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Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous Renal Replacement Therapy.

ABSTRACT: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder presenting as uncontrolled hyperglycemia during the first 6 months of life. Hyperglycemic hyperosmolar state (HHS) is quite rare in NDM patients, and reported experience with this condition is limited. Continuous renal replacement therapy (CRRT) is frequently used as a mode of dialytic treatment in critically ill patients with acute renal failure, but has seldom been used in patients with diabetic ketoacidosis (DKA) and HHS. We report the case of a 2-month-old infant admitted to our hospital presenting with dyspnea and lethargy. Blood gas showed severe hyperosmotic DKA. After 21 h of fluid and insulin therapy, the baby presented with increased drowsiness and irregular respiration, which suggested cerebral edema. Moreover, the DKA and HHS were exacerbated. After 18 h of CRRT, the patient gradually recovered from DKA and HHS. The gene analysis revealed a de novo mutation (c.602G > A (p.R201H)) of the KCNJ11 gene, and oral glibenclamide successfully replaced insulin treatment in the patient.

SUBMITTER: Chen T

PROVIDER: S-EPMC6167281 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous Renal Replacement Therapy.

Chen Ting T Zhang Dandan D Bai Zhenjiang Z Wu Shuiyan S Wu Haiying H Xie Rongrong R Li Ying Y Wang Fengyun F Chen Xiuli X Sun Hui H Wang Xiaoyan X Chen Linqi L

Diabetes therapy : research, treatment and education of diabetes and related disorders 20180809 5

Neonatal diabetes mellitus (NDM) is a rare monogenic disorder presenting as uncontrolled hyperglycemia during the first 6 months of life. Hyperglycemic hyperosmolar state (HHS) is quite rare in NDM patients, and reported experience with this condition is limited. Continuous renal replacement therapy (CRRT) is frequently used as a mode of dialytic treatment in critically ill patients with acute renal failure, but has seldom been used in patients with diabetic ketoacidosis (DKA) and HHS. We report ...[more]

PMID: 30094785

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Project description:Introduction: Glycemic management in the intensive care unit is an evolving practice area. This evolution has included the refinement of blood glucose targets, matching glycemic management to premorbid status, and investigations into the impact of glycemic variability and relative hypoglycemia on ICU outcomes. The interplay between these phenomena and absolute hypoglycemia has yet to be investigated in hyperglycemic emergencies. Objectives: To examine the incidence of and risk factors for relative hypoglycemia and absolute hypoglycemia in patients admitted to an intensive care unit for the management of hyperglycemic emergencies. Methods: This was a retrospective, single-center, exploratory analysis of adults admitted to the medical intensive care unit for diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome. The primary outcome was the incidence of relative hypoglycemia, defined as a blood glucose level 30% lower than baseline. The baseline was determined by the estimated average blood glucose calculated from hemoglobin A1c within 3 months of index admission. Secondary outcomes were ICU length of stay, glycemic variability, and incidence of absolute hypoglycemia.Results: Relative hypoglycemia was observed in 60% of patients in the cohort. Longer insulin infusion duration and higher hemoglobin A1c levels were found to statistically increase the risk of developing relative hypoglycemia. Higher glycemic variability and longer ICU length of stay were associated with the risk of developing absolute hypoglycemia. Conclusions: Relative hypoglycemia is a frequent occurrence in this patient population. Hemoglobin A1c and duration of the insulin infusion statistically influenced the risk of developing relative hypoglycemia. Higher glycemic variability and longer ICU stay were significantly associated with developing absolute hypoglycemia. While relative hypoglycemia is common in hyperglycemic emergencies, the clinical impact remains uncertain and warrants additional investigation.

Project description:Aims/hypothesisThe finding that patients with diabetes due to potassium channel mutations can transfer from insulin to sulfonylureas has revolutionised the management of patients with permanent neonatal diabetes. The extent to which the in vitro characteristics of the mutation can predict a successful transfer is not known. Our aim was to identify factors associated with successful transfer from insulin to sulfonylureas in patients with permanent neonatal diabetes due to mutations in KCNJ11 (which encodes the inwardly rectifying potassium channel Kir6.2).MethodsWe retrospectively analysed clinical data on 127 patients with neonatal diabetes due to KCNJ11 mutations who attempted to transfer to sulfonylureas. We considered transfer successful when patients completely discontinued insulin whilst on sulfonylureas. All unsuccessful transfers received ≥0.8 mg kg(-1) day(-1) glibenclamide (or the equivalent) for >4 weeks. The in vitro response of mutant Kir6.2/SUR1 channels to tolbutamide was assessed in Xenopus oocytes. For some specific mutations, not all individuals carrying the mutation were able to transfer successfully; we therefore investigated which clinical features could predict a successful transfer.ResultsIn all, 112 out of 127 (88%) patients successfully transferred to sulfonylureas from insulin with an improvement in HbA1c from 8.2% (66 mmol/mol) on insulin, to 5.9% (41 mmol/mol) on sulphonylureas (p = 0.001). The in vitro response of the mutation to tolbutamide determined the likelihood of transfer: the extent of tolbutamide block was <63% for the p.C166Y, p.I296L, p.L164P or p.T293N mutations, and no patients with these mutations successfully transferred. However, most individuals with mutations for which tolbutamide block was >73% did transfer successfully. The few patients with these mutations who could not transfer had a longer duration of diabetes than those who transferred successfully (18.2 vs 3.4 years, p = 0.032). There was no difference in pre-transfer HbA1c (p = 0.87), weight-for-age z scores (SD score; p = 0.12) or sex (p = 0.17).Conclusions/interpretationTransfer from insulin is successful for most KCNJ11 patients and is best predicted by the in vitro response of the specific mutation and the duration of diabetes. Knowledge of the specific mutation and of diabetes duration can help predict whether successful transfer to sulfonylureas is likely. This result supports the early genetic testing and early treatment of patients with neonatal diabetes aged under 6 months.

Dataset Information

Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous Renal Replacement Therapy.

Publications

Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous Renal Replacement Therapy.

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