Following the results of the EMPA-REG OUTCOME trial with Empagliflozin, is it possible to speak of a class effect?

The recently published cardiovascular outcomes data for the first sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors

Real-time estimation of plasma insulin concentration from continuous glucose monitor measurements

Continuous glucose monitors can measure interstitial glucose concentration in real time for closed-loop glucose control systems, known as artificial pancreas. These control systems use an insulin feedback to maintain plasma glucose concentration within a narrow and safe range, and thus to avoid health complications. As it is not possible to measure plasma insulin concentration in real time, insulin models have been used in literature to estimate them. Nevertheless, the significant interand intra-patient variability of insulin absorption jeopardizes the accuracy of these estimations. In order to reduce these limitations, our objective is to perform a real-time estimation of plasma insulin concentration from continuous glucose monitoring (CGM). Hovorka s glucose insulin model has been incorporated in an extended Kalman filter in which different selected time-variant model parameters have been considered as extended states. The observability of the original Hovorka s model and of several extended models has been evaluated by their Lie derivatives. We have evaluated this methodology with an in-silico study with 100 patients with Type 1 diabetes during 25 h. Furthermore, it has been also validated using clinical data from 12 insulin pump patients with Type 1 diabetes who underwent four mixed meal studies. Real-time insulin estimations have been compared to plasma insulin measurements to assess performance showing the validity of the methodology here used in comparison with that formerly used for insulin models. Hence, real-time estimations for plasma insulin concentration based on subcutaneous glucose monitoring can be beneficial for increasing the efficiency of control algorithms for the artificial pancreas.This work was partially supported by the Spanish Ministerio de Ciencia e Innovacion through Grant DPI-2010-20764-C02-01 and Grant DPI-2013-46982-C2-1-R, and the European Union through FEDER fund.De Pereda Sebastián, D.; Romero Vivó, S.; Ricarte Benedito, B.; Rossetti, P.; Ampudia Blasco, FJ.; Bondía Company, J. (2015). Real-time estimation of plasma insulin concentration from continuous glucose monitor measurements. Computer Methods in Biomechanics and Biomedical Engineering. Sep:1-9. https://doi.org/10.1080/10255842.2015.1077234S19Se

Hemorragia suprarrenal bilateral poscirugía. A propósito de un caso

Bilateral adrenal haemorrhage (BAH) is a rare but serious condition, which can lead to acute adrenal insufficiency. We present a case of an BAH that occurred after an intervention for lumbar canal stenosis. It was essential for the diagnosis falling hemoglobin and imaging tests. The patient was treated with hydrocortisone substitute orally. A stress situation is a risk factor for BAH, so this condition should be considered in the differential diagnosis of postoperative complications. It is important to suspect it to begin replacement therapy as soon as possible.La hemorragia suprarrenal bilateral (HSB) es una entidad rara pero grave, que puede derivar en insuficiencia suprarrenal aguda. Se presenta un caso de una HSB que tuvo lugar tras una intervención por estenosis de canal lumbar. Fue fundamental para el diagnóstico la caída de hemoglobina y las pruebas de imagen. La paciente recibió tratamiento sustitutivo con hidrocortisona vía oral. Una situación de estrés es un factor de riesgo para HSB, por lo que esta patología debe tenerse en cuenta en el diagnóstico diferencial de las complicaciones poscirugía. Es importante sospecharla para comenzar lo antes posible el tratamiento sustitutivo

Characteristics of patients with type 2 diabetes mellitus newly treated with GLP-1 receptor agonists (CHADIG Study): a cross-sectional multicentre study in Spain

Objective: Several glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1Ra) have been made recently available in Spain for type 2 diabetes mellitus (DM2) treatment. There are no published data on the clinical and sociodemographic profile of patients initiating treatment with GLP-1Ra in Spain. Our objective was to understand these patients' characteristics in a real-world clinical practice setting. Design: Cross-sectional observational study. Setting: Spanish specialist outpatient clinics. Participants: 403 adults with DM2 initiating GLP-1Ra treatment were included. Primary and secondary outcome measures: Sociodemographic and DM2-related clinical data, including treatment at and after GLP-1Ra initiation and comorbidities, were collected. Results: Evaluable patients (n=403; 50.9% female) were included ( July 2013 to March 2014) at 24 centres by 53 specialists (47 endocrinology, 6 internal medicine), with the following profile (value±SD): age (58.3±10.4 years), diabetes duration (9.9±7 years), body mass index (BMI; 36.2±5.5) and glycated haemoglobin (HbA1c; 8.4±1.4%); 14% had HbA1c≤7%. Previous antidiabetic treatment: 53.8% only oral antidiabetic drugs (OADs), 5.2% insulin and 40% insulin and OAD; of those receiving OAD, 35% single drug, 38.2% 2 drugs and 24% 3 drugs. Concomitant to GLP-1Ra, 55.3% were only on OAD, 36.2% on insulin and OAD, and 7.2% only on insulin. Of those receiving OAD, the GLP-1Ra was mainly associated with 1 drug (65%) or 2 drugs (31.8%). GLP-1Ra are frequently added to existing antidiabetic drugs, with dipeptidyl peptidase-4 inhibitors being the OAD most frequently switched (45% receiving 1 before starting GLP-1Ra, only 2.7% receiving it concomitantly). Conclusions: In Spain, GLP-1Ra therapy is usually started in combination with OADs or OADs and insulin. These drugs are used in relatively young patients often not reaching therapeutic goals with other treatment combinations, roughly a decade after diagnosis and with a relatively high BMI. The latter could be explaine

