The Associations Between Health-Related Knowledge and Health Beliefs Regarding Risk for Gestational Diabetes in American Indian and Alaska Native Female Adolescents and Young Adults at Risk for Gestational Diabetes and Their Female Caregivers: A Cross-Sectional Dyadic Analysis.

INTRODUCTION: Research on associations between knowledge and health beliefs for women at risk for gestational diabetes mellitus (GDM) has focused on adults at risk for or having GDM. Gaps also exist in examining interpersonal associations with family members or peers. We examined dyadic associations between knowledge and health beliefs about the risk for GDM between and within American Indian and Alaska Native (AIAN) female adolescents and young adults (FAYAs) at risk for GDM and their mothers or adult female caregivers (FCs). METHODS: Grounded in the Expanded Health Belief Model, we employed a cross-sectional design using baseline data from 147 dyads of AIAN FAYAs at risk for GDM and their FCs who participated in the Stopping GDM in Daughters and Mothers trial. FAYAs were 12.0 to 24.5 years of age, and 89.1% were students. FCs had a mean (SD) age of 44.0 (9.3) years, 87.0% were AIAN, 44.9% were college educated, 19.7% had ever had GDM, and 81.0% were the FAYA's mother. FAYAs and FCs completed surveys about knowledge and health beliefs (benefits, barriers, severity, susceptibility) regarding GDM risk and prevention. Bivariate correlational analyses were performed to examine associations between and within dyad members. Dyadic associations were investigated using actor-partner interdependence modeling (APIM) assuming distinguishable dyad members. RESULTS: Compared with their FCs, FAYAs had lower health-related knowledge and perceived benefits of GDM prevention and susceptibility regarding GDM risk. APIM revealed actor and partner effects of health-related knowledge on health beliefs for dyads. In particular, positive actor effects were found for FAYAs and FCs for GDM-related knowledge with perceived benefits (P < .001), and positive partner effects of GDM-related knowledge for FCs were related to perceived susceptibility and severity for FAYAs (P < .05). DISCUSSION: As shown in these AIAN dyads, FAYAs and their FCs, as members of one another's social network, may influence each other's health beliefs regarding GDM risk and prevention.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Technology for Augmenting Type 1 Diabetes Mellitus Management.

Type 1 diabetes mellitus has witnessed significant progress in its management over the past several decades. This review highlights technologic advancements in type 1 diabetes management. Continuous glucose monitoring systems are now available at various functionality and cost levels, addressing diverse patient needs, including a recently US Food and Drug Administration (FDA)-approved implantable continuous glucose monitoring system (CGMS). Another dimension to these state-of-the-art technologies is CGMS and insulin pump integration. These integrations have allowed for CGMS-based adjustments to basal insulin delivery rates and suspension of insulin delivery when a low blood glucose event is predicted. This review also includes a brief discussion of upcoming technologies such as patch-based CGMS and insulin-glucagon dual-hormonal delivery.

Evolving Pharmacotherapeutic Strategies for Type 1 Diabetes Mellitus.

Despite pharmacotherapeutic advancements in the management of type 1 diabetes mellitus during the past several decades, patients struggle to achieve glycemic goals. Additionally, hypoglycemia, especially in extremes of age, decreases quality of life. The lack of optimal glycemic control and risk for hypoglycemia are multifactorial. Nevertheless, endeavors aiming to develop pharmacotherapeutic options with enhanced pharmacokinetic, pharmacodynamic, and clinical profiles continue. This review article discusses recent ventures in 3 categories of insulin, non-insulin, and glucagon products.

Prolongation of growth by treatment of 11-hydroxylase deficiency with depot-leuprolide, growth hormone, and hydrocortisone.

A 4-10/12 year-old boy presented with tall stature and advanced secondary sexual characteristics. His bone age was 13 years giving him a height prediction of 147 cm. An initial 11-deoxycortisol level of 13,770 ng/dl and associated hypertension suggested the diagnosis of 11-hydroxylase deficiency, which was confirmed by dexamethasone suppression and genotyping. Treatment strategy was based on the premise that known hypothalamic priming resulting in early pubertal development could be averted by delaying puberty with leuprolide; also that effects of hydrocortisone and leuprolide on attenuating growth could be counteracted by growth hormone. The combined treatment resulted in a final height at age 12 years which was 25.4 cm greater than predicted, and bone density above average. We conclude that delaying puberty until an appropriate age, offsetting growth suppression, and improving bone mineralization can be effectively achieved using glucocorticoids, leuprolide and growth hormone in patients with 11-hydroxylase deficiency.

Type 2 diabetes in children: oxymoron or medical metamorphosis?

