Early Endothelial Dysfunction in Type 1 Diabetes Is Accompanied by an Impairment of Vascular Smooth Muscle Function: A Meta-Analysis

Figures

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  Figure 1. Flow-chart outlining the process of study selection.

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  Figure 2. Forest plots of studies on endothelial function, according to size of vessels studied, in subjects with type 1 diabetes vs. controls. (A) Forest plot of studies on endothelial function focusing on macrovascular function. (B) Forest plot of studies on endothelial function focusing on microvascular function. In these figures the priority was set on macrocirculation over microcirculation. Similar results are obtained when priority is placed on microcirculation (SMD −0.59; 95% CI −0.74, −0.43, P < 0.001). PORH, Post-occlusive reactive hyperaemia; FMD, Flow Mediated Dilation. For each subgroup, the following values are indicated: Z- and p-value; I2, heterogeneity and p for heterogeneity. When comparing macro and microcirculation with metaregressions (for qualitative data), the difference was significant (moderator P = 0.001) with a greater dysfunction due to type 1 diabetes for macrovessels.

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  Figure 3. Forest plots of studies on endothelial function, according to types of vessels studied, in subjects with type 1 diabetes vs. controls. For each subgroup, the following values are indicated: Z and p-value; I2, heterogeneity and p for heterogeneity. When comparing the three vessels types with metaregressions (for qualitative data), the difference was significant (moderator P = 0.005), with a greater dysfunction for artery compared to muscle microvessels (post-hoc comparison using Bonferroni correction, p < 0.05) and a tendency for a greater dysfunction at artery compared to cutaneous microvessels (post-hoc comparison using Bonferroni correction, P = 0.09).

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  Figure 4. Forest plots of studies on endothelial function, according to measurement techniques, in subjects with type 1 diabetes vs. controls. For each subgroup, the following values are indicated: Z and p-value; I2, heterogeneity and p for heterogeneity. When comparing the six types of techniques with metaregressions (for qualitative data), the difference was significant (moderator P = 0.02), with a more visible dysfunction when using ultrasounds vs. plethysmography (post-hoc comparison using Bonferroni correction, P < 0.01).

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  Figure 5. Forest plots of studies on endothelial function in response to exercise, according to the type of exercise, in subjects with type 1 diabetes vs. controls. For each subgroup, the following values are indicated: Z and p-value; I2, heterogeneity and p for heterogeneity. When comparing the two types of exercise with metaregressions (for qualitative data), the difference was significant (moderator P = 0.04), with a more visible dysfunction when using intermittent local exercise vs. aerobic exercise.

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  Figure 6. Forest plot of studies on VSM function in subjects with type 1 diabetes vs. controls. For each subgroup, the following values are indicated: Z and p-value; I2, heterogeneity and p for heterogeneity. There was no difference between macro and microcirculation (with metaregression for qualitative data: moderator P = 0.60).