Dr. Larson Ode 
Dr. Norris
Cystic fibrosis is a genetic disease that causes dysfunction in multiple systems, but especially in the lungs which progressively deteriorate. The past few years have seen massive progress in the medical treatment of cystic fibrosis. Drugs have come to market that correct the basic molecular defects that cause cystic fibrosis. These drugs are classified as “highly effective modulator therapies”. These therapies must be tailored to each person, by matching to the different mutations that cause cystic fibrosis. In 2019, a blend of three modulators was approved for treatment of the most common form of cystic fibrosis involving the “F508del” mutation. This therapy combines elexacaftor, tezacaftor, and ivacaftor (“ETI”). This therapy dramatically improves lung dysfunction in persons with cystic fibrosis due to F508del mutation. Persons with cystic fibrosis are at very high risk to develop diabetes. For example, those who have only have F508del mutation have an over 80% chance of developing diabetes by middle age. It is currently not known if ETI-therapy for cystic fibrosis will impact diabetes risk. To address this knowledge gap, investigators from 5 institutions conducted a study of twenty persons with cystic fibrosis. Each person underwent an oral glucose tolerance test before and roughly 10 months after starting ETI-therapy. Interestingly, there was not a significant change in glucose levels after starting ETI. However, C-peptide levels increased with ETI therapy, consistent increased insulin secretion. Accordingly, an insulin resistance index significantly increased as did body mass index. Taken together, these results suggest that ETI therapy produces a degree of insulin resistance, likely related to an increase in body mass index. The longer term impact of ETI and related therapies on diabetes risk and body weight will need careful ongoing study. The faculty investigators involved in the study from our division were Dr. Larson Ode and Dr. Norris. The publication describing the study and results can be found at this Pubmed link.