Body weight loss and glycemic control on the outcomes of patients with NAFLD. The role of new antidiabetic agents.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide affecting a third of adults and 12% of children in Western countries. In around 50-60%% of cases, NAFLD and type 2 diabetes mellitus (T2DM) coexist and act synergistically to increase the risk of adverse hepatic and extra-hepatic outcomes. T2DM is a strong risk factor for rapid progression of NAFLD to nonalcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma (HCC), which have become frequent indications of liver transplantation. The pathophysiology of NAFLD is complex and its relationship with T2DM is bidirectional, where lipotoxicity and insulin resistance (IR), act as the strongest pillars. To date, no pharmacological treatment has been approved for NAFLD. However, there is an intense research with numerous drugs focused on reversing inflammation and liver fibrosis through modulation of molecular targets without good results. It has been known for some time that weight reduction >10% is associated to histological improvement of NAFLD. Recently, glycemic control has been shown to induce similar results. Diet and physical exercise for weight reduction have limitations, so alternative methods (pharmacologic, endoscopic or surgical) may be required. Currently, new antidiabetic drugs inducing weight loss, have been recently approved for the treatment of obesity. Nevertheless, their therapeutic effects on NAFLD have not been extensively studied. We will review here, recently published data on the effects of weight loss and glycemic control on the histological and metabolic parameters of NAFLD and recent published data on therapeutic studies of NAFLD with new antidiabetic drugs.

Mitochondrial dysfunction: The pathological link between psoriasis and insulin resistance?

BACKGROUND: Psoriasis is strongly associated with insulin resistance (IR). Lipid profile disturbances and upregulation of enzymes crucial for fatty acid oxidation have been reported in patients with psoriasis. Mitochondrial ß-oxidation is altered in patients with IR. Common mitochondrial dysfunction may be involved in the origin of both diseases. OBJECTIVE: This study aimed to evaluate mitochondrial ß-oxidation, intermediary metabolism, and mitochondrial content in psoriatic patients with or without IR and compare them to healthy controls. METHODS: The participants were divided into three groups: (1) psoriasis and IR (n = 26); (2) psoriasis without IR (n = 17); and (3) healthy controls (n = 17). Quantification of amino acids and acylcarnitines (AC) by tandem mass spectrometry, determination of urinary organic acids by gas chromatography/mass spectrometry (GC/MS), and mitochondrial DNA quantification were performed in all groups. RESULTS: When comparisons were made between the two psoriatic groups, no differences were found between: C5DC + C6OH, C16:1, Met/Leu, Met/Phe, C16:1/C16, and C5DC + C6OH/C4DC + C5OH ratios. Nine analytes were different: phenylalanine, Cit/Phe, and Cit/Tyr ratios, C0, C3, C5, C6DC, C16, and C18:1OH. There were no correlations between psoriasis area and severity index (PASI), body mass index (BMI) and duration of disease with ACs. A higher proportion of patients with psoriasis showed increased urine levels of uric acid and hippuric acid (p = 0.01). The mtDNA content was significantly higher in cases than in controls, with no differences between IR and non-IR psoriatic patients. CONCLUSIONS: Psoriasis patients with and without IR have a different acylcarnitine profile reflecting impaired ß-oxidation. A distinctive profile of acylcarnitines suggests an involvement of mitochondrial function associated with an increase in stearoyl CoA desaturase (SCD) activity in psoriatic patients with and without IR.

Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives.

Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.

Arterial thrombosis and intracardiac thrombus as the initial presentation of a recurrent paraganglioma: case report and review of the literature

SUMMARY Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that result in the uncontrolled release of catecholamines and secondary hypertension. They usually manifest with episodic blood pressure fluctuations, headaches and palpitations. In some cases PPGLs may be asymptomatic until they are detected as a diagnostic approach to other diseases. There have been reports that have associated PPGLs with arterial thrombosis, some with the additional finding of intracardiac thrombi. We present the case of a 21-year-old male Hispanic patient with a recurrent para-aortic paraganglioma detected by persistent hypertension, bilateral lower limb artery thrombosis and an intracardiac thrombus.

Arterial thrombosis and intracardiac thrombus as the initial presentation of a recurrent paraganglioma: case report and review of the literature.

