Diabetes tipo 1 en pediatría durante la pandemia por COVID-19: tiempo de evolución de síntomas y formas de presentación en un centro de referencia / Type 1 diabetes in pediatrics during the COVID-19 pandemic: Time from symptom onset and forms of presentation at a referral hospital

Introducción. La pandemia por COVID-19 afectó la atención de pacientes con diabetes mellitus tipo 1 (DM1). Además, se reportó un aumento de cetoacidosis diabética (CAD) como forma de diagnóstico. Objetivos. Evaluar si durante la pandemia por COVID-19 se modificaron el tiempo de evolución de síntomas, las causas de hospitalización por DM1 y la proporción de formas graves, y describir la infección por SARS-CoV-2 en estos pacientes. Población y métodos. Estudio transversal que incluyó pacientes menores de 19 años hospitalizados por DM1 en un centro pediátrico de referencia de marzo de 2018 a agosto de 2019 (prepandemia) y de marzo de 2020 a agosto de 2021 (pandemia). Resultados. Se analizaron 231 internaciones, 135 prepandemia y 96 en pandemia. Los pacientes con debut diabético presentaron menor tiempo de evolución de síntomas en pandemia que en prepandemia (18,8 ± 10,2 vs. 52,1 ±12,1 días, respectivamente; p <0,001). Las hospitalizaciones por todas las formas de debut diabético y el debut con CAD fueron más frecuentes en pandemia que en prepandemia (59,4 % vs. 39,3 %; OR 2,3; IC95% 1,3-3,8; p = 0,003); y (40,6 % vs. 20,7 %; OR 2,6; IC95% 1,4-5,2; p = 0,006) respectivamente. La proporción de formas graves de CAD no se modificó entre ambos períodos (48,1 % vs. 59,9 %; p = 0,3). Solo 6 pacientes presentaron infección por SARS-CoV-2; 3 fueron formas graves. Conclusión. Durante la pandemia, disminuyó el tiempo de evolución de síntomas y aumentó la frecuencia de hospitalizaciones por debut de DM1, con mayor proporción de CAD. No se modificó la proporción de formas graves de CAD

Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported. Objectives. To assess whether there were changes in the time from symptom onset, the causes of hospitalization due to DM1, and the proportion of severe forms, and to describe SARS-CoV-2 infection in these patients. Population and methods. Cross-sectional study in patients younger than 19 years hospitalized due to DM1 from March 2018 to August 2019 (pre-pandemic) and from March 2020 to August 2021 (pandemic). Results. The assessment included 135 hospitalizations in the pre-pandemic period and 96 during the pandemic. The time from symptom onset during the pandemic in those with debutof diabetes was shorter than in the pre-pandemic period (18.8 ± 10.2 versus 52.1 ± 12.1 days, respectively; p < 0.001). Hospitalizations due to all forms of diabetes debut and debut with DKA were more common during the pandemic than before it (59.4% versus 39.3%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3­3.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.4­5.2; p = 0.006, respectively). Severe forms of DKA did not change between both periods (48.1% versus 59.9%; p = 0.3). Only 6 patients developed SARS-CoV-2 infection; 3 were severe. Conclusion. During the pandemic, the time from symptom onset decreased and the frequency of hospitalizations due to debut of DM1 increased. The proportion of severe forms of DKA did not change.

Combined hyperglycemic crises in adult patients already exist in Latin America / Las crisis hiperglucémicas combinadas en pacientes adultos ya existen en Latinoamérica

INTRODUCTION: Diabetes mellitus is one of the most common diseases worldwide, with a high morbidity and mortality rate. Its prevalence has been increasing, as well as its acute complications, such as hyperglycemic crises. Hyperglycemic crises can present with combined features of diabetic ketoacidosis and hyperosmolar state. However, their implications are not fully understood. OBJECTIVE: To describe the characteristics, outcomes, and complications of the diabetic population with hyperglycemic crises and to value the combined state in the Latin American population. MATERIALS AND METHODS: Retrospective observational study of all hyperglycemic crises treated in the intensive care unit of the Fundación Valle del Lili between January 1, 2015, and December 31, 2020. Descriptive analysis and prevalence ratio estimation for deaths were performed using the robust Poisson regression method. RESULTS: There were 317 patients with confirmed hyperglycemic crises, 43 (13.56%) with diabetic ketoacidosis, 9 (2.83%) in hyperosmolar state, and 265 (83.59%) with combined diabetic ketoacidosis and hyperosmolar state. Infection was the most frequent triggering cause (52.52%). Fatalities due to ketoacidosis occurred in four patients (9.30%) and combined diabetic ketoacidosis/hyperosmolar state in 22 patients (8.30%); no patient had a hyperosmolar state. Mechanical ventilation was associated with death occurrence (adjusted PR = 1.15; 95 % CI 95 = 1.06 - 1.24). CONCLUSIONS: The combined state was the most prevalent presentation of the hyperglycemic crisis, with a mortality rate similar to diabetic ketoacidosis. Invasive mechanical ventilation was associated with a higher occurrence of death.

