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 normoglicémica en el embarazo: caso clínico / Normoglycemic diabetic ketoacidosis in pregnancy: report of one case

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

Diabetic ketoacidosis: difference between potassium determined by blood gas analysis versus plasma measurement / Cetoacidose diabética: diferença entre as concentrações do potássio na gasometria sanguínea versus potássio plasmático

OBJECTIVE: To evaluate the accuracy of potassium concentrations measured by blood gas analysis (PBG) compared with laboratory serum potassium (LSP), in the initial care of patients with diabetic ketoacidosis (DKA). SUBJECTS AND METHODS: Fifty three patients with diabetes mellitus were evaluated in a retrospective analysis. PBG was carried out using the Radiometer ABL 700 (Radiometer Copenhagen®), and results were compared with LSP ADVIA 1650 Chemistry system (Siemens®), the gold standard method. Both methods are based on potentiometry. RESULTS: Mean PBG was 3.66 mmol/L and mean LSP was 4.79 mmol/L. Mean difference between PBG and LSP was -1.13 mmol/L (p < 0.0005, 95 percent CI, -1.39 to -0,86). Lin concordance correlation coefficient was rc = 0.28 (95 percent CIb, 0.10 to 0.45), demonstrating low concordance between the methods. CONCLUSION: Although PBG measurement is faster and easier, it should not be used as a surrogate for LSP in the clinical treatment of DKA.

OBJETIVO: Avaliar a acurácia da mensuração da concentração de potássio realizado nos analisa-dores de gasometria sanguínea (PGS) em relação ao potássio plasmático laboratorial (PPL) no atendimento inicial dos pacientes com cetoacidose diabética (CAD). SUJEITOS E MÉTODOS: Foram avaliados, retrospectivamente, 53 pacientes com diabetes melito e CAD. A análise do PGS foi realizada pelo equipamento ABL 700 (Radiometer Copenhagen®), sendo este comparado ao método padrão-ouro de PPL ADVIA 1650 (Siemens®), ambos por potenciometria. RESULTADOS: A média do PGS foi de 3,66 mmol/L e do PPL, de 4,79 mmol/L. A diferença das médias do PGS em relação ao PPL foi de -1,13 mmol/L (p < 0,0005, IC = 95 por cento; -1,39 a -0,86). O coeficiente de concordância de Lin foi de rc = 0,28 (ICb = 95 por cento; 0,10 a 0,45), demonstrando, assim, uma baixa concordância entre os métodos. CONCLUSÃO: Apesar de a realização do PGS ser tecnicamente mais rápida e fácil, não deve ser usada como parâmetro substituto ao PPL para o tratamento clínico da CAD.

Hipertrigliceridemia grave na cetoacidose diabética: relato de caso / Severe hypertriglyceridemia in diabetic ketoacidosis: case report

OBJETIVOS: A cetoacidose diabética é uma entidade frequente nos serviços de emergência que requer tratamento rápido e eficaz. Algumas vezes pode estar associada ao aumento do nível de triglicérides, expondo o paciente ao risco de pancreatite. MÉTODOS: Foi relatado o caso de uma paciente de 38 anos com cetoacidose diabética associada à hipertrigliceridemia grave (triglicérides: 11.758 mg/dL). RESULTADOS: Paciente foi admitida em Unidade de Terapia Intensiva, realizando-se hidratação e insulinoterapia endovenosa com resolução do quadro. Durante toda a internação, a paciente não apresentou elevação de amilase e lipase que pudessem sugerir pancreatite, e houve redução importante no nível de triglicérides. Não foram encontrados outros relatos de casos nacionais com esses valores de triglicérides. CONCLUSÃO: Concluiu-se que, em casos de cetoacidose diabética, deve-se pedir o perfil lipídico dos pacientes, incluindo a contagem de triglicérides, tendo em vista a prevalência não desprezível de complicações relacionadas à hipertrigliceridemia e à pancreatite.