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that result in the uncontrolled release of catecholamines and secondary hypertension. They usually manifest with episodic blood pressure fluctuations, headaches and palpitations. In some cases PPGLs may be asymptomatic until they are detected as a diagnostic approach to other diseases. There have been reports that have associated PPGLs with arterial thrombosis, some with the additional finding of intracardiac thrombi. We present the case of a 21-year-old male Hispanic patient with a recurrent para-aortic paraganglioma detected by persistent hypertension, bilateral lower limb artery thrombosis and an intracardiac thrombus.

Evaluation of Ovarian Reserve in Women With Rheumatoid Arthritis.

Objective: Subfertility is commonly observed in patients with rheumatoid arthritis (RA). Although the causes are not well established, the alteration of the ovarian reserve is thought to contribute to the lower chances of pregnancy. This cross-sectional study aimed to evaluate the ovarian reserve in patients with RA. Materials and methods: Two parameters associated with ovarian reserves such as the antral follicle count (AFC) and the anti-müllerian hormone (AMH) were assessed in 38 patients with RA. We also analyzed the correlation of these parameters with the medication used to treat this pathology and with the illness severity. Results: The AMH levels in women with RA were comparable to those found on healthy individuals although the RA patients were more likely to have a low AFC. Ovarian reserve and RA were neither influenced by parameters of disease activity nor by the use of medication. Conclusion: The ovarian reserve in women with RA was similar to that found in healthy individuals.

Association study in Mexican patients with thyrotoxic hypokalemic periodic paralysis.

Hypokalemic periodic paralysis type 1 (OMIM; HOKPP1) and type 2 (OMIM; HOKPP2) are diseases of the muscle characterized by episodes of painless muscle weakness, and is associated with low potassium blood levels. Hyperthyroidism has been associated with thyrotoxic periodic paralysis (TTPP) (OMIM; TTPP1 and TTPP2), and genetic susceptibility has been implicated. In the present study, the clinical and epidemiological characteristics of patients with TTPP are described, together with their association with genetic variants reported previously in other populations. A prospective and a retrospective search of the medical records of patients who attended the emergency department at the Hospital Universitario 'Dr. Jose E. Gonzalez' in Monterrey, Nuevo León, Mexico, and were diagnosed with TTPP was performed. A total of 16 gene variants in the genes MUC1, CACNA1S, KCNE3 and SCN4A, and nine ancestry informative markers (AIMs), were analysed by Multiplex TaqMan™ Open Array assay, and a genetic association study was performed. A total of 11 patients were recruited, comprising nine males and two females (age range, 19-52 years) and 64 control subjects. Only two cases (18%) had a previous diagnosis of hyperthyroidism; the rest were diagnosed subsequently with Graves' disease. Based on the analysis, two DNA variants were found to potentially confer an increased risk for TTPP: S1PR1 rs3737576 [odds ratio (OR), 4.38; 95% confidence interval (CI), 1.08-17.76] and AIM rs2330442 (OR, 4.50; 95% CI, 1.21-16.69), and one variant was suggested to be possibly associated with TTPP, namely MUC1 rs4072037 (OR, 3.08; 95% CI, 0.841-1.38). However, there were no statistically significant associations between any of the 24 DNA variants and TTPP in a population from northeast Mexico.

Gene Copy Number Quantification of SHOX, VAMP7, and SRY for the Detection of Sex Chromosome Aneuploidies in Neonates.

Aims: To explore the feasibility of detecting sex chromosome aneuploidies (SCAs) by means of gene copy number quantification of short stature homeobox (SHOX), vesicle-associated membrane protein 7 (VAMP7), and SRY in newborns. Materials and Methods: Gene doses of SHOX, VAMP7, and SRY were determined by quantitative polymerase chain reaction (qPCR) using DNA obtained from dried blood samples from newborns. Relative quantification values were obtained. An aneuploidy profile was established according to cutoff values. Samples with ≥2 gene doses (out of range) were reanalyzed, and those with aneuploidy profiles were confirmed by karyotyping. Sensitivity, specificity, and positive and negative predictive values were obtained. Results: A total of 10,033 samples were collected (4945 females and 5088 males). Of 244 (2.43%) samples with ≥2 gene doses that were retested, 20 cases were confirmed. The overall incidence of SCAs was 1 in 500 live newborns. There were six cases of Turner syndrome (1/824), 3 cases of XXX (1/1648), 7 cases of Klinefelter syndrome (1/726), and 4 cases of of XYY (1/1272). The sensitivity was 0.952 (95.42%); the specificity was 0.975 (97.56%); the positive predictive value was 0.909 (90.91%) and the negative predictive value was 0.987 (98.77%). Conclusions: Gene copy number analyses of the VAMP7, SHOX, and SRY genes by qPCR from blood samples spotted onto filter paper is a highly reliable method for the early detection of male and female SCAs.

