The moderating role of diabetes distress on the effect of a randomized eHealth intervention on glycemic control in Black adolescents with type 1 diabetes.

OBJECTIVE: Due to systemic inequities, Black adolescents with type 1 diabetes are more likely to have suboptimal glycemic control and high rates of diabetes distress, but tailored interventions for this population are lacking. In primary outcomes of a randomized clinical trial, a family-based eHealth intervention improved glycemic control in Black adolescents with type 1 diabetes and elevated depressive symptoms. The present study is a secondary analysis of these clinical trial data examining the moderating effect of diabetes distress on the efficacy of the intervention. METHODS: Using secondary data from a multicenter randomized clinical trial (Clinicaltrials.gov [NCT03168867]), caregiver-adolescent dyads were randomly assigned to either up to three sessions of an eHealth parenting intervention (n = 75) or a standard medical care control group (n = 74). Black adolescents (10 years, 0 months to 14 years, 11 months old) with type 1 diabetes and a caregiver willing to participate were eligible. Adolescents reported their diabetes distress at baseline, and hemoglobin A1c (HbA1c) data were collected at baseline, 6-, 13-, and 18-month follow-up. RESULTS: No between-group contrasts emerged in a linear mixed-effects regression (p's > .09). Within-group contrasts emerged such that adolescents assigned to the intervention who reported high diabetes distress had lower HbA1c at the 18-month follow-up relative to baseline (p = .004); the 18-month decrease in HbA1c was -1.03%. CONCLUSIONS: Black adolescents with type 1 diabetes and high levels of diabetes distress showed significant decreases in HbA1c following a family-based eHealth intervention, suggesting diabetes distress may be a key moderator of intervention efficacy within this population.

Diabetes distress in urban Black youth with type 1 diabetes and their caregivers: associations with glycemic control, depression, and health behaviors.

OBJECTIVES: Adolescents with type 1 diabetes (T1D) and their caregivers endorse high diabetes distress (DD). Limited studies have documented the impact of DD on Black youth. The aims of the present study were to (1) describe DD among a sample of Black adolescents with T1D and their caregivers, (2) compare their DD levels with published normative samples, and (3) determine how DD relates to glycemic outcomes, diabetes self-management, parental monitoring of diabetes, and youth depressive symptoms. METHODS: Baseline data from a multicenter clinical trial were used. Participants (N = 155) were recruited from 7 Midwestern pediatric diabetes clinics. Hemoglobin A1c (HbA1c) and measures of DD, parental monitoring of diabetes care, youth depression and diabetes management behaviors were obtained. The sample was split into (1) adolescents (ages 13-14; N = 95) and (2) preadolescents (ages 10-12; N = 60). Analyses utilized Cohen's d effect sizes, Pearson correlations, t-tests, and multiple regression. RESULTS: DD levels in youth and caregivers were high, with 45%-58% exceeding either clinical cutoff scores or validation study sample means. Higher DD in youth and caregivers was associated with higher HbA1c, lower diabetes self-management, and elevated depressive symptoms, but not with parental monitoring of diabetes management. CONCLUSIONS: Screening for DD in Black youth with T1D and caregivers is recommended, as are culturally informed interventions that can reduce distress levels and lead to improved health outcomes. More research is needed on how systemic inequities contribute to higher DD in Black youth and the strategies/policy changes needed to reduce these inequities.

Optimizing Recruitment of Black Adolescents into Behavioral Research: A Multi-Center Study.

OBJECTIVES: Adolescents of color are underrepresented in behavioral health research. Study aims were to quantify the amount and types of outreach effort needed to recruit young Black adolescents with type 1 diabetes and their primary caregiver into a clinical trial evaluating a parenting intervention and to determine if degree of recruitment difficulty was related to demographic, diabetes-related, or family characteristics. METHODS: Data were drawn from a multi-center clinical trial. Participants (N = 155) were recruited from seven pediatric diabetes clinics. Contact log data were used to quantify both number/type of contacts prior to study enrollment as well as length of time to enrollment. Families were coded as having expedited recruitment (ER) or prolonged recruitment (PR). Baseline study data were used to compare ER and PR families on sociodemographic factors, adolescent diabetes management and health status and family characteristics such as household organization and family conflict. RESULTS: Mean length of time to recruit was 6.6 months and mean number of recruitment contacts was 10.3. Thirty-nine percent of the sample were characterized as PR. These families required even higher levels of effort (mean of 9.9 months to recruit and 15.4 contacts). There were no significant between-group differences on any baseline variable for ER and PR families, with the exception of family income. CONCLUSIONS: Researchers need to make persistent efforts in order to successfully enroll adolescents of color and their caregivers into clinical trials. Social determinants of health such as family resources may differentiate families with prolonged recruitment within such samples.

