Reclassification of type 2 diabetes to type 1 diabetes in Asturias (Spain) between 2011 and 2020.

BACKGROUND: Differentiating between type 1 diabetes (T1D) and type 2 diabetes (T2D) can be difficult in adults. The aim of this study was to determine the frequency of diagnostic reclassification from T2D to T1D, the characteristics of the patients and the impact on the management of the disease. METHODS: Observational and descriptive study including patients diagnosed with T1D in Asturias (Spain) between 2011 and 2020 who had been considered as T2D for at least 12 months. RESULTS: A total of 205 patients were included, representing 45.3% of those diagnosed with T1D over 30 years of age. Median time of evolution as T2D was 7,8 years. The age was 59.1 ± 12.9 years. BMI was > 25 kg/m2 in 46.8% of patients. HbA1c was 9.1 ± 2.1%, 77 ± 22 mmol/mol, and 56.5% were using insulin. Pancreatic antibodies were present in 95.5%, the most frequent being GAD, 82.6%. At 6 months, basal insulin use increased from 46.9 to 86.3%, and HbA1c decreased, 9.2 ± 2.0%vs7.7 ± 1.2%, 77 ± 22vs60 ± 13 mmol/mol; p < 0.0001. CONCLUSIONS: Diagnosis as T2D in patients with T1D in adults is common. Age, BMI, insulin use and other clinical features are not definitely discriminatory. GAD is the antibody of choice in case of diagnostic suspect. Reclassification has important implications for metabolic control.

Circulating miRNA expression in long-standing type 1 diabetes mellitus.

Type 1 diabetes is a chronic autoimmune disease which results in inefficient regulation of glucose homeostasis and can lead to different vascular comorbidities through life. In this study we aimed to analyse the circulating miRNA expression profile of patients with type 1 diabetes, and with no other associated pathology. For this, fasting plasma was obtained from 85 subjects. Next generation sequencing analysis was firstly performed to identify miRNAs that were differentially expressed between groups (20 patients vs. 10 controls). hsa-miR-1-3p, hsa-miR-200b-3p, hsa-miR-9-5p, and hsa-miR-1200 expression was also measured by Taqman RT-PCR to validate the observed changes (34 patients vs. 21 controls). Finally, through a bioinformatic approach, the main pathways affected by the target genes of these miRNAs were studied. Among the studied miRNAs, hsa-miR-1-3p expression was found significantly increased in patients with type 1 diabetes compared to controls, and positively correlated with glycated haemoglobin levels. Additionally, by using a bioinformatic approach, we could observe that changes in hsa-miR-1-3p directly affect genes involved in vascular development and cardiovascular pathologies. Our results suggest that, circulating hsa-miR-1-3p in plasma, together with glycaemic control, could be used as prognostic biomarkers in type 1 diabetes, helping to prevent the development of vascular complications in these patients.

miR-24-3p and Body Mass Index as Type 2 Diabetes Risk Factors in Spanish Women 15 Years after Gestational Diabetes Mellitus Diagnosis.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance that is diagnosed for the first time during pregnancy. The objective of this study is to know the glucose tolerance status after 15 years of pregnancy in patients diagnosed with gestational diabetes and to assess the long-term effect of GDM on the circulating miRNA profile of these women. To answer these, 30 randomly selected women diagnosed with GDM during 2005-2006 were included in the study, and glucose tolerance was measured using the National Diabetes Data Group criteria. Additionally, four miRNAs (hsa-miR-1-3p, hsa-miR-24-3p, hsa-miR-329-3p, hsa-miR-543) were selected for their analysis in the plasma of women 15 years after the diagnosis of GDM. In our study we discovered that, fifteen years after the diagnosis of GDM, 50% of women have some degree of glucose intolerance directly related to body weight and body mass index during pregnancy. Dysglycemic women also showed a significantly increased level of circulating hsa-miR-24-3p. Thus, we can conclude that initial weight and BMI, together with circulating expression levels of hsa-miR-24-3p, could be good predictors of the future development of dysglycemia in women with a previous diagnosis of GDM.

Correlation between glucose measurement parameters of continuous flash monitoring and HbA1c. Real life experience in Asturias.

