Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children

OBJECTIVE To investigate the impact of new-onset diabetic ketoacidosis (DKA) during child- hood on brain morphology and function. RESEARCH DESIGN AND METHODS Patients aged 6–18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients under- went magnetic resonance imaging (MRI) and spectroscopy with cognitive assess- ment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses. RESULTS Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at base- line in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes. CONCLUSIONS DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.

The impact of diabetic ketoacidosis and age on behavior six months post-diagnosis in children with type 1 diabetes

Objectives: Children with type 1 diabetes mellitus (DM1) may be at increased risk of psychosocial and adjustment difficulties. We examined behavioral outcomes six months post-diagnosis in a group of children with newly diagnosed DM1. Methods: This study formed part of a larger longitudinal project examining pathophysiology and neuropsychological outcomes in diabetic patients with or without diabetic ketoacidosis (DKA). Participants were 61 children (mean age 11.8 years, SD 2.7 years) who presented with a new diagnosis of DM1 at the Royal Children’s Hospital, Melbourne. Twenty-three (11 female) presented in DKA and 38 (14 female) without DKA. Parents completed the behavior assessment system for children, second edition six months post-diagnosis. Results: There was a non-linear relationship between age and behavior. Internalising problems (i.e. anxiety depression, withdrawal) peaked in the transition from childhood to adolescence; children aged 10–13 years had elevated rates relative to the normal population (t = 2.55, P = 0.018). There was a non-significant trend for children under 10 to display internalising problems (P = 0.052), but rates were not elevated in children over 13 (P = 0.538). Externalising problems were not significantly elevated in any age group. Interestingly, children who presented in DKA were at lower risk of internalising problems than children without DKA (t = 3.83, P < 0.001). There was no effect of DKA on externalising behaviors. Conclusions: Children transitioning from childhood to adolescence are at significant risk for developing internalising problems such as anxiety and lowered mood after diagnosis of DM1. Somewhat counter-intuitively, parents of children presenting in DKA reported fewer internalising symptoms than parents of children without DKA. These results highlight the importance of monitoring and supporting psychosocial adjustment in newly diagnosed children even when they seem physically well.

Diabetic ketoacidosis and electroencephalographic changes in newly diagnosed pediatric patients

Objective: To document electroencephalogram (EEG) changes and their correlation with clinical parameters in a newly diagnosed pediatric cohort of type 1 diabetes mellitus (T1DM) patients with and without diabetic ketoacidosis (DKA) and to define their medium term utility and significance. Research design and methods: Prospective longitudinal study of children presenting with T1DM. EEGs were performed within 24 h of diagnosis, day 5, and at 6 months post-diagnosis and reviewed by a neurologist blinded to clinical status. Severity of encephalopathy was graded from 1 to 5 using the Aoki and Lombroso encephalopathy scale. Cognitive abilities were assessed using standardized tests of attention, memory, and intelligence. Results: Eighty eight children were recruited; 34 presented with DKA. Abnormal background slowing was more often observed in the first 24 h in children with DKA (p = 0.01). Encephalopathy scores on day 1 correlated with initial pH, CO2, HCO3, base excess, respiratory rate, heart rate, diastolic blood pressure, and IV fluid intake (all parameters p < 0.05). EEG scores at day 1 did not correlate with contemporaneous mental state or cognition in the medium term. Conclusions: DKA was associated with significant clinical and neurophysiologic signs of brain dysfunction at presentation. While EEG is sensitive to the detection of encephalopathy in newly diagnosed T1DM, it has limited use in identifying children at risk of later cognitive deficits.

Substantial reductions in the number of diabetic ketoacidosis and severe hypoglycaemia episodes requiring emergency treatment lead to reduced costs after structured education in adults with Type 1 diabetes

To determine the impact of structured education promoting flexible intensive insulin therapy on rates of diabetic ketoacidosis, and the costs associated with emergency treatment for severe hypoglycaemia and ketoacidosis in adults with Type 1 diabetes.

