Severe Metabolic Decompensation Research Articles

Il supporto nutrizionale nell’anoressia nervosa

Paediatric departments are increasingly faced with adolescents with anorexia nervosa in severe nutritional and metabolic decompensation. Artificial nutritional support, often indispensable in the most critical phases of the course, requires careful evaluation of the clinical conditions at the time of hospitalization and equally punctual monitoring of blood chemistry variables during re-feeding. Prolonged reduced caloric intake and malnutrition, especially in its most extreme forms, can cause damage to various organs and systems and the refeeding syndrome must be kept in mind as a further comorbidity and aggravating factor of the patient's conditions. Through the description of a clinical case of particular complexity, some aspects related to the hospital treatment of anorexia nervosa are discussed.

Clinical and molecular characterization of novel FARS2 variants causing neonatal mitochondrial disease

FARS2 encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS), which is essential for charging mitochondrial (mt-) tRNAPhe with phenylalanine for use in intramitochondrial translation. Many biallelic, pathogenic FARS2 variants have been described previously, which are mostly associated with two distinct clinical phenotypes; an early onset epileptic mitochondrial encephalomyopathy or a later onset spastic paraplegia. In this study, we report on a patient who presented at 3 weeks of age with tachypnoea and poor feeding, which progressed to severe metabolic decompensation with lactic acidosis and seizure activity followed by death at 9 weeks of age. Rapid trio whole exome sequencing identified compound heterozygous FARS2 variants including a pathogenic exon 2 deletion on one allele and a rare missense variant (c.593G > T, p.(Arg198Leu)) on the other allele, necessitating further work to aid variant classification. Assessment of patient fibroblasts demonstrated severely decreased steady-state levels of mtPheRS, but no obvious defect in any components of the oxidative phosphorylation system. To investigate the potential pathogenicity of the missense variant, we determined its high-resolution crystal structure, demonstrating a local structural destabilization in the catalytic domain. Moreover, the R198L mutation reduced the thermal stability and impaired the enzymatic activity of mtPheRS due to a lower binding affinity for tRNAPhe and a slower turnover rate. Together these data confirm the pathogenicity of this FARS2 variant in causing early-onset mitochondrial epilepsy.

Clinical/biochemical characteristics and related outcomes in people with new‐onset diabetes and COVID‐19: experience from a single centre

Abstract Aims: It is known that there is a bidirectional relationship between diabetes mellitus (DM) and coronavirus disease (COVID‐19). It has been described that those patients infected with SARS‐CoV‐2 could develop severe metabolic decompensation of pre‐existing or new‐onset DM, although diabetogenic effect of SARS‐CoV‐2 has still not been well consolidated. In fact, the coexistence of SARS‐CoV‐2 infection and new‐onset DM is an infrequent situation.Methods: We describe the clinical and analytical characteristics of 19 patients admitted to a Spanish tertiary hospital – all 19 having COVID‐19 infection and new‐onset DM.Results: 12/19 patients (63.2%) were female; the mean age at diagnosis of DM was 54 (39–65) years. The most frequent ethnic group was Caucasian (n=9), followed by Latin‐American (n=7); 7/19 (36.8%) previously met criteria for prediabetes due to altered basal glycaemia or HbA1c. The mean BMI at diagnosis was 32.26kg/m2 (27.62–35.18kg/m2). Eighteen of 19 patients (94.7%) showed bilateral bronchopneumonia. The mean blood glucose of the first blood was 17.5mmol/L (11.1–21.1mmol/L), and the mean HbA1c was 88mmol/mol (60–115mmol/mol). C‐peptide was requested in eight patients and it was within normal range in 87.5% (n=7) and below the inferior threshold in one case. Autoantibodies were requested in 26.3% (five patients), being negative in 4/5 (80%) and positive in 1/5 (20%). Regarding the type of diabetes diagnosed, 18 were type 2 DM and only one case was diagnosed with type 1 DM. Seventeen had simple hyperglycaemia and two suffered a diabetic ketoacidosis. The mean HbA1c at 8.0 months (5.0–12.0 months) follow‐up was 42mmol/mol (40–49mmol/mol).Conclusion: The majority of those described had type 2 DM that appears to have been unmasked by the COVID‐19 infection, since they had high HbA1c and several risk factors for diabetes development, such as obesity and prediabetes. Most of them had their pancreatic reserve preserved, and this may suggest insulin resistance as the aetiology rather than direct beta‐cell damage. A good evolution of diabetes after hospital discharge was observed in the patients followed up at our centre. Copyright © 2022 John Wiley & Sons.

