Evidence for a causal relationship between early exocrine pancreatic disease and cystic fibrosis-related diabetes: a Mendelian randomization study.

ABSTRACT: Circulating immunoreactive trypsinogen (IRT), a biomarker of exocrine pancreatic disease in cystic fibrosis (CF), is elevated in most CF newborns. In those with severe CF transmembrane conductance regulator (CFTR) genotypes, IRT declines rapidly in the first years of life, reflecting progressive pancreatic damage. Consistent with this progression, a less elevated newborn IRT measure would reflect more severe pancreatic disease, including compromised islet compartments, and potentially increased risk of CF-related diabetes (CFRD). We show in two independent CF populations that a lower newborn IRT estimate is associated with higher CFRD risk among individuals with severe CFTR genotypes, and we provide evidence to support a causal relationship. Increased loge(IRT) at birth was associated with

SUBMITTER: Soave D 

PROVIDER: S-EPMC4030111 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature