Discussion
diabetes, IAH, hypoglycaemia
DIABETES, TYPE 1 DIABETES, HYPOGLYCAEMIA
In this pilot study in people with type 1 diabetes who have IAH we found that, compared with control participants who used RT-CGM alone, participants who underwent 4 weeks of HIIT in combination with RT-CGM had greater noradrenaline, glucagon and total and autonomic symptom responses during a subsequent hypoglycaemia clamp study. In addition, while overall differences between groups were not statistically significant, possibly because of the relatively small number of participants in this pilot trial, there were 29% fewer total hypoglycaemic episodes, 21% fewer level 1 hypoglycaemic episodes and 56% fewer level 2 hypoglycaemic episodes in those undergoing HIIT in combination with RT-CGM compared with those using RT-CGM alone. These findings suggest that there are sustained effects of HIIT on the CRR to hypoglycaemia in people with type 1 diabetes and IAH, at least over a 4 week period, and that HIIT, at the very least, is a safe form of exercise in this cohort who are most at risk of hypoglycaemia. Our study population of adults with type 1 diabetes was typical of those people previously self-reported in Scotland to have IAH in terms of median age and duration of diabetes.Habituation is a form of adaptive memory described as a reduction of the psychological, behavioural or physiological responses to a stimulus as a result of repeated or prolonged exposure [The current study was designed to establish whether people with IAH and type 1 diabetes might adapt to recurrent HIIT in the same way as they do to recurrent hypoglycaemia, which would make this intervention less useful clinically. This is referred to as habituation to the dishabituating stimulus [Our results differ from those of previous experimental studies in people with type 1 diabetes that found that moderate intensity exercise led to suppression of the CRR to subsequent hypoglycaemia [The reduced symptom response following 4 weeks of RT-CGM in the control group was unexpected. This change in the symptom response was not accompanied by significant reductions in adrenaline and noradrenaline responses during the second hypoglycaemic clamp, which might have been expected if this was an effect of greater exposure to hypoglycaemia in the control participants. Nevertheless, while differences between groups in total exposure to level 1 and level 2 hypoglycaemia during the 4 week intervention period were not significant, there were fewer hypoglycaemic episodes (21% and 56%, respectively) in the HIIT cohort. Unfortunately, RT-CGM data were not collected prior to randomisation and so it is not clear if RT-CGM use resulted in an increase in participant exposure to hypoglycaemia. Longer-term RT-CGM interventions in people with well-controlled type 1 diabetes and IAH have shown that RT-CGM reduces hypoglycaemia frequency and duration [An unexpected finding in the present study was the significant increase in plasma glucagon during hypoglycaemia following RT-CGM+HIIT. A small, but non-significant increase in glucagon was also seen during next-day hypoglycaemia after a single bout of HIIT in our previous study [There are a number of limitations to this study. The hyperinsulinaemic–hypoglycaemic clamp is the gold standard technique for assessing CRR to hypoglycaemia [In conclusion, in this pilot clinical trial we have shown that a 4 week programme of HIIT using a cycle ergometer in combination with RT-CGM for people with type 1 diabetes who have IAH improves aspects of the CRR to hypoglycaemia in comparison to the use of RT-CGM alone. Importantly, we found that the glucagon CRR to hypoglycaemia was improved by HIIT both relative to the control condition and baseline. The unexpected HIIT-mediated amplification of the glucagon response to insulin-induced hypoglycaemia is a potentially important finding that warrants further investigation, given that the glucagon response to insulin-mediated hypoglycaemia is almost universally absent in people with type 1 diabetes of >5 years’ duration. Although our findings need to be explored further and replicated in studies of longer duration, they suggest that HIIT-mediated dishabituation, at least over a 4 week period, may remain beneficial to people with type 1 diabetes and IAH. In addition, the study also suggests that HIIT programmes may be safely implemented in type 1 diabetes, even in those individuals most at risk of hypoglycaemia.