Search

Background: Cardiovascular (CV) diseases are the most common cause of death worldwide. This study aimed to investigate the incidence and type of first CV event in a broad cohort of Spaniards, focusing on age and sex differences., Methods: This was a retrospective study using the SIDIAP database. Subjects aged 30-89 years in 2010 were included. Individuals with prevalent CV disease or atrial fibrillation were excluded. Subjects were followed until the occurrence of a CV event, death, or the study end (December 2016). CV outcomes (coronary heart disease [CHD], cerebrovascular or peripheral artery disease and heart failure [HF]) during follow-up were analyzed. Clinical, anthropometrical, and laboratory data were retrieved from clinical records., Results: Overall, 3,769,563 at-risk individuals (51.2 ± 15.2 years) were followed for a median of 7 years. The cumulative incidence of a first CV event was 6.66% (men vs. women, 7.48% vs. 5.90%), with the highest incidence (25.97%) among individuals >75 years. HF (29%) and CHD (28.8%) were the most common first events overall; in men it was CHD (33.6%), while in women it was HF and cerebrovascular disease (37.4% and 27.4%). In younger age groups, CHD was more prevalent, with HF in older age groups. Baseline CV risks factors conferred more risk in younger ages and differed between men and women., Conclusions: The incidence and type of the first CV event in this Mediterranean region were significantly influenced by age and sex. This information is relevant for tailoring primary prevention strategies including the treatment of risk factors., Competing Interests: EO has received funding to the institution from Pla estrat gic de recerca i innovaci en salut PERIS 2016-2020, Generalitat de Catalunya, Departament de Salut; consulting fees from Novo Nordisk, Lilly and Daiichi Sankyo; honoraria from Fundacio Clinic per la Recerca Biomedica, Novo Nordisk, Lilly, Glaxo Smith Klein, Boehringer Ingelheim, Pfizer, Daiichi Sankyo, Sanofi and AMGEN; support for attending meetings from Novo Nordisk, Lilly and AMGEN IG received honoraria from ARAN group and Edryx Healthcare and support for attending meetings from Lilly, Sanofi and Novo Nordisk. MM-C has received grants to institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, NovoNordisk and Sanofi; consulting fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; honoraria from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, Novo Nordisk and Sanofi. JF-N has received honoraria from Astra-Zeneca, Boehringer Ingelheim, Lilly and MSD; payment for expert testimony from MSD and Novo Nordisk. DM has received funding to the institution from Pla estrat gic de recerca i innovaci en salut PERIS 2016-2020, Generalitat de Catalunya, Departament de Salut and from CIBERDEM; consulting fees from Ferrer, MSD, NovoNordisk and Sanofi; honoraria from Almirall, Amgen, Ferrer, Lilly, MSD, Menarini, NovoNordisk and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Ortega, Genua, Mata-Cases, Roqué, Vlacho, Real Gatius, Franch-Nadal and Mauricio.)

Purpose: This study aims to identify gender disparities in knowledge, attitudes and behaviors related to self-management and control of Type 2 diabetes Mellitus (T2DM) among primary care patients. The research was conducted across multiple Spanish cities., Patients and Methods: The study involved 8 Primary Care Centres located in four distinct regions of Spain: East (Barcelona), Centre (Madrid), North (Pamplona and Zumaia) and South (Vélez-Málaga and Málaga). A total of 111 individuals diagnosed with T2DM, comprising 52 women and 59 men, participated in 12 group discussions at these primary healthcare centers from February to June 2015. Participation was voluntary, and all participants provided informed consent by signing the consent form. A qualitative hermeneutic phenomenological study with a maximum variation sample was done. Participant profiles were defined based on gender, age, place of residence, type of treatment, years living with T2DM and the presence or absence of a cardiovascular event. Thematic analysis was used to analyze the data., Results: Participants were aware that diabetes is a chronic condition, with varied levels of concern regarding the diagnosis. Participants' locus of control influenced their perception of the disease's cause, with women attributing it to stress and emotional situations, while men linked it to risky behaviors. Self-management strategies were shaped by beliefs about diabetes, with both genders facing challenges in implementing recommended practices. Gender differences were also evident in caregiving roles, with men receiving more family support for diet adherence, while women prioritized family needs over their self-care. Participants expressed satisfaction with professional-patient interactions but highlighted the need for more accessible information and specialist care, suggesting support groups for women and clear health guidelines for men., Conclusion: Gender differences significantly influence how patients perceive and manage type 2 diabetes, with women experiencing greater concern and care burden compared to men. Effective diabetes management requires tailored support that addresses these gender-specific challenges. Enhancing healthcare services with clear guidelines and support groups can improve self-management outcomes in both men and women., Competing Interests: The author reports no conflicts of interest in this work., (© 2024 Ramírez-Morros et al.)

Aim: We aimed to evaluate the impact of a multicomponent healthcare intervention, primarily designed to improve glycemic control, on blood pressure and lipids in individuals with poorly controlled type 2 diabetes mellitus (T2DM) in the Catalonian primary care setting METHODS: A cluster, non-randomized, controlled pragmatic trial was conducted across 11 primary care centers. The intervention group (N=225) received a comprehensive, patient-centered approach, including a dedicated monographic consultation to address therapeutic inertia. The control group (N=181) mirrored the intervention group but lacked the monographic consultation. Secondary endpoints included lipid and blood pressure control assessed at baseline and after a 12-month follow-up., Results: 245 participants completed the study over 12 months. We found no differences in the reduction of lipid laboratory parameters between the groups at the final visit. However, no significant differences were found between the groups for other lipids or the proportion of participants achieving lipid target values. Likewise, no differences were noted between the groups for blood pressure, its target control, and treatment at the final visit. Various clinical factors such as age, sex, diabetes duration, HbA1c levels, BMI, and macrovascular complications among the participants were associated with achieving lipid and blood pressure targets at the final visit., Conclusion: The pragmatic multicomponent intervention proposed in the INTEGRA study, showed that including a component designed to reduce clinical inertia in the management of glycemia did not demonstrate benefits in improving lipids and blood pressure in patients with poorly controlled T2DM., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The funders had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. M.M.-C. has received advisory and or speaking fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi. J. F.-N. has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the in-stitution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. D.M. has received advisory and/or speaking fees from AB Biotics, Amgen, Almirall, Ferrer, Gilead, Menarini, MSD, Novo Nordisk and Sanofi. A.M has received advisory and or speaking fees from Astra-Zeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, and Sanofi; he has received research grants to the institution from Sanofi. M.G, A.B., E.R. and B.V. have no conflict of interest to declare., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: To evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings., Methods: We built a cohort of people with a first DFD episode during 2010-2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events., Results: Overall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7-22.6, HR: 15.1, 95% CI: 13.8-16.5, respectively) was found., Conclusions: Although DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis., (© 2024. The Author(s).)

Aims: We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region., Material and Methods: We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD., Results: The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75., Conclusions: In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiménez, Vlacho, Mata-Cases, Real, Mauricio, Franch-Nadal and Ortega.)

(1) Background: Although DR screening is effective, one of its most significant problems is a lack of attendance. The aim of the present study was to demonstrate the effectiveness of our algorithm in predicting the development of any type of DR and referable DR. (2) Methods: A retrospective study with an 11-year follow-up of a population of 120,389 T2DM patients was undertaken. (3) Results: Applying the results of the algorithm showed an AUC of 0.93 (95% CI, 0.92-0.94) for any DR and 0.90 (95% CI, 0.89-0.91) for referable DR. Therefore, we achieved a promising level of agreement when applying our algorithm. (4) Conclusions: The algorithm is useful for predicting which patients may develop referable forms of DR and also any type of DR. This would allow a personalized screening plan to be drawn up for each patient.

