Diabetic Ketoacidosis at the Time of Diagnosis of Type 1 Diabetes in Children: Insights From TRIGR.
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ABSTRACT:
SUBMITTER: Nakhla M
PROVIDER: S-EPMC7835920 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
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Diabetic Ketoacidosis at the Time of Diagnosis of Type 1 Diabetes in Children: Insights From TRIGR.
Nakhla Meranda M Cuthbertson David D Becker Dorothy J DJ Pacaud Daniéle D Ludvigsson Johnny J Knip Mikael M Legault Laurent L
JAMA pediatrics 20210501 5
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Project description:The objective of this study was to evaluate the effectiveness of a brief, office-based educational intervention to increase parent or patient recognition of the early warning signs and symptoms of diabetic ketoacidosis (DKA). Forty-two patients aged > 13 years and 34 parents of children aged ≤ 13 years were given a pretest questionnaire about their knowledge of signs and symptoms of DKA and sick day management practices. They received a brief refresher course on sick day management specific to their treatment modality (pump vs. injection) and were given a take-home flow sheet of guidelines for diabetes sick day management. Subjects were retested with the same knowledge questionnaire after 6 to 12 months. Patients or parents scored higher on the posttest than the pretest and called the emergency line for assistance more frequently (p = .032) following the intervention. Emergency department visits were significantly reduced in adolescents (p = .024). A short educational intervention and printed management tool is effective in improving sick day and DKA knowledge and appears to be effective in reducing emergency department visits by increasing utilization of a diabetes emergency line for early outpatient intervention.
| S-EPMC7774356 | biostudies-literature
Project description:OBJECTIVE:Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type 1 diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged <2 and <5 years compared with population-based incidence studies and registries. RESEARCH DESIGN AND METHODS:Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register). RESULTS:A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children <2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P < 0.0001; Swediabkids, P = 0.02; SEARCH, P < 0.0001; Finnish Register, P < 0.0001). The prevalence of DKA in TEDDY children diagnosed at <5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P < 0.0001) and the German DPV Register (32.2%) (P < 0.0001) but not compared with Swediabkids or the Finnish Register. CONCLUSIONS:Participation in the TEDDY study is associated with reduced risk of DKA at diagnosis of type 1 diabetes in young children.
| S-EPMC3198296 | biostudies-literature
Project description:This longitudinal population-based study analyses the frequency of diabetic ketoacidosis (DKA) at type 1 diabetes diagnosis in Italian children under 15 years of age, during 2004-2013. DKA was defined as absent (pH ≥ 7.30), mild/moderate (7.1 ≤ pH < 7.30) and severe (pH < 7.1). Two multiple logistic regression models were used to evaluate the time trend of DKA frequency considered as present versus absent and severe versus absent, adjusted for gender, age group and geographical area of residence at diagnosis. Overall, 9,040 cases were ascertained. DKA frequency was 40.3% (95%CI: 39.3-41.4%), with 29.1% and 11.2% for mild/moderate and severe DKA, respectively. Severe DKA increased significantly during the period (OR = 1.03, 95%CI: 1.003-1.05). Younger-age children and children living in Southern Italy compared to Central Italy were at significantly higher risk of DKA and severe DKA. Family history of type 1 diabetes and residence in Sardinia compared to Central Italy were significantly associated with a lower probability of DKA and severe DKA. The high frequency of ketoacidosis in Italy over time and high variability among age groups and geographical area of residence, strongly suggests a continuing need for nationwide healthcare strategies to increase awareness of early detection of diabetes.