Prevalence of liver fibrosis in an unselected general population with high prevalence of obesity and diabetes mellitus. Time for screening?

INTRODUCTION: Cirrhosis and liver cancer are currently common causes of death worldwide. The global epidemic of obesity has increased the incidence of nonalcoholic fatty liver disease (NAFLD) and cirrhosis in recent years. Advanced fibrosis increases the morbimortality rate in NAFLD. The Mexican population has one of the highest prevalence of obesity and diabetes mellitus (DM) worldwide. AIM: To determine the prevalence of advanced liver fibrosis in Mexican general population. METHODS: Adult individuals, without a history of liver disease nor heavy alcohol consumption were randomly sampled from 20,919 participants of a health and nutrition survey applied to the general population. Clinical and laboratory evaluations were performed to calculate the NAFLD fibrosis score (NFS) (an extensively validated non-invasive method). Two cut-off points were used. Advanced fibrosis was defined as a result >0.676. RESULTS: In total 695 individuals were included. The mean age was 47.8±16.4. The majority were between 20 and 50 years (59%), 70.2% were female, 35.5% showed obesity and 15.8% DM. The 93% had normal serum ALT. Based on the NFS results, 56 individuals (8.1%) had a high probability of fibrosis. Most patients from this subgroup showed normal serum ALT (92.9%), 89.3% were >45yr. old, 52% were obese and 27% suffered from DM. CONCLUSIONS: Based on these results, 8.1% of Mexican general population without a history of liver disease is at high risk of having advanced liver fibrosis and complications and death derived from cardiovascular disease and cirrhosis. Most of them showed normal ALT serum levels.

Impact of diagnosis of overweight and obesity on weight management among hospitalized patients.

BACKGROUND: Obesity is a growing epidemic associated with a 30% increase in general mortality. Despite this, diagnosis and treatment is still deficient. A large number of patients with overweight and obesity enter hospitals daily; therefore, the hospital setting could be used as a scenario for intervention in this population. OBJECTIVES: To determine the frequency of diagnosis and treatment of overweight/obesity in hospitalized patients and to identify the factors involved in the probability of offering a diagnosis and treatment. METHODS: Cross-sectional data from 316 patients aged 18 years and over admitted in the Department of Internal Medicine during 2016-2017 period. Logistic regression was used to estimate the relationship between the possible predictors and the diagnosis of overweight and/or obesity and the development of a treatment. RESULTS: Only 10.8% of the population was diagnosed (overweight 2.6%, obesity 18.8%). Patients with a BMI >40kg/m2 had a greater probability of being diagnosed (OR=1.87; 95% CI, 2.2-19.4; p=0.001). Only 4.4% of the population received treatment (overweight 3.2%, obesity 5.6%) and the only factor that increased the probability of receiving treatment was having been diagnosed with overweight/obesity in the medical record (OR=2.28; 95% CI, 2.31-41.94; p=0.002). DISCUSSION: Despite the high prevalence of overweight and obesity among hospitalized patients, there is no adequate diagnosis and treatment. Future research should be directed at strategies that increase medical recognition of overweight/obesity as well as identifying the long-term benefits of diagnosing overweight/obesity for the reduction and control of body weight.

Are cord blood visfatin concentrations different depending on birth weight category? / Niveles de visfatina en sangre del cordón umbilical, ¿son diferentes según la categoría de peso al nacer?

Background and objective: Increased visceral adipose tissue mass is strongly associated to metabolic disorders. Visfatin is a visceral fat adipocytokine. There is epidemiological evidence of a link between a suboptimal gestational environment and a greater propensity to develop metabolic disease in adult life. The objective of this study was to establish whether visfatin concentrations in umbilical cord blood are different in newborns small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Subjects and methods: Term newborns from an university medical center were included in the study. A blood sample was taken from the umbilical cord vein of each baby immediately after birth. Visfatin was measured using an enzyme immunoassay in the study population, consisting of 35 subjects in the SGA group, 58 in the AGA group, and 35 in the LGA group. Results: Cord blood visfatin concentrations were not different in the three groups, with respective values of 2.78 (1.86-4.49) ng/mL, 3.28 (1.98-4.97) ng/mL, and 3.46 (2.48-5.38) ng/mL in the SGA, AGA and LGA groups (p=0.141). Gestational weight gain (GWG) (14.09±6.37kg) was negatively associated to visfatin levels (r=−0.218, p=0.036). GWG is an independent predictor of visfatin concentrations (r2=−0.067, p=0.027). Conclusions: There were no differences in cord blood visfatin concentrations depending on birth weight. GWG is an independent predictor of visfatin levels in the cord blood of term newborns