Current barriers to initiating insulin therapy in individuals with type 2 diabetes

Insulin is an essential drug in the treatment of diabetes, often necessary for managing hyperglycemia in type 2 diabetes mellitus (T2DM). It should be considered in cases of severe hyperglycemia requiring hospitalization, after the failure of other treatments, in advanced chronic kidney disease, liver cirrhosis, post-transplant diabetes, or during pregnancy. Moreover, in specific patient subgroups, early initiation of insulin is crucial for hyperglycemia control and prevention of chronic complications. Clinical guidelines recommend initiating insulin when other treatments fail, although there are barriers that may delay its initiation. The timing of initiation depends on individual patient characteristics. Typically, insulinization starts by adding basal insulin to the patient’s existing treatment and, if necessary, progresses by gradually introducing prandial insulin. Several barriers have been identified that hinder the initiation of insulin, including fear of hypoglycemia, lack of adherence, the need for glucose monitoring, the injection method of insulin administration, social rejection associated with the stigma of injections, weight gain, a sense of therapeutic failure at initiation, lack of experience among some healthcare professionals, and the delayed and reactive positioning of insulin in recent clinical guidelines. These barriers contribute, among other factors, to therapeutic inertia in initiating and intensifying insulin treatment and to patients’ non-adherence. In this context, the development of once-weekly insulin formulations could improve initial acceptance, adherence, treatment satisfaction, and consequently, the quality of life for patients. Currently, two once-weekly basal insulins, insulin icodec and basal insulin BIF, which are in different stages of clinical development, may help. Their longer half-life translates to lower variability and reduced risk of hypoglycemia. This review addresses the need for insulin in T2DM, its positioning in clinical guidelines under specific circumstances, the current barriers to initiating and intensifying insulin treatment, and the potential role of once-weekly insulin formulations as a potential solution to facilitate timely initiation of insulinization, which would reduce therapeutic inertia and achieve better early control in people with T2DM

The Controversial Role of Vitamin D in Thyroid Cancer Prevention

Thyroid cancer is the most common endocrine malignancy and exhibits rising incidence. Annual incidence varies by sex, age, and geographical location. It has been reported that impairment of vitamin D signalling promotes thyroid cancer progression. Recent studies have shown that vitamin D, a fat-soluble vitamin that acts as both a nutrient and a hormone, may have utility in the prevention of autoimmune thyroid-related diseases. However, the precise role of vitamin D in the pathobiology of thyroid cancer is controversial. Previous studies have suggested that elevated serum vitamin D levels have a protective role in thyroid cancer. However, there is also evidence demonstrating no inverse relationship between vitamin D levels and the occurrence of thyroid cancer. Furthermore, recent data provide evidence that circulating vitamin D concentration is inversely correlated with disease aggressiveness and poor prognosis, while evidence of an association with tumour initiation remains weak. Nevertheless, a variety of data support an anti-tumorigenic role of vitamin D and its potential utility as a secondary chemopreventive agent. In this review, we highlighted recent findings regarding the association of vitamin D status with the risk of thyroid cancer, prognosis, potential mechanisms, and possible utility as a chemopreventive agent

Following the results of the EMPA-REG OUTCOME trial with Empagliflozin, is it possible to speak of a class effect?

The recently published cardiovascular outcomes data for the first sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors

Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration

[EN] Background: Continuous glucose monitoring (CGM) accuracy during hypoglycemia is suboptimal. This might be partly explained by insulin or hypoglycemia-induced changes in the plasma interstitial subcutaneous (SC) fluid glucose gradient. The aim of the present study was to assess the role of plasma insulin (PI) and hypoglycemia itself in the plasma and interstitial SC fluid glucose concentration in patients with type 1 diabetes mellitus. Methods: Eleven subjects with type 1 diabetes (age 36.59.1 years, HbA(1c) 7.90.4% [62.8 +/- 2.02mmol/mol]; mean +/- standard deviation) were evaluated under hyperinsulinemic euglycemia and hypoglycemia. Each subject underwent two randomized crossover clamps with either a primed 0.3 (low insulin) or 1mU/(kgmin) (high insulin) insulin infusion. The raw CGM signal was normalized with median preclamp values to obtain a standardized measure of the interstitial glucose (IG) concentration before statistical analysis. Results: The mean PI concentration was greater in high insulin studies (HISs) versus low insulin studies (LISs) (412.89 +/- 13.63 vs. 177.22 +/- 10.05pmol/L). During hypoglycemia, glucagon, adrenaline, free fatty acids, glycerol, and beta-OH-butyrate were higher in the LIS (P<0.0001). Likewise, the IG concentration was significantly different (P<0.0001). This was due to lower IG concentration than plasma glucose (PG) concentration during the euglycemic hyperinsulinemic phases in the HIS. In contrast, no difference was observed during hypoglycemia. This was the result of an unchanged PG/IG gradient during the entire LIS, while in the HIS, this gradient increased during the hyperinsulinemic euglycemia phase. Conclusion: Both PI levels and hypoglycemia affect the relationship between IG and PG concentration. ClinicalTrials.gov Identifier: NCT01714895.The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007/2013) under the grant agreement 252085 and FEDER funds, as well as the Spanish Ministry of Economy and Competitiveness (MINECO) under the grants DPI2013-46982-C2-1-R and DPI2016-78831-C2-1-R.V.M. is recipient of an FPU grant ref FPU13/04253. We are grateful to Mrs. Sara Correa, Fundacion INCLIVA-Hospital Clinico Universitario de Valencia, and Mrs. Geles Viguer, Hospital Clinico Universitario de Valencia, for their invaluable help in conducting the study.Moscardo-Garcia, V.; Bondía Company, J.; Ampudia-Blasco, FJ.; Fanelli, CG.; Lucidi, P.; Rossetti, P. (2018). Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration. Diabetes Technology & Therapeutics. 20(4):263-273. https://doi.org/10.1089/dia.2017.0219S26327320

Evaluating the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) for type 2 diabetes in Spain based on real-world clinical evidence.

To evaluate the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus comparator regimens for type 2 diabetes in Spain, based on real-world evidence. Clinical data were taken from the European Xultophy Treatment Retrospective Audit (EXTRA) real-world evidence study in which patients failing to meet glycaemic targets were switched to IDegLira. Baseline regimens (prior to IDegLira treatment) were categorized as: multiple daily insulin injections (MDI; 28%); glucagon-like peptide-1 (GLP-1) receptor agonists in combination with insulin (24%); basal insulin (19%); GLP-1 receptor agonists (10%); and non-injectable medications (19%). The IQVIA CORE Diabetes Model was used to project long-term outcomes for patients switching to IDegLira or continuing their baseline regimens (excluding non-injectable regimens). Costs were accounted from a Spanish National Health System perspective. Future costs and clinical benefits were discounted at 3% annually and sensitivity analyses were performed. IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy versus all four comparators. IDegLira reduced direct medical costs versus GLP-1 receptor agonists in combination with insulin, and versus GLP-1 receptor agonist therapy, and was therefore considered dominant (cost saving while improving outcomes). IDegLira was found to be cost-effective versus MDI and basal insulin with incremental cost-effectiveness ratios of EUR 3013 per quality-adjusted life-year (QALY) gained and EUR 6890 per QALY gained, respectively. Long-term projections based on real-world evidence indicated that IDegLira is likely to improve clinical outcomes and reduce costs or be cost-effective compared with other injectable regimens in people with type 2 diabetes in Spain

Evaluating the long‐term cost‐effectiveness of fixed‐ratio combination insulin degludec/liraglutide (IDegLira) for type 2 diabetes in Spain based on real‐world clinical evidence

To evaluate the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus comparator regimens for type 2 diabetes in Spain, based on real-world evidence. Clinical data were taken from the European Xultophy Treatment Retrospective Audit (EXTRA) real-world evidence study in which patients failing to meet glycaemic targets were switched to IDegLira. Baseline regimens (prior to IDegLira treatment) were categorized as: multiple daily insulin injections (MDI; 28%); glucagon-like peptide-1 (GLP-1) receptor agonists in combination with insulin (24%); basal insulin (19%); GLP-1 receptor agonists (10%); and non-injectable medications (19%). The IQVIA CORE Diabetes Model was used to project long-term outcomes for patients switching to IDegLira or continuing their baseline regimens (excluding non-injectable regimens). Costs were accounted from a Spanish National Health System perspective. Future costs and clinical benefits were discounted at 3% annually and sensitivity analyses were performed. IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy versus all four comparators. IDegLira reduced direct medical costs versus GLP-1 receptor agonists in combination with insulin, and versus GLP-1 receptor agonist therapy, and was therefore considered dominant (cost saving while improving outcomes). IDegLira was found to be cost-effective versus MDI and basal insulin with incremental cost-effectiveness ratios of EUR 3013 per quality-adjusted life-year (QALY) gained and EUR 6890 per QALY gained, respectively. Long-term projections based on real-world evidence indicated that IDegLira is likely to improve clinical outcomes and reduce costs or be cost-effective compared with other injectable regimens in people with type 2 diabetes in Spain