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Abstract

Objective

Diabetes mellitus (DM) significantly affects microcirculation, leading to microvascular abnormalities that can result in severe systemic complications. Capillaroscopy is a non-invasive and painless method for observing capillary microvasculature, allowing for the assessment of microcirculatory damage. While it is known primarily for its application in rheumatic diseases, recent studies have emphasized its importance in non-rheumatic conditions, such as DM. This growing relevance has led to the aim of developing a classification system for capillary damage in diabetic patients.

Methods

Cross-sectional study. Eighty randomly selected patients with type 2 diabetes mellitus (T2DM) were evaluated using capillaroscopy to assess capillary damage and establish a classification system.

Results

Capillary damage was observed in all participants (100%), with greater severity associated with longer diabetes duration. Patients were categorized based on the severity of their damage.

Conclusions

The classification system identified three degrees of capillary damage: an early grade, which can be subdivided into initial or established; an intermediate grade, which can also be initial or established (both treatable for potential reversibility); and an advanced grade, which appears to be irreversible. This classification aids in better understanding and managing microvascular damage in diabetic patients.

Keywords

Capillaroscopy capillary damage microvascular damage diabetes mellitus microvascular classification

Introduction

Type 2 diabetes mellitus (T2DM) is one of the most common non-communicable diseases. The WHO reports that 14% of the adult population has T2DM.¹ In Mexico, according to the ENSANUT 2022 (National Health and Nutrition Survey), approximately 18% of Mexican adults have this disease,² and the International Diabetes Federation (IDF) Diabetes Atlas reports that nearly 50% of patients (47.5%) are undiagnosed.³ This high global prevalence is significant due to the elevated risk of morbidity and early mortality it represents.¹

T2DM is characterized by elevated serum glucose levels secondary to the development of insulin resistance, where the body's cells cannot effectively utilize insulin due to changes in the expression and function of insulin receptors. This leads to dysfunction of beta cells in the pancreas, which, over time, cannot produce enough insulin to overcome this resistance, resulting in sustained hyperglycemia.¹

According to the described pathophysiology, this hyperglycemia generates oxidative stress by increasing the production of reactive oxygen species (ROS), which damage endothelial cells and promote inflammation. This creates a cascade of damage and inflammatory responses, including the formation of advanced glycation end products (AGEs) that accumulate in tissues and activate their receptors (RAGE), causing inflammation and endothelial dysfunction. Additionally, the activation of protein kinase C (PKC) alters vascular function by increasing permeability and the production of pro-inflammatory factors. The polyol pathway is also activated, where excess glucose is converted to sorbitol via aldose reductase, accumulating in cells and causing osmotic damage and oxidative stress. This complex phenomenon contributes to endothelial glycocalyx damage, causing inflammation through the release of cytokines, interleukins, metalloproteinases, vascular and tumor growth factors, thereby increasing oxidative stress and leading to acute endothelial dysfunction.⁴ Clinically, this damage is observed as tissue necrosis, resulting in skin wounds and often necessitating lower limb amputations.⁵

These damage mechanisms contribute to basal membrane thickening, endothelial dysfunction, and inflammation, resulting in microvascular complications such as retinopathy, nephropathy, and lower limb complications, as well as diseases with micro and macrovascular complications generally observed as chronic venous insufficiency (CVI) or vascular diseases, including arteriosclerosis and hypertension (HBP, high blood pressure).^6,7

Endothelial damage is a component of persistent diabetic complications, emerging from the early stages of angiopathy and endothelial dysfunction pathogenesis, where arteries, veins, arterioles, venules, and capillaries—that is both macrovasculature and microvasculature—are affected. This alters capillary flow, permeability, and inflammatory balance, resulting in the thickening of the endothelium and the basal membrane. This vascular damage leads to congestion, hemorrhages, and loss of capillary architecture, as well as thrombosis, with destruction and reduction of capillary reserve.^8–10

Therefore, vascular damage caused by T2DM leads to morphological and functional changes that affect vascular reactivity. These changes can be monitored with techniques to measure and visualize vascular status, including 24-hour ambulatory blood pressure monitoring (24-h ABPM) or using oscillometric measures such as pulse wave velocity (PWV) or augmentation index (AIx) for macrovascular system damage and laser Doppler flowmetry and especially nailfold capillaroscopy for microvascular evaluation.¹¹