Hypercalcemia in Children Using the Ketogenic Diet: A Multicenter Study.

CONTEXT: The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment. OBJECTIVE: To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients. DESIGN: A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment, and course of this complication was collated centrally. RESULTS: There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range, 0.2-12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the 2 oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only 2 of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while 4 more stopped the diet during follow-up after resolution of hypercalcemia. CONCLUSIONS: Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.

Improving Diabetes-Related Parent-Adolescent Communication With Individualized Feedback.

Objective: To pilot a brief individualized feedback intervention to improve the communication skills of parents with an adolescent with type 1 diabetes. Methods: Parent-adolescent dyads (N = 79) discussed a diabetes-related problem, while an interventionist rated the parent's communication skills to give feedback to the parents. Parents were then randomized to a brief feedback session to target person-centered communication skills or an educational session. Dyads discussed another diabetes care problem to assess for change in communication skills. Independent raters coded parent communication skills from video recordings to rate behaviors in the service of examining possible changes in communication skills. Dyads completed ratings of perceived closeness and empathy after each conversation. Results: Controlling for overall positive communication at baseline, parents who received feedback showed more improvement in specific person-centered communication skills than parents in the control group. Adolescents in the feedback group reported greater increases in parental empathy and intimacy from pre- to postmanipulation than the control. Conclusions: The feedback intervention showed preliminary efficacy for increasing person-centered communication skills and perceived empathy and intimacy.

Brief Computer-Delivered Intervention to Increase Parental Monitoring in Families of African American Adolescents with Type 1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: African American adolescents with type 1 diabetes (T1D) are at elevated risk for poor diabetes management and metabolic control. Parental supervision and monitoring of adolescent diabetes management have been shown to promote better diabetes management among adolescents, but parents typically decrease their oversight during the transition to independent diabetes care. INTRODUCTION: The purpose of the study was to conduct a randomized clinical trial to test the feasibility and efficacy of a three-session, computer-delivered motivational intervention (The 3Ms) to promote increased parental monitoring among primary caregivers of young African American adolescents with T1D. The intervention was brief and optimized for delivery during routine diabetes clinic visits. MATERIALS AND METHODS: Sixty-seven adolescents with T1D aged 11-14 and their primary caregiver were randomly assigned to one of three arms: adolescent and parent motivational intervention (Arm 1), adolescent control and parent motivational intervention (Arm 2), or adolescent and parent control (Arm 3). Intervention effects were assessed 1 month after intervention completion. RESULTS: Parents in Arm 1 and Arm 2 had significant increases in knowledge of the importance of monitoring adolescents' diabetes care. Parents in Arm 2 also had trend to significant increases in direct observation and monitoring of adolescent diabetes care, and adolescents in Arm 2 had significant improvements in glycemic control. DISCUSSION AND CONCLUSIONS: Findings from the present study provide preliminary support for the efficacy of a brief, computer-delivered parenting intervention for improving family management practices and adolescent health outcomes among African American adolescents with T1D and their caregivers.

Effects of socio-demographic factors on parental monitoring, and regimen adherence among adolescents with type 1 diabetes: A moderation analysis.

Parental monitoring of adolescent diabetes care is an important predictor of adolescent regimen adherence. To date, no studies have investigated whether socio-demographic factors are associated with low levels of parental monitoring or differences in parental monitoring styles, and their moderating effects in families of adolescents with type 1 diabetes. The purpose of this cross-sectional study was to determine whether youth and family socio-demographic factors moderated the relationship between monitoring and youth regimen adherence (i.e., mean frequency of blood glucose testing [BGT]). Data were collected from 267 adolescents with type 1 diabetes and their parents. Hierarchical multiple regression analyses were employed. Socio-demographic factors accounted for 17.1% of the variance in adherence. After parental monitoring scales were entered, R2 in all eight equations increased and R2 change score in six of eight equations were significant. All models were significant after the interaction terms were entered. In the adolescent report models, parent age and family structure were both independently associated with adherence and also moderated the association between adolescent-report parental monitoring and adherence to diabetes care, in particular, adolescent report of parental direct observation/presence during diabetes care. In the parent report models, income was moderated the association between parent-report youth disclosure and adherence. Research should focus on identifying additional modifiable factors that place families at risk for low levels of parental monitoring of diabetes care. Future clinical research is needed to help identify risk factors for low levels of parental monitoring and develop interventions to promote optimal parenting skills that can support youth diabetes care.

