Sources of Inter-individual Variability in the Therapeutic Response of Blood Glucose Control to Exercise in Type 2 Diabetes: Going Beyond Exercise Dose

In the context of type 2 diabetes, inter-individual variability in the therapeutic response of blood glucose control to exercise exists to the extent that some individuals, occasionally referred to as "non-responders," may not experience therapeutic benefit to their blood glucose control. This narrative review examines the evidence and, more importantly, identifies the sources of such inter-individual variability. In doing so, this review highlights that no randomized controlled trial of exercise has yet prospectively measured inter-individual variability in blood glucose control in individuals with prediabetes or type 2 diabetes. Of the identified sources of inter-individual variability, neither has a prospective randomized controlled trial yet quantified the impact of exercise dose, exercise frequency, exercise type, behavioral/environmental barriers, exercise-meal timing, or anti-hyperglycemic drugs on changes in blood glucose control, in individuals with prediabetes or type 2 diabetes. In addition, there is also an urgent need for prospective trials to identify molecular or physiological predictors of inter-individual variability in the changes in blood glucose control following exercise. Therefore, the narrative identifies critical science gaps that must be filled if exercise scientists are to succeed in optimizing health care policy recommendations for type 2 diabetes, so that the therapeutic benefit of exercise may be maximized for all individuals with, or at risk of, diabetes.