Regarding the use of capillaroscopy for microvascular damage evaluation, it should be determined that the capillaroscopic pattern is not based on a single parameter but on the judgment of an overall pattern resulting from the combination of numerical and morphological characteristics such as capillary diameter (width), capillary length, shape, distribution, average capillary density, presence of avascular areas, and capillary hemorrhages.^10,12

Several capillary alterations in diabetes mellitus (DM) have been explained and visualized, especially in patients with poor metabolic control. However, despite these findings, there are few clinical studies on the relationship between microvascular changes observed in capillaroscopy and the characteristics of T2DM. This is important because early diagnosis of vascular pathology with capillaroscopy could be a reliable and crucial method for the timely treatment of patients with T2DM and microvascular complications. To our knowledge, there is currently no established classification of capillary damage in diabetic patients. Obtaining such classification would help to objectify the results of future studies and/or describe the progression of the disease.

Therefore, this study aims to generate and provide evidence of capillaroscopic evaluation of nailfolds in patients with T2DM, which can help classify the level of damage in patients, thereby improving diagnosis and treatment.

Background

Origin and use of capillaroscopy

Capillaroscopy is a non-invasive technique used to examine the capillaries of the nail fold. The procedure involves using an optical microscope with magnifications ranging from 20 to 200 times to examine the morphology, distribution, and quantity of capillaries. It is a painless procedure that requires no preparation for the patient, except for nail visibility, making it an easy technique to perform.^13,14

The method was described in the early 1970s when Drs. Bollinger A and Fagrell B in Zurich, Switzerland, developed capillaroscopic techniques to measure the dynamic diffusion of fluorescein in the microcirculation of human skin. In the mid-1970s, this technique was also employed to study skin microcirculation, leading to the development of a unique method to measure blood flow in the capillaries of human skin under both healthy and diseased conditions. This research led to collaboration with Intaglietta M in San Diego, California, USA, who helped optimize these techniques for use in research and clinical practice.^15–18

These studies were mainly used for diagnosis and prognosis by rheumatologists. Nailfold capillaroscopy (NFC) has recently been incorporated into the new classification criteria of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 for systemic sclerosis, considering the work of Van den Hoogen et al. “Classification Criteria for Systemic Sclerosis” and Sevdalina Nikolova Lambova on the qualitative and quantitative analysis of capillaroscopic findings, confirming the importance of the method in disease diagnosis.^19,20

Studies based on capillary morphology

Dr Rajaei Alireza, a rheumatologist at Shahid Beheshti University of Medical Sciences in Tehran, Iran, conducted a pilot study establishing the first capillaroscopic parameters for DM. This study, comparing the findings with the scleroderma pattern, described and analyzed microvascular architecture, alterations in capillary distribution, capillary morphology, capillary density, efferent/afferent branch ratio, subpapillary venular plexus, and morphological abnormalities. These studies served as a basis for using capillaroscopy as a tool to visualize capillary changes in other rheumatic diseases, as demonstrated by Dr Bouskela's group, showing changes in Sjogren's syndrome, lupus erythematosus, and primary antiphospholipid syndrome, among other pathologies.^21–23 Even dermatologists, other specialists, and researchers have utilized these studies, focusing on the application of capillaroscopy for the analysis, diagnosis, and management of DM and other diseases.^24,25 These studies were used by Maldonado-Vélez as part of his thesis, presenting an analysis of the different percentages of various types of capillary morphology in diabetic patients, describing a capillaroscopic pattern composed of avascular zones, capillary dilation, giant capillaries, ectasias, and tortuous morphology, noting that greater progression of DM shows more damage in patients.²⁶