Alternative management of diabetic ketoacidosis in a Brazilian pediatric emergency department

DKA is a severe metabolic derangement characterized by dehydration, loss of electrolytes, hyperglycemia, hyperketonemia, acidosis and progressive loss of consciousness that results from severe insulin deficiency combined with the effects of increased levels of counterregulatory hormones (catecholamines, glucagon, cortisol, growth hormone). The biochemical criteria for diagnosis are: blood glucose > 200 mg/dl, venous pH <7.3 or bicarbonate <15 mEq/L, ketonemia >3 mmol/L and presence of ketonuria. A patient with DKA must be managed in an emergency ward by an experienced staff or in an intensive care unit (ICU), in order to provide an intensive monitoring of the vital and neurological signs, and of the patient's clinical and biochemical response to treatment. DKA treatment guidelines include: restoration of circulating volume and electrolyte replacement; correction of insulin deficiency aiming at the resolution of metabolic acidosis and ketosis; reduction of risk of cerebral edema; avoidance of other complications of therapy (hypoglycemia, hypokalemia, hyperkalemia, hyperchloremic acidosis); identification and treatment of precipitating events. In Brazil, there are few pediatric ICU beds in public hospitals, so an alternative protocol was designed to abbreviate the time on intravenous infusion lines in order to facilitate DKA management in general emergency wards. The main differences between this protocol and the international guidelines are: intravenous fluid will be stopped when oral fluids are well tolerated and total deficit will be replaced orally; if potassium analysis still indicate need for replacement, it will be given orally; subcutaneous rapid-acting insulin analog is administered at 0.15 U/kg dose every 2-3 hours until resolution of metabolic acidosis; approximately 12 hours after treatment initiation, intermediate-acting (NPH) insulin is initiated at the dose of 0.6-1 U/kg/day, and it will be lowered to 0.4-0.7 U/kg/day at discharge from hospital.

Bilateral posterior ischaemic optic neuropathy after severe diabetic ketoacidosis, cardiopulmonary resuscitation and respiratory failure

A 44-year-old male European with type I diabetes mellitus fell into diabetic ketoacidosis. In the emergency room, he developed an episode of asystole and respiratory failure requiring one cycle of cardiopulmonary resuscitation and extracorporeal membrane oxygenation (ECMO). Waking up 7 days later, he presented a bilateral complete loss of vision. Ophthalmological examination including funduscopy on days 1 and 10, after extubation, showed bilateral large round pupils non-reactive to light and a normal fundus. Neuroimaging studies, including MRI and MRA of the brain, were all within normal limits. A lumbar puncture and comprehensive serological testing excluded an infectious or rheumatic cause. An empirical high-dose intravenous steroid treatment administered for 5 days had no effect on his vision. His eye examination at 1.5 months follow-up showed a normal fundus except for progressive bilateral optic nerve disc pallor, which pointed towards the diagnosis of a posterior ischaemic optic neuropathy.

Insulin increases serum leptin concentrations in children and adolescents with newly diagnosed type I diabetes mellitus with and without ketoacidosis.

AIMS/HYPOTHESIS The aims of this study were to analyse the changes of serum leptin in newly diagnosed children and adolescents with Type I (insulin-dependent) diabetes mellitus after insulin treatment and to examine the possible impact of ketoacidosis on these changes. METHODS Baseline serum leptin concentrations were measured in 28 newly diagnosed Type I diabetic patients [age 8.75 +/- 4.05 years (means +/- SD); BMI 15.79 +/- 2.47 kg/m(2); HbA(1 c) 11.3 +/- 1.9 %] with (n = 18) and without (n = 10) ketoacidosis before commencement of insulin treatment, at the time of diagnosis. Thereafter, during a 4-day course of continuous intravenous insulin injection to gain and maintain euglycaemia, serum leptin concentrations were assessed. RESULTS Baseline serum leptin concentrations, adjusted to age, BMI, sex and pubertal stage, differed among these patients. There was, however, an increase of leptin in all subjects from 1.37 +/- 0.56 ng/ml (mean +/- SD) up to 2.97 +/- 1.52 ng/ml by 117 % (p < 0.0001) after insulin therapy. On average, peak serum leptin concentration was obtained after 42 h of insulin treatment. Further, there was no difference in the mean increase of serum leptin concentrations in the two groups, namely with and without ketoadicosis, of insulin-dependent diabetic children and adolescents. In addition, there was no correlation between serum leptin concentrations and correction of ketoacidosis during insulin treatment. CONCLUSIONS/INTERPRETATION Insulin increases serum leptin, within 1 day, in children and adolescents with newly diagnosed Type I diabetes. Ketoacidosis does not influence this interaction between insulin and leptin.

