Exercise to preserve beta cell function in recent-onset type 1 diabetes mellitus (EXTOD) - a randomized controlled pilot trial

Physical exercise preserves beta cell function in humans with type 2 diabetes. Exercise also reduces insulitis and preserves beta cell function in the NOD mouse model of type 1 diabetes (T1D). We hypothesised that exercise will also preserve beta-cell function in humans with T1D, and undertook a pilot trial to test this hypothesis. A randomised controlled trial in adults diagnosed with T1D within the previous three-months was undertaken. Participants were assigned to usual care or exercise intervention, in a 1:1 ratio for 12-months. The primary outcomes were recruitment rate, exercise adherence, drop out, exercise uptake in the control group. The secondary outcome was rate of loss of beta-cell function. Of 507 individuals who were approached, 58 entered the study (28 usual care, 30 exercise arm). Exercise increased in the exercise group (245 to 273minutes/week) and 61% reached the exercise target of greater than 150minutes/week on atleast 42 weeks of the year. Exercise levels fell in the control group (280 to 231minutes/week). The exercise group became more insulin sensitive and required less insulin. The rate of loss of beta-cell function, estimated by AUC C peptide, did not differ between the study groups. However when the effect of the improved insulin sensitivity (which will contribute to a lower C peptide response) was accounted for, beta cell function was preserved in the exercise group, but fell in the usual care group. We show that it is possible to recruit and randomise newly-diagnosed T1D patients to a trial of an exercise intervention and increase and maintain their exercise levels for 12-months. We show also that physical exercise has the potential to preserve beta cell function in T1D, and mechanisms for this are being explored. Future trials need to include more appropriate measures of beta-cell function.