INTRODUCTION: Despite continuous glucose monitoring having been proven useful in patients with type 1 diabetes mellitus, A1C remains the gold standard for assessing disease management. MATERIAL AND METHODS: Descriptive, retrospective study which included 252 patients, 40.5% male, mean age 44.91±14.57 years, mean duration of diabetes 22.21±13.12 years, 88.1% on basal-bolus insulin therapy and 11.9% users of continuous subcutaneous insulin infusion. Glucose measurement, analytical and anthropometric data were obtained. RESULTS: The mean time in range was 60.18±15.60% and was associated with A1C after adjusting for age, gender, duration of diabetes, BMI, insulin regimen, %CV and time below range (ß: -0.548; p<0.01). The glucose management indicator (GMI) was 7.19±0.69% and was also associated with A1C (ß: 0.957; p<0.01) regardless of age, gender, duration of diabetes, BMI, insulin treatment, %CV and time in range. The average difference between A1C and GMI was 0.17±0.65% (-2.70-3.40%), being higher as A1C increased, in a linear and significant manner, without being influenced by the duration of diabetes or CV. CONCLUSIONS: Although we found a positive correlation between continuous glucose monitoring glucose measurement parameters and A1C, there is still not enough evidence to replace one parameter with another.

Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers.

Objective: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules. Design: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively. Methods: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique. Results: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98). Conclusions: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology. Significance statement: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.

Enfermedades cardiovasculares en personas con diabetes mellitus en España según la Base de Datos Clínicos de Atención Primaria (BDCAP) en 2017 / Cardiovascular diseases in people with diabetes mellitus in Spain according to the Primary Care Clinical Database (BDCAP) in 2017

Introducción y objetivosLa enfermedad cardiovascular ateroesclerótica y la insuficiencia cardiaca (IC) son la principal causa de morbimortalidad en los pacientes con diabetes. El objetivo de este trabajo es conocer la prevalencia de enfermedades cardiovasculares ateroscleróticas y de insuficiencia cardiaca en personas diagnosticadas de diabetes en España durante el año 2017, y compararlas con las de las personas no diagnosticadas de diabetes en función de la edad y el sexo.MétodosLos datos correspondientes a los diagnósticos de diabetes mellitus (DM), infarto agudo de miocardio (IAM), accidente cerebrovascular (ACV), arteriopatía periférica (AP) o IC del año 2017 se obtuvieron de la Base de Datos Clínicos de Atención Primaria (BDCAP) del Sistema Nacional de Salud.ResultadosComparando personas con diabetes y sin diabetes mayores de 35 años, la odds ratio (OR) de estar diagnosticado de IAM, ACV, AP o IC es de alrededor de 2 en el caso de los mayores de 64 años y superior a 4 en los menores de esa edad. Esta OR es mayor en las mujeres respecto a los varones para todos los diagnósticos con excepción de la AP.ConclusionesEste estudio muestra la elevada comorbilidad cardiovascular de los pacientes con diabetes en España, objetivando un mayor de riesgo en los menores de 65 años, más acentuado en mujeres, lo que hace necesario un tratamiento más intensivo en este colectivo de pacientes.

Introduction and objectives:Atherosclerotic cardiovascular disease and heart failure are the leading cause of morbidity and mortality in patients with diabetes. The objective of this work is to know the prevalence of atherosclerotic cardiovascular diseases and heart failure in people diagnosed with diabetes in Spain during 2017 and compare them with those not diagnosed with diabetes according to age and sex.Methods:Data for diagnoses of diabetes mellitus (DM), acute myocardial infarction (AMI), stroke, peripheral artery disease (PAD) or heart failure (HF) for 2017 were obtained from the National Health System's Primary Care Clinical Database (BDCAP).Results:Comparing people with diabetes and people without diabetes over 35 years of age, the Odds Ratio (OR) for being diagnosed with acute myocardial infarction, stroke, peripheral artery disease or heart failure is about 2 in those over 64 years of age and more than 4 in patients under that age. This OR is superior in females versus males for all diagnoses apart from peripheral artery disease.Conclusions:This study shows the high cardiovascular comorbidity of patients with diabetes in Spain, with a greater excess of risk in patients under 65 years of age, more pronounced in women. We should offer more intensive treatment for DM2 in women. (AU)

[Cardiovascular diseases in people with diabetes mellitus in Spain according to the Primary Care Clinical Database (BDCAP) in 2017]. / Enfermedades cardiovasculares en personas con diabetes mellitus en España según la Base de Datos Clínicos de Atención Primaria (BDCAP) en 2017.

INTRODUCTION AND OBJECTIVES: Atherosclerotic cardiovascular disease and heart failure are the leading cause of morbidity and mortality in patients with diabetes. The objective of this work is to know the prevalence of atherosclerotic cardiovascular diseases and heart failure in people diagnosed with diabetes in Spain during 2017 and compare them with those not diagnosed with diabetes according to age and sex. METHODS: Data for diagnoses of diabetes mellitus (DM), acute myocardial infarction (AMI), stroke, peripheral artery disease (PAD) or heart failure (HF) for 2017 were obtained from the National Health System's Primary Care Clinical Database (BDCAP). RESULTS: Comparing people with diabetes and people without diabetes over 35 years of age, the Odds Ratio (OR) for being diagnosed with acute myocardial infarction, stroke, peripheral artery disease or heart failure is about 2 in those over 64 years of age and more than 4 in patients under that age. This OR is superior in females versus males for all diagnoses apart from peripheral artery disease. CONCLUSIONS: This study shows the high cardiovascular comorbidity of patients with diabetes in Spain, with a greater excess of risk in patients under 65 years of age, more pronounced in women. We should offer more intensive treatment for DM2 in women.