Aim: To evaluate the cross-sectional association between severe periodontitis and diabetes mellitus (DM), in a representative sample of Spanish population., Materials and Methods: The di@bet.es epidemiological study is a population-based cohort study aimed to determine the prevalence and incidence of DM in the adult population of Spain. The at-risk sample at the final examination (2016-2017) included 1751 subjects who completed an oral health questionnaire. This questionnaire, together with demographic and risk factors, had been previously validated to build an algorithm to predict severe periodontitis in the Spanish population. Logistic regression models were used to evaluate the association between severe periodontitis and DM with adjustment for confounding factors., Results: In total, 144 subjects developed DM, which yielded 8.2% cumulative incidence. Severe periodontitis was detected in 59.0%, 54.7% or 68.8% of the subjects depending on three different selected criteria at the 2016-2017 exam. All criteria used to define severe periodontitis were associated with DM in unadjusted analysis, but the magnitude of the association decreased after adjusting for significant confounders. The criteria '≥50% of teeth with clinical attachment loss ≥5 mm' presented an odds ratio of 4.9 (95% confidence interval: 2.2-10.7; p ≤ .001) for DM., Conclusions: Severe periodontitis is associated with DM in the Spanish population., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Introduction: Gestational diabetes mellitus (GDM) is globally increasing due to changes in risk factors such as gestational age, obesity, and socioeconomic status (SES). This study examined trends of GDM prevalence over ten years using a real-world Primary Health Care database from Catalonia (Spain)., Methods: A retrospective analysis of pregnant women screened for GDM was conducted, using clinical and SES data from the SIDIAP database., Results: Among 221,806 women studied from 2010 to 2019,17,587 had GDM, equating to a 7.9% prevalence (95% CI 7.8-8.04). GDM subjects were older (33.5 ± 5.1 vs. 31.2 ± 5.6 years; p < 0.001) and had higher BMI (29.2 ± 5.1 vs .27.8 ± 4.8 kg/m²; p < 0.001) than non-GDM individuals. Overall GDM prevalence remained unchanged throughout the study, although an increase was observed in younger women (below 20 years: 1.28% [95% CI 0.59-2.42] in 2010 to 2.22% [95% CI 0.96-4.33] in 2019, p = 0.02; ages 20-25.9 years: 3.62% [95% CI 3.12-4.17] in 2010 to 4.63% [95% CI 3.88-5.48)] in 2019, p = 0.02). Age, BMI ≥ 25 kg/m2, deprived SES, and previous hypertension and dyslipidaemia were positively associated with GDM., Conclusions: This study offers insights into GDM prevalence in Catalonia (Spain),showing overall stability except for a rising trend among younger women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: In this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state., Methods: An untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The models were adjusted by sex, age, hypertension, dyslipidaemia, body mass index, glucose, smoking, systolic blood pressure, triglycerides, HDL cholesterol, LDL cholesterol, alternate Mediterranean diet score (aMED) and estimated glomerular filtration rate (eGFR); diabetes duration and glycated haemoglobin (HbA1c) were also included in the comparison between T1D and T2D., Results: A total of 54 unique lipid subspecies from 15 unique lipid classes were annotated. Lysophosphatidylcholines (LPC) and ceramides (Cer) showed opposite effects in subjects with T1D and subjects with T2D, LPCs being mainly up-regulated in T1D and down-regulated in T2D, and Cer being up-regulated in T2D and down-regulated in T1D. Also, Phosphatidylcholines were clearly down-regulated in subjects with T1D. Regarding sex-specific differences, ceramides and phosphatidylcholines exhibited important diabetes-associated differences due to sex. Concerning the glycaemic state, we found a gradual increase of a panel of 1-deoxyceramides from normoglycemia to prediabetes to T2D., Conclusions: Our findings revealed an extensive disruption of lipid metabolism in both T1D and T2D. Additionally, we found sex-specific lipidome changes associated with diabetes, and lipids associated with the glycaemic state that can be linked to previously described molecular mechanisms in diabetes., (© 2024. The Author(s).)

Background: Our study aimed to evaluate the performance of primary healthcare physicians (PCPs) in managing glycemia, lipids, and blood pressure in people with type 2 diabetes mellitus (T2DM) in Catalonia, Spain. Methods: We included 3267 PCPs with 367,132 T2DM subjects in a cross-sectional analysis of the SIDIAP (Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària) database for the year 2017. Results : 63.1% of PCPs were female, with an average practice size of 1512 subjects. T2DM individuals had a mean (standard deviation) age of 70 (±12.2) years old, a mean body mass index (BMI) of 30.2 (±5.21) kg/m 2 , and a median diabetes duration of 8.8 years. Overall, 42.6% of subjects achieved target glycemic control (glycated hemoglobin < 7%). Notably, 59.2% maintained blood pressure < 140/90 mmHg during the 12-month study period. The multivariable analysis identified positive associations between glycemic control and female PCPs, practice sizes (1000-1500 people), a higher proportion of patients aged ≥ 65 years, and rural practices. Combined glycemic, lipid, and blood pressure target attainment was associated with medium-sized practices and those with a higher proportion of patients aged ≥ 65 years. Conclusions: Practice size, patient age distribution, and rurality are factors associated with the performance of PCPs in the control of glycemia, lipids, and blood pressure in T2DM subjects in primary health care centers in our region.

Introduction: Women with type 2 diabetes mellitus (T2DM) face a greater risk of cardiovascular disease (CVD) and encounter challenges in managing cardiovascular risk factors (CVRF); however, limited data are available in individuals with newlydiagnosed T2DM., Methods: This study aimed to examine differences between women and men at the onset of T2DM in terms of clinical characteristics, glycaemic status, and CVRF management. This was a retrospective cohort study including subjects with newly-diagnosed T2DM from the System for the Development of Research in Primary Care (SIDIAP) database in Catalonia (Spain). Sex differences (Dif) were assessed at baseline and 1-year post-diagnosis, by calculating the absolute difference of means or proportions., Results: A total of 13,629 subjects with newly-diagnosed T2DM were analyzed. Women were older and had a higher BMI than men. At baseline, women had higher total cholesterol [Dif (95%CI) 10 mg/dL (9.1/10.8)] and low-density lipoprotein cholesterol (LDL-c) [Dif (95%CI) 7 mg/dL (6.3/7.7)], while men had higher rates of smoking and alcohol intake. Lipid target achievement was lower in women, in both primary prevention (LDL-c < 100 mg/dL) [Dif (95%CI) -7.3 mg/dL (-10.5/-4.1)] and secondary prevention (LDL-c < 70 mg/dL) [Dif (95%CI) -8.3 mg/dL (-17.3/0.7)], along with lower statin and antiplatelet prescriptions, especially one year after diagnosis. Changes in clinical and laboratory data one year post-diagnosis revealed that, in the primary prevention group, men experienced greater improvements in total cholesterol, LDL-c and triglycerides, while women had less success in achieving CVRF control targets compared to men. Additionally, cardiovascular events, such as coronary artery disease and peripheral artery disease increased more in men than in women within the first year of diagnosis, especially in primary prevention subjects., Conclusion: Differences between men and women CVRF are already apparent at the onset of T2DM, particularly in primary prevention, with notable differences in lipid profile and target level attainment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ramírez-Morros, Franch-Nadal, Real, Miró-Catalina, Bundó, Vlacho and Mauricio.)

Background and Aims: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain., Methods: We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 μm (PM 10 ), <2.5 μm (PM 2.5 ) and nitrogen dioxide (NO 2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model)., Results: In multivariate linear regression models, each IQR increase in PM 10 , PM 2.5 and NO 2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM 10 , PM 2.5 and NO 2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (10 and NO 2 and low HDL-p in men (p for interaction .008 and .034), and between NO 2 and low HDL-p in individuals with obesity (p for interaction .015)., Conclusions: Our study shows an association between the exposure to air pollutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosis., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Aim: The INTEGRA study evaluated whether a specially designed multicomponent health care intervention improved glycaemic control in subjects with poorly controlled type 2 diabetes compared with standard of care practice., Research Design and Methods: Pragmatic study in subjects from primary care centres with type 2 diabetes and glycated haemoglobin (HbA1c) >9% (75 mmol/mol). The multifaceted intervention (N = 225 subjects) included a diabetes-focused visit encouraging therapeutic intensification by health care professionals. Retrospective data from matched controls (N = 675) were obtained from electronic medical records of a primary care database. The primary outcome was to compare the change in HbA1c values between the groups at 12 months of follow-up., Results: The mean HbA1c decreased substantially in both groups after 3 months, and the mean reduction was significantly greater in the intervention group than in the usual care group after 12 months [mean difference -0.66% (-7 mmol/mol), 95% CI -0.4, -1.0; p < .001]. A larger percentage of participants in the intervention group achieved HbA1c <7% and <8% goals (15.5% vs. 5.3% and 29.3% vs. 13.5%, respectively; p < .001). The improvement in HbA1c levels was sustained throughout the study only in the intervention arm. Glucose-lowering therapy was more frequently intensified in patients in the intervention group at the initial and final time points of the study (between 0-3 and 6-12 months; p < .001), with a significant increase in the number of patients prescribed ≥2 antidiabetic therapies (p < .001)., Conclusions: A multifaceted intervention oriented at reducing therapeutic inertia by primary care physicians was associated with greater improvement in glycaemic control compared with patients treated as per usual care., (© 2023 John Wiley & Sons Ltd.)

Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network of microvessels beyond well-known and documented target organs, i.e., the retina, kidney, and peripheral nerves. Indeed, an intact microvascular bed is crucial for preserving each organ's specific functions and achieving physiological balance to meet their respective metabolic demands. Therefore, diabetes-related microvascular dysfunction leads to widespread multiorgan consequences in still-overlooked non-traditional target organs such as the brain, the lung, the bone tissue, the skin, the arterial wall, the heart, or the musculoskeletal system. All these organs are vulnerable to the physiopathological mechanisms that cause microvascular damage in diabetes (i.e., hyperglycaemia-induced oxidative stress, inflammation, and endothelial dysfunction) and collectively contribute to abnormalities in the microvessels' structure and function, compromising blood flow and tissue perfusion. However, the microcirculatory networks differ between organs due to variations in haemodynamic, vascular architecture, and affected cells, resulting in a spectrum of clinical presentations. The aim of this review is to focus on the multifaceted nature of microvascular impairment in diabetes through available evidence of specific consequences in often overlooked organs. A better understanding of diabetes microangiopathy in non-target organs provides a broader perspective on the systemic nature of the disease, underscoring the importance of recognising the comprehensive range of complications beyond the classic target sites., (© 2023. The Author(s).)

Background: Hypertriglyceridemia (HTG) increases the risk of cardiovascular disease and pancreatitis, and its prevalence varies across populations., Objective: To determine the prevalence of moderate-to-severe hypertriglyceridemia (msHTG, 500-879 mg/dl) and severe hypertriglyceridemia (sHTG, ≥ 880 mg/dl) in a primary care population in Catalonia, Spain, and to categorize them according to presence/absence of factors potentially causing HTG., Methods: Retrospective analysis of clinical and laboratory data in SIDIAP (Information System for the Development of Primary Care Research) from 2010, 2013, 2016, and 2019. We considered medications with hypolipidemic effects and those potentially increasing TG levels. We developed logistic regression models adjusted by age and sex to calculate the probability of having ms/sHTG according to covariates of interest., Results: In the study years, 36.2‒42.0% of the >3.5 million active primary care users had ≥1 TG determination. Prevalence for msHTG was 0.7% and for sHTG 0.2% among those with recorded TG. In 2019, 54.7% were female; median (IQR) age was 62.5 (49.4‒73.7) years. Prevalence was higher in 36‒50-year-old persons (1.3% msHTG, 0.4% sHTG) and men (1.1% msHTG, 0.3% sHTG). Most cases were associated with secondary and <20% with non-secondary causes, the latter being most prevalent in young patients. The secondary causes more strongly associated with msHTG/sHTG were obesity, uncontrolled diabetes mellitus (DM) and gamma-glutamyl transferase >100 U/L., Conclusion: The prevalence of msHTG was 0.7% and that of sHTG was 0.2% between 2010 and 2019 among individuals with recorded TG. msHTG/sHTG most often affected men around their fifties and people with obesity and uncontrolled DM. Most msHTG and sHTG cases were associated with the presence of secondary causes., (Copyright © 2023. Published by Elsevier Inc.)

Aim: To evaluate the efficacy of the self-management of insulin titration based on information received by the Short Message Service (SMS)., Methods: A case-control study including 59 subjects in each arm with 16 weeks of follow-up was performed. The inclusion criteria were: (1) Subjects with type 2 diabetes (T2D) under basal insulin treatment; (2) Suboptimal glycemic control: HbA1c ≥ 7.5% and fasting capillary blood glucose (FCBG) > 140 mg/dL (>3 times per week). Subjects were invited to use an insulin titration service based on SMS feedback aimed at optimizing glycemic control depending on fasting blood glucose levels. Psychological aspects were evaluated in the interventional group by means of validated questionnaires (DDS, HADS and SF-12)., Results: The intervention group achieved a lower mean FCBG (126 mg/dL ± 34 vs. 149 mg/dL ± 46, p = 0.001) and lower HbA1c (7.5% ± 1.3 vs. 7.9% ± 0.9, p = 0.021) than the control group. In addition, the intervention group showed a significant improvement in psychological aspects related to Emotional Burden ( p = 0.031), Regimen Distress ( p < 0.001), Depression ( p = 0.049) and Mental Health ( p < 0.01)., Conclusions: The SMS-guided titration was effective in terms of improving glucometric parameters in comparison with the standard of care and improved significant psychological aspects-mainly, the stress associated with insulin treatment.

Background and Aims: Current research on the association between dietary patterns and subclinical atherosclerotic disease (SAD) is still limited, and published results are inconsistent and often consist of small population sizes. We aimed to evaluate the association between the Mediterranean diet (MDiet) and SAD in a large cohort of Mediterranean individuals., Methods: This was a cross-sectional study that included 8116 subjects from the ILERVAS cohort. The presence of atherosclerotic plaques (AP) was assessed by ultrasound examination. Adherence to the MDiet was assessed using the 14-item Mediterranean Diet Adherence Score (MEDAS). Inclusion criteria were subjects with at least one cardiovascular risk factor. Exclusion criteria were a clinical history of diabetes, chronic kidney disease, or a prior cardiovascular event. Bivariable and multivariable models were performed., Results: Compared with subjects without SAD, participants with SAD were older and had a higher frequency of smoking habit, hypertension, dyslipidemia, HbA1c and waist circumference. The adjusted multivariable analysis showed that a higher MEDAS was associated with a lower risk of AP (incidence rate ratios [IRR] 0.97, 95% CI [0.96-0.98]; p<0.001). Furthermore, moderate or high adherence to the MDiet was associated with a lower number of AP compared with a low MDiet adherence (IRR 0.90, 95% CI [0.87-0.94]; p<0.001). In both models, female sex was associated with a lower risk of AP., Conclusions: Our findings point to a potentially protective role of MDiet for SAD in a Mediterranean population with low-to-moderate cardiovascular risk. Further research is needed to establish a causal relationship between both variables., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Early worsening of diabetic retinopathy (EWDR) due to the rapid decrease of blood glucose levels is a concern in diabetes treatment. The aim of the current study is to evaluate whether this is an important issue in subjects with type 2 diabetes with mild or moderate nonproliferative DR (NPDR), who represent the vast majority of subjects with DR attended in primary care., Research Design and Methods: This is a retrospective nested case-control study of subjects with type 2 diabetes and previous mild or moderate NPDR. Using the SIDIAP ("Sistema d'informació pel Desenvolupament de la Recerca a Atenció Primària") database, we selected 1,150 individuals with EWDR and 1,150 matched control subjects (DR without EWDR). The main variable analyzed was the magnitude of the reduction of HbA1c in the previous 12 months. The reduction of HbA1c was categorized as rapid (>1.5% reduction in <12 months) or very rapid (>2% in <6 months)., Results: We did not find any significant difference in HbA1c reduction between case and control subjects (0.13 ± 1.21 vs. 0.21 ± 1.18; P = 0.12). HbA1c reduction did not show significant association with worsening of DR, neither in the unadjusted analyses nor in adjusted statistical models that included the main confounding variables: duration of diabetes, baseline HbA1c, presence of hypertension, and antidiabetic drugs. In addition, when stratification by baseline HbA1c was performed, we did not find that those patients with higher levels of HbA1c presented a higher risk to EWDR., Conclusions: Our results suggest that the rapid reduction of HbA1c is not associated with progression of mild or moderate NPDR., (© 2023 by the American Diabetes Association.)

Background: Knowledge of the characteristics of first-ever cardiovascular events in type 1 diabetes may impact primary prevention strategies. This study describes the first-ever manifestation of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D) in Catalonia (Spain) and evaluates differences according to age and sex., Methods: Retrospective cohort study of patients with T1D > 30 years without CVD before 2010 registered in the SIDIAP database. The occurrence of a first cardiovascular event up to the end of 2016, the type of CV event and associations with baseline characteristics were analysed., Results: Of 8412 patients, 884 suffered a first CV event (incidence rate 1.62 per 100 persons-years). Overall, peripheral vascular disease (39.5%) was the most frequent event. We observed a higher proportion of heart failure in women (21.7%) than in men (10.1%). In women, heart failure was the most frequent event in those > 65 years (40.5%). Decreased glomerular filtration rate (hazard ratio [HR] 5.42 [95% CI 4.32;6.80]), elevated albumin/creatinine ratio (HR 3.39 [95% CI [2.47;4.66], microvascular complications (HR 3.27 [95% CI 2.85;3.75]), and hypertension (HR 3.21 [95% CI [2.80;3.67]) were most strongly associated with a first CV event. HbA1c > 7.0% was associated with incident CVD only in patients aged < 55/60 years., Conclusions: Peripheral artery disease in the whole cohort, and heart failure in elder subjects are the most frequent first-ever CVD events in T1D in our region. These findings deserve to be taken into account when considering primary prevention measures and when estimating CV risk in people with T1D., (© 2023. The Author(s).)

