title: Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial.
abstract: OBJECTIVE
  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 (24±2 years, HbA1c 7.7±0.4%/61±4 mmol.l-1) 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.kg-1BM; 380±10 kcal) and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.1±0.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg-1BM; 660±21 kcal) and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, β-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-α 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-1; 50% n = 6, Full n = 3). β-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-α 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 = -0.484, 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-α and IL-6 above fasting levels, or cause other adverse metabolic or hormonal disturbances.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01531855.
authors.affiliation: Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Campbell
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Walker
authors.affiliation: Institute for Ageing and Health, Faculty of Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Trenell
authors.affiliation: Diabetes Research Group, College of Medicine, Swansea University Swansea, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Luzio
authors.affiliation: Diabetes Research Group, College of Medicine, Swansea University Swansea, United Kingdom.
authors.forename: Gareth
authors.initials: G
authors.lastname: Dunseath
authors.affiliation: Applied Sports, Technology, Exercise and Medicine Research Centre, College of Engineering, Swansea University, Swansea, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tuner
authors.affiliation: Applied Sports, Technology, Exercise and Medicine Research Centre, College of Engineering, Swansea University, Swansea, United Kingdom.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bracken
authors.affiliation: Diabetes Research Group, College of Medicine, Swansea University Swansea, United Kingdom.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bain
authors.affiliation: Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Russell
authors.affiliation: Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Stevenson
authors.affiliation: Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: West
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D015444:Exercise; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D061266:Insulin, Short-Acting / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D012146:Rest; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D061266:Insulin, Short-Acting; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha