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Delayed referral is common even when new-onset diabetes is suspected in children. A Swedish prospective observational study of diabetic ketoacidosis at onset of Type 1 diabetes.
Wersäll, JH, Adolfsson, P, Forsander, G, Ricksten, SE, Hanas, R
Pediatric diabetes. 2021;(6):900-908
Abstract
OBJECTIVE Delayed treatment for new-onset diabetes Type 1 (T1D) can lead to diabetic ketoacidosis (DKA) with potentially devastating consequences. This prospective observational study aimed to characterize pediatric patients with DKA at hospital admission, regarding parental awareness of diabetes-related symptoms and delayed referrals from primary health care providers to pediatric emergency wards. RESEARCH DESIGN AND METHODS Patients 0-18 years admitted to hospital with new-onset T1D and DKA between 2015 and 2017 were invited to participate. Questionnaires were filled out separately by the caregivers and by the attending hospital staff. Data from the Swedish National Diabetes Registry (SWEDIABKIDS) were used for comparison. Delayed referral was defined as a primary healthcare contact due to diabetes-related symptoms 0-4 weeks before hospital admission without immediate referral, or registered elevated glucose levels at primary healthcare centers without immediate referral. RESULTS The study included 237 patients, among which parental suspicion of new-onset diabetes before healthcare contacts was reported in 39%. Parental suspicion of diabetes was associated with higher pH values at diagnosis. Patients in contact with primary health care providers before hospital admission had a delayed referral in 43% of the cases. Delayed referral was associated with lower pH values at hospital admission. Symptoms leading to primary healthcare contacts were similar regardless of whether delay occurred or not. CONCLUSIONS Parental suspicion of diabetes was associated with milder DKA at hospital admission. Delayed referral was seen in a considerable proportion of children with primary healthcare contacts for symptoms associated with diabetes. Increased awareness of diabetes symptoms is of paramount importance.
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Effectiveness of ketoacidosis prevention campaigns at diagnosis of type 1 diabetes in children: A systematic review and meta-analysis.
Cherubini, V, Marino, M, Carle, F, Zagaroli, L, Bowers, R, Gesuita, R
Diabetes research and clinical practice. 2021;:108838
Abstract
AIM: To determine if diabetes awareness campaigns are an effective intervention to reduce diabetes ketoacidosis at diagnosis of type 1 diabetes in children and youth. METHODS Search strategies included PubMed, Scopus, CINAHL and WOS electronic databases, hand search of select journals and a grey literature search "Google" search to include all relevant information. Studies included community-based interventions focused on children younger than 18 years old. The difference in the frequency of DKA was measured in two separate comparisons; before and after perform awareness campaigns in the same area, and between areas with and without intervention campaigns. RESULTS Of 1136 records identified, 14 studies were eligible for the analysis. The first group of 12 studies measured DKA at diagnosis, before (n = 6548 individuals) and after (n = 4931 individuals) the awareness campaigns. The pooled difference was a reduction of 7.20% (95%CI: 0.99-13.41). The second group of four studies measured the difference in an area with no intervention (n = 338 individuals) and in an area with an awareness campaign (n = 187 individuals). The pooled difference in DKA was 35.71% (95%CI: 5.81-65.61). CONCLUSIONS This review demonstrated that DKA awareness campaigns are effective to reduce DKA among children and adolescents with type 1 diabetes and the core components that explain why these campaigns are effective. Back to top.
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Predisposing factors for the development of diabetic ketoacidosis with lower than anticipated glucose levels in type 2 diabetes patients on SGLT2-inhibitors: a review.
Bamgboye, AO, Oni, IO, Collier, A
European journal of clinical pharmacology. 2021;(5):651-657
Abstract
PURPOSE SGLT2-inhibitors (SGLT-2i) have been linked to the risk of potential life-threatening diabetic ketoacidosis (DKA). The U.S. Food and Drug Administration and the European Medicines Agency issued warnings in 2015 and 2016 respectively on the predisposing factors to the development of DKA in individuals on an SGLT2i. New predisposing factors to DKA are still being discovered with the use of SGLT-2i. The list by FDA and EMA is yet to be updated. This article aims to provide a holistic list that includes the newer factors that have been implicated in the development of DKA. The overall aim is to guide physicians in prescribing this class of drugs for type 2 diabetes mellitus (T2D). METHOD A search was done using PUBMED, Google Scholar, and Directory of Open Access Journals with the following words: SGLT-2 Inhibitors AND Ketoacidosis were entered. We included articles from 2000 to 2020, those in English, those involving any of the approved SGLT2i medications in T2D patients, and studies that focused on DKA linked to SGLT-2i. These articles were reviewed, and relevant data extracted and compiled. RESULTS AND CONCLUSION The review has revealed that predisposing factors include (excess) alcohol consumption, female gender, starvation due to illness or fasting, withholding the use of SGLT2i for less than 48 h peri-operatively, and the existence of a variations in the expression of SGLT2 receptors. Patients should be advised on "sick day rules," and if a patient becomes unwell while on an SGLT2i, they should be advised to withhold the medication for the duration of the intercurrent illness.
