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^intFOXP3^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^intFOXP3^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.

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.

Objective—Childhood obesity is associated with risk factors for cardiovascular disease. Arterial stiffness is considered one of the earliest detectable measures of vascular damage. There is controversy in the literature regarding the effects of childhood obesity on arterial stiffness. The objective of this study is to systematically review the literature and to conduct a meta-analysis comparing measures of central arterial stiffness in children and adolescents with obesity to healthy body mass index controls. Approach and Results—Literature searches were conducted using databases (eg, MEDLINE, EMBASE) and citations cross-referenced. Studies assessing central pulse wave velocity or β-stiffness index were included. A random effects meta-analysis of the standardized mean difference and 95% confidence intervals in arterial stiffness between children with obesity and control children was performed for each arterial stiffness measure. A total of 523 studies were identified. Fifteen case–control studies were included, with 2237 children/adolescents (1281 with obesity, 956 healthy body mass index controls) between 5 and 24 years of age. All studies measuring carotid and aortic β-stiffness index and 10/12 studies measuring central pulse wave velocity reported greater arterial stiffness in children/adolescents with obesity compared with controls. A random effects meta-analysis was performed revealing a significant effect of obesity on pulse wave velocity (standardized mean difference=0.718; 95% confidence interval=0.291–1.415), carotid β-stiffness index (0.862; 0.323–1.402), and aortic β stiffness index (1.017; 0.419–1.615). Conclusion—These findings indicate that child/adolescent obesity is associated with greater arterial stiffness. However, further research is needed to address confounders, such as pubertal status, that may affect this relationship in children. In the future, these techniques may be useful in risk stratification and guiding clinical management of obese children to optimize cardiovascular outcomes.

Importance Acute kidney injury (AKI) in children is associated with poor short-term and long-term health outcomes; however, the frequency of AKI in children hospitalized for diabetic ketoacidosis (DKA) has not been previously examined. Objectives To determine the proportion of children hospitalized for DKA who develop AKI and to identify the associated clinical and biochemical markers of AKI. Design, Setting, and Participants This medical record review of all DKA admissions from September 1, 2008, through December 31, 2013, was conducted at British Columbia Children’s Hospital, the tertiary pediatric hospital in British Columbia, Canada. Children aged 18 years or younger with type 1 diabetes and DKA and with complete medical records available for data analysis were included (n = 165). All data collection occurred between September 8, 2014, and June 26, 2015. Data analysis took place from August 25, 2015, to June 8, 2016. Main Outcomes and Measures Acute kidney injury was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. Multinomial logistic regression was used to identify potential factors associated with AKI. Results Of the 165 children hospitalized for DKA, 106 (64.2%) developed AKI (AKI stage 1, 37 [34.9%]; AKI stage 2, 48 [45.3%]; and AKI stage 3, 21 [19.8%]). Two children required hemodialysis. In the adjusted multinomial logistic regression model, a serum bicarbonate level less than 10 mEq/L (compared with ≥10 mEq/L) was associated with a 5-fold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio [aOR], 5.22; 95% CI, 1.35-20.22). Each increase of 5 beats/min in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39). Initial corrected sodium level of 145 mEq/L or greater (compared with 135-144 mEq/L) was associated with a 3-fold increase in the odds of mild (stage 1) AKI (aOR, 3.29; 95% CI, 1.25-8.66). There were no cases of mortality in patients with or without AKI. Conclusions and Relevance This study is the first to date to document that a high proportion of children hospitalized for DKA develop AKI. Acute kidney injury was associated with markers of volume depletion and severe acidosis. Acute kidney injury is concerning because it is associated with increased morbidity and mortality as well as increased risk of chronic renal disease, a finding that is especially relevant among children who are already at risk for diabetic nephropathy. Strategies are needed to improve the diagnosis, management, and follow-up of AKI in children with type 1 diabetes.