Introducción. La diabetes mellitus es una de las enfermedades más frecuentes en todo el mundo, con una tasa elevada de morbimortalidad. Su prevalencia ha ido en aumento y, también, sus complicaciones agudas, como las crisis hiperglucémicas. Las crisis hiperglucémicas pueden presentar características combinadas de cetoacidosis diabética y estado hiperosmolar. Aún no se conocen completamente sus implicaciones. Objetivo. Describir las características, los resultados y las complicaciones de la población diabética con crisis hiperglucémicas, y valorar el estado mixto en la población latinoamericana. Materiales y métodos. Se trata de un estudio observacional retrospectivo de pacientes con crisis hiperglucémicas atendidos en la unidad de cuidados intensivos de la Fundación Valle del Lili, entre el 1º de enero de 2015 y el 31 de diciembre de 2020. Se realizó un análisis descriptivo y se estimó la razón de prevalencia para muerte mediante el método de regresión de Poisson. Resultados. Se incluyeron 317 pacientes con crisis hiperglucémica confirmada, 43 (13,56 %) con cetoacidosis diabética, 9 (2,83 %) en estado hiperosmolar y 265 (83,59 %) en estado mixto. La causa desencadenante más frecuente fue la infección (52,52 %). Cuatro pacientes fallecieron por cetoacidosis (9,30 %), 22 (8,30 %), por un estado mixto; ninguno se encontraba en estado hiperosmolar. La asistencia respiratoria mecánica se asoció con la muerte (razón de prevalencia ajustada = 1,15; IC95%: 1,06-1,24). Conclusiones. El estado combinado fue la presentación más prevalente de la crisis hiperglucémica, con una tasa de mortalidad similar a la de la cetoacidosis diabética, y la asistencia respiratoria mecánica invasiva se asoció con una mayor ocurrencia de muerte.

Diabetic Ketoacidosis Induces Tau Hyperphosphorylation in Rat Brain.

Background: Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer's disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear. Objective: Our objective was to understand how DKA can promote neurodegeneration in AD. Methods: We induced DKA in rats through intraperitoneal injection of streptozotocin, followed by starvation for 48 hours and investigated AD-related brain alterations focusing on tau phosphorylation. Results: We found that DKA induced hyperphosphorylation of tau protein at multiple sites associated with AD. Studies of tau kinases and phosphatases suggest that the DKA-induced hyperphosphorylation of tau was mainly mediated through activation of c-Jun N-terminal kinase and downregulation of protein phosphatase 2A. Disruption of the mTOR-AKT (the mechanistic target of rapamycin-protein kinase B) signaling pathway and increased levels of synaptic proteins were also observed in the brains of rats with DKA. Conclusions: These results shed some light on the mechanisms by which DKA may increase the risk for AD.

Fluids in the treatment of diabetic ketoacidosis in children: A systematic review.

AIM: To determine the comparative effectiveness of fluid schemes for children with diabetic ketoacidosis (DKA). METHODS: We conducted a systematic review with an attempt to conduct network meta-analysis (NMA). We searched MEDLINE, EMBASE, CENTRAL, Epistemonikos, Virtual Health Library, and gray literature from inception to July 31, 2022. We included randomized controlled trials (RCTs) in children with DKA evaluating any intravenous fluid schemes. We planned to conduct NMA to compare all fluid schemes if heterogeneity was deemed acceptable. RESULTS: Twelve RCTs were included. Studies were heterogeneous in the population (patients and DKA episodes), interventions with different fluids (saline, Ringer's lactate (RL), and polyelectrolyte solution-PlasmaLyte®), tonicity, volume, and administration systems. We identified 47 outcomes that measured clinical manifestations and metabolic control, including single and composite outcomes and substantial heterogeneity preventing statistical combination. No evidence was found of differences in neurological deterioration (main outcome), but differences were found among interventions in some comparisons to normalize acid-base status (∼2 h less with low vs. high volume); time to receive subcutaneous insulin (∼1 h less with low vs. high fluid rate); length of stay (∼6 h less with RL vs. saline); and resolution of the DKA (∼3 h less with two-bag vs. one-bag scheme). However, available evidence is scarce and poor. CONCLUSIONS: There is not enough evidence to determine the best fluid therapy in terms of fluid type, tonicity, volume, or administration time for DKA treatment. There is an urgent need for more RCTs, and the development of a core outcome set on DKA in children.

Type 1 diabetes in pediatrics during the COVID-19 pandemic: Time from symptom onset and forms of presentation at a referral hospital. / Diabetes tipo 1 en pediatría durante la pandemia por COVID-19: tiempo de evolución de síntomas y formas de presentación en un centro de referencia.

Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported. Objectives. To assess whether there were changes in the time from symptom onset, the causes of hospitalization due to DM1, and the proportion of severe forms, and to describe SARS-CoV-2 infection in these patients. Population and methods. Cross-sectional study in patients younger than 19 years hospitalized due to DM1 from March 2018 to August 2019 (pre-pandemic) and from March 2020 to August 2021 (pandemic). Results. The assessment included 135 hospitalizations in the pre-pandemic period and 96 during the pandemic. The time from symptom onset during the pandemic in those with debut of diabetes was shorter than in the pre-pandemic period (18.8 ± 10.2 versus 52.1 ± 12.1 days, respectively; p < 0.001). Hospitalizations due to all forms of diabetes debut and debut with DKA were more common during the pandemic than before it (59.4% versus 39.3%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3-3.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.4-5.2; p = 0.006, respectively). Severe forms of DKA did not change between both periods (48.1% versus 59.9%; p = 0.3). Only 6 patients developed SARS-CoV-2 infection; 3 were severe. Conclusion. During the pandemic, the time from symptom onset decreased and the frequency of hospitalizations due to debut of DM1 increased. The proportion of severe forms of DKA did not change.

Introducción. La pandemia por COVID-19 afectó la atención de pacientes con diabetes mellitus tipo 1 (DM1). Además, se reportó un aumento de cetoacidosis diabética (CAD) como forma de diagnóstico. Objetivos. Evaluar si durante la pandemia por COVID-19 se modificaron el tiempo de evolución de síntomas, las causas de hospitalización por DM1 y la proporción de formas graves, y describir la infección por SARS-CoV-2 en estos pacientes. Población y métodos. Estudio transversal que incluyó pacientes menores de 19 años hospitalizados por DM1 en un centro pediátrico de referencia de marzo de 2018 a agosto de 2019 (prepandemia) y de marzo de 2020 a agosto de 2021 (pandemia). Resultados. Se analizaron 231 internaciones, 135 prepandemia y 96 en pandemia. Los pacientes con debut diabético presentaron menor tiempo de evolución de síntomas en pandemia que en prepandemia (18,8 ± 10,2 vs. 52,1 ±12,1 días, respectivamente; p <0,001). Las hospitalizaciones por todas las formas de debut diabético y el debut con CAD fueron más frecuentes en pandemia que en prepandemia (59,4 % vs. 39,3 %; OR 2,3; IC95% 1,3-3,8; p = 0,003); y (40,6 % vs. 20,7 %; OR 2,6; IC95% 1,4-5,2; p = 0,006) respectivamente. La proporción de formas graves de CAD no se modificó entre ambos períodos (48,1 % vs. 59,9 %; p = 0,3). Solo 6 pacientes presentaron infección por SARS-CoV-2; 3 fueron formas graves. Conclusión. Durante la pandemia, disminuyó el tiempo de evolución de síntomas y aumentó la frecuencia de hospitalizaciones por debut de DM1, con mayor proporción de CAD. No se modificó la proporción de formas graves de CAD.

Estudio de casos y controles sobre factores asociados a crisis hiperglucémicas en adultos diabéticos atendidos en la unidad de emergencia de un hospital general de Lima / Case-Control study on factors associated with hyperglycemic crises in diabetic adults attended in the emergency unit of a general hospital in Lima

RESUMEN Introducción: La diabetes mellitus representa un desafío significativo para la salud pública; las crisis hiperglucémicas son complicaciones serias que pueden resultar en morbilidad o muerte. Objetivo: Establecer factores asociados a las crisis hiperglucémicas (CH) en adultos diabéticos atendidos en un hospital de Lima. Métodos: Se realizó un estudio observacional, retrospectivo y analítico de casos y controles en un Hospital General de Lima entre 2015 y 2019. Se seleccionaron 186 historias clínicas (62 casos y 124 controles) mediante muestreo aleatorio simple. El desenlace fueron las CH, definidas como cetoacidosis diabética, el estado hiperosmolar hiperglucémico y el estado mixto. Las variables incluyeron edad, sexo, zona de residencia, seguro de salud, tiempo de enfermedad, comorbilidades, infecciones agudas y adherencia a la medicación. Los datos se analizaron con pruebas de Chi Cuadrado y la prueba exacta de Fisher, calculando Odds Ratios crudos (ORc) y ajustados (ORa). Resultados: En el análisis bivariado los factores que se asociaron con las CH fueron; el sexo (p=0,029), edad (p<0,001), tiempo de enfermedad (p=0,001) y adherencia a la medicación (p<0,001). No se halló relación con las variables residencia, seguro de salud, procesos infecciosos agudos y comorbilidades (p>0,05). En el análisis multivariado los factores asociados a las CH fueron la edad (ORa: 2,85; IC95%: 1,41-5,79; p=0,004) y la no adherencia a la medicación (ORa: 3,87; IC95%: 1,84-8,18; p<0,001). Conclusión: Los factores asociados a las CH son la edad y la no adherencia a la medicación.

ABSTRACT Introduction: Diabetes mellitus represents a significant public health challenge; hyperglycemic crises are serious complications that can result in morbidity or death. Objective: To establish factors associated with hyperglycemic crises (HC) in diabetic adults attended in a hospital in Lima. Methods: An observational, retrospective, and analytical case-control study was conducted in a General Hospital in Lima between 2015 and 2019. A total of 186 medical records (62 cases and 124 controls) were selected through simple random sampling. The outcome was HC, defined as diabetic ketoacidosis, hyperosmolar hyperglycemic state, and mixed state. The variables included age, sex, area of residence, health insurance, duration of disease, comorbidities, acute infections, and medication adherence. Data were analyzed using Chi-Square tests and Fisher's exact test, calculating crude (cOR) and adjusted (aOR) Odds Ratios. Results: In the bivariate analysis, factors associated with HC were sex (p=0.029), age (p<0.001), duration of disease (p=0.001), and medication adherence (p<0.001). No relationship was found with variables such as residence, health insurance, acute infectious processes, and comorbidities (p>0.05). In the multivariate analysis, factors associated with HC were age (aOR: 2.85; 95% CI: 1.41-5.79; p=0.004) and non-adherence to medication (aOR: 3.87; 95% CI: 1.84-8.18; p<0.001). Conclusion: Factors associated with HC are age and non-adherence to medication.