| S-EPMC5171855 | biostudies-literature
Project description:BackgroundConsidering the roles of 25-hydroxyvitamin D (25OHD) in glucose homeostasis and immune modulation, vitamin D deficiency may be related to the development of type 1 diabetes (T1DM) and diabetic ketoacidosis (DKA). We evaluated the total, free, bioavailable 25OHD levels and vitamin D binding protein (VDBP) levels and genotypes between T1DM patients and controls.MethodsThis retrospective, cross-sectional study included 84 children with T1DM (38 boys and 46 girls, 8.0 ± 3.6 years) and 1:1 age- and sex-matched healthy controls. A multiplex liquid chromatography-tandem mass spectrometry-based assay was used to simultaneously measure vitamin D metabolites.ResultsPatients with T1DM had lower levels of total 25OHD (16.3 ± 5.1 vs. 19.9 ± 6.5 ng/mL, P< 0.001) and VDBP (146.0 ± 27.8 vs. 224.9 ± 36.1 µg/mL, P = 0.001), but higher free 25OHD (8.0 ± 2.5 vs. 6.5 ± 2.3 pg/mL, P< 0.001) than controls. Patients who presented with DKA had lower levels of 25OHD in the total (15.0 ± 4.6 vs. 17.6 ± 5.2 ng/mL, P = 0.020), free (7.5 ± 2.6 vs. 8.4 ± 2.4 pg/mL, P = 0.059), and bioavailable (2.3 ± 0.9 vs. 2.8 ± 0.8 ng/mL, P = 0.014) forms than those without DKA at the T1DM diagnosis. The lower the total, free, and bioavailable 25OHD levels at diagnosis, the lower the pH and HCO3-. The proportions of the VDBP genotypes did not differ between the patients and controls.ConclusionPatients with T1DM had higher levels of free 25OHD than healthy children, despite lower levels of total 25OHD. However, patients with DKA exhibited lower levels of bioavailable 25OHD than those without DKA at the T1DM diagnosis. The lower the concentrations of free and bioavailable 25OHD, the more severe the acidosis at the initial T1DM presentation.
| S-EPMC9631212 | biostudies-literature
Project description:Diabetic ketoacidosis (DKA) is a serious complication of complete insulin deficiency and insulin resistance in Type 1 diabetes (T1D). This results in the body producing high levels of serum ketones in an attempt to compensate for the insulin deficiency and decreased glucose utilization. DKA's metabolic and immunologic dysregulation results in gradual increase of systemic and cerebral oxidative stress, along with low grade systemic and cerebral inflammation and the development of pretreatment subclinical BE. During treatment the early progression of oxidative stress and inflammation is hypothesized to advance the possibility of occurrence of crisis of clinical brain edema (BE), which is the most important cause of morbidity and mortality in pediatric DKA. Longitudinal neurocognitive studies after DKA treatment show progressive and latent deficits of cognition and emphasize the need for more effective DKA treatment of this long-standing conundrum of clinical BE, in the presence of systemic osmotic dehydration, metabolic acidosis and immune dysregulation. Candidate biomarkers of several systemic and neuroinflammatory pathways prior to treatment also progress during treatment, such as the neurotoxic and neuroprotective molecules in the well-recognized tryptophan (TRP)/kynurenine pathway (KP) that have not been investigated in DKA. We used LC-MS/MS targeted mass spectrometry analysis to determine the presence and initiation of the TRP/KP at three time points: A) 6-12 hours after initiation of treatment; B) 2 weeks; and C) 3 months following DKA treatment to determine if they might be involved in the pathogenesis of the acute vasogenic complication of DKA/BE. The Trp/KP metabolites TRP, KYN, quinolinic acid (QA), xanthurnenic acid (XA), and picolinic acid (PA) followed a similar pattern of lower levels in early treatment, with subsequent increases. Time point A compared to Time points B and C were similar to the pattern of sRAGE, lactate and pyruvic acid. The serotonin/melatonin metabolites also followed a similar pattern of lower quantities at the early stages of treatment compared to 3 months after treatment. In addition, glutamate, n-acetylglutamate, glutamine, and taurine were all lower at early treatment compared to 3 months, while the ketones 3-hydroxybutaric acid and acetoacetate were significantly higher in the early treatment compared to 3 months. The two major fat metabolites, L-carnitine and acetyl-L-carnitine (ALC) changed inversely, with ALC significantly decreasing at 2 weeks and 3 months compared to the early stages of treatment. Both anthranilic acid (AA) and 3-OH-anthranilic acid (3OH-AA) had overall higher levels in the early stages of treatment (A) compared to Time points (B and C). Interestingly, the levels of AA and 3OH-AA early in treatment were higher in Caucasian females compared to African American females. There were also differences in the metabolite levels of QA and kynurenic acid (KA) between genders and between races that may be important for further development of custom targeted treatments. We hypothesize that the TRP/KP, along with the other inflammatory pathways, is an active participant in the metabolic and immunologic pathogenesis of DKA's acute and chronic insults.
