases in UPDRS (r = -0.58, p = 0.04). Conclusions: Our findings suggest that high-intensity tandem bicycle improves motor function and biochemical and functional neuroimaging variables in PD patients. Trial registration number: ISRCTN 13047118, Registered on February 8, 2018.

The chronic practice of exercise induces a series of cellular and organismal adaptations that modify the way the human body metabolizes all macronutrients, including lipids. Endurance exercise and resistance exercise elicit different responses that result in differential effects on lipid and lipoprotein metabolism. These effects are quantitatively and qualitatively different and mediated by distinct signaling pathways. In this review, we summarize relevant evidence on the impact of exercise on lipid and lipoprotein metabolism, and finalize with some practical recommendations on exercise practice for patients with dyslipidemia in the primary care setting

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.

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.

Despite major advances in pharmacologic therapy over the last few decades, dyslipidemia remains a prevalent, insufficiently recognized, and undercontrolled risk factor for cardiovascular disease. Statins are the mainstay of hypercholesterolemia treatment, but because of adherence and tolerability issues that limit dose titration, there is a need for additional therapies with good efficacy and better tolerability. Adenosine triphosphate (ATP) citrate lyase, a cytoplasmic enzyme responsible for the generation of acetyl coenzyme A for the de novo synthesis of fatty acids and cholesterol, is a very interesting molecular target for the reduction of plasma lipids. Furthermore, ATP citrate lyase inhibition may be accompanied by activation of 5'-adenosine monophosphate-activated protein kinase, a key signaling molecule that acts a central hub in cellular metabolic regulation. ETC-1002 is a small molecule inhibitor of ATP citrate lyase that also activates 5'-adenosine monophosphate-activated protein kinase, effectively reducing low-density lipoprotein cholesterol and inducing some other positive metabolic changes. Recent evidence from phase I and II clinical trials in humans has shown a positive efficacy and safety profile of ETC-1002, with low-density lipoprotein cholesterol reductions similar to those attainable by usual doses of many statins and with no major apparent side effects. These results potentially introduce a new family of medications that may expand our therapeutic arsenal against hypercholesterolemia.

Background: Myokines are a group of protein mediators produced by skeletal muscle under stress or physical exertion. Even though their discovery and effects in cell culture and animal models of disease have elicited great enthusiasm, very little is known about their role in human metabolism. We assessed whether plasma concentrations of three known myokines (myonectin, myostatin and fibroblast-derived growth factor 21 [FGF-21]) would be associated with direct and indirect indicators of insulin resistance (IR) in individuals who did not have a diagnosis of diabetes. Methods We studied 81 adults of both sexes comprising a wide range of body adiposity and insulin sensitivity. All participants underwent a thorough clinical assessment and a 5-point oral glucose tolerance test (OGTT) with calculation of multiple IR and insulin sensitivity indices. Twenty-one of them additionally underwent a hyperinsulinemic-euglycemic clamp with determination of steady-state whole-body insulin-stimulated glucose disposal (“M”). We compared plasma myokine concentrations across quartiles of IR indices and clinical IR surrogates, and explored the correlation of each myokine with the M value. Results Plasma myonectin levels increased monotonically across quartiles of the incremental area under the insulin curve (iAUCins, higher values indicate more insulin resistance) (p-trend=0.021) and decreased monotonically across quartiles of the insulin sensitivity index (ISI – higher values indicate less insulin resistance) (p-trend=0.012). After multivariate adjustment for other relevant determinants of IR (body-mass index, age, and sex), the negative association of myonectin with ISI persisted (standardized beta= -0.235, p=0.023). Myostatin was not associated with any clinical IR indicator or direct IR index measure. In multivariate analyses, FGF-21 showed a trend toward a positive correlation with glucose disposal that did not reach statistical significance (standardized beta=0.476, p=0.091). Conclusion The secretion of myonectin may constitute an attempt at a compensatory mechanism against IR in humans.

Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.