Diferencias de género en la mortalidad de personas con diabetes tipo 2: Estudio Asturias 2018 / Gender differences in the mortality of people with type 2 diabetes: Asturias Study 2018

OBJETIVO: Investigar la influencia del sexo en la mortalidad según la presencia o ausencia de diabetes mellitus tipo 2 (DM2) y otros factores de riesgo cardiovascular en la cohorte del Estudio Asturias. MÉTODO: El Estudio Asturias (iniciado en 1998) es un estudio de cohortes observacional, prospectivo, de una muestra representativa de la población asturiana de entre 30 y 75 años. Se dividió la población en grupos según la presencia o ausencia de DM2 y el sexo para valorar el control de los factores de riesgo cardiovascular. Además, conociendo el estatus vital de la cohorte 18 años después del inicio del estudio, se analizaron las diferencias en causas de mortalidad según las categorías anteriores. RESULTADOS: En 1998 iniciaron el estudio 1034 personas, de las cuales 561 eran mujeres (54,25%) y 473 eran hombres (45,75%). Padecían diabetes 131 (12,66%; 75 varones y 56 mujeres). Las mujeres con DM2 presentaron una hazard ratio (HR) para mortalidad total de 1,64 (intervalo de confianza del 95% [IC95%]: 0,97-2,77), y los hombres de 1,63 (IC95%: 1,07-2,50); para mortalidad cardiovascular, la HR fue de 3,06 (IC95%: 1,44-6,47) en las mujeres y de 1,49 (IC95%: 0,64-3,46) en los hombres. La tasa de mortalidad para las personas con DM2 en ambos sexos fue más alta que para las personas sin DM2. CONCLUSIONES: Las mujeres con DM2 tienen un riesgo de fallecer por causas cardiovasculares tres veces mayor que las mujeres sin DM2. Deberían implementarse estrategias de tratamiento en las mujeres con esta condición

OBJECTIVE: To investigate the influence of gender on mortality according to the presence or absence of type 2 diabetes mellitus (DM2) and other cardiovascular risk factors in the Asturias Study cohort. METHOD: The Asturias Study (started in 1998) is an observational, prospective cohort study of a representative sample of a population of Asturias aged 30-75 years. The population was divided into groups according to the presence or absence of DM2 and according to gender to assess control of cardiovascular risk factors. In addition, aware of the vital status of the cohort 18 years after the beginning of the study, we analyzed differences in causes of mortality according to the previous categories. RESULTS: In 1998, 1034 people started the study, 561 women (54.25%) and 473 men (45.75%). Of these, 131 (12.66%) had diabetes (75 men and 56 women). The women with T2D presented a hazard ratio (HR) for total mortality of 1.64 (95% confidence interval [95%CI]: .97-2.77), which was 1.63 (95%CI: 1.07-2.50) for the men and, for cardiovascular mortality, 3.06 (95%CI: 1.44-6.47) for the females, versus 1.49 (95%CI: 0.64-3.46) for the males. The mortality rate for people with T2D of both sexes was higher than for people without T2D. CONCLUSIONS: Women with T2D have a risk more than three times higher than women without diabetes of dying from cardiovascular causes. We should implement treatment strategies in women with this condition

No genome-wide DNA methylation changes found associated with medium-term reduced graphene oxide exposure in human lung epithelial cells.

The presence of nanomaterials in our everyday life is ever increasing, and so too are concerns about the possible health consequences of exposure to them. While evidence of their biological activity is growing, there is still scant knowledge of the epigenetic mechanisms that could be at play in these processes. Moreover, the great variability in the chemical and physical structures of these compounds handicaps the study of their possible health risks. Here we have synthesized reduced graphene oxide (rGO) through the thermal exfoliation/reduction of graphite oxide, and characterized the resulting material. We have then made use of Illumina's MethylationEPIC arrays and bisulphite pyrosequencing to analyse the genome-wide and global DNA methylation dynamics associated with the medium-term exposure of human lung epithelial cells to rGO at concentrations of 1 and 10 µg/mL. The results show no genome-wide or global DNA methylation changes associated with either condition. Our observations thus suggest that medium-term rGO exposure does not have significant effects on the DNA methylation patterns of human lung epithelial cells.

