Constadina Panagiotopoulos

OBJECTIVE: To determine in Canadian children aged <18 years the 1) incidence of type 2 diabetes, medication-induced diabetes, and monogenic diabetes; 2) clinical features of type 2 diabetes; and 3) coexisting morbidity associated with type 2 diabetes at diagnosis. RESEARCH DESIGN AND METHODS: This Canadian prospective national surveillance study involved a network of pediatricians, pediatric endocrinologists, family physicians, and adult endocrinologists. Incidence rates were calculated using Canadian Census population data. Descriptive statistics were used to illustrate demographic and clinical features. RESULTS: From a population of 7.3 million children, 345 cases of non-type 1 diabetes were reported. The observed minimum incidence rates of type 2, medication-induced, and monogenic diabetes were 1.54, 0.4, and 0.2 cases per 100,000 children aged <18 years per year, respectively. On average, children with type 2 diabetes were aged 13.7 years and 8% (19 of 227) presented before 10 years. Ethnic minorities were overrepresented, but 25% (57 of 227) of children with type 2 diabetes were Caucasian. Of children with type 2 diabetes, 95% (206 of 216) were obese and 37% (43 of 115) had at least one comorbidity at diagnosis. CONCLUSIONS: This is the first prospective national surveillance study in Canada to report the incidence of type 2 diabetes in children and also the first in the world to report the incidence of medication-induced and monogenic diabetes. Rates of type 2 diabetes were higher than expected with important regional variation. These results support recommendations that screening for comorbidity should occur at diagnosis of type 2 diabetes.

CD4(+)FOXP3(+) regulatory T cells are essential for immune tolerance, and murine studies suggest that their dysfunction can lead to type 1 diabetes (T1D). Human studies assessing regulatory T cell dysfunction in T1D have relied on analysis of FOXP3-expressing cells. Recently, distinct subsets of CD4(+)FOXP3(+) T cells with differing function were identified. Notably, CD45RA(-)CD25(int)FOXP3(low) T cells lack suppressive function and secrete the proinflammatory cytokine IL-17. Therefore, we evaluated whether the relative fractions of CD4(+)FOXP3(+) subsets are altered in new-onset T1D subjects. We report that children with new-onset T1D have an increased proportion of CD45RA(-)CD25(int)FOXP3(low) cells that are not suppressive and secrete significantly more IL-17 than other FOXP3(+) subsets. Moreover, these T1D subjects had a higher proportion of both CD4(+) and CD8(+) T cells that secrete IL-17. The bias toward IL-17-secreting T cells in T1D suggests a role for this proinflammatory cytokine in the pathogenesis of disease.

BACKGROUND: The use of antipsychotics, especially second generation antipsychotics (SGAs), for children with mental health disorders in Canada has increased dramatically over the past five years. These medications have the potential to cause major metabolic and neurological complications with chronic use. OBJECTIVE: Our objective was to synthesize the evidence for specific metabolic and neurological side effects associated with the use of SGAs in children and make evidence-based recommendations for the monitoring of these side effects. METHODS: We performed a systematic review of controlled clinical trials of SGAs in children. Recommendations for monitoring SGA safety were made according to a classification scheme based on the GRADE system. When there was inadequate evidence to make recommendations, recommendations were based on consensus and expert opinion. A multi-disciplinary consensus group reviewed all relevant evidence and came to consensus on recommendations. RESULTS: Evidence-based recommendations for monitoring SGA safety are provided in the guideline. The strength of recommendations for specific physical examination maneuvers and laboratory tests are provided for each SGA medication at specific time points. CONCLUSION: Multiple randomized controlled trials (RCTs) have established the efficacy of many of the SGAs in pediatric mental health disorders. These benefits however do not come without risk; both metabolic and neurological side effects occur in children treated with these SGAs. The risk of weight gain, increased BMI and abnormal lipids appears greatest with olanzapine, followed by clozapine and quetiapine. The risk of neurological side effects of treatment appears greatest with risperidone, olanzapine and aripiprazole. Appropriate monitoring procedures for adverse effects will improve the quality of care of children treated with these medications.