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Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro. Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m2, and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m

Introduction: Hyperlipidemia, traditionally defined with fasting lipid values, is a common cardiovascular risk factor, particularly in patients with insulin resistance, prediabetes and type 2 diabetes mellitus (DM). Nonfasting triglyceride levels (TG), however, have shown a stronger association with heart disease and stroke than fasting levels, independent of traditional CV risk factors. The objective of this study was to determine the relationship between TG and glucose levels after administration of a sucrose load (equal parts glucose and fructose) in individuals without a previous diagnosis of DM. Hypothesis: Sugar as a sole energy source will elicit both a lipemic and a glycemic response. Methods: We use a unique dataset from a single health clinic in Barranquilla, Colombia in which 1,446 adults aged 18 to 80 years (mean age, 49 years, 3 months, 77 percent female) were enrolled from 2002 - 2005. Serum TG and glucose levels were measured after an overnight fast and at two hours after administration of 75 gm of mixed carbohydrate in the form of Panela, a mixed carbohydrate made from an unrefined whole cane sugar used in beverages and in cooking in this area of Colombia. A solid form of sucrose, it contains equal parts of glucose and fructose. Regression analysis was performed to evaluate factors associated with the glycemic and lipemic responses. Results: We found that the absolute 2-hour glucose (range: 32-526 mg/dL) is significantly associated (p Conclusion: These data suggest that a diet rich in refined carbohydrate may pose a significant risk for hyperlipidemia, particularly in younger patients. The independent role of fructose as a trigger for de novo lipogenesis may be relevant in the observed response

Background and aim Currently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function. Objective To evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function. Methods and results Ten healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0–36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5–33.3), independently of the type of oil ingested ( p =0.44) and regardless of its deep-fry level ( p =0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment ( r =−0.22, p =0.09). Conclusions No difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.

A whole-body DXA study of 1450 healthy Caucasian individuals [Bone 22 (1998) 683] found that mineral mass, either crude (BMC) or statistically adjusted to fat mass (FM-adjusted BMC), correlated linearly with lean mass (LM, proportional to muscle mass). The results showed similar slopes but decreasing intercepts (ordinate values) in the order: pre-MP women > men > post-MP women > children. This supports the hypothesis that sex hormones influence the control of bone status by muscle strength in all species. Now we further study those relationships in 2512 healthy Hispanic adults (307 men, 753 pre-MP women, 1452 post-MP women), including separate determinations in their upper and lower limbs. The slopes of the BMC or FM-adjusted BMC vs. LM relationships were parallel in all the studied regions. However, region-related differences were found between the ordinates of the curves. In the whole body, the crude-BMC/LM relationships showed the same ordinate differences as previously observed. In the lower limbs, those differences were smaller in magnitude but highly significant, showing the order: pre-MP women > men = post-MP women. In the upper limbs, the decreasing ordinate order was: men > pre-MP women > post-MP women. After fat adjustment of the BMC, order in both limbs was: men > pre-MP women > post-MP women. Parallelism of the curves was maintained in all cases. LM had a larger independent influence on these results than FM, body weight, or age. The parallelism of the curves supports the idea that a common biomechanical control of bones by muscles occurs in humans. Results suggest that sex-hormone-associated differences in DXA-assessed muscle-bone proportionality in humans could vary according to the region studied. This could be related to the different weight-bearing nature of the musculoskeletal structures studied. Besides the obvious anthropometric associations, FM would exert a mechanical effect as a component of body weight, evident in the lower limbs, while muscle contractions would induce a more significant, dynamical effect in both lower and upper limbs. Muscles seem to exert a larger influence than FM, body weight, and age on BMC in the whole body and lower limbs, regardless of the gender and reproductive status of the individual. The muscle-bone relationships studied may provide a rationale for a future differential diagnosis between disuse-related and other types of osteopenia.

Hormone replacement therapy is used in postmenopausal women to improve symptoms of menopause and to protect bone and the cardiovascular system. We have evaluated the effects of parity in terms of number of deliveries on bone density and fracture risk at different ages.We evaluated 1875 Hispanic womenor =50 years old (61.3 +/- 8.3 years), 425 with a history of nonselective fractures and 1450 without previous fractures. Body mass index was 27.3 +/- 4.3 kg/m(2). Bone mineral densities were determined for the total body in 1468 cases, the femur in 221 cases, and the lumbar spine in 189 cases. Women were classified according to lifetime number of deliveries (from 0 toor =5), and bone mineral densities and odds ratios for fracture risk were calculated relative to the number of deliveries.Bone mineral densities in total body, pelvis, and legs and total calcium and total mineral contents increased (P.001) withor =2 deliveries among women 50 to 59 years old but not among thoseor =70 years old. The prevalence of fractures was higher in nulliparous than in multiparous women at all ages. Fracture risk was lower in multiparous women at all age groups, including thoseor =70 years old (odds ratio, 0.47; 95% confidence interval, 0.26-0.84; P.006).Bone mineral density increases with the number of deliveries until the age of 69 years. Fracture prevalence and fracture risk are lower among multiparous women even at older ages. These findings suggest that hormone replacement therapy can be delayed until 65 years of age for multiparous women but should be initiated at the beginning of menopause for nulliparous women.

