Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.

Comprehensive approach to people with type 2 diabetes. Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition.

OBJECTIVE: To provide practical recommendations for the comprehensive approach of people with type 2 diabetes according to evidence-based medicine. PARTICIPANTS: Members of the Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition. METHODS: The recommendations were formulated according to the degrees of evidence of the Standards of Medical Care in Diabetes-2022. After reviewing the available evidence and formulating recommendations by the authors of each section, several rounds of comments were developed incorporating the contributions and voting on controversial points. Finally, the final document was sent to the rest of the members of the area for review and incorporation of contributions, to finally carry out the same process with the members of the Spanish Society of Endocrinology and Nutrition Board of Directors. CONCLUSIONS: The document establishes practical recommendations based on the latest available evidence for the management of people with type 2 diabetes.

Executive summary: Position document: Evaluation and management of hypoglycemia in the patient with diabetes mellitus 2020. Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition.

OBJECTIVE: To provide practical recommendations for the evaluation and management of hypoglycemia in patients with diabetes mellitus. PARTICIPANTS: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN). METHODS: The recommendations were made based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to establish both the strength of the recommendations and the level of evidence. A systematic search was made in MEDLINE (PubMed) for the available evidence on each subject, and articles written in English and Spanish with an inclusion date up to 30 November 2019 were reviewed. This executive summary takes account of the evidence incorporated since 2013. CONCLUSIONS: The document establishes practical evidence-based recommendations regarding the evaluation and management of hypoglycemia in patients with diabetes mellitus.

Executive summary: Position document: Evaluation and management of hypoglycemia in the patient with diabetes mellitus 2020. Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition. / Resumen ejecutivo: Documento de posicionamiento: evaluación y manejo de la hipoglucemia en el paciente con diabetes mellitus 2020. Grupo de Trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición.

OBJECTIVE: To provide practical recommendations for the evaluation and management of hypoglycemia in patients with diabetes mellitus. PARTICIPANTS: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN). METHODS: The recommendations were made based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to establish both the strength of the recommendations and the level of evidence. A systematic search was made in MEDLINE (PubMed) for the available evidence on each subject, and articles written in English and Spanish with an inclusion date up to 28 February 2020 were reviewed. This executive summary takes account of the evidence incorporated since 2013. CONCLUSIONS: The document establishes practical evidence-based recommendations regarding the evaluation and management of hypoglycemia in patients with diabetes mellitus.

People living with type 1 diabetes point of view in COVID-19 times (COVIDT1 study): Disease impact, health system pitfalls and lessons for the future.

AIMS: To analyse the effects of confinement among people with type 1 diabetes (T1D) and their caregivers over the course of the COVID-19 crisis and to evaluate contemporary changes in medical assistance and patient preferences. METHODS: An observational cross-sectional study designed as a self-reported web-based survey was conducted over the course of the COVID-19 pandemic. RESULTS: A total of 769 subjects participated in the survey (603 people with T1D and 166 caregivers). Changes in glycaemic control were reported in 66% of cases, weight gain in 40.4% of cases and decreased exercise levels in 65.4% of cases. Of the cohort, 53% maintained contact with the healthcare team, and 23% received specific information related to COVID-19. Emotional support was requested by 17% of respondents. Regarding telemedicine, 97.9% agreed with its use with the following preferences regarding the future: telephone call (84.5%), video-call (60.6%) and platform devices (39.7%). CONCLUSIONS: Over the course of the COVID-19 pandemic, at least two-thirds of people with T1D underwent changes in the management of their condition. Almost all participants agreed with the concept of telemedicine, favouring telephone and video calls as their preferred means of communication.

Use of intravitreal dexamethasone implants in the treatment of diabetic macular edema: Expert recommendations using a Delphi approach.

OBJECTIVE: The aim of this study is to develop guidance on the use of intravitreal dexamethasone implants in the treatment of diabetic macular edema. METHOD: The study was performed using the modified Delphi method to obtain a consensus among a panel of experts on management of patients with diabetic macular edema and use of intravitreal dexamethasone implants in clinical practice. Thirty-seven panel members, experts on retina, from different Spanish centers were invited to participate. Individual and anonymous opinions were asked by answering a 76-item questionnaire across 11 topic areas (two rounds were done). Level of agreement was assessed using a Likert-type scale of 9 points. RESULTS: Agreement on "consensus" was reached during the first round in 63 items. The 13 remaining items underwent a second round of voting. After the second round, agreement on "consensus" was reached on five items. Finally, eight items remained without consensus. CONCLUSION: Intravitreal dexamethasone implants are useful in the treatment of patients with diabetic macular edema with different profiles, for example, pseudophakic, poor-adherents, vitrectomized, candidates for cataract surgery, patients with high inflammatory component, and with a history of cardiovascular events. The use of intravitreal dexamethasone reduces the number of visits and facilitates compliance. Experts thought that the switch from anti-vascular endothelial growth factor therapy to intravitreal dexamethasone implants should be done preferably after three injections. Also, pro re nata treatment provides better results in diabetic macular edema patients as it helps to prevent undertreatment. Finally, experts concluded that clinical guidelines and treatment protocols for diabetic macular edema need to be updated.