La terapia insulinica nel diabete mellito di tipo 2

Type 2 diabetes is a very common metabolic disorder worldwide. The main defects of this disease are insulin resistance and a β cell dysfunction, leading to a reduction of insulin secretion over time. Insulin secretion is a complex mechanism that involves interactions among all the cells of the pancreatic insula. In addition, glucolipotoxicity may affect reversibly insulin secretion in type 2 diabetes. In recent years, several novel treatments have been becoming available for type 2 diabetes, nevertheless insulin still maintains an important role overall in specific situations including severe metabolic decompensation or pregnancy. The aim of the present narrative review is to discuss the main indications of insulin in the treatment of type 2 diabetes.

IDF21-0097 Concomitant COVID-19 Infection and Ketosis Prone Diabetes. Coincidence or Relationship? A Case Report

Background: Since the beginning of COVID 19 pandemic, great evidence has emerged regarding higher risk of coronavirus disease, its severity and complications in patients with type 2 diabetes mellitus (DM). Otherwise, it had been postulated that SARS-CoV-2 could induce severe metabolic decompensation of pre-existing or new-onset diabetes. In this report, we explore the possibility of COVID 19 induced diabetes. Results: Case presentation: A 39-year-old man was admitted to a tertiary referral hospital with a 10-day history of thirst, polyuria and feeling generally unwell. He referred fever and cough, and he had lost 3 kg in weight over the past 2 weeks. He did not report dyspnoea, abdominal pain or dysuria. There was no significant past medical history of note. Family history included type 2 diabetes in his mother and uncle. On examination, he was tired, tachycardic at 105 beats/min, had a temperature of 37.6°C, blood pressure of 125/70 mmHg, body mass index (BMI) 28.77 kg/m2 and respiratory rate of 28/min, with otherwise normal chest examination. Cardiac auscultation and abdominal palpation were normal. Arterial blood gas revealed a pH of 7.34, bicarbonate 19 mmol/L, PaO2 of 96 mmHg, PaCO2 of 41 mmHg. Serum glucose was 27.53 mmol/L with strong positive uric ketones. A chest X-ray was performed and reported as normal. He was sent for testing for COVID-19 with a positive result. He was initially managed with insulin intravenous infusion at around 0.1 U/kg/h and fluid and potassium replacement. He received antipyretic and analgesic drugs but no other therapy for COVID-19 infection as he had not respiratory symptoms. The diabetes study was completed in the conventional hospital ward. Haemoglobin A1c was 14.3%. C peptide was at lower limit of normal values and autoantibodies were negative. Those findings were sufficient to establish a diagnosis of ketosis-prone diabetes mellitus (KPDM). He underwent a good evolution and could start during the remaining hospitalization a subcutaneous basal-bolus insulin therapy. His insulin requirement was approximately 1.5 U/kg/d. He was finally discharged with an insulin regimen. During the next weeks of follow-up the insulin requirements were progressively lower so that the prandial insulin was retired, basal insulin dose was decreased and metformin was introduced finally achieving an appropriate metabolic control. Discussion: KPMD is a clinical entity characterized by an acute onset with severe hyperglycemia and ketosis similar to the presenting form of type 1 DM, but without its autoimmune component. Subsequently, its evolution resembles that of type 2 DM. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. In our case, KPDM onset is occurring in a patient at the same time he was infected by coronavirus disease. We hypothesize that SARS-CoV-2 could perform a role when triggering the diabetes onset, as coronavirus can induce beta cell damage due to either its direct lytic effects and the host inflammatory response induced. However, there is not enough evidence to say if it was a trigger or simply COVID-19 infection and diabetes onset concurred at the same time.

Organic Acidemias.

Organic Acidemias.

Heterogeneity of Type 1 Diabetes at Diagnosis Supports Existence of Age-Related Endotypes.