Additionally, Dr Mohita Mahajan from the Department of Dermatology, Venereology, and Leprosy at Government Medical College, Amritsar, India, investigated nailfold capillaroscopic alterations in patients with T2DM who presented with diabetic retinopathy and compared them with healthy controls. The study reveals that patients with DM exhibit significantly higher frequencies of tortuous, dilated, branched, serpentine, and angled capillaries, as well as avascular areas and microhemorrhages, compared to healthy controls.²⁷ The results indicate that patients with proliferative diabetic retinopathy (PDR) exhibit a higher frequency of tortuous, branched capillaries, avascular areas, and reduced capillary density compared to those with non-proliferative diabetic retinopathy (NPDR). Additionally, a longer disease duration (>20 years in this study) shows a significant increase in tortuous capillaries, avascular areas, serpentine, angled, and dilated capillaries, and poorer glycemic control (HbA1c > 11) shows higher frequencies of tortuosity, avascular areas, and branched areas.²⁷

These findings underscore the importance of capillaroscopy and the relationship between nailfold damage and retinal status. The evaluation of microcirculation in patients with diabetic retinopathy and capillary characteristics can vary according to disease severity, duration, and glycemic control.²⁸

These are not all the studies conducted on capillaroscopy and DM. Other authors have contributed by comparing capillary morphology in comparative or descriptive studies of diabetic and healthy patients, demonstrating an interest in evaluating diabetic patients based on their microcirculation status. This can provide insight into the actual state of hyperglycemia-induced damage in the patient. This nailfold damage appears to have a direct relationship with retinal and renal status, as well as other target sites, such as the lower limbs.^24,29–31

Methodology

To establish the classification of capillary damage in adult patients with T2DM, a cross-sectional study was conducted on patients who underwent evaluative capillaroscopy. The included patients were evaluated between March 2022 and February 2023 at the CEDIME Vascular Disease Center in Mérida, Mexico. The reporting of this study complies with STROBE guidelines.³²

Patient selection criteria

Inclusion

Patients who voluntarily presented at the CEDIME Vascular Disease Center with a known diagnosis of T2DM, or who, where diagnosed in the center, based on elevated fasting glucose and/or glycated hemoglobin (HbA1c), with or without symptoms of diabetic decompensation, with or without comorbid disease, regardless of the duration of the disease to evaluate changes between recent-onset diabetes (<10 years) and long-standing diabetes (>10 years) patients.

Exclusion

Patients with known autoimmune disease, critically ill or terminal patients at risk of death, and all patients from whom the necessary data for analysis could not be obtained. Patients with CVI, obesity, or smoking were also excluded to reduce selection bias, as these characteristics can cause microvascular damage.

Capillaroscopy examination

A capillaroscope with the DINOLITE system was used; the presence or absence of the following variables was analyzed.

Morphological changes

Changes in capillary architecture, such as elongation, tortuosity, trident capillaries, total capillary dilation, efferent loop dilation, afferent loop dilation, opening of A-V fistulas (AVFs) (precapillary shunts), collateral branches, and presence of dilated venous plexuses.

Physiological Changes

Hemodynamic changes due to increased flow through AVFs, efferent loop dilation (venous hypertension), appearance of underlying venous plexuses (local escape collateralization), appearance of subpapillary venous plexuses (territorial venous flow and hypertension), capillary-venous congestion, venous plexus congestion, hemorrhages, and capillary destruction.

Edema

Pericapillary edema, venous interstitial edema, and lymphovenous edema are always present, depending on the different degrees (early, intermediate, and advanced). Edema can vary from local to compressive.

An angiologist expert in vascular diseases and vascular laboratory conducts each study. Direct capillaroscopy is used to examine all of the patient's fingernail and toenail beds, and relevant images of the affected areas are captured and stored for further analysis. Each image obtained from the study is reviewed by two of the center's angiologist experts. For the assessment and determination of capillary damage, morphological and physiological changes, and edema characteristics are described. If there is any disagreement, a third expert is consulted.

All patients underwent a Doppler examination to determine the coexistence of arterial and capillary disease; in cases of doubt, an arterial duplex examination was performed. The vascular assessment included the iliac, femoral, popliteal, tibial, peroneal, and plantar arteries as a part of the systematic protocol.

The results led to classification into three groups, divided according to the findings, into early, intermediate, and advanced diseases, depending on the presence of morphological and physiological changes. The greater the damage, the higher the classification. According to the patient care center's standards, recent-onset diabetes patients underwent conjunctival capillaroscopy and fundus examination. For long-standing diabetes patients, glomerular filtration and general urine examination were also performed.

