Impaired skin microcirculation in paediatric patients with type 1 diabetes mellitus

Abstract

Aims/hypothesis: We used Laser Doppler Fluximetry (LDF) to define "normal" endothelial function in a large cohort of healthy children and adolescents and to evaluate skin microcirculation in paediatric patients with type 1 diabetes mellitus.

Methods: LDF was performed in 102 healthy children (12.8 ± 3.3 years of age; 48 male) and 68 patients (12.9 ± 3.3 years of age; 33 male). Duration of disease was 5.0 ± 3.97 years. Each participant sequentially underwent three stimulation protocols (localized thermal hyperaemia with localized warming to maximum 40°C, iontophoretic delivery of pilocarpine hydrochloride (PCH) and sodium nitroprusside (SNP)). The maximum relative increase in skin blood flow and the total relative response, i.e. the area under the curve (AUC) to each stimulus (AUCheat, AUCPCH, AUCSNP) was determined. In addition, the area of a right-angled triangle summarizing the time to and the amplitude of the first peak, which represents the axon reflex mediated neurogenic vasodilation (ARR) was calculated.

Results: In healthy controls, AUCheat, AUCPCH, AUCSNP, and ARR turned out to be independent of sex, age, and anthropometric values. Per parameter the 10th percentile generated from data of healthy controls was used as the lower threshold to define normal endothelial function. Diabetic patients showed significantly reduced vasodilatative response to either physical or pharmacological stimulation with SNP, whereas the response to PCH was comparable in both cohorts. In patients compared to controls i) a significantly higher frequency of impaired vasodilatation in response to heat and SNP was noted and ii) vascular response was classified as pathological in more than one of the parameters with significantly higher frequency.

Conclusions/interpretation: Skin microvascular endothelial dysfunction is already present in about 25% of paediatric type 1 diabetic patients suffering from type 1 diabetes for at least one year. Future studies are needed to assess the predictive value of endothelial dysfunction in the development of long-term (cardio)vascular comorbidity in these patients.

Figure 1

Parameters calculated from the normalized time related response to local heat. A, normalized axon reflex response, t, time to the axon reflex response starting from the time that the local skin temperature was set to 40°C (arrow head, 9min. after start of local warming). The area under the curve (AUC_heat) equals the maximum response to localized heating, with beginning and end of the time interval set to 0 and 40 min, respectively. Insert: the amplitude of the axon reflex (A) together with the time required to peak (t) are summarized as the area of a triangle. The time interval begins 9 min after start of localized warming, i.e. the time the heating device was set to 40°C.

Figure 2

ARR, AUC_heat, AUC_PCH and AUC_SNP as a function of age in healthy children. ARR (A), AUC_heat(B), AUC_PCH(C) and AUC_SNP(D) as a function of age in healthy children (open symbols: male; closed symbols: female).

Figure 3

Correlation between AAR and weight-SDS (A) and between ARR and BMI-SDS (B) in patients. A: r= 0.37; B: r=0.34, each p<0.005.

Figure 4

Correlation between AUC_heat and AAR (A, C) and between AUC_heat and AUC_SNP (B, D) in healthy children (A, B) and patients (C, D). A: r= 0.92, p<0.001; B: r=0.37, p<0.001; C: r=0.80, p<0.001; D: r=0.32, p<0.05; per parameter the 10th percentile is indicated by a horizontal or vertical line, respectively.

Figure 5

Comparison of AUC_heat, AUC_PCH and AUC_SNP in healthy controls (open bars) and diabetic patients (grey bars).