Cohort Profile: CArdiovascular Risk in patients with DIAbetes in NAvarra (CARDIANA cohort).

PURPOSE: The CArdiovascular Risk in patients with DIAbetes in Navarra (CARDIANA cohort) cohort was established to assess the effects of sociodemographic and clinical variables on the risk of cardiovascular events in patients with type 1 (T1D) or type 2 (T2D) diabetes, with a special focus on socioeconomic factors, and to validate and develop cardiovascular risk models for these patients. PARTICIPANTS: The CARDIANA cohort included all patients with T1D and T2D diabetes registered in the Public Health Service of Navarra with prevalent disease on 1 January 2012. It consisted of 1067 patients with T1D (ages 2-88 years) and 33842 patients with T2D (ages 20-105 years), whose data were retrospectively extracted from the Health and Administrative System Databases. FINDINGS TO DATE: The follow-up period for wave 1 was from 1 January 2012 to 31 December 2016. During these 5 years, 9 patients (0.8%; 95% CI (0.4% to 1.6%)) in the T1D cohort developed a cardiovascular disease event, whereas for the T2D cohort, 2602 (7.7%; 95% CI (7.4% to 8.0%)) had an event. For the T2D cohort, physical activity was associated with a reduced risk of cardiovascular events, with adjusted estimated ORs equal to 0.84 (95% CI 0.66 to 1.07) for the partially active group and 0.71 (95% CI 0.56 to 0.91) for the active group, compared with patients in the non-active group. FUTURE PLANS: The CARDIANA cohort is currently being used to assess the effect of sociodemographic risk factors on CV risk at 5 years and to externally validate cardiovascular predictive models. A second wave is being conducted in late 2022 and early 2023, to extend the follow-up other 5 years, from 1 January 2016 to 31 December 2021. Periodic data extractions are planned every 5 years.

Relationship between soluble protein ST2 (sST2) levels and microvascular complications in a cohort of patients with type 1 diabetes.

AIM: To determine the association and the prognostic value of soluble ST2 (sST2) levels in the development of diabetic retinopathy (DR), diabetic macular oedema (DMO) or diabetic nephropathy (DN), in a cohort of patients with type 1 diabetes (T1D). METHODS: A total of 269 individuals with T1D (154 males and 115 females) were recruited. The overall mean age was 43.2±14.9 years, and the diabetes duration was 17.1±12.1 years. Levels of sST2 in serum were evaluated, and the presence as well as the degree of DR, DMO and DN was recorded. Additionally, other clinical and analytical parameters including demographic variables were recovered from patients' electronic health record. Ten years later, the presence and stage of DR, DMO and DN were again recorded under the same criteria. The association between previously mentioned parameters with DR and DN was analysed by univariate and multivariate logistic regression. The variables in the final multivariate models were adjusted from complete models via backward elimination and maintained only when significant. RESULTS: An increase of 10ng/ml in the levels of sST2 was associated with a 1.50 (1.02-2.19) and 1.48 (1.05-2.08) prevalence odds ratio (OR) in DMO and DR, respectively. There was no association between sST2 levels and DN. Meanwhile, sST2 levels did not display a prognostic effect in any of the microangiopathic diabetic complications studied. CONCLUSIONS: Levels of sST2 are associated with the presence of DR and DMO, they do not seem to be predictive for the development or deterioration of DR, DMO or DN.

Relationship between soluble protein ST2 (sST2) levels and microvascular complications in a cohort of patients with type 1 diabetes.

AIM: To determine the association and the prognostic value of soluble ST2 (sST2) levels in the development of diabetic retinopathy (DR), diabetic macular oedema (DMO) or diabetic nephropathy (DN), in a cohort of patients with type 1 diabetes (T1D). METHODS: A total of 269 individuals with T1D (154 males and 115 females) were recruited. The overall mean age was 43.2±14.9 years, and the diabetes duration was 17.1±12.1 years. Levels of sST2 in serum were evaluated, and the presence as well as the degree of DR, DMO and DN was recorded. Additionally, other clinical and analytical parameters including demographic variables were recovered from patients' electronic health record. Ten years later, the presence and stage of DR, DMO and DN were again recorded under the same criteria. The association between previously mentioned parameters with DR and DN was analysed by univariate and multivariate logistic regression. The variables in the final multivariate models were adjusted from complete models via backward elimination and maintained only when significant. RESULTS: An increase of 10ng/ml in the levels of sST2 was associated with a 1.50 (1.02-2.19) and 1.48 (1.05-2.08) prevalence odds ratio (OR) in DMO and DR, respectively. There was no association between sST2 levels and DN. Meanwhile, sST2 levels did not display a prognostic effect in any of the microangiopathic diabetic complications studied. CONCLUSIONS: Levels of sST2 are associated with the presence of DR and DMO, they do not seem to be predictive for the development or deterioration of DR, DMO or DN.

