Citation: Armaghanian N, Hetherington J, Parameswaran V, Chua EL, Markovic TP, Brand-Miller J, Steinbeck K (2020). Hypoglycemia in cystic fibrosis during an extended oral glucose tolerance test. Pediatric Pulmonology. 2020; 55: 3391– 3399.



Background: Hypoglycemia in cystic fibrosis (CF), in the absence of glucose-lowering therapies, has long been identified as an important issue in the management of CF. There is currently still no unifying hypothesis for its etiology.

Aim: The aims of this study were to perform a 3-h oral glucose tolerance test (OGTT) in participants with CF and (1) document glucose, insulin, glucagon, glucagon-like-peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) release patterns within varying glucose tolerance groups during the OGTT; (2) determine the prevalence of hypoglycemia during the OGTT; and (3) define any association between hypoglycemia and patterns of insulin, glucagon, GLP-1, and GIP release.

Methods: Eligible participants attending an adult CF clinic completed a 3-h OGTT. Hypoglycemia on OGTT was defined as mild (glucose 3.4–3.9 mmol/L), moderate (glucose 3.1–3.3 mmol/L), and severe (glucose ≤ 3 mmol/L). Hormones were measured at fasting, 30, 60, 120, and 180 min.

Results: Twenty-four participants completed the study, of which 7 had normal glucose tolerance, 12 had abnormal glucose tolerance, and 5 had cystic fibrosis related diabetes (CFRD). All participants had a delayed insulin response compared with normative data. All glucose tolerance groups showed appropriate and similar suppression of fasting glucagon. Four participants (17%) had mild hypoglycemia, three (13%) had moderate hypoglycemia, and eight (33%) had severe hypoglycemia. No participant with CFRD demonstrated hypoglycemia. Of the 19 participants without CFRD, 15 (79%) experienced hypoglycemia. Participants with hypoglycemia had greater peak glucose and insulin responses than those that did not have hypoglycemia, and this approached significance (p = .0625 for glucose and p = .0862 for insulin). No significant mean differences between GLP-1 and GIP release were found. There was no relationship between hypoglycemia and modulator therapy.

Conclusion: Postprandial hypoglycemia was unmasked by the extension of an OGTT to 3 h. Delayed and abnormal insulin release, and ineffective counter-regulatory action of glucagon may have a role in its etiology.

About The Authors


Dr Natasha Armaghanian is a research officer based at the Academic Department of Adolescent Medicine...


Kate Steinbeck is an endocrinologist and adolescent physician, and Professor and Medical Foundation ...