Aim: To evaluate whether a specially designed multicomponent healthcare intervention improves glycaemic control in subjects with poorly controlled type 2 diabetes., Materials and Methods: A cluster, non-randomized, controlled, pragmatic trial in subjects from 11 primary care centres with type 2 diabetes and HbA1c of more than 9% (> 75 mmol/mol) was conducted. The intervention (N = 225 subjects) was professional and patient-centred, including a dedicated monographic visit that encouraged therapeutic intensification by physicians. The sham control (N = 181) was identical to that of the intervention group except that the dedicated visit was omitted. The primary outcome was to compare the reductions in HbA1c values between the groups at 12 months of follow-up., Results: The mean age at baseline was 59.5 years, mean diabetes duration was 10.7 years and mean HbA1c was 10.3% (89.0 mmol/mol). Patients in the intervention arm achieved significantly greater HbA1c reduction than those in the sham control group at 12 months (mean difference -0.62%, 95% CI = -0.2%, -1.04%; P = .002). A larger percentage of intervention participants achieved an HbA1c of less than 8% (44.8% vs. 25.5%; P = .003) and were more frequently treated with more than three antidiabetic therapies (14.4% vs. 3.5%; P = .0008). Intervention was the only variable associated with higher odds of HbA1c less than 8% (odds ratio = 2.52; 95% CI = 1.54-4.12; P < .001)., Conclusions: A multicomponent intervention including a dedicated visit oriented at reducing therapeutic inertia by primary care physicians can improve glycaemic control in poorly controlled patients with type 2 diabetes., (© 2022 John Wiley & Sons Ltd.)

Introduction: Clinical practice guidelines are helpful for clinicians, and their proper implementation could improve the quality of care and management of participants with diabetes. This study aimed to evaluate the degree of adherence to the Clinical Practice Guidelines (CPG) recommendations among obese, frail, or recently diagnosed type 2 diabetes mellitus (T2DM) participants in primary care centers in Spain., Methods: We perform a cross-sectional study on a national level in two phases. In the first phase, study participants were recruited, and their clinical data were collected. In the second phase, data related to the participating physicians were collected., Results: In total, 882 participants from 240 physicians were analyzed. According to the study questionnaire, most participants from all three clinical groups had adequate adherence to the CPG. This percentage was highest among the recently diagnosed T2DM (91.6%) and lowest percent of frail T2DM persons (74.7%). The inadequate adherence to the guidelines was observed mainly among the obese and frail participants with T2DM from medical doctors with low CPG knowledge (3.4% and 3.5%, respectively). Regarding the patient's characteristics and degree of adherence to the guidelines, the participants with inadequate adherence were generally older, with higher BMI, poorer HbA1c control, and fewer visits with primary care physicians. Most (57%) primary care physicians had moderate CPG knowledge. In our multivariable logistic model, we did not observe statistically significant odds ratios for different characteristics related to the physicians/consultation and low CPG knowledge., Discussion: The results of our cross-sectional study observe adequate adherence to the clinical guidelines by the primary care physicians for the majority of the participants with obesity, frailty, or newly diagnosed with T2DM., Competing Interests: MM-C has received advisory and or speaking fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi. JF-N has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vlacho, Mata-Cases, Fernandez-Camins, Romera Liébana, Barrot-de la Puente and Franch-Nadal.)

Background: Diabetic foot and lower limb complications are an important cause of morbidity and mortality among persons with diabetes mellitus. Very few studies have been carried out in the primary care settings. The main objective was to assess the prognosis of diabetic foot ulcer (DFU) in patients from primary care centers in Catalonia, Spain, during a 12-month follow-up period., Methods: We included participants with type 2 diabetes and a new DFU between February 2018 and July 2019. We estimated the incidence of mortality, amputations, recurrence and healing of DFU during the follow-up period. A multivariable analysis was performed to assess the association of these outcomes and risk factors., Results: During the follow-up period, 9.7% of participants died, 12.1% required amputation, 29.2% had a DFU recurrence, and 73.8% healed. Having a caregiver, ischemia or infection were associated with higher mortality risk (hazard ratio [HR]:3.63, 95% confidence interval [CI]:1.05; 12.61, HR: 6.41, 95%CI: 2.25; 18.30, HR: 3.06, 95%CI: 1.05; 8.94, respectively). Diabetic retinopathy was an independent risk factor for amputation events (HR: 3.39, 95%CI: 1.37; 8.39). Increasing age decreased the risk for a DFU recurrence, while having a caregiver increased the risk for this event (HR: 0.97, 95%CI: 0.94; 0.99). The need for a caregiver and infection decreased the probability of DFU healing (HR: 0.57, 95%CI: 0.39; 0.83, HR: 0.64, 95%CI: 0.42; 0.98, respectively). High scores for PEDIS (≥7) or SINBAD (≥3) were associated with an increased risk for DFU recurrence and a lower probability of DFU healing, respectively., Conclusions: We observed high morbidity among subjects with a new DFU in our primary healthcare facilities. Peripheral arterial disease, infection, and microvascular complications increased the risk of poor clinical outcomes among subjects with DFU., (© 2023. The Author(s).)

Aim: We estimate the incidence and risk factors for fatal and non-fatal events among the COVID-19 infected subjects based on the presence of obesity or diabetes during the initial three epidemiological waves in our region., Methods: This was a retrospective cohort study. A primary care database was used to identify persons with COVID-19. We stratified for subjects who either had diabetes mellitus or obesity. The follow-up period for study events was up to 90 days from inclusion., Results: In total, 1238,710 subjects were analysed. Subjects with diabetes mellitus or obesity were older and had a worse comorbidity profile compared with groups without these conditions. Fatal events were more frequent among people with diabetes and during the first wave. In the second and third waves, the number of study events decreased. Diabetes was a risk factor for fatal events in all models, while obesity was only in the model adjusted for age, sex, diabetes and COVID-19 waves. HIV, cancer, or autoimmune diseases were risk factors for mortality among subjects with COVID-19 in the fully-adjusted model., Conclusions: Diabetes was an independent risk factor for mortality among people with COVID-19. The number of fatal events decreased during the second and third waves in our region, both in those with diabetes or obesity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E.O has received advisory and or speaking fees from Astra-Zeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi, and Amgen; they received research grants for the institution from MSD and Amgen. M. M-C. has received an advisory honorarium from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; they received speaker honoraria from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, Novo Nordisk, and Sanofi; he received research grants for the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi. J. F-N has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he received research grants for the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. D. M. has received advisory and/or speaking fees from Almirall, Esteve, Ferrer, Lilly, Janssen, Menarini, Lilly, MSD, Novo Nordisk, and Sanofi. B. V, FX.C-C, J.R, and BF-C have no conflict of interest to declare. Conflict of interest The funders had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia., Material and Methods: A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively., Results: Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa., Conclusions: In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD., Competing Interests: Author JF-N has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, NovoNordisk and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, NovoNordisk, Sanofi and Boehringer. Author KC has received research support as principal investigator from National Institutes of Health NIH, Cirius, Inventiva, Janssen, Novartis, Novo Nordisk, and Zydus. He is consultant for Allergan, AstraZeneca, BMN, Cirius, Coherus, Deuterex, Janssen, Genentech, Gilead, Merck, Novo Nordisk, Pzifer, Poxel. Author DM has received advisory and/or speaking fees from Almirall, AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novartis, Novo Nordisk and Sanofi. He has received research grants to the institution from AstraZeneca, GSK, Lilly, MSD, Novartis, NovoNordisk, Sanofi and Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Julián, Ballesta, Pera, Pérez-Montes de Oca, Soldevila, Caballería, Morillas, Expósito, Martínez–Escudé, Puig-Domingo, Franch-Nadal, Torán, Cusi, Julve, Mauricio and Alonso.)