Ethical criteria

The study was approved by the Ethics and Research Committee of the CEDIME Vascular Disease Center. All patients signed a confidentiality agreement and provided their consent for the use of their data for research purposes.

Statistical analysis

A statistical analysis was performed to provide descriptive results, using measures of central tendency, percentages, and ranges. Missing data accounted for less than 3% and were deemed Missing Completely At Random (MCAR) based on pattern analysis and Listtle’s test. Multiple imputation using chained equations (MICE) was performed with five imputations for age, years with DM2, presence of DMN (diabetic microvascular nephropathy), DMR (diabetic microvascular retinopathy), and arterial disease. Post-imputation analyses were combined using Rubin's rules. To assess the correlation between age, years, and the degree of capillary damage, a logistic regression analysis was conducted. To identify any potential subgroup that might exhibit different behaviors, a multivariate PCA analysis was performed, noting differences with a cutoff at 10 years of the disease. For comparison of differences, a post hoc analysis was carried out using the Mann–Whitney U test, followed by a Kolmogorov–Smirnov normality test. The significance level used was α = 0.05. The statistical analysis was performed with SPSS version 25.

Tables and graphs were generated for data visualization.

Results and classification of capillary damage

A total of 80 patients from the vascular disease center were included, comprising 48 men and 32 women. The age range of the participants was 19 to 86 years, with 55 of them being over 50 years old. Morphological changes, physiological changes, and edema were found in 100% of the participants. The characteristics of the patients are shown in Table 1.

Table 1.

General and clinical data.

Clinical data	Recent-onset diabetes patients (<10 years with DM) n = 16	Long-standing diabetes patients (≥10 years with DM) n = 64	Total	Advance degree of capillary damage n = 26
Gender	7 f, 9 m	25 f, 39 m	32 f, 48 m	11 f, 15 m
Age, years (mean)	27.18 ± 6.47	58.09 ± 14.93	51.9 ± 18.45	70.92 ± 10.03
range age, years	19–37	39–86	19–86	39–86
n > 50 years	0	55	55	25
Years with DM (mean)	6.06 ± 1.94	23.11 ± 10.71	19.7 ± 11.8	29.92 ± 12.48
Range in years with DM	3–9	11–54	3–54	13–54
DMR	5	46	51	26
DMN	N/A	34	34	26
Arterial disease	1	17	18	14

General clinical data and characteristics of the included patients are described. The column of data for patients with advanced degrees of capillary damage is described given the finding that 100% of the patients also showed renal and retinal diabetic microangiopathy. DMR: diabetic microvascular retinopathy; DMN: diabetic microvascular nephropathy; N/A: not applicable (in acute patients, only conjunctival capillaroscopy and fundus examination were performed).

Morphological and physiological changes were used for classification, which is shown in Table 2. The identification of capillary disease grades through capillaroscopy is generally performed by finding repetitive patterns in the nailfold examination, which should be conducted on both hands and feet. Regarding the results of the vascular disease assessment in the patients, coexistence of microvascular (capillary) damage and macrovascular (arterial) disease was observed in 18 patients; of these, 14 showed damage at the infrapopliteal level (popliteal and tibial arteries), and the remaining 4 had multisegmental involvement (femoral, popliteal, and tibial).

Table 2.

Classification of capillary damage in patients with type 2 diabetes mellitus (obtained by capillaroscopy).

Capillary disease		Observed changes
Capillary disease		Morphological	Physiological	Edema
Early (n = 30)	Initial (n = 18)	Capillary elongation, capillary dilation	Opening of arteriovenous fistula	Pericapillary Edema
Early (n = 30)	Established (n = 12)	Trident capillaries, megacapillaries	Dilation of the efferent loop (venous) due to arterial flow steal	Venous Interstitial Edema
Intermediate (n = 24)	Initial (n = 9)	Multiple capillaries with efferent loop (venous) dilation	Venous congestion manifested by collateralization to nearby or underlying venous plexuses and subpapillary or subcutaneous collector venous plexuses	Lympho-Venous Edema
Intermediate (n = 24)	Established (n = 15)	Efferent loop (venous) congestion with the beginning of loss of venular architecture	Leakage causing hemorrhagic spots and/or thrombosis	Lympho-Venous Edema, Compressive Edema
Advanced (n = 26)		Loss of capillary architecture, congestive spots	Severe hemorrhages	Terminal edema of lympho-venous nature with consequent protein and fat congestion

Details of the morphological and physiological data for each grade. For grades higher than early initial, the characteristics of the previous grades should be added.

