Cerebral vs. Cardiovascular Responses to Exercise in Type 2 Diabetic Patients

Abstract

The human brain is constantly active and even small limitations to cerebral blood flow (CBF) may be critical for preserving oxygen and substrate supply, e.g., during exercise and hypoxia. Exhaustive exercise evokes a competition for the supply of oxygenated blood between the brain and the working muscles, and inability to increase cardiac output sufficiently during exercise may jeopardize cerebral perfusion of relevance for diabetic patients. The challenge in diabetes care is to optimize metabolic control to slow progression of vascular disease, but likely because of a limited ability to increase cardiac output, these patients perceive aerobic exercise to be more strenuous than healthy subjects and that limits the possibility to apply physical activity as a preventive lifestyle intervention. In this review, we consider the effects of functional activation by exercise on the brain and how it contributes to understanding the control of CBF with the limited exercise tolerance experienced by type 2 diabetic patients. Whether a decline in cerebral oxygenation and thereby reduced neural drive to working muscles plays a role for "central" fatigue during exhaustive exercise is addressed in relation to brain's attenuated vascular response to exercise in type 2 diabetic subjects.

Keywords: cardiac output; cerebral blood flow; cerebral metabolism; cerebral oxygenation; diabetes; vascular conductance.

Figure 1

Cerebrovascular response to exercise in eight male type 2 diabetic patients without symptomatic cardio-vascular disease (closed circles) vs. seven age and gender matched healthy subjects (open circles) at the same absolute (left panels) and relative workload (right panels). (A) Cerebral blood flow derived from the Fick principle (CBF_Fick) from inverse arterial-jugular venous oxygen difference, (B) middle cerebral artery mean blood flow velocity (MCA V_mean), (C) cerebrovascular conductance index (CVCi), and (D) rating of perceived exertion (RPE; Borg scale). The patients demonstrated a decline in cerebral perfusion and oxygenation during incremental exercise associated with attenuated increases in cerebral and systemic vascular conductance compared with healthy controls. Cerebral oxygenation reached its lowest level at exhaustion at a 20% lower workload in type 2 diabetes mellitus (T2DM) patients than healthy controls and patients expressed a higher RPE than healthy controls. ^†p < 0.05 and ^‡p < 0.01 vs. rest; ^*p < 0.05 and ^**p < 0.01 vs. control subjects. Values are mean ± SD (modified from Kim et al., 2015).

Figure 2

Middle cerebral artery mean blood flow velocity (MCA V_mean) at rest and during exercise at the same relative workload in young individuals (black circles), and in middle-aged subjects without (gray circles), and with type 2 diabetes (T2DM; open circles). During submaximal and during maximal exercise, cerebral perfusion was reduced in older individuals compared with young individuals, and the more so in the older diabetic patients. Values are mean ± SEM (adapted from Fisher et al., 2013; Kim et al., 2015).