Spontaneous and iatrogenic hypoglycemia in cystic fibrosis

Spontaneous episodes of hypoglycemia can occur in people with cystic fibrosis (CF) without diabetes, who are not on glucose lowering medications. Spontaneous hypoglycemia in CF could occur both in the fasting or postprandial state (reactive hypoglycemia). The pathophysiology of fasting hypoglycemia is thought to be related to malnutrition and increased energy expenditure in the setting of inflammation and acute infections. Reactive hypoglycemia is thought to be due to impaired first phase insulin release in response to a glucose load, followed by a delayed and extended second phase insulin secretion; ineffective counterregulatory response to dropping glucose levels may also play a role. The overall prevalence of spontaneous hypoglycemia varies from 7 to 69% as examined with oral glucose tolerance test (OGTT) or with continuous glucose monitoring (CGM) under free living conditions. Spontaneous hypoglycemia in CF is associated with worse lung function, higher hospitalization rates, and worse clinical status. In addition, patients with CF related diabetes on glucose-lowering therapies are at risk for iatrogenic hypoglycemia. In this article, we will review the pathophysiology, prevalence, risk factors, clinical implications, and management of spontaneous and iatrogenic hypoglycemia in patients with CF.