Dynamic cerebral autoregulatory capacity is affected early in Type 2 diabetes

Abstract

Type 2 diabetes is associated with an increased risk of endothelial dysfunction and microvascular complications with impaired autoregulation of tissue perfusion. Both microvascular disease and cardiovascular autonomic neuropathy may affect cerebral autoregulation. In the present study, we tested the hypothesis that, in the absence of cardiovascular autonomic neuropathy, cerebral autoregulation is impaired in subjects with DM+ (Type 2 diabetes with microvascular complications) but intact in subjects with DM- (Type 2 diabetes without microvascular complications). Dynamic cerebral autoregulation and the steady-state cerebrovascular response to postural change were studied in subjects with DM+ and DM-, in the absence of cardiovascular autonomic neuropathy, and in CTRL (healthy control) subjects. The relationship between spontaneous changes in MCA V(mean) (middle cerebral artery mean blood velocity) and MAP (mean arterial pressure) was evaluated using frequency domain analysis. In the low-frequency region (0.07-0.15 Hz), the phase lead of the MAP-to-MCA V(mean) transfer function was 52+/-10 degrees in CTRL subjects, reduced in subjects with DM- (40+/-6 degrees ; P<0.01 compared with CTRL subjects) and impaired in subjects with DM+ (30+/-5 degrees ; P<0.01 compared with subjects with DM-), indicating less dampening of blood pressure oscillations by affected dynamic cerebral autoregulation. The steady-state response of MCA V(mean) to postural change was comparable for all groups (-12+/-6% in CTRL subjects, -15+/-6% in subjects with DM- and -15+/-7% in subjects with DM+). HbA(1c) (glycated haemoglobin) and the duration of diabetes, but not blood pressure, were determinants of transfer function phase. In conclusion, dysfunction of dynamic cerebral autoregulation in subjects with Type 2 diabetes appears to be an early manifestation of microvascular disease prior to the clinical expression of diabetic nephropathy, retinopathy or cardiovascular autonomic neuropathy.

The Leicester cerebral haemodynamics database: normative values and the influence of age and sex

“…Due to the highly effective control exerted by the mechanism of pressure-autoregulation, CBF is normally maintained within narrow limits for mean blood pressures (MBP) in the range 60-150 mm Hg (Paulson, Strandgaard & Edvinsson 1990). Not surprisingly, it is the CBF autoregulation mechanism itself that has been shown to be impaired in a number of conditions such as ischaemic stroke, severe head injury, carotid artery disease, intracranial hypertension, diabetes and liver failure (Aries et al 2010, Czosnyka et al 1996, Dawson et al 2000, Hauerberg, Juhler 1994, Kim et al 2008, Lagi et al 2002, Panerai 2008, White, Markus 1997, van Beek et al 2008.…”

High-Intensity Interval Exercise and Cerebrovascular Health: Curiosity, Cause, and Consequence

“…83,91 CA requires~5 seconds to initiate its protective influence; 101 therefore, explosive HIT protocols could expose the cerebrovasculature to potentially damaging increases in perfusion pressure, particularly in diseased populations with impaired autoregulation (e.g., diabetes, 102 hypertension, 103 and Alzheimer's disease 104 ). Furthermore, intense exercise can increase BBB permeability subsequent to a free radical-mediated impairment in CA, rendering the brain more susceptible to overperfusion and extracellular (vasogenic) edema; which has been shown to occur even in response to a more graduated incremental exercise test to exhaustion.…”

The Role of Actin Filament Dynamics in the Myogenic Response of Cerebral Resistance Arteries

“…Enhanced myogenic constriction at low pressure and reduced force generation with increasing pressure are observed in several conditions that have an impact on neurologic function in humans, including hypertension, cerebral vasospasm, hemorrhagic and ischemic stroke, diabetes, and head trauma. 1,[12][13][14][15][16][17]158,160,161 Impaired dilatation at low perfusion pressure in hypertension compromises blood flow reserve and increases the risk of ischemia. Conversely, impaired myogenic constriction leading to uncontrolled elevated levels of blood flow (i.e., 'breakthrough') in malignant hypertension, hemorrhagic stroke, type 2 diabetes, and trauma is associated with secondary damage owing to bloodbrain barrier disruption, small vessel rupture (microbleeds), edema, and increased intracranial pressure.…”

“…2,7 Inappropriate myogenic control of cerebral blood flow is observed in animal models of hypertension, stroke, and diabetes, and is prognostic of neurologic deterioration and poor outcome in patients with these conditions. [12][13][14][15][16][17] Current strategies to optimize cerebral perfusion pressure and improve flow autoregulation are crude (e.g., volume expansion, dopamine, or epinephrine to increase systemic pressure) and not appropriate in some clinical situations. 16 Progress in the treatment of dysfunctional cerebral autoregulation requires elucidation of the molecular basis of the myogenic response and the defects responsible for abnormal myogenic control of cerebral blood flow.…”