Factors Predicting the Response to a Vitamin D-Fortified Milk in Healthy Postmenopausal Women.

BACKGROUND: Milk products fortified with vitamin D may constitute an alternative to pharmacological supplements for reaching the optimal levels of serum 25-hydroxyvitamin D [25(OH)D]. Our aim was to analyze the response of serum 25(OH)D and its predictive factors in postmenopausal healthy women after a dietary intervention with a milk fortified with vitamin D and calcium. METHODS: We designed a prospective study including 305 healthy postmenopausal women who consumed a fortified milk with calcium (900 mg/500 mL) and vitamin D3 (600 IU/500 mL) daily for 24 months. RESULTS: The 25(OH)D concentrations at 24 months were correlated to weight, to body mass index, to the percentage of fat, triglycerides and to baseline 25(OH)D levels. We found significant differences in the levels of 25(OH)D at 24 months according to baseline 25(OH)D levels (p < 0.001) and body mass index (p = 0.019) expressed at quartiles. Multivariate analysis showed an association between levels of 25(OH)D after the intervention and at baseline 25(OH)D (Beta = 0.47, p < 0.001) and percentage of body fat (Beta = -0.227, p = 0.049), regardless of the body mass index. CONCLUSIONS: In healthy postmenopausal women, the improvement in 25(OH)D after an intervention with a fortified milk for 24 months depends mainly on the baseline levels of serum 25(OH)D and on the percentage of body fat.

Documento de abordaje integral de la diabetes tipo 2 / Document on a comprehensive approach to type 2 diabetes mellitus

Objetivo: El tratamiento de la diabetes tipo 2 (DM2) es complejo y su propósito es reducir la morbimortalidad, por lo que su manejo tiene que incluir: un control glucémico individualizado precoz (mediante una adecuada educación diabetológica, modificaciones del estilo de vida y tratamiento farmacológico), el control de los factores de riesgo cardiovascular (CV), la detección y tratamiento precoz de las complicaciones y la evaluación de las comorbilidades asociadas. El objetivo fue elaborar un documento para unificar los aspectos necesarios para el abordaje integral de las personas con DM2. Participantes: Miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Métodos: Se realizó una revisión de la evidencia disponible relativa a cada aspecto del manejo de la diabetes: objetivos de control glucémico, dieta y ejercicio, tratamiento farmacológico, tratamiento y control de factores de riesgo, detección de complicaciones y manejo del paciente frágil con DM2. Las recomendaciones se formularon según los grados de evidencia recogidos en los Standards of Medical Care in Diabetes 2018. Tras la formulación de las recomendaciones el documento fue consensuado por los miembros del Grupo de trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición. Conclusiones: El objetivo de este documento es proporcionar, desde el punto de vista del endocrinólogo clínico, unas recomendaciones prácticas basadas en la evidencia acerca de todos los aspectos necesarios para el abordaje integral de la DM2

Objective: Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. Participants: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology. Methods: The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. Conclusions: This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists

Trends on Diabetes Mellitus's healthcare management in Spain 2007-2015.

AIMS: To analyze the trends on diabetes mellitus (DM) healthcare management in Spain. METHODS: Retrospective observational study between January 1st 2007 and 31th December 2015 with DM as the principal diagnosis. The main clinical outcome measures were all-cause, in-hospital mortality and 30-day readmissions. We also analyze three Prevention Quality Indicators (PQI) for DM. RESULTS: The number of hospitalization episodes decreased significantly as well as the frequentation rate and average length of stay (Incidence Rate Ratio [IRR] = 0.963, p < 0.001; 0.91, p < 0.001 and 0.986, p < 0.001, respectively). Crude in-hospital mortality and readmissions rates and risk-standardized in-hospital mortality rates (RSMR), however, remained stable (IRR = 0.988, p = 0.073; IRR = 1.003, p = 0.334 and IRR = 0.997, p = 0.116, respectively). A relevant variability in RSMR, both at hospital (Median Odds Ratio 1.49) and regional level, was found. High volume hospitals (≥105 DM discharges at year) showed better outcomes. High variability was also found in PQI indicators al regional level. CONCLUSION: The present analysis shows an improvement in hospitalizations related to DM in Spain in the period 2007-2015. There was also a decrease in the frequentation rate and in the average length of stay. These findings are probably explained by quality improvements in the healthcare management of the DM at the ambulatory level. However, there were important differences in the management of diabetic inpatients both at the hospital and the regional level.