Some of the figures obtained from the patients in this study are used to exemplify the grades:

Early Grade: In panoramic views, AVFs, trident loops, capillary elongations, capillary dilation, and tortuosity are observed. In the Initial Early Grade, these are observed sporadically, whereas in the Established Early Grade, they are observed in most panoramic views, as shown in Figure 1. The disease progresses with greater distal capillary damage and increased venous flow, manifested by efferent capillary loop dilation, collateralization, and the appearance of underlying capillary plexuses and subpapillary venous plexuses.

Figure 1.

Classification of capillary damage. Early grade.

Intermediate Grade: The continuation of the pathophysiological process transforms capillary morphology into congestive changes manifested by highly dilated capillaries, loss of normal capillary anatomy, hemorrhages, and increased pericapillary and interstitial edema (Figure 2). It should be noted that at this grade, it is still possible to reverse or limit the progression of vascular disease; however, this regression does not appear to be possible in the next grade.

Figure 2.

Classification of capillary damage. Intermediate grade.

Advanced Grade: In the advanced or terminal grade, highly dilated and congestive subpapillary venous plexuses, balloon-shaped or highly dilated capillaries, megacapillaries, massive congestion, hemorrhage, and capillary death are generally observed. Edema is described as terminal, which is compressive pericapillary edema, interstitial edema, and lymphovenous edema (Figure 3). This grade coincides with renal and retinal capillary damage, presented in 100% of the patients in this study.

Figure 3.

Classification of capillary damage. Advanced grade.

A sub-analysis was conducted based on the patients’ age, the degree of capillary damage, and the duration in years since the DM diagnosis, to observe a possible progression of microvascular disease, given that a preliminary relationship between these factors was observed. The results show that older age and longer duration with DM diagnosis were associated with greater capillary damage. Additionally, a difference was observed in patients with less than 10 years of diabetes; this subgroup was identified after the general analysis, as it followed a different trend compared to the results for patients who have had the disease for more than 10 years. The results indicate that younger age and having less than 10 years of DM progression show a lower probability of having an advanced grade of capillary disease progression. These results are shown in Figure 4.

Figure 4.

Correlation between age, years with a diagnosis of diabetes mellitus, and the degree of capillary damage. Each bubble represents a patient, with the “Y” axis showing the degree of damage, where grade 1 is for early initial damage, 2 for early established damage, 3 for intermediate initial damage, 4 for intermediate established damage, and 5 for advanced grade. The location of the bubble on the “X” axis corresponds to the patient's age, and the size of the bubble depends on the years with the diagnosis of diabetes mellitus. An ascending trend line can be observed. The older the age, the longer the years with DM, and the higher the degree of capillary damage. Sub-groups: The bubbles in white (show different behavior) correspond to patients with less than 10 years of diagnosis of DM, it shows less number of cases with advanced degree when compared with the rest of population; a Wilcoxon test was made for the comparison (p < 0.05). DM: diabetes mellitus; Dx: diagnostic.

Discussion

The classification obtained from the results of this study should help establish an objective evaluation of capillary damage in future studies, enabling the identification of improvements through therapies or treatments, as well as defining worsening due to the natural progression of the microvascular disease or treatment failure.