Antecedentes y objetivo: El aumento de la masa de tejido adiposo visceral está fuertemente asociado con trastornos metabólicos. La visfatina es una adipocitoquina de la grasa visceral. Existe evidencia epidemiológica de un vínculo entre un entorno gestacional subóptimo y una mayor propensión a desarrollar enfermedades metabólicas en la vida adulta. El objetivo de este estudio es determinar si las concentraciones de visfatina en la sangre del cordón umbilical son diferentes entre recién nacidos pequeños para edad gestacional (PEG), apropiados para edad gestacional (AEG) y grandes para edad gestacional (GEG). Materiales y métodos: Se incluyeron los recién nacidos a término de un centro médico universitario. Se tomó una muestra de sangre de la vena del cordón umbilical de cada niño inmediatamente después del nacimiento. La visfatina se midió mediante inmunoensayo enzimático en la población de estudio, que incluyó 35 sujetos en el grupo PEG, 58 en el AEG y 35 en el GEG. Resultados: Las concentraciones de visfatina en sangre del cordón umbilical no fueron diferentes entre los 3 grupos de estudio, 2,78 (1,86-4,49) ng/ml, 3,28 (1,98-4,97) ng/ml, 3,46 (2,48-5,38) ng/ml para el PEG, AEG y GEG, respectivamente (p=0,141). El aumento de peso gestacional (GWG) (14,09±6,37kg) se asoció negativamente con los niveles de visfatina (r=−0,218, p=0,036). El GWG es un predictor independiente de los niveles de visfatina (r2=−0,067, p=0,027). Conclusiones: Los niveles de visfatina en sangre del cordón umbilical no tienen un comportamiento diferenciado según el peso al nacer. El GWG es un predictor independiente de los niveles de visfatina en la sangre del cordón umbilical de recién nacidos a término

Are cord blood visfatin concentrations different depending on birth weight category?

BACKGROUND AND OBJECTIVE: Increased visceral adipose tissue mass is strongly associated to metabolic disorders. Visfatin is a visceral fat adipocytokine. There is epidemiological evidence of a link between a suboptimal gestational environment and a greater propensity to develop metabolic disease in adult life. The objective of this study was to establish whether visfatin concentrations in umbilical cord blood are different in newborns small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). SUBJECTS AND METHODS: Term newborns from an university medical center were included in the study. A blood sample was taken from the umbilical cord vein of each baby immediately after birth. Visfatin was measured using an enzyme immunoassay in the study population, consisting of 35 subjects in the SGA group, 58 in the AGA group, and 35 in the LGA group. RESULTS: Cord blood visfatin concentrations were not different in the three groups, with respective values of 2.78 (1.86-4.49) ng/mL, 3.28 (1.98-4.97) ng/mL, and 3.46 (2.48-5.38) ng/mL in the SGA, AGA and LGA groups (p=0.141). Gestational weight gain (GWG) (14.09±6.37kg) was negatively associated to visfatin levels (r=-0.218, p=0.036). GWG is an independent predictor of visfatin concentrations (r2=-0.067, p=0.027). CONCLUSIONS: There were no differences in cord blood visfatin concentrations depending on birth weight. GWG is an independent predictor of visfatin levels in the cord blood of term newborns.

Factors associated with glycemic status and ability to adapt to changing demands in people with and without type 2 diabetes mellitus: A cross-sectional study.

