Curriculum · Metabolic and Endocrine and Diabetes Mellitus
Cystic fibrosis-related diabetes
What it is
CF-related diabetes, written CFRD, is the endocrine half of pancreatic involvement in cystic fibrosis. Under organ involvement the pancreas carries two words, exocrine and endocrine, and the endocrine one is CFRD.
It appears twice more in the same set. Among the complications it is listed as one of the CF-related diseases together with liver disease, written CFLD. And among the manifestations it is listed under endocrine and other, together with infertility in males. In the list of how the child presents, diabetes mellitus stands first, ahead of recurrent infections with cough, purulent sputum and SOB; the gastrointestinal symptoms of steatorrhoea, failure to thrive in childhood, rectal prolapse, meconium ileus or distal intestinal obstruction; heat stroke and salt depletion; and sterility in men, with no vas deferens and epididymis, with decreased fertility in women. The genetic basis is autosomal recessive on chromosome 7, affecting the protein for cAMP-regulated chloride channels, and the commonest gene is F508.
Causes and risk
The table of CFTR mutation classes is presented as the type of mutations in the CFTR gene including those that increase the risk for diabetes development, so the mutation is where the risk is set.
The six classes are: class I, no CFTR synthesis, prevalence 10%; class II, CFTR trafficking defect, 88%; class III, defective channel regulation, 4%; class IV, decreased channel conductance; class V, reduced CFTR synthesis; and class VI, decreased CFTR stability. Increased risk for CFRD is written over the first three of these classes - class I, class II and class III - while classes IV, V and VI fall outside it, and the class-specific therapy runs alongside each: read-through compounds for class I, correctors for class II, and potentiators for classes III and IV. Chronic pancreatitis makes the same link from the other side. Its causes are alcohol, the most common, and cystic fibrosis; exocrine pancreatic insufficiency gives steatorrhea and endocrine pancreatic insufficiency gives diabetes, with an increase in serum glucose and HbA1c on investigation. Young adults with chronic pancreatitis require CF testing.