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Fluid and electrolyte therapy in childhood diabetic ketoacidosis management: A rationale for new national guideline.
Agwu, JC, Ng, SM
Diabetic medicine : a journal of the British Diabetic Association. 2021;(8):e14595
Abstract
Fluid and electrolyte therapy in childhood diabetic ketoacidosis (DKA) management has been controversial. Previous National Institute for Health and Care Excellence (NICE) 2015 guidance advocated a restricted fluid regimen while more recent guidelines have advocated a more liberal approach to fluid replacement in DKA. At the core of the debate is the need to avoid developing cerebral oedema as a complication. Although subtle asymptomatic cerebral oedema is common in children presenting in DKA, clinically apparent cerebral oedema is rare and has been reported in approximately 0.5%-1% of DKA cases in children. Recent research evidence has shown that there was no clear evidence of a difference in rates of clinically apparent cerebral injury in children in DKA managed with a range of fluid volumes and rates of rehydration. In view of this, NICE has updated its guideline. In this paper, we review literature evidence underpinning the current understanding of the pathophysiology of cerebral oedema in children and discuss the rationale for the new NICE guidance.
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Sodium/Glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis: An Example of Complementary Evidence for Rare Adverse Events.
Alkabbani, W, Pelletier, R, Gamble, JM
American journal of epidemiology. 2021;(8):1572-1581
Abstract
Evidence from observational studies may be considered complementary to that of randomized controlled trials (RCTs), particularly when assessing rare outcomes of drug therapies. Sodium/glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic agents that have been linked to an increased risk of diabetic ketoacidosis (DKA). We conducted a systematic review and separately meta-analyzed data from RCTs (n = 18; 2013-2019) and cohort studies (n = 7; 2017-2020) to assess the consistency of the magnitude of association between SGLT-2 inhibitors and DKA risk. We illustrate the strengths and weaknesses of the 2 designs. Results from RCTs and observational studies consistently showed almost a doubling in the risk of DKA among patients using an SGLT-2 inhibitor as compared with placebo or an active comparator. In a random-effects model, the pooled relative risk was 2.08 (95% confidence interval (CI): 1.28, 3.40) from placebo-controlled RCTs and 0.82 (95% CI: 0.25, 2.68) from active-comparator RCTs. The pooled adjusted hazard ratio from observational studies was 1.74 (95% CI: 1.28, 2.38). Notably, the 2 designs complement each other in several domains, including external and internal validity and power. This demonstrates a need for more comprehensive evidence when assessing rare adverse events for both sources.
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Early prediction models for prognosis of diabetic ketoacidosis in the emergency department: A protocol for systematic review and meta-analysis.
Li, Q, Lv, L, Chen, Y, Zhou, Y
Medicine. 2021;(21):e26113
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Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is one of the most serious complications after diabetes poor control, which seriously threatens human life, health, and safety. DKA can rapidly develop within hours or days leading to death. Early evaluation of the prognosis of DKA patients and timely and effective intervention are very important to improve the prognosis of patients. The combination of several variables or characteristics is used to predict the poor prognosis of DKA, which can allocate resources reasonably, which is beneficial to the early classification intervention and clinical treatment of the patients. METHODS For the acquisition of required data of eligible prospective/retrospective cohort study or randomized controlled trials (RCTs), we will search for publications from PubMed, Web of science, EMBASE, Cochrane Library, Google scholar, China national knowledge infrastructure (CNKI), Wanfang and China Science and Technology Journal Database (VIP). Two independent reviewers will read the full English text of the articles, screened and selected carefully, removing duplication. Then we evaluate the quality and analyses data by Review Manager (V.5.4). Results data will be pooled and meta-analysis will be conducted if there's 2 eligible studies considered. RESULTS This systematic review and meta-analysis will evaluate the value of the prediction models for the prognosis of DKA in the emergency department. CONCLUSIONS This systematic review and meta-analysis will provide clinical basis for predicting the prognosis of DKA. It helps us to understand the value of predictive models in evaluating the early prognosis of DKA. The conclusions drawn from this study may be beneficial to patients, clinicians, and health-related policy makers. STUDY REGISTRATION NUMBER INPLASY202150023.
