Muscle oxygen supply impairment during exercise in poorly controlled type 1 diabetes

Semah Tagougui, Erwan Leclair, Pierre Fontaine, Régis Matran, Gaelle Marais, Julien Aucouturier, Aurélien Descatoire, Anne Vambergue, Kahina Oussaidene, Georges Baquet, Elsa Heyman, Semah Tagougui, Erwan Leclair, Pierre Fontaine, Régis Matran, Gaelle Marais, Julien Aucouturier, Aurélien Descatoire, Anne Vambergue, Kahina Oussaidene, Georges Baquet, Elsa Heyman

Abstract

Purpose: Aerobic fitness, as reflected by maximal oxygen (O2) uptake (VO2max), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence O2 supply including O2 delivery and release to active muscles during maximal exercise.

Methods: Two groups of patients with uncomplicated type 1 diabetes (T1D-A, n = 11, with adequate glycemic control, HbA1c <7.0%; T1D-I, n = 12 with inadequate glycemic control, HbA1c >8%) were compared with healthy controls (CON-A, n = 11; CON-I, n = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine VO2max. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O2 transport and factors able to shift the oxyhemoglobin dissociation curve.

Results: Arterial O2 content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, VO2max was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A.

Conclusions: Poorly controlled patients displayed lower VO2max and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy.

Trial registration: ClinicalTrials.gov NCT02051504.

Figures

FIGURE 1
FIGURE 1
Recordings made by NIRS from the vastus lateralis. Change in ΔTHb (A and B), change in ΔO2Hb (C and D), and change in ΔHHb (E and F). Values are means ± SE. T1D-I, black squares; CON-I, white squares; T1D-A, black triangles; CON-A, white triangles. Post hoc analyses for group effect: significantly different from controls at *P < 0.05 and ***P < 0.01. Post hoc analyses for time effect: significantly different from rest at †P <0.05, ††P < 0.01, and †††P < 0.001.

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