Influence of Peripheral Neuropathy and Microangiopathy on Skin Hydration in the Feet of Patients With Diabetes Mellitus

Sik Namgoong, MD, PhD; Jong-Phil Yang, MD; Seung-Kyu Han, MD, PhD; Ye-Na Lee, MSc, RN, CWCN; Eun Sang Dhong, MD, PhD


Wounds. 2019;31(7):173-178. 

In This Article


Human skin is an organ composed of layered composite tissues, and it acts as an essential physical and chemical barrier to the external environment.[18] The outermost layer of the skin, or the stratum corneum, regulates water loss and protects the underlying living tissue from environmental pathogens and insults. Upon rupture, the stratum corneum loses its function and becomes ineffective in regulating water loss[18] or preventing external pathogens from infecting the underlying living tissue.[19] Therefore, preserving skin integrity is essential, particularly in patients with diabetes mellitus.

There is an extensive body of literature implicating the importance of adequate hydration for maintaining the integrity of the skin.[2,3,11,20,21] Papanas et al[2] demonstrated that abnormally dry skin develops fissures, thereby increasing vulnerability to ulceration and infection. Further, Boulton et al[3] found a strong relationship between xerosis and ulceration of the skin. Adequately hydrated skin acts as a primary barrier to external pathogens and creates an optimal environment for effective wound healing. It has long been observed that mucosal wounds, in which healing occurs in a moist environment, heal with minimal scarring and exhibit early return to baseline expression levels of inflammatory cytokines.[22,23] These observations highlight the importance of epithelial hydration in wound healing. As such, balancing skin hydration levels is important not only as a primary defender of skin integrity but also as a regulator of cutaneous homeostasis in wound healing. The authors undertook this study to focus on the important issues that have not been addressed previously and to evaluate and compare the influence of nerve function and microcirculation on skin hydration of diabetic feet.

The results of this study demonstrate that skin hydration is little influenced by nerve function in diabetic feet. This result contradicts the traditional concepts in skin hydration. Nerve function is regarded as the powerhouse for maintaining adequate skin hydration; contrary to this conventional concept, the present study showed that nerve function was not significantly correlated with skin hydration, whereas microvascular function was significantly correlated with skin hydration. This study may be the first clinical report to demonstrate a correlation between microcirculation and skin hydration in patients with diabetic foot disease.

Different types of peripheral neuropathy have been identified depending on the damage to the type of nerve (ie, motor, sensory, or autonomic). According to the traditional concept of sweating and skin hydration, the activity of sweat glands is controlled by the division of the sympathetic system, the postsympathetic cholinergic nerve fibers, which release acetylcholine and provoke sweat output.[5,24] The results of this study demonstrated that nerve function is not a sufficient condition for adequately maintaining skin hydration. In other words, the results indicate unimpaired peripheral nerve function alone does not guarantee a moist environment in diabetic feet. This may be attributed to the fact that the skin hydration level is regulated by many factors other than the activity of sweat glands, such as the epidermal function in cutaneous homeostasis, specifically, mechanical and cytoskeletal activities of epithelial ion channels that regulate water loss; hyperosmotic stress related to diffusion through the ion channels;[25,26] and the barrier function to prevent moisture loss through the high lipid content in the stratum corneum. Throughout the body, sodium homeostasis is highly regulated through the combination of specialized sodium channels and aquaporins, which indirectly regulate sodium concentration by water transport; consequently so, nerve function was not significantly related to the skin hydration level in the present study.

The reason for the strong correlation between skin hydration and microcirculation can be inferred. There are several reports on skin hydration that discuss the effect of interstitial fluid transfer through the dermal collagen unfolding mechanism. McGee et al[27] demonstrated that collagen unfolding accelerates water influx, determining skin hydration. Collagen organizes and supports the extracellular matrix of blood vessels. In the dermis, the collagen bundle structure mediates the interchange of water nutrients between the blood, lymph, interstitial cell network, and epidermal layers.[28,29] When microcirculation is well maintained, water transport through the collagen unfolding mechanism occurs smoothly, and the resulting higher hydration potential and accelerated fluid influx can be explained by emerging surface tension gradients and decreased resistance to local flow; therefore, an adequate skin hydration level can be maintained.[29] However, when the microcirculation is poor, fluid transfer between the blood, lymph, interstitial cell network, and epidermal layers is not efficient. In the present study, patients with poor microcirculation tended to show decreased skin hydration levels.

The results of this study also can be applied to the assessment of microcirculation in patients with diabetic foot disease. It is beyond dispute that microcirculation needs to be assessed early in order to decide the treatment plan for patients with diabetic foot disease. It is evident that early detection and appropriate diagnosis of ischemia and impaired microcirculation in the lower limb is an important research field. For this purpose, several diagnostic modalities have been used, including the ankle-brachial index, Doppler ultrasound, angiography imaging, and TcpO2. Unlike in individuals without diabetes, microcirculation in patients with diabetes is commonly compromised, regardless of the status of the macrocirculation.[30] Hence, assessment of the microvascular state in diabetic feet is essential, and TcpO2, which represents the actual tissue oxygen perfusion, is widely acknowledged to be a reliable method for evaluating microcirculation in patients with diabetes.[29] Even so, the method of measuring TcpO2 is very cumbersome, because it requires expensive equipment and trained personnel.

On the contrary, corneometry, an established method for the determination of skin hydration, is an efficient instrument to measure the water content in the stratum corneum in a straightforward manner.[32,33] The advantages of corneometry are its high reproducibility, easy handling, short measurement time, and economic feasibility.[34–36] A corneometry device registers the electrical conductance of the skin surface as an indication of stratum corneum hydration, which is dependent on the high dielectric constant of water content relative to other skin components. Thus, it may be possible to use this device to conveniently assess the microcirculation state in diabetic feet.