OBJECTIVES: Diabetic ketoacidosis is a recurrent problem in the emergency room that requires prompt and effective treatment. Usually, it may be associated with an increase in triglyceride levels, exposing the patient to the risk of pancreatitis. METHODS: We report the case of a 38-year-old female patient with diabetic ketoacidosis and severe hypertriglyceridemia (triglycerides: 11.758 mg/dL). RESULTS: The patient was admitted to the Intensive Care Unit. Hydration and intravenous insulin were performed with success. During hospitalization, the levels of triglycerides decreased significantly and the levels of amylase and lipase remained at normal ranges, not suggesting pancreatitis. No other Brazilian cases with these levels of triglycerides were found. CONCLUSION: We conclude that, in diabetic ketoacidosis, lipid profile, including triglycerides, should be requested, due to a not negligible prevalence of complications such as hypertriglycerides and pancreatitis.

Serum interleukin-18 levels are raised in diabetic ketoacidosis in Chinese children with type 1 diabetes mellitus.

OBJECTIVE: To investigate the role of serum interleukin (IL-18) in children with type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). DESIGN: Case-control study. SUBJECTS: Sixty-one children with T1DM including 28 with DKA and 33 without DKA and 30 age - and sex-matched healthy controls were recruited. METHODS: Serum IL-18, IL-12, and IFN-gamma levels were measured in all subjects by enzyme linked immunosorbent assay. RESULTS: Serum IL-18 levels were significantly higher in patients with DKA than those in patients without DKA (759.2 +/- 353.8 pg/mL vs. 634.9 +/- 399.7 pg/mL, P = 0.001) and healthy controls (310.0 +/- 265.3 pg/mL). The serum IL-12 and IFN-gamma levels were not different between patients and controls (277.5 +/- 207 pg/mL vs. 351.4 +/- 223.4 pg/mL, P = 0.45 and 7.02 +/- 7.53 pg/mL vs. 5.59 +/- 5.34 pg/mL, P = 0.21, respectively). CONCLUSION: Serum IL-18 levels are increased in children with type 1 diabetes mellitus and could be a predictor of diabetic ketoacidosis.

Permanent neonatal diabetes due to KCNJ11 gene mutation.

Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of diabetes within the first six months of life and insulin dependence life long. It has been recently discovered that mutation in KCNJ11 gene encoding Kir6.2, the pore forming subunit of ATP sensitive potassium channel (K ATP) is the most common cause and such patients may respond better to oral sulphonylurea drugs than insulin. Here is a rare case of permanent neonatal diabetes due to R20IC mutation in KCNJ11 gene.

Relato de caso: diabetes Flatbush - da cetoacidose ao tratamento não-farmacológico / Case report: diabetes Flatbush - from ketoacidosis to non pharmacological treatment

Um subgrupo de pacientes, em sua maioria negros ou hispânicos e obesos, tem a cetoacidose diabética (CAD) como forma de apresentação de diabetes mellitus (DM), mas, devido à sua evolução clínica, posteriormente é classificado como DM tipo 2. Estes indivíduos têm pesquisa de auto-anticorpos anti-GAD, anti-IA2 e anti-insulina negativa, mas freqüentemente em associação com HLA classe II de risco para DM tipo 1 (DRB1*03 e/ou DRB1*04). Este subtipo peculiar de DM é denominado diabetes flatbush. Neste artigo, relatamos o caso de uma paciente de origem caucasiana com tais características, na qual foi possível retirada da insulinoterapia. Os possíveis fatores associados a esta evolução favorável serão discutidos.

A subgroup of patients presents diabetic ketoacidosis at the onset of diabetes mellitus (DM) but later is classified as type 2 DM based on the clinical follow-up. These individuals, most commonly obese of African or Hispanic origin, have negative auto-antibodies associated with type 1 DM, but frequently HLA class II DRB1*03 and/or DRB1*04 are detected. This peculiar subtype of DM is commonly referred to as diabetes flatbush. Here we report the case of a Caucasian patient that exhibited the described evolution and in whom it was possible to withdraw insulin therapy. The possible factors associated with this favorable development are also discussed.

Beta-hydroxybutirate levels as a determinant for the success of diabetic ketoacidosis management.