OBJECTIVES: Type 2 diabetes mellitus studies focus on metabolic indicators and different self-reported lifestyle or care behaviors. Self-reported instruments involve conscious process therefore responses might not reflect reality. Meanwhile implicit responses involve automatic, unconscious processes underlying social judgments and behavior. No studies have explored the combined influence of both metabolic indicators and implicit responses on lifestyle practices in type 2 diabetes mellitus patients. The purpose was to investigate the explained variance of socio-demographic, metabolic, anthropometric, clinical, psychosocial, cognitive, and lifestyle variables on glycemic status and on the ability to adapt to changing demands in people with and without type 2 diabetes mellitus in Monterrey, Mexico. METHODS: Adults with (n = 30, mean age 46.90 years old, 33.33% male) and without (n = 32, mean age: 41.69 years old, 21.87% male) type 2 diabetes mellitus were studied. Glycemic status was assessed using Bio-Rad D-10 Hemoglobin A1c Program, which uses ion-exchange high-performance chromatography. Stroop 2 test was used to assess the ability to changing demands. RESULTS: In participants with type 2 diabetes mellitus, less years of education, negative self-actualization, and higher levels of cholesterol and triglycerides explained more than 50% of the variance in glycemic status. In participants without type 2 diabetes mellitus, the variance (38.7%) was explained by total cholesterol, metabolic syndrome, high-density lipoprotein, and self-actualization scores; the latter in opposite direction. The ability to adapt to changing demands was explained by total cholesterol, malondialdehyde, insulin resistance, and triglycerides. In participants without type 2 diabetes mellitus, the contributing variables were metabolic syndrome and nutrition scores. CONCLUSION: Results showed significant effect on at least one of the following variables (socio-demographic, metabolic, or lifestyle subscale) on glycemic status in people with and without type 2 diabetes mellitus. The ability to adapt to changing demands was explained by metabolic variables but only in participants without type 2 diabetes mellitus. Preference for unhealthy behaviors (implicit or automatic responses) outweighs healthy lifestyle practices in people with and without type 2 diabetes mellitus.

[Evaluation of vitamin D serum levels in asthmatic adults and their relationship with asthma control].

BACKGROUND: Decreased levels of vitamin D influence on the control and severity of asthma. OBJECTIVE: To evaluate the relationship between vitamin D serum levels and asthma control, as well as nutritional status, quality of life and patient comorbidities. METHODS: Cross-sectional, observational, descriptive study of 43 asthmatic patients older than 18 years of age. Multiple logistic and multiple linear regression multivariate analyses of variance were performed; a p-value ≤ 0.05 was considered to be statistically significant. RESULTS: Insufficient vitamin D levels were determined in 83.7 % of patients; 93 % had at least one asthma exacerbation in the previous year. There was no relationship between vitamin D serum levels and asthma control as measured by ACT and FEV1. There was a significant association between body mass index and vitamin D levels (p = 0.013). With a quality of life questionnaire for asthmatic adults, 76.7 % were recorded to have a poor quality of life. CONCLUSIONS: No relationship was observed between vitamin D serum levels and asthma control in the patients. Most patients had insufficient vitamin D serum levels, uncontrolled asthma, and poor quality of life. Overweight and grade I obesity were associated with vitamin D insufficient levels.

Antecedentes: Los niveles disminuidos de vitamina D influyen en el control y la gravedad del asma. Objetivo: Evaluar la relación entre niveles séricos de vitamina D y control del asma, así como estado nutricional, calidad de vida y comorbilidades del paciente. Métodos: Estudio transversal, observacional y descriptivo de 43 pacientes asmáticos mayores de 18 años. Se realizó análisis de varianza multivariados de regresión logística múltiple y lineal múltiples; se consideró estadísticamente significativa una p ≤ 0.05. Resultados: Se determinaron niveles insuficientes de vitamina D en 83.7 % de los pacientes; 93 % presentó al menos una exacerbación asmática en el último año. No se evidenció relación entre los niveles séricos de vitamina D y control del asma medido por el Asthma Control Test (ACT) y el volumen espiratorio forzado el primer segundo (FEV1). Se obtuvo asociación significativa entre el índice de masa corporal y niveles de vitamina D (p = 0.013). Con un cuestionario de calidad de vida en adultos asmáticos se registró que 76.7 % tenía mala calidad de vida. Conclusiones: No se observó relación entre los niveles séricos de vitamina D y el control del asma en los pacientes. La mayoría de los pacientes tenía niveles séricos de vitamina D insuficientes, asma descontrolada y mala calidad de vida. El sobrepeso y la obesidad grado I se asociaron con niveles insuficientes de vitamina D.

Vitamin D deficiency in Mexican mothers and their newborns. / Deficiencia de vitamina D en madres y neonatos mexicanos.

