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Diabetology & Metabolic Syndrome Sep 2023Glycaemic control of Type 1 Diabetes Mellitus (T1DM) remains a challenge due to hypoglycaemic episodes and the burden of insulin self-management. Advancements have been... (Review)
Review
BACKGROUND
Glycaemic control of Type 1 Diabetes Mellitus (T1DM) remains a challenge due to hypoglycaemic episodes and the burden of insulin self-management. Advancements have been made with the development of automated insulin delivery (AID) devices, yet, previous reviews have only assessed the use of AID over days or weeks, and potential benefits with longer time of AID use in this population remain unclear.
METHODS
We performed a systematic review and meta-analysis of randomised controlled trials comparing AID (hybrid and fully closed-loop systems) to usual care (sensor augmented pumps, multiple daily insulin injections, continuous glucose monitoring and predictive low-glucose suspend) for adults and children with T1DM with a minimum duration of 3 months. We searched PubMed, Embase, Cochrane Central, and Clinicaltrials.gov for studies published up until April 4, 2023. Main outcomes included time in range 70-180 mg/dL as the primary outcome, and change in HbA1c (%, mmol/mol), glucose variability, and psychosocial impact (diabetes distress, treatment satisfaction and fear of hypoglycaemia) as secondary outcomes. Adverse events included diabetic ketoacidosis (DKA) and severe hypoglycaemia. Statistical analyses were conducted using mean differences and odds ratios. Sensitivity analyses were performed according to age, study duration and type of AID device. The protocol was registered in PROSPERO, CRD42022366710.
RESULTS
We identified 25 comparisons from 22 studies (six crossover and 16 parallel designs) including a total of 2376 participants (721 in adult studies, 621 in paediatric studies, and 1034 in combined studies) which were eligible for analysis. Use of AID devices ranged from 12 to 96 weeks. Patients using AID had 10.87% higher time in range [95% CI 9.38 to 12.37; p < 0.0001, I = 87%) and 0.37% (4.77 mmol/mol) lower HbA1c (95% CI - 0.49% (- 6.39 mmol/mol) to - 0.26 (- 3.14 mmol/mol); p < 0·0001, I = 77%]. AID systems decreased night hypoglycaemia, time in hypoglycaemia and hyperglycaemia and improved patient distress, with no increase in the risk of DKA or severe hypoglycaemia. No difference was found regarding treatment satisfaction or fear of hypoglycaemia. Among children, there was no difference in glucose variability or time spent in hypoglycaemia between the use of AID systems or usual care. In sensitivity analyses, results remained consistent with the overall analysis favouring AID.
CONCLUSION
The use of AID systems over 12 weeks, regardless of technical or clinical differences, improved glycaemic outcomes and diabetes distress without increasing the risk of adverse events in adults and children with T1DM.
PubMed: 37759290
DOI: 10.1186/s13098-023-01144-4 -
Journal of the American College of... Dec 2023Euglycemic diabetic ketoacidosis (EDKA) carries serious risks for mortality and morbidity for both the mother and the baby, and it is essential to recognize it early and...
BACKGROUND
Euglycemic diabetic ketoacidosis (EDKA) carries serious risks for mortality and morbidity for both the mother and the baby, and it is essential to recognize it early and start immediate treatment.
CASE PRESENTATION
We present a case of EDKA in a 28-week pregnant woman known to have type 1 diabetes. She was found to have severe acidosis with a blood sugar level of 10.6 mmol/L (190.8 mg/dL) and normal anion gap. She was found to have EDKA, which was confirmed later with a depressed venous pH and bicarbonate level and an increased serum ketone level. The patient's acidosis was not improving significantly with 0.05 units/kg/h of insulin infusion, so a full dose of 0.1 unit/kg/h of insulin infusion was started following a full diabetic ketoacidosis (DKA) protocol regardless of her blood sugar level. The patient showed gradual improvement and was discharged home after 4 days, with follow-up with endocrinology and obstetrics.
CONCLUSION
In conclusion, EDKA is a critical complication of diabetes, especially in pregnant women. Therefore, it is crucial to treat it early and potentially consider following a full DKA protocol using 0.1 unit/kg/h insulin infusion instead of 0.05 unit/kg/h.
PubMed: 38124991
DOI: 10.1002/emp2.13089 -
Diabetes Care Jul 2023Adolescence is associated with high-risk hyperglycemia. This study examines the phenomenon in a life course context.
