Brief assessment of diabetes-specific psychological flexibility in racially and income diverse youth with type 1 diabetes.

OBJECTIVE: Diabetes-specific psychological flexibility (the ability to engage in valued behaviors, be open to internal experiences, with present-moment awareness, while living with diabetes) is associated with HbA1c and health-related quality of life in youth with type 1 diabetes (T1D). Having brief diabetes-specific psychological flexibility assessments that perform equivalently across diverse individuals is important for research and clinical work addressing health disparities. The present study aimed to create 9-and 3-item short forms (DAASito-9 and -3) of the Diabetes Acceptance and Action Scale (DAAS-22), and evaluate their validity, reliability, and measurement invariance (MI). RESEARCH DESIGN AND METHODS: Youth with T1D (n = 179, Mage  = 14.64, 50% female, 56% Black/African American) completed self-report measures at an endocrinology clinic visit. HbA1c was extracted from medical records. One-half of the sample was used to develop the DAASitos with the highest reliability, McDonald's 𝜔 ≥ 0.75, and convergent validity (r ≥ 0.90 to DASS-22). Confirmatory factor analyses evaluated structural validity. MI was assessed across demographic (race, gender, grade, household income) and disease characteristic (illness duration, HbA1c) groups. Correlations with measures of psychological flexibility assessed additional convergent validity, and latent mean differences across groups were evaluated after confirming MI. RESULTS: MI was supported. The DAASito-9 and -3 were correlated in expected directions with other psychological flexibility measures, HbA1c, and health-related quality of life. CONCLUSIONS: The psychometric properties of the DAASito-9 and -3 support their use in research and clinical care of diverse youth with T1D. Significant differences in psychological flexibility across race, income, and glycemic health warrant further research and clinical intervention.

Examining Risk Factors of Health-Related Quality of Life Impairments Among Adolescents with Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) is a chronic, costly, and burdensome disease that is typically diagnosed during adolescence. Despite the use of effective treatments, rates of relapse and intestinal inflammation remain high and put patients at risk for long term physical and psychosocial health complications. Given the costs associated with IBD, it is critical to examine potential risk factors of poor health-related quality of life (HRQoL) among patients for the enhancement and further development of interventions. As such, the aim of the current study was to examine how sociodemographic and disease characteristics, psychosocial problems, and adherence behaviors impact HRQoL among a sample of youth with IBD. 107 adolescents with IBD and their caregiver completed self- and parent-report measures as part of a psychosocial screening service. Medical records were reviewed to obtain information regarding diagnosis, insurance, medication use, illness severity, and disease activity. Results revealed lower HRQoL scores among adolescents with more psychosocial problems (Est. = -3.08; p < .001), greater disease severity (Est. = -.40; p = .001), and those who identified as Black (Est. = -.38; p < .05). Greater disease severity (Est. = .13 p = .004), use of nonpublic insurance (Est. = .32 p = .004), and fewer psychosocial problems (Est. = -.13 p = .04) were associated with greater adherence behaviors. These findings suggest that implementing individually tailored, evidence-based psychological interventions focused on coping with psychosocial problems and symptoms may be important in enhancing adherence behaviors and HRQoL among adolescents with IBD.

Development and initial validation of the diabetes family conflict scale (revised)-short form in a racially and income diverse sample.

OBJECTIVE: The purpose of the study was to develop a short form of the revised diabetes family conflict scale (DFCS) in a racially and income diverse sample while retaining strong psychometric properties. METHODS: One seventy nine youth with type 1 diabetes (ages 12-18 years) and caregivers completed the DFCS-Revised as well as assessments of adherence, psychosocial functioning, and diabetes-related stress. Hemoglobin A1c was also obtained. The sample was split at random into a development sample and validation sample. RESULTS: Confirmatory factor analyses in the validation sample supported the use of a six-item short form (DFCS-SF) either as a total score (6-items) or a direct (3-item) and indirect (3-item) score. Variations of the DFCS-SF (three items of the 6-item short form) also had acceptable model fit. The short-form questionnaires had acceptable internal consistency and convergent validity (6-item: Cronbach's a = 0.865, full scale DFCS r = 0.954; 3-item: Cronbach's a = 0.757, full scale DFCS r = 0.912). The DFCS-SF showed measurement invariance across both youth and caregiver respondents. Greater report of the DFCS-SF by both youth and caregivers was significantly associated with higher HbA1c, more diabetes-related stress, and more psychosocial concerns. CONCLUSIONS: The DFCS-SF developed in the present study shows psychometric integrity in a diverse population of youth and can be utilized by providers to rapidly assess and potentially implement interventions to reduce diabetes family conflict, a psychosocial concern which is associated with elevated HbA1c, non-optimal adherence, diabetes-related stress, and psychological distress.

