Faculty Bibliography

Mental health comorbidities can negatively affect disease management in adolescents with chronic illnesses. This study sought to determine the prevalence and impact of mental health issues in a population of adolescents and young adults with type 1 diabetes. A cross-sectional study of 150 patients aged 11 to 25 years with type 1 diabetes from an urban, academic diabetes center was conducted. Participants completed 3 validated mental health disorder screening instruments: Beck's Depression Inventory, the Screen for Child Anxiety Related Emotional Disorders-41 anxiety screen, and the Eating Disorder Screen for Primary Care. More than a third screened positive: 11.3% for depression, 21.3% for anxiety, and 20.7% for disordered eating (14.7% had >/=2 positive screens). Patients with a positive screen had twice the odds of having poor glycemic control as those without, as measured by HgbA1c. This study supports screening for mental health issues in adolescents and young adults with type 1 diabetes.

The clinical care of patients with type 1 diabetes (T1D) has greatly improved over the past few decades; however, it remains impossible to completely normalize blood sugar utilizing currently available tools. Research is underway with a goal to improve the care and, ultimately, to cure T1D by preserving beta cells. This review will outline the progress that has been made in trials aimed at preserving insulin secretion in T1D by modifying the immune assault on the pancreatic beta cell. Although not yet ready for clinical use, successful trials have been conducted in new-onset T1D that demonstrated utility of three experimental agents with disparate modes of action (anti-T cell, anti-B cell, and costimulation blockade) to preserve insulin secretion. In contrast, prevention studies have so far failed to produce positive results but have shown that such studies are feasible and have identified new promising agents for study.

A key feature of the immune system is its ability to discriminate self from nonself. Breakdown in any of the mechanisms that maintain unresponsiveness to self (a state known as self-tolerance) contributes to the development of autoimmune conditions. Recent studies in mice show that CD8(+) T cells specific for the unconventional MHC class I molecule Qa-1 bound to peptides derived from the signal sequence of Hsp60 (Hsp60sp) contribute to self/nonself discrimination. However, it is unclear whether they exist in humans and play a role in human autoimmune diseases. Here we have shown that CD8(+) T cells specific for Hsp60sp bound to HLA-E (the human homolog of Qa-1) exist and play an important role in maintaining peripheral self-tolerance by discriminating self from nonself in humans. Furthermore, in the majority of type 1 diabetes (T1D) patients tested, there was a specific defect in CD8(+) T cell recognition of HLA-E/Hsp60sp, which was associated with failure of self/nonself discrimination. However, the defect in the CD8(+) T cells from most of the T1D patients tested could be corrected in vitro by exposure to autologous immature DCs loaded with the Hsp60sp peptide. These data suggest that HLA-E-restricted CD8(+) T cells may play an important role in keeping self-reactive T cells in check. Thus, correction of this defect could be a potentially effective and safe approach in the therapy of T1D.

The medical management of children with congenital adrenal hyperplasia (CAH) can be challenging with regard to optimizing final height. Insufficient glucocorticoid suppression of adrenal hormone production will result in acceleration of bone maturation and premature epiphyseal fusion, while appropriate or excessive glucocorticoid therapy can be accompanied by suppression of the growth axis. The extent of the growth suppression appears to be affected by the type and dose of glucocorticoid. Some studies suggest that such growth suppression can be ameliorated through concomitant use of growth hormone (GH) therapy. Available data published over the last 10 years on height outcomes in CAH patients treated with glucocorticoids will be reviewed

Acanthosis nigricans in children is usually a benign condition most commonly associated with obesity. Generalized acanthosis nigricans is a very rare condition, especially in childhood. We report a 6-year-old boy with a 4-year history of generalized hyperpigmentation and velvety thickening of the skin. Despite an extensive examination, no evidence for an underlying neoplastic or endocrinologic disease was found.

We describe three siblings with congenital myopathy, bullous eruption of the skin, secretory diarrhea, apparent zinc deficiency, failure to thrive, deafness, and microcephaly. The parents are not consanguineous and there are no other affected relatives. This new syndrome, which follows an apparent autosomal recessive pattern, appears to be distinct from known syndromes of secretory diarrhea, myopathy, deafness, microcephaly, and zinc deficiency.