The coexistence of T2DM and capillary disease seems undeniable after reviewing the obtained results. These data show that all DM patients included in the study developed changes in the anatomy and function of capillary vessels, depending on the duration of the disease and possibly its severity. These data are obtained through observation, where a capillary pattern is observed in both recent-onset diabetes and long-standing diabetes patients, with capillary changes increasing with the progression of chronicity. For example, in long-standing diabetes patients, alterations in the conjunctival capillary pattern and damage in the fundus of the eye are observed, along with decreased glomerular filtration and microproteinuria or proteinuria indicating patient deterioration^28,33; in other words, in the 26 patients with advanced disease, the coexistence of retinopathy and renal disease was observed, confirmed with fundus examination and glomerular filtration. Therefore, in all patients, a review and diagnosis should be conducted in the three target sites where microvascular damage typically occurs (the eye, the kidney, and the feet) to provide appropriate treatment.³⁴ Some studies and clinical experience show that to achieve regression, optimal metabolic control must be maintained by monitoring patients’ glucose levels, that is controlling DM status and providing treatment that modifies capillary disease, such as compressive and surgical therapy if necessary. So far, it appears that this grade cannot be reversed, unlike the lower grades, where treatment can achieve disease reversal. This reversibility has been observed in patients who are adequately treated, which includes compressive or decongestive therapy using physiotherapy and/or compression stockings and bandages, with adequate glucose level control through diet, exercise, and oral antidiabetics, if necessary.^35,36

Additionally, lifestyle changes are necessary, including reducing smoking and increasing physical activity. Regarding pharmacological treatment, it should have evidence of preserving and protecting microvascular anatomy, as well as reducing venous wall apoptosis, which would decrease vascular pressure and reduce extravasation edema. It should also help limit DM pathogenesis by generating anti-inflammatory and antioxidant activity. Venoactive drugs (VADs) represent a standard medical therapy approach in patients with chronic venous diseases. Among this category of medications, an interesting treatment option that has shown positive results for both chronic venous disease and diabetic microangiopathy possessing the aforementioned characteristics is calcium dobesilate. Additionally, complications that these patients often present, such as ulcerations, infections, or thrombosis, should be treated, so the use of antibiotics and/or antithrombotics is widely used in these patients.^37–41

Furthermore, capillaroscopy is proposed as a method to classify the disease directly in the feet and indirectly in other target organs, such as the eye and kidney.⁴²

These results can be attributed to the inflammatory response associated with T2DM, which contributes to edema. This results in poor distal capillary flow, which, as a means of conserving systemic capillary endothelium, leads to the generation of vascular wall edema and pericapillary return flow, thereby opening precapillary A-V shunts that form AVFs (Figure 5).⁴³

Figure 5.

Morphology of A-V shunt for fistula formation. The anatomical location and formation of the arteriole-venule relationship are shown, along with a diagram of the formation of an A-V shunt, where the increase in intravascular pressure increases the possibility of generating an A-V fistula.

Based on our observations, it seems that this phenomenon begins in the early stages of DM evolution, and it could even start in prediabetic patients. All patients exhibited a capillary inflammatory pattern, leading to the opening of precapillary AVFs (at the beginning of the afferent capillary loop), which caused congestion of the efferent capillary loop and venous congestion of the underlying venous plexuses and subpapillary venous plexuses, mainly in chronic states, with pericapillary and interstitial edema. This fact increases arterial capillary flow steal and the increase of flow and pressure in the venous capillary system. Morphologically, the opening of AVFs and trident loops can be appreciated, as well as the increase of venous flow in the venous capillary loop with efferent loop dilation from the early stages.

These changes occur because the capillary is composed of a single endothelial cell resting on a skinny basal membrane. When the capillary becomes inflamed, the endothelial cell swells, increasing in volume, which causes the capillary loop to become obstructed, resulting in tissue ischemia of the extracellular matrix and interstitial cells. This promotes the release of prostacyclin from platelets, which produces the opening of AVFs to preserve venous return, relieving loop hypertension. If this diversion does not occur, the capillary becomes thrombosed or ruptures, causing tissue ischemia (Figure 6).^37,38

Figure 6.

Evolution of capillary damage. The progression of capillary damage and the anatomical changes caused by the presence of an arteriovenous shunt and the subsequent opening of a fistula, induced by the presence of diabetes, are shown. AV: arteriovenous.

