Genetics: Is LADA just late onset type 1 diabetes?

Background: There is a controversy regarding Latent Autoimmune Diabetes in Adults (LADA) classification and whether it should be considered a slowly progressing form of type 1 (T1) diabetes (DM) or a distinct type of DM altogether. Methods: This cross-sectional study assessed major genes associated with T1DM (class II Results: A total of 578 participants were included: 248 with T1DM (70 diagnosed after the age of 30), 256 with T2DM and 74 with LADA. High risk HLA alleles were significantly more frequent in LADA than in T2DM, whereas the opposite was true for protective alleles. We found a lower frequency of the high-risk DRB1*04-DQB1*03:02-DQA1*03:01 haplotype in LADA (21.1%) than in the overall T1DM (34.7%) (p\u3c0.05), whereas no differences were found between these groups for DRB1*03-DQB1*02:01-DQA1*05:01 or for protective alleles. Only 12% the overall T1DM group had no risk alleles vs 30% of LADA (p\u3c0.0005). However, HLA allele distribution was similar in LADA and T1DM diagnosed after the age of 30. A total of 506 individuals (195 with T1DM [21 diagnosed after age 30] 253 with T2DM and 58 with LADA) were genotyped for the Conclusion: In this relatively small cross-sectional study, the genetic profile of subjects with LADA showed a similar T1DM-related risk allele distribution as in participants with T1DM diagnosed after the age of 30, but fewer risk alleles than those diagnosed before 30. Differences were present for HLA, as well a

Effectiveness of a comprehensive care protocol in patients with new diagnoses of type 2 diabetes mellitus and associated comorbidities in primary care : study protocol of a quasi-experimental trial

Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic disease in the Spanish population. Typically, T2DM is associated with other chronic conditions. Intensive medication at the time of diagnosis has proven effective in reducing cardiovascular risk, improving glycaemic control and preventing T2DM complications. However, it has not yet been demonstrated that a comprehensive and intensive health education protocol at the time of diagnosis has the benefits described previously. Currently, there is great variability in the practices of primary care nurses regarding health education at the time of disease diagnosis.We aimed to evaluate the effectiveness of a systematic protocol with a comprehensive care programme in people with newly diagnosed T2DM with associated comorbidities. A multicentre quasi-experimental design comparing a group of individuals taking part in the intervention (intervention group (IG)) with a similar group receiving standard diabetes care (comparison group (CG)) is planned. The intervention will take place during the 3 months after study enrolment. Data will be collected at baseline and at 3, 6 and 12 months. Ten primary care centres in Barcelona city will be selected for participation: 5 for the IG and 5 for the CG. The IG will include five structured individual visits postdiagnosis with the primary care nurse, during which aspects of diabetes education will be discussed with the patient and his/her family. The results will be measured in terms of health-related quality of life and the change in main outcomes (glycated haemoglobin and weight). The study fully met the requirements of the Ethical Committee of Clinical Investigation of the IDIAP Jordi Gol (approval code: P13/118). Patients will be informed that their data are confidential, and they have the right to withdraw at any time without penalty. Dissemination will include publishing the findings in peer-reviewed journals and sharing our findings at scientific conferences. TRIAL REGISTRATION NUMBER: NCT03990857; Pre-results

Circulating CD5L is associated with cardiovascular events and all-cause mortality in individuals with chronic kidney disease

This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age was 62 years, 38.8% were female, and 26.8% had diabetes. There were 98 (6.5%) CVEs and 72 (4.8%) deaths, of which 26 (36.1%) were of CV origin. Higher baseline CD5L concentration was associated with increased risk of CVE (HR, 95% CI, 1.17, 1.0-1.36), and all-cause mortality (1.22, 1.01-1.48) after adjusting for age, sex, diabetes, systolic blood pressure, dyslipidemia, waist circumference, smoking, and CKD stage. sCD36 showed no association with adverse CV outcomes or mortality. Our study showed for the first time that higher concentrations of CD5L are associated with future CVE and all-cause mortality in individuals with CKD

Embryonic vitamin D deficiency programs hematopoietic stem cells to induce type 2 diabetes

Environmental factors may alter the fetal genome to cause metabolic diseases. It is unknown whether embryonic immune cell programming impacts the risk of type 2 diabetes in later life. We demonstrate that transplantation of fetal hematopoietic stem cells (HSCs) made vitamin D deficient in utero induce diabetes in vitamin D-sufficient mice. Vitamin D deficiency epigenetically suppresses Jarid2 expression and activates the Mef2/PGC1a pathway in HSCs, which persists in recipient bone marrow, resulting in adipose macrophage infiltration. These macrophages secrete miR106-5p, which promotes adipose insulin resistance by repressing PIK3 catalytic and regulatory subunits and down-regulating AKT signaling. Vitamin D-deficient monocytes from human cord blood have comparable Jarid2/Mef2/PGC1a expression changes and secrete miR-106b-5p, causing adipocyte insulin resistance. These findings suggest that vitamin D deficiency during development has epigenetic consequences impacting the systemic metabolic milieu

Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0–8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01–1.47], p = 0.041 and HR 1.04 [95% CI 1.01–1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients.Tis work was supported by Grants from Fundació La MARATÓ de TV3 (201502 and 201516 to AB-G, 201602- 30-31 to NA and JJ), Ministerio de Educación y Ciencia (SAF2014-59892 to AB-G), AdvanceCat (2014-2020 to AB-G), Ministerio de Economía y Competitividad (MINECO)—Instituto de Salud Carlos III (ISCIII) (PI17- 00232 to JJ, PI17-01362 to NA, PI15-00625 to DM, and RED2018-102799-T to JJ), and by CIBER on Cardiovascular Diseases (CIBERCV, CB16/11/00403) and CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM, CB15/00071 and CB07/08/0016) are an initiative from ISCIII, Spain with co-funding from the European Regional Development Fund (ERDF). JJ is supported by funds provided by ISCIII (Grant CPII18/00004, Miguel Servet II program)

Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure

Altres ajuts: Fundació la Marató de TV3: 201602-30-31; 201502Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0-8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01-1.47], p = 0.041 and HR 1.04 [95% CI 1.01-1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients

Interrogation of the perturbed gut microbiota in gouty arthritis patients through in silico metabolic modeling

Recent studies have shown perturbed gut microbiota associated with gouty arthritis, a metabolic disease characterized by an imbalance between uric acid production and excretion. To mechanistically investigate altered microbiota metabolism associated with gout disease, 16S rRNA gene amplicon sequence data from stool samples of gout patients and healthy controls were computationally analyzed through bacterial community metabolic models. Patient-specific community models constructed with the metagenomics modeling pipeline, mgPipe, were used to perform k-means clustering of samples according to their metabolic capabilities. The clustering analysis generated statistically significant partitioning of samples into a Bacteroides-dominated, high gout cluster and a Faecalibacterium-elevated, low gout cluster. The high gout cluster was predicted to allow elevated synthesis of the amino acids D-alanine and L-alanine and byproducts of branched-chain amino acid catabolism, while the low gout cluster allowed higher production of butyrate, the sulfur-containing amino acids L-cysteine and L-methionine, and the L-cysteine catabolic product H2S. By expanding the capabilities of mgPipe to provide taxa-level resolution of metabolite exchange rates, acetate, D-lactate and succinate exchanged from Bacteroides to Faecalibacterium were predicted to enhance butyrate production in the low gout cluster. Model predictions suggested that sulfur-containing amino acid metabolism generally and H2S more specifically could be novel gout disease markers

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4