Cyclical variation in the incidence of childhood-onset type 1 diabetes during 40 years in Navarra (Spain).

OBJECTIVE: To trace the evolution of type 1 diabetes (T1D) in Navarre in children under 15, between 1977 and 2016, and their characteristics at onset regarding age and sex. SUBJECTS AND METHODS: We performed a descriptive analysis, using prospective-retrospective information. The study included all cases of T1D diagnosed in Navarre in children aged 0 to 14 years old from 1 January 1977 until 31 December 2016. The capture-recapture method was used, retrieving information from three independent sources: the five hospitals in Navarre as a primary source, and the Navarre Association of Diabetics (ANADI) and the primary healthcare system as the secondary source. Estimates and confidence intervals were calculated assuming a subjacent Poisson distribution. Chi square test was used to compare incidence between groups. The analysis of changes in incidence since 1977, adjusted for age group, sex and year of diagnosis, were evaluated with a multivariate Poisson regression model and joinpoint regression. RESULTS: A total of 577 cases were registered resulting in a crude incidence rate of 14.99/100 000 inhabitants-year (95% confidence interval [CI]: 13.79-16.26). From 1977, the incidence has increased in cycles, reaching an incidence rate of 22.98 (95% CI: 18.52-28.21) in 2016. The relative annual increase is 3% (95% CI: 2.3-3.8). The highest incidence is in the 10 to 14 age group (P < 0.001). No differences in sex were found. The mean age at onset in children under 15 years has not changed significantly (P = 0.572). CONCLUSIONS: The incidence of T1D in Navarre has increased 4-fold in the last four decades but is stable since 2001.

La incidencia de diabetes tipo 1, en Navarra, se ha estabilizado en los últimos 8 años / Incidence of type 1 diabetes mellitus in Navarre stabilized in the last eight years

Objetivo: La incidencia de diabetes tipo 1 plantea diversas controversias. Nuestro objetivo consiste en contribuir a responder a las siguientes preguntas: ¿Está aumentando la incidencia? ¿Se adelanta la edad al comienzo? ¿Cuáles son las diferencias entre sexos? y ¿Cuáles son las características en adultos? Métodos: Estudio transversal descriptivo, con los datos obtenidos de una fuente primaria y 3 secundarias, entre el 01/01/2009 y el 31/12/2016, en Navarra. Se estimaron las tasas anuales y la tasa de incidencia, expresada por 100.000 personas-año de riesgo, en el período estudiado, por grupos de edad y sexo. La comparación de la incidencia por sexo y edad se ha realizado estimando la razón de incidencia a partir de métodos de regresión de Poisson. La exhaustividad del Registro fue del 96,08%. Resultados: Durante estos 8 años, se registraron 428 nuevos casos (incidencia: 8,4/100.000 habitantes-año; IC95%: 7,6-9,2). La incidencia ha permanecido estable y en menores de 15 años (21,5) es mayor que en adultos (5,9). El grupo de edad con mayor incidencia es el de 10 a 14 años en varones y el de 5 a 9 años en mujeres. A partir de aquí, disminuye con la edad. Predomina en hombres entre los 10 y 45 años y, separando por cuatrienios, no hay cambios en la edad al comienzo. Conclusiones: Navarra muestra muy alta incidencia de diabetes tipo 1 en la infancia y baja incidencia en adultos. El pico de incidencia se da antes en las niñas, pero la enfermedad predomina en varones. Ni la incidencia ni la edad al comienzo se han modificado

Objectives: Incidence of type 1 diabetes mellitus raises a number of controversies. Our study aim was to contribute to answer the following questions: Is incidence of T1DM increasing? Is age at onset of type 1 diabetes mellitus decreasing? Which are the sex differences? Which are the characteristics in adults? Methods: A cross-sectional descriptive study using data from a primary source and 3 secondary sources from Navarre collected between 01/01/2009 and 12/31/2016. Annual incidence rates and incidence rate expressed as 100,000 person-years were estimated in the study period by age and sex group. The comparison of the sex and age incidence was made estimating the incidence rate using Poisson's regression methods. The completeness of the register was 96.08%. Results: During the 8 years analyzed, 428 new cases of type 1 diabetes mellitus were reported (incidence: 8.4/100,000 person-years, 95% CI: 7.6-9.2). Incidence has remained stable and is higher in the group under 15 years old (21.5) than in adults (5.9). Males aged 10-14 years and females aged 5-9 years were the groups with the highest incidence. Incidence then decreased with increasing age. Type 1 diabetes mellitus predominates in males aged 10-45 years, and no changes were seen in age at onset when analized by four-year periods. Conclusion: Navarre shows a very high incidence of type 1 diabetes mellitus in childhood and a low incidence in adulthood. Peak incidence is seen earlier in girls, but the disease predominates in males. Neither incidence nor age at onset have changed

