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Conference Summaries

Exercise & Diabetes

Exercise therapy for type 2 diabetes: a responder/non-responder issue?

Presented by:
Dominik Pesta, PhD
German Center for Diabetes Research (DZD), München-Neuherberg, Germany

Exercise interventions are recommended in most guidelines for the treatment of type 2 diabetes (T2D). Although most guidelines suggest a combination of both aerobic and resistance training, the exact benefits of these interventions remain unclear.

Two types of exercise have been extensively examined in T2D: endurance training and resistance training. It is widely held that exercise in general has many health benefits for individuals with T2D, and it has been known for many decades that muscle contraction stimulates glucose uptake by cells. Notwithstanding, variable responses to aerobic exercise training have been reported by several groups. Indeed, roughly 20% of subjects can be considered as ‘non-responders’ to exercise training as seen by endpoints such as changes on VO2 max, fasting glucose, body weight and insulin sensitivity.

Some authors have suggested that intersubject variability in restoring glycaemic control following exercise might be explained mainly by changes in insulin secretion1. In fact, a decreased capacity to secrete insulin may be related to the profound degree of glucotoxicity that exists in subjects with T2D, and glucotoxicity also predicts poorer training induced increases in ß-cell function. However, other factors should also be considered such as meal timing and time of day, as for example peak performance depends on the circadian phenotype. There may also be effects of drugs such as metformin on exercise, and exercise is also known to induce changes in the gut microbiome. Thus, response variability to exercise may be explained by a range of factors.

It has been reported that for a fixed amount of exercise, increasing exercise intensity to that consistent with consensus recommendations eliminated the cardiorespiratory fitness nonresponse2. Unfortunately, low-intensity exercise may not be sufficient to improve cardiorespiratory fitness for a substantial proportion of sedentary obese adults. The relatively high proportion of non-responders also poses compelling challenges for personalised, preventive medicine.

However, it is likely that some degree of metabolic improvement will be obtained by exercise, independent of the level of cardiovascular fitness achieved, with likely improvement, albeit variable, in HbA1c levels. This was shown in the HART-D study wherein participants were randomised to a control group or one of three supervised exercise training groups for 9 months3. In that study, both fitness responders and non-responders had significant improvements in HbA1c and measures of adiposity.

A number of genetic factors have been linked with exercise-mediated metabolic changes. Some of the polymorphisms identified include those in PPARγ, ß3-adrenergic receptor and PPARδ. Kacerovsky-Bielesz and colleagues also identified a single nucleotide polymorphism that is associated with the response of muscle ATP synthesis to long-term exercise training4. In particular, 6 of 8 responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (p = 0.019), which encodes a subunit of mitochondrial complex I, suggesting that genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.

Unpublished data by Dr. Pesta has shown that the NDUFB6 polymorphism can indeed identify responders and non-responders to exercise training. The long-term study also looked at the association between physical activity levels and changes in insulin sensitivity over a 5-year period. Metabolic changes in non-responders were found, including improvements in fasting C-peptide and HbA1c. Baseline insulin sensitivity was also seen to affect the response to changes in physical activity.

Key messages / Clinical Perspectives

  • Improvement in metabolic parameters can occur independently of changes in cardiorespiratory fitness.
  • Insulin sensitivity and hyperglycaemia at baseline can potentially impact training induced modifications in whole-body glucose disposal.
  • Genetic predisposition, amount (min/week) and intensity are important determinants of cardiorespiratory fitness and metabolic response to exercise.
  • Response variability after exercise training with regards to certain endpoints exists in the general population as well as in individuals with T2D.
  • Further understanding of the physiological basis of non-response to exercise training is clinically important and will help to further personalise exercise prescription strategies.


Present disclosure: The presenter has reported that no relationships exist relevant to the contents of this presentation.

Written by: Patrick Moore, PhD

Reviewed by: Marco Gallo, MD


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