Hypoglycaemia in cystic fibrosis during an extended oral glucose tolerance test.

BACKGROUND Hypoglycaemia 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 aetiology. AIM The aims of this study were to perform a three hour OGTT in participants with CF and 1) document glucose, insulin, glucagon, GLP-1 and GIP release patterns within varying glucose tolerance groups during the OGTT; 2) determine the prevalence of hypoglycaemia during the OGTT and 3) define any association between hypoglycaemia and patterns of insulin, glucagon, GLP-1 and GIP release. METHOD Eligible participants attending an adult CF clinic completed a three hour OGTT. Hypoglycaemia on OGTT was defined as mild (glucose 3.4-3.9mmol/L), moderate (glucose 3.1- 3.3mmol/L) and severe (glucose ≤ 3mmol/L). Hormones were measured at fasting, 30, 60, 120 and 180 minutes. RESULTS Twenty-four participants completed the study, of which seven had normal glucose tolerance (NGT), twelve had abnormal glucose tolerance (AGT) and five had cystic fibrosis related diabetes (CFRD). All participants had a delayed insulin response compared to normative data. All glucose tolerance groups showed appropriate and similar suppression of fasting glucagon. Four participants (17%) had mild hypoglycaemia, 3 (13%) had moderate hypoglycaemia and eight (33%) had severe hypoglycaemia. No participant with CFRD demonstrated hypoglycaemia. Of the 19 participants without CFRD, 15 (79%) experienced hypoglycaemia. Participants with hypoglycaemia had greater peak glucose and insulin responses than those that did not have hypoglycaemia, and this approached significance (p=0.0625 for glucose and p=0.0862 for insulin). No significant mean differences between GLP-1 and GIP release were found. There was no relationship between hypoglycaemia and modulator therapy. CONCLUSION Post-prandial hypoglycaemia was unmasked by the extension of an OGTT to three hours. Delayed and abnormal insulin release, and ineffective counter-regulatory action of glucagon may have a role in its aetiology. This article is protected by copyright. All rights reserved.