Incidence of type 1 diabetes mellitus in Navarre stabilized in the last eight years. / La incidencia de diabetes tipo 1, en Navarra, se ha estabilizado en los últimos 8 años.

OBJECTIVES: Incidence of type 1 diabetes mellitus raises a number of controversies. Our study aim was to contribute to answer the following questions: Is incidence of T1DM increasing? Is age at onset of type 1 diabetes mellitus decreasing? Which are the sex differences? Which are the characteristics in adults? METHODS: A cross-sectional descriptive study using data from a primary source and 3 secondary sources from Navarre collected between 01/01/2009 and 12/31/2016. Annual incidence rates and incidence rate expressed as 100,000 person-years were estimated in the study period by age and sex group. The comparison of the sex and age incidence was made estimating the incidence rate using Poisson's regression methods. The completeness of the register was 96.08%. RESULTS: During the 8 years analyzed, 428 new cases of type 1 diabetes mellitus were reported (incidence: 8.4/100,000 person-years, 95% CI: 7.6-9.2). Incidence has remained stable and is higher in the group under 15 years old (21.5) than in adults (5.9). Males aged 10-14 years and females aged 5-9 years were the groups with the highest incidence. Incidence then decreased with increasing age. Type 1 diabetes mellitus predominates in males aged 10-45 years, and no changes were seen in age at onset when analized by four-year periods. CONCLUSION: Navarre shows a very high incidence of type 1 diabetes mellitus in childhood and a low incidence in adulthood. Peak incidence is seen earlier in girls, but the disease predominates in males. Neither incidence nor age at onset have changed.

Socioeconomic inequalities in cardiometabolic control in patients with type 2 diabetes.

BACKGROUND: The aim of this study was to determine if the achievement of control targets in patients with type 2 diabetes was associated with personal socioeconomic factors and if these associations were sex-dependent. METHODS: This cross-sectional, population-based study was conducted in Spain. Glycated haemoglobin (HbA1c) level and other clinical parameters were obtained from electronic primary care records (n = 32,638 cases). Socioeconomic status was determined using education level and yearly income. Among patients, having their HbA1c level checked during the previous year was considered as an indirect measure of the process of care, whereas tobacco use and clinical parameters such as HbA1c, low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) were considered intermediate control outcomes. General linear mixed effect models were used to assess associations. RESULTS: The achievement of metabolic and cardiovascular control targets in patients with type 2 diabetes was associated with educational level and income, and socioeconomic gradients differed by sex. The probability of having had an HbA1c test performed in the previous year was higher in patients with lower education levels. Patients in the lowest income and education level categories were less likely to have reached the recommended HbA1c level. Males in the lowest education level categories were less likely to be non-smokers or to have achieved the blood pressure targets. In contrast, patients within the low income categories had a higher probability of reaching the recommended LDL-c level. CONCLUSIONS: Our results suggest the presence of socioeconomic inequalities in the achievement of cardiovascular and metabolic control that differed in direction and magnitude depending on the measured outcome and sex of the patient. These findings may help health professionals focus on high-risk individuals to decrease health inequalities.

Low Serum Levels of Prealbumin, Retinol Binding Protein, and Retinol Are Frequent in Adult Type 1 Diabetic Patients.

Aim. To determine the serum prealbumin (PA), retinol binding protein (RBP), and retinol levels in adult patients with type 1 diabetes (T1D) and to analyze some factors related to those levels. Methods. A total of 93 patients (47 women) were studied. Age, gender, BMI, duration of diabetes, chronic complications, HbA1c, lipid profile, creatinine, albumin, PA, RBP, and retinol were recorded. High and low parameter groups were compared by Mann-Whitney U and χ2 tests. Correlation between parameters was analyzed by Spearman's test. Odds of low levels were analyzed by univariate logistic regression and included in the multivariate analysis when significant. Results. 49.5%, 48.4%, and 30.1% of patients displayed serum PA, RBP, and retinol levels below normal values, respectively. A high correlation (Rho > 0.8) between PA, RBP, and retinol serum levels was found. Patients presenting low levels of any of them were predominantly women, normal-weighted, and with lower levels of triglycerides and serum creatinine. No differences in age, macrovascular complications, duration of diabetes, or HbA1c values were observed when comparing low and normal parameter groups. Conclusion. Low serum levels of PA, RBP, and retinol are frequent in T1D adult patients. This alteration is influenced by female sex and serum creatinine and triglyceride levels.