Previous findings suggest that there are age-related endotypes of type 1 diabetes with different underlying etiopathological mechanisms in those diagnosed at age <7 years compared with those diagnosed at age ≥13 years. We set out to explore whether variation in demographic, clinical, autoimmune, and genetic characteristics of children and adolescents with newly diagnosed type 1 diabetes support the existence of these proposed endotypes. We used data from the Finnish Pediatric Diabetes Register to analyze characteristics of 6,015 children and adolescents diagnosed with type 1 diabetes between 2003 and 2019. We described and compared demographic data, clinical characteristics at diagnosis, autoantibody profiles, and HLA class II-associated disease risk between three groups formed based on age at diagnosis: <7, 7-12, and ≥13 years. We found significant age-related differences in most of the characteristics analyzed. Children diagnosed at age <7 years were characterized by a higher prevalence of affected first-degree relatives, stronger HLA-conferred disease susceptibility, and higher number of autoantibodies at diagnosis, in particular a higher frequency of insulin autoantibodies, when compared with older children. Those diagnosed at age ≥13 years had a considerably higher male preponderance, higher frequency of glutamic acid decarboxylase autoantibodies, longer duration of symptoms before diagnosis, and more severe metabolic decompensation, reflected, for example, by a higher frequency of diabetic ketoacidosis. Our findings suggest that the heterogeneity of type 1 diabetes is associated with the underlying disease process and support the existence of distinct endotypes of type 1 diabetes related to age at diagnosis.

Neonatal sudden death caused by a novel heterozygous mutation in SLC25A20 gene: A case report and brief literature review

Carnitine-acylcarnitine translocase deficiency (CACTD) is a rare and life-threatening autosomal recessive disorder of fatty acid β-oxidation (FAO). Most patients with CACTD develop severe metabolic decompensation which deteriorates progressively and rapidly, causing death in infancy or childhood. As CACTD in some patients is asymptomatic or only with some nonspecific symptoms, the diagnosis is easy to be ignored, resulting in sudden death, which often triggers medical disputes. Herein, we report a case of neonatal sudden death with CACTD. The neonate showed a series of severe metabolic crisis, deteriorated rapidly and eventually died 3 days after delivery. Tandem mass spectrometry (MS-MS) screening of dry blood spots before death showed that the level of long-chain acylcarnitines, especially C12-C18 acylcarnitine, was increased significantly, and therefore a diagnosis of inherited metabolic disease (IMD) was suspected. Autopsy and histopathological results demonstrated that there were diffuse vacuoles in the heart and liver of the deceased. Mutation analysis revealed that the patient was a compound heterozygote with c.199–10 T > G and a novel c.1A > T mutation in the SLC25A20 gene. Pathological changes such as heart failure, arrhythmia and cardiac arrest related to mitochondrial FAO disorders are the direct cause of death, while gene mutation is the underlying cause of death.

Pathogenic SLC25A26 variants impair SAH transport activity causing mitochondrial disease.

The SLC25A26 gene encodes a mitochondrial inner membrane carrier that transports S-adenosylmethionine (SAM) into the mitochondrial matrix in exchange for S-adenosylhomocysteine (SAH). SAM is the predominant methyl-group donor for most cellular methylation processes, of which SAH is produced as a by-product. Pathogenic, biallelic SLC25A26 variants are a recognized cause of mitochondrial disease in children, with a severe neonatal onset caused by decreased SAM transport activity. Here, we describe two, unrelated adult cases, one of whom presented with recurrent episodes of severe abdominal pain and metabolic decompensation with lactic acidosis. Both patients had exercise intolerance and mitochondrial myopathy associated with biallelic variants in SLC25A26, which led to marked respiratory chain deficiencies and mitochondrial histopathological abnormalities in skeletal muscle that are comparable to those previously described in early-onset cases. We demonstrate using both mouse and fruit fly models that impairment of SAH, rather than SAM, transport across the mitochondrial membrane is likely the cause of this milder, late-onset phenotype. Our findings associate a novel pathomechanism with a known disease-causing protein and highlight the quests of precision medicine in optimizing diagnosis, therapeutic intervention and prognosis.

