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.

Diabetic ketoacidosis in a pediatric intensive care unit / Cetoacidose diabética em uma unidade de terapia intensiva pediátrica

Abstract Objective: To describe the characteristics of children aged 0-14 years diagnosed with diabetic ketoacidosis and compare the following outcomes between children with prior diagnosis of type 1 diabetes mellitus and children without prior diagnosis of type 1 diabetes mellitus length of hospital stay, severity on admission, insulin dosage, time of continuous insulin use, volume of fluids infused during treatment, and complications. Methods: A retrospective descriptive study with review of medical records of patients admitted to the pediatric intensive care unit of a referral hospital from June 2013 to July 2015. The following data regarding 52 admissions were analyzed: age, sex, weight, body surface area, signs, symptoms and severity on admission, blood gas, blood glucose, glycated hemoglobin, serum osmolarity, and index of mortality. The insulin dosage, time of continuous insulin use, volume administered in the expansion phase and in the first 24 h, length of stay, and complications such as electrolyte disturbances, hypoglycemia, cerebral edema, and death were compared between the two groups. Results: Patients without a previous diagnosis of DM1 were younger at admission, with mean age of 8.4 years (p < 0.01), reported more nausea or vomiting, polydipsia and polyuria, and showed more weight loss (p < 0.01). This study also observed a higher prevalence of hypokalemia (p < 0.01) and longer hospital stay in this group. Conclusions: No differences in severity between groups were observed. The study showed that children without prior diagnosis of type 1 diabetes mellitus were younger at admission, had more hypokalemia during the course of treatment, and had greater length of hospital stay.

Resumo Objetivo: Descrever as características de pacientes até 14 anos admitidos com diagnóstico de cetoacidose diabética e comparar desfechos entre os pacientes com diabete melito tipo 1 prévio e aqueles sem diabete melito tipo 1 prévio: tempo de internação, gravidade na admissão, dose de insulina usada, tempo de insulinização contínua, volume de líquido infundido durante o tratamento e complicações. Métodos: Estudo descritivo retrospectivo com revisão de prontuários de pacientes internados na UTI pediátrica de um hospital de referência de junho de 2013 a julho de 2015. Analisamos os seguintes dados referentes a 52 internações: idade, sexo, peso, superfície corporal, sinais, sintomas, gravidade na admissão, gasometrias, glicemia, hemoglobina glicada, osmolaridade sérica e índice de mortalidade. As crianças com diabete já diagnosticado foram comparadas com aquelas sem diagnóstico prévio quanto à dose de insulina, tempo de insulinização contínua, volume infundido na fase de expansão e nas primeiras 24 horas, tempo de internação e complicações como distúrbios hidroeletrolíticos, hipoglicemia, edema cerebral e morte. Resultados: Os pacientes sem diagnóstico prévio de DM I eram mais jovens no momento da admissão, com média de 8,4 anos (p < 0,01). Relataram mais sintomas como vômitos, polidipsia e poliúria e apresentaram mais perda de peso (p < 0,01). Observamos maior prevalência de hipocalemia (p < 0,01) e maior tempo de internação no grupo acima citado. Conclusões: Não observamos diferenças quanto à gravidade entre os grupos. Pacientes diabéticos prévios eram mais jovens na admissão, apresentaram mais hipocalemia durante o tratamento e permaneceram mais tempo internados.

Diabetes Mellitus tipo 2 con tendencia a la cetosis: Caso clínico / Ketosis prone type 2 diabetes (KPD)

Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations.

Cetoacidosis diabética: Casuística 2008-2012, epidemiología y fisiopatología / Treatment of diabetic ketoacidosis using 2009 American Diabetes Association guidelines