AIM: To obtain a greater understanding of the diagnosis and evaluation of success in diabetic ketoacidosis management. METHODS: A prospective observational study was performed on patients with diabetic ketoacidosis at the Emergency Unit of Cipto Mangunkusumo General Hospital. All patients that were admitted were had their blood glucose, beta-hydroxybutirate, acetoacetate, pH, pCO2, HCO3, anion gap and consciousness levels serially monitored on upon admittance (0 hour) and the 2nd, 6th, 12th, 18th and 24(th) hours. The correlation coefficient of each examination was also calculated. The benefit of serial examination of each variable was also determined for each ketoacidosis undergoing the study. RESULTS: Out of the 19 available samples, a strong negative correlation was found between beta-hydroxybutirate and pH with a value of r>0.5 (from -0.524 to -0.833 with p<0.05) for 24 hours, compared to acetoacetate with the lowest r of -0.515 to -0.731 lasting up to 12 hours. Blood glucose and pH is correlated only at 0 hour, the same with the correlation between beta-hydroxybutirate and HCO(3). pCO2 and anion gap is better compared to that of blood glucose and acetoacetate. There is no correlation between the three and the level of consciousness. Significant serial examinations to perform are blood glucose, beta-hydroxybutirate, and HCO(3). CONCLUSION: beta-Hydroxybutirate has a stronger correlation compared to blood glucose and or acetoacetate towards pH, pCO2, HCO(3), and anion gap. Patients with ketoacidosis are recommended to undergo blood beta-hydroxybutirate examination. Serial examination should be performed for blood glucose, beta-hydroxybutirate, and bicarbonate.

Lipaemia retinalis in a case of juvenile diabetic ketoacidosis.

A rare case of diabetic retinal lipaemia is described in a 5-year-old child.

Factors Contributing to Alterations in the Level of Consciousness in Patients with Diabetic Ketoacidosis: Analysis of 189 Cases

The relation between serum osmolality, glucose, sodium, bicarbonate, arterial pH, BUN and level of consciousness was studied in 189 patients with diabetic ketoacidosis [DKA]. There was much overlap between all laboratory values among various groups, even when there was a statistically significant difference. To find a better predictor, we defined a new factor as serum osmolality/arterial pH. This factor was significantly higher in drowsy and stuporous compared with alert and drowsy patients [p=0.007 and p= 0.03 respectively], but not different between stuporous and comatose patients [p= 0.46]. Again much overlap could be seen between groups. There was at least one other problem, either as a coexisting or a precipitating factor, in 18 [23.3%] of the alert, 24 [29.2%] of the drowsy, 11 [43.4%] of the stuporous and 4 [57.1%] of the comatose group. We conclude that none of these clinico-biochemical parameters can be a reliable predictor of the level of consciousness in patients with DKA, and consideration and exclusion of other conditions associated with altered consciousness that may occur in diabetics should be routine

Reliability of serum magnesium values during diabetic ketoacidosis in children

OBJECTIVE: To determine the prevalence of hypomagnesemia in diabetic children during diabetic ketoacidosis and following restitution of acid-base balance. METHODS: Eight consecutive diabetic children, ranging in age from 8 to 16 years, hospitalized in the pediatric intensive care unit with diabetic ketoacidosis from October 1st. through December 31st, 1995. A control group of 33 metabolically stable diabetic children, and a control group of 30 healthy children. Both control groups were similar in composition regarding age and sex to the study group. None of the patients in the study group and none of the controls had Magnesium supplementation given to them during the study period. MEASUREMENTS: Total serum Magnesium concentrations were measured from peripheral venous blood in all 71 patients. For the study group serum Magnesium was determined in a serial fashion: 1. upon admission in diabetic ketoacidosis 2. 24 hours after admission 3. 72 hours after admission RESULTS: The prevalence of hypomagnesemia was 62.4 in patients with diabetic ketoacidosis, (Group 1), 25 in patients after partial correction of ketoacidosis, (Group 2), and none in patients after resolution of ketoacidosis, (Group 3). The prevalence of hypomagnesemia was 6 for the chronic, metabolically stable diabetic control group, (Group 4), but 0 for the non-diabetic control group, (Group 5). Average serum Magnesium levels were significantly lower (p less than 0.05), in patients admitted in diabetic ketoacidosis compared to those of both the diabetic and the non-diabetic control groups. Also average serum Magnesium levels were significantly lower (p less than 0.05), in patients with corrected diabetic ketoacidosis than those of the healthy control group. But there were no significant differences (p = 0.59263) in average serum Magnesium levels between the diabetic control group and the diabetic patients after resolution of ketoacidosis. CONCLUSIONS: In this study the prevalence of hypomagnesemia was documented to be higher than the average described elsewhere for pediatric, adult, and coronary intensive care units. As hypomagnesemia is an indication of Magnesium depletion, we speculate that the transient hypomagnesemia detected in our study group is an expression of a state of Magnesium depletion that is masked by correction of acidosis and the Magnesium shifts associated with it. Consequently serum Magnesium values ought to be considered most reliable during and not after correction of