An Updated View on the Molecular Pathomechanisms of Human Dihydrolipoamide Dehydrogenase Deficiency in Light of Novel Crystallographic Evidence

Dihydrolipoamide dehydrogenase (LADH, E3) deficiency is a rare (autosomal, recessive) genetic disorder generally presenting with an onset in the neonatal age and early death; the highest carrier rate has been found among Ashkenazi Jews. Acute clinical episodes usually involve severe metabolic decompensation and lactate acidosis that result in neurological, cardiological, and/or hepatological manifestations. Clinical severity is due to the fact that LADH is a common E3 subunit to the alpha-ketoglutarate, pyruvate, alpha-ketoadipate, and branched-chain alpha-keto acid dehydrogenase complexes, and is also a constituent in the glycine cleavage system, thus a loss in LADH function adversely affects multiple key metabolic routes. However, the severe clinical pictures frequently still do not parallel the LADH activity loss, which implies the involvement of auxiliary biochemical mechanisms; enhanced reactive oxygen species generation as well as affinity loss for multienzyme complexes proved to be key auxiliary exacerbating pathomechanisms. This review provides an overview and an up-to-date molecular insight into the pathomechanisms of this disease in light of the structural conclusions drawn from the first crystal structure of a disease-causing hE3 variant determined recently in our laboratory.

Pharmacologic Glycemic Management of Type 2 Diabetes in Adults.

Pharmacologic Glycemic Management of Type 2 Diabetes in Adults.

Management and long-term evolution of a patient with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency

Background3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error of metabolism characterized by recurrent metabolic crises caused by fasting, intercurrent illness and excessive physical exercise. Non ketotic hypoglycemia is normally the cause of primary symptoms but without an immediate treatment the illness can evolve into a worsening metabolic state resembling the Reye’s syndrome that may cause the patient’s death. We report a case with some clinical and therapeutic features not previously described.Case presentationPatient with HMG-CoA lyase deficiency whom after diagnosis at 2 years of age was re-admitted 12 years later, after severe metabolic decompensation following consumption of alcohol. Despite a quick correction of hypoglycemia, within the following few hours, the patient fell into a coma. Suspecting intracranial hypertension (ICH), the patient required mechanical ventilation. Although liver cytolysis was minimal, hyperamoniemia reached 1394 μmol/L, returning to normal, a few hours after administering sodium phenylacetate and sodium benzoate, whose use has not been reported in these patients. Brain edema was evidenced in the computed tomography and by the magnetic resonance imaging that determined that the edema was cytotoxic, as quantified with the restriction of diffusion in the apparent diffusion coefficient map. During the recovery of the ICH, we belatedly, detected vasospasm moderate-severe that was treated with nimodipine. Currently, the patient maintains clinical normality.ConclusionsThe alcohol consumption must be avoided in patients with HMG-CoA lyase deficiency. In our patient hyperamoniemia was effectively treated with sodium phenylacetate and sodium benzoate. Magnetic resonance imaging showed and quantified the cytotoxic brain edema. Belatedly, a cerebral vasospasm was an additional mechanism of cerebral injury. None of these observations has been previously reported.

Perioperative management of living-donor liver transplantation for methylmalonic acidemia.

Methymalonic acidemia (MMA) is a hereditary metabolic disorder characterized by a defect of the methylmalonyl-CoA mutase that breaks down propionate. The efficacy of liver transplantation for MMA was recently reported. However, the anesthetic management of liver transplant for MMA is not clear. The aim of this article is to describe an anesthetic management algorithm of liver transplant for MMA by reviewing our cases of liver transplant for MMA. Fourteen patients received a liver transplant; three cases showed metabolic decompensation during the transplant and two of the patients died. In the two patients who expired, propofol was used for maintenance anesthesia and preoperative continuous hemodiafiltration was used to reduce plasma methylmalonic acid level in one case, and to control severe metabolic decompensation before transplant for the other case. Their renal function was also worse than others and they were already experiencing metabolic decompensation before induction of anesthesia. Based on our experience of these 14 cases, we have established an anesthetic algorithm for patients with MMA undergoing liver transplant or other procedures. There are three important points in our experience: propofol should be avoided, dextrose infusion therapy should be continued to prevent metabolic decompensation, and liver transplant or other procedures should be avoided during metabolic decompensation.

Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study

IntroductionType 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes...

A novel homozygous YARS2 mutation causes severe myopathy, lactic acidosis, and sideroblastic anemia 2

Mitochondrial diseases are associated with defects of adenosine triphosphate production and energy supply to organs as a result of dysfunctions of the mitochondrial respiratory chain. Biallelic mutations in the YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase cause myopathy, lactic acidosis, and sideroblastic anemia 2 (MLASA2), a type of mitochondrial disease. Here, we report a consanguineous Turkish family with two siblings showing severe metabolic decompensation including recurrent hypoglycemia, lactic acidosis, and transfusion-dependent anemia. Using whole-exome sequencing of the proband and his parents, we identified a novel YARS2 mutation (c.1303A>G, p.Ser435Gly) that was homozygous in the patient and heterozygous in his parents. This mutation is located at the ribosomal protein S4-like domain of the gene, while other reported YARS2 mutations are all within the catalytic domain. Interestingly, the proband showed more severe symptoms and an earlier onset than previously reported patients, suggesting the functional importance of the S4-like domain in tyrosyl-tRNA synthetase.

