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

Cetoacidosis diabética posterior a vacuna contra SARS-CoV-2: reporte de un caso / Diabetic ketoacidosis following SRS-CoV-2 vaccination: a one case report

Las emergencias hiperglicémicas como la cetoacidosis diabética (CAD) y el síndrome hiperglicémico hiperosmolar (SHH) se han descrito en el contexto de infección por SARS-CoV-2, como también secundarias a las múltiples vacunas desarrolladas contra el virus. La fisiopatología que explicaría esta asociación aún no está clara, pero existen diversas teorías que incluyen la destrucción directa de los islotes pancreáticos por el virus o secundario a mecanismos inmuno-inflamatorios. Presentamos el caso de un paciente que debutó con CAD al tercer día de la primera dosis de CoronaVac, y que posteriormente presentó hiperglicemia sin cumplir criterios de CAD luego de la segunda y tercera dosis de CoronaVac y Pfizer respectivamente. La temporalidad, como la falta de gatillante y la evolución del cuadro, apuntan a la vacuna como el principal precipitante. Por lo anterior, es importante mantener una vigilancia estricta de los efectos adversos de las vacunas y educar sobre los síntomas sugerentes de una crisis hiperglicémica para pesquisarla a tiempo y actuar oportunamente.

Hyperglycemic emergencies such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) have been reported in SARS-CoV-2 infections and after vaccination. The pathophysiology behind this association is still unclear, several theories have been described that include the direct destruction of the pancreatic islets by the virus, and some immuno-inflammatory mechanisms. We present the case of a patient who develope DKA the third day after the first dose of CoronaVac vaccine, and then hypergycemia after the second and third dose of CoronaVac and Pfizer repectively. The temporal relation, lack of a trigger and evolution of the disease, point the vaccine as the main precipitant. The strict surveillance of vaccines adverse effects and education of symptoms suggestive of hyperglicemic emergency are critical to prevent and treat promptly this kind of situations.

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.

Cetosis normoglicémica en adolescente con diabetes tipo 1 recibiendo insulina y dapaglifozina: Reporte de un caso / Euglycemic ketosis in an adolescent with type 1 diabetes on insulin and dapaglifozin: Case report

Dapaglifozina, un inhibidor del cotransportador de sodio-glucosa 2 (I-SGLT2) induce glucosuria y reduce la glicemia en adultos con diabetes tipo 2. Objetivo: Presentar una cetosis diabética “normoglicémica” en una adolescente con diabetes tipo 1 (DM1) que recibía dapaglifozina y alertar sobre el riesgo del uso I-SGLT2 que parece promisorio, pero no está aprobado en niños ni en DM1. Caso clínico: Paciente de 17 años sin cetosis durante 9 años con DM1, inició dapaglifozina 10 mg/día para reducir la insulina y el peso. Durante 11 meses de tratamiento tuvo cetonas capilares indetectables, redujo el índice de masa corporal 23,9 a 21,1 kg/m², la insulina basal 40 a 17 U, la hemoglobina glicosilada 8,3 a 7,5%, la glicemia capilar 175 a 161 mg/dl y la variabilidad de la glucosa (desvío estándar 85 a 77). Inesperadamente aparecieron náuseas y vómitos. La paciente portaba bomba de insulina con monitorización continua de glucosa, bien calibrada (glucosas intersticiales concordantes con glicemias), que mostraba glucosa estable bajo 200 mg/dl. Recibió insulina pero los vómitos persistieron; en tres horas, aparecieron deshidratación y desmayos, con cetonas 4,6 nmol/l y glicemia 224 mg/dl. Recibió suero fisiológico, ondansetrón, carbohidratos y varias dosis de insulina con pronta recuperación del estado general e hidratación, sin embargo, la cetosis continuó durante 24 horas. Cabe destacar que la bomba estaba funcionando bien y no se cambió la cánula. Al superar la cetosis, continuó con la misma cánula con buen control metabólico. Conclusión: Es importante sospechar la cetosis diabética normoglicémica por ser de riesgo vital.

Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 inhibitor (SGLT2-I) induces glycosuria and reduces hyperglycemia in adults with type 2 diabetes. Objective: To present an “euglycemic” diabetic ketosis in an adolescent with type 1 diabetes (T1D) receiving dapagliflozin, to alert about the risk of a drug not approved in children nor in T1D. Case report: A 17 years old adolescent with T1D during 9 years, was started on dapagliflozin 10 mg / day to reduce insulin dose and weight. During 11 months on treatment, capillaries ketones were undetectable and she exhibited a reduction in body mass index 23.9 to 21.1 kg/m2, basal insulin 40 to 17 U, glycated hemoglobin 8.3 to 7.5%, capillary glucose 175 to 161 mg/dl and glucose variability (standard deviation) 85 to 77. Suddenly nausea and vomits appeared. The patient was on an insulin pump and well calibrated continuous glucose monitoring, showing stable glucose levels under 200 mg/dl, and an insulin bolus was delivered. Vomiting without hyperglycemia persisted; three hours later, she was severely dehydrated and fainting, with ketones 4.6 nmol/l and glucose 224 mg/dl. She received IV saline fluids, ondansetron, carbohydrates and several insulin boluses. Hydration and general condition improved soon, however despite several insulin doses, ketosis continued for 24 hours. It is remarkable that the pump was working well and the cannula was not changed. After the ketosis was resolved, she continued using the same cannula with good metabolic control. Conclusion: Euglycemic ketosis is a life-threatening condition that must be suspected.

