Dataset Information

Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review.

ABSTRACT:

Aims/hypothesis

Type 1 diabetes is the most frequent endocrine disease in children, with 65,000 children diagnosed worldwide every year. Up to 80% of these children present with diabetic ketoacidosis (DKA), which is associated with both short-term risks and long-term consequences. This study aimed to characterise the worldwide variation in presentation of type 1 diabetes to inform future interventions to reduce this excess morbidity and mortality.

Methods

This was a systematic review of studies indexed on PubMed, EMBASE, Web of Science, Scopus or CINAHL before March 2011 that included unselected groups of children presenting with new-onset type 1 diabetes, reported the proportion presenting with DKA and used a definition of DKA based on measurement of pH or bicarbonate.

Results

Sixty-five studies of cohorts comprising over 29,000 children in 31 countries were included. The frequency of DKA at diagnosis ranged from 12.8% to 80%, with highest frequencies in the United Arab Emirates, Saudi Arabia and Romania, and the lowest in Sweden, the Slovak Republic and Canada. Multivariable modelling showed the frequency of DKA was inversely associated with gross domestic product, latitude and background incidence of type 1 diabetes.

Conclusions/interpretation

This is the first description of the variation in frequency of DKA at presentation of type 1 diabetes in children across countries. It demonstrates large variations that may, at least in part, be explained by different levels of disease awareness and healthcare provision and suggests ways to decrease the excess morbidity and mortality associated with DKA at diagnosis.

SUBMITTER: Usher-Smith JA

PROVIDER: S-EPMC3464389 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

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.

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.