Longitudinal Predictors of Diabetic Ketoacidosis Hospitalizations and Hemoglobin A1c: Examining Adaptation to Type-1 Diabetes in Adolescents

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. 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 number of DKA hospitalizations and HbA1c approximately one year after assessment, accounting for socio-demographics. 174 Youth 12-18 years old with T1D (M = 14.78, SD = 1.65) 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 closest to 1-year follow-up. Thirty-one participants had at least one episode of DKA based on chart review. Identifying as Black/ African American, a younger age, and higher baseline HbA1c significantly predicted higher HbA1c at follow-up (p \u3c .05). For DKA Count, greater duration of diabetes, higher baseline HbA1c, lower income, and identifying as Non-Hispanic White and higher Youth report of internalizing symptoms were significant predictors (p \u3c 0.05). Utilizing screeners for internalizing symptoms in endocrinology clinics may be critical for early detection of youth with T1D at risk for DKA

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

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

Hepatic lipids promote liver metastasis

Obesity predisposes to cancer and a virtual universality of nonalcoholic fatty liver disease (NAFLD). However, the impact of hepatic steatosis on liver metastasis is enigmatic. We find that while control mice were relatively resistant to hepatic metastasis, those which were lipodystrophic or obese, with NAFLD, had a dramatic increase in breast cancer and melanoma liver metastases. NAFLD promotes liver metastasis by reciprocal activation initiated by tumor-induced triglyceride lipolysis in juxtaposed hepatocytes. The lipolytic products are transferred to cancer cells via fatty acid transporter protein 1, where they are metabolized by mitochondrial oxidation to promote tumor growth. The histology of human liver metastasis indicated the same occurs in humans. Furthermore, comparison of isolates of normal and fatty liver established that steatotic lipids had enhanced tumor-stimulating capacity. Normalization of glucose metabolism by metformin did not reduce steatosis-induced metastasis, establishing the process is not mediated by the metabolic syndrome. Alternatively, eradication of NAFLD in lipodystrophic mice by adipose tissue transplantation reduced breast cancer metastasis to that of control mice, indicating the steatosis-induced predisposition is reversible

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

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\u27 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

Predictors of Diabetic Ketoacidosis Hospitalizations and Hemoglobin A1c among Youth with Type 1 Diabetes

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

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 \u3c.001), greater disease severity (Est. = -.40; p =.001), and those who identified as Black (Est. = -.38; p \u3c.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

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 (\u3c9th grade or \u3e9th 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