Predictors of HbA1c Trajectories in Predominantly Black Adolescents With Type 1 Diabetes.

OBJECTIVE: Following the Journal of Pediatric Psychology's special edition on health disparities, calling for Phase 2 research exploring mechanisms of racial groups in health disparities, this study aims to explore social information processing predictors of longitudinal hemoglobin A1c (HbA1c) trajectories in a racially diverse group of adolescents. The social information processing model of glycemic control in type 1 diabetes (T1D) posits that adolescents who make negative attributions about reactions of friends are likely to find adherence difficult in social situations, have increased stress, and have suboptimal glycemic control. METHODS: One hundred eighty-four youth with T1D completed self-report measures and HbA1c at three time points within 1 year was extracted from medical records. Growth mixture modeling empirically derived classes of HbA1c trajectories and explored predictive relationships of social information processing variables, demographics, and diabetes characteristics. RESULTS: Three classes emerged: High Decelerating, Mid-High Accelerating, and Near-Optimal Accelerating. Black/African American participants were highly likely to be in the High and Mid-High groups. Higher anticipated adherence difficulties in social situations predicted increased odds of being in the Mid-High versus Near-Optimal HbA1c group. Increased diabetes stress predicted increased odds of being in the High versus Near-Optimal and Mid-High groups. CONCLUSIONS: Continuing research on mechanisms behind this health disparity is necessary with more representation from varied racial and ethnic groups. Equal access to diabetes technology and psychosocial treatments are recommended and implications for clinical intervention development are discussed.

Toward the Development of a Culturally Humble Intervention to Improve Glycemic Control and Quality of Life among Adolescents with Type-1 Diabetes and Their Families.

Type-1 Diabetes (T1D) is a prevalent and costly disorder associated with substantial morbidity that differentially impacts low-income and/or minority adolescents and their families. The primary study objective was to develop a guiding model to inform culturally humble interventions for Mid-southern youth with T1D presenting with multiple correlates of suboptimal glycemic control and their families. In order to develop a clinic specific guiding model, conceptualizations of health, the need/type of intervention thought to be most helpful, the optimal structure, and strategies to improve the cultural/regional fit was ascertained from (A) youth with T1D (n = 13) and caregivers (n = 11) via qualitative interviews and, (B) pediatric endocrinologists and nurse practitioners (n = 6), and (C) nurses, diabetes educators, dietitians, and social workers (n = 9) via focus groups. Qualitative themes were synthesized to guide the treatment development model whereby Quality of Life and Glycemic Control would be directly enhanced by interventions to promote Coping, Support, Education, and Improved Psychosocial Functioning and indirectly through improved Adherence and T1D Autonomy delivered in a culturally humble way that affirms youths' T1D identify. These finding suggest that existing evidence-based treatments may provide a great fit for low-income, and/or minority youth with T1D and their families living in the mid-south, provided these interventions are delivered in culturally humble manner.

Measuring psychological flexibility in youth with type 1 diabetes.

OBJECTIVE: To determine reliability and validity of the acceptance and action diabetes questionnaire (AADQ) and the diabetes acceptance and action scale for children and adolescents (DAAS), measures of diabetes-specific psychological flexibility. METHODS: One hundred and eight-one youth with type 1 diabetes completed the AADQ, DAAS, and measures of mindfulness, cognitive fusion, and health-related quality of life. HbA1c was extracted from medical records. Confirmatory factor analysis (CFA) was used to cull items and evaluate the factor structures of the AADQ and DAAS. Bivariate correlations were conducted between all measures to explore content validity. RESULTS: CFAs supported a one-factor structure of the AADQ (for youth and parent report) and a second-order DAAS solution with a total score indicated by avoidance, values impairment, and avoidance subscales. All scales and subscales displayed strong internal consistency (α = .86-.95). The AADQ and DAAS evidence good content validity based on associations with other measures. CONCLUSIONS: The AADQ and DAAS are reliable, valid measures of diabetes-specific psychological flexibility.

