The Burden of Suboptimal Insulin Dosing in People with Diabetes in Spain: Barriers and Solutions from the Physician Perspective.

Background: This study aimed to determine physicians' perceptions of the extent of suboptimal insulin dosing and the barriers and solutions to optimal dosing in people with diabetes (PwD) treated with insulin. Methods: A cross-sectional online survey was conducted in four countries with primary care physicians and endocrinologists treating PwD using insulin pens, which included 53 questions on physicians' characteristics and their perceptions of the behaviors of PwD in relation to insulin dosing routines, unmet needs and potential solutions. Analyses were descriptive. Results: Of the 160 physicians (80 primary care physicians, 80 specialists) surveyed in Spain, 58.1% were male and 88.8% had been qualified to practice for more than five years. Most physicians (>65%) indicated that 0-30% of PwD missed or skipped, mistimed, or miscalculated an insulin dose in the last 30 days. Common reasons for these actions were that PwD forgot, were out of their normal routine, were too busy or distracted, or were unsure of how much insulin to take. To optimize insulin dosing, over 75% of physicians considered it very helpful for PwD to have real-time insulin dosing calculation guidance, mobile app reminders, a device automatically recording glucose measurements and/or insulin, having insulin and glucose data in one place, and having the time for more meaningful conversations about insulin dosing routines. Conclusion: According to physicians' perspectives, suboptimal insulin dosing remains common among PwD. This survey highlights the need for integrated and automated insulin dosing support to manage the complexity of insulin treatment, improve communications between PwD and physicians, and ultimately improve outcomes for PwD.

Descriptive study of a clinical and educational telemedicine intervention in patients with diabetes receiving glargine 300 U/ml (Toujeo) in Spain: results of the T-Coach programme.

Background: Diabetes is one of the most prevalent chronic diseases worldwide, and innovative patient support programmes can help and inform patients about their disease and improve their quality of life. The purpose of this study was to evaluate the effect of the T-Coach programme in terms of improvement of disease knowledge, self-management and adherence to treatment in a real-world setting in Spain between July 2016 and October 2018. Methods: We analyzed data from the T-Coach programme, a telephone platform that gives support to patients with type 2 diabetes mellitus treated with insulin glargine 300 U/ml (Gla-300). Support was provided by diabetes care nurses. Patients followed their treatment and aimed to achieve fasting blood glucose targets through diabetes education. Results: A total of 479 patients were included in the programme. The mean (SD) dose of Gla-300 was 28.5 (16.3) U at baseline and 31.8 (16.1) U, 31.4 (16.4) U and 32.2 (16.3) U, respectively, at 3, 6 and 12 months. A satisfaction survey was completed by 240 (50.1%) patients, who, on average, were very highly satisfied with the programme, general assistance provided, recommendations received, and calls from nurses. Conclusions: T-Coach could be an effective tool to help patients achieve their optimal dose of Gla-300 insulin and manage their blood glucose levels. It could also act as an effective support for diabetes education.

Accuracy and Potential Interferences of Continuous Glucose Monitoring Sensors in the Hospital.

For years, the standard of care for monitoring dysglycemia in hospitalized patients was capillary blood glucose (CBG) testing with point-of-care glucose meters. Recently, there has been a revolution in novel factory-calibrated continuous glucose monitoring (CGM) systems. Newer CGMs are smaller and less expensive, have improved accuracy and longer wear time, and do not require fingerstick CBG for calibration, resulting in increased utilization in ambulatory settings. Consequently, hospitals have noticed increased usability of CGMs among hospitalized patients and expect a progressive continued increase. During the COVID-19 pandemic, there was a critical need for innovative approaches to glycemic monitoring, with several pilot implementation projects using CGM in the intensive care unit and non-intensive care unit settings, further boosting the evidence in this area. Hence, recent guidelines have provided recommendations for the use of CGM in specific hospital scenarios and highlighted the potential of CGM to overcome CBG limitations for glucose monitoring in the inpatient setting. In this review, we provide the following: 1) an up-to-date review of the accuracy of the newer CGMs in hospitalized patients, 2) a discussion of standards for CGM accuracy metrics, 3) a contemporary overview of potential interferences that may cause inaccuracies or poor CGM performance, and 4) required steps for full regulatory approval of CGMs in the hospital and future research steps to advance the field forward.

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.

Expert Consensus on Morphofunctional Assessment in Disease-Related Malnutrition. Grade Review and Delphi Study.