The full public health effects of the new epidemic of obesity and diabetes in children and adolescents may not be known for many years but are certain to be substantial. Diagnosed diabetes, which is present in only 4.2% of the US population, along with its consequences, already represents approximately 19% of the total personal healthcare expenditures in this country. Between 1997 and 2002, the estimated direct medical cost of diabetes increased from 44 billion dollars to 92 billion dollars, a staggering increase of 8 billion dollars a year. In 2002, diabetes annual costs per capita rose by more than 30% to 13,243 dollars per person, compared with the average annual health care costs for persons without diabetes of 2560.92 dollars. An estimate from the CDC indicates that approximately one-third of children born in 2000 will develop diabetes at some time in their life, and nearly one-half of all Hispanic children born in 2000 will develop diabetes. As type 2 diabetes is being diagnosed at an earlier age, more young people can expect to live many more years with diabetes and its complications, adding even further to this already enormous health burden. An appropriate starting place is recognition of the magnitude of the problem by physicians, politicians, public health policy makers, and other healthcare workers. An aggressive approach to management of diabetes must begin well before the appearance of cardiovascular, eye, renal, and other complications of diabetes appear, and even before obesity leads to diabetes. Currently, physicians and other healthcare workers are poorly reimbursed for management of obesity, for diabetes education, and for ongoing telephone contact with diabetic patients and families, essential for optimal diabetes management. National policies and priorities must be readjusted to emphasize prevention, rather than crisis management, if we are to avoid a catastrophic public health crisis within the next several decades.

Metabolic syndrome and daily ambulation in children, adolescents, and young adults.

PURPOSES: To compare daily ambulatory measures in children, adolescents, and young adults with and without metabolic syndrome and to assess which metabolic syndrome components, demographic measures, and body composition measures are associated with daily ambulatory measures. METHODS: Two-hundred fifty subjects between the ages of 10 and 30 yr were assessed on metabolic syndrome components, demographic and clinical measures, body fat percentage, and daily ambulatory strides, durations, and cadences during seven consecutive days. Of the 250 subjects, 45 had metabolic syndrome, as defined by the International Diabetes Federation. RESULTS: Subjects with metabolic syndrome ambulated at a slower daily average cadence than those without metabolic syndrome (13.6 ± 2.2 vs 14.9 ± 3.2 strides per minute; P = 0.012), and they had slower cadences for continuous durations of 60 min (P = 0.006), 30 min (P = 0.005), 20 min (P = 0.003), 5 min (P = 0.002), and 1 min (P = 0.001). However, the total amount of time spent ambulating each day was not different (P = 0.077). After adjustment for metabolic syndrome status, average cadence is linearly associated with body fat percentage (P < 0.001) and fat mass (P < 0.01). Group difference in average cadence was no longer significant after adjusting for body fat percentage (P = 0.683) and fat mass (P = 0.973). CONCLUSIONS: Children, adolescents, and young adults with metabolic syndrome ambulate more slowly and take fewer strides throughout the day than those without metabolic syndrome, although the total amount of time spent ambulating is not different. Furthermore, the detrimental influence of metabolic syndrome on ambulatory cadence is primarily a function of body fatness.

Metabolic syndrome and arterial elasticity in youth.

OBJECTIVE: To compare arterial elasticity in children, adolescents, and young adults with and without metabolic syndrome (MetS), and to assess which MetS components, demographic measures, and body composition measures are associated with arterial elasticity. MATERIALS/METHODS: Two-hundred six subjects (107 females and 99 males) between the ages of 10 and 20years were recruited by local newspaper advertisements, university email advertisements, and informational flyers. Subjects were assessed on MetS components, demographic measures, body composition measures, and arterial elasticity via radial tonometry. Forty-five subjects (22%) had MetS, as defined by the International Diabetes Federation, and 161 subjects (78%) did not. RESULTS: The primary novel finding was that group differences were not observed for large artery elasticity index (LAEI) (MetS=16.1±4.4 (ml×mmHg(-1))×10 (mean±SD), control=15.4±4.9, (ml×mmHg(-1))×10, p=0.349), and small artery elasticity index (SAEI) (MetS=9.2±2.7 (ml×mmHg(-1))×100, control=8.4±2.9, (ml×mmHg(-1))×100, p=0.063). In the MetS group, fat free mass was positively associated with arterial elasticity, and was the strongest multivariate predictor of LAEI (partial R(2)=0.41) and SAEI (partial R(2)=0.29). CONCLUSIONS: Youth with MetS did not exhibit differences in LAEI and SAEI compared to controls. Furthermore, fat free mass of youth with MetS was positively associated with arterial elasticity, and was the strongest predictor of both LAEI and SAEI. The clinical implication is that exercise intervention designed to increase fat free mass might increase arterial elasticity in youth, particularly in youth with MetS.