Objective: The purpose of this study is to establish the prevalence of vitamin D deficiency and their newborns and analyze the risk factors related to this deficiency. Methods: This is an observational, transversal, and prospective study. It included 191 puerperal women and their full-term newborns. Serum 25 hydroxyvitamin D values were analyzes by enzyme immunoassay. Results: 61% of the puerperal presented deficiency and 26% insufficiency of vitamin D. In the newborn group 98% showed deficiency and 66% of them presented severe deficiency. There is a positive correlation between the values of vitamin D in mothers and their newborns (r2 = 0.173 ng/ml; p = 0.017). The lowest levels were in autumn. (15.75 ng/mL mothers, 6 ng/mL newborns). There was no correlation between vitamin D levels in mothers and their dietary intake, maternal skin type, sun time exposure and prenatal body mass index. Conclusions: This is the first study that shows the existence of a high deficiency of vitamin D in Mexican mothers and their newborns.

Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study.

The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low-density lipoprotein (LDL), very LDL (VLDL), high-density lipoprotein (HDL) and triglycerides were evaluated. Three genetic markers previously associated with metabolic syndromes were identified in the sample population, including KCNJ11, TCF7L2 and HNF4A. The KCNJ11 SNP rs5210 was associated with T2DM, the TCF7L2 SNP rs11196175 was associated with BMI and cholesterol and LDL levels, the TCF7L2 SNP rs12255372 was associated with BMI and HDL, VLDL and triglyceride levels, and the HNF4A SNP rs1885088 was associated with LDL levels (P<0.05).

Randomized clinical trial of the safety and immunogenicity of the Tdap vaccine in pregnant Mexican women.

Immunization with the tetanus, diphtheria, and pertussis (Tdap) vaccine raises controversies on immunogenicity and possible antibody interference. We performed an experimental, double-blind, parallel group controlled clinical trial to evaluate the safety and immunogenicity of the Tdap vaccine in 204 pregnant women and their children and to determine its interference in antibody production. Pregnant women 18 to 38 y of age with 12 to 24 weeks gestation, a low obstetric risk, and without serious disease were randomly selected. The experimental group received 0.5 mL IM of Tdap and the control group normal saline. Six blood samples were drawn before and after solution application, and from the umbilical cord of the infants and at 2, 4, and 6 months of age. Pertactin and Pertussis toxin antibodies and possible interference of maternal antibodies with the vaccine were determined. In the experimental group, antibodies against Bordetella pertussis pertactin (anti-PRN) (112 E/mL 95% CI 89.9-139.9) and antibodies against pertussis toxin (anti-PT) (24.0 E/mL, 95% CI 18.3-31.4) were elevated in the mother before vaccination. These were higher in the umbilical cord and descended in the infant at 2 months (71.4 (95% CI 56.8-89.7 and 10.9; 95% CI 8.7-13.7, respectively). Anti-PT showed a delay in production. Tdap safety was confirmed with only mild local pain at 24 and 48 hours. Anti-PRN and anti-PT antibodies in the infant descend at 2 months of age. There is a delay in anti-PT in children of immunized mothers. Further studies are needed to elucidate its clinical significance.

Hepatogenous diabetes: Is it a neglected condition in chronic liver disease?

Diabetes mellitus (DM) that occurs because of chronic liver disease (CLD) is known as hepatogenous diabetes (HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus (HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.

Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant.

CONTEXT: Efforts to find a cure for type 1 diabetes have focused on the removal of the autoimmune pathophysiologic substrate, with the use of immunosuppressive regimens including autologous hematopoietic stem cell transplantation (AHSCT). OBJECTIVE: The main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Secondary outcomes were procedure morbidity and the need for hospital management. DESIGN: We enrolled patients with type 1 diabetes between 2012 and 2014. Median follow-up was 34 months (range, 25-56 mo). SETTING: Ambulatory care. INTERVENTIONS: We decided to carry out an AHSCT protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting. PATIENTS: Patients were of both sexes, age 8-25 years, with positive levels of anti-GAD antibodies, a C-peptide level >1.0 ng/mL, and <3 months since diagnosis. MAIN OUTCOME MEASURE(S): Insulin independence. RESULTS: Sixteen patients were included. Overall response was 81% with seven patients achieving insulin independence (44%); six were partial responders (37%) whereas three were nonresponders (19%). The HbA1c level showed a mean decrease of -2.3% at 6 months in the Insulin Independence group. Median age was 12 years old (range, 8-17 years old). A mean of 11.5 × 10(6) CD34+ cells (SD ± 8.2) was obtained. Related mortality at 100 days was 0% as well as during follow-up. Outpatient setting was 100%. CONCLUSIONS: Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.

Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy.

Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus­hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.