Disease-related malnutrition (DRM) affects approximately a third of hospitalized patients and is associated with an increased risk of morbimortality. However, DRM is often underdiagnosed and undertreated. Our aim is to evaluate the prognostic value of morphofunctional tools and tests for nutritional assessment in clinical practice. A systematic literature review was conducted to identify studies relating to the morphofunctional assessment of nutritional status and mortality or complications. Evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) method. Twelve GRADE recommendations were made and divided into seven topics: food intake and nutrient assimilation, anthropometry, biochemical analysis, hand grip strength, phase angle, muscle imaging, and functional status and quality of life. From these recommendations, 37 statements were developed and scored in a two-survey Delphi method by 183 experts. A consensus was reached on accepting 26/37 statements. Surveys had high internal consistency and high inter-rater reliability. In conclusion, evidence-based recommendations were made on the prognostic value of morphofunctional assessment tools and tests to assess malnutrition, most of which were found to be feasible in routine clinical practice, according to expert opinions.

Changing trends in transgender demographics and morbidity: baseline data from a Spanish cohort.

The number of transgender people who request hormone treatment is increasing worldwide. We obtained base clinical and demographic information from transgender people treated at a specialised clinic in Spain (n =484) and studied changes over time. Transgender women treated in 2009-14 were older than those treated in 2015-20 (29years vs 17years), had a lower academic level and had higher anxiolytics consumption. Transgender men treated in 2009-14 were older than those treated later (27years vs 17years) and had a lower academic level. These trends reflect favourable changes in how the transgender population is treated by society and health services.

Effectiveness and Safety of an Advanced Hybrid Closed-Loop System in Adolescents and Adults with Type 1 Diabetes Previously Treated with Continuous Subcutaneous Insulin Infusion and Flash Glucose Monitoring.

This study aimed to evaluate the effectiveness and safety of the MiniMed™ 780G advanced hybrid closed-loop (AHCL) system in people with type 1 diabetes (T1D) previously treated with continuous subcutaneous insulin infusion combined with flash glucose monitoring in a real-life setting. A total of 47 subjects (mean age 41 ± 13.6 years, 60% females, diabetes duration 28 ± 11 years) were included and switched to an AHCL system. Baseline and 6-month data were analyzed. Time in range 70-180 mg/dL increased from 65.3% at baseline to 73.8% at 6 months. Time in hyperglycemia >180 mg/dL decreased from 26.6% to 19.3%. Time in hypoglycemia <70 mg/dL decreased from 4.6% to 2.3%. The coefficient of variation also decreased from 36% to 31.6%. No episodes of severe hypoglycemia, diabetes ketoacidosis, or diabetes-related hospital admissions occurred. In conclusion, the MiniMed 780G AHCL system enables the safe achievement of recommended glycemic targets in people with T1D after 6 months of use.

Expert Recommendations for Using Time-in-Range and Other Continuous Glucose Monitoring Metrics to Achieve Patient-Centered Glycemic Control in People With Diabetes.

New metrics for assessing glycemic control beyond HbA1c have recently emerged due to the increasing use of continuous glucose monitoring (CGM) in diabetes clinical practice. Among them, time in range (TIR) has appeared as a simple and intuitive metric that correlates inversely with HbA1c and has also been newly linked to the risk of long-term diabetes complications. The International Consensus on Time in Range established a series of target glucose ranges (TIR, time below range and time above range) and recommendations for time spent within these ranges for different diabetes populations. These parameters should be evaluated together with the ambulatory glucose profile (AGP). Using standardized visual reporting may help people with diabetes and healthcare professionals in the evaluation of glucose control in frequent clinical situations. The objective of the present review is to provide practical insights to quick interpretation of patient-centered metrics based on flash glucose monitoring data, as well as showing some visual examples of common clinical situations and giving practical recommendations for their management.

Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice.