The development of a self-directed learning module for rural emergency nurses on pediatric diabetic ketoacidosis

Background: Newfoundland and Labrador has a high incidence of type 1 diabetes and diabetic ketoacidosis (DKA) is a complication of type 1 diabetes. A clinical practice guideline was developed for the treatment of pediatric diabetic ketoacidosis (DKA) to standardize care in all Emergency Departments and improve patient outcomes. Rural emergency nurses are requires to maintain their competency and acquire new knowledge as stated by the Association of Registered Nurses of Newfoundland and Labrador (ARNNL). Purpose: The purpose of this practicum was to develop a self-learning module for rural emergency nurses to increase their knowledge and understanding of the clinical practise guideline to assess, treat, and prevent pediatric ketoacidosis. Methods: Two methodologies were used in this practicum. A review of the literature and consultations with key stakeholders were completed. Results: The self-learning module created was composed of three units and focused on the learning needs of rural emergency nurses in the areas of assessment, treatment, and prevention of pediatric DKA. Conclusion: The goal of the practicum was to increase rural emergency nurses’ knowledge and implementation of the clinical practice guideline when assessing and treating children and families experiencing DKA to improve patient outcomes. A planned evaluation of the self-learning module will be conducted following dissemination of the module throughout the rural Emergency Departments.

Patient Characteristics Associated with Differences in Admission Frequency for Diabetic Ketoacidosis in U.S. Children’s Hospitals

Thesis (Master's)--University of Washington, 2016-08

Geographical variation of presentation at diagnosis of Type I diabetes in children: the EURODIAB Study

Aims/hypothesis. We aimed to describe the frequency and degree of diabetic ketoacidosis in children across Europe at the time of diagnosis of Type I (insulin-dependent) diabetes mellitus and to determine if factors such as age and geographical region contribute to the risk of diabetic ketoacidosis.

Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration:the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005)

Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM.

Is the formula of Traub still up to date in antemortem blood glucose level estimation?

According to the hypothesis of Traub, also known as the 'formula of Traub', postmortem values of glucose and lactate found in the cerebrospinal fluid or vitreous humor are considered indicators of antemortem blood glucose levels. However, because the lactate concentration increases in the vitreous and cerebrospinal fluid after death, some authors postulated that using the sum value to estimate antemortem blood glucose levels could lead to an overestimation of the cases of glucose metabolic disorders with fatal outcomes, such as diabetic ketoacidosis. The aim of our study, performed on 470 consecutive forensic cases, was to ascertain the advantages of the sum value to estimate antemortem blood glucose concentrations and, consequently, to rule out fatal diabetic ketoacidosis as the cause of death. Other biochemical parameters, such as blood 3-beta-hydroxybutyrate, acetoacetate, acetone, glycated haemoglobin and urine glucose levels, were also determined. In addition, postmortem native CT scan, autopsy, histology, neuropathology and toxicology were performed to confirm diabetic ketoacidosis as the cause of death. According to our results, the sum value does not add any further information for the estimation of antemortem blood glucose concentration. The vitreous glucose concentration appears to be the most reliable marker to estimate antemortem hyperglycaemia and, along with the determination of other biochemical markers (such as blood acetone and 3-beta-hydroxybutyrate, urine glucose and glycated haemoglobin), to confirm diabetic ketoacidosis as the cause of death.