Cetoacidosis diabética euglicémica asociada a inhibidor de cotransportador de sodio glucosa Tipo 2 en paciente con diabetes Mellitus Tipo 1 / Diabetic ketoacidosis with mild hyperglycemia associated with the use of canagliflozin. report of one case with type 1 diabetes

Diabetic ketoacidosis with mild hyperglycemia is a major complication of sodium-glucose cotransporter 2 inhibitors. Although its use is not approved for patients with type 1 diabetes mellitus, the drug is often prescribed with the hope of optimizing metabolic control. We report a 20 years old female with hypothyroidism and type 1 diabetes consulting for vomiting and abdominal pain. The patient had used canagliflozin during the two previous months. Laboratory showed a blood glucose of 200 mg/dl, a severe metabolic acidosis (pH 7.1) and ketonemia. The patient was successfully treated in the intensive care unit.

Olanzapine-induced diabetic ketoacidosis in a Saudi female

A twenty-seven-year-old Saudi woman with a 10-year history of bipolar affective disorder required numerous hospitalizations. On her last admission, Olanzapine [15 mg q.i.d.] and Clonazepam [2 mg bid] were initiated. Before treatment with Olanzapine, she had normal random serum glucose levels. Her body weight was 75 kg, and her body mass index [BMI] was 33.3 kg/m[2]. On discharge, controlled-release sodium valproate [750 mg bid] was added to her regimen and Olanzapine dose was decreased to 10 mg/day. After few months, she developed progressive somnolence, polyuria, and polydipsia. Serum glucose was 800 mg/dl, and urine was positive [+3] for ketones. She was diagnosed as diabetic ketoacidosis [DKA]. Her weight had increased 9 kg. The patient was treated with intravenous fluids and insulin. She was placed on a sliding scale insulin regimen besides Metformin. Olanzapine was discontinued and replaced with Haloperidol

Diabetes mellitus associado com drogas antipsicóticas atípicas: relato de caso e revisão da literatura / Diabetes mellitus associated with atypical antipsychotic medications: case report and review of the literature

Desde a introdução das medicações antipsicóticas atípicas, iniciando com a clozapina, em 1990, muitos relatos associam essas drogas ao desenvolvimento de diabetes mellitus, entre outros distúrbios metabólicos, assim como abertura da doença como cetoacidose. Relatamos o caso de um paciente de 28 anos, com esquizofrenia, admitido em cetoacidose diabética 1 mês após início da terapia com clozapina, sem relação com ganho de peso, mantendo-se com níveis satisfatórios de glicemia, sem tratamento, após suspensão da droga. Revisamos o assunto, com outros casos relatados até o momento, incluindo a associação de outros antipsicóticos atípicos igualmente envolvidos em distúrbios endócrinos. Objetivamos, com o relato deste caso, aumentar a atenção dos clínicos envolvidos no tratamento dos pacientes portadores de distúrbios psiquiátricos para a possibilidade do surgimento de diabetes durante a terapia, e enfatizar a necessidade de aumento da vigilância e do acompanhamento metabólico desses pacientes.

Since the introduction of atypical antipsychotic medications, starting with clozapine in 1990, many studies have associated these drugs with the development of diabetes among other metabolic disorders, as well as with the onset of the disease as ketoacidosis. We report the case of a 28-year-old patient with schizophrenia who was admitted with diabetic acidosis 1 month after the beginning of clozapine therapy. No weight gain was reported and the patient maintains satisfactory glycemia levels with no treatment required after discontinuation of the drug. The literature on this subject and cases reported so far are reviewed, including the association of other atypical antipsychotic drugs also involved in endocrine disorders. The objective of this report is to raise the awareness of physicians treating psychiatric patients to the possibility of new-onset diabetes during therapy with atypical antipsychotic drugs and to emphasize the necessity for increased vigilance and close metabolic follow-up of these patients.

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.

Acute pancreatitis and diabetic ketoacidosis in non-diabetic person while on treatment with sodium valproate, chlorpromazine and haloperidol.

A nondiabetic young male patient in hypomanic phase of bipolar disorder on maintenance treatment with sodium valproate, developed transient episode of acute pancreatitis and diabetic ketoacidosis after addition of chlorpromazine and halopridol. It subsided completely within six weeks and his blood sugar was normal without any antidiabetic therapy. Simultaneous occurrence of acute pancreatitis and diabetic ketoacidosis is reported as a very rare complication of combination of antipsychotic drugs sodium valproate, chlorpromazine and haloperidol. Blood sugar should be periodically monitored in patients on sodium valproate and antipsychotic medication.

Hyperglycemic ketoacidosis with diazinon poisoning.

The toxic manifestations of organophosphates including diazinon have been nicely described by many authors after their use as pesticides during the last three decades, but there is no report to show ketoacidosis with organophosphate compounds while literature is available mentioning the absence of ketois with these compounds. This report describes a case of hyperglycemic ketoacidosis after diazinon poisoning of a 13 year old girl student