Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Connected Insulin Pens and Caps: An Expert's Recommendation from the Area of Diabetes of the Spanish Endocrinology and Nutrition Society (SEEN).

Undoubtedly, technological advances have revolutionised diabetes management in recent years. The development of advanced closed hybrid loop insulin pumps or continuous glucose monitoring (CGM) systems, among others, have increased the quality of life and improved glycaemic control of people with diabetes. However, only some patients have access to such technology, and only some want to use it. CGM has become much more widespread, but in terms of insulin delivery, most people with type 1 diabetes (T1D) and almost all people with type 2 diabetes (T2D) on insulin therapy are treated with multiple-dose insulin injections (MDI) rather than an insulin pump. For these patients, using connected insulin pens or caps has shown benefits in reducing missed insulin injections and promoting correct administration over time. In addition, using these devices improves the quality of life and user satisfaction. The integration of insulin injection and CGM data facilitates both users and the healthcare team to analyse glucose control and implement appropriate therapeutic changes, reducing therapeutic inertia. This expert's recommendation reviews the characteristics of the devices marketed or in the process of being marketed and their available scientific evidence. Finally, it suggests the profile of users and professionals who would benefit most, the barriers to its generalisation and the changes in the care model that implementing these devices can bring with it.

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.

Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients.

BACKGROUND: Nowadays, 65-80% of pheochromocytoma and paraganglioma (PPGL) cases are explained by germline or somatic mutations in one of 22 genes. Several genetic testing algorithms have been proposed, but they usually exclude sporadic-PPGLs (S-PPGLs) and none include somatic testing. We aimed to genetically characterise S-PPGL cases and propose an evidence-based algorithm for genetic testing, prioritising DNA source. METHODS: The study included 329 probands fitting three criteria: single PPGL, no syndromic and no PPGL family history. Germline DNA was tested for point mutations in RET and for both point mutation and gross deletions in VHL, the SDH genes, TMEM127, MAX and FH. 99 tumours from patients negative for germline screening were available and tested for RET, VHL, HRAS, EPAS1, MAX and SDHB. RESULTS: Germline mutations were found in 46 (14.0%) patients, being more prevalent in paragangliomas (PGLs) (28.7%) than in pheochromocytomas (PCCs) (4.5%) (p=6.62×10(-10)). Somatic mutations were found in 43% of those tested, being more prevalent in PCCs (48.5%) than in PGLs (32.3%) (p=0.13). A quarter of S-PPGLs had a somatic mutation, regardless of age at presentation. Head and neck PGLs (HN-PGLs) and thoracic-PGLs (T-PGLs) more commonly had germline mutations (p=2.0×10(-4) and p=0.027, respectively). Five of the 29 metastatic cases harboured a somatic mutation, one in HRAS. CONCLUSIONS: We recommend prioritising testing for germline mutations in patients with HN-PGLs and T-PGLs, and for somatic mutations in those with PCC. Biochemical secretion and SDHB-immunohistochemistry should guide genetic screening in abdominal-PGLs. Paediatric and metastatic cases should not be excluded from somatic screening.

Impacto económico y sanitario de las hipoglucemias nocturnas asociadas al tratamiento de la diabetes mellitus tipo 2 con insulina glargina o insulina NPH / Economic impact of nocturnal hypoglycemia associated with the treatment of type 2 diabetes with insulin glargine or NPH insulin

OBJETIVO: Estimar el impacto sanitario y económico en España de las hipoglucemias nocturnas ligadas al tratamiento de la diabetes tipo2 (DM2) de insulina glargina (IG) o insulina NPH, administradas al acostarse. MÉTODOS: Se calcularon el coste actual de las hipoglucemias nocturnas graves y sintomáticas y los ahorros que se producirían para el Sistema Nacional de Salud (SNS) por la reducción de estas en el caso de que el tratamiento con NPH fuese parcialmente sustituido por IG. El uso de recursos sanitarios en la práctica clínica y el coste anual de las hipoglucemias se estimó mediante un panel de expertos clínicos de atención primaria y hospitalaria. La reducción en la tasa de hipoglucemias con IG frente a NPH se obtuvo de un metaanálisis publicado. RESULTADOS: Coste anual de las hipoglucemias: 1.121,98 (Euro) (518,90-1.990,19 (Euro)) en el caso de las graves, 473,85 (Euro) (243,22-733,82 (Euro)) las sintomáticas con niveles de glucosa < 36 mg/dl, y 295,83 (Euro) (149,63-406,59 (Euro)) con niveles < 70 mg/dl. Para una sustitución de NPH por IG del 4, del 7, del 10 y y del 11% en 4 años, en España se evitarían 6.772 episodios de hipoglucemia (487, 756 y 5.529, respectivamente, según su gravedad). El ahorro monetario para el SNS de este beneficio sanitario ascendería a 1,6 millones de euros (entre 829.000(Euro) y 2,5 millones de euros). CONCLUSIONES: El tratamiento al acostarse de la DM2 con IG (en comparación con NPH) podría reducir la tasa de hipoglucemias nocturnas y sus costes asociados para el SNS