Psychometric properties of the revised Parental Monitoring of Diabetes Care questionnaire in adolescents with type 1 diabetes.

PURPOSE: We evaluated the psychometric properties of a revised version of the Parental Monitoring of Diabetes Care questionnaire (PMDC-R) designed to evaluate parental supervision and monitoring of adolescent diabetes care behaviors. The revised measure was intended to capture a broad range of ways used by parents to gather information about youth adherence to diabetes care. METHODS: Two hundred sixty-seven caregivers of 12-18-year-old adolescents with type 1 diabetes completed the PMDC-R. Measures of parental knowledge of youth illness management, illness management behavior, and metabolic control were also obtained. RESULTS: The PMDC-R demonstrated good internal consistency (alpha coefficient = .91) and test-retest reliability (r = .79, p < .001). Supporting the instrument's construct validity, a bifactor model with one primary factor and three secondary factors had an acceptable fit to the data (comparative fit index = .92, root mean square error of approximation = .06). Concurrent validity was also supported. In structural equation models, parental monitoring, as assessed by the PMDC-R, had a significant direct effect on parental knowledge of adolescent diabetes management and, through knowledge, an indirect effect on adolescent diabetes management and metabolic control. CONCLUSIONS: The PMDC-R displayed strong psychometric properties and represents an important next step in refining the measurement of parental monitoring for youth with chronic illnesses.

Prevalence of elevated thyroid-stimulating hormone levels in obese children and adolescents.

OBJECTIVE: To determine the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents referred to pediatric endocrinology clinics. METHODS: We undertook a retrospective review of medical records of 191 obese and 125 nonobese children (younger than 18 years old). Data about age, sex, body mass index, TSH, thyroid functions, thyroid antibodies, thyroid size, and medications were collected. RESULTS: Six obese patients had Hashimoto disease and TSH values from 0.73 to 12.73 mIU/L; they were excluded from the study analyses. Of the remaining 185 obese subjects, 20 (10.8%) had TSH levels >4 mIU/L, but no control subject measurement exceeded this TSH value. The highest TSH concentration in an obese study subject was 7.51 mIU/L. When obese children with TSH levels >4 mIU/L were classified in a third group, the mean TSH in the rest of the obese children was comparable with that in the control group (1.98 +/- 0.84 [SD] and 1.95 +/- 0.80 mIU/L, respectively; post hoc analysis of variance, P = .945). Obese subjects with increased TSH values had a mean body mass index similar to that for obese subjects with normal TSH levels (34.98 +/- 6.12 [SD] and 34.29 +/- 7.84 kg/m2, respectively). CONCLUSION: Mild elevation of TSH values in the absence of autoimmune thyroid disease is not uncommon in some obese children and adolescents. This is the second study in the United States to report this observation. Our study did not identify any special characteristics of obese subjects with TSH elevation in comparison with obese children with normal TSH levels and the control group. Current medical knowledge does not support routine screening for thyroid dysfunction in obese children.

Pseudohypoparathyroidism type 1A and morbid obesity in infancy.

OBJECTIVE: To describe an infant with early excessive weight gain as the principle manifestation of pseudohypoparathyroidism (PHP) type 1a and Albright hereditary osteodystrophy (AHO). METHODS: We describe the clinical and laboratory findings in an infant with early excessive weight gain without evidence of hyperphagia and review relevant literature. RESULTS: The proband's birth weight was 4047 g (1.4 SD). She was breastfed from birth. Excessive weight gain was noted by 1 month of age. At 3 months of age, hard subcutaneous nodules were observed, and histologic analysis of a biopsied lesion suggested a possible diagnosis of ossified pilomatricoma. At 6 months of age, she was documented to have mild hypothyroidism. Abnormal weight gain continued despite a caloric intake of about 65 kcal/kg per day. At 11 months of age, 2 new subcutaneous hard nodules were identified, which in the context of excessive weight gain and evolving mild primary hypothyroidism, suggested a unifying diagnosis of PHP type 1a and AHO. GNAS sequence analysis was performed, which revealed a 4-base deletion (Nt565delGACT) in exon 8. CONCLUSIONS: As more monogenic causes of severe early obesity are described, it is important to consider PHP type 1a in the differential diagnosis. Lack of short stature, skeletal abnormalities, or absence of PTH resistance should not exclude this diagnosis in a young child.

