OGTT Glucose Response Curves, Insulin Sensitivity, and ß-Cell Function in RISE: Comparison Between Youth and Adults at Randomization and in Response to Interventions to Preserve ß-Cell Function.

OBJECTIVE: We examined the glucose response curves (biphasic [BPh], monophasic [MPh], incessant increase [IIn]) during an oral glucose tolerance test (OGTT) and their relationship to insulin sensitivity (IS) and ß-cell function (ßCF) in youth versus adults with impaired glucose tolerance or recently diagnosed type 2 diabetes.RESEARCH DESIGN AND METHODSThis was both a cross-sectional and a longitudinal evaluation of participants in the RISE study randomized to metformin alone for 12 months or glargine for 3 months followed by metformin for 9 months. At baseline/randomization, OGTTs (85 youth, 353 adults) were categorized as BPh, MPh, or IIn. The relationship of the glucose response curves to hyperglycemic clamp-measured IS and ßCF at baseline and the change in glucose response curves 12 months after randomization were assessed.RESULTSAt randomization, the prevalence of the BPh curve was significantly higher in youth than adults (18.8% vs. 8.2%), with no differences in MPh or IIn. IS did not differ across glucose response curves in youth or adults. However, irrespective of curve type, youth had lower IS than adults (P < 0.05). ßCF was lowest in IIn versus MPh and BPh in youth and adults (P < 0.05), yet compared with adults, youth had higher ßCF in BPh and MPh (P < 0.005) but not IIn. At month 12, the change in glucose response curves did not differ between youth and adults, and there was no treatment effect.CONCLUSIONSDespite a twofold higher prevalence of the more favorable BPh curve in youth at randomization, RISE interventions did not result in beneficial changes in glucose response curves in youth compared with adults. Moreover, the typical ß-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of ß-cell dysfunction in youth with this least favorable glucose response curve.

Youth-Onset Type 2 Diabetes Consensus Report: Current Status, Challenges, and Priorities.

Type 2 diabetes is a significant and increasing burden in adolescents and young adults. Clear strategies for research, prevention, and treatment of the disease in these vulnerable patients are needed. Evidence suggests that type 2 diabetes in children is different not only from type 1 but also from type 2 diabetes in adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as well as the risk of complications and the psychosocial impact, will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate both current and future research, treatment, and prevention approaches. This Consensus Report characterizes type 2 diabetes in children, evaluates the fundamental differences between childhood and adult disease, describes the current therapeutic options, and discusses challenges to and approaches for developing new treatments.

Morning blood pressure is associated with sleep quality in obese adolescents.

OBJECTIVE: To examine relationships among blood pressure (BP), adiposity, and sleep quality with the use of overnight polysomnography in obese adolescents. STUDY DESIGN: Overnight polysomnogram and morning BP measurements were performed in obese (body mass index [BMI] >95th percentile) nondiabetic adolescents (eligible age range 12-18 years, n = 49). Subjects were stratified into 2 groups, one with normal BP, and one with elevated BP, and demographic and clinical characteristics were compared between the groups. Multiple linear regression analysis was used to assess the effects of sleep quality on BP. RESULTS: Participants (n = 27) had a normal morning BP, and 22 (44.9%) had elevated morning BP. There were no differences in age (P = .53), sex (P = .44), race (P = .58), or BMI (P = .56) between the 2 BP groups. The group with elevated BP spent shorter percentages of time in rapid eye movement (REM; P = .006) and slow-wave sleep (SWS; P = .024). Multiple linear regression analysis showed that a lower percentage of both REM and SWS was associated with increased morning BP after we adjusted for pubertal stage, sex, race, and BMI. CONCLUSION: Lack of deeper stages of sleep, REM sleep, and SWS is associated with greater morning BP in obese adolescents, independent of BMI. Poor sleep quality should be considered in the work-up of obese youth with hypertension. Intervention studies are needed to evaluate whether improving the quality of sleep will decrease BP elevation.

Relationships among obstructive sleep apnea, anthropometric measures, and neurocognitive functioning in adolescents with severe obesity.

OBJECTIVE: To explore associations between measures of obstructive sleep apnea (OSA) and sleep quality, anthropometrics, and neurocognitive functioning in severely obese adolescents. STUDY DESIGN: This was a cross-sectional pilot study performed at an academic medical center in 37 severely obese (body mass index [BMI] >97th percentile) adolescents. Study evaluations included polysomnography, BMI, waist circumference, and standardized neurocognitive tests to assess memory, executive functioning, psychomotor efficiency, academic achievement, and an approximation of full-scale IQ. Outcome data were evaluated categorically, based on clinical criteria for the diagnosis of OSA, and continuously to quantify associations between sleep parameters, anthropometrics, and neurocognitive test results. RESULTS: Sleep fragmentation and poorer sleep quality were associated with reduced psychomotor efficiency, poorer memory recall, and lower scores on standardized academic tests. Having evidence of OSA was associated with lower math scores, but not with other neurocognitive measures. BMI and waist circumference were negatively associated with oxygen saturation. CONCLUSION: Our pilot study findings suggest that sleep fragmentation and poorer sleep quality have implications for neurocognitive functioning in obese adolescents. The epidemic of childhood obesity has dire implications, not only for increasing cardiometabolic pathology, but also for possibly promoting less readily apparent neurologic alterations associated with poor sleep quality.

Prolonged remission of severe Cushing syndrome without adrenalectomy in an infant with McCune-Albright syndrome.

A 4 month-old girl presented with severe Cushing syndrome caused by McCune-Albright syndrome. After undergoing 19 months of pharmacologic suppression of cortisol production, she has been in clinical remission for more than 6 years. Adrenalectomy may be avoidable even in severe cases of Cushing syndrome associated with McCune-Albright syndrome.

Infant with classic congenital adrenal hyperplasia (CAH) born to a mother with classic CAH.

We report a female infant with classic congenital adrenal hyperplasia (CAH), secondary to 21-hydroxylase deficiency, who was born to a mother with salt-wasting CAH.

Is McCune-Albright syndrome overlooked in subjects with fibrous dysplasia of bone?

OBJECTIVE: McCune-Albright syndrome (MAS) is characterized by a clinical triad of endocrinopathies, café au lait pigmentation, and polyostotic fibrous dysplasia of bone. We hypothesized that children diagnosed with fibrous dysplasia are not routinely being evaluated for coexisting endocrine dysfunction or MAS. Our objective was to prospectively screen subjects with fibrous dysplasia for endocrine disease and G(s)alpha gene (GNAS1 )-activating mutations. STUDY DESIGN: Nine subjects who presented with fibrous dysplasia and were followed in orthopedic clinics were evaluated for other manifestations of MAS. Genomic DNA was isolated from blood, and mutation analysis of GNAS1 was performed. RESULTS: On physical examination, 5 of 9 subjects were found to have café au lait pigmentation. Three of 9 subjects had TSH levels below the normal range. One of these subjects was found to have hyperthyroidism and was treated by total thyroidectomy. GNAS1 mutations were identified in 5 of 9 subjects with either monostotic or polyostotic fibrous dysplasia of bone. CONCLUSIONS: We conclude that a substantial proportion of children being followed for fibrous dysplasia of bone have unrecognized clinical and laboratory features of MAS. These children are at risk for endocrinopathy and should be screened accordingly.