When this precapillary diversion occurs at the beginning of the afferent loop (arterial), the blood content flows below the efferent loop (venous), resulting in the passage of arterial capillary blood flow to the venous capillary, demonstrated by a decrease in the diameter of the afferent loop and an increase in the efferent loop, observed in capillaroscopy. This fact, which temporarily benefits tissue perfusion by avoiding tissue ischemia, continuously increases venous flow at the capillary level, resulting in venous capillary hypertension and collateralization of regional and subpapillary venous collector vessels. This hypertension proportionally causes pericapillary and interstitial edema. Venous and collector capillary beds dilate and, in advanced stages, become thrombosed and rupture, causing tissue hemorrhages and thrombosis observed in capillaroscopy as hemorrhagic spots and avascular areas (Figure 6).^37,38

Capillary stasis and compressive edema

Capillary stasis and compressive edema lead to ischemia, which causes anesthesia detected by sensory nerve microfibers. In reversible treatment stages, when capillary ischemia decreases or disappears, the patient regains sensitivity, a phenomenon that can be confused with neuropathy. The neuropathy observed in terminal patients results from nerve capillary damage, not the other way around.^37,38

Unlike venous microangiopathy, diabetic microangiopathy manifested in the lower limbs is of arterial capillary origin, and venous microangiopathy results from venous stasis and hypertension generated retrogradely from the central venous trunks due to valvular damage areas.³⁷

We believe that capillary damage is the initial step before clinical organ injury. This process likely results from a pro-inflammatory state, edema, and tissue hypoxia. Typically, such damage is seen in the feet, retina, and kidneys. Visualization of the nailfold capillaries through capillaroscopy may reflect damage in these organs or other tissues and could serve as a basis for providing appropriate treatment.

These studies demonstrate that the presence of T2DM significantly influences the morphology and structure of microcirculation, which can predispose the occurrence of severe complications. Nailfold capillaroscopy is a non-invasive diagnostic method that provides important information to understand the disease status, allowing for better control of it. It is a tool with predictive and preventive value for vascular and metabolic complications or sequelae.

Conclusion

This study presents to the medical community a classification of capillary damage in the presence of DM using capillaroscopy, consisting of three grades: early grade, which can be subdivided into initial or established, where morphological and functional changes can be visualized due to the presence of AVFs with capillary-venous edema; intermediate grade, which can be initial or established, showing venous dilation and congestion, hemorrhages, and lymphovenous edema; both grades are reversible. The third grade, advanced, is irreversible, showing destruction of anatomy, severe hemorrhages, and terminal congestive edema.

Capillaroscopy can be a valuable tool for observing and classifying capillary damage. This has the benefit of allowing the observation and monitoring of the reversibility of capillary pathology through comparative figures before and after treatment. In our experience, the most effective treatment involves lifestyle changes, decongestive or compressive therapy, glycemic control, calcium dobesilate, and, if necessary, antibiotics and/or antiplatelet agents to manage infections and/or thrombosis.

Footnotes

ORCID iDs

Abdel Kerim Raffoul-Orozco

Daniel Zingg

Ethical approval

The study conformed to the principles outlined in the Declaration of Helsinki and was and evaluated approved by the ethical and research ethics committee, “Comité de Investigación de CEDIME Instituto Vascular” 22042025.

Informed consent

All patients provided informed consent in accordance with the method prescribed by CEDIME Vascular Disease Center and Ethical Committee.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Abdel K. Raffoul-Orozco reports a relationship with Grünenthal GMBH that includes: employment. Daniel Zingg reports a relationship with OM Pharma Ltd that includes: employment. The other authors declare have no conflicts of interest.

Data availability statement

The data generated and/or analyzed during this study will be shared upon reasonable request to the corresponding author.

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Classification of capillary damage in patients with type 2 diabetes mellitus: Clinical parameters obtained through capillaroscopy—A cross-sectional study

Abstract

Objective

Methods

Results

Conclusions

Keywords

Introduction

Background

Origin and use of capillaroscopy

Studies based on capillary morphology

Methodology

Patient selection criteria

Inclusion

Exclusion

Capillaroscopy examination

Morphological changes

Physiological Changes

Edema

Ethical criteria

Statistical analysis

Results and classification of capillary damage

Discussion

Capillary stasis and compressive edema

Conclusion

Footnotes

ORCID iDs

Ethical approval

Informed consent

Funding

Declaration of conflicting interests

Data availability statement

References