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In this randomised, placebo-controlled trial, adults with impaired sleep (Pittsburgh Sleep Quality Index ≥ 5) were randomly assigned using a minimization algorithm to receive a formulation containing L-theanine plus lemon balm, valerian, and saffron extracts, or placebo, during 6 weeks. Objective sleep quality parameters were measured using an actigraphy device. We enrolled and randomised 64 individuals, 31 from the active group and 27 from the placebo group completed the 6 week follow-up. Mean sleep efficiency remained unmodified in the active group, and increased by 3% in the placebo group, the between-group difference in the change was not statistically significant (p = 0.49). Total sleep time also improved more with placebo (13.0 vs. 1.33 min, p = 0.66). Time wake after sleep onset (WASO) decreased more in the active group (4.6% vs. 2.4%), but the difference was not significant (p = 0.33). Mean PSQI decreased by 3.11 points (32.3%) in the active group, and by 3.86 points (39.5%) in the placebo group (p = 0.41). SF-36 increased more with placebo (+ 18.3 in active, + 32.1 in placebo, p = 0.68). Salivary cortisol remained unchanged in both groups. No serious adverse events were reported. Among adults with impaired sleep, a nutraceutical combination did not improve objective or subjective sleep parameters more than a placebo infusion.

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Abstract Familial chylomicronemia syndrome (FCS) is an autosomal recessive disorder, characterized by alterations in the catabolism of chylomicrons and by increased levels of plasma triglycerides. It has been shown that about 60-90% of FCS patients have biallelic mutations in the LPL gene and the remaining patients have mutations in genes encoding proteins closely related to LPL function. The objective of this manuscript is to illustrate the different clinical scenarios of FCS presentation, and to guide practitioners on the usefulness of genetic tests in each of them. To this end, several published papers about recommendations for the diagnosis of FCS are discussed briefly, in addition to the presentation of several hypothetical cases, highlighting different clinical presentations and possible associated genetic findings. These cases illustrate the multiplicity of potential aspects of family history, clinical manifestations, biochemical parameters, and patterns of genetic variants found in genomic analyses of FCS.

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INTRODUCTION: We compared the association of glomerular filtration rate (GFR) estimated with the Cockcroft-Gault, Modification of Diet in Renal Disease study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or the new CKD-EPI without race (CKD-EPI-NR) equations, with 4-year all-cause mortality in patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed a nationwide, centralized database of all adults diagnosed with diabetes assisted by the Colombian Health System between July 1, 2015, and June 30, 2019. Plasma creatinine was used to calculate baseline estimated glomerular filtration rate (eGFR) and classify each patient in a chronic kidney disease (CKD) stage, by each of the four equations. We used multivariate logistic regression to compare the association between CKD stage and mortality, and receiver operating characteristic (ROC) analyses to assess the overall association of eGFR by each equation and mortality. RESULTS: The study included 758,219 patients (58% female, 7.2% black race, mean age 62.3, Glycated hemoglobin A1c [HbA1c] 7.4%). There were 35,296 deaths over the study follow-up. Considering eGFR by each equation as a continuous variable, the odds of death decreased by 1.1%-1.5% for each additional mL/min. Compared with CKD stage 1 of each equation, being placed in CKD stages 3a, 3b, or 4 by MDRD or CKD-EPI-NR was associated with greater odds of death than being categorized in the same stages by CKD-EPI. Among patients of black race, the adjusted OR of mortality for CKD stage 4 relative to stage 1 was 4.63 (95% CI 3.39 to 6.35) for MDRD, 3.66 (2.85 to 4.69) for CKD-EPI-NR, 3.01 (2.38 to 3.81) for CKD-EPI, and 2.82 (2.29 to 3.49) for Cockcroft-Gault. The area under the ROC curve to discriminate by survival status was greatest for MDRD, followed by CKD-EPI-NR, CKD-EPI, and Cockcroft-Gault, in that order (p<0.001 for all differences). CONCLUSIONS: Compared with other eGFR equations, MDRD showed the strongest association with all-cause mortality in a sample of Latin-American patients with diabetes. This difference was most pronounced among patients of black race.

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There is great interest on medium chain fatty acids (MCFA) for cardiovascular health. We explored the effects of MCFA on the expression of lipid metabolism and inflammatory genes in macrophages, and the extent to which they were mediated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR ß/δ). J774A.1 murine macrophages were exposed to octanoate or decanoate as MCFA, a long-chain fatty acid control (palmitate), or the PPAR ß/δ agonist GW501516, with or without lipopolysaccharide (LPS) stimulation, and with or without an siRNA-induced knockdown of PPAR ß/δ. MCFA increased the expression of Plin2, encoding a lipid-droplet associated protein with anti-inflammatory effects in macrophages, in a partially PPAR ß/δ-dependent manner. Both MCFA stimulated expression of the cholesterol efflux pump ABCA1, more pronouncedly under LPS stimulation and in the absence of PPAR ß/δ. Octanoate stimulated the expression of Pltp, encoding a phospholipid transfer protein that aids ABCA1 in cellular lipid efflux. Only palmitate increased expression of the proinflammatory genes Il6, Tnf, Nos2 and Mmp9. Non-stimulated macrophages exposed to MCFA showed less internalization of fluorescently labeled lipoproteins. MCFA influenced the transcriptional responses of macrophages favoring cholesterol efflux and a less inflammatory response compared to palmitate. These effects were partially mediated by PPAR ß/δ.

