Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10-8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

Post-cardioversion time Course of Atrial Remodeling Markers and their Association with Recurrence in Subjects with Long-standing, Persistent Atrial Fibrillation.

BACKGROUND: Activation of the renin-angiotensin-aldosterone axis with elevation of inflammatory markers and the resulting fibrosis play a very important role in atrial remodeling in patients with atrial fibrillation (AF), which is associated with post-cardioversion recurrence. AIM OF THE STUDY: The purpose of the study was to describe the time course of angiotensin II (AngII), aldosterone, and of the amino terminal pro-peptide of type III pro-collagen (PIIINP) following cardioversion, and their association with arrhythmia recurrence. METHODS: Ninety-nine subjects with long-standing, persistent, non-valvular atrial fibrillation who underwent successful electrical cardioversion were included, with a 6 month follow up. Angiotensin II (AngII), aldosterone and PIIINP concentrations were measured at 0, 1, 7, 30, and 180 d. Two groups were formed for the analysis: continuing sinus rhythm and recurrence of AF. RESULTS: 53% of the subjects experienced recurrence of AF. Subjects with recurrence had larger left atrial diameters and lower global peak atrial longitudinal strain (8.7 vs. 19.7%; p <0.001), higher levels of AngII (431.85 vs. 257.97 pg/mL; p = 0.003) at 180 d, higher pre-cardioversion levels of aldosterone, (11.42 vs. 5.46 pg/mL; p = 0.048) at 1 d (12.01 vs. 5.05 pg/mL; p = 0.004) and at 180 d (12.66 vs. 7.51 pg/mL; p = 0.011). There were no differences in PIIINP levels between both groups. CONCLUSIONS: Electrical post-cardioversion recurrence in subjects with long-standing, persistent AF is associated with elevated levels of AngII and aldosterone.

[Comprehensive care in type 2 diabetes: from DiabeIMSS to CADIMSS]. / Atención integral en diabetes tipo 2: transición del modelo DiabetIMSS a CADIMSS.

In diabetes, obtaining optimal control is key to reducing chronic complications. Unfortunately, not all patients achieve the recommended goals. Therefore, the challenges to develop and evaluate comprehensive care models are enormous. In October 2008, the Diabetic Patient Care Program (DiabetIMSS) was designed and implemented in family medicine. Its principal component is the multidisciplinary team (doctor, nurse, psychologist, dietitian, dentist, and social worker) that offers coordinated health care; monthly medical consultation and individual, family and group education on self-care and prevention of complications for 12 months. Due to the COVID-19 pandemic, the percentage of attendance at the DiabetIMSS modules decreased significantly. This is how the Medical Director considered it necessary to strengthen them, and the Diabetes Care Centers (CADIMSS) arose. In addition to providing medical care with a comprehensive and multidisciplinary approach, the CADIMSS encourages the co-responsibility of the patient and his family. It consists of monthly medical consultation and nursing staff provides monthly educational sessions for 6 months. Pending tasks remain and there are still areas of opportunity to modernize and reorganize services that contribute to improving the health of the population with diabetes.

En un paciente con diabetes, la obtención de un control óptimo es clave para reducir las complicaciones crónicas. Desafortunadamente, no todos los pacientes logran las metas recomendadas. Por ello, son substanciales los desafíos para desarrollar y evaluar modelos de atención integral. En octubre del 2008, se diseñó e implementó el Programa de Atención al Paciente Diabético (DiabetIMSS) en medicina familiar. Su componente básico es el equipo multidisciplinario (médico, enfermera, psicólogo, dietista, dentista y trabajador social) que ofrece asistencia sanitaria coordinada, consulta médica mensual y educación individual, familiar y grupal sobre autocuidado y prevención de complicaciones durante 12 meses. Debido a la pandemia de COVID-19, el porcentaje de asistencia a los módulos DiabetIMSS disminuyó importantemente. Es así como la Dirección de Prestaciones Médicas consideró necesario su fortalecimiento, por lo que surgen los Centros de Atención a la Diabetes (CADIMSS). Además de proporcionar atención médico-asistencial con enfoque integral y multidisciplinario, en los CADIMSS se fomenta la corresponsabilidad del paciente y su familia, y se otorga consulta médica mensual y sesiones educativas a cargo de personal de enfermería durante 6 meses. Sin embargo, siguen tareas pendientes, y aún hay áreas de oportunidad para modernizar y reorganizar los servicios que contribuyan a mejorar la salud de la población con diabetes.

Bioimpedance vector analysis in stable chronic heart failure patients: Level of agreement between single and multiple frequency devices.

BACKGROUND & AIMS: The accuracy of estimating body composition compartments is critical in the clinical setting. Currently, there are different bioelectrical impedance analysis (BIA) devices available for obtaining raw BIA parameters. The aim of this study was to determine the level of agreement between multiple frequency (MF)-BIA and single frequency (SF)-BIA devices in obtaining raw BIA measurements (resistance (R), reactance (Xc), and phase angle (PhA)), as well as the agreement on the classification of hydration status and body cell mass by the bioelectrical impedance vector analysis (BIVA) method. METHODS: This cross-sectional study included 406 outpatients with stable chronic heart failure (HF). The raw BIA measurements at 50 kHz obtained by tetrapolar MF-BIA (Bodystat QuadScan 4000) were compared with those obtained by tetrapolar SF-BIA (RJL Quantum X). In addition, the patients were classified by their hydration status and body cell mass according to the BIVA method. RESULTS: Strong and significant correlations were observed between the two methods in all raw BIA variables (r ≥ 0.90). Lin's concordance correlation coefficient (CCC) values were almost perfect for R (CCC = 0.99; 95% CI 0.997 to 0.998), moderate for Xc (CCC = 0.93; 95% CI 0.92 to 0.94), and poor for PhA (CCC = 0.88; 95% CI 0.85 to 0.90). The agreement obtained in the two classifications (quadrants and hydration status) was >0.81. CONCLUSIONS: MF-BIA and SF-BIA demonstrated good agreement for measurement of the R parameter; however, the Xc and PhA parameters must be used carefully due to the previously reported variability. Likewise, the agreement in all classifications by the BIVA method was almost perfect.

The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects.

We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35-2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13-2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14-3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10-6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10-5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.

Sex/Gender Modifies the Association Between the MC4R p.Ile269Asn Mutation and Type 2 Diabetes in the Mexican Population.

CONTEXT: Studies in mice and humans suggest that melanocortin-4 receptor (MC4R) deficiency affects body weight in a sex-/gender-dependent manner. However, similar evidence for type 2 diabetes (T2D) is scarce. OBJECTIVE AND DESIGN: We investigated whether sex/gender modifies the association between the loss-of-function MC4R p.Ile269Asn mutation and T2D in 6929 Mexican adults (3175 T2D cases and 3754 normal glucose tolerance [NGT] controls). The 2003 American Diabetes Association criteria were used to define NGT and T2D. The MC4R p.Ile269Asn mutation was genotyped in all participants using TaqMan technology. RESULTS: The MC4R p.Ile269Asn mutation was associated with T2D in 6929 Mexican adults (Ncontrols = 3754, Ncases = 3175, odds ratio [OR] = 2.00, 95% confidence interval [CI], 1.35-2.97; P = 5.7 × 10-4). The MC4R p.Ile269Asn mutation had a frequency of 0.86 and 1.05% in women with NGT and T2D, and 0.78 and 1.32% in men with NGT and T2D, respectively. We identified a significant interaction between the MC4R p.Ile269Asn mutation and sex/gender on T2D risk (P = 0.049). Although a strong association between the mutation and T2D was observed in men (Ncontrols = 2418, Ncases = 1807, OR = 2.63, 95% CI, 1.62-4.28, P = 9.3 × 10-5), results were not significant in women (Ncontrols = 1336, Ncases = 1368, OR = 1.16, 95% CI, 0.60-2.26, P = 0.65). Further adjustment for body mass index in the logistic regression model did not alter the sex-/gender-specific pattern of association (men: OR = 2.22, 95% CI, 1.34-3.67, P = 0.0019; women: OR = 1.02, 95% CI, 0.51-2.02, P = 0.95). CONCLUSION: This is the first report of a male-specific association between the MC4R p.Ile269Asn loss-of-function mutation and T2D in the Mexican population.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

Evaluation of predictive value of olfactory dysfunction, as a screening tool for COVID-19.

