Flow-Mediated Skin Fluorescence (FMSF) Technique for Studying Vascular Complications in Type 2 Diabetes

Skin, the largest organ of human body, is characterized by a unique metabolism. As the epidermal layer of the skin is not directly vascularized, oxygen and nutrients are transported from the dermis by diffusion processes. Epidermal cell metabolism may therefore be regarded as a unique and sensitive marker of early dysfunction in the vascular circulation and metabolic regulation. The efforts of the authors of the present contribution have resulted in a new diagnostic technique named Flow-Mediated Skin Fluorescence (FMSF), which enables noninvasive evaluation of the vascular circulation and metabolic regulation. ¹

Flow-Mediated Skin Fluorescence technique is based on monitoring the intensity of Nicotinamide Adenine Dinucleotide-reduced form (NADH) fluorescence from skin tissue on the forearm as a function of time, in response to blocking and releasing blood flow. Measurements are performed using the AngioExpert, a diagnostic device constructed by Angionica Ltd.

The FMSF technique has been tested on various pathologies and disorders, as well as in sport physiology. A number of papers documenting the diagnostic potential of FMSF have been published.^2-5 Recently, using FMSF, we identified an unexpected effect of age on the vascular circulation and metabolic regulation in patients with type 1 diabetes (DM1). ⁶

The present contribution briefly describes the diagnostic potential of FMSF in the case of type 2 diabetes (DM2). Special attention is given to the ability of the FMSF technique to predict complications related to cardiovascular disease (CVD) associated with the progress of DM2.

Figure 1 compares the values of HR_index, a major diagnostic parameter of FMSF technique, for the DM2 subgroups and the control group. Clinical characteristics of patients with DM2: age, 63.0 ± 8.1 years; male/female ratio, 38/32; HbA1c (%), 8.2 ± 1.4; disease duration, 14.6 ± 7.4; and Body Mass Index (BMI), 31.4 ± 5.5. It is important to notice that HR_index parameter differentiates with statistical significance the subgroup with evident CVD (B) from the subgroup without CVD (A).

Figure 1.

Comparison of HR_index for DM2 subgroups without CVD (A) and with evident CVD (B) vs control group. The presence of microvascular complications was diagnosed in 25 patients of subgroup A and in 20 patients of subgroup B. CVD, cardiovascular disease (ischemic heart disease, heart failure, myocardial infraction, and stroke).

As can clearly be seen from the results presented in Figure 1, the HR_index parameter has the interesting ability to identify the patients with DM2 with the risk related to CVD. Interestingly, 5 patients out of 39 (subgroup A) have the values of HR_index parameter varied from 12.7% to 18.4% despite long disease duration. These values are typical for healthy individuals and a risk related to CVD seems to be low.

The FMSF technique allows also for the quantitative analysis of the oscillations in the microcirculation that can be observed on the baseline and the hyperemic (reperfusion) part of the FMSF trace. ¹ Such analysis of the oscillations present on the baseline allows for the identification of the patients with DM2 with microvascular complications. The oscillations present on the reperfusion line can be used for the identification of the patients with DM2 with a low sensitivity to hypoxia. These aspects will be discussed in detail in the forthcoming articles.