Document on a comprehensive approach to type 2 diabetes mellitus. / Documento de abordaje integral de la diabetes tipo 2.

OBJECTIVE: Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. PARTICIPANTS: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology. METHODS: The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. CONCLUSIONS: This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists.

High Irisin levels in nondiabetic HIV-infected males are associated with insulin resistance, nonalcoholic fatty liver disease, and subclinical atherosclerosis.

OBJECTIVE: HIV infection is associated with an increased risk of cardiovascular disease. Irisin is a miokyne secreted by skeletal muscle, which may influence insulin homeostasis, nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. Our objective was to evaluate the relationships between serum irisin, insulin homeostasis, NAFLD and subclinical atherosclerosis in HIV-infected males. DESIGN: Cross-sectional study in a cohort of HIV-infected patients. PATIENTS: Inclusion criteria: men older than 18 years; antiretroviral therapy (ART) -naïve or on effective ART (<50 HIV-1 RNA copies/mL) without changes in the previous 6 months; no diabetes or hepatitis C. MEASUREMENTS: Irisin was measured by enzymatic immunoassay (Phoenix Pharmaceuticals), insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR), as well as the 2-hour continuous infusion of glucose with model assessment (CIGMA-HOMA). Hepatic steatosis was measured by 1-H magnetic resonance spectroscopy, subclinical atherosclerosis by evaluation of carotid intima-media thickness (C-IMT), measured by Ultrasonography. RESULTS: Eight nine men (age 42.0 ± 8.3 years, duration of HIV infection 7.9 ± 5.6 years, CD4 count 547 ± 279 cells/mL) were included. Circulating irisin was positively related to HOMA-IR and CIGMA-HOMA, hepatic triglyceride content, and to VAT/SAT ratio. Higher irisin concentrations were associated with higher C-IMT, although this association did not persist in multivariate analysis. Lipodystrophy and a higher baseline PAI-1 concentration were independently associated with C-IMT. CONCLUSIONS: In male HIV patients without diabetes, higher irisin concentrations are positively associated with insulin resistance, NAFLD and subclinical atherosclerosis. However, waist-hip-ratio is the main determinant of insulin resistance, and PAI-1 and lipodystrophy were the strongest determinants of IMT in this population.

Higher Levels of Serum 25-Hydroxyvitamin D Are Related to Improved Glucose Homeostasis in Women with Postmenopausal Osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMO) is associated with other comorbidities such as impaired glucose homeostasis and cardiovascular disease. Vitamin D insufficiency is highly prevalent and may be a common link between these disorders. However, the relationship between circulating 25-hydroxyvitamin D [25(OH)D] and insulin resistance in women with PMO has not been well evaluated. The aim of this study was to assess the relationship between circulating levels of 25(OH)D and parameters of glucose homeostasis in a cohort of women with PMO to establish a serum concentration threshold of 25(OH)D for improved glycemic parameters. MATERIALS AND METHODS: This cross-sectional study included 40 women with PMO. We measured 25(OH)D serum levels and glucose homeostasis parameters (glucose and insulin levels, insulin sensitivity, and ß-secretion index HOMA2-%S and HOMA2-%B, respectively). Anthropometric, biochemical, and clinical parameters and bone markers were also evaluated. RESULTS: Circulating levels of 25(OH)D were related to glucose parameters (negatively with HOMA2-%B and insulin levels and positively with HOMA2-%S) in women with PMO, resulting in an indicator of insulin sensitivity independent of age, body mass index, percent body fat, and undercarboxylated osteocalcin. Patients with serum 25(OH)D ≥45 ng/mL showed lower HOMA2-%B values and insulinemia and greater HOMA2-%S. CONCLUSIONS: Our results support the hypothesis that circulating 25(OH)D levels are related to improved glucose homeostasis in women with PMO. However, this relationship was apparent only in the presence of high circulating levels of 25(OH)D.

