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.

Pediatric mucormycosis associated with COVID-19: A systematic review of clinical cases.

The occurrence of mucormycosis has been observed in individuals with COVID-19. However, there is limited information on the epidemiological factors, presentation, diagnostic certainty, and outcome of this infection in children. PubMed, MEDLINE, Scopus, Embase, Web of Science, LitCovid, and back-references of the identified manuscripts were systematically searched from December 2019 to March 2023. We have identified 14 cases of pediatric mucormycosis in patients with COVID-19. The median age of patients was 10.7 years. Among these cases, 10 were associated with active COVID-19. In 7 cases, the patients had pre-existing diabetes mellitus and concomitant diabetic ketoacidosis. Corticosteroids were administered to treat COVID-19 in 7 of the patients. The most common clinical presentation of the disease was rhino-orbital cerebral mucormycosis. Seven patients died (50%). Given the high mortality rate, clinicians should maintain a high level of clinical suspicion of mucormycosis in pediatric patients with COVID-19.

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.

Analysis of the variables involved in the time to resolution of metabolic parameters in adults with diabetic ketoacidosis / [Análisis de las variables involucradas en el tiempo de resolución de los parámetros metabólicos en adultos con cetoacidosis diabética.]

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication characterized by hyperglycemia, metabolic acidosis, and ketonemia. Although the time to resolution of DKA has been estimated at 12 to 18 hours, the factors that could prolong it have not been fully studied. Methods: Retrospective study of medical records of adult patients admitted to the general ward with a diagnosis of DKA. They were classified according to severity as mild, moderate and severe. The time to resolution of crisis (TRC) was defined as that necessary until normalization of metabolic parameters. A logistic regression analysis was performed to evaluate the association between TRC>12 hours and continuous variables. ROC analysis and survival analysis were performed using a Cox regression model. Results: 85 patients were studied. 48.23% presented severe DKA. The TRC was 14 hours, being higher in severe DKA. Patients with TRC>12 hours had a lower pH and HCO3-, and a higher anion gap, white blood cells, and volume of crystalloids used. Logistic regression analysis showed that pH and crystalloid volume correlated with TRC>12 hours. ROC analysis determined a pH cutoff value of 7.13 for TRC>12 hours (sensitivity 77%, specificity 88%). The Cox regression showed that a pH<7.13 on admission is associated with a higher TRC (HR 3.30). Conclusion: A pH lower than 7.13 at the time of hospital admission identifies patients with DKA who will need a longer time to resolve their metabolic parameters.

Introducción: La cetoacidosis diabética (CAD) es una complicación potencialmente mortal caracterizada por hiperglucemia, acidosis metabólica y cetonemia. Aunque el tiempo para la resolución de la CAD se ha estimado en 12 a 18 horas, los factores que podrían prolongarlo no se han estudiado con exhaustividad. Métodos: Estudio retrospectivo de historias clínicas de pacientes adultos admitidos a sala general con diagnóstico de CAD. Se clasificaron según la severidad en leve, moderada y severa. El tiempo de resolución de la crisis (TRC) se definió como aquel necesario hasta normalización de parámetros metabólicos. Se realizó un análisis de regresión logística para evaluar la asociación entre TRC>12 horas y variables continuas. Se realizó un análisis ROC y un análisis de supervivencia utilizando un modelo de regresión de Cox. Resultados: Se estudiaron 85 pacientes. El 48.23% presentó CAD severa. El TRC fue de 14 horas, siendo mayor en CAD severa. Los pacientes con TRC>12 horas presentaron menor pH y HCO3, y mayor anión gap, glóbulos blancos y volumen de cristaloides utilizados. El análisis de regresión logística demostró que el pH y el volumen de cristaloides correlacionaron con TRC>12 horas. El análisis ROC determinó un valor de corte de pH de 7.13 para TRC>12 horas (sensibilidad 77%, especificidad 88%). La regresión de Cox demostró que un pH <7.13 al ingreso se asocia a mayor TRC (HR 3.30). Conclusión: Un pH menor a 7.13 al momento de admisión hospitalaria identifica a pacientes con CAD que necesitarán un mayor tiempo para resolver sus parámetros metabólicos.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Recurrent hypoglycemic coma and diabetic ketoacidosis caused by insulin antibody. A rare case of type 1 diabetes mellitus.

Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: < 5%), and the concentrations of insulin and C-peptide were > 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.

Hypokalemia in Diabetes Mellitus Setting.

Diabetes mellitus is a public health problem that affects millions of people worldwide regardless of age, sex, and ethnicity. Electrolyte disturbances may occur as a consequence of disease progression or its treatment, in particular potassium disorders. The prevalence of hypokalemia in diabetic individuals over 55 years of age is up to 1.2%. In patients with acute complications of diabetes, such as diabetic ketoacidosis, this prevalence is even higher. Potassium disorders, either hypokalemia or hyperkalemia, have been associated with increased all-cause mortality in diabetic individuals, especially in those with associated comorbidities, such as heart failure and chronic kidney disease. In this article, we discuss the main conditions for the onset of hypokalemia in diabetic individuals, briefly review the pathophysiology of acute complications of diabetes mellitus and their association with hypokalemia, the main signs, symptoms, and laboratory parameters for the diagnosis of hypokalemia, and the management of one of the most common electrolyte disturbances in clinical practice.

Comparative Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase 4 Inhibitors and Sulfonylureas on the Risk of Diabetic Ketoacidosis.

OBJECTIVE: To assess the association of sodium-glucose cotransporter 2 (SGLT2) inhibitors with diabetic ketoacidosis compared with dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a new-user active comparator cohort study to examine two pairwise comparisons: 1) SGLT2 inhibitors versus DPP-4 inhibitors and 2) SGLT2 inhibitors versus sulfonylureas. The main outcome was diabetic ketoacidosis present on hospital admission. We adjusted for confounders through propensity score matching. We used Cox proportional hazards regression with a robust variance estimator to estimate hazard ratios (HRs) and corresponding 95% CIs while adjusting for calendar time. RESULTS: In cohort 1 (n = 85,125 for SGLT2 inhibitors and n = 85,125 for DPP-4 inhibitors), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.0 and 4.3 for SGLT2 inhibitors and DPP4 inhibitors, respectively. In cohort 2 (n = 72,436 for SGLT2 inhibitors and n = 72,436 for sulfonylureas), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.3 and 4.5 for SGLT2 inhibitors and sulfonylureas, respectively. In Cox proportional hazards regression models, the use of SGLT2 inhibitors was associated with a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors (adjusted HR [aHR] 1.63; 95% CI 1.36, 1.96) and sulfonylureas (aHR 1.56; 95% CI 1.30, 1.87). CONCLUSIONS: In this comparative safety study using real-world data, patients with type 2 diabetes who were newly prescribed SGLT2 inhibitors had a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors and sulfonylureas. Clinicians should be vigilant about this association.

Recurrent hypoglycemic coma and diabetic ketoacidosis caused by insulin antibody: a rare case of type 1 diabetes mellitus / Hipoglicemia hiperinsulinémica causada por anticuerpos antiinsulina: informe de un caso

ABSTRACT Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.

Los anticuerpos contra la insulina (AI) inducidos por la insulina exógena raramente causan hipoglucemia. No obstante, los autoanticuerpos contra la insulina (AIA) en el síndrome autoinmune de insulina (SAI) pueden causar hipoglucemia. Las manifestaciones típicas del SAI son la hipoglucemia en ayunas o posprandial, niveles elevados de insulina, la disminución del nivel de péptido C y AIA positivos. Presentamos un paciente hombre de 45 años con diabetes mellitus de tipo 1 (DMT1) tratado con análogos de insulina, que sufría comas hipoglucémicos recurrentes y cetoacidosis diabética (CAD). Sus síntomas fueron causados por la insulina exógena y fueron similares al SAI. La posible razón fue que la insulina exógena indujo AI. El título de AI era del 61,95% (Normal: 300 mU/L y < 0,02 nmol/L cuando se producía la hipoglucemia. Basados en sus síntomas clínicos y otros exámenes, se le diagnosticó hipoglucemia hiperinsulinémica causada por la AI. Sus síntomas mejoraron después de cambiar el régimen de insulina de lispro más insulina detemir a insulina humana recombinante (Gensulin R) y de empezar a tomar prednisona.

Differentiating Diabetic Ketoacidosis and Hyperglycemic Ketosis Due to Cannabis Hyperemesis Syndrome in Adults With Type 1 Diabetes.