Aims: To understand geographical and temporal patterns in the diabetes gap, the excess mortality risk associated with type 2 diabetes (T2D), in three high-income countries., Methods: Using databases from Canada (Ontario), Spain (Catalonia) and the UK (England), we harmonized the study design and the analytical strategy to extract information on subjects aged over 35 years with incident T2D between 1998 and 2018 matched to up to five subjects without diabetes. We used Poisson models to estimate age-specific mortality trends by diabetes status and rate ratios and rate differences associated with T2D., Results: In more than 6 million people, 694 454 deaths occurred during a follow-up of 52 million person-years. Trends in all-cause mortality rates differed between Ontario and England; yet, the diabetes gaps were very similar in recent years: in 2018, we estimated 1.3 (95% confidence interval: 0.8, 1.8) and 0.8 (0.2, 1.5) more deaths per 1000 person-years in 50-year-old men with diabetes in Ontario and England, respectively, and 8.9 (6.1, 11.7) and 12.1 (9.1, 15.1) in 80-year-old men; between-country differences were small also in women. In Catalonia, rate ratios comparing T2D with no diabetes in men in 2018 were 1.53 (1.11, 2.11) at 50 years old, 0.88 (0.72, 1.06) at 60 years old, 0.74 (0.60, 0.90) at 70 years old and 0.81 (0.66, 1.00) at 80 years old, indicating lower mortality rates in men with T2D from the age of 60 years; rates were similar in women with and without diabetes at all ages. The diabetes gaps in cardiorenal mortality mirrored those of all-cause mortality: we observed consistent reductions in the proportions of cardiorenal deaths in subjects aged 80 years but variations in subjects aged ≤70 years, regardless of the presence of diabetes., Conclusions: By reducing the confounding impact of epidemiological and analytical differences, this study showed geographical similarities and differences in the diabetes gap: an excess risk of all-cause and cardiorenal mortality in subjects with T2D is still present in Ontario and England in recent years, particularly in elderly subjects. Conversely, there were very small gaps in young men with T2D or even lower mortality rates in older subjects with T2D in Catalonia., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: Obesity, an increasing global health problem, can affect people with other disease conditions. The prevalence of obesity in people with type 1 diabetes (T1D) is not well known. The aim of this study was to describe extensively the characteristics and prevalence of different classes of obesity according to BMI (body mass index) categories in a large cohort of patients with T1D., Material and Methods: This was a retrospective, cross-sectional study in Catalonia. We reviewed all patients with T1D diagnosis, ≥ 18 years old and with BMI data from the SIDIAP database. Sociodemographic and clinical data, cardiovascular risk factors, laboratory parameters and concomitant medications were collected., Results: A total of 6,068 patients with T1D were analyzed. The prevalence of obesity in the total sample was 18% (13.8% with class 1 obesity [BMI 30-34.9 kg/m2]). Patients with obesity had a higher prevalence of other cardiovascular risk factors (i.e. hypertension was 61.4% vs. 37.5%; dyslipidemia 63.6% vs 44%, and chronic kidney disease 38.4% vs. 24.4%; p<0.001 in all cases) and poorer control of them. The higher prevalence was regardless of sex, age and duration of diabetes. The increase in these comorbidities was noticeable from a BMI > 25 kg/m2. Patients with obesity did not have poorer glycemic control., Conclusion: The presence of obesity in people with T1D is frequent and cardiovascular risk factors are more common and more poorly controlled in T1D patients with obesity., Competing Interests: IG received support for attending meetings form Boehringer Ingelheim, Lilly, MSD, Novo-Nordisk and Sanofi. JF-N received advisory and/or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi. Received research grants to the institution from Astra-Zeneca. GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. DM has received advisory and/or speaking fees from Almirall, Esteve, Ferrer, Janssen, Lilly, Menarini, MSD, NovoNordisk and Sanofi. GG-P has received speaking fees from Lilly and Astra-Zeneca. MM-C has received advisory honorarium from for Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, NOVARTIS, NovoNordisk, Sanofi; speaker honorarium from Astra- Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, NovoNordisk, and Sanofi; and research grants to institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, NovoNordisk, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Genua, Franch-Nadal, Navas, Mata-Cases, Giménez-Pérez, Vlacho, Mauricio and Goday.)

Aims: To identify clinical predictors associated with a response in terms of glycemic control and weight loss in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs)., Methods: A retrospective observational study was performed with real-world databases in primary care. Patients with type 2 diabetes-initiated treatment with GLP-1RAs during the study period, and response to GLP-1RAs were determined six months from treatment initiation. An optimal glycated hemoglobin (HbA1c) or weight response was defined as a reduction of ≥ 1% or ≥ 3%, respectively. A "great" response was defined as both an optimal HbA1c and weight response. Bivariate and multivariate analyses with intention-to-treat were performed., Results: A sample of 2944 patients with type 2 diabetes was recruited. Higher HbA1c at baseline was the main clinical predictor of an optimal HbA1c response (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 1.96-2.71 in men and OR: 2.03, 95% CI: 1.76-2.33 in women). Treatment without insulin at baseline was associated with a greater weight reduction in men (OR: 2.50, 95% CI: 1.41-4.44). Older age and a higher weight at baseline were related with this in women (OR: 1.02, 95% CI: 1.00-1.05 and OR: 1.01, 95% CI: 1.00-1.02, respectively)., Conclusions: A high HbA1c at baseline and previous non-insulin therapy were the main predictors of a greater response (optimal HbA1c and weight response) to GLP1ra in both men and women. This may aid in treatment decision-making before initiating treatment with GLP-1RAs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. J. F.-N. has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. M. M.-C. has received an advisory honorarium from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received a speaker honorarium from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi. E.O. has received advisory and or speaking fees from Astra-Zeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi, and Amgen; he has received research grants to the institution from MSD and Amgen. D.M. has received advisory and/or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. M.G.-C. and B.V. have no conflicts of interest to declare., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Aims: To determine the degree and factors related to non-insulin antidiabetic drug (NIAD) adherence in people with type 2 diabetes mellitus (DM2) treated in primary carecentres in Spain., Methods: We did a cross-sectional study. During the study visit, variables related todifferent clinical characteristics, Adherence to Refills and Medications Scale Spanishversion (ARMS-e) and usage of NIAD were collected. We estimated the adherence toNIADs using the proportion of days covered (PDC) equation., Results: In total, 515 participants were included in the study. The mean PDC ratio was70.6 ( ± 28.9), and 50.5% (260) were classified as good adherent (PDC ≥80). Good adherence was highest among users of metformin (67.3%) and lowest among the participants using thiazolidinedione (0.8%). The score for ARMS-e was higher in the poor adherence group. In the multivariable analysis, HbA1c and the use of GLP1-RA or SGLT-2i were negatively associated with good adherence (odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.54, 0.82, OR: 0.20, 95%CI: 0.08, 0.46; OR: 0.56, 95%CI: 0.35, 0.89, respectively)., Conclusions: Adherence to NIADs observed in our study is far from optimal. HbA1c and ARMS-e items could be used as adherence indicators to encourage treatment changes to improve T2DM control., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.M-C has received advisory and or speaking fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra- Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi. J.F-N has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. D.A. and X.C. are full-time employees of Almirall, S.A. F.L-S has received advisory and or speaking fees from Astra-Zeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, and Sanofi. B.V., S.M. and J.E. declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Sexual dimorphism has been reported in non-alcoholic fatty liver disease (NAFLD), similar to the sex differences evident with cardiovascular disease. Type 2 diabetes mellitus (T2D) significantly increases the risk and severity of NAFLD, but there is scarce information on whether T2D or altered glucose metabolism can modify the prevalence of NAFLD in men and women of reproductive age., Purpose: To investigate the relationship between age, sex and NAFLD in subjects with and without dysglycemia., Materials and Methods: We analyzed 2,790 patients. NAFLD was characterized using established diagnostic criteria: one or more positive results on the fatty liver index and hepatic ultrasound. Liver fibrosis (liver stiffness measurement [LSM] ≥8.0 kPa) was assessed by Fibroscan ® . For analysis purposes, we included both T2D and prediabetes under the predefined condition of dysglycemia., Results: The global prevalence of NAFLD was higher in men than in women (50% and 34%; P<0.001), and the prevalence increased with age in both sexes. Older women (≥ 50 years) had a higher prevalence than younger women (<50 years), both in the overall cohort and in non-dysglycemic subjects. In dysglycemic subjects, the prevalence of NAFLD was slightly higher in men (68% vs 61%, p=0.021); in younger subjects, there were no differences in the prevalence of NAFLD between men and women (68% vs 64%, respectively; p=0.635). We found an interaction between dysglycemia and female sex (odds ratio [OR] 1.6 95% confidence interval [CI] 1.0-2.4, p=0.030), and between and age ≥50 years (OR 0.6, 95% CI 0.3-1.0, p=0.046). The global prevalence of LSM ≥8.0 kPa was higher in men compared with women (8% vs 4%; p< 0.001). This prevalence increased with age, mainly in men. We did not find any association between liver fibrosis and age and gender., Conclusions: While the global prevalence of NAFLD is higher in men than in women across all ages, younger women with dysglycemia have a similar risk of developing NAFLD as men of a similar age. Therefore, the presence of dysglycemia may erase the protective effect of female sex against fatty liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pérez-Montes de Oca, Julián, Pera, Caballería, Morillas, Torán, Expósito, Franch-Nadal, Mauricio and Alonso.)