Effects of Daily Intake of Calcium and Vitamin D-Enriched Milk in Healthy Postmenopausal Women: A Randomized, Controlled, Double-Blind Nutritional Study.

OBJECTIVE: To determine the effect of the daily intake of calcium and vitamin D-enriched milk (with or without fructooligosaccharides [FOS]) on vitamin D, bone metabolism, and cardiovascular risk factors. MATERIALS AND METHODS: Two-year randomized controlled study, including 500 healthy postmenopausal women, assigned to 500 mL/day of skimmed milk to one of three groups: Low-dose (L): (120 mg/100 mL calcium, vitamin D3 30 UI/100 mL), group A: calcium and vitamin D (180 mg/100 mL and 120 UI/100 mL), and group B: calcium and vitamin D (180 mg/100 mL and 120 UI/100 mL) and FOS (5 g/L). We evaluated serum 25(OH)D, bone mineral density (BMD) by Dual Energy X-ray Absorptiometry, and biochemical data of glucose and lipid metabolism. RESULTS: After 24 months, vitamin D concentrations did not change in the control group, but increased in group A and group B, p < 0.001. We observed an increase in femoral neck BMD and an improvement in fasting plasma glucose, HbA1c, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B 100. CONCLUSIONS: Daily intake of milk enriched with calcium and vitamin D in postmenopausal healthy women induces a significant improvement in vitamin D status, a significant increase in BMD at femoral neck, and also favorable effects on glucose and lipid profile.

Electrical changes during hypoglycaemia in patients with type 1 and type 2 diabetes and high cardiovascular risk.

The relationship between glycaemia, arrhythmia and changes in electrocardiogram (ECG) has been addressed showing mixed results. The objective of this study was to evaluate the changes in ECG, evaluated by Holter monitoring, induced by clinical hypoglycaemia in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM), aged 50 or older, with high cardiovascular risk. Five-lead Holter monitoring (BL-900 Braemar, Inc, Norav Medical NH301-2.4.5 software), and blinded interstitial continuous glucose monitoring (CGM) (Dexcom G4-Platinum, range 40-400 mg/dl) was performed with time synchronization. In the Holter registry, in patients with hypoglycemic episodes, mean QTc during hypoglycaemia was longer compared to mean QTc in total group (+4.6 ms, p = 0.037) and T1DM patients (+5.5 ms, p = 0.048) but not in T2DM patients (+3 ms, p = 0.459). During hypoglycaemia, non-clinical significant disturbances in heart rhythm were observed. In conclusion, we observed a prolongation in QTc during hypoglycemia, mainly in T1DM. However, our study does not show a relationship between episodes of hypoglycaemia and clinical arrhythmias, at least in T1DM and T2DM patients with high cardiovascular risk.

Recommendations on the effect of antidiabetic drugs in bone. / Recomendaciones sobre el efecto de los fármacos antidiabéticos en el hueso.

OBJECTIVE: To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. CONCLUSIONS: The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk.

Recommended vitamin D levels in the general population. / Recomendaciones de vitamina D para la población general.

OBJECTIVE: To provide recommendations based on evidence on the management of vitaminD deficiency in the general population. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. CONCLUSIONS: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes.

Recomendaciones sobre el efecto de los fármacos antidiabéticos en el hueso / Recommendations on the effect of antidiabetic drugs in bone

Objetivo: Proporcionar recomendaciones sobre el efecto de las diferentes terapias antidiabéticas en la fragilidad ósea con el fin de ayudar a seleccionar el tratamiento antidiabético más adecuado, especialmente en pacientes diabéticos con elevado riesgo de fractura. Participantes: Miembros del Grupo de trabajo de Osteoporosis y Metabolismo Mineral de la SEEN. Métodos: Se empleó el sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en PubMed usando las siguientes palabras clave asociadas al nombre de cada tratamiento antidiabético: AND 'osteoporosis', 'fractures', 'bone mineral density', 'bone markers', 'calciotropic hormones'. Se revisaron artículos escritos en inglés con fecha de inclusión hasta 30 de abril de 2016. Tras la formulación de las recomendaciones, estas se discutieron de forma conjunta por el Grupo de Trabajo. Conclusiones: Este documento resume los datos acerca de los potenciales efectos de los diferentes tratamientos antidiabéticos sobre el metabolismo óseo y el riesgo de fractura (AU)

Objective: To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. Participants: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. Methods: The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND 'osteoporosis', 'fractures', 'bone mineral density', 'bone markers', 'calciotropic hormones'. Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. Conclusions: The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk (AU)