GENOTYPE ANALYSIS IN CYSTIC-FIBROSIS IN RELATION TO THE OCCURRENCE OFDIABETES-MELLITUS

Carbohydrate intolerance and frank diabetes mellitus (DM) are recognis ed features of cystic fibrosis (CF), but their cause has not been esta blished. Damage to the islet cells due to pancreatic fibrosis is the m ost common explanation. The relationship between the genotype and the occurrence of diabetes mellitus has been examined in 21 cystic fibrosi s patients attending our out-patient chest clinics. DNA samples were t ested for the presence of the most common mutation (DELTAF508) and the results related to the degree of carbohydrate intolerance. We found t hat in CF patients over 18 years of age diabetes is more frequent amon g those homozygous for the DELTAF508 allele than the heterozygotes (P < 0.05). Those homozygous for DELTAF508 were diagnosed as CF at an ear lier age than the heterozygotes (P < 0.05). Both the mean age and the female/male ratio were similar in the diabetic and non-diabetic groups . The prevalence of the DELTAF508 allele was similar to that expected in a random sample of East Anglian cystic fibrosis patients. These dat a suggest that the occurrence of diabetes mellitus in patients with cy stic fibrosis is related to the genotype, which could be secondary to the way the genetic factors influence the degree of pancreatic disease and its rate of progression.