Background: Diabetes mellitus (DM) is one of the leading chronic diseases globally and one of the most common causes of death, morbidity, and poor quality of life. According to the WHO, DM is also one of the main risk factors for developing active tuberculosis (TB). Subjects with DM are at a higher risk of infections, in addition to frequent micro and macrovascular complications, and therefore sought to determine whether poor glycemic control is linked to a higher risk of developing TB., Methods: We used a retrospective cohort of diabetic subjects to predict the incidence of TB. All DM patients were recruited from Ciutat Vella (the inner-city of Barcelona) from January 2007 until December 2016, with a follow-up period until December 2018 (≥2 years). Data were extracted from Barcelona's Primary Care medical record database - SIDIAP, and linked to the Barcelona TB Control Program. The incidence of TB and the impact of glycemic control were estimated using time-to-event curves analyzed by Cox proportional hazard regression. Hazard ratios (HRs) and 95% confidence intervals (CIs), unadjusted and adjusted by potential confounding variables, were also assessed, which included age, sex, diabetes duration, macrovascular and microvascular signs, BMI, smoking habit, alcohol consumption and geographical origin., Results: Of 8,004 DM patients considered for the study (equating to 68,605 person-years of follow-up), 84 developed TB [incidence rate = 70 (95% CI: 52-93) per 100,000 person-years]. DM subjects with TB were younger (mean: 52.2 vs. 57.7 years old), had higher values of glycosylated hemoglobin (HbA1c) (7.66 vs. 7.41%) and total triglycerides (122 vs. 105 mg/dl), and had twice the frequency of diabetic nephropathy (2.08 vs. 1.18%). The calculated incidence rate increased with increasing HbA1c: 120.5 (95% CI 77.2-179.3) for HbA1c ≥ 7.5%, 143 (95% CI 88.3-218.1) for HbA1c ≥ 8% and 183.8 (95% CI 105-298) for HbA1c ≥ 9%. An increase in the risk of TB was also observed according to a poorer optimization of glycemic control: adjusted HR 1.80 (95% CI 0.60-5.42), 2.06 (95% CI 0.67-6.32), and 2.82 (95% CI 0.88-9.06), respectively., Conclusion: Diabetic subjects with worse glycemic control show a trend toward a higher risk of developing TB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Antonio-Arques, Caylà, Real, Moreno-Martinez, Orcau, Mauricio, Mata-Cases, Julve, Navas Mendez, Puig Treserra, Millet, Del Val García, Vlacho and Franch-Nadal.)

Background/objectives: Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up., Subjects/methods: A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria., Results: A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category., Conclusion: Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables., (© 2022. The Author(s).)

Type 2 diabetes mellitus (T2DM) is a highly heterogeneous chronic disease with different pathophysiological and genetic characteristics affecting its progression, associated complications and response to therapies. The advances in deep learning (DL) techniques and the availability of a large amount of healthcare data allow us to investigate T2DM characteristics and evolution with a completely new approach, studying common disease trajectories rather than cross sectional values. We used an Kernelized-AutoEncoder algorithm to map 5 years of data of 11,028 subjects diagnosed with T2DM in a latent space that embedded similarities and differences between patients in terms of the evolution of the disease. Once we obtained the latent space, we used classical clustering algorithms to create longitudinal clusters representing different evolutions of the diabetic disease. Our unsupervised DL clustering algorithm suggested seven different longitudinal clusters. Different mean ages were observed among the clusters (ranging from 65.3±11.6 to 72.8±9.4). Subjects in clusters B (Hypercholesteraemic) and E (Hypertensive) had shorter diabetes duration (9.2±3.9 and 9.5±3.9 years respectively). Subjects in Cluster G (Metabolic) had the poorest glycaemic control (mean glycated hemoglobin 7.99±1.42%), while cluster E had the best one (mean glycated hemoglobin 7.04±1.11%). Obesity was observed mainly in clusters A (Neuropathic), C (Multiple Complications), F (Retinopathy) and G. A dashboard is available at dm2.b2slab.upc.edu to visualize the different trajectories corresponding to the 7 clusters., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Enrico Manzini reports was provided by Pulso. Enrico Manzini, Alexandre Perera-Lluna reports a relationship with Spanish Ministry of Economy and Competitiveness that includes: funding grants. Enrico Manzini, Alexandre Perera-Lluna reports a relationship with Networking Biomedical Research Centre in the subject area of Bioengineering, Biomaterials and Nanomedicine that includes: funding grants. Enrico Manzini, Alexandre-Perera-Lluna reports a relationship with Instituto de Investigación Carlos III that includes: funding grants. Enrico Manzini, Alexandre Perera-Lluna reports a relationship with Share4Rare project that includes: funding grants. Josep Franch-Nadal, Didac Mauricio reports a relationship with AstraZeneca Pharmaceuticals LP that includes: funding grants and speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with Ascensia Diabetes Care pain L that includes: speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with Boehringer Ingelheim GmbH that includes: funding grants and speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with G K that includes: funding grants and speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with Lilly pain that includes: funding grants and speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with M D that includes: funding grants and speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with Novartis Pharmaceuticals Corporation that includes: funding grants and speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with Novo Nordisk Inc that includes: funding grants and speaking and lecture fees. Josep Franch-Nadal, Didac Mauricio reports a relationship with Sanofi that includes: funding grants and speaking and lecture fees., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Our study aimed to assess the prevalence of diabetic foot disease (DFD) and its associated risk factors among subjects attending primary care centers in Catalonia (Spain)., Methods: We undertook a cross-sectional analysis of data from the primary health care (SIDIAP) database. The presence of comorbidities and concomitant medication were analyzed for subjects with or without DFD. DFD prevalence was estimated from 1st January 2018 to 31st December 2018., Results: During the 12-month observational period, out of 394,266 people with type 2 diabetes, we identified 3,277 (0.83%) active episodes of DFD in the database. The majority of these episodes were foot ulcers (82%). The mean age of patients with DFD was 70.3 (± 12.5) years and 55% were male. In the multivariable descriptive models, male gender, diabetes duration, hypertension, macrovascular, microvascular complications, and insulin and antiplatelet agents were strongly associated with DFD. A previous history of DFD was the stronger risk factor for DFD occurrence in subjects with T2DM (OR: 13.19, 95%CI: 11.81; 14.72)., Conclusions: In this real-world primary care practice database, we found a lower prevalence of DFD compared to similar previous studies. Risk factors such as male sex, duration of diabetes, diabetes complications and previous history of DFD were associated with the presence of DFD., Competing Interests: MM-C has received advisory and/or speaking fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, NOVARTIS, NovoNordisk, and Sanofi. He has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, NovoNordisk, and Sanofi. He has received research grants from Institut Universitari d’Investigació en Atenció Primària Jordi Gol IDIAP Jordi Gol Barcelona, Spain, Instituto de Salud Carlos III Madrid, Spain, Generalitat de Catalunya. Peris 2016-2020. The Strategic Plan for Health Research and Innovation Barcelona, Spain. JF-N has received advisory and/or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, NovoNordisk, and Sanofi. He has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, NovoNordisk, Sanofi, and Boehringer. DM has received advisory and/or speaking fees from Almirall, Esteve, Ferrer, Janssen, Lilly, Menarini, MSD, NovoNordisk and Sanofi. MB and JL have received advisory and speaking fees from MSD. EJ has received educational, sponsorship and speaker fees from Astra Zeneca, Bayer, Lilly, Novonordisk and Sanofi. XC has received speaker’s bureau and advisory board honoraria from AstraZeneca, Boehringer Ingelheim, Esteve, Lilly Diabetes, Novo Nordisk A/S, Roche, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bundó, Vlacho, Llussà, Puig-Treserra, Mata-Cases, Cos, Jude, Franch-Nadal and Mauricio.)

Background: It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19., Methods: We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020-October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis., Results: Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83-2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29-1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31-0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40-0.68], I 2 37%) were significantly lower for people with previous macrovascular disease., Conclusions: This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup., (© 2022. The Author(s).)

Objective: To assess the health status of the homeless population., Design: Cross-sectional descriptive study., Setting: Raval Sud Primary Care Health Center (Barcelona)., Participants: Homeless legal age people who have slept rough at some point in their lives., Main Measurements: Sociodemographic data and time in a situation of homelessness. Chronic pathologies, transmissible infectious diseases, mental illnesses and substance use disorders. HAD questionnaire on anxiety and depression. CVRS EQ-5D-3L questionnaire. Descriptive statistics., Results: The information of 146 patients with a mean age of 51.6 years (SD=12.8), 87% male and a mean of 12 years (SD=11.9) in a situation of homelessness was analyzed. The burden of disease was compared between the CAS profile (Drug addiction center - Baluard) and the socio-sanitary profile (Arrels Foundation). CAS users presented higher percentages of substance use disorders, mental illnesses and transmissible infectious diseases. People with a socio-health profile presented a higher percentage of chronic diseases (respiratory, cardiovascular and oncological) and more than half presented an alcohol use disorder and a higher percentage of disease associated with its consumption., Conclusions: The homeless population presents a high burden of disease, especially for mental illness, addictions and transmissible infectious diseases. We believe that studies are necessary to evaluate the disease excess compared to the general population with its derived costs and to design new strategies to address this burden of disease and its specificity., (Copyright © 2022 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: To identify principal components of free-living patterns of sedentary behaviour in office employees with type 2 diabetes (T2D) compared to normal glucose metabolism (NGM) office employees, using principal component analysis (PCA)., Methods: 213 office employees ( n = 81 with T2D; n = 132 with NGM) wore an activPAL inclinometer 24 h a day for 7 consecutive days. Comparions of sedentary behaviour patterns between adults with T2D and NGM determined the dimensions that best characterise the sedentary behaviour patterns of office employees with T2D at work, outside work and at weekends., Results: The multivariate PCA technique identified two components that explained 60% of the variability present in the data of sedentary behaviour patterns in the population with diabetes. This was characterised by a fewer number of daily breaks and breaks in time intervals of less than 20 min both at work, outside work and at weekends. On average, adults with T2D took fewer 31 breaks/day than adults without diabetes., Conclusion: Effective interventions from clinical practice to tackle prolonged sedentary behaviour in office employees with T2D should focus on increasing the number of daily sedentary breaks.

