A Single Load of Fructose Attenuates the Risk of Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes on Ultra-Long-Acting Basal Insulin: A Randomized, Open-Label, Crossover Proof-of-Principle Study

Abstract

Objective: While the adjustment of insulin is an established strategy to reduce the risk of exercise-associated hypoglycemia for individuals with type 1 diabetes, it is not easily feasible for those treated with ultra-long-acting basal insulin. The current study determined whether pre-exercise intake of fructose attenuates the risk of exercise-induced hypoglycemia in individuals with type 1 diabetes using insulin degludec.

Research design and methods: Fourteen male adults with type 1 diabetes completed two 60-min aerobic cycling sessions with or without prior intake (30 min) of 20 g of fructose, in a randomized two-period crossover design. Exercise was performed in the morning in a fasted state without prior insulin reduction and after 48 h of standardized diet. The primary outcome was time to hypoglycemia (plasma glucose ≤3.9 mmol/L) during exercise.

Results: Intake of fructose resulted in one hypoglycemic event at 60 min compared with six hypoglycemic events at 27.5 ± 9.4 min of exercise in the control condition, translating into a risk reduction of 87.8% (hazard ratio 0.12 [95% CI 0.02, 0.66]; P = 0.015). Mean plasma glucose during exercise was 7.3 ± 1.4 mmol/L with fructose and 5.5 ± 1.1 mmol/L in the control group (P < 0.001). Lactate levels were higher at rest in the 30 min following fructose intake (P < 0.001) but were not significantly different from the control group during exercise (P = 0.32). Substrate oxidation during exercise did not significantly differ between the conditions (P = 0.73 for carbohydrate and P = 0.48 for fat oxidation). Fructose was well tolerated.

Conclusions: Pre-exercise intake of fructose is an easily feasible, effective, and well-tolerated strategy to alleviate the risk of exercise-induced hypoglycemia while avoiding hyperglycemia in individuals with type 1 diabetes on ultra-long-acting insulin.

Trial registration: ClinicalTrials.gov NCT03497260.