Kalydeco (ivacaftor), an approved therapy for cystic fibrosis (CF) patients with a specific mutation, improves insulin secretion in those with CF-related diabetes, researchers led by Ronald Rubenstein, MD, with the Children’s Hospital of Philadelphia, found. The mechanism underlying this benefit, however, remains unknown.
The results were presented today at the 30th Annual North American Cystic Fibrosis Conference, in Orlando, Florida, in a talk titled “β-cell secretory capacity improves in cystic fibrosis with ivacaftor therapy.” The conference, which opened on Thursday, Oct. 27, ends Saturday, Oct. 29.
CF-related diabetes is associated with worse disease outcomes. The effect of Kalydeco — known to help CF patients with a G551D mutation in the cystic fibrosis transmembrane regulator (CFTR) gene — on those with diabetes remains unknown. Specifically, how Kalydeco impacts insulin secretion and glucose tolerance in pancreatic exocrine sufficient and pancreatic insufficient individuals with CF is largely unaddressed.
Beta cells are unique cells in the pancreas, as they are responsible for producing, storing and secreting the hormone insulin.
Researchers performed a pilot study to evaluate how Kalydeco affects insulin secretion, incretin secretion (incretin is a hormone that stimulates insulin secretion in response to meals), and glucose tolerance in both types of CF patients, pancreatic sufficient and insufficient.
They enrolled CF patients with at least one CFTR gating or conductance mutation, and analyzed them at two different time-points — before and after 16 weeks of treatment with Kalydeco – assessing several parameters and their changes before and after Kalydeco therapy.
Patients were at least 6 years old, and assessment included oral glucose tolerance tests (OGTT), mixed meal tolerance tests (MMTT), and glucose-potentiated arginine-induced insulin secretion tests (GPA).
Preliminary data from 11 patients revealed that four months of Kalydeco therapy improved insulin secretion in young CF patients with pancreatic sufficiency and pancreatic insufficiency, and normal glucose tolerance. Incretin, on the other hand, showed no alterations.
According to Rubenstein, results suggest that Kalydeco treatment affects beta-cells function and improves their secretion capacity. However, another possible mechanism is Kalydeco having an indirect action on other pathways that improve CF outcomes, including an increase in insulin secretion, without affecting beta-cell secretion capacity.
Future studies are required to understand the direct and indirect roles of Kalydeco in beta-cells function and its link to CF-related diabetes.