Impact of dysglycemia and obesity on the brain in adolescents with and without type 2 diabetes: A pilot study.

OBJECTIVE: Both diabetes and obesity can affect the brain, yet their impact is not well characterized in children with type 2 (T2) diabetes and obesity. This pilot study aims to explore differences in brain function and cognition in adolescents with T2 diabetes and obesity and nondiabetic controls with obesity and lean controls. RESEARCH DESIGN AND METHODS: Participants were 12-17 years old (5 T2 diabetes with obesity [mean HgbA1C 10.9%], 6 nondiabetic controls with obesity and 10 lean controls). Functional MRI (FMRI) during hyperglycemic/euglycemic clamps was performed in the T2 diabetes group. RESULTS: When children with obesity, with and without diabetes, were grouped (mean BMI 98.8%), cognitive scores were lower than lean controls (BMI 58.4%) on verbal, full scale, and performance IQ, visual-spatial and executive function tests. Lower scores correlated with adiposity and insulin resistance but not HgbA1C. No significant brain activation differences during task based and resting state FMRI were noted between children with obesity (with or without diabetes) and lean controls, but a notable effect size for the visual-spatial working memory task and resting state was observed. CONCLUSIONS: In conclusion, our pilot study suggests that obesity, insulin resistance, and dysglycemia may contribute to relatively poorer cognitive function in adolescents with T2 diabetes and obesity. Further studies with larger sample size are needed to assess if cognitive decline in children with obesity, with and without T2 diabetes, can be prevented or reversed.

Short Stature Homeobox-Containing Haploinsufficiency in Seven Siblings with Short Stature.

Deficiency of the short stature homeobox-containing (SHOX) gene is a frequent cause of short stature in children (2-15%). Here, we report 7 siblings with SHOX deficiency due to a point mutation in the SHOX gene. Index case was a 3-year-old male who presented for evaluation of short stature. His past medical history and birth history were unremarkable. Family history was notable for multiple individuals with short stature. Physical exam revealed short stature, with height standard deviation score (SDS) of -2.98, as well as arm span 3 cm less than his height. His laboratory workup was noncontributory for common etiologies of short stature. Due to significant familial short stature and shortened arm span, SHOX gene analysis was performed and revealed patient is heterozygous for a novel SHOX gene mutation at nucleotide position c.582. This mutation is predicted to cause termination of the SHOX protein at codon 194, effectively causing haploinsufficiency. Six out of nine other siblings were later found to also be heterozygous for the same mutation. Growth hormone was initiated in all seven siblings upon diagnosis and they have demonstrated improved height SDS.

Evaluating Substance Use and Insulin Misuse in Adolescents With Type 1 Diabetes.

PURPOSE: Substance use behaviors often emerge during adolescence, and adolescents with type 1 diabetes (T1D) may be at risk for engaging in traditional substance use (eg, alcohol, tobacco, and illicit substances) as well as a unique form of substance use: insulin misuse. The purpose of this exploratory study was to examine substance use and insulin misuse in adolescents with T1D. METHODS: Sixty adolescents aged 12 to 20 years with T1D (n = 60) completed surveys on substance use, insulin misuse, and diabetes self-management during a routine diabetes appointment. Demographic measures were summarized by mean (SD) or percentage. Prevalence of substance use and insulin misuse was calculated and stratified by demographic and clinical characteristics. Two-sample t test (continuous variables) and chi-square analysis (categorical variables) determined statistically significant differences. RESULTS: The prevalence of ever using substances was 36.7%, and that for ever misusing insulin was 19%. Older participants (17.1 ± 1.8 vs 15.6 ± 1.9 years; P < .01) and those with depression (31.8% vs 7.9%; P = .02) were more likely to use substances. Disordered eating behaviors were the most frequently reported reason for insulin misuse. Self-harm intent was reported by one-third of insulin misusers. Substance use and insulin misuse were not related to glycemic control or diabetes self-management behaviors. CONCLUSIONS: The diabetes care team should be aware that substance use and insulin misuse are common in adolescents with T1D. Screening for these risky behaviors is critical in those who are older or have mental health disorders. Effective education, prevention, and treatment strategies targeted at these behaviors are needed to improve the overall health of this population.