Type 2 Diabetes in Children and Adolescents

Type 2 Diabetes in Children and Adolescents

New clinical and molecular insights on Barth syndrome

BackgroundBarth syndrome (BS) is an X-linked infantile-onset cardioskeletal disease characterized by cardiomyopathy, hypotonia, growth delay, neutropenia and 3-methylglutaconic aciduria. It is caused by mutations in the TAZ gene encoding tafazzin, a protein involved in the metabolism of cardiolipin, a mitochondrial-specific phospholipid involved in mitochondrial energy production.MethodsClinical, biochemical and molecular characterization of a group of six male patients suspected of having BS. Three patients presented early with severe metabolic decompensation including respiratory distress, oxygen desaturation and cardiomyopathy and died within the first year of life. The remaining three patients had cardiomyopathy, hypotonia and growth delay and are still alive. Cardiomyopathy was detected during pregnancy through a routine check-up in one patient. All patients exhibited 3-methylglutaconic aciduria and neutropenia, when tested and five of them also had lactic acidosis.ResultsWe confirmed the diagnosis of BS with sequence analysis of the TAZ gene, and found five new mutations, c.641A>G p.His214Arg, c.284dupG (p.Thr96Aspfs*37), c.678_691del14 (p.Tyr227Trpfs*79), g.8009_16445del8437 and g.[9777_9814del38; 9911-?_14402del] and the known nonsense mutation c.367C>T (p.Arg123Term). The two gross rearrangements ablated TAZ exons 6 to 11 and probably originated by non-allelic homologous recombination and by Serial Replication Slippage (SRS), respectively. The identification of the breakpoints boundaries of the gross deletions allowed the direct detection of heterozygosity in carrier females.ConclusionsLactic acidosis associated with 3-methylglutaconic aciduria is highly suggestive of BS, whilst the severity of the metabolic decompensation at disease onset should be considered for prognostic purposes. Mutation analysis of the TAZ gene is necessary for confirming the clinical and biochemical diagnosis in probands in order to identify heterozygous carriers and supporting prenatal diagnosis and genetic counseling.

Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children

OBJECTIVETo determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of β-cell autoimmunity, and HLA genotype in the index case.RESEARCH DESIGN AND METHODSChildren (n = 1,488) with type 1 diabetes diagnosed under 15 years of age were included in a cross-sectional study from the Finnish Pediatric Diabetes Register. Data on family history of diabetes and metabolic decompensation at diagnosis were collected using a questionnaire. Antibodies to β-cell autoantigens (islet cell antibodies, insulin autoantibodies, GAD antibodies, and antibodies to the islet antigen 2 molecule) and HLA genotypes were analyzed.RESULTSA total of 12.2% of the subjects had a first-degree relative with type 1 diabetes (father 6.2%, mother 3.2%, and sibling 4.8%) and 11.9% had an affected second-degree relative. Children without affected relatives had lower pH (P < 0.001), higher plasma glucose (P < 0.001) and β-hydroxybutyrate concentrations (P < 0.001), a higher rate of impaired consciousness (P = 0.02), and greater weight loss (P < 0.001). There were no differences in signs of β-cell autoimmunity. The familial cases carried the HLA DR4-DQ8 haplotype more frequently than sporadic cases (74.0 vs. 67.0%, P = 0.02).CONCLUSIONSWhen the extended family history of type 1 diabetes is considered, the proportion of sporadic diabetes cases may be reduced to <80%. A positive family history for type 1 diabetes associates with a less severe metabolic decompensation at diagnosis, even when only second-degree relatives are affected. Autoantibody profiles are similar in familial and sporadic type 1 diabetes, suggesting similar pathogenetic mechanisms.