How Peer Conflict Profiles and Socio-Demographic Factors Influence Type 1 Diabetes Adaptation.

OBJECTIVE: This study aimed to (a) validate the factor structure for a measure of peer conflict in youth with type 1 diabetes (T1D); (b) determine empirical patterns of peer conflict in terms of context (friend vs. nonfriend) and content (diabetes-specific vs. general) within a broader context of socio-demographic factors; and (c) examine how these patterns and socio-demographic factors relate to adolescents' T1D adherence, quality of life, and glycemic control (HbA1c). METHODS: Youth with T1D (N = 178), ages 12-18, reported demographic variables, illness duration, adherence, quality of life, and peer conflict. HbA1c was extracted from medical records. Confirmatory factor analysis validated a factor structure for the Diabetes Peer Conflict Scale (DPCS) and latent profile analysis (LPA) determined profiles of peer conflict. RESULTS: A four-factor structure emerged for the DPCS: general friend conflict, general nonfriend conflict, T1D friend conflict, and T1D nonfriend conflict. Using these factors as indicators in LPA, four profiles were confirmed: (a) Low Overall Conflict (LOC) and (b) Moderate Overall Conflict (MOC), (c) a Nonfriend Conflict (NFC), and (d) a Friend Conflict (FC) profile. Differences were not identified between diabetes specific versus general conflict. Socio-demographic variables did not predict class membership. The LOC profile reported the highest quality of life and best glycemic control, whereas the FC profile reported the lowest adherence behaviors. Conclusions: Peer conflict uniquely contributes to diabetes adaptation above and beyond socio-demographic and illness factors.

Cognitive and Psychosocial Development in Young Children with Brain Tumors: Observations from a Clinical Sample.

Survivors of pediatric brain tumor (BT) are known to be at risk for developing cognitive and psychosocial late effects. Young age at treatment (≤6 years) is typically considered to put patients at increased risk. However, there is limited research specifically exploring functioning in these young patients. Cognitive and psychosocial data were retrospectively abstracted from medical charts for 79 young patients (54.4% male) treated for BT with a variety of treatment modalities (e.g., surgery, radiation therapy, chemotherapy). Children were clinically assessed at 4.52 years of age (range = 1.48-5.98) and most were off-therapy (74.4%). Mean performances on developmental (68.3 ± 10.02), cognitive (88.09 ± 18.38), and pre-academic (86.84 ± 19.75) measures were all below average. Parent report of adaptive functioning was also below average (82.10 ± 16.21), but psychosocial functioning was generally within normal limits. Most patients had impaired functioning (scores <10th percentile) in at least one domain assessed. Exploratory analyses revealed that many patients (27.3-60.6%) exhibited a significant discrepancy between domains of cognitive functioning (e.g., verbal and spatial). Young children treated for BT experienced high rates of impairment in cognitive, pre-academic, and adaptive domains. Future work is needed to focus on serial longitudinal assessment of these young patients, as well as dedicated intervention and prevention efforts.

Predictors of diabetic ketoacidosis hospitalizations and hemoglobin A1c among youth with Type 1 diabetes.

OBJECTIVE: Diabetic ketoacidosis (DKA) and elevated hemoglobin A1c (HbA1c) in youth with Type 1 diabetes (T1D) can result in significant morbidity and mortality. Elucidating the risk factors for poor glycemic control and DKA hospitalizations is crucial for the refinement and development of prevention and treatment efforts. METHOD: Based on a conceptual framework, this study used path analysis to evaluate individual and family characteristics, psychosocial responses, and individual and family responses that prospectively predict the number of DKA hospitalizations and HbA1c approximately 1 year after assessment, accounting for sociodemographics. A total of 174 youth 12-18 years old with T1D (M = 14.68, SD = 1.77) and their caregivers completed measures assessing demographics, internalizing symptoms, diabetes stress, diabetes-related family conflict, and adherence. Medical records were reviewed to obtain the number of episodes of DKA and the HbA1c at 1-year follow-up. RESULTS: Thirty-one participants had at least 1 episode of DKA based on chart review. Greater duration of diabetes, higher baseline HbA1c, lower income, identifying as non-Hispanic White, and higher youth report of internalizing symptoms were significant predictors of DKA at follow-up (p < .05). Identifying as Black-African American, a younger age, and higher baseline HbA1c significantly predicted higher HbA1c at follow-up (p < .05). CONCLUSIONS: Future studies should assess the utility and accuracy of using screeners for internalizing symptoms in pediatric endocrinology clinics to identify youth at risk for DKA hospitalizations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Inherited Deletion of 1q, Hyperparathyroidism and Signs of Y-chromosomal Influence in a Patient with Turner Syndrome