Aim: To assess the prevalence of autoimmune diseases (AID) in patients with type 1 diabetes (T1D) and to evaluate whether the rate of diabetes-related complications differs depending on the presence of AID., Methods: Cross-sectional analysis of 13,570 T1D patients aged ≥ 18 years registered in the SIDIAP database. The association between AID and diabetes-related complications was assessed by multivariable logistic regression models., Results: The prevalence of AID was 18.3% with thyroid AID being the most common. Patients with T1D and AID were more often female and their current age, age of diabetes onset and diabetes duration were higher. Patients with only thyroid AID experienced a lower risk of peripheral artery disease (odds ratio [OR] = 0.51, 95%; confidence interval [CI] 0.31 to 0.81) and kidney disease (OR = 0.68, 95%; 95% CI 0.54 to 0.85), whereas patients with other AID had an increased risk of ischemic heart disease (OR = 1.48, 95%; 95% CI 1.04 to 2.06)., Conclusions: The burden of diabetes-related complications in patients with T1D differs according to the type of additional AID. The presence of diabetes complications is lower in those with autoimmune thyroid disease while the presence of other AID is associated with higher rates of ischemic heart disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To assess the potential risk of overtreatment in patients with type 2 diabetes (T2DM) aged 75 years or older in primary care. Methods: Electronic health records retrieved from the SIDIAP database (Catalonia, Spain) in 2016. Variables: age, gender, body mass index, registered hypoglycemia, last HbA1c and glomerular filtration rates, and prescriptions for antidiabetic drugs. Potential overtreatment was defined as having HbA1c < 7% or HbA1c < 6.5% in older patients treated with insulin, sulfonylureas, or glinides. Results: From a total population of 138,374 T2DM patients aged 75 years or older, 123,515 had at least one HbA1c available. An HbA1c below 7.0% was present in 59.1% of patients, and below 6.5% in 37.7%. Overall, 23.0% of patients were treated with insulin, 17.8% with sulfonylureas, and 6.6% with glinides. Potential overtreatment (HbA1c < 7%) was suspected in 26.6% of patients treated with any high-risk drug, 47.8% with sulfonylureas, 43.5% with glinides, and 28.1% with insulin. Using the threshold of HbA1c < 6.5%, these figures were: 21.6%, 24.4%, 17.9%, and 12.3%, respectively. Conclusion: One in four older adults with T2DM treated with antidiabetic drugs associated with a high risk of hypoglycemia might be at risk of overtreatment. This risk is higher in those treated with sulfonylureas or glinides than with insulin.

Background: Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain., Methods: The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5μm (PM 2.5 ) and Nitrogen Dioxide (NO 2 ), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche)., Results: In multivariate linear regression models, there was a highly significant negative correlation between PM 2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM 2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM 2.5 (4.86 μg/m 3 ). There was no association between NO 2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women., Conclusions: Exposures to PM 2.5 in the general population were associated with mild alterations in thyroid function., (© 2022. The Author(s).)

This study aimed to evaluate the predictive value of diabetic retinopathy (DR) and its stages with the incidence of major cardiovascular events and all-cause mortality in type 2 diabetes mellitus (T2DM) persons in our large primary healthcare database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated incidence rates of major cardiovascular events [coronary heart disease (CHD), stroke, or both-macrovascular events] and all-cause mortality for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the probability of occurrence between DR and the study events. About 22,402 T2DM subjects with DR were identified in the database and 196,983 subjects without DR. During the follow-up period among the subjects with DR, we observed the highest incidence of all-cause mortally. In the second place were the macrovascular events among the subjects with DR. In the multivariable analysis, fully adjusted for DR, sex, age, body mass index (BMI), tobacco, duration of T2DM, an antiplatelet or antihypertensive drug, and HbA1c, we observed that subjects with any stage of DR had higher risks for all of the study events, except for stroke. We observed the highest probability of all-cause death events (adjusted hazard ratios, AHRs: 1.34, 95% CI: 1.28; 1.41). In conclusion, our results show that DR is related to CHD, macrovascular events, and all-cause mortality among persons with T2DM., Competing Interests: JB has received speaking fees from Boehringer Ingelheim, Astra-Zeneca, Lilly, MSD, Novo Nordisk, Sanofi. DM has received advisory and/or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. JF-N has received advisory and/or speaking fees from Astra-Zeneca. Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. XM-T has received advisory and/or speaking fees from Boehringer Ingelheim, Lilly, MSD, Novartis. MM-C has received advisory honorarium from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received speaker honorarium from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barrot, Real, Vlacho, Romero-Aroca, Simó, Mauricio, Mata-Cases, Castelblanco, Mundet-Tuduri and Franch-Nadal.)

Background: The aim of the present study was to determine the prevalence and incidence of diabetic retinopathy (DR) and its changes in the last 20 years in type 2 diabetes mellitus (T2DM) patients in Spain., Methods: A systematic review with a meta-analysis was carried out on the studies published between 2001-2020 on the prevalence and incidence of DR and sight-threatening diabetic retinopathy (STDR) in Spain. The articles included were selected from four databases and publications of the Spanish Ministry of Health and Regional Health Care System (RHCS). The meta-analysis to determine heterogeneity and bias between studies was carried out with the MetaXL 4.0., Results: Since 2001, we have observed an increase in the detection of patients with DM, and at the same time, screening programs for RD have been launched; thus, we can deduce that the increase in the detection of patients with DM, many of them in the initial phases, far exceeds the increased detection of patients with DR. The prevalence of DR was higher between 2001 and 2008 with values of 28.85%. These values decreased over the following period between 2009 and 2020 with a mean of 15.28%. Similarly the STDR prevalence decrease from 3.67% to 1.92% after 2008. The analysis of the longitudinal studies determined that the annual DR incidence was 3.83%, and the STDR annual incidence was 0.41%., Conclusion: In Spain, for T2DM, the current prevalence of DR is 15.28% and 1.92% forSTDR. The annual incidence of DR is 3.83% and is 0.41% for STDR.