[Diabetic ketoacidosis secondary to immunotherapy]. / Cetoacidosis diabética secundaria a inmunoterapia.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are increasingly used in cancer treatments. As experience in the use of immunotherapy increases, more is known about its safety profile and immune-mediated adverse effects. Among them is diabetic ketoacidosis (DKA), a rare but serious fatal complication of treatment. In this paper we describe the cases of three patients who presented with episodes of DKA during treatment with ICIs, two of which manifested with fulminant forms, leading to an acute course with initially normal glycosylated hemoglobin values. In addition, we conducted a review of the literature on DKA associated with ICIs in order to highlight the importance of noticing these potentially fatal complications and promptly establishing appropriate therapy.

Los inhibidores de puntos de control inmune (ICIs) son anticuerpos monoclonales cada vez más utilizados en tratamientos oncológicos. A medida que aumenta la experiencia en el uso de inmunoterapia, se conoce cada vez más su perfil de seguridad y los efectos adversos inmunomediados. Entre ellos se encuentra la cetoacidosis diabética (CAD), complicación infrecuente, grave y potencialmente mortal. En este trabajo describimos los casos de tres pacientes que se presentaron con episodios de CAD durante el tratamiento con ICIs, dos de los cuales manifestaron con formas fulminantes, llevando un curso agudo con valores de hemoglobina glicosilada inicialmente normales. Asimismo, realizamos una revisión de la literatura sobre la CAD asociada a ICIs a fines de resaltar la importancia de advertir estas complicaciones potencialmente fatales e instaurar rápidamente la terapéutica apropiada.

Causas precipitantes de crisis hiperglicémicas agudas en pacientes internados en el Centro Médico Nacional - Hospital Nacional / Precipiting causes of acute hyperglycemic crisis in patients in the Centro Médico Nacional - Hospital Nacional

Introducción: las crisis hiperglicémicas agudas son las emergencias endocrinológicas más frecuentes en la práctica clínica y junto a la hipoglucemia se las describe como las complicaciones metabólicas agudas graves del paciente diabético. Objetivo: identificar las causas precipitantes de crisis hiperglicémicas agudas en pacientes internados en el Centro Médico - Hospital Nacional. Metodología: estudio observacional, descriptivo, de corte transversal de pacientes internados en el Centro Médico Hospital Nacional, durante el periodo de mayo 2021 a octubre del 2023. Los datos fueron obtenidos con la revisión de las fichas clínicas. Resultados: de los 100 pacientes evaluados, la crisis hiperglicémica aguda más frecuente fue la Cetoacidosis diabética (CAD) 53 %, seguida del Estado hiperosmolar hiperglicémico (EHH) 25 % y el estado mixto 22 %. Los desencadenantes más frecuentes fueron el abandono del tratamiento, debut de la enfermedad e infecciones. La mortalidad global fue del 12 %. Conclusión: la causa más frecuente de descompensación fueron el abandono del tratamiento, la diabetes de novo y procesos infecciosos.

Introduction: hyperglycemic crises are the most frequent endocrinological emergencies in clinical practice and, along with hypoglycemia, are described as serious acute metabolic complications in diabetic patients. Objective: to identify the precipiting causes of acute hyperglycemic crisis in hospitalized patients in the Centro Médico Nacional - Hospital National. Methodology: this was an observational, descriptive, cross -sectional study of patients hospitalized at the Centro Médico Nacional - Hospital National, from May 2021 to October 2023. The data were obtained from a review of the clinical records. Results: Of the 100 patients evaluated, the most frequent acute hyperglycemic crisis was diabetic ketoacidosis (CAD) 53 %, followed by the hyperglycemic hyperosmolar state (EHH) 25 % and the mixed state 22 %. The most frequent triggers were the abandonment of treatment, disease debut and infections. Global mortality was 12 %. Conclusion: the most frequent causes of decompensations were abandoning treatment, novo diabetes and infectious processes.

Mucormycosis-induced hypercalcemia: a case report.