Transition from pediatric to adult care for adolescents and young adults with a disorder of sex development.

Over the past twenty years, there has been an increasing awareness of the transition to adult-oriented health care in adolescents and young adults with a chronic illness. While general guidelines for health care transition have been established, some have called for illness-specific guidelines which are tailored to the needs of specific illness populations. The current paper sought to outline illness-specific guidelines for health care transition in adolescents and young adults with disorders of sex development based upon the recent American Academy of Pediatrics guidelines. We also suggest indicators of successful transition for adolescents and young adults with disorders of sex development as well as areas for future research.

A model of delivering multi-disciplinary care to people with 46 XY DSD.

In 2006, a consensus statement was jointly produced by the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society of Paediatric Endocrinology (ESPE) concerning the management of disorders of sex development (DSD) [1]. A recommendation provided by this consensus was that evaluation and long-term care for people affected by DSD should be performed at medical centers with multi-disciplinary teams experienced in such conditions. Here we provide our team's interpretation of the 2006 consensus statement recommendations and its translation into a clinical protocol for individuals affected by 46 XY DSD with either female, or ambiguous, genitalia at birth. Options for medical and surgical management, transitioning of care, and the use of mental health services and peer support groups are discussed. Finally, we provide preliminary data to support the application of our model for delivering multi-disciplinary care and support to patients and their families.

Normal sex differences in prenatal growth and abnormal prenatal growth retardation associated with 46,XY disorders of sex development are absent in newborns with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common presentation of a disorder of sex development (DSD) in genetic females. A report of prenatal growth retardation in cases of 46,XY DSD, coupled with observations of below-optimal final height in both males and females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, prompted us to investigate prenatal growth in the latter group. Additionally, because girls with congenital adrenal hyperplasia are exposed to increased levels of androgens in the absence of a male sex-chromosome complement, the presence or absence of typical sex differences in growth of newborns would support or refute a hormonal explanation for these differences. METHODS: In total, 105 newborns with congenital adrenal hyperplasia were identified in our database. Gestational age (weeks), birth weight (kg), birth length (cm) and parental heights (cm) were obtained. Mid-parental height was considered in the analyses. RESULTS: Mean birth weight percentile for congenital adrenal hyperplasia was 49.26%, indicating no evidence of a difference in birth weight from the expected standard population median of 50th percentile (P > 0.05). The expected sex difference in favor of heavier males was not seen (P > 0.05). Of the 105 subjects, 44 (27%; 34 females, 10 males) had birth length and gestational age recorded in their medical chart. Mean birth length for this subgroup was 50.90 cm (63rd percentile), which differed from the expected standard population median of 50th percentile (P = 0.0082). The expected sex difference in favor of longer males was also not seen (P > 0.05). CONCLUSION: The prenatal growth retardation patterns reported in cases of 46,XY disorders of sex development do not generalize to people with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Sex differences in body weight and length typically seen in young infants were not seen in the subjects who participated in this study. We speculate that these differences were ameliorated in this study because of increased levels of prenatal androgens experienced by the females infants.

Paradoxical increase in arterial compliance in obese pubertal children.

We determined whether arterial compliance measured by pulse wave analysis is impaired in obese pubertal children compared to normal weight controls, and assessed whether arterial compliance is associated with ambulatory activity. Body fat percentage was significantly different between the normal (n = 33) and obese (n = 34) participants (P < .001). Large (P = .012) and small (P < .001) arterial compliance were lower in the normal-weight group. After adjusting for height, systolic and diastolic blood pressure, race, sex, and Tanner stage, large arterial compliance was no longer different between groups (P = .066), whereas small arterial compliance remained higher in the obese group (P < .001). Obese pubertal children have paradoxically increased small arterial compliance compared to that of normal weight children, even after adjusting for height, blood pressure, race, sex, and Tanner stage. Thus, obesity in adolescence is not associated with impairments in small arterial compliance.

An Evidence-Based Model of Multidisciplinary Care for Patients and Families Affected by Classical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency.

In 2002 a consensus statement pertaining to the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency was jointly produced by the Lawson Wilkins Pediatric Endocrine Society and the European Society of Pediatric Endocrinology. One of the recommendations of this consensus was that centers should maintain multidisciplinary teams for providing care and support to these patients and their families. However, the specifics for how this should be accomplished were not addressed in the original consensus statement. Here we interpret and translate the 2002 consensus statement recommendations into medical, surgical and mental health protocols. Additionally, we provide preliminary evidence that such protocols result in improved care and support for patients and families.