The re-emerging association between tuberculosis and diabetes: lessons from past centuries

The association between tuberculosis (TB) and diabetes mellitus (DM) had a common place in the literature up to the first half of the 20th century, but virtually disappeared with the discovery of insulin to treat DM and antibiotics to cure TB. In the late 1990s the literature began to re-emerge with the worldwide increase in type 2 DM, particularly in TB-endemic countries. Today, type 2 DM is the most prevalent comorbidity among TB patients and the World Health Organization considers it a threat to TB control. We summarize the literature on TB and DM up to the 1960s. Then we evaluate unique aspects of this comorbidity in older times, such as the frequent diabetic comas that suggest challenges for proper DM management as insulin was being implemented, or the absence of antibiotics to cure TB. Despite the unique aspects of each study period, the literature across times is consistent in key aspects of the association. Namely, a higher TB prevalence among DM (versus non-DM patients), the importance of glucose control and chronic DM on TB susceptibility and the higher risk of death among patients with the comorbidity. From the older literature, we can infer the likely contribution of type 1 DM to TB (in addition to type 2), regardless of their differing autoimmune or metabolic pathophysiology, respectively. Furthermore, in the older literature there was a notable reporting of DM development among TB patients, even though DM usually preceded TB. This observation deserves further epidemiological and basic studies to elucidate this intriguing aspect of the relationship between TB and DM

Familial chylomicronemia syndrome: A family case report in U.S./Mexico border by CEDIAMET

Primary familiar hyperchylomicronemia syndrome (FHS) is an extremely rare autosomal recessive condition. In 80% of cases is a result of a mutation in lipoprotein lipase, meanwhile, the 20% is a malfunctioning enzyme due to APOC2, APOA5, LMF1, or GP1HBP1. It is estimated FHS affects 3000 to 5000 individuals globally, with no correlation by sex or race. We are presenting a family with FHS in Reynosa, Mexico. The index patient was a male 36 years old who attended the CEDIAMET clinic after his 6th episode of acute pancreatitis. He has triglycerides 1300 mg/dl and CT scan with Balthazar C score. He suffered other five episodes of acute pancreatitis since 20 years old with serum triglycerides between 1,000 and 3,000 mg/dL. Each episode progressed in pain intensity and Balthazar score from A to C. The patient received treatment with bezafibrate and captopril because of hypertension. The physical exam shows eruptive xanthomas on his back, otherwise no other clinical relevant findings. He has a family history of recurrent pancreatitis in his father, and two older sisters (from a total of 3 sisters). This is the first case of FHS presented in RGV. To our knowledge, only one mutation in lipoprotein lipase had been described in Guanajuato, Mexico (Colima-Fausto 2017). The p.Gly188Glu mutation affects the lipid-binding region, leading to a complete loss of LPL function. We will research this case to determine if they have a mutation on any of the known genes and if negative, to sequence the regions for seeking new mutation on the U.S.-Mexico border. The common treatment for lowering triglycerides works small or not at all. Other conditions like hypothyroidism or Cushing were ruled out. A specialized exam is the post-heparin activation of lipoprotein lipase inadequate release of the enzyme. The dietary treatment includes a very low-fat diet (no more than 20 to 30 g fat/day), and avoiding alcohol. Plasmapheresis is an option for avoiding acute pancreatitis treatment. Recently, tiparvovec was discontinued in Europe (2007), and was the first gene therapy approved. Volanesorsen is another option that reduces triglycerides by 50 to 80%, currently in phase II and III trials

The intensity of physical activity improves cognitive performance among aging Americans

Background: Currently there is no pharmacological cure for Alzheimer’s disease and related dementias, physical activity (PA) has emerged as a promising approach. The optimal intensity of PA to improve cognitive health remains unknown. Therefore, this study aimed to evaluate associations between different durations and intensities of PA on performance across cognitive domains (executive function, processing speed, and memory) among aging Americans. Methods: 2377 adults aged ≥ 60 years from the cross-sectional National Health and Nutrition Examination Survey 2011-2014, were included. Linear regression in hierarchical blocks and the size of effect (η2) were analyzed with R software. Results: The mean age was 69.3±6.73, 50.86% females. Despite the attenuation of association following adjustments for covariates, participants who engaged in 3-6 hr/wk of vigorous- and \u3e 1 hr/wk of moderate-intensity PA performed significantly higher in executive function and processing speed tests compared to inactive peers (η2= 0.005 & 0.007 respectively, p \u3c 0.05). However, there was no clear dose-response relationship between the executive function and processing speed test scores and duration of weekly moderate-intensity PA. For the adjusted model, the effects of 1-3 hr/wk of vigorous-intensity PA became trivial for the delayed recall memory test scores (β=0.33; 95% CI: -0.01, 0.67; η2=0.002; p=0.56). Interestingly, higher handgrip strength and higher late-life body-mass-index were associated with a higher performance across all cognitive domains. Conclusion: Observed associations provide evidence linking habitual PA with superior cognition health among older adults. Furthermore, increased muscle strength and higher late-life adiposity may impact cognition and require further investigation

