Assessment of Microvascular Disturbances in Children with Type 1 Diabetes-A Pilot Study

Abstract

Endothelial dysfunction appears early in type 1 diabetes (T1D). The detection of the first vascular disturbances in T1D patients is crucial, and the introduction of novel techniques, such as flow-mediated skin fluorescence (FMSF) and adaptive optics retinal camera (Rtx) imaging, gives hope for better detection and prevention of angiopathies in the future. In this study, we aimed to investigate microcirculation disturbances in pediatric patients with T1D with the use of FMSF and Rtx imaging. This research focused especially on the relationship between microvascular parameters obtained in FMSF and Rtx measurements, and the glycemic control evaluated in continuous glucose monitoring (CGM) reports. We observed significantly increased wall thickness (WT) and wall-to-lumen ratio (WLR) values in T1D patients in comparison to the control group. Although we did not observe significant differences between the T1D and control groups in the FMSF results, a trend toward significance between the time in range (TIR) and hyperemic response (HR_max) and an interesting correlation between the carotid intima-media thickness (cIMT_max) and HR_max. were observed. In conclusion, FMSF and Rtx measurments are innovative techniques enabling the detection of early microvascular disturbances.

Keywords: carotid intima-media thickness; diabetic angiopathies; microcirculation; type 1 diabetes.

Figure 1

Summary of study group recruitment process. T1D—type 1 diabetes; CGM—continuous glucose monitoring; FMSF—flow-mediated skin fluorescence.

Figure 2

Comparison of carotid intima-media thickness for the (A) cIMT_max, (B) cIMT_min, and (C) cIMT_mean between patients with T1D and healthy subjects. The middle line displays the median, whereas the whisker spans the lower and upper quantiles. The statistically significant differences are marked with “*”. T1D—type 1 diabetes; cIMT_max—highest value of carotid intima-media thickness from both artery measurements; cIMT_min—lowest value of carotid intima-media thickness from both artery measurements; cIMT_mean—mean value of carotid intima-media thickness from both artery measurements.

Figure 3

Comparison of adaptive optics retinal camera examination of the (A) lowest wall thickness, (B) highest wall thickness, (C) mean wall thickness, and (D) wall-to-lumen ratio results between patients with type 1 diabetes (T1D) and healthy subjects. The middle line displays the median, whereas the whisker spans the lower and upper quantiles. The statistically significant differences between the groups are marked with “*”. T1D—type 1 diabetes; WT_min—lowest measurement of both wall thicknesses; WT_max—highest measurement of both wall thicknesses; WT_mean—mean value from both wall thickness measurements; WLR—wall-to-lumen ratio.

Figure 4

Correlation heatmap (A) of glycemic control parameters and carotid intima-media thickness (cIMT), flow-mediated skin fluorescence (FMSF), and adaptive optics retinal camera (Rtx) examinations, as well as scatter plots (B–D) presenting the relationship between the time in range (70–180 mg/dL) and adaptive optics retinal camera examination results for the (B) highest wall thickness, (C) lowest wall thickness, and (D) mean wall thickness in patients with type 1 diabetes (T1D). Statistically significant correlations are denoted by ‘*’, whereas statistically significant correlations adjusted with T1D duration are marked with ‘^#’. cIMT_max—the highest value of carotid intima-media thickness from both artery measurements; cIMT_min—the lowest value of carotid intima-media thickness from both artery measurements; cIMT_mean—mean value of carotid intima-media thickness from both artery measurements; HR—hyperemic response; RHR—reactive hyperemia response; HS—hypoxia sensitivity; WT_min—lowest measurement of both wall thicknesses; WT_max—highest measurement of both wall thicknesses; WT_mean—mean value from both wall thickness measurements; WLR—wall-to-lumen ratio; WCSA—wall cross-section area; TIR (70–180)—time in range (70–180 mg/dL); TBR (<70)—time below range (<70 mg/dL); TAR (>180)—time above range (>180 mg/dL); CV—coefficient of variability; HbA1c—hemoglobin A1C.