Se ha hecho énfasis en la relación que existe entre la producción de tumores hipofisiarios y el déficit hormonal debido a falla en el órgano Terminal. Se hace énfasis en la importancia de un tratamiento sustitutivo adecuado en pacientes con menopausia precoz no sólo como suplencia hormonal sino para prevenir la aparición posterior de tumores hipofisiarios.

Se estudiaron 21 controles y 43 pacientes con baja talla, analizándoles T3, T4 y TSH basal y post-TRH, HGH post-ejercicio y carpograma. Se clasificó desarrollo sexual según Tanner. Las edades de los pacientes variaron entre 4 y 16 años con promedio de 11.34. Los pacientes fueron clasificados según respuesta de TSH al TRH en tres grupos: hipotiroideos, dudosos y “normales”.

Se presenta el caso de una niña de siete años con diagnóstico de pubertad precoz. Se plantean los diagnósticos diferenciales, los posibles mecanismos fisiopatológicos, se hace una breve revisión bibliográfica y se discute el caso.

En este artículo se revisan las endocrinopatías más frecuentes y sus repercusiones sobre el sistema cardiovascular, así como manifestaciones clínicas, diagnóstico y tratamiento.

Objective: This study evaluated dual-energy x-ray absorptiometry-assessed whole-body bone-muscle relationship (bone mineral content/lean mass [BMC/LM]) as an indicator of its nonmechanical perturbations (ie, systemic) in pre- and postmenopausal women. A total of 3,205 women were studied, either healthy (no fracture [No Fx] groups, 1,035 premenopausal, 1,556 postmenopausal) or with recent fractures (Fx groups, 139 premenopausal, 475 postmenopausal) located at osteoporotic sites (hip, spine, long-bone metaphyses; Type II Fx, n = 386) or at other skeletal sites (Type I Fx, n = 228) to evaluate the impact of decreased muscle mass on fracture incidence before and after menopause. Design: SD-scored graphs of BMC/LM proportionality were obtained from the No Fx groups as normal references. Based on the reference BMC versus LM curves obtained from their respective No Fx pre- and postmenopausal controls, BMC-LM SD scores were calculated for all women with fractures. Results: BMC-LM SD scores in all premenopausal women with fractures and in Type I Fx postmenopausal women were similar to the reference. In contrast, SD scores in Type II Fx postmenopausal women were lower than the reference, especially in those with hip fractures. Except for Type II Fx postmenopausal women, all groups showed linear and similar BMC versus LM curves. Type II Fx postmenopausal women showed nonlinear relationships, with progressively decreasing BMC and BMC-LM SD scores as their LM decreased. Conclusions: Results suggest that both LM and BMC-LM SD scores can help to differentiate between systemic and mechanical (disuse-related) osteopenia/osteoporosis after menopause. Low LM values or BMC-LM SD scores seem to constitute additional fracture risk factors beyond those usually detected in premenopausal women or in women with other types of fractures. This application of dual-energy x-ray absorptiometry technology may lead to more effective diagnosis and treatment at low cost.

This report summarizes some preliminary absorptiometric (DXA, QCT/pQCT) studies from our laboratory, supporting the following assumptions. 1. In Homo sapiens at all ages, natural proportionality between DXA-assessed bone mineral mass (bone mineral content, BMC) and muscle mass (lean mass, LM) of the whole body or limbs is specific for ethnicity, gender, and reproductive status, but not for body weight, height, or body mass index. 2. This proportionality is sensitive to many kinds of endocrine-metabolic perturbations. 3. Percentilized or Z-scored charts of the BMC/LM correlations as determined in large samples of healthy individuals can provide a diagnostic reference for evaluating proportionality in different conditions. 4. Employing exclusively DXA, this methodology can be applied to discriminate between "disuse-related" and "metabolic" osteopenias based on the finding of normal or low BMC/LM percentiles or Z-scores respectively, with important therapeutic and monitoring implications.