Objectives: The aim of this study is to investigate in depth diabetes mellitus associated with immune checkpoint inhibitors (DM-ICIs) by analysing a case series. We also evaluated the clinical impact of flash glucose monitoring (FGM) systems in the management of this entity. Methods: We conducted an observational cohort study of DM-ICIs diagnosed in two hospitals in Seville (Spain). Patients with a new diagnosis of diabetes mellitus (DM) or with sudden worsening of preexisting DM after starting treatment with ICIs, with a random 5 hour-postprandial C-peptide value of <0.6 nmol/L and without possibility of subsequent withdrawal of insulin treatment, were included. Results: A total of 7 cases were identified, mostly males (n = 6; 85.7%), with a mean age of 64.9 years. The mean glycated hemoglobin (HbA1c) upon diagnosis was 8.1%, with diabetic ketoacidosis (DKA) observed in 6 cases (85.7%). Subcutaneous flash glucose monitoring (FGM) systems were used in six cases, with a mean follow-up period of 42.7 weeks. During the first 90 days of use, mean average glucose was 167.5 mg/dL, with a coefficient of variation (CV) of 34.6%. The mean time in the range 70-180 mg/dL (TIR) was 59.7%, with a mean time above range (TAR) 181-250 mg/dL of 27.8% and a mean TAR > 250 mg/dL of 10.2%. The mean time below range (TBR) 54-69 mg/dL was 2%, while the mean TBR < 54 mg/dL was 0.3%. The mean glucose management indicator (GMI) was 7.3%. No significant differences were observed in FGM values for the following 90 days of follow-up. A progressive improvement in all parameters of glycaemic control was observed between the first month of FGM use and the sixth month of FGM use. Of note, there was a decrease in mean CV (40.6% to 34.1%, p = 0.25), mean TAR 181-250 (30.3% to 26%, p = 0.49), mean TAR > 250 mg/dL (16.3% to 7.7%, p = 0.09), mean TBR 54-69 mg/dL (5.2% to 2%, p = 0.16), and mean TBR < 54 mg/dL (1.8% to 0.2%, p = 0.31), along with an increase in mean values of TIR 70-180 mg/dL (46.5% to 60.5%, p = 0.09). The lack of statistical significance in the differences observed in the mean FGM values over the follow-up period may be related to the small sample size. Conclusion: DM-ICI is recognised by a state of sudden-onset insulinopenia, often associated with DKA. The use of FGM systems may be a valid option for the effective management of DM-ICIs and for the prevention of severe hyperglycaemic and hypoglycaemic episodes in this condition.

Once-Weekly Semaglutide Use in Patients with Type 2 Diabetes: Results from the SURE Spain Multicentre, Prospective, Observational Study.

Type 2 diabetes (T2D) is a complex disease for which an individualised treatment approach is recommended. Once-weekly (OW) semaglutide is a glucagon-like peptide-1 receptor agonist approved for the treatment of insufficiently controlled T2D. The aim of this study was to investigate the use of OW semaglutide in adults with T2D in a real-world context. SURE Spain, from the 10-country SURE programme, was a prospective, multicentre, open-label, observational study, approximately 30 weeks in duration. Adults with T2D and ≥1 documented HbA1c value ≤12 weeks before semaglutide initiation were enrolled. Change in HbA1c from baseline to end of study (EOS) was the primary endpoint, with change in body weight (BW), waist circumference, and patient-reported outcomes as secondary endpoints. Of the 227 patients initiating semaglutide, 196 (86.3%) completed the study on-treatment with semaglutide. The estimated mean changes in HbA1c and body weight between baseline and EOS were -1.3%-points (95% confidence interval (CI) -1.51;-1.18%-points) and -5.7 kg (95% CI -6.36;-4.98 kg). No new safety concerns were identified. Therefore, in routine clinical practice in Spain, OW semaglutide was shown to be associated with statistically significant and clinically relevant reductions in HbA1c and BW in adults with T2D.

Effectiveness and safety of dapagliflozin in real-life patients: data from the DAPA-RWE Spanish multicentre study.

BACKGROUND: This study aims to evaluate dapagliflozin in patients with type 2 diabetes (T2D) in clinical practice in Spain. METHODS: This is a retrospective study including adults with T2D under stable antidiabetic therapy, with either dapagliflozin or sitagliptin ≥6 months, before inclusion. Data about the effectiveness and safety of dapagliflozin are presented. RESULTS: A total of 594 patients (61.8±9.9 years, 21.7% cardiovascular disease) were included. After 6 months, HbA1c, weight, blood pressure, urine albumin-to-creatinine ratio and uric acid significantly decreased (1.63%, 2.88 kg, 4.82/2.70 mmHg, -17.38 mg/g and -0.30 mg/dL, respectively), whereas glomerular filtration rate and haematocrit significantly increased (3.72 mL/min/1.73 m2 and 1.8%, respectively). No cases of hypoglycaemia, diabetic ketoacidosis, Fournier gangrene, fractures or amputations were reported. CONCLUSION: Thus, dapagliflozin provides a comprehensive cardiometabolic protection in patients with T2D.