OBJECTIVE: To estimate the health and economic impact in Spain of nocturnal hypoglycemia linked to the treatment of type2 diabetes with insulin glargine (IG) or NPH insulin, both administered before bedtime. METHODS: The current cost of severe and symptomatic nocturnal hypoglycemia and the savings for the National Health Service (NHS) as a result of the reduction in the rate of occurrence of nocturnal hypoglycemia was calculated in the hypothetical case that the treatment with NPH was partially replace by IG. The use of health resources in clinical practice and the annual cost of hypoglycemic events were estimated by an expert panel of primary care and hospital clinicians. The reduction in the rate of hypoglycemic events with IG versus NPH was obtained from a published meta-analysis. RESULTS: The annual cost of hypoglycemia was estimated at 1,121.98 (Euro) (518.90-1,990.19 (Euro)) in the case of severe hypoglycemia, 473.85 (Euro) (243.22-733.82 (Euro)) in case of symptomatic hypoglycemia with plasma glucose levels < 36 mg/dl, and 295.83 (Euro) (149.63-406.59 (Euro)) with levels < 70 mg/dl. For an estimated replacement of NPH by IG of 4%, 7%, 10%, and 11% in four years, in Spain 6,772 hypoglycemic events would be avoided (487, 756, and 5,529, respectively, depending on its severity). The savings for the NHS would correspond to 1.6 million (Euro) (ranging from (Euro) 829,000 to 2.5 million(Euro)). CONCLUSIONS: The treatment of diabetes type2 with IG (vs. NPH), both administered at bedtime, could reduce the rate of nocturnal hypoglycemia and the associated costs for the NHS

Diabetes mellitus y síndrome diarreico en mujer de edad avanzada / Diabetes mellitus and diarrhea in an elderly woman

Entre un 5 y un 10% de los adultos diagnosticados inicialmente de diabetes mellitus tipo 2 (DM2) en realidad tienen diabetes autoinmunitaria de inicio en la edad adulta. Dado el elevado número de pacientes con diagnóstico de DM2, la entidad que ha sido denominada por algunos autores como LADA (latent autoimmune diabetes in adults) podría suponer la mitad de todos los diabéticos con DM1A. Presentamos el caso de una mujer de 75 años de edad, con antecedentes de diabetes mellitus con labilidad en el control glucémico y síndrome de colon irritable, que finalmente fue diagnosticada de diabetes autoinmunitaria con enfermedad celíaca concomitante (AU)

Between 5 and 10% of adults initially diagnosed with type 2 diabetes mellitus (DM) actually have adult-onset autoimmune diabetes. Given the large number of patients diagnosed with DM type 2, the entity called latent autoimmune diabetes in adults (LADA) by some authors could represent half of all diabetics with type 1A diabetes. We report the case of a 75-year-old woman, with a history of brittle diabetes and irritable bowel syndrome, who was finally diagnosed with autoimmune diabetes and celiac disease (AU)

Diabetes and diarrhea in an elderly woman.

Between 5 and 10% of adults initially diagnosed with type 2 diabetes mellitus.(DM) actually have adult-onset autoimmune diabetes. Given the large number of patients diagnosed with DM type 2, the entity called latent autoimmune diabetes in adults (LADA) by some authors could represent half of all diabetics with type 1A diabetes. We report the case of a 75-year-old woman, with a history of brittle diabetes and irritable bowel syndrome, who was finally diagnosed with autoimmune diabetes and celiac disease.

Transformación anaplásica tardía de dos bocios multinodulares / Late anaplastic transformation of two multinodular

El carcinoma anaplásico de tiroides es un tumor muy agresivo con una supervivencia media de 3 a 7 meses. El 50% se desarrolla a partir de bocios multinodulares de larga evolución y el 20-30% coexiste con carcinomas diferenciados. Presentamos los casos de 2 pacientes ancianas con bocio multinodular en seguimiento durante años que sufrieron, de forma brusca, una transformación anaplásica. Ante esta posibilidad, y dado el pronóstico infausto de este tipo de carcinoma, se aconseja realizar un seguimiento de por vida en estos pacientes

Anaplastic thyroid carcinoma is a highly aggressive tumor with a mean survival of 3-7 months. Up to one half of patients have long-standing multinodular goiter and 20-30% have a coexisting differentiated carcinoma. We present two elderly patients under follow-up for multinodular goiters that suddenly showed anaplastic transformation many years after the initial diagnosis. Given the possibility of malignant transformation and the fatal prognosis of this carcinoma, life-long surveillance of these patients is advisable