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Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder that causes extremely elevated plasma triglyceride levels, with limited therapeutic options. Volanesorsen is an antisense oligonucleotide approved for its treatment. A 24-year-old woman with genetically diagnosed FCS secondary to a pathogenic variant in APOA5 and a history of recurrent hypertriglyceridemia-induced pancreatitis episodes was being treated with volanesorsen, 285 mg every 2 weeks. Treatment with volanesorsen achieved normalization of triglycerides to <200 mg/dl. However, after the fifth dose of the medication, the patient developed urticaria and volanesorsen was discontinued. In the absence of alternative pharmacological treatments, the patient received a novel desensitization protocol for volanesorsen that allowed continuation of therapy, without evidence of hypersensitivity reactions after subsequent administrations. FCS requires aggressive multimodal therapy and close follow-up. Volanesorsen has shown great efficacy, but a significant rate of discontinuation due to side effects has been observed. Here, the patient presented an immediate hypersensitivity reaction to volanesorsen, but the provision of a desensitization protocol was effective, facilitating continued treatment and impacting the survival and quality of life of the patient.

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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.

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Objective: The magnitude of the mortality benefit conferred by good integral metabolic control in diabetes in not sufficiently known, especially among Latin American patients. We prospectively studied the association between sustained control of blood glucose (HbA1c<7%), systolic blood pressure (SBP) (<130 mmHg) and LDL (LDLc, <100mg/dL) and non-HDL (non-HDLc, <130 mg/dL) cholesterol, and death from any cause among all adult patients with diagnosed diabetes in Colombia. Methods: We retrospectively analyzed data from a nationwide, centralized, mandatory registry of all patients with diagnosed diabetes assisted by the Colombian health system between July 1, 2015, and June 30, 2019. We estimated the associations of sustained achievement of each goal, and of the joint triple goal (HbA1c + SBP + LDLc) with all-cause death. Associations were assessed after adjustment for sex, age, race, insurance type and BMI in multivariable logistic models. Results: We studied 1 352 846 people with diabetes. Sustained SBP (OR 0.42 [0.41-0.43]), HbA1c (OR 0.25 [0.24-0.26]) and LDLc (OR 0.28 [0.27-0.29]) control had strong negative associations with death. Moreover, among the 5.4% of participants who achieved joint, sustained metabolic control, the OR for death was 0.19 (0.18-0.21). Importantly, the impact of sustained, joint metabolic control was significantly smaller for patients of black race compared to other races (OR 0.31 [0.23-0.43] versus 0.18 [0.17-0.20], p-value for interaction <0.001), mostly at the expense of a smaller impact of LDLc control. The results were similar across body-mass index categories. Conclusions: Sustained and simultaneous metabolic control was associated with remarkably lower odds of death.

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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.

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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.

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BACKGROUND: It is important to identify patients at increased risk of worsening of left ventricular ejection fraction (LVEF) after a myocardial infarction (MI). We aimed to identify the association of various potential biomarkers with LVEF impairment after an MI in South American patients. METHODS: We studied adult patients admitted to a University Hospital and diagnosed with an acute MI. Plasma concentrations of high-sensitivity C-reactive protein (hsCRP), proprotein convertase subtilisin/kexin type 9 (PCSK9), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and heart-type fatty-acid-binding protein (FABP3) were determined in samples drawn shortly after the event. Participants had a follow-up visit at least 45 days after the event. The primary endpoint was defined as any decline in LVEF at follow-up relative to baseline. RESULTS: The study included 106 patients (77.4% men, 22.6% women), mean age was 64.1, mean baseline LVEF was 56.6, 19% had a prior MI. We obtained a follow-up evaluation in 100 (94.4%) of participants, mean follow-up time was 163 days. There was a significant correlation between baseline PCSK9 and hsCRP (r = 0.39, p < 0.001). Baseline hsCRP concentrations were higher in patients who developed the endpoint than in those who did not (32.1 versus 21.2 mg/L, p = 0.066). After multivariate adjustment, baseline PCSK9, male sex and age were significantly associated with impairment in LVEF. The absolute change in LVEF was inversely correlated with baseline hsCRP (standardized coefficient = - 0.246, p = 0.004). CONCLUSION: High plasma levels of PCSK9 and hsCRP were associated with early decreases in LVEF after an MI in Latin American patients.

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