Hypercalcemia is a vital laboratory marker because it can show underlying severe diseases like cancer and infections. Of all the causes of hypercalcemia, primary hyperparathyroidism, and malignancies are the most common, but granulomatous diseases, such as certain fungal infections, can also be the cause. Here we describe the case of a 29-year-old woman, an insulin-dependent diabetic, found unconscious and tachypneic at home. In the emergency room, the medical team diagnosed diabetic ketoacidosis (DKA) and acute kidney injury (AKI). During hospitalization, despite resolving acidemia, persistent hypercalcemia attracted attention. Laboratory tests showed decreased parathyroid hormone (PTH) levels, confirming non-PTH-dependent hypercalcemia. Computed tomography (CT) of the chest and abdomen demonstrated no alterations, but an upper digestive endoscopy revealed an ulcerated and infiltrative lesion in the stomach. A biopsy showed a granulomatous infiltrate due to mucormycosis infection. The patient received liposomal amphotericin B for 30 days and isavuconazonium for two months. Serum calcium levels improved during treatment. Inquiry of the etiology of hypercalcemia should begin with the PTH assay; high levels are consistent with hyperparathyroidism; low levels, with calcium or vitamin D intoxication, malignancies, prolonged immobilization, and granulomatous diseases. In the latter cases, the overproduction of 1-alpha-hydroxylase by the granulomatous tissue increases the conversion of 25(OH)vitamin D into 1-25(OH)vitamin D, which causes the intestinal absorption of calcium. We have described the first hypercalcemia related to mucormycosis infection in a young diabetic patient, although case presentations associate other fungal infections with elevated serum calcium.

Cetoacidosis diabética secundaria a inmunoterapia / Diabetic ketoacidosis secondary to immunotherapy

Resumen Los inhibidores de puntos de control inmune (ICIs) son anticuerpos monoclonales cada vez más utilizados en tratamientos oncológicos. A medida que aumenta la experiencia en el uso de inmunoterapia, se conoce cada vez más su perfil de seguridad y los efectos adversos inmunomediados. Entre ellos se encuentra la cetoaci dosis diabética (CAD), complicación infrecuente, grave y potencialmente mortal. En este trabajo describimos los casos de tres pacientes que se presentaron con episo dios de CAD durante el tratamiento con ICIs, dos de los cuales manifestaron con formas fulminantes, llevando un curso agudo con valores de hemoglobina glicosilada inicialmente normales. Asimismo, realizamos una revi sión de la literatura sobre la CAD asociada a ICIs a fines de resaltar la importancia de advertir estas complica ciones potencialmente fatales e instaurar rápidamente la terapéutica apropiada.

Abstract Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are increasingly used in cancer treat ments. As experience in the use of immunotherapy increases, more is known about its safety profile and immune-mediated adverse effects. Among them is dia betic ketoacidosis (DKA), a rare but serious fatal compli cation of treatment. In this paper we describe the cases of three patients who presented with episodes of DKA during treatment with ICIs, two of which manifested with fulminant forms, leading to an acute course with initially normal glycosylated hemoglobin values. In ad dition, we conducted a review of the literature on DKA associated with ICIs in order to highlight the importance of noticing these potentially fatal complications and promptly establishing appropriate therapy.

The effect of serum biochemical parameters on clinical prognosis in children presenting with diabetic ketoacidosis

SUMMARY OBJECTIVE: The aim of this study was to determine whether diabetes mellitus has a high risk of diabetic ketoacidosis-related complications. Biochemical parameters affect the resolution time of diabetic ketoacidosis. METHODS: The present study is based on a retrospective evaluation of the records of patients who presented to the Pediatrics Clinic of Adiyaman University Hospital between January 1, 2017, and October 1, 2022, with a diagnosis ofdiabetic ketoacidosis. The demographic characteristics, serum biochemical parameters, blood gas results, and time to transition to subcutaneous insulin therapy were all recorded. RESULTS: This study included 49 (49%) female and 51 (51%) male patients aged 1-17 years (mean age: 9.05±4.33 years). The average time to clinical improvement of the sample, that is, transition to subcutaneous insulin therapy, was 21.04±7.8 h. An evaluation of the presence of acute kidney injury based on serum urea and creatinine levels and eGFR values revealed no significant effect on the rate of clinical recovery (respective p-values: p=0.076, p=0.494, and p=0.884). A univariate analysis identified blood glucose (p=0.025), blood gas pH (p<0.001), and blood bicarbonate (p=0.004) values as prognostic factors, while a multivariate analysis revealed pH values had an independent and significant effect on the resolution time of diabetic ketoacidosis. CONCLUSION: Serum glucose, pH, and bicarbonate levels are the most important determinants of clinical prognosis in patients with diabetic ketoacidosis. These findings can serve as a guide for clinicians in the follow-up and treatment of such patients.

Caracterización de las complicaciones intrahospitalarias de los estados hiperglucémicos en pacientes adultos internados en el Hospital Nacional de Itauguá, Paraguay, en 2015-2022

Introducción: las complicaciones más graves de la diabetes mellitus son la cetoacidosis diabética y el estado hiperglucémico hiperosmolar, muchas veces se observan alteraciones clínicas y laboratoriales que abarcan los dos espectros y que denominamos estado mixto, representan cerca del 50% de las hospitalizaciones en el servicio de urgencias en pacientes diabéticos. Objetivo: determinar las complicaciones intrahospitalarias y los desenlaces de los estados hiperglucémicos en pacientes adultos internados en el Hospital Nacional, Itauguá, Paraguay, en el periodo 2015-2022. Metodología: se aplicó un diseño de cohortes retrospectivas. Se seleccionaron pacientes con diagnósticos de diabetes mellitus tipo 1 y tipo 2, mayores de 18 años, de ambos sexos, agrupados en tres cohortes que corresponden a cada una de las descompensaciones agudas de la diabetes mellitus. La muestra estuvo conformada por 180 pacientes distribuidos en tres grupos de cohortes con 60 pacientes cada una. Resultados: 51% correspondió al sexo masculino. Se halló mayor desarrollo de eventos cardiovasculares, infecciones intrahospitalarias, requerimiento de cuidados intensivos y mortalidad en la cohorte con estado hiperosmolar. Conclusión: la cohorte con estado hiperosmolar hiperglucémico se caracterizó por la mayor cantidad de complicaciones.