Influence of Age at Diagnosis and Time-Dependent Risk Factors on the Development of Diabetic Retinopathy in Patients with Type 1 Diabetes.

Aim. To determine the influence of age at onset of type 1 diabetes and of traditional vascular risk factors on the development of diabetic retinopathy, in a cohort of patients who have been followed up after onset. Methods. Observational, retrospective study. The cohort consists of 989 patients who were followed up after diagnosis for a mean of 10.1 (SD: 6.8) years. The influence of age at diagnosis, glycemic control, duration of diabetes, sex, blood pressure, lipids, BMI, and smoking is analyzed using Cox univariate and multivariate models with fixed and time-dependent variables. Results. 135 patients (13.7%) developed diabetic retinopathy. The cumulative incidence was 0.7, 5.9, and 21.8% at 5-, 10-, and 15-year follow-up, respectively. Compared to the group with onset at age <10 years, the risk of retinopathy increased 2.5-, 3-, 3.3-, and 3.7-fold in the groups with onset at 10-14, 15-29, 30-44, and >44 years, respectively. During follow-up we also observed an association between diabetic retinopathy and HbA1c levels, HDL-cholesterol, and diastolic blood pressure. Conclusion. The rate of diabetic retinopathy is higher in patients who were older at type 1 diabetes diagnosis. In addition, we confirmed the influence of glycemic control, HDL-cholesterol, and diastolic blood pressure on the occurrence of retinopathy.

Incidence and Risk Factors Involved in the Development of Nephropathy in Patients with Type 1 Diabetes Mellitus: Follow Up Since Onset.

OBJECTIVES: Estimation of the incidence of nephropathy as well as potential risk factors involved in its onset in a cohort of patients with type 1 diabetes who were followed from diagnosis. METHODS: We studied 716 patients, who were followed for a mean (standard deviation [SD]) of 10.1 (SD: 5.3) years. We analyzed the influence of demographic characteristics and levels of glycated hemoglobin (A1C), lipids and blood pressure during the course of the disease by univariate and multivariate survival methods. RESULTS: The cumulative incidence of nephropathy was 2.6%, 6.3% and 11.9% at 5, 10 and 15 years of evolution, respectively. The factors associated with increased risk for nephropathy were systolic blood pressure and A1C levels. An increment of 10 mm Hg in systolic blood pressure increases the risk by 36%, and an increment of 1% in A1C levels raises the risk by 13% at 5 years since onset and 68% at 10 years, and it doubles the risk at 15 years. Women have higher risk than men (hazard ratio 1.79; p=0.024). CONCLUSIONS: Our study suggests that female gender and high levels of A1C and systolic blood pressure throughout the course of the disease are the main factors associated with an increased risk for development of nephropathy in patients with type 1 diabetes mellitus.

Documento de consenso sobre el tratamiento con infusión subcutánea continua de insulina en el medio hospitalario / Position statement on continuous subcutaneous insulin infusion in the hospital setting

En España hay un número creciente de personas con diabetes tipo 1 tratadas con la terapia de infusión subcutánea continua de insulina (ISCI), pero no hay directrices nacionales sobre cómo manejar la terapia con bomba de insulina en el ámbito hospitalario. El Grupo de Nuevas Tecnologías de la Sociedad Española de Diabetes ha revisado la literatura y varias directrices internacionales y propone un documento de consenso sobre el manejo de la terapia con bomba de insulina para los pacientes hospitalizados. El documento contiene recomendaciones sobre las indicaciones, las contraindicaciones y los requisitos necesarios para el mantenimiento de la terapia con ISCI en el hospital. Esta revisión proporciona una guía para el manejo de pacientes ISCI en entornos especiales, tales como la sala de urgencias, cirugía, parto y para pacientes pediátricos. Por último, el grupo propone un conjunto de documentos necesarios para establecer una política ISCI en el hospital. En conclusión, la terapia con ISCI se puede utilizar con seguridad en el hospital en pacientes seleccionados después de haberse implementado un protocolo estandarizado