[Gender differences in the mortality of people with type 2 diabetes: Asturias Study 2018]. / Diferencias de género en la mortalidad de personas con diabetes tipo 2: Estudio Asturias 2018.

OBJECTIVE: To investigate the influence of gender on mortality according to the presence or absence of type 2 diabetes mellitus (DM2) and other cardiovascular risk factors in the Asturias Study cohort. METHOD: The Asturias Study (started in 1998) is an observational, prospective cohort study of a representative sample of a population of Asturias aged 30-75 years. The population was divided into groups according to the presence or absence of DM2 and according to gender to assess control of cardiovascular risk factors. In addition, aware of the vital status of the cohort 18 years after the beginning of the study, we analyzed differences in causes of mortality according to the previous categories. RESULTS: In 1998, 1034 people started the study, 561 women (54.25%) and 473 men (45.75%). Of these, 131 (12.66%) had diabetes (75 men and 56 women). The women with T2D presented a hazard ratio (HR) for total mortality of 1.64 (95% confidence interval [95%CI]: .97-2.77), which was 1.63 (95%CI: 1.07-2.50) for the men and, for cardiovascular mortality, 3.06 (95%CI: 1.44-6.47) for the females, versus 1.49 (95%CI: 0.64-3.46) for the males. The mortality rate for people with T2D of both sexes was higher than for people without T2D. CONCLUSIONS: Women with T2D have a risk more than three times higher than women without diabetes of dying from cardiovascular causes. We should implement treatment strategies in women with this condition.

Correction: Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

[This corrects the article DOI: 10.1371/journal.pone.0211070.].

Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

People who develop type 2 diabetes (T2D) are known to have a higher mortality risk. We estimated all-cause, cardiovascular, and cancer mortality-risks in our patient cohort according to categories of impaired glucose metabolism. This 18-year retrospective analysis included a region-wide, representative sample of a population aged 30-75 years. Age- and sex-stratified hazard ratios (HRs) were calculated for 48 participants with diagnosed T2D, 83 with undiagnosed T2D (HbA1c ≥6.5%, fasting glycemia ≥126 mg/dL, or glycemia after 75 g glucose load ≥200 mg/dL); 296 with prediabetes (HbA1c 5.7%-6.4%, fasting glycemia 100-125 mg/dL, or glycemia after 75 g glucose load 140-199 mg/dL), and 607 with normoglycemia. Over 18,612 person-years, 32 individuals with undiagnosed T2D, 30 with diagnosed T2D, 62 with prediabetes, and 80 with normoglycemia died. Total sample crude mortality rate (MR) was 10.96 deaths per 1,000 person-years of follow-up. MR of the diagnosed T2D group was more than 3-times higher and that of newly diagnosed T2D was 2-times higher (34.72 and 21.42, respectively) than total sample MR. Adjusted HR for all-cause mortality was 2.02 (95% confidence interval 1.29-3.16) and 1.57 (95% CI 1.00-2.28) in the diagnosed T2D group and the newly diagnosed T2D group, respectively. Adjusted HR for cardiovascular mortality in the T2D group was 2.79 (95% CI 1.35-5.75); this risk was greatly increased in women with T2D: 6.72 (95% CI 2.50-18.07). In Asturias, age- and sex-standardized all-cause mortality is more than 2-times higher for adults with T2D than for adults without T2D. The HR for cardiovascular mortality is considerably higher in T2D women than in normoglycemic women.

Altered intragenic DNA methylation of HOOK2 gene in adipose tissue from individuals with obesity and type 2 diabetes.

AIMS/HYPOTHESIS: Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue (VAT) samples in a population of individuals with obesity and assessed whether differential methylation profiles are associated with the presence of type 2 diabetes (T2D). METHODS: More than 485,000 CpG genome sites from VAT samples from women with obesity undergoing gastric bypass (n = 18), and classified as suffering from type 2 diabetes (T2D) or not (no type 2 diabetes, NT2D), were analyzed using DNA methylation arrays. RESULTS: We found significant differential methylation between T2D and NT2D samples in 24 CpGs that map with sixteen genes, one of which, HOOK2, demonstrated a significant correlation between differentially hypermethylated regions on the gene body and the presence of type 2 diabetes. This was validated by pyrosequencing in a population of 91 samples from both males and females with obesity. Furthermore, when these results were analyzed by gender, female T2D samples were found hypermethylated at the cg04657146-region and the cg 11738485-region of HOOK2 gene, whilst, interestingly, male samples were found hypomethylated in this latter region. CONCLUSION: The differential methylation profile of the HOOK2 gene in individuals with T2D and obesity might be related to the attendant T2D, but further studies are required to identify the potential role of HOOK2 gene in T2D disease. The finding of gender differences in T2D methylation of HOOK2 also warrants further investigation.