Introduction: The most serious complications of diabetes mellitus are diabetic ketoacidosis and the hyperosmolar hyperglycemic state. Clinical and laboratory alterations are often observed that cover both spectrums and which we call a mixed state. They represent close to 50% of hospitalizations in the service. of emergencies in diabetic patients. Objective: To determine in-hospital complications and outcomes of hyperglycemic states in adult patients admitted to the Hospital Nacional, Itauguá, Paraguay, in the period 2015-2022. Methodology: A retrospective cohort design was applied. Male and female patients with diagnoses of type 1 and type 2 diabetes mellitus, who were over 18 years of age, were selected and grouped into three cohorts that corresponded to each of the acute decompensations of diabetes mellitus. The sample was made up of 180 patients distributed into three cohort groups with 60 patients each. Results: Fifty one percent were male. A greater development of cardiovascular events, hospital-acquired infections, intensive care requirements and mortality were found in the cohort with hyperosmolar state. Conclusion: the cohort with hyperglycemic hyperosmolar state was characterized by the highest number of complications.

[Succinyl CoA:3 oxoacid CoA transferase deficiency: A case report]. / Deficiencia de succinil-CoA acetoacetato transferasa: reporte de un caso.

Background: Succinyl-CoA:3 oxoacid CoA transferase deficiency (SCOTD) is a rare autosomal recessive disease, characterized by altered utilization of ketone bodies, with acute episodes of ketoacidosis. Clinical case: It is presented the case of a patient with SCOTD, with a first atypical episode accompanied by hyperglycemia, with 4 subsequent episodes with classic manifestations of the disease, presenting with a biochemical pattern of permanent ketonuria with marked elevation of ketone bodies (acetoacetate, 3 beta-hydroxybutyrate) in the study of urinary organic acids by gas chromatography and mass spectrometry, together with the clinical picture granting the diagnosis. It was started a maintenance therapy with a characteristic feeding plan; it was shown an adequate response to treatment, and the absence of permanent ketosis was surmised. Conclusion: Being a rare disease, the categorization of these patients as diabetic ketoacidosis is frequent. The clinical and biochemical characteristics with ketosis or persistent ketonuria should be analyzed very carefully, especially in patients presenting with hyperglycemia, which is an atypical manifestation of the disease, in order to make an early diagnosis and treatment, positively impacting the prognosis of patients.

Introducción: la deficiencia de succinil-CoA acetoacetato transferasa (SCOT) es una enfermedad rara, autosómica recesiva, caracterizada por alteración en la utilización de cuerpos cetónicos, con episodios agudos de cetoacidosis. Caso clínico: se presenta el caso de un paciente con deficiencia de SCOT, con un primer episodio atípico acompañado con hiperglucemia, con 4 episodios posteriores con manifestaciones clásicas de la enfermedad, que presentó patrón bioquímico de cetonuria permanente con marcada elevación de cuerpos cetónicos (acetoacetato, 3 beta-hidroxibutirato) en estudio de ácidos orgánicos urinarios por cromatografía de gases y espectrometría de masas, aunado a cuadro clínico que otorgó el diagnóstico. Se inició terapia de mantenimiento con plan de alimentación característico; se demostró una adecuada respuesta al tratamiento, y se infirió una ausencia de cetosis permanente. Conclusiones: al ser una enfermedad rara, la categorización de estos pacientes como cetoacidosis diabética es frecuente. Se deben analizar de forma muy minuciosa las características clínicas y bioquímicas con cetosis o cetonuria persistente, sobre todo en pacientes que se presenten con hiperglucemia, que es una manifestación atípica de la enfermedad, para realizar un diagnóstico y tratamiento temprano que impacte de forma positiva el pronóstico de los pacientes.

Diabetes mellitus tipo 1 de presentación súbita inducida por inhibidores del punto de control inmunitario en el tratamiento de cáncer avanzado. Serie de casos / Sudden onset type 1 diabetes mellitus induced by immune checkpoint inhibitors in the treatment of advanced cancer. Cases report

Tres pacientes con cáncer avanzado en tratamiento con inhibidores del punto de control inmunitario (inmune checkpoint inhibitors, ICIs), sin antecedentes de diabetes mellitus (DM), ingresaron al Servicio de Urgencias con poliuria, polidipsia y pérdida de peso, y diagnóstico de cetoacidosis diabética, sin evidencia clínica de infección. Fueron tratados con líquidos e infusión de insulina pasando luego a un régimen de insulina bolo basal que continuó después del alta. Las pruebas de detección de autoanticuerpos para DM resultaron negativas, y se les diagnosticó DM inducida por ICIs, pembrolizumab en dos de ellos y nivolumab en el otro. El propósito de esta serie de casos es demostrar el desarrollo de la DM1 en forma aguda en pacientes tratados con inhibidores de PD-1. Sobre la base de estos casos y la literatura revisada, se buscaron determinar las características clínicas, y sugerir estrategias para la identificación, control, tratamiento precoz y seguimiento de los pacientes tratados con ICIs a fin de minimizar el impacto de la disfunción autoinmune.

Three patients with advanced cancer, treated with inmune checkpoint inhibitors (ICIs), with no history of diabetes mellitus (DM), were admitted to the Emergency Department with polyuria, polydipsia, and weight loss and a diagnosis of diabetic ketoacidosis without clinical evidence of infection. They were treated with fluids and insulin infusion transitioning to a basal-bolus insulin regimen, which continued after discharge. Autoantibody detection tests for DM were negative and they were diagnosed with DM induced by ICIs, pembrolizumab in two of them, and nivolumab in another. The purpose of this case report is to show the development of DM1 in an acute form in patients treated with PD-1 inhibitors. Based on these cases and the reviewed literature, we seek to identify clinical characteristics and suggest strategies for the proper identification, control, treatment, and follow-up of patients treated with ICIs to minimize the impact of autoimmune dysfunction.

The Relationship between Type 1 Diabetes Mellitus, TNF-α, and IL-10 Gene Expression.

Type 1 diabetes mellitus (T1DM) is one of the major chronic diseases in children worldwide. This study aimed to investigate interleukin-10 (IL-10) gene expression and tumor necrosis factor-alpha (TNF-α) in T1DM. A total of 107 patients were included, 15 were T1DM in ketoacidosis, 30 patients had T1DM and HbA1c ≥ 8%; 32 patients had T1DM and presented HbA1c < 8%; and 30 were controls. The expression of peripheral blood mononuclear cells was performed using the reverse transcriptase-polymerase chain reaction in real time. The cytokines gene expression was higher in patients with T1DM. The IL-10 gene expression increased substantially in patients with ketoacidosis, and there was a positive correlation with HbA1c. A negative correlation was found for IL-10 expression and the age of patients with diabetes, and the time of diagnosis of the disease. There was a positive correlation between TNF-α expression with age. The expression of IL-10 and TNF-α genes showed a significant increase in DM1 patients. Once current T1DM treatment is based on exogenous insulin, there is a need for other therapies, and inflammatory biomarkers could bring new possibilities to the therapeutic approach of the patients.

Increased risk of death following recurrent ketoacidosis admissions: a Brazilian cohort study of young adults with type 1 diabetes.

BACKGROUND: Recurrent DKA (rDKA) remains an acute type 1 diabetes complication even in post-insulin era. This study aimed to analyze the predictors and effects of rDKA on the mortality of patients with type 1 diabetes. METHODS: Patients hospitalized (n = 231) wih diabetic ketoacidosis (between 2007 and 2018) were included. Laboratorial and clinical variables were collected. Mortality curves were compared in four groups: diabetic ketoacidosis as a new-onset type 1 diabetes (group A), single diabetic ketoacidosis episode after diagnosis of type 1 diabetes (group B), 2-5 diabetic ketoacidosis events (group C), and > 5 diabetic ketoacidosis events during follow-up period (group D). RESULTS: During the follow-up period (approximately 1823 days), the mortality rate was 16.02% (37/231). The median age at death was 38.7 years. In the survival curve analysis, at 1926 days (5 years), the probabilities of death were indicated by ratios of 7.78%, 4.58%, 24.40%, and 26.63% in groups A, B, C, and D, respectively. One diabetic ketoacidosis episode compared with ≥ 2 events had a relative risk of 4.49 (p = 0.004) of death and > 5 events had 5.81 (p = 0.04). Neuropathy (RR 10.04; p < 0.001), retinopathy (relative risk 7.94; p < 0.01), nephropathy (RR 7.10; p < 0.001), mood disorders (RR 3.57; p = 0.002), antidepressant use (RR 3.09; p = 0.004), and statin use (RR 2.81; p = 0.0024) increased the risk of death. CONCLUSIONS: Patients with type 1 diabetes with > 2 diabetic ketoacidosis episodes have four times greater risk of death in 5 years. Microangiopathies, mood disorders, and use of antidepressants and statins were important risk factors for short-term mortality.

