Hypoglycaemia in Type 1 Diabetes Patients : A Randomised Clinical Trial

Aim: To examine the metabolic, gluco-regulatory-hormonal and inflammatory cytokine responses to large reductions in rapid-acting insulin dose administered prandially before and after intensive running exercise in male type 1 diabetes patients. Methods: This was a single centre, randomised, controlled open label study. Following preliminary testing, 8 male patients (2462 years, HbA1c 7.760.4%/6164 mmol.l) treated with insulin’s glargine and aspart, or lispro attended the laboratory on two mornings at ,08:00 h and consumed a standardised breakfast carbohydrate bolus (1 g carbohydrate.kgBM; 380610 kcal) and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.160.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg BM; 660621 kcal) and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, b-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-a concentrations were measured for 180 minutes post-meal. Results: All participants were analysed. All glycaemic, metabolic, hormonal, and cytokine responses were similar between conditions up to 60 minutes following exercise. Following the post-exercise meal, serum insulin concentrations were lower under 50% (p,0.05) resulting in 75% of patients experiencing hyperglycaemia (blood glucose $8.0 mmol.l; 50% n = 6, Full n = 3). b-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-a concentrations remained similar to fasting levels under 50% but declined under Full. Under 50% IL-6 concentrations were inversely related with serum insulin concentrations (r = 20.484, p = 0.017). Conclusions: Heavily reducing rapid-acting insulin dose with a carbohydrate bolus before, and a meal after intensive running exercise may cause hyperglycaemia, but does not augment ketonaemia, raise inflammatory cytokines TNF-a and IL6 above fasting levels, or cause other adverse metabolic or hormonal disturbances. Trial Registration: ClinicalTrials.gov NCT01531855 Citation: Campbell MD, Walker M, Trenell MI, Luzio S, Dunseath G, et al. (2014) Metabolic Implications when Employing Heavy Preand Post-Exercise RapidActing Insulin Reductions to Prevent Hypoglycaemia in Type 1 Diabetes Patients: A Randomised Clinical Trial. PLoS ONE 9(5): e97143. doi:10.1371/journal.pone. 0097143 Editor: Susanne Breuer Votruba, NIDDK/NIH, United States of America Received November 18, 2013; Accepted April 14, 2014; Published May 23, 2014 Copyright: 2014 Campbell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was funded by Diabetes UK (www.diabetesorg.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: d.j.west@northumbria.ac.uk