Changing profile of diabetic ketosis.

Forty-three cases of diabetic ketosis were analysed to determine the mode of presentation, treatment modalities and outcome. Among these cases 62.8% were non-insulin dependent diabetes mellitus (NIDDM) patients and 37.2% belonged to the insulin dependent diabetes mellitus (IDDM) group. Six patients had blood glucose levels of more than 250 mg/dl but less than 300 mg/dl who were grouped separately for analysis under the term "euglycaemic diabetic ketoacidosis (EGDK)". Infection was the commonest precipitating factor in diabetic ketosis in all groups. Abdominal pain and vomiting occurred with NIDDM and EGDK cases. Drowsiness was common and coma was rare. Acute myocardial infarction (MI) and pulmonary oedema occurred with NIDDM cases. Shock, acidosis, acquired respiratory distress syndrome (ARDS) and mucor mycosis were seen with IDDM cases. Mortality was 7 out of 43(16.3%). Saline requirement was lower in NIDDM and EGDK cases. Intensive insulin therapy with hourly intravenous doses were needed for IDDM cases while majority of NIDDM cases could be managed with 6 hourly doses of insulin given subcutaneously or intramuscularly.

Clinical significance of glycosylated haemoglobin (HbA1C) over fasting blood sugar for monitoring metabolic control in diabetic patients with or without complications.

Glycosylated haemoglobin was studied in 30 cases of mild to severe diabetes in the age group 12-60 years. Ten patients were keto-acidotic. Glycosylated haemoglobin and fasting blood sugar levels were studied in patients with various complications of diabetes like neuropathy, nephropathy, retinopathy, keto-acidosis, cardiac and respiratory complications. There was a significant correlation between fasting blood sugar and glycosylated haemoglobin in normal subjects as well as in diabetic patients. There was a significant correlation between levels of glycosylated haemoglobin and blood sugar over preceding 4-6 weeks. Most frequent complication being retinopathy and keto-acidosis was associated with maximum glycosylated haemoglobin with poor metabolic control.

Clinical profile and treatment outcome of diabetic ketoacidosis.

Data on 143 consecutive cases with diabetic ketoacidosis (DKA) seen during the past 6 years were analysed. The group included 60 males and 83 females, aged 8-70 years (21.5 +/- 4.2). Ninety five (66.5%) were known diabetics, while 48 had DKA as the first clinical presentation. The major recognised precipitating factors were infection in 42 patients (30%) and omission of insulin in 29 patients (20%). The approximate duration of DKA prior to hospital admission ranged from 4 to 96 hours. The range of biochemical alterations on admission were: blood glucose 9.7-51.1 mmol/l, (19 +/- 4.6), potassium 3.0 to 6.9 mmol/l (5.8 +/- 1.2), sodium 132 to 148 mmol/l (138 +/- 7.5), urea 4.67 to 26.17 mmol/l (11.3 +/- 2.9) and arterial pH 6.9 to 7.34. Therapy in all patients consisted of correction of fluid and electrolyte imbalance, insulin and suitable antibiotics. Forty three patients received low dose hourly insulin while others received it in the conventional schedule. Thirty four patients (23.7%) died. The parameters which could be related to mortality included (1) duration of DKA prior to admission, (2) severity of acidosis, and (3) severity of peripheral vascular insufficiency.