The South Pacific Islands Resist Diabetes With Intense Training (SPIRIT) Study : investigation of obesity markers and morphological, functional and genetic changes in the skeletal muscle : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Health Sciences, Institute of Food, Nutrition and Human Health, College of Health, Massey University at Wellington, New Zealand
The skeletal muscle (SM), the major tissue for disposal of excess blood glucose, plays a big
role in development of insulin resistance leading to type 2 diabetes mellitus (T2DM). Lipid
accumulation and decline in mitochondrial activity in SM has been observed in people with T2DM.
Several studies have demonstrated that exercise has the ability to increase SM lipid oxidation and
mitochondrial activity and hence is effective as a treatment strategy for people with T2DM for
improving blood glucose control and insulin sensitivity.
The SPIRIT study was the first clinical randomised exercise trial involving a cohort of Polynesian
New Zealanders with T2DM. The uniqueness of this study is that it is the first clinical trial in
Polynesian population with grade 3 obesity (n=18; BMI 43.8 ± 9.5 kg/m2) and T2DM. The SPIRIT cohort
underwent 16 weeks of progressive resistance training (PRT) or aerobic exercise (AER) training. The
cohort showed no changes in HbA1c levels after 16 weeks of exercise and hence no improvement in
their blood glucose control. This was an unexpected result and led to the following hypothesis
which underlines this PhD study – ?In skeletal muscle of SPIRIT cohort, metabolic adaptation
to exercise is delayed due to metabolic inflexibility?.
To investigate this hypothesis, mitochondrial function and morphology, lipid droplet content and
changes in gene expression pre and post exercise intervention were examined in the SM. Since the
SPIRIT cohort showed no changes in weight, waist circumference and BMI, examination of the
concentration of specific obesity markers pre and post exercise training also occurred.
Mitochondrial function was examined pre and post 16 weeks exercise intervention by measuring the
SM activity of three key mitochondrial enzymes; citrate synthase (CS) involved in Krebs
cycle, beta-hydrxoyacyl-CoA dehydrogenase (BHAD) involved in fat oxidation and cytochrome c oxidase
(COX) involved in electron transport chain. The PRT cohort showed statistically significant
increases in activity for COX (P=0.005) and CS (P=0.007) with very large effect size (2.3 ± 1.3 and
1.8 ± 1.3 respectively). AER exercise led to significant increases in the activity for all three
enzymes COX (P=0.01), CS (P=0.03), BHAD (P=0.03) with moderate effect size for both COX and CS
activity but very large effect for BHAD (6.7 ± 1.2). For all three enzymes there were statistically
significant differences (P<0.05) between the AER and PRT groups. These results demonstrate
increased mitochondrial activity and functioning after 16 weeks of PRT or AER exercise.