Heterogeneity in limb fatty acid kinetics in type 2 diabetes

Abstract

Aims/hypothesis: In order to test the hypothesis that disturbances in skeletal muscle fatty acid metabolism with type 2 diabetes are not equally present in the upper and lower limbs, we studied fatty acid kinetics simultaneously across the arm and leg of type 2 diabetic patients (n=6) and matched control subjects (n=7) for 5 h under baseline conditions and during a 4-h hyperinsulinaemiceuglycaemic clamp. Methods: Limb fatty acid kinetics was determined by means of continuous [U-13 C]palmitate infusion and measurement of arteriovenous differences. Results: The systemic palmitate rate of appearance was 3.6±0.4 and 2.7±0.3 μmol·kg lean body mass −1 ·min −1 and decreased during the clamp by 26% (p=0.04) and 43% (p<0.01) in the diabetic patients and in the control subjects respectively. At baseline, palmitate uptake across the arm was similar in the two groups, whereas leg palmitate uptake was lower than in the arm in the diabetic patients. During the clamp, palmitate uptake decreased in the arm (−48%, p=0.02) and the leg (−38%, p=0.04) of the control subjects, whereas it decreased in the arm (−30%, p=0.04) but not in the leg of the diabetic patients. Similarly, during the clamp palmitate release was substantially suppressed in the arm (−47%, p<0.01) and the leg of the control subjects (−45%, p<0.01), but only in the arm of the diabetic patients (−45%, p<0.01). Conclusions/interpretation: The present data indicate that type 2 diabetes is characterised by heterogeneity in the dysregulation of skeletal muscle fatty acid metabolism, with only the leg, but not the arm, showing an impairment of fatty acid kinetics at baseline and during a hyperinsulinaemic-euglycaemic clamp causing a physiological increase in insulin concentration.

Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery

“…Fasting whole-body fat oxidation rates were greater in the diabetes patients. This seems to be in contrast to some [14][15][16][17][18][19], but not all [12,13,36], previous studies, which describe normal and/or decreased basal whole-body fatty acid oxidation rates in the type 2 diabetic state [14][15][16][17][18][19]. These apparently contradictory findings are explained by the fact that long-term-diagnosed diabetes patients were selected to participate in the present study.…”

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans

“…53 The present findings have several implications. As previously shown by others, [18][19][20] our data indicate that muscle metabolism has a non-homogeneous distribution between arms and legs. The fact that, in other populations, arm and leg muscles are different in terms of glucose clearance 18 and also in FA kinetics, with the legs but not the arms being impaired at baseline and during a hyperinsulinemiceuglycaemic clamp, 20 is in line with our findings, in which increased fat oxidation in PO subjects was only observed during leg exercise, but not during arm exercise.…”

“…19 Furthermore, there is some evidence of heterogeneity in limb fatty acid (FA) kinetics in patients with type 2 diabetes compared with controls (C), 20 implying that arm muscle may be metabolically different from leg muscle. In a recent study, we demonstrated that maximal fat oxidation (MFO) was lower during exercise with the arms than with the legs in type 2 diabetics and in lean and O controls.…”

Effect of exercise training on neuromuscular function of elbow flexors and knee extensors of type 2 diabetic patients

“…The upper and lower 13 extremities have been previously shown to be affected by type 2 diabetes to different 14 extents, with lower limbs showing a more pronounced impairment of strength and 15 greater metabolic derangement (Andersen et al, 2004;Christer . et al, 2006;Ibáñez 16 et al, 2008;Ijzerman et al, 2012;Won Park et al, 2006Olsen et al, 2005;17 Sacchetti et al, 2005). The higher neuromuscular impairment in the KE could be 18 responsible for a lower baseline muscular capacity compared to the EF and, thus, a 19 greater "gap to fill" with training.…”