OBJECTIVE: To differentiate diabetic ketoacidosis (DKA) from hyperglycemic ketosis due to cannabis hyperemesis syndrome (HK-CHS) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: Of 295 adults with type 1 diabetes who were seen with DKA-related ICD-10 codes, 68 patients with 172 DKA events meeting the inclusion criteria were analyzed. Cannabis use was defined as a positive urine test result for cannabis. Linear mixed models were used to define HK-CHS (pH ≥7.4 with bicarbonate ≥15 mmol/L [mEq/L]), and sensitivity and specificity were calculated using the receiver operating characteristic (ROC) curve. RESULTS: Cannabis users had significantly higher pH (7.42 ± 0.01 vs. 7.09 ± 0.02) and bicarbonate (19.2 ± 0.61 vs. 9.1 ± 0.71 mmol/L) (P < 0.0001) compared with nonusers. The area under the ROC curve for a positive cannabis urine test result predicting HK-CHS was 0.9892. CONCLUSIONS: In patients who present with DKA and higher pH, especially pH ≥7.4, cannabis use should be considered in the differential diagnosis.

Diabetic ketoacidosis and COVID-19: what have we learned so far?

In December 2019, a pandemic emerged due to a new coronavirus that imposed various uncertainties and discoveries. It has been reported that diabetes is a risk factor for worst outcomes of COVID-19 and also that SARS-CoV-2 infection was correlated with the occurrence of diabetic ketoacidosis (DKA) in patients. The aim of this work is to discuss this correlation emphasizing the main case reports from 2020 while exploring the management of DKA during the course of COVID-19. Web of Science, PubMed, and Scopus databases were searched using two sets of Medical Subject Heading (MeSH) search terms or Title/Abstract words: Coronavirus Infections (Coronavirus Infections, Middle East Respiratory Syndrome, COVID-19) and Diabetic Ketoacidosis (Diabetic Ketoacidosis, Diabetic Acidosis, Diabetic Ketosis). There is a clear correlation between COVID-19 and DKA. The SARS-Cov-2 infection may precipitate both a hyperglycemic state and ketoacidosis occurrence in patients with diabetes and nondiabetic patients, which may lead to fatal outcomes. DKA in patients with COVID-19 may increase risk and worse outcomes. Hence, the SARS-Cov-2 infection presents a new perspective toward the management of glycemia and acidosis in patients with diabetes and nondiabetic patients, highlighting the need for rapid interventions to minimize the complications from COVID-19 while reducing its spreading.

Incidence, characteristics and long-term outcomes of patients with diabetic ketoacidosis: a prospective prognosis cohort study in an emergency department.

BACKGROUND: Diabetic ketoacidosis is the most frequent hyperglycemic complication in the evolution of diabetes mellitus. Common precipitating factors include newly diagnosed diabetes mellitus, noncompliance with therapy and infections. However, few studies have been conducted in Brazil and none were prospective in design. OBJECTIVE: To describe the incidence, clinical and laboratory characteristics and precipitating factors of diabetic ketoacidosis among emergency department patients in a tertiary-level teaching hospital in Brazil. We also aimed to identify immediate and long-term mortality within two years. DESIGN AND SETTING: Prospective prognosis cohort study conduct at a tertiary-level teaching hospital in São Paulo, Brazil. METHODS: All patients > 12 years old presenting diabetic ketoacidosis who were admitted to the emergency department from June 2015 to May 2016 were invited to participate. RESULTS: The incidence of diabetic ketoacidosis per 1,000 admissions was 8.7. Treatment noncompliance and infection were the most common causes of diabetic ketoacidosis. The immediate mortality rate was 5.8%, while the six-month, one-year and two-year mortality rates were 9.6%, 13.5% and 19.2%, respectively. Death occurring within two years was associated with age, type 2 diabetes, hypoalbuminemia, infection at presentation and higher sequential organ failure assessment (SOFA) score at admission. CONCLUSIONS: Diabetic ketoacidosis among patients presenting to the emergency department was relatively frequent in our hospital. Treatment noncompliance and infection were major precipitating factors and presence of diabetic ketoacidosis was associated with immediate and long-term risk of death.

