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Pediatric Diabetes 2024ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved -cell function in...
High Prevalence of Ketosis-Prone Diabetes in Children with Type 2 Diabetes and Diabetic Ketoacidosis at Diagnosis: Evidence from the Rare and Atypical Diabetes Network (RADIANT).
BACKGROUND
ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved -cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric KPD within this cohort.
METHODS
We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics.
RESULTS
Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)).
CONCLUSIONS
In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for KPD. They manifest the key characteristics of obesity, preserved -cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with KPD.
Topics: Humans; Female; Male; Diabetic Ketoacidosis; Child; Diabetes Mellitus, Type 2; Adolescent; Prevalence; Insulin-Secreting Cells; Retrospective Studies
PubMed: 38765897
DOI: 10.1155/2024/5907924 -
Cureus May 2024The immune checkpoint inhibitor (ICI) cemiplimab is a human monoclonal antibody used in the treatment of locally advanced and metastatic cutaneous squamous cell...
The immune checkpoint inhibitor (ICI) cemiplimab is a human monoclonal antibody used in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) not amenable to surgery or radiation therapy. Although cemiplimab shows excellent efficacy with a good tolerability profile, it can cause side effects, including potentially life-threatening endocrinopathies. We discuss the case of a 77-year-old Caucasian female with CSCC treated with only three cycles of cemiplimab who presented with altered mental status and was found to have severe hyperglycemia, hyperosmolarity, ketonemia, glucosuria, and ketonuria concerning for hyperosmolar hyperglycemic syndrome (HHS) with concurrent diabetic ketoacidosis (DKA). The patient made a rapid recovery in the hospital while on standard therapies for HHS/DKA and cemiplimab was discontinued upon discharge. While there have been reports of cemiplimab-induced DKA, to our knowledge, this is the first reported case of cemiplimab-induced HHS-DKA. This report aims to shed light on cemiplimab-induced HHS-DKA and to underscore the need to elucidate the molecular mechanisms underlying ICI-induced diabetes mellitus (ICI-DM).
PubMed: 38764707
DOI: 10.7759/cureus.60565 -
Heliyon May 2024Fulminant type 1 diabetes is a subtype of type 1 diabetes characterised by a rapid progression to diabetic ketoacidosis combined with a background of rapid and almost...
Fulminant type 1 diabetes is a subtype of type 1 diabetes characterised by a rapid progression to diabetic ketoacidosis combined with a background of rapid and almost complete pancreatic islet destruction. FT1D induced by secondary SARS-CoV-2 infection is rare. Herein, we present the case of a 42-year-old male patient with new-onset FT1D after a secondary SARS-CoV-2 infection, with recurrent hyperglycaemia and ketosis as the primary manifestations. Eventually, the patient responded well after receiving more than 50 units of insulin daily. This case illustrates the importance of paying attention to severe hyperglycaemia accompanying recurrent ketosis, particularly among patients with secondary SARS-CoV-2 infection.
PubMed: 38756607
DOI: 10.1016/j.heliyon.2024.e30750 -
Cureus Apr 2024Euglycemic diabetic ketoacidosis (EDKA) though rare is a life-threatening complication of sodium-glucose cotransporter 2 (SGLT2) inhibitors. With their increasing use...
Euglycemic diabetic ketoacidosis (EDKA) though rare is a life-threatening complication of sodium-glucose cotransporter 2 (SGLT2) inhibitors. With their increasing use in the management of type 2 diabetes mellitus (T2DM) due to long-term beneficial effects, the incidence of this complication is on the rise. We report a case of a 58-year-old lady with a history of T2DM on multiple anti-diabetes medications including dapagliflozin for one year, who during intercurrent illness developed EDKA. Her blood sugar on admission was 203 mg/dL, and arterial blood gas showed high anion-gap metabolic acidosis (HAGMA) with ketonuria and ketonemia (blood beta-hydroxybutyric (BOHB) acid level: 5.4 mmol/L). Low carbohydrate intake, dehydration resulting from repeated vomiting, and skipping the previous two days' dose of insulin could have precipitated this condition. She was treated with intravenous fluids, insulin, 5% dextrose infusion, and potassium supplements with complete resolution of acidosis after about 90 hours. This case signifies the importance of awareness of the link between the use of SGLT2 inhibitors and EDKA and early recognition of this complication to reduce morbidity and mortality. Furthermore, it also emphasizes the need for clinicians to educate their patients taking these drugs to stop them during the intercurrent illness to prevent them from developing EDKA.