Correlations between dual-energy X-ray absorptiometry (DXA)-assessed bone mineral content and lean mass (BMC-LM curves), and between BMC/LM ratio and age ([BMC/LM]-age curves), were analyzed in the whole body (WB), the upper limbs (ULs) and the lower limbs (LLs) of 3,063 healthy Hispanic adults. Groups of 472 men aged 25-87 years, 1,035 premenopausal (pre-MP) women aged 27-54 years, and 1,556 post-menopausal (post-MP) women aged 48-93 years were studied with a GE-Lunar DPX-Plus device. BMC-LM curves confirmed previous observations that BMC and LM masses always correlate linearly, with similar slopes within each region, but differing in intercepts according to gender and hormonal status. Multiple regression tests showed little or no independent interaction of body weight or height with those relationships. [BMC/LM]-age curves were flat in men but showed the positive influence of estrogens throughout the age range in women. Z-scored graphs of all the corresponding relationships were compiled, showing the confidence intervals for means +/-1, +/-2, and +/-3 SDs of the data (+/-1, +/-2, +/-3 z-scores) along BMC-LM and [BMC/LM]-age curves. These charts are proposed as references for assessing how well bone mass (as assessed by BMC) and muscle mass (assumed proportional to LM) follow the natural anthropometric/biomechanical proportionality in Hispanic men and women within the age range studied, employing similar devices. Charts for LLs, showing the lowest variance amongst the studied correlations and approaching the origin as an exclusive feature, could provide the most accurate reference curves. Differences between data from ULs and LLs may provide information about any eventual interaction of body-weight bearing with the general results. The proposed analysis may provide useful information for approaching a differential diagnosis between disuse-related and other types of osteopenias employing only DXA.

Objectives: Pregnancy has been proposed as a risk factor for the development of osteoporosis; however, the results are controversial. Women in Colombia are multiparous, and therefore they represent an ideal population for the investigation of the effect of parity on osteoporosis. Methods: The study included 1855 post-menopausal Hispanic women from Barranquilla, Colombia who were referred to our osteoporosis clinic for a routine evaluation of their bone mineral status. Bone mineral density (BMD, g/cm2) was measured using dual energy X-ray absorptiometry. Total body, femoral and lumbar areas were scanned. Results: BMD of total body, hip and legs (P

The effect of thyroid replacement therapy (TRT) was evaluated in 372 children with minimal thyroid dysfunction (MTD; augmented TSH response to TRH, deficient iodine consumption, goiter, short stature and retarded bone age), by comparison of pre- with post-observation height in periods of 6 months with and without TRT alternated. A significant (P < 0.05) height recovery was observed when children received TRT; however, during the period without TRT they showed a negative height recovery. Additionally, we followed 51 children with MTD who were observed from Tanner I until final height. The group with L-thyroxine (n = 43) during all follow-up (97 months) showed an important recovery in height (SDS-H = 1.67 +/- 0.93 vs. 1.08 +/- 0.74) which when compared with the untreated group (n = 8; 114 months; SDS-H = -1.50 +/- 0.83 vs. -1.93 +/- 0.33) was significant (P < 0.001).

Se estudiaron 12 pacientes con osteoporosis, con edades promedio de 75 a 79 años. Se les evaluó su capacidad funcional en escala de 0 a 3 y dolor osteoarticular en escala de 0 a 5 repitiendo las evaluaciones semanalmente durante el período experimental de 13 semanas. Los resultados obtenidos sugieren que el tratamiento de la osteoporosis con calcitonina asociado con medidas generales de higiene, ejercicio, aporte adecuado de sol y calcio puede ser beneficioso para el manejo de la osteoporosis senil.

Objective The association between parity and type 2 diabetes has been studied in developed countries and in Singapore and Chinese women but not in Hispanics. Herein we evaluated the association between parity (number of live births) with diabetes in a group of Hispanic postmenopausal women from Colombia. Research design and methods Herein we evaluated the association between parity and diabetes in a population of 1,795 women from Colombia. Women were divided in birth categories (0 [referent], 1 or 2, 3–5, 6 or > births). Medical history of diabetes and anthropometric characteristics were recorded. Logistic regressions were performed in order to find the association between parity and diabetes in bivariable and multivariable models after controlling for age, body mass index (BMI), waist hip ratio (WHR) and diabetes family history, among other variables. Results In our study, there was an association between parity and diabetes after adjusting for age, BMI and diabetes family history in the multiparous women groups when compared to the women with no births (Referent group) [1–2 births vs. referent OR 5.2 (95 CI 1.2–22.9), 3–5 births vs. referent OR 5.5 (1.3–23.0) and ≥6 births vs. referent OR 7.5 (1.8–31.8), respectively]. The association was maintained in two of the groups in the multivariable analysis [OR 5.0 (1.1–22.9) and 5.3 (1.2–23.5)], for 1 or 2 births and 6 or > births versus 0 births, respectively. Positive diabetes family history and WHR were also associated with an increased risk of diabetes [OR 4.6 (3.0–7.0) and 4.1 (2.0–8.1), respectively]. Conclusions In postmenopausal Hispanic women, multiparity, as well as a positive family history of diabetes and a high waist-hip ratio were associated with higher diabetes risk.