TNF-alpha and glucocorticoid receptor interaction in L6 muscle cells: a cooperative downregulation of myosin heavy chain.

Sepsis is associated with increased expression of TNF-alpha with subsequent activation of nuclear factor-kappa B (NF-kappaB). The glucocorticoid receptor (GR) and NF-kappaB function as mutual antagonists and induction of the latter is believed to play a major role in the acquired glucocorticoid resistance that occurs in some septic patients. GR expression and function has been reported to be elevated in septic muscle suggesting a limited effect of the activated NF-kappaB on GR function in this context. In this study, the L6 myocyte cell line was used as an in vitro model for a sepsis-like condition in skeletal muscle. While short or long term treatment with TNF-alpha had no effect on GR expression, glucocorticoid-dependent downregulation of GR occurred with a kinetic profile that is accelerated relative to that observed in most cells. This downregulation was not affected by co-treatment or prior priming of L6 cells with TNF-alpha. The synthetic glucocorticoid, dexamethasone (DEX) blunted TNF-alpha-stimulated NF-kappaB activation in L6 cells. However, although effective at activating an NF-kappaB transcriptional response, TNF-alpha treatment exerted a minimal effect in myoblasts and no effect in myotubes on GR transcriptional activity. This limited impact of TNF-alpha on GR activity was not universal as TNF-alpha and DEX exerted an additive effect on the reduction in myosin heavy chain (MHC) protein expression caused by either agent alone. Thus, the selective perseverance of GR function in the presence of increased levels of glucocorticoids and TNF-alpha during sepsis or other inflammatory states may exacerbate muscle protein breakdown.

Recent advances in hyperinsulinemic hypoglycemia of infancy.

UNLABELLED: Hyperinsulinemia-induced hypoglycemia is the most common cause of persistent hypoglycemia in adults, children, and infants. Our understanding of the disorders responsible for this type of hypoglycemia has been increasing due to the recent discoveries in the molecular and biochemical regulation of insulin secretion. In this article, we review the current knowledge of the pathophysiology, clinical presentation, and diagnosis of disorders that cause hyperinsulinemic hypoglycemia of infancy. We highlight the distinction between the diffuse and focal forms of the disease, especially the promising results with (18)F-L-dopa positive emission tomography (PET) scanning for preoperative localization and distinction to guide the extent of surgical removal of pancreatic tissue that may result in cure rather than persistence of disturbed carbohydrate metabolism. CONCLUSION: Despite all these discoveries, much remains to be learned, as currently about one third of infants with hyperinsulinemic hypoglycemia have no identifiable cause.

Hyperinsulinemic hypoglycemia of infancy: the challenge continues.

Hypoglycemia due to hyperinsulinemia is the most common cause of persistent hypoglycemia in infants and children. Recent discoveries in the molecular and biochemical regulation of insulin secretion have dramatically increased our understanding of the disorders responsible for syndromes of hyperinsulinemic hypoglycemia. Here, we briefly review the current knowledge of disorders of the K(ATP) channel, activating mutations of glucokinase and glutamate dehydrogenase (GDH) and other disorders that may be associated with specific phenotypes and permit appropriate targeted therapies. Despite these advances, much remains to be learned. We do not understand the mechanisms or defects in many instances, including defective carbohydrate glycosylation syndromes and perinatal hypoxia, both of which may be associated with hyperinsulinemia. Most importantly, preoperative distinction between diffuse and focal lesions cannot be always reliably made even after selective arterial infusion with calcium, glucose or a sulfonylurea with concurrent hepatic venous sampling for insulin. The ability to distinguish diffuse from localized lesions has profound implications for therapeutic approaches, prognosis and genetic counseling. To date, about 50% of individuals with hyperinsulinemic hypoglycemia of infancy can be correctly categorized. Thus, the challenge continues.