PubMed: 38756291
DOI: 10.7759/cureus.58341 -
JPGN Reports May 2024Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic...
INTRODUCTION
Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic control. Clinical characteristics and natural history of GH are not completely understood in children. In this study, we investigated clinical, biochemical, histologic parameters and outcomes in children with GH.
METHOD
This was a retrospective review of patients less than 18 years old diagnosed with GH and DM. GH was confirmed on liver biopsy. Medical records were reviewed for clinical presentation, laboratory tests, and clinical outcomes. Liver biopsy findings were reviewed by a pediatric pathologist (I. A. G.).
RESULTS
Nine children were diagnosed with GH and type 1 DM. The median age at diagnosis of GH was 16 (IQR 14.5-17) years. Duration of diagnosis of DM until GH diagnosis was 7 (IQR 5-11) years. The median frequency of diabetic ketoacidosis before GH diagnosis was three times (IQR 2-5.25). Peak Aspartate transaminase (AST) and Alanine transaminase (ALT) ranged from 115 to 797, and 83-389 units/L, respectively. Only two children had mild fibrosis. Seven of nine had steatosis without steatohepatitis. There was no correlation between glycosylated hemoglobin (HbA1c), or other laboratory tests and liver fibrosis on biopsy. HbA1c was 11.2 (IQR 10.2-12.8) at GH diagnosis and 9.8 (IQR 9.5-10.8) with normalization of liver enzymes.
CONCLUSION
GH appears to be related to poor glycemic control in teenagers with long-term diabetes. GH presents with high to very high aminotransferase especially AST > ALT and resolves with modestly improved glycemic control. Diffuse hepatocyte swelling, steatosis, minimal fibrosis without hepatocyte ballooning or lobular inflammation are most common histological features.
PubMed: 38756113
DOI: 10.1002/jpr3.12046 -
Journal of Clinical Research in... May 2024Neonatal Diabetes Mellitus (NDM) is a disorder characterized by persistent, severe hyperglycemia presenting during the first 6 months of life. These disorders are rare...
Neonatal Diabetes Mellitus (NDM) is a disorder characterized by persistent, severe hyperglycemia presenting during the first 6 months of life. These disorders are rare and the incidence is approximately 1 in 90,000 live births. To describe the clinical presentation, molecular genetics and outcome of patients with NDM from a single paediatric endocrine center from a low middle income country. A retrospective study was conducted on patients diagnosed with NDM. Medical records were reviewed for demographic data and data on clinical, biochemical and genetic analysis. 96% of patients who underwent mutation analysis had pathogenic genetic mutations on Sanger sequencing. Permanent NDM (PNDM) was diagnosed in 19 patients with 3 of them having a syndromic diagnosis. The commonest mutation was found in KCNJ11 gene. Majority of the PNDM (63%) presented with severe diabetic ketoacidosis. All patients with Transient NDM (TNDM) remitted by 6 months of age. 47% of the cases with PNDM made a switch to sulfonylurea therapy with good glycemic control (glycosylated Haemoglobin A1C 6-7.5). Data from the Sri Lankan cohort is comparable with other populations. The majority of cases are due to KCNJ11 mutations resulting in PNDM.
PubMed: 38752501
DOI: 10.4274/jcrpe.galenos.2024.2024-2-17 -
Frontiers in Endocrinology 2024This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute...
PURPOSE
This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy.
METHODS
Breath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).
RESULTS
SESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis.
CONCLUSION
This study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.
Topics: Humans; Diabetic Ketoacidosis; Breath Tests; Male; Female; Adult; Middle Aged; Insulin; Feasibility Studies; Fluid Therapy; Aged; Biomarkers; Spectrometry, Mass, Electrospray Ionization
PubMed: 38752172
DOI: 10.3389/fendo.2024.1360989 -
Case Reports in Endocrinology 2024Mauriac syndrome is a rare disorder that occurs in patients with type 1 diabetes mellitus (T1DM) with glucose levels significantly above target, characterized by...