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Diabetic Ketoacidosis at the Time of Diagnosis of Type 1 Diabetes in Children: Insights From TRIGR.
Nakhla, M, Cuthbertson, D, Becker, DJ, Pacaud, D, Ludvigsson, J, Knip, M, Legault, L
JAMA pediatrics. 2021;(5):518-520
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This cohort study assesses the risk of diabetic ketoacidosis at the diagnosis of type 1 diabetes among children who participated in the Trial to Reduce Insulin-Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR).
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Hyperlactatemia associated with diabetic ketoacidosis in pediatric intensive care unit.
Liu, J, Yan, H, Li, Y
BMC endocrine disorders. 2021;(1):110
Abstract
BACKGROUND Children with diabetic ketoacidosis often have elevated lactate. In this study, we investigated the clinical variables associated with hyperlactatemia in children with diabetic ketoacidosis. METHODS We designed a single-center retrospective descriptive study of children with diabetic ketoacidosis in a pediatric intensive care unit. RESULTS Of the 107 patients with diabetic ketoacidosis included in the analysis, 61 developed hyperlactatemia. Multivariate logistic regression analysis showed that heart rate (p = 0.003),diastolic blood pressure (p = 0.001) and stage of severity (p = 0.042) were independently associated with the development of hyperlactatemia in diabetic ketoacidosis. We found that lactate level was not significantly associated with length of hospital stay (p = 0.115) or the length of time to diabetic ketoacidosis resolution (p = 0.143). CONCLUSIONS Children with diabetic ketoacidosis presenting with severer stage, elevated heart rate and higher diastolic blood pressure may be prone to hyperlactatemia. Hyperlactatemia was not associated with length of time to DKA resolution and length of hospital stay.
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Steroid-Induced Diabetes Ketoacidosis in an Immune Thrombocytopenia Patient: A Case Report and Literature Review.
Alakkas, Z, Alzaedi, OA, Somannavar, SS, Alfaifi, A
The American journal of case reports. 2020;:e923372
Abstract
BACKGROUND Steroids are used as anti-inflammatory agents, administered for a variety of medical conditions, either as short- or long-term treatment. Steroid use is associated with many adverse effects, including hyperglycemia, but ketoacidosis is rare. CASE REPORT We present the case of a 53-year-old woman who developed diabetic ketoacidosis after administration of methylprednisolone during treatment of immune thrombocytopenic purpura. She did not have diabetes or a family history of diabetes. Steroid-induced hyperglycemia with insulin resistance, lipolysis, and ketogenesis occurred and were likely to have precipitated the ketoacidosis. Blood glucose, blood gases, and urine test results were diagnostic for ketoacidosis. CONCLUSIONS The risk of ketoacidosis and hyperglycemia should be considered in the course of steroid therapy, even without a diagnosis of diabetes, especially in patients who have risk factors for diabetes mellitus including obesity and long-term use of steroids, so that early identification of diabetic ketoacidosis can prevent further morbidity and mortality in chronic patients.
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Is Age a Risk Factor for Cerebral Edema in Children With Diabetic Ketoacidosis? A Literature Review.
Glackin, S, Metzger, D, Hanas, R, Chanoine, JP
Canadian journal of diabetes. 2020;(1):111-118
Abstract
Cerebral edema (CE) is a rare but potentially fatal complication of diabetic ketoacidosis (DKA) in children with type 1 diabetes. CE is frequently mentioned as being more common in young children. The primary objective of this study was to review the evidence suggesting that younger age is a risk factor for the development of CE during DKA. The secondary objective was to assess if younger children are at a higher risk of DKA and severe DKA. A literature review was performed, and studies which reported the frequency of CE, DKA and severe DKA in children <3 and 3 to 5 years of age were included. Among the 6 studies reporting the frequency of CE that were identified, 5 good-quality studies found no significant association between younger age and higher risk of CE. Twenty-seven studies (DKA frequency: 11.3% to 54%) reported DKA frequency as a function of age. Most published studies found a higher frequency of DKA in children <5 years of age (20/25 studies), and in particular in those in the first 2 to 3 years of life (8/8 studies). There was inconclusive evidence to determine whether the severity of DKA was influenced by age. In conclusion, the commonly held view that CE is more common in younger children is not supported by the existing literature. Published data suggest that DKA (and possibly severe DKA) is more common in very young children. Regardless of age, all children with DKA should be monitored carefully for the development of CE.