OBJECTIVES: At the end of 2019, SARS-CoV-2 was identified, the one responsible for the COVID-19 disease. Between a 5.1% and a 98% of COVID-19 patients present some form of alteration in their sense of smell. The objective of this study is to determine the diagnostic yield of the smell dysfunction as screening tool for COVID-19. METHODS: Cross-sectional, observational, and pro-elective study was performed in a tertiary care hospital from May 25th to June 30th, 2020. One hundred and thirty-nine patients were included in the study. Demographic characteristics were collected from anamnesis. A Self-Perception Questionnaire and psychophysical olfactory test (POT) were applied to all participants. The presence of SARS-CoV2, was detected by RT-PCR methods. RESULTS: 51.7% of patients were SARS-CoV-2 positive. A sensitivity of 50% was obtained for the self-perception questionnaire as a screening tool for SARS-CoV2, with a specificity of 80.59%. The positive predictive value (PPV) was of 73.46%, the negative predictive value (NPV) was of 60%. The POT as a screening tool had a PPV of 82.35%, a NPV of 52.45%, a LR+ of 4.34, a LR- 0.84. The combination of anosmia (according to the POT) plus cough and asthenia got an OR of 8.25 for the SARS CoV-2 infection. CONCLUSION: There is a strong association between olfactory dysfunction and COVID-19. However, it is not really efficient in the screening of SARS-CoV-2 infection and thus, they should not be considered as a single diagnostic instrument. LEVEL OF EVIDENCE: 4.

Association between glycemic control and dietary patterns in patients with type 2 diabetes in a Mexican institute.

OBJECTIVE: The aim of this study was to evaluate the association between glycemic control (hemoglobin (Hb) A1c <7%) and the dietary patterns identified in Mexican patients with type 2 diabetes mellitus (T2DM). METHODS: This was a secondary analysis conducted with 4838 patients with T2DM in Mexico. Biochemical blood profiles, socioeconomic level, anthropometric measurements, and dietary data were obtained. Dietary data from a food frequency questionnaire were used to derive dietary patterns. Factor analysis was conducted to ascertain dietary patterns, and multivariate analysis was fitted to assess the relationship between glycemic control and consumption of dietary patterns. RESULTS: Three dietary patterns were identified. After control for potential cofounders (age, sex, duration of T2DM, body mass index, pharmacologic treatment, intensity of physical activity, socioeconomic level, and kcal/kg ideal weight), we found that consuming a Western-style diet (odds ratio [OR], 1.533, 95% confidence interval [CI], 1.253-1.875; P < 0.000), and the sweets and dairy diet (fats and sugars; OR, 1.444; 95% CI, 1.133-1.841; P = 0.003) patterns were associated with HbA1c ≥7%, whereas consuming a healthy dietary patter (OR, 0.800; 95% CI, 0.642-0.998; P = 0.048) was associated with HbA1c <7%. CONCLUSIONS: Consuming a healthy diet was associated with glycemic control; whereas the Western-style or sweets and dairy patterns promoted a lack of metabolic control. These results support the promotion of a healthy pattern in the Mexican population with T2DM.

Causal Association of Haptoglobin With Obesity in Mexican Children: A Mendelian Randomization Study.

CONTEXT: Little is known about the association between haptoglobin level and cardiometabolic traits. A previous genome-wide association study identified rs2000999 in the HP gene as the stronger genetic contributor to serum haptoglobin level in European populations. OBJECTIVE AND DESIGN: We investigated the association of HP rs2000999 with serum haptoglobin and childhood and adult obesity in up to 540/697 and 592/691 Mexican cases and controls, respectively. Anthropometric and biochemical data were collected. Serum haptoglobin was measured by an immunoturbidimetry assay. HP rs2000999 was genotyped using the TaqMan technology. Mendelian randomization analysis was performed using the Wald and inverse variance weighting methods. RESULTS: Haptoglobin level was positively associated with childhood and adult obesity. HP rs2000999 G allele was positively associated with haptoglobin level in children and adults. HP rs2000999 G allele was positively associated with childhood but not adult obesity. The association between HP rs2000999 and childhood obesity was removed after adjusting for haptoglobin level. In a Mendelian randomization analysis, haptoglobin level genetically predicted by HP rs2000999 showed a significant causal effect on childhood obesity by the Wald and inverse variance weighting methods. CONCLUSION: Our data provide evidence for the first time for a causal positive association between serum haptoglobin level and childhood obesity in the Mexican population. Our study contributes to the genetic elucidation of childhood obesity and proposes haptoglobin as an important biomarker and treatment target for obesity.

The Melanocortin 4 Receptor p.Ile269Asn Mutation Is Associated with Childhood and Adult Obesity in Mexicans.