National Trends in Hyperglycemia and Diabetic Ketoacidosis in Children, Adolescents, and Young Adults With Type 1 Diabetes: A Challenge Due to Age or Stage of Development, or Is New Thinking About Service Provision Needed?
OBJECTIVE
Adolescence is associated with high-risk hyperglycemia. This study examines the phenomenon in a life course context.
RESEARCH DESIGN AND METHODS
A total of 93,125 people with type 1 diabetes aged 5 to 30 years were identified from the National Diabetes Audit and/or the National Paediatric Diabetes Audit for England and Wales for 2017/2018-2019/2020. For each audit year, the latest HbA1c and hospital admissions for diabetic ketoacidosis (DKA) were identified. Data were analyzed in sequential cohorts by year of age.
RESULTS
In childhood, unreported HbA1c measurement is uncommon; however, for 19-year-olds, it increases to 22.3% for men and 17.3% for women, and then reduces to 17.9% and 13.1%, respectively, for 30-year-olds. Median HbA1c for 9-year-olds is 7.6% (60 mmol/mol) (interquartile range 7.1-8.4%, 54-68 mmol/mol) in boys and 7.7% (61 mmol/mol) (8.0-8.4%, 64-68 mmol/mol) in girls, increasing to 8.7% (72 mmol/mol) (7.5-10.3%, 59-89 mmol/mol) and 8.9% (74 mmol/mol) (7.7-10.6%, 61-92 mmol/mol), respectively, for 19-year-olds before falling to 8.4% (68 mmol/mol) (7.4-9.7%, 57-83 mmol/mol) and 8.2% (66 mmol/mol) (7.3-9.7%, 56-82 mmol/mol), respectively, for 30-year-olds. Annual hospitalization for DKA rose steadily in age from 6 years (2.0% for boys, 1.4% for girls) and peaked at 19 years for men (7.9%) and 18 years for women (12.7%), reducing to 4.3% for men and 5.4% for women at age 30 years. For all ages over 9 years, the prevalence of DKA was higher in female individuals.
CONCLUSIONS
HbA1c and the prevalence of DKA increase through adolescence and then decline. Measurement of HbA1c, a marker of clinical review, falls abruptly in the late teenage years. Age-appropriate services are needed to overcome these issues.
Topics: Male; Child; Humans; Female; Adolescent; Young Adult; Adult; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Hyperglycemia; England
PubMed: 37216620
DOI: 10.2337/dc23-0180 -
Cancers Dec 2023Malignant neoplasms are currently one of the leading causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in... (Review)
Review
Malignant neoplasms are currently one of the leading causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in research in cancer biology and immunity have led to the development of immunotherapy, which is now used on an everyday basis in cancer treatment in addition to surgical treatment, classical cytostatics, and radiotherapy. The efficacy of immunotherapy has promoted the great popularity of this treatment among patients, as well as significant research interest. The increasing number of patients being treated with immunotherapy not only reassures physicians of the efficacy of this technique but also shows the wide spectrum of side effects of this therapy, which has not been considered before. Immune-related adverse events may affect many systems and organs, such as digestive, cardiovascular, respiratory, skin, or endocrine organs. Most complications have a mild or moderate course, but there are life-threatening manifestations that are essential to be aware of because if they are not properly diagnosed and treated on time, they can have fatal consequences. The purpose of this paper was to present the results of a literature review on the current state of knowledge on life-threatening endocrine side effects (such as adrenal crisis, thyroid storm, myxoedema crisis, diabetic ketoacidosis, and severe hypocalcaemia) of immune checkpoint inhibitors to provide information on symptoms, diagnostics, and management strategies.
PubMed: 38136332
DOI: 10.3390/cancers15245786 -
Frontiers in Immunology 2023Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can... (Review)
Review
BACKGROUND
Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient's immune system. Here, we report a rare case of a new onset of diabetes mellitus (DM), caused by nivolumab, and we discuss the feasible treatment options with a focus on TNF antagonism.
