Alcohol and cigarette use among adolescents with type 1 diabetes.

In this study, we compare the prevalence of alcohol and cigarette use among Polish adolescents with type 1 diabetes mellitus (T1DM) (n = 209), aged 15-18 years, with that of a large cohort of their healthy peers, using standardized questionnaire used in the European School Survey Project on Alcohol and Drugs (ESPAD). The lifetime, previous year, and past 30-day prevalence of alcohol consumption was high among adolescents with T1DM but lower than in the controls (82.8 vs 92.0%, 71.7 vs 85.6%, and 47.5 vs 69.7%, respectively, p < 10-5). The lifetime and 30-day prevalence of cigarette use was also lower among patients than the controls (54.6 vs 65.5%, p = 0.001 and 27.3 vs 35.9%, p = 0.012, respectively). Patients who admitted smoking exhibited worse metabolic control than non-smokers (p < 0.0001) and had a higher chance of developing diabetic ketoacidosis. The incidence of severe hypoglycemia was higher among those who reported getting drunk in the previous 30 days (p = 0.04) and lifetime smoking (p = 0.01). CONCLUSIONS: Although alcohol and cigarette consumption is lower than in controls, it is common among teenagers with type 1 diabetes, effecting metabolic control and causing the risk of acute diabetes complications. Better prevention strategies should be implemented in this group of patients in their early teen years. What is Known: • Substance use remains a significant cause of morbidity and mortality among teenagers with type 1 diabetes. • Current medical literature contains inconsistent data on the prevalence of alcohol and cigarette use among adolescents with type 1 diabetes, mostly due to methodological problems with conducting such surveys. What is New: • Methodological approach: we used a validated questionnaire from the European School Survey Project on Alcohol and Other Drugs (ESPAD) and compared the results to a large national control group of 12,114 healthy students who took part in ESPAD in 2011.

Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion.

OBJECTIVE: Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide. RESEARCH DESIGN AND METHODS: To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5'-triphosphate inhibition were associated with the most severe neurologic symptoms. CONCLUSIONS: We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.

Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction.

Maturity-onset diabetes of the young (MODY) is a subtype of diabetes defined by an autosomal pattern of inheritance and a young age at onset, often before age 25. MODY is genetically heterogeneous, with 8 distinct MODY genes identified to date and more believed to exist. We resequenced 732 kb of genomic sequence at 8p23 in 6 MODY families unlinked to known MODY genes that showed evidence of linkage at that location. Of the 410 sequence differences that we identified, 5 had a frequency <1% in the general population and segregated with diabetes in 3 of the families, including the 2 showing the strongest support for linkage at this location. The 5 mutations were all placed within 100 kb corresponding to the BLK gene. One resulted in an Ala71Thr substitution; the other 4 were noncoding and determined decreased in vitro promoter activity in reporter gene experiments. We found that BLK--a nonreceptor tyrosine-kinase of the src family of proto-oncogenes--is expressed in beta-cells where it enhances insulin synthesis and secretion in response to glucose by up-regulating transcription factors Pdx1 and Nkx6.1. These actions are greatly attenuated by the Ala71Thr mutation. These findings point to BLK as a previously unrecognized modulator of beta-cell function, the deficit of which may lead to the development of diabetes.