CONTEXT: Rare partial/complete loss-of-function mutations in the melanocortin-4 receptor (MC4R) gene are the most common cause of Mendelian obesity in European populations, but their contribution to obesity in the Mexican population is unclear. OBJECTIVE AND DESIGN: We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults. RESULTS: We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols = 952, Ncases = 661, odds ratio (OR) = 3.06, 95% confidence interval (95%CI) [1.94-4.85]) and adult obesity (Ncontrols = 1445, Ncases = 2,487, OR = 2.58, 95%CI [1.52-4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52 to 0.59% and 1.53 to 1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in 5 multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than noncarriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population. CONCLUSION: The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.

Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study.

The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells. The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus. A cohort study was conducted in 308 individuals with a diagnosis of type 2 diabetes mellitus of less than 3 years and who had metformin monotherapy. Three measurements of blood glycated hemoglobin (HbA1c ) were obtained at the beginning of the study and after 6 and 12 months. Five polymorphisms were analyzed in the SLC22A1 (rs622342, rs628031, rs594709), SLC22A2 (rs316019), and SLC47A1 (rs2289669) genes by real-time polymerase chain reaction. The results showed a significant association among genotypes CC-rs622342 (ß = 1.36; P < .001), AA-rs628031 (ß = 0.98; P = .032), and GG-rs594709 (ß = 1.21; P = .016) in the SLC22A1 gene with an increase in HbA1c levels during the follow-up period. Additionally, a significant association was found in the CGA and CAG haplotypes with an increase in HbA1c levels compared to the highest-frequency haplotype (AGA). In conclusion, the genetic variation in the SLC22A1 gene was significantly related to the variation of the HbA1c levels, an important indicator of glycemic control in diabetic patients. This information may contribute to identifying patients with an altered response to metformin before starting their therapy.

Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.

Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

[Association between depression and hearing loss in patients with type 2 diabetes]. / Asociación entre depresión e hipoacusia en pacientes con diabetes tipo 2.

BACKGROUND: The association between diabetes, hearing loss and depression is unknown, and needs to be understood clearly and precisely. Our objective was to estimate the association between depression and hearing loss in patients with type 2 diabetes. METHODS: Cross-sectional analytical study. Patients of 40 years or older with type 2 diabetes were studied. Anthropometric measurements and biochemical parameters were recorded. The Beck Depression Inventory and a pure tone audiometry were applied. Groups were compared with chi squared test and logistic regression for confounders. RESULTS: 150 patients were included (76 % women). Average age was 56 ± 9.3 years, with 12.4 ± 6.5 years of progression of diabetes, weight 67.4 ± 11.6 kg; 31 % were obese; 25.5 % hypertensive (126.3 ± 19.3 / 79.4 ± 19.7 mm Hg) and 80.7 % had poor metabolic control (HbA1c ≥ 7 %). Of all the patients, 45.3 % presented hearing loss and 32.4 % depression. Diagnosis of depression in patients with hearing loss remained significant after adjusting for confounders (odds ratio [OR] = 2.3; 95 % confidence interval [CI] = 1.051-5.333, p = 0.037). Women had greater risk of depression, difference that remained significant (OR = 3.2; 95 % CI = 1.268-8.584, p = 0.014) after adjustment. CONCLUSIONS: Almost half of the patients with diabetes presented hearing loss and more than three times the risk of depression. Subjects with depression and diabetes presented more hearing loss (> 20 dB) than those without diabetes and/or without depression.

Introducción: se desconoce y es necesario entender con mayor claridad y precisión cuál es la asociación entre la diabetes, la hipoacusia y la depresión. Nuestro objetivo fue estimar la asociación entre depresión e hipoacusia en pacientes con diabetes tipo 2 (DT2). Métodos: estudio transversal analítico. Se estudiaron pacientes con DT2 mayores de 40 años. Se registraron medidas antropométricas y parámetros bioquímicos. Se aplicó el cuestionario de depresión de Beck y un estudio audiológico tonal. Se compararon los grupos con chi cuadrada y regresión logística. Resultados: se incluyeron 150 pacientes (76 % mujeres). El promedio de edad fue de 56 ± 9.3 años, con 12.4 ± 6.5 años de evolución de diabetes, con peso de 67.4 ± 11.6kg; fueron obesos el 31 %; 25.5 % hipertensos (126.3 ± 19.3/79.4 ± 19.7 mm Hg) y el 80.7 % presentó descontrol metabólico (HbA1c ≥ 7 %). El 45.3 % presentó hipoacusia y el 32.4 % depresión. El diagnóstico de depresión en pacientes con hipoacusia permaneció significativo después de ajustar para conseguir confusores (razón de momios [RM] = 2.3; intervalo de confianza [IC] al 95 % 1.051-5.333, p = 0.037). Las mujeres tuvieron mayor riesgo de padecer depresión, diferencia que permaneció significativa al ajustarse (RM = 3.2; IC 95 % 1.268-8.584, p = 0.014). Conclusiones: casi la mitad de los pacientes con diabetes presentaron hipoacusia y más de tres veces el riesgo de depresión. Los sujetos con depresión y diabetes mostraron mayor hipoacusia (> 20 dB) que aquellos sin diabetes o sin depresión.