Aims To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. Methods We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). Results PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend = 0.029; for RBP-4 p-trend = 0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9 ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6 ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. Conclusions Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes.

Objective: There is insufficient evidence about the impact of cesarean delivery on maternal request (CDMR). This study was designed to evaluate different maternal and neonatal outcomes comparing CDMR with vaginal deliveries in low-risk pregnancies. Materials and methods: Prospective observational study including women aged 18 to 45 with a low-risk, term pregnancy, who delivered between June 2008 2017 and April 2012 at a University Hospital in Bogota Colombia. The occurrence of any of 5 pre-specified adverse maternal events (maternal outcome) and of any of 17 pre-specified adverse neonatal events (neonatal outcome) was compared between CDMR and vaginal deliveries. Induced vaginal deliveries were analyzed separately. All women received the same standard of care. The effect of confounders was adjusted using multivariate logistic regression. Results: The study included 214 women with CDMR, 341 with spontaneous vaginal delivery (SVD) and 376 with induced vaginal delivery (IVD). Relative to the SVD group, the multivariate-adjusted odds ratios for adverse maternal outcomes were 0.21 (95% CI: 0.05-0.97) in the CDMR group and 0.93 (95% CI: 0.42-2.06) in the IVD group. The multivariate ORs for adverse neonatal outcoms were 0.51 (95% CI: 0.30-0.87) for CDMR and 0.75 (95% CI: 0.50-1.14) for IVD. The frequency of hospitalization of the newborn was lowest in the cesarean delivery group (10.3% versus 15.8% for spontaneous deliveries, 16.2% for induced vaginal deliveries). Conclusions: Among low-risk pregnancy women who entered a standardized obstetric care protocol, CDMR was associated with a lower rate of adverse perinatal outcomes when compared to spontaneous vaginal delivery. Further studies are needed to assess long-term the safety of CDMR.

Hereditary fructose intolerance, caused by mutations in the ALDOB gene, is an unusual cause of hypoglycemia. ALDOB encodes the enzyme aldolase B, responsible for the hydrolysis of fructose 1-phosphate in the liver. Here, we report the case of a 33-year-old female patient who consulted due to repetitive episodes of weakness, dizziness and headache after food ingestion. An ambulatory 72-h continuous glucose monitoring revealed multiple short hypoglycemic episodes over the day. After biochemical exclusion of other endocrine causes of hypoglycemia, hereditary fructose intolerance seemed a plausible diagnosis. Repeated measurements of urinary fructose revealed pathologic fructosuria, but genetic testing for the three most common mutations in ALDOB resulted negative. We decided to perform complete Sanger sequencing of the ALDOB gene and encountered a variant consisting of a T>A substitution in position 1963 of the ALDOB transcript (c.1693T>A). This position is located within the 3′ untranslated region of exon 9, 515 nucleotides downstream the stop codon. After complete withdrawal of dietary fructose and sucrose, the patient presented no new hypoglycemic episodes.