Beyond the Glycaemic Control of Dapagliflozin: Microangiopathy and Non-classical Complications.

Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor (SGLT2i) indicated for the treatment of type 2 diabetes mellitus (T2DM), heart failure (HF) with reduced ejection fraction (EF) and chronic kidney disease (CKD). In monotherapy or as an additive therapy, dapagliflozin aids glycaemic control, is associated with reductions in blood pressure and weight, and promotes a favourable lipid profile. In this review, we address the impact of dapagliflozin on cardiovascular risk factors and common microangiopathic complications such as kidney disease and retinopathy in patients with T2DM. Furthermore, we evaluate its potential beneficial effects on other less frequent complications of diabetes, such as macular oedema, cognitive impairment, non-alcoholic fatty liver disease and respiratory disorders during sleep. Moreover, the underuse of SGLT2i in clinical practice is discussed. Our goal is to help translate this evidence into clinical practice.

Description of a Cohort of Type 1 Diabetes Patients: Analysis of Comorbidities, Prevalence of Complications and Risk of Hypoglycemia.

BACKGROUND: Despite major medical advances, Type 1 Diabetes (T1D) patients still have greater morbimortality than the general population. Our aim was to describe our cohort of T1D patients and identify potential risk factors susceptible to prevention strategies. METHODS: Cross-sectional, observational study, including T1D patients treated at our center, from 1 March 2017 to 31 March 2020. INCLUSION CRITERIA: T1D, age > 14 years and signed informed consent. EXCLUSION CRITERIA: diabetes other than T1D, age < 14 years and/or refusal to participate. RESULTS: Study population n = 2181 (49.8% females, median age at enrollment 41 years, median HbA1c 7.7%; 38.24% had at least one comorbidity). Roughly 7.45% had severe hypoglycemia (SH) within the prior year. Macro/microvascular complications were present in 42.09% (5.83% and 41.14%, respectively). The most frequent microvascular complication was diabetic retinopathy (38.02%), and coronary disease (3.21%) was the most frequent macrovascular complication. The risk of complications was higher in males than in females, mainly macrovascular. Patients with SH had a higher risk of complications (OR 1.42; 1.43 in males versus 1.42 in females). CONCLUSIONS: Our T1D population is similar to other T1D populations. We should minimize the risk of SH, and male patients should perhaps be treated more aggressively regarding cardiovascular risk factors.

COVID-19 and Diabetes.

Diabetes mellitus (DM) is one of the most common comorbid conditions in persons with COVID-19 and a risk factor for poor prognosis. The reasons why COVID-19 is more severe in persons with DM are currently unknown although the scarce data available on patients with DM hospitalized because of COVID-19 show that glycemic control is inadequate. The fact that patients with COVID-19 are usually cared for by health professionals with limited experience in the management of diabetes and the need to prevent exposure to the virus may also be obstacles to glycemic control in patients with COVID-19. Effective clinical care should consider various aspects, including screening for the disease in at-risk persons, education, and monitoring of control and complications. We examine the effect of COVID-19 on DM in terms of glycemic control and the restrictions arising from the pandemic and assess management of diabetes and drug therapy in various scenarios, taking into account factors such as physical exercise, diet, blood glucose monitoring, and pharmacological treatment. Specific attention is given to patients who have been admitted to hospital and critically ill patients. Finally, we consider the role of telemedicine in the management of DM patients with COVID-19 during the pandemic and in the future.

The Challenge of Sustainable Access to Telemonitoring Tools for People with Diabetes in Europe: Lessons from COVID-19 and Beyond.

Telemedicine in diabetes care has been evolving over several years, particularly since the advent of cloud-connected technologies for diabetes management, such as glucose monitoring devices, including continuous glucose monitoring (CGM) systems, that facilitate sharing of glucose data between people with diabetes and their healthcare professionals in near-real time. Extreme social distancing and shielding in place for vulnerable patients during the COVID-19 pandemic has created both the challenge and the opportunity to provide care at a distance on a large scale. Available evidence suggests that glucose control has in fact improved during this period for people with diabetes who are able to use CGM devices for remote glucose monitoring. The development of telemedicine as part of the standard of care in diabetes faces significant challenges in the European context, particularly in terms of providing consistent and effective care at a distance to large populations of patients while using robust systems that can be supported by large regional and national healthcare services. These challenges include a fragmented approach to healthcare technology assessment and reimbursement, lack of eHealth education and literacy, particularly amongst healthcare professionals, lack of data integration, as well as concerns about electronic health records, patient consent and privacy. Here we review the benefits of and challenges to wider application of telemedicine and telemonitoring in the post-pandemic future, with the aim to ensure that the value of these eHealth services is provided to patients, healthcare providers and health systems.