Triggering factors of primary care costs in the years following type 2 diabetes diagnosis in Mexico.

BACKGROUND AND AIMS: Diabetes represents a high epidemiological and economic burden worldwide. The cost of diabetes care increases slowly during early years, but it accelerates once chronic complications set in. There is evidence that adequate control may delay the onset of complications. Management of diabetes falls almost exclusively into primary care services until chronic complications appear. Therefore, primary care is strategic for reducing the expedited growth of costs. The objective of this study was to identify predictors of primary care costs in patients without complications in the years following diabetes diagnosis. METHODS: Direct medical costs for primary care were determined from the perspective of public health services provider. Information was obtained from medical records of 764 patients. Microcosting and average cost techniques were combined. A generalized linear regression model was developed including characteristics of patients and facilities. Primary health care costs for different patient profiles were estimated. RESULTS: The mean annual primary care cost was USD$465.1. Gender was the most important predictor followed by weight status, insulin use, respiratoty infections, glycemic control and dyslipidemia. A gap in costs was observed between genders; women make greater use of resources (42.1% on average). Such differences are reduced with obesity (18.1%), overweight (22.8%), respiratory infection (20.8%) and age >80 years (26.8%). Improving glycemic control shows increasing costs but at decreasing rates. CONCLUSIONS: Modifiable factors (glycemic control, weight status and comorbidities) drive primary care costs the first 10 years. Those factors had a larger effect in costs for males than in for females.

[Childhood obesity and dyslipidemia]. / Obesidad infantil y dislipidemia.

Screening and treatment of plasma lipid abnormalities secondary to obesity are among the interventions that should be implemented in children who are overweight or obese, in order to prevent a cardiovascular event. Dyslipidemias are a group of asymptomatic diseases that are commonly caused by abnormal levels of lipoproteins in blood; they are a comorbidity that is commonly related to obesity, without considering the age of the patient. Among dyslipidemias, hypertriglyceridemia has the highest prevalence. The etiology of the dyslipidemia should be identified; it allows the proper selection of therapy for the patients and their family. The goal is the prevention of cardiovascular complications. Reduced caloric intake and a structured physical activity plan should be considered for initial treatment for all the overweight and obese patients. For adherence to treatment to be successful, the participation of the primary care physician and a multidisciplinary team is required. With treatment, the risks and complications can be reduced. The participation of a specialist in handling the pediatric obese patient with dyslipidemia should be limited to severe cases or those at risk for having pancreatitis.

En todos los niños o adolescentes con sobrepeso u obesidad debe buscarse de manera intencionada la presencia de dislipidemias que sean secundarias a la obesidad, con el fin de poder prevenir un evento cardiovascular. Las dislipidemias son un grupo de enfermedades asintomáticas que comúnmente son causadas por concentraciones anormales de las lipoproteínas sanguíneas; son una comorbilidad que es común en la obesidad, independientemente de la edad del paciente. De estas enfermedades, la que tiene mayor prevalencia es la hipertrigliceridemia. Identificar anormalidades en el perfil de lípidos de la población pediátrica permite seleccionar la intensidad y el tipo de tratamiento para el paciente y su familia. El manejo inicial que debe recibir todo niño y adolescente con obesidad y dislipidemia debe basarse en la promoción de un estilo de vida saludable con la dieta y el ejercicio. Para que la adherencia al tratamiento sea exitosa, es fundamental la participación del médico en combinación con un equipo multidisciplinario. Con el tratamiento se pueden reducir los riesgos de complicaciones. La participación del especialista en el manejo del paciente pediátrico obeso con dislipidemias debe limitarse a los casos con dislipidemias severas o a aquellos en los que se busque prevenir una pancreatitis.