Incidence, characteristics and long-term outcomes of patients with diabetic ketoacidosis: a prospective prognosis cohort study in an emergency department

ABSTRACT BACKGROUND: Diabetic ketoacidosis is the most frequent hyperglycemic complication in the evolution of diabetes mellitus. Common precipitating factors include newly diagnosed diabetes mellitus, noncompliance with therapy and infections. However, few studies have been conducted in Brazil and none were prospective in design. OBJECTIVE: To describe the incidence, clinical and laboratory characteristics and precipitating factors of diabetic ketoacidosis among emergency department patients in a tertiary-level teaching hospital in Brazil. We also aimed to identify immediate and long-term mortality within two years. DESIGN AND SETTING: Prospective prognosis cohort study conduct at a tertiary-level teaching hospital in São Paulo, Brazil. METHODS: All patients > 12 years old presenting diabetic ketoacidosis who were admitted to the emergency department from June 2015 to May 2016 were invited to participate. RESULTS: The incidence of diabetic ketoacidosis per 1,000 admissions was 8.7. Treatment noncompliance and infection were the most common causes of diabetic ketoacidosis. The immediate mortality rate was 5.8%, while the six-month, one-year and two-year mortality rates were 9.6%, 13.5% and 19.2%, respectively. Death occurring within two years was associated with age, type 2 diabetes, hypoalbuminemia, infection at presentation and higher sequential organ failure assessment (SOFA) score at admission. CONCLUSIONS: Diabetic ketoacidosis among patients presenting to the emergency department was relatively frequent in our hospital. Treatment noncompliance and infection were major precipitating factors and presence of diabetic ketoacidosis was associated with immediate and long-term risk of death.

QTc Prolongation in Pediatric Patients with Diabetic Ketoacidosis.

OBJECTIVE: To investigate the association between diabetic ketoacidosis (DKA) and prolonged QTc interval and to assess for correlation between DKA severity and QTc prolongation. STUDY DESIGN: Retrospective observational study in a pediatric hospital. Patients admitted with DKA diagnosed by laboratory criteria and an electrocardiogram (ECG) performed during a period of acidosis were identified using Looking Glass Clinical Analytics. Data including age, sex, pH, electrolytes, anion gap, and ECG variables were collected. Patients were excluded if they had a prior diagnosis of prolonged QTc or were taking QTc prolonging medications. Severity of DKA was classified as mild (pH 7.24-7.3), moderate (pH 7-7.24), or severe (pH <7). ECGs were read by a pediatric electrophysiologist and QTc interval was manually calculated utilizing the Bazett formula. RESULTS: Ninety-six patients were included (mean age 15.2 ± 4.2 years, pH 7.12 ± 0.12, bicarbonate 8.6 ± 3.7 mmol/L, potassium 5.3 ± 1.1 mEq/L). Mean QTc interval for all patients in DKA was 454 ± 32 msec. Mean QTc in the mild group was 441 ± 22 msec, moderate group 460 ± 36 msec, and severe group 461 ± 34 msec. There was a significant difference in QTc interval across DKA severity groups (P = .05). There was a significant association between higher anion gaps and greater QTc intervals (r = 0.21, P = .04). CONCLUSIONS: Thirty-one percent of pediatric patients with DKA demonstrated QTc prolongation on ECG. Severity of DKA and worsening acidosis were associated with increased prolongation of the QTc. Further study is required to evaluate the clinical impact of these findings.

Protocolo de cetoacidose diabética: manejo clínico no pronto socorro infantil / Diabetic ketoacidosis protocol: clinical management in the pediatric emergency room

Realização de protocolo para manejo clinico de crianças e adolescentes atendidos no Hospital do Servidor Público Municipal-SP com diagnóstico de cetoacidose diabética (CAD).A CAD caracteriza-se clinicamente por desidratação, respiração acidótica e alteração do sensório e laboratorialmente por hiperglicemia, acidose metabólica e cetonemia. É uma complicação grave do diabetes meliantes tipo 1.A prevalência varia de acordo com a população estudada, podendo chegar até 45 % dos diagnósticos iniciais de diabetes melito tipo 1(DM1) e 10% do DM2. O reconhecimento e tratamento precoce das alterações clínicas ameaçadoras a vida, como choque hipovolêmico, distúrbios eletrolíticos e ácido básicos é necessário para evitar complicações e evolução para o óbito. Palavras-chaves: cetoacidose diabética, protocolo, pediatria, manejo clínico