Technetium-99m sestamibi retention in skeletal muscles, a potential indicator of mitochondrial function and anaerobic threshold in patients with type 2 diabetes

Abstract

In this study, we investigated the retention of technetium-99m sestamibi (MIBI), a radiopharmaceutical that accumulates in mitochondria, in patients with type 2 diabetes. We hypothesized that patients with type 2 diabetes had lower MIBI counts in their legs than nondiabetic volunteers, and that these abnormalities reflected a low anaerobic threshold (AT) during cardiopulmonary exercise testing (CPX). Eight non-diabetic volunteers (Group N) and 11 patients with type 2 diabetes (Group D) underwent CPX. Mitochondrial function was assessed using MIBI imaging of both legs. The MIBI counts in the legs were significantly lower in Group D than in Group N (D vs. N: 74.1 vs. 94.1 counts/pixel, p < 0.05). Similarly, peak oxygen uptake (peakV ・ O 2 ) and AT were lower in Group D than in Group N (peakV ・ O 2 : 19.8 vs. 26.5 ml/kg/min, p < 0.05; AT: 13.1 vs. 17.2 ml/kg/min, p < 0.05). A strong correlation was observed between MIBI counts and the peakV ・ O 2 and AT (peakV ・ O 2 : r = 0.62, p < 0.01; AT: r = 0.76, p < 0.01). After the exclusion of an outlying subject, the correlation between peakV ・ O 2 and MIBI count in the legs was lost (r = 0.28, p = 0.26); however, the AT correlation was maintained (r = 0.59, p = 0.01). Patients with type 2 diabetes had reduced skeletal muscle MIBI counts, indicating reduced mitochondrial function. This abnormality may be linked to a low AT.

Evaluation of oxygen uptake adjusted by skeletal muscle mass in cardiovascular disease patients with type 2 diabetes

“…Recent genetic research in patients with diabetes revealed a positive correlation between general aerobic capacity and the expression of a coregulated subset of oxidative phosphorylation (OXPHOS) genes (OXPHOS-CR) regulated by PGC-1α, which is positively correlated with general VO 2 34) . Our finding of a lower peak VO 2 in patients with diabetes mellitus may be related to muscle metabolism, as described in previous studies [25][26][27][28][29][30][31][32][33][34] . Endothelial dysfunction in diabetic patients is also one of the causes of impaired exercise tolerance 35) , however, it could not be evaluated in this study.…”

“…These results suggest that the difference of peak VO 2 /SMM might be an effect of skeletal muscle metabolism. Impairment of skeletal muscle metabolism in patients with diabetes [25][26][27][28][29] reduces exercise tolerance due to impairment of carbohydrate metabolism, lipid metabolism 30) , insulin resistance, and insulin sensitivity [31][32][33] . Recent genetic research in patients with diabetes revealed a positive correlation between general aerobic capacity and the expression of a coregulated subset of oxidative phosphorylation (OXPHOS) genes (OXPHOS-CR) regulated by PGC-1α, which is positively correlated with general VO 2 34) .…”