Epidemiology of type 1 diabetes in Latin America.

Latin America is among the regions with the highest diabetes-related burden. Research and treatment programs have increased in number and complexity in recent years, but they are focused in type 2 diabetes, because this condition explains a large proportion of the cases. In contrast, the information regarding the epidemiology of type 1 diabetes is scant in this area. Here, we analyze the available information on this topic and identify potential areas of opportunity to generate new knowledge through the study of type 1 diabetes in Latin Americans. Both, the prevalence and the incidence of type 1 diabetes, are lower in Latin American countries compared to that reported in Europe, North America, southern Asia and northern Africa. Biologic and methodological factors may explain the smaller contribution of type 1. The presence of some putative 'protective' environmental exposures or the absence of those prevalent in a region may explain the lower type 1 diabetes prevalence observed in most Latin American countries. However, the number and quality of the diabetes registries are not enough in this region. During the past decade, the incidence of type 1 diabetes has grown worldwide. The same trend has been reported in Latin America. This epidemiologic transition is a unique opportunity to identify interactions between rapidly changing environmental factors in subjects with different genetic backgrounds (such as the admixed Latin American populations). Finally, on-going therapeutic initiatives in this region are highlighted.

[Clinical practice guidelines. Diagnosis and treatment of diabetic retinopathy]. / Guía de práctica clínica. Diagnóstico y tratamiento de la retinopatía diabética.

OBJECTIVE: to develop a guideline available to the staff of the second and third level of medical care, that includes recommendations based on the best available evidence about diagnosis and management of diabetic retinopathy (DR). METHODS: clinical questions were formulated and structured. A standardized sequence was established to search for practice guidelines from the clinical questions raised on diagnosis and treatment of DR. The working group searched clinical practice guidelines and found eleven on this topic. For recommendations not included in the reference guide, the search process was conducted in PubMed and Cochrane Library. The results were expressed as levels of evidence and grade of recommendation. CONCLUSIONS: in Mexico diabetic retinopathy is a main cause of blindness in the active working population. It is necessary to establish a program for detection of at-risk population that allow make early diagnosis and opportune management for reducing blindness in patients. It is equally important to be aware of the need for long-term good metabolic control, which is associated with better quality of life.

[Clinical research III. The causality studies]. / Investigación clínica III. Estudios de causalidad.

The need to solve a clinical problem leads us to establish a starting point to address (risk, prognosis or treatment studies), all these cases seek to attribute causality. Clinical reasoning described in the book Clinical Epidemiology. The architecture of clinical research, offers a simple guide to understanding this phenomenon. And proposes three basic components: baseline, maneuver and outcome. In this model, different systematic errors (bias) are described, which may be favored by omitting characteristics of the three basic components. Thus, omissions in the baseline characteristics cause an improper assembly of the population and susceptibility bias, omissions in the application or evaluation of the maneuver provoke performance bias, and omissions in the assessment of out-come cause detection bias and transfer bias. Importantly, if this way of thinking facilitates understanding of the causal phenomenon, the appropriateness of the variables to be selected in the studies to which attribute or not causality, require additional arguments for evaluate clinical relevance.

[Clinical research II. Studying the process (the diagnosis test)]. / Investigación clínica II. Estudios de proceso (prueba diagnóstica).

A diagnosis test is carried out to establish the presence of health or illness. In the latter it could grade the severity. Due to its importance in clinical decisions, the diagnosis test is evaluated by mathematical strategies. We estimate the sensitivity and specificity once we know the existence or not of the disease, but we act in the reverse direction; with the presence "X" test positive or negative we estimate the presence of the disease, therefore, we use the positive and negative predictive values. Mathematical strategy allow us to quantify the observation, but it requires judgment to determine the quality making use of a minimum of features: a) selection under the same criteria for cases and controls; b) the inclusion of the full spectrum of disease severity (from mild to the most serious, ensuring that all levels have an enough number of subjects); c) the interpretation of both, the gold standard and the new tool of diagnosis, it must be blind and conducted by experts; d) the interpretation of results should show us what is their application in everyday clinical practice; e) the reproducibility must be checked. Do not forget that usually, we treat only one patient at once, what enforce us to have full knowledge of the performance of the diagnostic test, and to consider all clinical aspects for its proper implementation.