Insulin for Hypoglycemia?: The Case for Initiating Prandial Insulin First in Cystic Fibrosis Related Diabetes

Cystic fibrosis related diabetes (CFRD) is the most common non-respiratory comorbidity in cystic fibrosis (CF), occurring in 40-50% of adults with CF. CF mediated destruction of the pancreatic tissue from progressive fibrosis and fatty infiltration leads to loss of beta cells and insulin deficiency, but alteration of beta cell function and insulin resistance due to inflammation or infection are also possible mechanisms for diabetes development.

Case Description:

This case describes an 18-year-old female who was diagnosed with CF in infancy and presented to our clinic for evaluation of possible CF related diabetes and hypoglycemia. Lab tests 4 months earlier revealed a HgbA1c of 5.7, oral glucose tolerance testing (OGTT) showed a fasting blood glucose level of 87 mg/dL, 246 mg/dL one hour and 222 mg/dL two hours after glucose load. She reported that after large meals- especially those that were carbohydrate rich- she felt sweaty, anxious, and weak. Her initial CGM tracing revealed marked post-prandial hyperglycemia above 250mg/dL followed by precipitous drops to 70mg/dL or less. We chose to initiate our patient on a bolus only regimen (rapid acting insulin prior to meals) which resulted in less post-prandial hyperglycemia and resolution of her hypoglycemic episodes.

Discussion:

The patient’s elevated OGTT with normal fasting glucose are consistent with the diagnosis of CFRD without FH (fasting hyperglycemia). Insulin use in CFRD patients is associated with better lung function, improvement in nutritional status, and reduction in pulmonary complications. Traditional management of CFRD starts with daily basal insulin, and published clinical care guidelines suggest CFRD with FH be started on basal or basal-bolus insulin regimens, but guidelines for patients without FH are less clear. One study showed benefits of prandial insulin in reversing weight loss, but more research is needed. An additional concern in our case was post-prandial hypoglycemia. This hypoglycemia in CF patients is likely due to impaired early insulin secretion with delayed and possibly compensatory increase in late insulin release, as well as diminished glucagon secretion in the setting of alpha cell failure. In this case, prandial insulin not only treated her hyperglycemia, but also- paradoxically- prevented her hypoglycemia.

Although there is a lack of research around initiating bolus only insulin regimens for CFRD, we believe that this is an important and appropriate first line treatment for many patients with CFRD without FH, and for prevention of hypoglycemia due to delayed and dysregulated endogenous insulin secretion.