CASE PRESENTATION
A 50-year-old man was diagnosed with metastatic renal cell carcinoma. Due to systemic progression, a combined immunotherapy with ipilimumab and nivolumab was initiated, according to the current study protocol (SAKK 07/17). The administration of ipilimumab was stopped after 10 months, due to partial response as seen in the computer tomography (CT), and nivolumab was continued as monotherapy. Fourteen months after the start of the treatment, the patient was admitted to the emergency department with lethargy, vomiting, blurred vision, polydipsia, and polyuria. The diagnosis of DM with diabetic ketoacidosis was established, although autoantibodies to β-cells were not detectable. Intravenous fluids and insulin infusion treatment were immediately initiated with switching to a subcutaneous administration after 1 day. In addition, the patient received an infusion of the TNF inhibitor infliximab 4 days and 2 weeks after the initial diagnosis of DM. However, the C-peptide values remained low, indicating a sustained insulin deficiency, and the patient remained on basal bolus insulin treatment. Two months later, nivolumab treatment was restarted without destabilization of the diabetic situation.
CONCLUSIONS
In contrast to the treatment of other irAEs, the administration of corticosteroids is not recommended in ICI-induced DM. The options for further treatment are mainly based on the low numbers of case series and case reports. In our case, the administration of infliximab-in an attempt to salvage the function of β-cells-was not successful, and this is in contrast to some previous reports. This apparent discrepancy may be explained by the absence of insulin resistance in our case. There is so far no evidence for immunosuppressive treatment in this situation. Prompt recognition and immediate start of insulin treatment are most important in its management.
Topics: Male; Humans; Middle Aged; Nivolumab; Ipilimumab; Carcinoma, Renal Cell; Antineoplastic Agents, Immunological; Infliximab; Kidney Neoplasms; Diabetes Mellitus; Insulins
PubMed: 37965350
DOI: 10.3389/fimmu.2023.1248919 -
Cardiovascular Endocrinology &... Sep 2023SGLT2i are now recommended in a wide spectrum of indications including type 2 diabetes (T2DM), heart failure, and chronic kidney disease. This medication class is now...
SGLT2i are now recommended in a wide spectrum of indications including type 2 diabetes (T2DM), heart failure, and chronic kidney disease. This medication class is now available in combination with metformin, which is still a fundamental treatment in patients with T2DM. Despite excellent proven safety profile for both drugs, the expanding use of these agents in clinical practice may lead to an increased incidence of rare side effects, like metformin-associated lactic acidosis (MALA) and euglycemic diabetic ketoacidosis (EDKA), which can be life-threatening. A 58-year-old woman with T2DM and severe heart failure treated by metformin and empagliflozin developed progressive EDKA triggered by fasting that was also complicated by severe acute renal failure and MALA. She was successfully treated with intermittent hemodialysis. This case report highlights the importance of the recognition of rare, but very serious adverse effects due to combined metformin and SGLT2i therapy.
PubMed: 37424794
DOI: 10.1097/XCE.0000000000000287 -
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 -
Cureus Dec 2023A leukemoid reaction is a rare condition characterized by an elevation in white blood cell count exceeding 50,000 cells/μL in response to severe medical conditions,...
A leukemoid reaction is a rare condition characterized by an elevation in white blood cell count exceeding 50,000 cells/μL in response to severe medical conditions, which can mimic the presentation of chronic myeloid leukemia (CML). Distinguishing between leukemoid reaction and CML depends on a thorough clinical history and comprehensive laboratory evaluation. We present a case of leukemoid reaction associated with severe diabetic ketoacidosis, where the patient's white blood cell count returned to the normal range after the correction of hyperglycemia and electrolyte imbalances.
PubMed: 38205495
DOI: 10.7759/cureus.50325 -
JMIR Diabetes Jul 2023Although prior research has identified multiple risk factors for diabetic ketoacidosis (DKA), clinicians continue to lack clinic-ready models to predict dangerous and...
BACKGROUND
Although prior research has identified multiple risk factors for diabetic ketoacidosis (DKA), clinicians continue to lack clinic-ready models to predict dangerous and costly episodes of DKA. We asked whether we could apply deep learning, specifically the use of a long short-term memory (LSTM) model, to accurately predict the 180-day risk of DKA-related hospitalization for youth with type 1 diabetes (T1D).
OBJECTIVE
We aimed to describe the development of an LSTM model to predict the 180-day risk of DKA-related hospitalization for youth with T1D.