| S-EPMC8289002 | biostudies-literature
Project description:BackgroundDiabetic ketoacidosis at type 1 diabetes diagnosis is a preventable life-threatening complication. Canadian data on the temporal trends of the prevalence of diabetic ketoacidosis at the onset of type 1 diabetes in children are unknown. We aimed to determine the temporal changes in diabetic ketoacidosis prevalence at diabetes diagnosis in Quebec.MethodsWe conducted a population-based cohort study of children (aged 1-17 yr) living in Quebec who were diagnosed with diabetes between 2001 and 2014, using multiple health administrative linked databases available at the Institut national de santé publique du Québec through the Quebec Integrated Chronic Surveillance System. We used multivariate Poisson regression analysis with robust error variance to determine trends in the prevalence of diabetic ketoacidosis.ResultsWe found that 25.6% (1471/5741) of children presented with diabetic ketoacidosis at diabetes diagnosis. The incidence of diabetes was stable at 30 cases per 100 000 children per year during the study period. The age- and sex-standardized rates of diabetic ketoacidosis increased from 22% (95% confidence interval [CI] 17%-26%) in 2001 to 30% (95% CI 24%-36%) in 2014. The relative increase of diabetic ketoacidosis prevalence at diabetes diagnosis over the study period was 2.0% per year (rate ratio 1.02; 95% CI 1.01-1.03).InterpretationDespite a stable incidence of type 1 diabetes, we found that the prevalence of diabetic ketoacidosis at diabetes onset increased between 2001 and 2014. Our findings are concerning and demonstrate a need to continue to campaign to recognize type 1 diabetes before diabetic ketoacidosis supervenes.
| S-EPMC6517121 | biostudies-literature
Project description:Aim/hypothesisTo compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019.MethodsForty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019.ResultsOverall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively).Conclusions/interpretationThere was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks.
| S-EPMC9247264 | biostudies-literature
Project description:ImportanceDiabetic kidney disease is among the most important causes of end-stage kidney disease worldwide. Risk factors for diabetic kidney disease remain incompletely defined. Recent studies document a high frequency of acute kidney injury (AKI) during diabetic ketoacidosis (DKA) in children, raising the question of whether these AKI episodes might contribute to future risk of diabetic kidney disease.ObjectiveTo determine whether episodes of AKI occurring during DKA in children are associated with increased risk of development of microalbuminuria.Design, setting, and participantsThis retrospective review of medical records included children with type 1 diabetes with 1 or more urine albumin levels measured during routine diabetes care from 2 university-affiliated urban tertiary children's hospitals in the United States from January 2006 to December 2019. Age at diagnosis of diabetes, hemoglobin A1c levels, episodes of DKA, pH and creatinine levels during DKA, and urine albumin and creatinine measurements were analyzed. Cox proportional hazards regression models were used to identify variables affecting the hazard rate for microalbuminuria development. Analyses began January 2021 and ended May 2021.ExposuresEpisodes of DKA and episodes of AKI occurring during DKA.Main outcomes and measuresAKI occurrence and AKI stage were determined from serum creatinine measurements during DKA using Kidney Disease: Improving Global Outcomes criteria. Microalbuminuria was defined as urine albumin-to-creatinine ratio of 30 mg/g or more or excretion of 30 mg or more of albumin in 24 hours.ResultsOf 2345 children, the mean (SD) age at diagnosis was 9.4 (4.4) years. One or more episodes of DKA occurred in 963 children (41%), and AKI occurred during DKA in 560 episodes (47%). In multivariable models adjusting for the associations of age at diagnosis and mean hemoglobin A1c level since diagnosis, each episode of AKI during DKA was associated with a hazard ratio of 1.56 (95% CI, 1.3-1.87) for development of microalbuminuria. Four or more episodes increased the hazard rate by more than 5-fold. DKA episodes without AKI did not significantly increase the hazard rate for microalbuminuria development after adjusting for other covariates.Conclusions and relevanceThese data demonstrate that episodes of AKI occurring during DKA in children with type 1 diabetes are significantly associated with risk of developing microalbuminuria. Greater efforts are necessary to reduce the frequency of DKA.
