optimal insulin correction factor in post- high intensity exercise hyperglycemia in adults with type 1 diabetes (fit)

Conditions: Diabetes Mellitus, Type 1

Summary: the overall objective of this study is to investigate the glycemic response of a 0%, 50%, 100% and 150% bolus insulin correction (based on personal insulin correction factor) of post-exercise hyperglycemia in physically active adults with type 1 diabetes (t1d) using multiple daily injections (mdi) in a controlled, but clinically representative, experimental setting.

fit is an open-label, repeated measures cross-over study. the overall objective of this study is to investigate the glycemic response of a 0%, 50%, 100% and 150% bolus insulin correction (based on personal insulin correction factor) of post-exercise hyperglycemia in physically active adults with type 1 diabetes (t1d) using multiple daily injections (mdi) in a controlled, but clinically representative, experimental setting. following a 2 week screening phase, patients will enter an 8 week transition to insulin glargine u300 (toujeo®) if on another basal insulin, in order to optimize their insulin dose and determine their individual insulin correction factor. the final phase of the study is the intervention phase, which consists of 4 separate visits. at each visit, the patient will perform 15 minutes of high intensity exercise in the morning. if they become hyperglycemic following exercise (blood glucose \>8.0 mmol/l), they will receive one of four insulin correction doses (0% 50%, 100%, or 150% of their usual correction factor) in a randomized order. they will be monitored in the clinical pharmacology unit by study staff for the rest of the day and overnight. the patient will wear a continuous glucose monitor (cgm) during each intervention visit. the primary outcome of the study is the greatest net reduction in plasma glucose (ysi) following a 50%, 100% and 150% bolus insulin correction of post-exercise hyperglycemia, compared to no bolus insulin correction. key secondary outcomes include the mean time spent in post-exercise hyperglycemia (\>8.0 mmol/l), post-exercise euglycemia (4.0-8.0 mmol/l) and post-exercise hypoglycaemia (≤ 3.9 mmol/l) within 180 minutes and 24 hours following bolus insulin correction.

Eligibility criteria:
inclusion criteria * male or female * clinical diagnosis of presumed autoimmune t1d * age 18-55 years, inclusive * duration of t1d ≥ 6 months * using mdi therapy for at least 6 months * fasting c-peptide value of \< 0.7 ng/ml (0.23 nmol/l) at screening visit * patient must be willing to undergo an 8-week run-in phase prior to the study period where they will be required to use mdi therapy at least 4 times per day, and switch from their usual basal insulin to insulin glargine u300 * exercise regularly: i.e. ≥ 30 minutes of moderate or vigorous aerobic activity ≥ 3 times/week for a minimum of 90 minutes weekly * vo2peak ≥32 ml/kg/min for females and ≥ 35 ml/kg/min for males * hba1c between 6.0-9.0% inclusive at screening visit. * insulin total daily dose (tdd) ≥ 30 u/day * in good general health with no known conditions that could influence the outcome of the trial, and in the judgement of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations * willing to adhere to the protocol requirements for the duration of the study exclusion criteria * pregnant or lactating * active diabetic retinopathy (proliferative diabetic retinopathy, or vitreous haemorrhage in past 6 months) that could potentially be worsened by the exercise protocol * any evidence of unstable cardiovascular disease, disorders or abnormalities as per physician's discretion. . * currently following a very low calorie or other weight-loss diet which may impact glucose control and mask the primary and secondary outcome measures * more than one episode of severe hypoglycemia with seizure, coma or requiring assistance of another person during the past 6 months * known hypoglycemia unawareness * use of acetaminophen (tylenol) during the run-in phase or study period * medications other than insulin that might impact outcome measures: * beta blockers * agents that affect hepatic glucose production such as beta adrenergic agonists and antagonists, xanthine derivatives * pramlintide * any non-insulin diabetes therapy

Keywords: diabetes exercise insulin