Clinical ScienceBlunted cerebral oxygenation during exercise in women with gestational diabetes mellitus: associations with macrovascular function and cardiovascular risk factors
Introduction
Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed after the first trimester of pregnancy that is not either type 1 (T1DM) or type 2 diabetes (T2DM) [1]. GDM, despite its transient nature, it has been associated with an increased risk of maternal long-term complications. Women with a history of GDM are at increased risk of developing cardiovascular disease (CVD), although to a lesser extent than patients with type 1 and type 2 diabetes [[2], [3], [4]]. On top of CVD, T1DM and T2DM have been associated with an increased risk of cerebrovascular disease, as metabolic disturbances and blood flow dysregulation can have profound effects on brain structure and vasculature [5]. These disturbances can preferentially affect frontal and temporal regions of the brain, with possible implications on cognitive function and motor control [6]. In fact, lower cerebral oxygenation and increased fatigability during exercise have been described in non-pregnant adults with T2DM [7]. However, the association between GDM and cerebrovascular function and disease is less clear [8]. A recent study [9] demonstrated that women with a history of GDM are at increased risk of ischemic stroke, seven years after delivery as compared with unaffected women. Despite this scarce evidence, the early effect of GDM on cerebrovascular function during pregnancy has not been studied so far.
Cerebral oxygenation can serve as an indirect index of cerebrovascular function, as it depends on blood flow and endothelial integrity [10,11]. Near-infrared spectroscopy (NIRS) has been used to continuously and non-invasively study cerebral oxygenation [12,13]. NIRS assesses cerebral oxygen delivery and usage by cerebral tissue, through the evaluation of oxy- (O2Hb) and deoxy-hemoglobin (HHb) alterations, thus, indirectly providing information on cerebrovascular endothelial function [14,15]. During exercise, cerebral oxygenation increases in healthy humans [16], due to an increase in regional total hemoglobin (tHb) and O2Hb [17]. This increase in O2 delivery is important, as brain function can deteriorate when its oxygenation is reduced. Moreover, a blunted cerebral oxygenation can reduce motor drive to the exercising muscle and accelerate fatigue [18].
The primary aim of this study was to examine cerebral oxygenation estimated by NIRS during intermittent submaximal handgrip exercise and recovery, in pregnancies complicated by GDM and unaffected pregnancies. A secondary aim was to evaluate the association of cerebral oxygenation parameters with macrovascular dysfunction indices and cardiovascular risk factors.
Section snippets
Study Characteristics
Cross-sectional, observational, controlled study.
Participants
The study included 37 pregnant women, 25–42 years old, referred to the Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Greece during 2015–2016. The GDM group consisted of 21 pregnant women diagnosed with GDM and the control group of 16 healthy pregnant women. Inclusion criteria for the GDM group were: gestational age 26–32 weeks, maternal age > 18 years, singleton pregnancy,
Baseline and Exercise Protocol Characteristics
Demographic and somatometric characteristics, such as age, height, and gestational age did not differ between the GDM and the control group (Table 1). Hb and biochemical parameters, such as fasting glucose, were also similar between the two groups (at the time of the NIRS testing, with women with GDM under treatment). SBP and DBP at rest did not differ between GDM and control groups. MVC and RPE were similar between the two groups. Despite that, GDM women were not able to maintain a similar
Main Findings
This study, for the first time, provided evidence that cerebral oxygenation during exercise, as assessed by NIRS, is significantly impaired in women with GDM as compared to uncomplicated pregnancies. Specifically, despite the similar increase in blood pressure during exercise in the two groups, women with GDM showed a blunted O2Hb increase during exercise. The GDM group also exhibited a delayed recovery in O2Hb in the post-exercise period. However, the above differences were not retained in the
Conclusions
This study provided novel evidence for impaired cerebral oxygenation during exercise, as assessed by NIRS, in patients with GDM compared to uncomplicated pregnancies. NIRS parameters were correlated to markers of vascular dysfunction. Given the mild glucose intolerance and short duration that characterize GDM and despite similar baseline cardiovascular markers, such as urine albumin excretion, and blood pressure, the finding of impaired cerebral oxygenation, in women with GDM as compared with
Contribution Statement
Conception and design of the study: K.D., D.G.G., A.T., A.Z., S.D., E.K.; Researched data: K.D., A.T., I.G., E.K., N.K., V.S., P.P.; Manuscript preparation: E.K, D.G.G., E.B., K.D., A.T., S.D., A.Z.; Contributed to the discussion and reviewed the manuscript: I.G., N.K., P.P., I.S.V., S.D., A.Z. E.B.; Reviewed/edited and approved the manuscript: E.K., K.D., A.T., I.G., N.K., V.S., P.P., I.S.V., A.Z., E.B., S.D., D.G.G.; Guarantor: D.G.G.
Funding
No funding was received for this study.
Conflicts of Interest
The authors declare that there is no duality of interest associated with this manuscript.
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