Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects

Abstract

Aims/hypothesis Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls. Methods In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.4±1 and 29.3±0.9 kg/m 2 respectively) in vivo mitochondrial function was determined by measuring phosphocreatine recovery halftime (PCr half-time) immediately after exercise, using phosphorus-31 magnetic resonance spectroscopy. IMCL content was determined by proton magnetic resonance spectroscopic imaging and insulin sensitivity was measured with a hyperinsulinaemic-euglycaemic clamp. Results The PCr half-time was 45% longer in diabetic patients compared with controls (27.3±3.5 vs 18.7±0.9 s, p<0.05), whereas IMCL content was similar (1.37±0.30 vs 1.25±0.22% of the water resonance), and insulin sensitivity was reduced in type 2 diabetes patients (26.0±2.2 vs 18.9± 2.3 μmol min −1 kg −1 , p<0.05 [all mean±SEM]). PCr halftime correlated positively with fasting plasma glucose (r 2 =0.42, p < 0.01) and HbA 1c (r 2 = 0.48, p <0.05) in diabetic patients. Conclusions/interpretation The finding that in vivo mitochondrial function is decreased in type 2 diabetes patients compared with controls whereas IMCL content is similar suggests that low mitochondrial function is more strongly associated with insulin resistance and type 2 diabetes than a high IMCL content per se. Whether low mitochondrial function is a cause or consequence of the disease remains to be investigated.

Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes

“…When mitochondrial activity was determined per muscle weight (i.e. muscle oxidative capacity), studies have either shown no differences [3][4][5] or a lower [6][7][8][9][10][11][12] mitochondrial activity in insulin-resistant participants. Studies that have related mitochondrial activity to markers of mitochondrial volume (intrinsic mitochondrial activity) have either shown a lower [6,12,13] or no difference [9-11, 14, 15] in mitochondrial activity in insulin-resistant participants.…”

Comparison of measuring energy metabolism by different 31P‐magnetic resonance spectroscopy techniques in resting, ischemic, and exercising muscle

“…An alternate 31 P-magnetic resonance spectroscopy technique, based on exercise recovery experiments, has been used extensively to investigate mitochondrial function in various phenotypes (7,8) and more recently also in insulin resistance and T2DM (9,10). Purely aerobic, mixed, or anaerobic exercise is used to deplete PCr.…”

Phosphorus‐31 magnetic resonance spectroscopy of skeletal muscle in maternally inherited diabetes and deafness A3243G mitochondrial mutation carriers

“…The recently published results of de Feyter et al (17) did not show an effect of insulin resistance or type 2 DM on mitochondrial function when compared to healthy normoglycemic controls, which is in accordance with our study results. In the current study we did not perform proton MRS to further evaluate mitochondrial dysfunction and the association with insulin resistance, as shown in previous studies (15,17). Thus, the exact relationship between DM per se and skeletal muscle phosphate metabolism remains to be clarified, but our results clearly indicate an effect of the MIDD mutation itself on phosphate metabolism.…”

“…Recently, Schrauwen-Hinderling et al (15) applied 31 P-MR spectroscopy in the vastus lateralis muscle to study mitochondrial function in overweight type 2 DM patients and BMI-matched control subjects. They reported a longer PCr recovery half-time in the type 2 diabetes group when compared to the control group.…”

“…Accordingly, the objective of the current study was to investigate with 31 P-MRS whether the presence of the A3243G mitochondrial mutation in the MIDD phenotype affects high-energy phosphate metabolism in the striated skeletal muscle of patients with the A3243G MIDD mutation. As alterations in phosphate metabolism in MIDD patients may be attributed to DM (15)(16)(17)(18)(19), we included both DM and non-DM MIDD patients.…”