Relationship Between Cognitive Performance, Physical Activity, and Socio-Demographic/Individual Characteristics Among Aging Americans

Background: Physical activity (PA) has emerged as a promising approach to delay Alzheimer’s disease and related dementias, but the optimal intensity of PA to improve cognitive health remains unknown. Objective: To evaluate the association between duration and intensity of PA and cognitive domains (executive function, processing speed, and memory) in aging Americans. Methods: Linear regressions in hierarchical blocks for variable adjustment and the size of effect (η2) were analyzed by using the data of 2,377 adults (age = 69.3±6.7 years) from the NHANES 2011–2014. Results: Participants with 3–6 h/week of vigorous- and \u3e 1 h/week of moderate-intensity PA scored significantly higher in executive function and processing speed domains of cognition compared to inactive peers (η2 = 0.005 & 0.007 respectively, p \u3c 0.05). After adjustment, the beneficial effects of 1–3 h /week of vigorous-intensity PA became trivial for delayed recall memory domain test scores (η2 = 0.33; 95%CI: –0.01,0.67; η2 = 0.002; p = 0.56). There was no linear dose-response relationship between the cognitive test scores and weekly moderate-intensity of PA. Interestingly, higher handgrip strength and higher late-life body mass index were associated with a higher performance across all cognitive domains. Conclusion: Our study supports habitual PA with superior cognition health in some but not all domains among older adults. Furthermore, increased muscle strength and higher late-life adiposity may also impact cognition

The impact of an exercise program on selfefficacy in women with overweight and obesity

Introducción: En México la prevalencia combinada de sobrepeso y obesidad en mujeres es de 73%, problema de salud pública que se relaciona con las principales causas de muerte. Las principales estrategias se realizan a través de la práctica de ejercicio y alimentación saludable; sin embargo, no se ha tenido el impacto deseado; es necesario obtener indicadores cognitivos para fortalecer las estrategias de salud. Objetivo: Analizar el impacto de un programa de entrenamiento físico aeróbico gradual sobre el nivel de Autoeficacia (AE) para practicar ejercicio y dieta saludable en mujeres con sobrepeso y obesidad. Material y métodos: Se trató de un experimento en el que se incluyeron mujeres de 18 a 24 años con un IMC≥27. La muestra se conformó por 34 mujeres divididas en los grupos control y experimental (17 mujeres respectivamente), seleccionadas y asignadas mediante muestreo aleatorio. Las mediciones se realizaron mediante un inventario valido y confiable que mide la AE en dieta y ejercicio. La dosis de ejercicio fue calculada por la fórmula de Karvonen durante diez semanas de manera gradual y controlada. El estadístico utilizado fue un MANOVA de mediciones repetidas, se consideró un nivel de significancia <.05. Resultados: Posterior a la intervención se apreciaron cambios estadísticamente significativos, AE en ejercicio 40.3±4.0 vs. 35.8±5.4; y AE en dieta 85.8±10.5 vs. 78.8±10.7 (p<.05). Conclusiones: El ejercicio a la dosis establecida mejoró la condición de AE que favoreció la práctica de ejercicio y la dieta saludable en mujeres con sobrepeso y obesidad.Introduction: In Mexico, the combined prevalence of overweight and obesity in women is 73%, public health problem that is related to the leading causes of death. The main strategies are done through exercise and healthy eating; however, it has not had the desired impact; it is necessary to obtain cognitive indicators to strengthen health strategies. Objective: To analyze the impact of a gradual program of aerobic exercise training on the level of self-efficacy (AE) for exercise and healthy diet in overweight and obesity. Methods: This was an experiment in which women 18 to 24 years included, with a BMI≥27. The sample was composed of 34 women divided into control and experimental (17 women respectively), selected and assigned by random sampling groups. Measurements were made using a valid and reliable inventory that measures the AE in diet and exercise. The exercise dose was calculated by the Karvonen formula for 10 weeks in a gradual and controlled. The statistic used was a repeated measure MANOVA, a significance level <.05 was considered. Results: After the intervention statistically significant changes were observed, AE in 40.3 ± 4.0 vs. exercise 35.8 ± 5.4; AE and 85.8 ± 10.5 vs. diet 78.8 ± 10.7 (p <.05). Conclusions: Exercise at the target dose AE improved the condition that favored the practice of exercise and healthy diet in overweight and obesity

Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers

Background: Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity. Aim: To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern. Methods: 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their reported alcohol consumption pattern. Blood samples were obtained and hematic biometry and liver enzyme analysis were performed. Peripheral CD8 profile was established by expression of Granzyme B (GB), CD137, CD127, CD69, TLR4, PD1, CCR2, CCR4, CCR5 and CXCR4 by FACS. Data was analyzed by ANOVA, posthoc DMS and Tamhane, and principal component analysis (PCA) with varimax rotation, p\u3c0.05. Results: The Binge drinking group showed increased γGT together with increased expression of CD69 and reduced expression of TLR4, PD1, CCR2 and CXCR4 in peripheral CD8 cells. Other parameters were also specific to Binge drinkers. PCA established 3 factors associated with alcohol consumption: Early Activation represented by CD69 and TLR4 expression in the CD8 population; Effector Activation by CD69 expression in CD8 CD127(+)CD137(+) and CD8 CD25(+) CD137(+); and Trafficking by CXCR4 expression on total CD8 and CD8 GB(+)CXCR4(+), and CCR2 expression on total CD8. Binge drinking pattern showed low expression of Early Activation and Trafficking factors while Light drinking pattern exhibited high expression of Effector Activation factor. Conclusions: Alcohol consumption affects the immune phenotype of CD8 cells since binge drinking pattern was found to be associated with high CD69 and low TLR4, CXCR4 and CCR2 expression, which suggest recent activation, decreased sensitivity to LPS and lower migration capacity in response to chemokines SDF-1 and MCP-1. These results indicate that a binge-drinking pattern of alcohol consumption may induce an altered immune profile that could be related with liver damage and the increased susceptibility to infection reported to this behavior

Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial

Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary. Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity. Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo. Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of insulin resistance significantly improved in the CLA group (P = 0.045). After analysis of covariance was performed and the influence of body mass index, age, Tanner stage, prescribed diet, and fitness achievement was controlled, a clinically relevant effect size on insulin sensitivity remained evident in the CLA group (37%) and exceeded lifestyle program benefits. Moreover, upregulated expression of the insulin receptor substrate 2 was evident in muscle biopsies of the CLA group. Conclusions: Improvement of insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp and IRS2 upregulation, favored patients treated with CLA. Trial registration: ClinicalTrials.gov NCT02063802

Burden of Type 2 Diabetes and Associated Cardiometabolic Traits and Their Heritability Estimates in Endogamous Ethnic Groups of India: Findings From the INDIGENIUS Consortium

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits

Neuropsychiatric Symptoms Among Hispanics: Results of the Maracaibo Aging Study

Background: Neuropsychiatric symptoms play an important role in diagnosing and clinical follow-up of cognitive impairment and dementia. Objective: We investigated the relationship between neuropsychiatric symptoms, cognitive impairment, and dementia in Hispanics. Methods: We included 529 participants (age ≥40 years) from the Maracaibo Aging Study with standardized neuropsychiatric assessments, including the Neuropsychiatric Inventory (NPI). Based on the Clinical Dementia Rating and the Mini-Mental State Examination scores, participants’ cognitive status was categorized into normal cognition, mild/moderate, and severe cognitive impairment. Diagnosis of dementia was established in a consensus conference. Statistical analyses included multivariable logistic regression models and area under the curve (AUC). Results: The mean age of participants was 59.3 years, and 71.8% were women. The proportion of dementia was 6.8%. Disturbed sleep, anxiety, and depression were the most common neuropsychiatric symptoms in the study sample. In crude analyses, the proportions of hallucinations, aberrant motor behavior, agitation/aggression, apathy, delusions, irritability, eating disturbance, depression, and euphoria were differently distributed among cognitive status groups (p \u3c 0.05). After accounting for confounders, aberrant motor behavior and agitation/aggression remained significantly associated with cognitive impairment and dementia (p \u3c 0.05). The inclusion of the NPI domains significantly improved the AUC to discriminate severe cognitive impairment and dementia above of a basic model that included sex, age, education, alcohol, obesity, serum glucose, total cholesterol, hypertension, and stroke. Conclusion: Neuropsychiatric symptoms are associated with severe cognitive impairment and dementia. The addition of NPI items to the global cognitive assessment might help early detection of dementia in primary care settings