Background: During 2009, new guidelines for the treatment of diabetic ketoacidosis were published by the American Diabetes Association. Aim: To assess the impact of new treatment guidelines on the evolution of patients treated for diabetic ketoacidosis (KAD). Patients and Methods: Anonymous data was obtained from computational medical records of patients treated for KAD at our institution two years before (“Traditional Protocol”) and TWO years after (“ADA-2009 Protocol”) the publication of the 2009 American Diabetes Association (ADA) KAD guidelines. Results: Twenty three patients aged 36.5 ± 15.1 years were treated with the traditional method and 23 patients aged 44.4 ± 21.1 years were treated following 2009 ADA guidelines. Among patients treated with the traditional protocol and treated following ADA 2009 guidelines, the diabetes type 1/type 2 ratio was18/5 and 19/16 respectively (p = NS), the glycosylated hemoglobin on admission was 12.6 ± 2.5 and 14.3 ± 2.7% respectively (p = 0.03), minimal blood pH was 7.15 ± 0.14 and 7.19 ± 0.09 respectively (p = NS), bicarbonate was required in seven and no patient respectively (p = 0.01), hypokalemia < 3.5 mEq/L occurred in 78.2 and 48.5% of patients (p = 0.03), the lapse until resolution was 28.7 ± 28.0 and 28.8 ± 20.6 hours (p = NS). Only one patient, treated following ADA 2009 guidelines, died. Conclusions: Introduction of the ADA-2009 protocol for the treatment of KAD resulted in decrease in the use of intravenous bicarbonate and a reduction in the incidence of hypokalemia. There was no impact neither in the lapse until resolution or lethality.

Occurrence of diabetic ketoacidosis and autoimmune thyroiditis in a patient treated with pegylated interferon-alpha 2b and ribavirin for chronic hepatitis C / 대한간학회지

Combined pegylated interferon and ribavirin therapy for chronic hepatitis C infection cause a wide range of side effects, including flu-like syndrome, hematological abnormalities, cardiovascular symptoms, gastrointestinal symptoms, pulmonary dysfunction, depression, and retinopathy. Interferon-alpha has been shown to be related to the development of various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, and type 1 diabetes mellitus (DM). Type 1 DM and thyroid disease respectively develop in 0.08~2.61% and 10~15% of patients treated with combined interferon-alpha and ribavirin for chronic hepatitis C. The coexistence of type 1 DM and autoimmune thyroiditis was rarely reported. We report a case of a 33-year-old female patient with chronic hepatitis C who simultaneously developed diabetic ketoacidosis and autoimmune thyroiditis after treatment with pegylated interferon-alpha 2b and ribavirin.

Cetoacidose diabética em pediatria: relato de caso / Diabetic ketoacidosis in children: case report

A cetoacidose diabética é a principal complicação aguda do Diabetes Mellitus (DM) e responsável por importante causa de morte, principalmente devido ao desenvolvimento de edema cerebral. É discutida neste trabalho a evolução clínica de um jovem de 10 anos de idade, diabético tipo I, admitido no Pronto Socorro do Hospital das Clínicas da UFMG com sintomatologia compatível com cetoacidose diabética, com melhora inicial dos padrões laboratoriais não acompanhada de melhora clínica.

The diabetic ketoacidosis is the main Diabetes Mellitus (DM) acute complication and responsible for an important cause of death, mainly due to the development of cerebral edema. This article reports a case of a 10 year old boy, previously diagnosed with DM I, admitted to the pediatric emergency of Hospital das Clínicas da UFMG with signs and symptoms compatible with diabetic ketoacidosis. Despite the initial improvement of laboratorial findings, there was not a significant clinical recovery. This scenery required new arrangements, like the use of sodium bicarbonate, which is not recommended by current consensus guidelines, considering that the patient’s venous pH was higher than 6,9.

Transient neonatal diabetes due to activating mutation in the ABCC8 gene encoding SUR1.

We report a 2 month male child presenting with diabetic ketoacidosis (DKA) and seizures treated with intravenous fluids and intravenous insulin infusion till the ketoacidosis was reversed, thereafter responding well to sulphonylureas and at age of 13 months going into complete remission. At age of 11 mo developmental delay in the form of negative neck holding and inability to sit without support was seen. The child is 3 yr of age now ,euglycemic without any insulin or oral hypoglycemic agents but has severe developmental delay. Genetic analysis was negative for mutations of KCNJ11, 6q24, Glucokinase and IPF-1 genes. A mutation R1183W was found in the ABCC8 gene encoding SUR1, which was the cause of neonatal diabetes in this case.