Comprender el estado del diagnóstico y el tratamiento de la prediabetes en América Latina y evaluar el uso de la metformina para la prevención de la diabetes en este contexto.Un panel de 15 expertos en diabetes de siete países de América Latina se reunió del 14 al 15 de agosto de 2014 en Lima, Perú, para revisar la literatura disponible, discutir el papel de la prediabetes en la diabetes mellitus tipo 2 y la enfermedad cardiovascular, analizar la información recolectada y formular conclusiones para el diagnóstico y el tratamiento de la prediabetes en América Latina.Se analizaron el diagnóstico, el tamizaje y el tratamiento de la prediabetes, inclusive los cambios en el estilo de vida, el tratamiento farmacológico y la relación costo-eficacia. Se emitieron cinco conclusiones para América Latina: la prediabetes es un problema clínico y de salud pública; los sistemas de atención de la salud actualmente no diagnostican o no tratan la prediabetes; el uso de herramientas de detección del riesgo de prediabetes es necesario en toda la región; el tratamiento incluye cambios en el estilo de vida, educación multidisciplinaria y metformina; y se debe brindar apoyo para llevar registros de historias clínicas y realizar estudios adicionales.El panel de expertos concluyó que en América Latina el tratamiento preventivo basado en cambios en el estilo de vida y administración de metformina son intervenciones eficaces en relación al costo. Es importante mejorar la identificación y el manejo de la prediabetes en el nivel de atención primaria.Entender o estado do diagnóstico e tratamento do prediabetes na América Latina e avaliar o uso de metformina para prevenção de diabetes neste contexto.Um painel de 15 especialistas em diabetes de sete países da América Latina reuniu-se de 14 a 15 de agosto de 2014 em Lima, Peru, para analisar a literatura disponível, discutir o papel do prediabetes em diabetes mellitus tipo 2 e doenças cardiovasculares, analisar informações coletadas e fazer conclusões para o diagnóstico e tratamento do prediabetes na América Latina.O diagnóstico, rastreio e tratamento pré-diabetes, incluindo mudanças de estilo de vida, tratamento farmacológico e custo-efetividade foram discutidos. Foram emitidas cinco conclusões resultantes para a América Latina: o prediabetes é um problema clínico e de saúde pública; os sistemas de saúde atualmente não diagnosticam/tratam prediabetes; o uso de ferramentas de detecção de risco de prediabetes é necessário em toda a região; o tratamento inclui mudanças de estilo de vida, educação multidisciplinar e metformina; e devem ser suportados registros de pacientes e outros estudos.O painel de especialistas concluiu que na América Latina, o tratamento preventivo através de mudanças de estilo de vida e metformina são intervenções efetivas em relação ao custo. É importante melhorar a identificação e gestão do prediabetes no nível de atenção primária.

To assess the proportion of patients on vildagliptin add-on dual therapy who respond to treatment over a 12 month follow-up, relative to comparator oral anti-diabetes dual therapy, in a usual care setting.Participants were patients with type 2 diabetes (T2DM) aged 18 years and older from 311 centers in Argentina, Colombia, Ecuador, Mexico and Venezuela. Patients were taking monotherapy with an oral anti-diabetes drug (OAD), and were prescribed a new add-on OAD based on the judgment of their personal physician. According to this choice, patients were assigned to one of the two cohorts: vildagliptin or comparator OADs.The primary endpoint was the proportion of patients achieving an A1c drop0.3% without edema, hypoglycemia, weight gain or discontinuation due to gastrointestinal (GI) events. The secondary endpoint was the proportion of patients with baseline A1c ≥7% who reached the goal of an A1c7% without hypoglycemia or weight gain.The per-protocol population (a subset of the intention-to-treat population that excluded patients with pre-specified protocol deviations) comprised 3773 patients, 3002 in the vildagliptin cohort and 771 in the comparator cohort. The proportion of patients reaching the primary endpoint was higher in the vildagliptin cohort (60.3%) than the comparator cohort (50.7%), OR 1.48 (95% CI: 1.25-1.73). The same was observed for the secondary endpoint (44.8 versus 33.1%) OR 1.64 (95% CI: 1.37-1.98). The incidence of adverse events was low and similar between treatment cohorts.In a usual care setting, patients treated with a vildagliptin combination succeeded in lowering A1c to7%, without weight gain, hypoglycemia or peripheral edema more often than patients treated with comparator combinations, without increased risk of adverse events. Key limitations are the observational nature of the study and its relatively limited 12 month timeframe.

Background Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it. Methods We studied 36 young Hispanic adults without diabetes (ages 18–40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups. Results Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese. Conclusions Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.

Background: Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their poten tial as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles. Methods: We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secre tion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glu cose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices. Results: Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=-0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC). Conclusion: In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.