METHODS
We used 17 consecutive calendar quarters of clinical data (January 10, 2016, to March 18, 2020) for 1745 youths aged 8 to 18 years with T1D from a pediatric diabetes clinic network in the Midwestern United States. The input data included demographics, discrete clinical observations (laboratory results, vital signs, anthropometric measures, diagnosis, and procedure codes), medications, visit counts by type of encounter, number of historic DKA episodes, number of days since last DKA admission, patient-reported outcomes (answers to clinic intake questions), and data features derived from diabetes- and nondiabetes-related clinical notes via natural language processing. We trained the model using input data from quarters 1 to 7 (n=1377), validated it using input from quarters 3 to 9 in a partial out-of-sample (OOS-P; n=1505) cohort, and further validated it in a full out-of-sample (OOS-F; n=354) cohort with input from quarters 10 to 15.
RESULTS
DKA admissions occurred at a rate of 5% per 180-days in both out-of-sample cohorts. In the OOS-P and OOS-F cohorts, the median age was 13.7 (IQR 11.3-15.8) years and 13.1 (IQR 10.7-15.5) years; median glycated hemoglobin levels at enrollment were 8.6% (IQR 7.6%-9.8%) and 8.1% (IQR 6.9%-9.5%); recall was 33% (26/80) and 50% (9/18) for the top-ranked 5% of youth with T1D; and 14.15% (213/1505) and 12.7% (45/354) had prior DKA admissions (after the T1D diagnosis), respectively. For lists rank ordered by the probability of hospitalization, precision increased from 33% to 56% to 100% for positions 1 to 80, 1 to 25, and 1 to 10 in the OOS-P cohort and from 50% to 60% to 80% for positions 1 to 18, 1 to 10, and 1 to 5 in the OOS-F cohort, respectively.
CONCLUSIONS
The proposed LSTM model for predicting 180-day DKA-related hospitalization was valid in this sample. Future research should evaluate model validity in multiple populations and settings to account for health inequities that may be present in different segments of the population (eg, racially or socioeconomically diverse cohorts). Rank ordering youth by probability of DKA-related hospitalization will allow clinics to identify the most at-risk youth. The clinical implication of this is that clinics may then create and evaluate novel preventive interventions based on available resources.
PubMed: 37224506
DOI: 10.2196/47592 -
International Journal of Endocrinology... Oct 2023The coronavirus disease 2019 (COVID-19) vaccine is one of the few vaccines that obtained emergency authorization to combat the fatal pandemic. Despite the fact that some...
BACKGROUND
The coronavirus disease 2019 (COVID-19) vaccine is one of the few vaccines that obtained emergency authorization to combat the fatal pandemic. Despite the fact that some available literature addressed its short-term side effects, there are still limitations on its effects on type 1 diabetes mellitus (T1DM).
OBJECTIVES
The aim of the present study was to assess the association between COVID-19 vaccination and diabetic ketoacidosis (DKA) among individuals with T1DM. Additionally, the study aimed to determine the effects of the vaccine on glucose control, variability, and risk of hypoglycemia.
METHODS
This retrospective study was conducted at King Fahad Specialist Hospital (KFSH) in Qassim Region, Saudi Arabia. Diabetic ketoacidosis cases admitted to the hospital within February 2020 and August 2022 were included in the study based on specific inclusion criteria. Finally, a total of 49 patients were included in statistical analyses.
RESULTS
Out of the 62 patients admitted to the hospital, 49 met the diagnostic criteria for DKA and agreed to participate in the study. The majority of the remaining patients (n = 13) refused to participate, and only a few of them lacked complete documentation. Of the 49 patients who were included in the study, 46 cases had a history of T1DM; nevertheless, 3 patients were newly diagnosed with T1DM. Additionally, among these participants, 16 (32.7%), 19 (38.8%), and 14 (28.6%) patients had mild, moderate, and severe DKA, respectively. There were 27 male (55.1%) and 22 female (44.9%) patients. About 91% of the patients were vaccinated against COVID-19, 30.6% of whom were vaccinated within 29 days of being diagnosed with DKA. The pH and bicarbonate levels were observed to be significantly high among those who were diagnosed with DKA within 29 days of vaccination, with p-values of 0.031 and 0.037, respectively. Similarly, pH and random blood sugar (RBS) were observed to be significantly higher among the vaccinated patients than in the non-vaccinated subjects (P = 0.044 and P = 0.032, respectively).
CONCLUSIONS
The study findings revealed that some of the DKA indicators were evident among the vaccinated patients. However, larger-scale and multi-center studies are recommended in order to have more conclusive evidence and generalize the findings.
PubMed: 38694238
DOI: 10.5812/ijem-135866