Cetoacidosis diabética en adultos: causas y su manejo en un hospital regional / Management of diabetic ketoacidosis: retrospective analysis of 117 episodes

Background: In 2005, the Chilean Ministry of Health developed Clinical Guidelines to ensure the correct diagnosis and acute treatment of diabetic ketoacidosis (DKA). Aim: To analyze the real impact of the use of the Clinical Guidelines, comparing the diagnosis and treatment of DKA beforeand after 2005. Patients and Methods: Retrospective analysis of clinical records of adults with DKA, treated between 2001 and 2008 in a regional hospital. Results: One hundred seventeen DKA episodes, that occurred in 82 patients aged 15 to 90 years (47 percent females), were analyzed. Eightytwo percent of patients were known diabetics. Treatment discontinuation was the cause of DKA in 37 percent of patients, followed by infections in 37 percent and onset of diabetes mellitus in 17 percent. Ninety seven percent of patients previous episode of DKA were using insulin. Two patients died (1.7 percent) and DKA complications were uncommon. Bicarbonate and potassium were over prescribed despite therecommendation of Clinical Guidelines (p < 0.05). The use of infusion pumps increased after the incorporation of the Clinical Guidelines. Conclusions: A low impact of Clinical Guidelines on themanagement of DKA was observed in this group of patients. Insulin users have a higher risk for developing DKA.

Clinical profile and outcome of diabetic ketoacidosis in children.

Background. There is little information on the clinical profile and outcome of children with diabetic ketoacidosis in India. We analysed the data of children managed by us at a tertiary care hospital. Methods. We retrospectively analysed the case records of 21 children (13 boys and 8 girls) with diabetic ketoacidosis admitted to our hospital from January 2004 to August 2008. They were managed using a standard protocol including intravenous fluids and insulin infusion. Blood glucose, serum electrolytes, blood urea, arterial blood gases and urinary ketones were monitored at regular intervals. The outcomes were assessed. Results. The median age at presentation was 8 years and 17 children (80%) were detected to have diabetes mellitus at the time of presentation. Twelve children (57%) presented with severe diabetic ketoacidosis. Polyuria with polydipsia was the commonest clinical presentation (17). All of them had elevated HbA1C levels. The average length of stay in the paediatric intensive care unit was 2.9 days. The median time for the arterial blood gases to become normal was 19 hours and for urinary ketones to become non-detectable was 28 hours. None of the children received bicarbonate and there were no complications or mortality. All the children were doing well on follow up at 3 months. Conclusion. The outcome of active management of diabetic ketoacidosis in children is rewarding. The use of a standard protocol for management was associated with no complications or mortality in our series.

Complicações hiperglicêmicas agudas no diabetes melito tipo 1 do jovem: [revisão] / Hyperglycemic acute crisis in type 1 diabetes mellitus in youth: [review]

A principal complicação hiperglicêmica no diabetes melito tipo 1 (DM1) é a cetoacidose diabética (CAD). Embora variações nos protocolos possam ocorrer, os princípios básicos que norteiam o tratamento devem ser os mesmos. A recuperação inicial da capacidade circulatória, com a infusão rápida de solução salina na dose de 20 mL/kg, que pode ser repetida, é o ponto de partida para o tratamento. A partir daí, a reposição de volume é relativamente lenta, e o objetivo principal é corrigir gradualmente os distúrbios metabólicos instalados, sem ocasionar variações muito intensas e muito rápidas na osmolalidade, fator de risco para complicações. Atenção ao desenvolvimento de edema cerebral que, uma vez suspeitado, deve ser imediatamente corrigido, sob pena de óbito ou seqüelas neurológicas. A administração de insulina ultra-rápida, por via subcutânea, mostra-se eficaz e simplifica o atendimento do paciente. A CAD é uma situação grave, ainda com alta mortalidade, e seu tratamento deve ser dirigido aos pontos principais que levaram ao quadro clínico, com correções graduais, sob risco de se agravar o quadro.