| S-EPMC8630664 | biostudies-literature
Project description:Background/objectiveThe prevalence of diabetic ketoacidosis (DKA) in gestational diabetes mellitus (GDM) is very low. We describe a patient with GDM in whom severe DKA with intrauterine fetal demise developed in the setting of nonadherence to therapy.Case reportA 33-year-old woman, G2P0010, with no preexisting diabetes mellitus (DM) presented at 30 weeks of gestation with acute-onset altered sensorium, nausea, and emesis. GDM was diagnosed at 15 weeks of gestation with a serum glucose level of 266 mg/dL (70-134 mg/dL) after 1-hour 50-gram glucose challenge test. Glycated hemoglobin (HbA1C) was 5.9% (41 mmol/mol) at the time of GMD diagnosis. Insulin was initiated at week 20 of gestation. On presentation, serum glucose level of 920 mg/dL (70-110 mg/dL), pH of 7.02 (7.32-7.43), anion gap level of 38 mmol (5-17 mmol), bicarbonate level of 5.0 mEq/L (22-29 mEq/L), and large serum ketones were found. Ultrasound showed intrauterine fetal demise. She received intravenous fluids and continuous insulin. Following the spontaneous delivery of a nonviable fetus, DKA was resolved. Negative antiglutamic acid decarboxylase, islet cell, and zinc transporter 8 antibodies, C-peptide level of 2.4 ng/dL (1.1-4.4 ng/dL), and HbA1C level of 9% (75 mmol/mol) were found. Inpatient management included basal-bolus and sliding scale insulin therapies. Metformin was added upon discharge 7 days after admission. The HbA1C levels were 5.3% (34 mmol/mol) and 5% (31 mmol/mol) at the 3- and 6-month follow-ups, respectively. Insulin was discontinued. Currently, the patient is on metformin and glucagon-like peptide 1 receptor agonist.DiscussionThe development of insulin resistance during pregnancy is driven by multiple factors. Approximately 1% to 2% of pregnant women with impaired glucose tolerance develop DKA; most cases occur in women with type 1 DM. The approximate incidence of DKA in GDM is 0.02%.ConclusionDKA complicating GDM is extremely infrequent, but it cannot be dismissed. Early recognition along with prompt and appropriate medical and obstetrical management is critical.
| S-EPMC9508574 | biostudies-literature
Project description:ObjectiveTo identify the factors associated with diabetic ketoacidosis at diagnosis of type 1 diabetes in children and young adults.DesignSystematic review.Data sourcesPubMed, EMBASE, Web of Science, Scopus, and Cinahl and article reference lists.Study selectionCohort studies including unselected groups of children and young adults presenting with new onset type 1 diabetes that distinguished between those who presented in diabetic ketoacidosis and those who did not and included a measurement of either pH or bicarbonate in the definition of diabetic ketoacidosis. There were no restrictions on language of publication.Results46 studies involving more than 24,000 children in 31 countries were included. Together they compared 23 different factors. Factors associated with increased risk were younger age (for <2 years old v older, odds ratio 3.41 (95% confidence interval 2.54 to 4.59), for <5 years v older, odds ratio 1.59 (1.38 to 1.84)), diagnostic error (odds ratio 3.35 (2.35 to 4.79)), ethnic minority, lack of health insurance in the US (odds ratio 3.20 (2.03 to 5.04)), lower body mass index, preceding infection (odds ratio 3.14 (0.94 to 10.47)), and delayed treatment (odds ratio 1.74 (1.10 to 2.77)). Protective factors were having a first degree relative with type 1 diabetes at the time of diagnosis (odds ratio 0.33 (0.08 to 1.26)), higher parental education (odds ratios 0.4 (0.20 to 0.79) and 0.64 (0.43 to 0.94) in two studies), and higher background incidence of type 1 diabetes (correlation coefficient -0.715). The mean duration of symptoms was similar between children presenting with or without diabetic ketoacidosis (16.5 days (standard error 6.2) and 17.1 days (6.0) respectively), and up to 38.8% (285/735) of children who presented with diabetic ketoacidosis had been seen at least once by a doctor before diagnosis.ConclusionsMultiple factors affect the risk of developing diabetic ketoacidosis at the onset of type 1 diabetes in children and young adults, and there is potential time, scope, and opportunity to intervene between symptom onset and development of diabetic ketoacidosis for both parents and clinicians.
| S-EPMC3131115 | biostudies-literature