Abstract
Background: A large yet heterogeneous body of literature exists suggesting that endothelial dysfunction appears early in type 1 diabetes, due to hyperglycemia-induced oxidative stress. The latter may also affect vascular smooth muscles (VSM) function, a layer albeit less frequently considered in that pathology. This meta-analysis aims at evaluating the extent, and the contributing risk factors, of early endothelial dysfunction, and of the possible concomitant VSM dysfunction, in type 1 diabetes.Methods: PubMed, Web of Sciences, Cochrane Library databases were screened from their respective inceptions until October 2019. We included studies comparing vasodilatory capacity depending or not on endothelium (i.e., endothelial function or VSM function, respectively) in patients with uncomplicated type 1 diabetes and healthy controls.Results: Fifty-eight articles studying endothelium-dependent function, among which 21 studies also assessed VSM, were included. Global analyses revealed an impairment of standardized mean difference (SMD) (Cohen's d) of endothelial function: −0.61 (95% CI: −0.79, −0.44) but also of VSM SMD: −0.32 (95% CI: −0.57, −0.07). The type of stimuli used (i.e., exercise, occlusion-reperfusion, pharmacological substances, heat) did not influence the impairment of the vasodilatory capacity. Endothelial dysfunction appeared more pronounced within macrovascular than microvascular beds. The latter was particularly altered in cases of poor glycemic control [HbA1c > 67 mmol/mol (8.3%)].Conclusions: This meta-analysis not only corroborates the presence of an early impairment of endothelial function, even in response to physiological stimuli like exercise, but also highlights a VSM dysfunction in children and adults with type 1 diabetes. Endothelial dysfunction seems to be more pronounced in large than small vessels, fostering the debate on their relative temporal appearance.
Highlights
Despite significant advances in diabetes care, individuals with type 1 diabetes remain to be prone to the development of comorbidities, in particular those associated with vascular complications
All of the following terms, alone and in combination, were used: “type 1 diabetes,” “InsulinDependent Diabetes Mellitus (IDDM),” “macrovascular,” “microvascular,” “endothelial function,” “endothelium,” “exercise,” “physical activity,” “sport∗,” “contraction,” “hemodynamic∗,” “acetylcholine,” “sodium nitropusside,” “flow-mediated dilation,” “hyperaemia,” “iontophoresis,” “blood flow,” “blood pressure,” “Flow-mediated dilation (FMD),” “Nitrate-Mediated Dilation (NMD),” “vasodilation,” “vasodilatation,” “vascular,” “vasoreactivity.” We excluded the terms “type 2 diabetes,” “mice,” “mouse,” “rat.” Only articles written in English were included
58 studies among which 3 involved two [52, 57] or three [31] cohorts of patients vs. controls assessing the endothelial function and 21 studies among which 1 involved 2 cohorts [52] focusing on the vascular smooth muscles (VSM) were included in the meta-analysis
Summary
Despite significant advances in diabetes care, individuals with type 1 diabetes remain to be prone to the development of comorbidities, in particular those associated with vascular complications. Endothelial dysfunction in diabetes may be the result of a combination of multiple stressors including hyperglycaemia and oxidative stress [1, 8]. A large yet heterogeneous body of literature exists suggesting that endothelial dysfunction appears early in type 1 diabetes, due to hyperglycemia-induced oxidative stress. The latter may affect vascular smooth muscles (VSM) function, a layer albeit less frequently considered in that pathology. This meta-analysis aims at evaluating the extent, and the contributing risk factors, of early endothelial dysfunction, and of the possible concomitant VSM dysfunction, in type 1 diabetes
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