Diabetic ketoacidosis (DKA) is the main hyperglycemic complication in type 1 Diabetes Mellitus (DM1). The basic principles in treatment have to be followed carefully. The patient with DKA has a very deep volume depletion. To restore the circulatory capacity is the first step. From this point on, the restoration of the lost fluids is slow, around 1 percent per hour, aiming at the correction of the metabolic disturbance already on and avoiding great fluctuations in osmolality, which increases the risk of having complications. Attention to the development of cerebral edema, which, once suspected, deserves an urgent treatment plan, trying to avoid neurologic sequelae or even death. Subcutaneous ultra-rapid insulin has been demonstrated to be efficient and easier to use. As the perfusion gets improved and the levels of insulin increase, the lipolysis is blocked, as well as the generation of ketones and so the acidemia tends to be solved. DKA is still a high-mortality condition. And to be in a hurry frequently leads to neurologic sequelae and even to a fatal outcome.

Euglycemic ketoacidosis

The purpose of this ariticle is to highlight the importance of not relying exclusively on blood glucose measurements when assessing sick type I diabetics. Urinary ketones and venous bicarbonate are essential in making the diagnosis of relatively low blood glucose plus ketoacidosis, that we call euglycaemic ketoacidosis

Acidose metabólica na infância: por que, quando e como tratá-la? / Metabolic acidosis in childhood: why, when and how to treat

OBJETIVO: Apresentar uma revisão atualizada e crítica sobre os mecanismos das principais patologias associadas e o tratamento da acidose metabólica, discutindo aspectos controversos quanto aos benefícios e riscos da utilização do bicarbonato de sódio e outras formas de terapia. FONTES DOS DADOS: Revisão da literatura publicada, obtida através de busca eletrônica com as palavras-chave acidose metabólica, acidose láctica, cetoacidose diabética, ressuscitação cardiopulmonar, bicarbonato de sódio e terapêutica nas bases de dados PubMed/MEDLINE, LILACS e Cochrane Library, entre 1996 e 2006, além de publicações clássicas referentes ao tema, sendo selecionadas as mais atuais e representativas, buscando-se consensos e diretrizes. SíNTESE DOS DADOS: A utilização de bicarbonato de sódio não demonstra benefícios no quadro hemodinâmico, evolução clínica, morbidade e mortalidade nos quadros de acidose metabólica de anion gap elevado, relacionados à acidose láctica, cetoacidose diabética e ressuscitação cardiorrespiratória. Assim, a sua utilização rotineira não é indicada. Devem ser considerados os potenciais efeitos colaterais. O tratamento da doença de base é fundamental para reversão do processo. Outras terapias alternativas não demonstram efetividade comprovada em grande escala. CONCLUSÕES: Apesar dos efeitos conhecidos da acidemia em situações críticas no organismo, discute-se o papel protetor da acidemia nas células sob hipoxemia e os riscos da alcalemia secundária à intervenção medicamentosa. Existe consenso na reposição de álcalis e bicarbonato de sódio nos casos de acidose de anion gap normal; entretanto, nos casos de acidose de anion gap elevado, particularmente na acidose láctica, cetoacidose diabética e na ressuscitação cardiorrespiratória, o uso de bicarbonato de sódio não demonstra benefícios, além dos potenciais efeitos adversos, o que torna restrita sua indicação. Apesar da controvérsia, o único ponto concordante refere-se à abordagem...

OBJECTIVES: To critically discuss the treatment of metabolic acidosis and the main mechanisms of disease associated with this disorder; and to describe controversial aspects related to the risks and benefits of using sodium bicarbonate and other therapies. SOURCES: Review of PubMed/MEDLINE, LILACS and Cochrane Library databases for articles published between 1996 and 2006 using the following keywords: metabolic acidosis, lactic acidosis, ketoacidosis, diabetic ketoacidosis, cardiopulmonary resuscitation, sodium bicarbonate, treatment. Classical publications concerning the topic were also reviewed. The most recent and representative were selected, with emphasis on consensus statements and guidelines. SUMMARY OF THE FINDINGS: There is no evidence of benefits resulting from the use of sodium bicarbonate for the hemodynamic status, clinical outcome, morbidity and mortality in high anion gap metabolic acidosis associated with lactic acidosis, diabetic ketoacidosis and cardiopulmonary resuscitation. Therefore, the routine use of sodium bicarbonate is not indicated. Potential side effects must be taken into consideration. Treating the underlying disease is essential to reverse the process. The efficacy of other alternative therapies has not been demonstrated in large-scale studies. CONCLUSIONS: Despite the known effects of acidemia on the organism in critical situations, a protective role of acidemia in hypoxic cells and the risk of alkalemia secondary to drug interventions are being considered. There is consensus regarding the advantages of alkali and sodium bicarbonate therapy in cases with normal anion gap; however, in the presence of high anion gap acidosis, especially lactic acidosis, diabetic acidosis and cardiopulmonary resuscitation, the use of sodium bicarbonate is not beneficial and has potential adverse effects, limiting its indication. The only points of agreement in the literature refer to the early treatment of the underlying disease...

