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

Abstract

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.

Effectiveness of high‐intensity interval training combined with resistance training versus continuous moderate‐intensity training combined with resistance training in patients with type 2 diabetes: A one‐year randomized controlled trial

“…Similar results were found for medium‐term interventions (8–16 weeks), with small to large improvements in HbA1c and in oral glucose tolerance test‐derived variables, including fasting blood glucose and HOMA‐IR . The differences between these results and our own might be explained by several sources of inter‐individual variability, including exercise dose, exercise frequency, exercise type, behavioral/environmental barriers, exercise‐meal timing, or the effect of anti‐hyperglycaemic drugs on changes in blood glucose control . For instance, although substantial changes in pharmacological therapy (ie, changing from oral medication to insulin therapy) constituted removal from PPA, more subtle changes in oral medication were not controlled, which may have blunted the effects of the exercise groups on glycaemic control.…”

“…10,13,14,16,27,28 The differences between these results and our own might be explained by several sources of inter-individual variability, including exercise dose, exercise frequency, exercise type, behavioral/ environmental barriers, exercise-meal timing, or the effect of antihyperglycaemic drugs on changes in blood glucose control. 29 For instance, although substantial changes in pharmacological therapy (ie, changing from oral medication to insulin therapy) constituted removal from PPA, more subtle changes in oral medication were not controlled, which may have blunted the effects of the exercise groups on glycaemic control. On the other hand, the first month and a half was used as a period of adaptation in the HIIT group, in order to prepare patients for the HIIT protocol (1:1 bouts at 90% HRR).…”

GWAS reveal a role for the central nervous system in regulating weight and weight change in response to exercise

“…With regard to the exercise-induced weight change, the large amount of variation seen in the response, ranging from weight gain to weight loss, is consistent with what has been observed in mice as well as humans (Hiramatsu & Garland, 2018;Kelly et al, 2014;King et al, 2017;Pickering & Kiely, 2019;Solomon, 2018;Stephens & Sparks, 2015;Vellers et al, 2018). The fact that female flies show a clear correlation between the amount of exercise performed and the exercise-induced weight change is a promising result, that will require further study.…”

Prevalence of responders for hepatic fat, adiposity and liver enzyme levels in response to a lifestyle intervention in children with overweight/obesity: EFIGRO randomized controlled trial

“…Previous studies have observed that several individuals reduced their resting energy expenditure, increased energy intake, lowered physical activity levels or reduced fat oxidation rate in response to the exercise‐associated increase of energy expenditure or energy intake restriction programs . On the other hand, although differences in the adherence to the intervention programs could also explain interindividual variability in the responsiveness, it has not been previously studied . As far as we are aware, there are no previous studies comparing the prevalence of responders between two different lifestyle programs differentiated by the inclusion or not of exercise.…”