Debut de diabetes tipo 1 en niños durante la pandemia Covid-19 en el Hospital de Pediatría Juan P. Garrahan / Debut of type-1 diabetes in children during the COVID-19 pandemic at Hospital de Pediatría Juan P. Garrahan

Introducción: Según numerosos reportes, la pandemia por COVID­19 aumentó la incidencia de diabetes tipo 1 (DBT1) y cetoacidosis (CAD). Nuestro objetivo fue describir la frecuencia de nuevos casos de DBT1 y su severidad al ingreso en el Hospital J. P. Garrahan durante la pandemia, comparando con el periodo anterior. Material y métodos: Se realizó un estudio descriptivo, observacional, con análisis retrospectivo. Se incluyeron todos los nuevos casos entre 19/03/20- 31/12/21, comparados con el período 19/03/18-31/12/19. El diagnóstico de DBT1, CAD y su severidad se realizó según la International Society for Pediatric and Adolescent Diabetes. Se analizó el requerimiento de cuidados intensivos (UCI), presencia de COVID-19, hemoglobina glicosilada A1C (HbA1C) y autoanticuerpos (GADA, IAA, IA2, ZNT8). Se consideró significativa una p < 0,05. Resultados: En el período 2020-2021 se observó un incremento del 107% de nuevos casos, ingresando 56 pacientes con DBT1. La media y mediana de edad disminuyeron (8 vs 9,1 y 7,7 vs 10,4, respectivamente), con un incremento del 35% de menores de 5 años. Aumentó la frecuencia de CAD severa (41.1% vs 25.9%) y de requerimiento de UCI (17.9% vs 11.1%). La Hb A1C y la glucemia de ingreso mostraron incremento significativo (10.1% vs 12.32%, p<0.003 y 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectivamente). Conclusión: En 2020-2021 se incrementó el número de nuevos casos de DBT1 en nuestra institución. Al ingreso hubo mayor proporción de niños pequeños y casos severos. Las dificultades de acceso a la consulta de atención primaria podrían relacionarse con nuestro hallazgo (AU)

Introduction: Numerous reports have shown that during the COVID-19 pandemic the incidence of type-1 diabetes (T1DB) and ketoacidosis (DKA) increased. The aim of this study was to describe the frequency of new cases and their severity on admission of T1DB at Hospital J. P. Garrahan during the pandemic, compared with the previous period. Material and methods: A descriptive, observational study with a retrospective analysis was conducted. All new cases seen between 19/03/20-31/12/21 were included and compared with the period 19/03/18-31/12/19. The diagnosis of T1DB, DKA, and its severity was made according to the International Society for Pediatric and Adolescent Diabetes. Intensive care (ICU) requirement, presence of COVID-19, glycosylated hemoglobin A1C (HbA1C), and autoantibodies (GADA, IAA, IA2, ZNT8) were analyzed. A p < 0.05 was considered significant. Results: In the period 2020-2021, a 107% increase in new cases was observed including 56 patients with T1DB. Mean and median age decreased (8 vs 9.1 and 7.7 vs 10.4, respectively), with a 35% increase in children under 5 years of age. The frequency of severe DKA (41.1% vs 25.9%) and ICU requirement (17.9% vs 11.1%) increased. Hb A1C and glycemia on admission also showed a significant increase (10.1% vs 12.32%, p<0.003 and 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectively). Conclusion: In 2020-2021 an increase in the number of new cases of T1DB was observed at our institution. On admission, a higher rate of young children and severe cases was found. Difficulties to access primary care may have been related to our finding (AU)

Pyuria in Children with Diabetic Ketoacidosis.

Acute kidney injury occurs frequently during pediatric diabetic ketoacidosis (DKA). We reviewed urinalyses from 561 children with DKA; pyuria was detected in 19% overall and in 40% of children with more comprehensive urine testing (≥3 urinalyses) during DKA.

Necrotizing fasciitis and fatal septic shock associated with Streptococcus constellatus.

Streptococcus constellatus is usually a benign, commensal bacteria but has increased incidence in blood cultures and abscesses. This pathogenic involvement is most prevalent in individuals with underlying medical conditions, such as solid tumors and type 2 diabetes mellitus, as well as in cases of community-acquired infections. We report a 43-year-old male with a right medial thigh ulcer and necrotic scrotal skin. The wound culture from surgical debridement grew Streptococcus constellatus, and histology was consistent with stage III necrotizing fasciitis. Regardless of etiology, the mortality rate of patients with necrotizing fasciitis is greatly decreased with early intervention and thorough surgical debridement.

Cetoacidosis diabética como debut de diabetes mellitus inmunomediada en paciente en tratamiento con inhibidores de checkpoint / Diabetic ketoacidosis as debut of immune-mediated diabetes mellitus in a patient in treatment with immune checkpoint inhibitors

Los inhibidores de checkpoint (ICP) son anticuerpos usados en inmunoterapia contra el cáncer. Uno de sus blancos de acción es el receptor de muerte celular programada-1 (PD-1), el cual es importante para mantener la tolerancia inmunitaria. Sin embargo, este mecanismo se asocia a riesgo de eventos adversos relacionados a la inmunidad que pueden afectar a múltiples órganos incluyendo el sistema endocrino. Se describe el caso inhabitual de un paciente que a los 18 meses de terapia con ICP debutó con cetoacidosis diabética (CAD).

Immune checkpoint inhibitors consist in antibodies used in immunotherapy against cancer. One of their targets is the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, this mechanism is associated with a risk for immune-related adverse events potentially affecting multiple organs, including the endocrine system. We describe the unusual case of a patient who, after 18 months of treatment with an immune checkpoint inhibitor, debuted with diabetic ketoacidosis