We report a detailed phenotypic, cytogenetic and molecular characterization of a patient prenatally diagnosed with Turner syndrome (TS). In addition to having typical TS clinical characteristics including webbed neck, high arched palate and coarctation of the aorta, the patient had features less frequently seen in TS. These included recurrent parathyroid adenomas, growth along the 75th-90th centiles on the TS height curve despite minimal treatment with growth hormone, behavioral problems and evidence of gonadal dysgenesis with testicular-like structures, such as seminiferous tubules lined by Sertoli cells and a contiguous nodule of Leydig cells. While fluorescence in situ hybridization (FISH) failed to detect Y-chromosome material in gonadal tissue or blood samples, chromosomal microarray analysis (CMA) confirmed X monosomy and a 4.69 Mb copy number loss on 1q31.2q31.3 (bp 192,715,814 to 197,401,180). This region contains the CDC73 gene which has been associated with hyperparathyroidism-jaw tumor syndrome, features of which include recurrent, functional parathyroid adenomas and behavioral issues. This case illustrates how atypical features in a TS patient, such as robust growth and recurrent parathyroid adenomas, may suggest an underlying molecular etiology that should be explored by additional genetic diagnostic modalities. It is therefore appropriate in such cases to conduct further genetic testing, such as CMA and FISH, to explore other diagnostic possibilities and possibly prevent further complications.

Validity, Reliability, and Measurement Invariance of the Diabetes Stress Questionnaire-Short Form.

OBJECTIVE: The purpose of this study was to develop a short form of the Diabetes Stress Questionnaire (DSQ) with adequate psychometric properties (i.e., internal consistency, convergent, criterion, discriminant validity, construct validity, and measurement invariance). METHODS: In total, 181 youth with type 1 diabetes (T1D) completed the 65-item DSQ, and archival data were obtained from 142 youth with T1D to serve as an independent cross-validation sample. Twenty-four items were chosen to retain the original eight scales of the DSQ and to maximize internal consistency and correlations to full subscales. Confirmatory factor analyses were used to evaluate the proposed factor structure of the Diabetes Stress Questionnaire-Short Form (DSQ-SF) and to assess invariance of the DSQ-SF across sex, race, grade level, glycemic control, illness duration, and annual income categories. RESULTS: The 24-item DSQ-SF was found to have good internal consistency, factor structure and fit, correlated highly to the full scale (r = .98), and was invariant across sex, race, grade level (<9th grade or >9th grade), glycemic control, illness duration, and annual income. CONCLUSIONS: The DSQ-SF appears to be a psychometrically robust measure of diabetes-specific stress in youth with T1D. Present findings suggest that the DSQ-SF has the potential to be a useful, quick, cost-effective, and comprehensive screening tool for identifying youth with T1D who may benefit from T1D-specific stress reduction interventions as a way to improve health behaviors, psychosocial well-being, and glycemic control.

Dissociation Between Hormonal Counterregulatory Responses and Cerebral Glucose Metabolism During Hypoglycemia.

Hypoglycemia is the most common complication of diabetes, causing morbidity and death. Recurrent hypoglycemia alters the cascade of physiological and behavioral responses that maintain euglycemia. The extent to which these responses are normally triggered by decreased whole-brain cerebral glucose metabolism (CMRglc) has not been resolved by previous studies. We measured plasma counterregulatory hormonal responses and whole-brain CMRglc (along with blood-to-brain glucose transport rates and brain glucose concentrations) with 1-[11C]-d-glucose positron emission tomography during hyperinsulinemic glucose clamps at nominal plasma glucose concentrations of 90, 75, 60, and 45 mg/dL (5.0, 4.2, 3.3, and 2.5 mmol/L) in 18 healthy young adults. Clear evidence of hypoglycemic physiological counterregulation was first demonstrated between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L) with increases in both plasma epinephrine (P = 0.01) and glucagon (P = 0.01). In contrast, there was no statistically significant change in CMRglc (P = 1.0) between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L), whereas CMRglc significantly decreased (P = 0.02) between 60 mg/dL (3.3 mmol/L) and 45 mg/dL (2.5 mmol/L). Therefore, the increased epinephrine and glucagon secretion with declining plasma glucose concentrations is not in response to a decrease in whole-brain CMRglc.