Time-in-range for monitoring glucose control: Is it time for a change?

The HbA1c value has been the gold standard for evaluating glucose control for decades. However, it has limitations such as the lack of information on glycemic variability or the risk of hypoglycemia. The increasing use of continuous glucose monitoring has provided patients and healthcare professionals with a range of useful metrics for the management of diabetes. Among them, Time in Range (TIR) is a simple and intuitive metric that gives information regarding the quality of glucose control. It is defined as the time spent in an individual's target glucose range. TIR is strongly correlated with HbA1c, and it has been linked to the risk of developing microvascular and macrovascular complications. The International Consensus on Time in Range has recently set targets for different diabetes populations. For the majority of people with type 1 or type 2 diabetes, a TIR (70-180 mg/dL or 3.9-10.0 mmol/L) of >70%, a time below range (TBR) <70 mg/dL (<3.9 mmol/L) of <4% and a TBR <54 (<3.0 mmol/L) of <1% are recommended. In this review, we address the latest evidence for the use of TIR as an essential parameter in the management of diabetes.

DAPA-RWE: a retrospective multicenter study comparing dapagliflozin and sitagliptin in patients with Type 2 diabetes treated under routine clinical practice in Spain.

Background: Weight reduction and glycemic control are key goals during Type 2 diabetes management. However, there are few country-specific, real-world data on cotransporter 2 inhibitors. Materials & methods: DAPA-RWE was a retrospective, multicenter study comparing the efficacy of dapagliflozin versus sitagliptin in Type 2 diabetes patients in Spain. Results: The study population comprised 1046 patients (594 with dapagliflozin, 452 with sitagliptin). Age was 61.8 ± 10.0 and 66.2 ± 11.4 years and glycosylated hemoglobin (HbA1c) 8.9 and 8.8%, respectively. The main end point (reduction in weight and HbA1c) was reached by 24.4 and 56.1% of patients, respectively; p < 0.05. This was confirmed with a propensity score matching analysis balanced for obesity-related variables at baseline. Conclusion: DAPA-RWE confirmed dapagliflozin to be more effective than sitagliptin in reducing HbA1c and weight.

Targeted inhibition of allergen-induced histamine production by neutrophils.

Histamine is a critical inflammatory mediator in allergic diseases. We showed in a previous work that neutrophils from allergic patients produce histamine in response to allergens to which the patients were sensitized. Here, we investigate the molecular mechanisms involved in this process using peripheral blood neutrophils. We challenged these cells in vitro with allergens and analyzed histamine release in the culture supernatants. We also explored the effect of common therapeutic drugs that ameliorate allergic symptoms, as well as allergen-specific immunotherapy. Additionally, we examined the expression of histidine decarboxylase and diamine oxidase, critical enzymes in the metabolism of histamine, under allergen challenge. We show that allergen-induced histamine release is dependent on the activation of the phosphoinositide 3-kinase, mitogen-activated protein kinase p38, and extracellular signal-regulated kinase 1/2 signaling pathways. We also found a contribution of the phosphatase calcineurin to lesser extent. Anti-histamines, glucocorticoids, anti-M3-muscarinic receptor antagonists, and mainly ß2 -receptor agonists abolished the allergen-dependent histamine release. Interestingly, allergen-specific immunotherapy canceled the histamine release through the downregulation of histidine decarboxylase expression. Our observations describe novel molecular mechanisms involved in the allergen-dependent histamine release by human neutrophils and provide new targets to inhibit histamine production.

Inpatient Hyperglycemia Management and COVID-19.

Diabetes is one of the most common comorbidities in hospitalized patients with coronavirus disease 2019 (COVID-19). Inpatient hyperglycemia during this pandemic has been associated with worse outcomes, so it is mandatory to implement effective glycemic control treatment approaches for inpatients with COVID-19. The shortage of personal protective equipment, the need to prevent staff exposure, or the fact that many of the healthcare professionals might be relatively unfamiliar with the management of hyperglycemia may lead to worse glycemic control and, consequently, a worse prognosis. In order to reduce these barriers, we intend to adapt established recommendations to manage hyperglycemia during this pandemic in critical and noncritical care settings.