Introduction: Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain., Methods: Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14 mg versus empagliflozin 25 mg and liraglutide 1.8 mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14 mg versus sitagliptin 100 mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin., Results: Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with direct costs EUR 168 higher versus empagliflozin and EUR 236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14 mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR 1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7 mg was associated with improvements of 0.11 QALYs and increased costs of EUR 226 versus sitagliptin and was therefore associated with an ICER of EUR 2011 per QALY gained., Conclusion: Oral semaglutide 14 mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Aims: Randomized controlled trials have demonstrated the efficacy of several dietary patterns plus physical activity to reduce diabetes onset in people with prediabetes. However, there is no evidence on the effect from the Mediterranean diet on the progression from prediabetes to diabetes. We aimed to evaluate the effect from high adherence to Mediterranean diet on the risk of diabetes in individuals with prediabetes., Methods: Prospective cohort study in Spanish Primary Care setting. A total of 1184 participants with prediabetes based on levels of fasting plasma glucose and/or glycated hemoglobin were followed up for a mean of 4.2 years. A total of 210 participants developed diabetes type 2 during the follow up. Hazard ratios of diabetes onset were estimated by Cox proportional regression models associated to high versus low/medium adherence to Mediterranean diet. Different propensity score methods were used to control for potential confounders., Results: Incidence rate of diabetes in participants with high versus low/medium adherence to Mediterranean diet was 2.9 versus 4.8 per 100 persons-years. The hazard ratios adjusted for propensity score and by inverse probability weighting (IPW) had identical magnitude: 0.63 (95% confidence interval, 0.43-0.93). The hazard ratio in the adjusted model using propensity score matching 1:2 was 0.56 (95% confidence interval, 0.37-0.84)., Conclusions: These propensity score analyses suggest that high adherence to Mediterranean diet reduces diabetes risk in people with prediabetes., (© 2021 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Tuberculosis is the leading cause of mortality from lung infectious disease worldwide in recent years, and its incidence has re-emerged in large cities in low-incidence countries due to migration and socioeconomic deprivation causes. Diabetes mellitus and tuberculosis are syndemic diseases, with diabetes being considered a risk factor for developing tuberculosis., Objective: To investigate whether diabetic patients were at increased risk of tuberculosis living in an inner-district of a large city of northeastern Spain., Methods: Observational matched retrospective cohort study based on clinical records from the population of the lowest socioeconomic status in Barcelona (Ciutat Vella district). A cohort including patients with type 1 and type 2 diabetes mellitus in 2007 and new cases until 2016 (8004 subjects), matched 1:1 by sex and age with a non-diabetic cohort. Follow-up period was until December 31st 2018. We evaluated the risk of developing tuberculosis in diabetic patients compared to non-diabetic patients during the follow up period. We used time-to-event analysis to estimate the incidence of tuberculosis, and competing risks regression by clusters and conditional Cox regression models to calculate the hazard ratio (HR) and its 95% confidence intervals (CI)., Results: Among the 16,008 included subjects, the median follow-up was 8.7 years. The mean age was 57.7 years; 61.2% men and 38.8% women in both groups. The incidence of tuberculosis was 69.9 per 100,000 person-years in diabetic patients, and 40.9 per 100,000 person-years in non-diabetic patients (HR = 1.90; CI: 1.18-3.07). After adjustment for the country of origin, chronic kidney disease, number of medical appointments, BMI, alcoholism and smoking, the risk remained higher in diabetic patients (1.66: CI 0.99-2.77). Additionally, subjects from Hindustan or with a history of alcohol abuse also showed a higher risk of developing tuberculosis (HR = 3.51; CI:1.87-6.57, and HR = 2.73; CI:1.22-6.12 respectively)., Conclusion: People with diabetes mellitus were at higher risk of developing tuberculosis in a large cohort recruited in an inner-city district with a high incidence for this outcome, and low socioeconomic conditions and high proportion of migrants. This risk was higher among Hindustan born and alcohol abusers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Antonio-Arques, Franch-Nadal, Moreno-Martinez, Real, Orcau, Mauricio, Mata-Cases, Julve, Navas Mendez, Puig Treserra, Barrot de la Puente, Millet, Del Val García, Vlacho and Caylà.)

Prediabetes and not just diabetes can cause kidney damage. This study assess the association of prediabetes with development of impaired renal function (IRF). We used data from PREDAPS prospective study a cohort of 1072 subjects with prediabetes and another cohort of 772 subjects without prediabetes were follow-up from 2012 to 2017. Prediabetes was defined according to American Association of Diabetes criteria. IRF was defined as having a glomerular filtration rate < 60 mL/min/1.73 m 2 . Incidence rates of IRF in both cohorts and in different categories of prediabetes, based on impaired glycosylated hemoglobin (HbA1c) and/or fasting plasma glucose (FPG), were calculated. Hazard ratios (HR) for the association of the prediabetes with IRF, adjusting for potential confounders, were estimated by Cox regression models. Incidence rates of IRF per 100 person-years were 1.72 (95% confidence interval [CI]: 1.34-2.21) and 1.79 (95%CI: 1.45-2.20) for those without and with prediabetes, respectively .The HR of IRF in subjects with prediabetes with respect to subjects without prediabetes was 0.76 (95% CI: 0. 54-1.07). Corresponding HRs for type of prediabetes was 0.68 (95%CI: 0.40-1.15) for those with both altered parameters, 0.68 (95%CI: 00.40-1.15) for those with only impaired HbA1c and 1.12 (95%CI: 0.68-1.85) for those with only impaired FPG. The present study reflects an overall trend towards a slightly decreased risk of IRF onset associated to prediabetes except for individuals with only isolated impaired FPG. Further studies are warranted to fully assess the renal progression of each group., (© 2022. The Author(s).)

Women with type 2 diabetes mellitus (T2DM) have a 40% excess risk of cardiovascular diseases (CVD) compared to men due to the interaction between sex and gender factors in the development, risk, and outcomes of the disease. Our aim was to assess differences between women and men with T2DM in the management and degree of control of cardiovascular risk factors (CVRF). This was a matched cross-sectional study including 140,906 T2DM subjects without previous CVD and 39,186 T2DM subjects with prior CVD obtained from the System for the Development of Research in Primary Care (SIDIAP) database. The absolute and relative differences between means or proportions were calculated to assess sex differences. T2DM women without previous CVD showed higher levels of total cholesterol (12.13 mg/dL (0.31 mmol/L); 95% CI = 11.9−12.4) and low-density lipoprotein cholesterol (LDL-c; 5.50 mg/dL (0.14 mmol/L); 95% CI = 5.3−5.7) than men. The recommended LDL-c target was less frequently achieved by women as it was the simultaneous control of different CVRF. In secondary prevention, women showed higher levels of total cholesterol (16.89 mg/dL (0.44 mmol/L); 95% CI = 16.5−17.3), higher levels of LDL-c (8.42 mg/dL (0.22 mmol/L); 95% CI = 8.1−8.8), and higher levels of triglycerides (11.34 mg/dL (0.13 mmol/L); 95% CI = 10.3−12.4) despite similar rates of statin prescription. Recommended targets were less often achieved by women, especially LDL-c < 100 mg/dL (2.59 mmol/L). The composite control was 22% less frequent in women than men. In conclusion, there were substantial sex differences in CVRF management of people with diabetes, with women less likely than men to be on LDL-c target, mainly those in secondary prevention. This could be related to the treatment gap between genders.

The identification of nutritional patterns associated with the development of type 2 diabetes (T2D) might help lead the way to a more efficient and personalized nutritional intervention. Our study is aimed at evaluating the association between fatty acids (FA) in red blood cell (RBC) membranes, as a quantitative biomarker of regular dietary fat intake, and incident type 2 diabetes in a Spanish population. We included 1032 adult Spaniards (57% women, age 49 ± 15 years, 18% prediabetes), without diabetes at study entry, from the Di@bet.es cohort. Incident diabetes was diagnosed at the end of the study follow-up. The FA percentage in RBC was determined at baseline by gas chromatography. Participants were followed on average 7.5 ± 0.6 years. Lower percentages of linoleic acid (LA), α-linolenic (ALA), and eicosapentaenoic acid (EPA), and higher percentages of docosahexaenoic acid (DHA) in RBC membranes were associated, independently of classical risk factors, with worse glucose metabolism at the end of the study follow-up. In addition, higher percentages of ALA and EPA, and moderate percentages of DHA, were associated with lower risk of diabetes. No significant associations were found for LA and diabetes risk. Dietary patterns rich in vegetables are independently associated with lower risk of both deterioration of glucose regulation and incident diabetes, and should be reinforced for the prevention of diabetes.

The GenoDiabMar registry is a prospective study that aims to provide data on demographic, biochemical, and clinical changes in type 2 diabetic (T2D) patients attending real medical outpatient consultations. This registry is also used to find new biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. With this purpose, longitudinal serum and urine samples, DNA banking, and data on 227 metabolomics profiles, 77 immunoglobulin G glycomics traits, and other emerging biomarkers were recorded in this cohort. In this study, we show a detailed longitudinal description of the clinical and analytical parameters of this registry, with a special focus on the progress of renal function and cardiovascular events. The main objective is to analyze whether there are differential risk factors for renal function deterioration between sexes, as well as to analyze cardiovascular events and mortality in this population. In total, 650 patients with a median age of 69 (14) with different grades of chronic kidney disease—G1−G2 (eGFR > 90−60 mL/min/1.73 m2) 50.3%, G3 (eGFR; 59−30 mL/min/1.73 m2) 31.4%, G4 (eGFR; 29−15 mL/min/1.73 m2) 10.8%, and G5 (eGFR < 15 mL/min/1.73 m2) 7.5%—were followed up for 4.7 (0.65) years. Regardless of albuminuria, women lost 0.93 (0.40−1.46) fewer glomerular filtration units per year than men. A total of 17% of the participants experienced rapid deterioration of renal function, 75.2% of whom were men, with differential risk factors between sexes—severe macroalbuminuria > 300 mg/g for men OR [IQ] 2.40 [1.29:4.44] and concomitant peripheral vascular disease 3.32 [1.10:9.57] for women. Overall mortality of 23% was detected (38% of which was due to cardiovascular etiology). We showed that kidney function declined faster in men, with different risk factors compared to women. Patients with T2D and kidney involvement have very high mortality and an important cardiovascular burden. This cohort is proposed as a great tool for scientific collaboration for studies, whether they are focused on T2D, or whether they are interested in comparing differential markers between diabetic and non-diabetic populations.