Background— Low-density lipoprotein (LDL) that contains apolipoprotein (apo) C-III makes up only 10% to 20% of plasma LDL but has a markedly altered metabolism and proatherogenic effects on vascular cells. Methods and Results— We examined the association between plasma LDL with apoC-III and coronary heart disease in 320 women and 419 men initially free of cardiovascular disease who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow-up and matched controls who remained free of coronary heart disease. Concentrations of LDL with apoC-III (measured as apoB in this fraction) were associated with risk of coronary heart disease in multivariable analysis that included the ratio of total cholesterol to high-density lipoprotein cholesterol, LDL cholesterol, apoB, triglycerides, or high-density lipoprotein cholesterol and other risk factors. In all models, the relative risks for the top versus bottom quintile of LDL with apoC-III were greater than those for LDL without apoC-III. When included in the same multivariable-adjusted model, the risk associated with LDL with apoC-III (relative risk for top versus bottom quintile, 2.38; 95% confidence interval, 1.54–3.68; P for trend P for trend=0.97; P for interaction Conclusions— The risk of coronary heart disease contributed by LDL appeared to result to a large extent from LDL that contains apoC-III.

There are few data regarding insulin levels in the lungs during diabetes therapy with inhaled insulin. We examined the disposition of inhaled human insulin (Exubera(®) [EXU] human insulin [recombinant DNA origin], Pfizer, New York, NY) in the lungs by measuring trough insulin levels in bronchoalveolar lavage (BAL) fluid after 12 weeks of EXU treatment.After a 4-week run-in period of subcutaneous insulin therapy, 24 subjects with type 1 diabetes mellitus (T1DM) and 26 with type 2 diabetes mellitus (T2DM) continued their basal insulin regimen and received premeal subcutaneous (SC) insulin for 13 weeks, followed by 12 weeks of premeal EXU. BAL was performed approximately 12 h after the last insulin dose at (1) baseline, (2) following SC insulin, and (3) following EXU.Twenty patients with T1DM and 24 patients with T2DM completed all three bronchoscopies. BAL trough insulin levels were undetectable at baseline or following SC insulin. After EXU therapy, they increased to a median of 4.5 nM (1.6-9.0 nM) and 2.3 nM (0.5-9.4 nM) in T1DM and T2DM, respectively. BAL trough insulin levels did not correlate with treatment efficacy, adverse effects, plasma insulin levels, or changes in pulmonary function. A larger proportion of previous EXU doses was present in the BAL in patients with T1DM. We found no correlation between average daily insulin doses and BAL trough insulin levels.BAL trough insulin increased following EXU therapy, but this increase did not correlate with other clinical or laboratory parameters, suggesting no significant biological action. Further studies are warranted to better understand inhaled insulin deposition and clearance and possible effects of increased insulin levels on the lungs.

OBJECTIVE: To estimate prevalence and distribution of cardiovascular risk factors and Metabolic Syndrome (MS) in young individuals admitted to the National University of Colombia in Bogota. METHODS: An analytic cross-sectional study was conducted in a sample of 249 individuals of both genders aged 15 to 20 years. A questionnaire was personally administered to collect demographic, socioeconomic, smoking, perinatal, and women's health data. Anthropometric measurements, blood pressure, and a fasting blood sample were taken. Prevalence of MS was determined and compared using criteria from several qualified institutions. RESULTS: We found a high prevalence of smoking (18.9%), arterial prehypertension (14.1%) and overweight (11.2%), 9.2% of study participants had prediabetes, and the most frequent dyslipidemia was low HDL cholesterol (13.3%). Alcoholic beverage consumption was declared by 60.6% of study terol and plasma triglyceride levels. Gestational age at birth was inversely associated with presence of low HDL cholesterol levels and high blood pressure. Prevalence of the MS varied markedly according to the definition employed: 9.2% using REGODCI (Research Group on Diabetes and Chronic Illnesses) criteria, 2% using IDF (International Diabetes Federation) criteria, and 2.4% using AHA (American Heart Association) criteria. CONCLUSION: The encountered prevalence of modifiable cardiovascular risk factors justifies promotion of therapeutic lifestyle changes among this age group in Colombia. Further harmonization of MS criteria in young individuals is needed.