Care of people with diabetes : a manual of nursing practice

Contents: Diagnosing and classifying diabetes -- Assessment and nursing diagnosis -- Monitoring diabetes mellitus -- Nutritional aspects of caring for people with diabetes -- Medication commonly used in diabetes management -- Hypoglycaemia -- Hyperglycaemia, diabetic ketoacidosis (DKA), hyperosmolar coma and lactic acidosis -- Long term complications of diabetes -- Management during surgical and investigative procedures -- Special situations and unusual conditions related to diabetes -- Diabetes and sexual health -- Diabetes in the older person -- Diabetes in children and adolescents -- Women, pregnancy, and gestational diabetes -- Psychological and quality of life issues related to having diabetes -- Diabetes education -- Discharge planning -- Community and primary care nursing and home-based care -- Complementary therapies and diabetes -- Managing diabetes in the emergency situations.

The ADKnowl: identifying knowledge deficits in diabetes care

Aims To present the ADKnowl measure of diabetes-related knowledge and evaluate its use in identifying the nature and extent of patient and health professional knowledge deficits.

Method The ADKnowl was used in a large-scale study of 789 patients (451 treated with insulin and 338 treated with tablets and/or diet) attending for annual review at one of two hospital out-patient diabetes clinics

Results Knowledge deficits were apparent in the patients. For example, 57% did not recognize the inaccuracy of the statement `fresh fruit can be eaten freely with little effect on blood glucose levels'. Seventy-five percent of patients did not know that it is advisable to trim toenails to the shape of the toe. Knowledge deficits were identified for many other areas of diabetes management, e.g. prevention of hypoglycaemia, avoidance of ketoacidosis. Sixteen health professionals at the clinics answered the same items. Contrary to recommendations, 25% of health professionals thought that fresh fruit could be eaten freely. Seventy-five percent of health professionals did not know the current recommendations for trimming toenails. As expected, HbA1c did correlate with scores from two specific items, while HbA1c did not correlate with summed ADKnowl score.

Conclusions Patient knowledge deficits were identified. Some specific knowledge deficits among health professionals may be the cause of some patient knowledge deficits. The ADKnowl is a useful tool in assessing both patient and health professional knowledge deficits and is available for use in a context of continuing evaluation.

Pilot Study of clinician attitudes to insulin pump therapy: international differences and the need for a greater understanding of the patient perspective

OBJECTIVES: To identify and survey health care professionals (HCPs) attitudes to insulin pump therapy (CSII).

METHODS: Eight specialists were interviewed to explore the attitudes and beliefs about CSII. Responses were analysed thematically and used to inform the design of a new 22-item questionnaire: the Attitudes to Pump Therapy (APT) Survey. The APT was pilottested among 95 HCPs (54% male; 75.5% diabetologists/DSNs, 13.8% general practitioners) at the International Diabetes Federation (IDF) conference, 2006. Results were analysed using non-parametric statistics with bonferroni correction.

RESULTS: Analyses of interview data identified 9 themes: biomedical, perceived control of care/diabetes, technology, quality of life, financial resources, training, education & support, suitability, and evidence-base. Items were designed to reflect these themes with responses scored on a 5-point Likert scale (strongly agree—strongly disagree). No statistically significant differences
were found by gender, HCP speciality, country (and continent) of origin or proportion of patients using CSII. Most notable differences were found in relation to gross domestic product (GDP) and the potential for pump therapy to achieve tight blood glucose control (lower GDP = more agreement: p = 0.001), and result in diabetic ketoacidosis (DKA) (lower GDP = less agreement: p < 0.005). Ranked mean scores showed a split between biomedical/clinical items (N = 11) and items concerned with patient experience (N = 11). Attitudes about biomedical/clinical issues were generally clear (i.e. for 7/11 items, the mean score was “agree”) but less decisive about patient experience (i.e. for 8/11 items, the mean score was “neither agree nor disagree”).

CONCLUSION: Few subgroup differences existed, but those that did may be explained by lack of access to treatment (directly corresponding to GDP). Clinicians’ were generally clear in their attitudes regarding biomedical aspects but less so regarding patient experience. Research focusing on patient-reported outcomes is likely to offer clinicians a greater understanding of the patients’ perspective of insulin pump therapy.