There is an increasing number of people with type 1 diabetes treated with continuous subcutaneous insulin infusion therapy (CSII) in Spain, but there are no national guidelines on how to manage insulin pump therapy in the hospital setting. The Group on New Technologies in Diabetes of the Spanish Diabetes Society has reviewed the literature and several international guidelines, and proposes a consensus document on the management of insulin pump therapy for inpatients. The document contains recommendations on indications, contraindications and the requirements needed to maintaining CSII therapy. This review provides a guide for the management of CSII patients in special settings such as the emergency room, surgery, delivery, and for pediatric patients. Finally, the group proposes a set of documents needed to establish a CSII policy in the hospital. In conclusion, CSII therapy can safely be used in the hospital in selected patients after the implementation of a standardized protocol

Luces y sombras en la epidemiología de la diabetes de tipo 1 / Epidemiology of type 1 diabetes: Lights and shades

La incidencia de diabetes de tipo 1 varía hasta 576 veces entre los distintos países del mundo y alcanza una relación de 2/1 entre comunidades autónomas españolas. En las 2 últimas décadas, se han publicado numerosos estudios con respecto a la incidencia, prevalencia, tendencias y características al comienzo de la diabetes de tipo 1: edad, sexo, raza, agrupación familiar y estacionalidad. Estos datos suponen las luces que la epidemiología aporta al estudio de la diabetes, ya que contribuyen a generar hipótesis sobre las que investigar posteriormente. Las sombras vienen representadas por las limitaciones en la recogida de los datos, la calidad de algunos Registros y la falta de resultados obtenidos hasta ahora en cuanto a eficacia, al seguir las pistas que la epidemiología nos ha proporcionado. Para mejorar las expectativas, es fundamental disponer de Registros amplios y fidedignos que proporcionen datos precisos y, posteriormente, buscar los factores ambientales implicados para poder combatirlos

The incidence rate of type 1 diabetes varies by up to 576 times between different countries around the world. In Spain, the highest incidence rate is twice that of the lowest between Autonomous Communities. Many studies have been published in the last twenty years on the incidence, prevalence, trends, and characteristics at diagnosis of type 1 diabetes. The age at diagnosis, sex, racial group, familial clustering, and seasonal variation have been the characteristics analysed. These data are the lights that epidemiology provides us, in order to have a better understanding of diabetes aetiopathology. They allow us to create hypotheses to be investigated. The shades are the quality of some registries and the lack of success of trials conducted up until now. In order to improve these results, is necessary to develop more reliable registries to get accurate data in order to combat the environment risk factors

[Differences by age and gender in the incidence of type 1 diabetes in Navarre, Spain (2009-2011)]. / Diferencias por edad y sexo en la incidencia de diabetes tipo 1 en Navarra (2009-2011).

OBJECTIVE: To determine the incidence of type 1 diabetes in Navarre, irrespective of age, from 2009 to 2011, and its characteristics at onset by age and gender. METHOD: A descriptive cross-sectional study was conducted. Data were obtained from one primary and three secondary sources. Poisson regression models were used to analyze differences in incidence rates among age groups and between male and female patients. RESULTS: We detected 167 new cases (incidence: 8.7/100,000 inhabitants-year; 95%CI: 7.4-10.1). The incidence was higher in children than in adults and was highest in the group aged 10-14 years. The incidence was higher in males than in females. The incidence increased with age in boys under 15 years but not in girls. CONCLUSIONS: The incidence of type 1 diabetes in children and young adults in Navarre is among the highest in Europe. Differences were found by age and gender.

Bilateral Leydig cell tumour of the ovary: a rare cause of virilization in postmenopausal patient.

BACKGROUND: Leydig cell tumours of the ovary are very rare benign neoplasms, frequently associated with symptoms of virilisation, in postmenopausal patients. Only four cases of bilateral Leydig tumours have been reported in the literature. CASE REPORT: We report an additional case of bilateral presentation. A 77-year-old postmenopausal patient was referred from the Endocrinology Service due to a biochemical diagnosis of hyperandrogenism during hospital admission with unbalanced diabetes mellitus. The patient had suffered from alopecia and hirsutism for many years. Biological data confirmed an increment of androgen production. Ultrasonography showed a well-defined hyperechoic lesion of 12 mm in the right ovary. A CT scan demonstrated adrenal glands and ovaries without tumour. Bilateral adnexectomy by laparoscopy was carried out. RESULT: The pathological finding was a bilateral Leydig cell tumour, measuring 15 mm in the right ovary and 3 mm in the left ovary. Following treatment the patient experienced regression of the hirsutism and the plasma testosterone dropped to a normal level. CONCLUSION: In spite of its low incidence, it is a possibility that must be considered in all postmenopausal women with hyperandrogenism, and bilateral adnexectomy by laparoscopy is recommended as a diagnostic test and definitive treatment.