Severity of clinical presentation in youth with type 1 diabetes is associated with differences in brain structure.

OBJECTIVE: Differences in cognition and brain structure have been found in youth with type 1 diabetes compared with controls, even after relatively short disease duration. To determine whether severity of clinical presentation contributes to these differences, we obtained structural magnetic resonance imaging (MRI) scans in youth ages 7-17 who were either newly diagnosed with type 1 diabetes (<3.5 months from diagnosis, n = 46) or a sibling without diabetes (n = 28). RESEARCH DESIGN AND METHODS: Severity of presentation was measured by the presence of diabetic ketoacidosis (DKA) and degree of hyperglycemia exposure [hemoglobin A1c (HbA1c)] at diagnosis. MRI were obtained using T1-weighted, T2-weighted, and diffusion-weighted sequences. RESULTS: Within the group with type 1 diabetes, 12 subjects presented in DKA and 34 did not. After controlling for age, sex, and multiple comparisons, the type 1 diabetes group had lower volume in the left temporal-parietal-occipital cortex compared with controls. Within the type 1 diabetes group, DKA at presentation was associated with lower radial, axial, and mean diffusivity (MD) throughout major white matter tracts and higher HbA1c was associated with lower hippocampal, thalamic, and cerebellar white matter volumes, lower right posterior parietal cortical thickness, and greater right occipital cortical thickness. CONCLUSION: These data suggest that severity of clinical presentation is an important factor in predicting brain structural differences in youth with type 1 diabetes approximately 3 months after diagnosis.

Hypoglycemia during moderate intensity exercise reduces counterregulatory responses to subsequent hypoglycemia.

Hypoglycemia, which occurs commonly during and following exercise in people with diabetes, is thought to be due to attenuated counterregulation in the setting of therapeutic insulin excess. To better understand the pathophysiology of counterregulation, we aimed to determine if dextrose administration to maintain euglycemia during moderate intensity exercise alters the attenuation of counterregulatory responses to subsequent hypoglycemia in healthy adults : Counterregulatory responses to hypoglycemia were assessed in 18 healthy adults after bed rest and following exercise with (n = 9) and without (n = 9) dextrose infusion. Responses were measured during a stepped euglycemic-hypoglycemic clamp 24 h after either bed rest or two 90-min bouts of exercise at 70% peak oxygen uptake : Hypoglycemia occurred during the second bout of exercise without dextrose infusion. Plasma glucagon and epinephrine responses to stepped hypoglycemia after antecedent exercise without dextrose infusion were significantly lower at the 45 mg/dL glycemic level compared to after bed rest. However, no attenuation of the counterregulatory responses to hypoglycemia was evident after antecedent exercise when dextrose was infused. This study suggests that the attenuation of the counterregulatory responses during hypoglycemia after exercise is likely due to the hypoglycemia that occurs during moderate prolonged exercise and not solely due to exercise or its intensity.

Clinical presentation and memory function in youth with type 1 diabetes.

OBJECTIVE: While cerebral edema and diabetic ketoacidosis (DKA) in type 1 diabetes (T1DM) have well-described acute effects on cognition, little is known about the impact of clinical presentation on longer term cognitive outcomes. We hypothesized that clinical factors (degree of hyperglycemia exposure and DKA) at the time of diagnosis would relate to cognition within 3.5 months later in children with T1DM. METHODS: Cognitive testing was performed on children 7-17 years old with T1DM (n = 66) within 3.5 months of diagnosis and siblings without T1DM (n = 33). Overall intelligence, processing speed, and memory (including a sensitive long-delay spatial memory test; spatial delayed response or SDR) were assessed. Medical records were reviewed for hemoglobin A1c (HbA1c), DKA status, and other clinical factors at diagnosis. RESULTS: Within the group with T1DM, 17 children presented in DKA and 49 did not. After adjusting for age, gender, and socioeconomic status, the subgroup with T1DM and DKA at diagnosis performed worse on the long-delay SDR task compared to sibling controls (p = 0.006). In addition, within the group with T1DM, higher HbA1c at diagnosis was associated with worse performance on the long-delay SDR task (p = 0.027). Performance on the other cognitive tasks was not different across groups or subgroups. CONCLUSIONS: DKA and degree of hyperglycemia exposure at diagnosis have implications for long-delay spatial memory function within 3.5 months of diagnosis. These findings suggest that early detection of T1DM, which decreases risk for prolonged exposure to hyperglycemia and DKA, may avoid negative effects on memory function.

