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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 -
Cureus Apr 2024Recently termed pancreoprivic diabetes, type 3c diabetes refers to high blood sugar values secondary to disease of the exocrine pancreas. The disease is most commonly...
Recently termed pancreoprivic diabetes, type 3c diabetes refers to high blood sugar values secondary to disease of the exocrine pancreas. The disease is most commonly misdiagnosed as type 2 diabetes mellitus (DM) and is overlooked by physicians and the general public. Chronic pancreatitis (CP) accounts for most cases of type 3c diabetes. Diabetic ketoacidosis (DKA) is a rare occurrence in type 3c diabetes as both alpha and beta cell dysfunction occur concurrently. In this case, the major hormones involved in lipolysis and ketone body production would be catecholamines, cortisol, and growth hormone. We report a case of a 37-year-old female with a history of endocrine pancreatic insufficiency secondary to CP who presented with DKA, one of the life-threatening but preventable complications of diabetes. Noncompliance with insulin and concurrent urinary tract infection were the inciting factors. Her condition improved with DKA management according to standard protocol, intravenous antibiotics, and other supportive care. She got discharged after optimization of insulin therapy, with proper advice for home blood sugar monitoring and regular follow-up. A patient with pancreatic pathology may present to the emergency with DKA as the first manifestation, and if not properly evaluated, the diagnosis of type 3c diabetes can be missed.
PubMed: 38725776
DOI: 10.7759/cureus.57873 -
Internal Medicine (Tokyo, Japan) May 2024Patients often present with severe fatty liver (FL) due to insulin deficiency at the onset of diabetic ketoacidosis (DKA). On the other hand, glycogenic hepatopathy (GH)...
Patients often present with severe fatty liver (FL) due to insulin deficiency at the onset of diabetic ketoacidosis (DKA). On the other hand, glycogenic hepatopathy (GH) is a possible cause of liver dysfunction in patients with DKA. We herein report a case of type 1 diabetes mellitus with severe FL at the onset of DKA, who demonstrated subsequent marked liver dysfunction after achieving an improvement of FL. As liver dysfunction persisted even after the FL improved, GH was suspected to be the cause of liver dysfunction. FL and GH have different prognoses and should therefore be differentiated using imaging studies and biopsies.
PubMed: 38719597
DOI: 10.2169/internalmedicine.3488-24 -
Journal of Cardiovascular Pharmacology... 2024Sodium-glucose cotransporter- 2 (SGLT2) inhibitors have become a cornerstone in heart failure (HF), Type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD)...
INTRODUCTION
Sodium-glucose cotransporter- 2 (SGLT2) inhibitors have become a cornerstone in heart failure (HF), Type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) management. In the current retrospective study, we aimed to assess efficacy and safety of SGLT2 inhibitors early following acute myocardial infarction (AMI).
METHODS
Patients with T2DM hospitalized for AMI in 2017-2020 were divided according to SGLT2 inhibitors therapy status on discharge (with vs without therapy). Primary outcome was defined as a composite of hospitalizations for HF, recurrent AMI, and cerebrovascular accident (CVA). Secondary outcomes included hospitalizations for any cause, total cumulative number of hospitalizations, and all-cause mortality.
RESULTS
A total of 69 patients (mean age 59.2 ± 8.2 years) with AMI discharged with SGLT2 inhibitors were compared to 253 patients (mean age 62.5 ± 9.8) with no SGLT2 inhibitors. During the first year post-AMI, 4 (5.8%) patients in the treatment group and 16 (6.3%) in the control group were hospitalized for CV events (p = 1.0). Patients in the SGLT2 inhibitors group had lower rates of hospitalization for any cause (31.9% vs 47.8%, P = 0.02), with no change in mortality (0% vs 3.6%, P = 0.21). After multivariate regression analysis, only female gender was associated with increased risk for readmission, mainly due to urinary tract infections. No events of diabetic ketoacidosis (DKA) or limb amputation were reported.
CONCLUSIONS
We found that early initiation of SGLT2 inhibitors in T2DM patients following AMI is safe and decreases the risk of hospitalization for any cause.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Retrospective Studies; Male; Female; Middle Aged; Diabetes Mellitus, Type 2; Aged; Myocardial Infarction; Treatment Outcome; Time Factors; Risk Factors; Risk Assessment; Hospitalization; Recurrence; Stroke
PubMed: 38711298
DOI: 10.1177/10742484241252474 -
Health Economics Review May 2024In 2022, updated guidance from NICE expanded the options for self-monitoring of blood glucose for patients with type 2 diabetes (T2DM), to include continuous glucose...
INTRODUCTION
In 2022, updated guidance from NICE expanded the options for self-monitoring of blood glucose for patients with type 2 diabetes (T2DM), to include continuous glucose monitoring (CGM). In this budget impact analysis, the cost impact of CGM was compared with traditional self-monitoring of blood glucose (SMBG) in adults with T2DM over 1 year from the commissioner perspective in England.
RESEARCH DESIGN AND METHODS
The NICE-eligible T2DM cohort was split into 4 subgroups to enable nuanced costing by insulin administration frequency: basal human insulin, premixed insulin, basal-bolus insulin and bolus insulin. The model's cost components comprised mild and severe hypoglycaemia (SH), diabetic ketoacidosis (DKA), consumables and healthcare resource utilisation in primary and secondary care.
RESULTS
The introduction of CGM is estimated to be cost additive by approximately £4.6 million in the basecase, driven by increased spending on the CGM device. Overall, healthcare activity was reduced by approximately 20,000 attendances, due to fewer SH and DKA episodes in the CGM arm. General Practitioner (GP) practice-based activity is expected to drop after the first year as patients requiring CGM training is reduced. The budget impact could be neutralised if the CGM sensor was discounted by 13.2% (£29.76 to £25.83).
CONCLUSIONS
CGM may result in increased spending in the NICE-eligible T2DM cohort but is expected to reduce demand on secondary care services and GP time. These findings may be of interest to local decision-makers who wish to resolve the COVID-19 backlog with transformational investment in primary care to reduce secondary care activity.
PubMed: 38709338
DOI: 10.1186/s13561-024-00505-7