Anesthetic management for a patient with very-long-chain acyl-coenzyme A dehydrogenase deficiency

To the Editor: A 28-year-old woman with the adult form of very-longchain acyl-coenzyme A dehydrogenase (VLCAD) deficiency was scheduled for hysteroscopic myomectomy. She complained of muscle pain on fasting and hard exercise, which was alleviated by having food or resting. She was taking carnitine and could usually tolerate overnight fasting. So she fasted for 8 h before the operation, and fluid infusion was begun in the operation room with maintenance fluid containing 10 % glucose at 4.5 mg/kg/min. We used diazepam for premedication. General anesthesia was induced with thiopental, remifentanil, and rocuronium and maintained with sevoflurane and remifentanil. A diclofenac suppository was administered for postoperative analgesia. During the surgery, hyperglycemia (254 mg/dl) was treated with insulin (2 units). Lactate was slightly elevated. The operation was completed uneventfully. Neuromuscular blockade was antagonized with sugammadex; she awoke completely and made no complaint of pain, nausea, vomitting or shivering. An infusion containing 5 % glucose was continued until the next morning, with oral feeding being started the afternoon of the same day. VLCAD is one of the enzymes involved in mitochondrial long-chain fatty acid b-oxidation. A lack of VLCAD activity leads to a shortage of the energy normally derived from long-chain fatty acids [1, 2]. This means that energy is supplied only by glucose, amino acids, or lipids other than very-long-chain and long-chain fatty acids. Catabolic fasting, certain stresses, and an elevated energy demand can induce severe metabolic decompensation [2]. Additionally, the increases in acyl-coenzyme A and acylcarnitine are harmful. The symptoms of VLCAD deficiency are derived from organs/tissues such as the heart, liver, and skeletal muscle, where mitochondrial fatty acid b-oxidation is most marked. The severe form of VLCAD deficiency manifests with cardiomyopathy and has a high mortality rate [1]. Treatment of VLCAD deficiency is directed at preventing catabolic situations by the avoidance of prolonged fasting, by avoiding emotional or physical stress, and by dietary restriction of long-chain fatty acids. In the present patient, our aims were: (1) not to elevate plasma free fatty acids, (2) not to increase energy demand, and (3) to give sufficient glucose. We chose general anesthesia to avoid the physical and/or psychological stresses that could be induced by a possibly inadequate level of spinal anesthesia. Some cases have been reported in which propofol or sevoflurane was used safely in patients with VLCAD deficiency [3]. However, propofol contains long-chain fatty acids, and we therefore avoided using this agent. Some stresses (anxiety, shivering, nausea, and vomiting) can increase energy demand, and a previous report has recommended glucose, at 6 mg/kg/min, for perioperative use in infants with VLCAD deficiency; as well, it was suggested that the fasting period should not exceed 4 h in children with this condition [4]. However, it is not clear how much glucose is necessary during an operation in adult patients with VLCAD deficiency. Because glucose demand may decrease with age and because myopathic symptoms did not occur and the creatine kinase level was not elevated just after the operation in our patient, we think that the intraoperative glucose infusion she received was adequate. However, creatine kinase was elevated on postoperative day 2, and we speculate that the postoperative glucose infusion was not K. Iwata K. Tanabe (&) Y. Sugiyama M. Tanaka M. Takenaka H. Iida Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan e-mail: kumiko-t@m2.gyao.ne.jp

Clinical features and management of diabetic ketoacidosis in different age groups of children: children less than 5 years of age are at higher risk of metabolic decompensation

To characterize the clinical features and biochemical status at presentation of diabetic ketoacidosis (DKA) in different age groups of children, and to analyze the outcomes of a certain treatment protocol. We reviewed records of patients with DKA who were admitted to our hospital between January 2007 and December 2010. Patients were divided into three subgroups according to age, and the results were compared between these groups. One hundred thirty-four episodes in 111 patients (64 females, 47 males) were analyzed. Of these 134 episodes, 60% was in patients with new-onset diabetes and 40% was in those with established diabetes. Patients younger than 5 years had lower C-peptide and HbA1c levels than older patients at clinical onset. They were also given more alkali therapy. The initial conscious level was found closely related to plasma osmolality and serum sodium levels. Seven of 11 patients with recurrent DKA were females. No major complication was observed. Our study indicates that younger children are at higher risk for severe metabolic decompensation and require more attention and closer monitoring during treatment. We suggest the use of low-dose insulin in this subgroup of patients with DKA without slowing the correction of acidosis.