Cetoacidosis diabética reversible con metotrexato: Resistencia al tratamiento insulínico. Caso clínico / Diabetic ketoacidosis responsive to methotrexate in a patient with a mixed connective tissue disease

We report a 42 year-old woman with a hypothyroidism and a mixed connective tissue disease treated with prednisone and methotrexate. The patient had normal blood glucose levels but when the methotrexate dose was tapered, she presented a diabetic ketoacidosis that required up to 520 units of insulin per day. Due to the intensification of the mixed connective tissue disease symptoms, the doses of methotrexate and prednisone were increased again with a simultaneous normalization of serum glucose levels and glucose tolerance. In the following six months, when the dose of methotrexate was tapered again, the hyperglycemia reappeared and was again controlled increasing the dose. Thirty months after the episode of keotacidosis, the patient was with a weekly dose of methotrexate, asymptomatic and with a normal glucose tolerance. Anti insulin antibodies were not detected and anti islet antibodies were indeterminate, due to interference with antinuclear antibodies. It is possible that the episode of ketoacidosis was unveiled by an autoimmune phenomenon.

Cetoacidose diabética desencadeada por resistência imunológica à insulina / Diabetic ketoacidosis induced by immunologic insulin resistance

A cetoacidose diabética (CAD) é a emergência endocrinológica mais freqüente e de boa evoluçäo, na maior parte dos casos. Os autores apresentam evoluçäo atípica de três casos de CAD precipitada por resistência imunológica à insulina (RII). RELATO DE CASO. Três pacientes: H.M.L. (46 anos, diabetes mellitus (DM) tipo II, há 6 anos), D.R.J (39 anos, DM, secundário à pancreatopatia, há 11 anos) e D.L.S. (54 sanos, DM tipo II, há 9 anos) foram admitidos na Unidade de primeiro Atendimento do Hospital Säo Paulo em CAD: H.M.L. (glicemia: 716mg/dL, pH: 6,8), D.R.J. (glicemia: 684mg/dL, pH 6,.9) e D.L.S. (glicemia: 384mg/dL, pH: 7,2), todos apresentavam cetonúria. As necessidades de insulina para o controle metabólico foram: H.M.L.: 1.369UI, D.R.J.: 1.496UI, D.I.S. 1.369UI em, respectivamente: 212, 206 e 72 horas. Os anticorpos antiinsulina (AI) foram dosados por RE e ELISA: H.M.L.: 7.186nU/ml, 3,6IE; D.R.J.: 7,879nU/mL, 3,24IE; D.I.S: 8.377nU/mL, 2,88IE. O seguimento ambulatorial revelou queda progressiva dos níveis de AI:H.M.L.: 3.393nU/mL, 1,39, após dez meses da CAD; d.r.j.: 4,673Nu/Ml, 2,34 E d.i.s.: 1,510nU/mL, ambos após 18 meses da CAD. A queda nos níveis de anticorpos foi significativa nos três pacientes e foi acompanhada de melhor controle metabólico. Discussäo. A ausência de fator desencadeante, o elevado tempo, as altas doses de insulina empregadas para a compensaçäo metabólica levaram os autores à suspeita diagnóstica de RII. O diagnóstico foi confirmado pelos altos níveis séricos dos AI. O controle metabólico nestes pacientes foi obtido somente após a introduçäo de insulina na humanizada. CONCLUSAO. A resistência imunológica à insulina pode ser uma das causas de CAD sem fator precipitante aparente e má resposta às medidas terapêuticas habituais