Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial

Abstract

Introduction: Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes.

Methods: Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, β-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise.

Results: Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar.

Conclusions: Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances.

Clinical trials number: NCT02204839, ClinicalTrials.gov.

Keywords: Exercise; Hypoglycemia; Insulin; Type 1.

Figure 1

Time-course changes in morning time fasted and daytime blood glucose concentrations. Data presented as mean±SEM. Diamonds=100%, circles=80%. *Indicates a significant difference in blood glucose between 100% and 80% (p≤0.05). Morning 1, baseline morning.

Figure 2

(A–C) Time-course changes in morning time fasted, and daytime (A) IL-6, (B) TNF-α, and (C) β-hydroxybutyrate concentrations. Data presented as mean±SEM. Diamonds=100%, circles=80%. *Indicates a significant difference in blood glucose between 100% and 80% (p≤0.05). Morning 1, baseline morning visit; Morning 2, next day morning visit; IL-6, interleukin 6; TNF-α, tumor necrosis factor α.

Figure 3

Time-course changes in interstitial glucose concentrations throughout the postlaboratory period. Data presented as mean±SEM. Black trace=100%, red trace=80%. *Indicates a significant difference in interstitial glucose area under the curve between 100% and 80% (p≤0.05). Vertical dashed line break indicates late-evening, nocturnal or daytime periods.