Depression in type 2 diabetes mellitus: prevalence, impact, and treatment.

Clinically significant depression is present in one of every four people with type 2 diabetes mellitus (T2DM). Depression increases the risk of the development of T2DM and the subsequent risks of hyperglycemia, insulin resistance, and micro- and macrovascular complications. Conversely, a diagnosis of T2DM increases the risk of incident depression and can contribute to a more severe course of depression. This linkage reflects a shared etiology consisting of complex bidirectional interactions among multiple variables, a process that may include autonomic and neurohormonal dysregulation, weight gain, inflammation, and hippocampal structural alterations. Two recent meta-analyses of randomized controlled depression treatment trials in patients with T2DM concluded that psychotherapy and antidepressant medication (ADM) were each moderately effective for depression and that cognitive behavior therapy (CBT) had beneficial effects on glycemic control. However, the number of studies (and patients exposed to randomized treatment) included in these analyses is extremely small and limits the certainty of conclusions that can be drawn from the data. Ultimately, there is no escaping the paucity of the evidence base and the need for additional controlled trials that specifically address depression management in T2DM. Future trials should determine both the effects of treatment and the change in depression during treatment on measures of mood, glycemic control, and medical outcome.

Prescription Opioid Analgesics Increase Risk of Major Depression: New Evidence, Plausible Neurobiological Mechanisms and Management to Achieve Depression Prophylaxis.

More than 200 million prescriptions are written annually for opioid analgesics despite limited evidence of their long-term efficacy. These medications currently are prescribed to 10% - 15% of Americans with use of long-acting opioids projected to double in the next three to four years. Despite this widespread use, little is known about the risks of opioids, particularly with chronic use. New data from our research group published in the Journal of General Internal Medicine provides clear evidence that prescription opioid used for non-cancer, non-HIV pain increases significantly the risk of development of major depressive disorder in opioid naïve individuals with no recent history of depression and substance used disorders. The risk of depression increased as the dose and/or the duration of opioid use increased. The purpose of the present paper is to elucidate the details of this study, to examine potential neurobiological mechanisms responsible for the depressogenic effect of opioid analgesics, and to discuss management options that emphasize depression prophylaxis.

Glycemic extremes in youth with T1DM: the structural and functional integrity of the developing brain.

The adult brain accounts for a disproportionally large percentage of the body's total energy consumption (1). However, during brain development,energy demand is even higher, reaching the adult rate by age 2 and increasing to nearly twice the adult rate by age 10, followed by gradual reduction toward adult levels in the next decade (1,2). The dramatic changes in brain metabolism occurring over the first two decades of life coincide with the initial proliferation and then pruning of synapses to adult levels.The brain derives its energy almost exclusively from glucose and is largely driven by neuronal signaling, biosynthesis, and neuroprotection (3­6).Glucose homeostasis in the body is tightly regulated by a series of hormones and physiologic responses. As a result, hypoglycemia and hyperglycemia are rare occurrences in normal individuals, but they occur commonly inpatients with type 1 diabetes mellitus (T1DM) due to a dysfunction of peripheral glucose-insulin-glucagon responses and non-physiologic doses of exogenous insulin, which imperfectly mimic normal physiology. These extremes can occur more frequently in children and adolescents with T1DM due to the inadequacies of insulin replacement therapy, events leading to the diagnosis [prolonged untreated hyperglycemia and diabetic ketoacidosis (DKA)], and to behavioral factors interfering with optimal treatment. When faced with fluctuations in glucose supply the metabolism of the body and brain change dramatically, largely to conserve resources and, at a cost to other organs, to preserve brain function (7). However,if the normal physiological mechanisms that prevent these severe glucose fluctuations and maintain homeostasis are impaired, neuronal function and potentially viability can be affected (8­11).