Mauriac syndrome is a rare disorder that occurs in patients with type 1 diabetes mellitus (T1DM) with glucose levels significantly above target, characterized by hepatomegaly, growth delay, and cushingoid features. Another distinguishing feature of Mauriac syndrome is persistent lactatemia during diabetic ketoacidosis (DKA) management. We present a case of an 18-year-old patient with T1DM who presented in DKA and then developed elevated lactate levels leading to a diagnosis of Mauriac syndrome. The cause of the persistent lactatemia is not well understood though it is likely related to glycogenic hepatopathy causing hepatomegaly, abnormalities in glucose metabolism, and subsequent inappropriate lactate production. Since the liver changes seen in Mauriac syndrome are reversible with optimal blood glucose control, these patients should be connected to intensive psychosocial and medical support to help them improve their blood glucose levels.
PubMed: 38746831
DOI: 10.1155/2024/5599984 -
Journal of Alzheimer's Disease Reports 2024Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer's disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also...
BACKGROUND
Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer's disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear.
OBJECTIVE
Our objective was to understand how DKA can promote neurodegeneration in AD.
METHODS
We induced DKA in rats through intraperitoneal injection of streptozotocin, followed by starvation for 48 hours and investigated AD-related brain alterations focusing on tau phosphorylation.
RESULTS
We found that DKA induced hyperphosphorylation of tau protein at multiple sites associated with AD. Studies of tau kinases and phosphatases suggest that the DKA-induced hyperphosphorylation of tau was mainly mediated through activation of c-Jun N-terminal kinase and downregulation of protein phosphatase 2A. Disruption of the mTOR-AKT (the mechanistic target of rapamycin-protein kinase B) signaling pathway and increased levels of synaptic proteins were also observed in the brains of rats with DKA.
CONCLUSIONS
These results shed some light on the mechanisms by which DKA may increase the risk for AD.
PubMed: 38746631
DOI: 10.3233/ADR-240040 -
Saudi Medical Journal May 2024To evaluate clinical indicators in order to examine the intensity of diabetes ketoacidosis (DKA) episodes in children and adolescents diagnosed with type 1 diabetes...
OBJECTIVES
To evaluate clinical indicators in order to examine the intensity of diabetes ketoacidosis (DKA) episodes in children and adolescents diagnosed with type 1 diabetes mellitus (T1DM).
METHODS
Data from 156 T1DM patients aged 6 months to 14 years, who presented with DKA to the emergency room, were retrospectively reviewed from 2018 to 2022. Data on demographic characteristics, economic status, initial clinical presentation, glycemic control, DKA severity, and laboratory evaluations were also collected.
RESULTS
Diabetes ketoacidosis episodes were more prevalent among male patients during the middle childhood age group. Notably, these episodes displayed seasonal patterns. The severity was found to be inversely associated with economic status and positively correlated with early adolescence. Newly diagnosed T1DM patients constituted 52.9%, with a statistically significant connection observed between severe DKA and this subgroup. Furthermore, there was a significant escalation in poor glycemic control with episode severity. Prolonged episode duration also exhibited a statistically significant association with more severity. Gastrointestinal symptoms were commonly reported during the presentation. Moreover, several clinical signs and symptoms, including decreased consciousness, reduced activity, drowsiness, Kussmaul breathing, shortness of breath, vomiting, tachycardia, and severe dehydration, were significantly correlated with the severity of DKA (<0.05). Hypernatremia was more frequent among children with severe DKA.
CONCLUSION
Diabetes ketoacidosis was observed to occur more frequently among males in middle childhood with seasonal variations. Furthermore, the severity of DKA was associated with lower economic status, early adolescence, and the presence of hypernatremia.
Topics: Humans; Diabetic Ketoacidosis; Male; Adolescent; Child; Severity of Illness Index; Female; Infant; Child, Preschool; Retrospective Studies; Diabetes Mellitus, Type 1; Sex Factors; Seasons; Age Factors; Hypernatremia; Blood Glucose
PubMed: 38734437
DOI: 10.15537/smj.2024.45.4.20240058