The Potential Causes of Cystic Fibrosis-Related Diabetes.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity, affecting more than 50% of adult CF patients. Despite this high prevalence, the etiology of CFRD remains incompletely understood. Studies in young CF children show pancreatic islet disorganization, abnormal glucose tolerance, and delayed first-phase insulin secretion suggesting that islet dysfunction is an early feature of CF. Since insulin-producing pancreatic ß-cells express very low levels of CFTR, CFRD likely results from ß-cell extrinsic factors. In the vicinity of ß-cells, CFTR is expressed in both the exocrine pancreas and the immune system. In the exocrine pancreas, CFTR mutations lead to the obstruction of the pancreatic ductal canal, inflammation, and immune cell infiltration, ultimately causing the destruction of the exocrine pancreas and remodeling of islets. Both inflammation and ductal cells have a direct effect on insulin secretion and could participate in CFRD development. CFTR mutations are also associated with inflammatory responses and excessive cytokine production by various immune cells, which infiltrate the pancreas and exert a negative impact on insulin secretion, causing dysregulation of glucose homeostasis in CF adults. In addition, the function of macrophages in shaping pancreatic islet development may be impaired by CFTR mutations, further contributing to the pancreatic islet structural defects as well as impaired first-phase insulin secretion observed in very young children. This review discusses the different factors that may contribute to CFRD.

Stability of the Gross Motor Function Classification System in adults with cerebral palsy.

To determine the stability of Gross Motor Function Classification System (GMFCS) levels between approximately 12 years of age and adulthood (i.e. > 16y) using a matched chart review. Adult health records from the Ottawa Rehabilitation Centre were matched with childhood health records from the Ottawa Children's Treatment Centre (OCTC). Health records were available for 103 adults (52 males, 51 females) with cerebral palsy (CP; age range 17-38y; mean age 22y [SD 4y]) who had also been seen at the OCTC at a mean age of 12 years (SD 1y). GMFCS levels as adults were: Level I, n= 10; Level II, n= 24; Level III, n= 21; Level IV, n= 30; and Level V, n= 18. Adult participants were classified using the GMFCS at the time they were last seen by a rehabilitation specialist, sometime between June 2002 and June 2005. Corresponding paediatric charts were reviewed and classified by two independent raters blinded to the adult GMFCS levels. GMFCS levels around age 12 were: Level I, n= 20; Level II, n= 13; Level III, n= 22; Level IV, n= 35; and Level V, n= 13. Interrater reliability for childhood health records was determined with a quadratic weighted kappa and was 0.978. Stability of GMFCS levels was also assessed using the quadratic weighted kappa and was 0.895. The positive predictive value of the GMFCS at 12 years of age to predict walking without mobility aids by adulthood is 0.88. If the child is a wheelchair user at around age 12 years, the positive predictive value is 0.96 that the individual will still be a wheelchair user as an adult. This study supports previous findings that interrater reliability when using the GMFCS is very high. It also shows that the GMFCS level observed around the age of 12 years is highly predictive of adult motor function. This provides important information for individuals with CP, their families, and care providers as they plan for future care needs and rehabilitation intervention.