|Ahead of print publication
Nail Fold Capillary Changes in Diabetes Mellitus and Their Correlation with Diabetic Retinopathy
Niraj Bohania1, Sumeet Singla2, Sanjay Pandit2, Anuj Achyut Ban2, Richa Agarwal3, Parul Jain3
1 Consultant Physician, RR Medical and Research Centre, Dalkhola, West Bengal, India
2 Department of Medicine, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
3 Department of Ophthalmology, Maulana Azad Medical College and Guru Nanak Eye Centre, New Delhi, India
|Date of Submission||22-Jan-2022|
|Date of Decision||31-Jan-2022|
|Date of Acceptance||20-Apr-2022|
|Date of Web Publication||11-Jul-2022|
Department of Medicine, Room no 115, 1st floor, BL Taneja block, Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah Zafar Marg, New Delhi-110002
Source of Support: None, Conflict of Interest: None
Abstract Nail fold capillaroscopy (NFC) is mainly used in connective tissue diseases (scleroderma, mixed connective tissue disease, and inflammatory myositis). It is not used routinely in the evaluation of diabetic patients and no specific patterns of nail fold capillary changes have been established in diabetes. We studied morphological patterns of nail fold capillaries by video capillaroscope in diabetic patients and their association with diabetic retinopathy (DR). Fifty diabetics were recruited after informed consent. The mean age of patients was 49.5 ± 10.6 years. Seventeen patients had DR. Capillary length, capillary density, and various morphological parameters were assessed and these parameters were compared between patients with DR and without DR. The most frequent NFC morphological alterations, among diabetics as a group, were tortuous capillaries (56%), giant capillaries (46%), and cross-linked capillaries (44%). Overall, mean nail fold capillary length was reduced in diabetic patients. When individual morphological alterations were compared in patients with DR versus without DR, statistically significant differences were seen for presence of giant capillaries, tortuous capillaries, and avascular areas. On further analysis, mean nail fold capillary length and mean nail fold capillary density were also significantly lesser in patients with DR versus without DR. The presence of nail fold capillary morphological abnormalities among diabetics and a significant association with microangiopathic changes in the retina suggest that microvascular changes can be detected early using a simple, non-invasive office-based method of NFC. More large-scale studies in the future can establish a characteristic pattern for diabetes as seen in systemic sclerosis so that microvascular changes in diabetics can be detected at the earliest with the simple noninvasive method by using NFC.
Keywords: Diabetes, diabetic retinopathy, nail fold capillaries, nail fold video capillaroscope
|How to cite this URL:|
Bohania N, Singla S, Pandit S, Achyut Ban A, Agarwal R, Jain P. Nail Fold Capillary Changes in Diabetes Mellitus and Their Correlation with Diabetic Retinopathy. MAMC J Med Sci [Epub ahead of print] [cited 2022 Nov 26]. Available from: https://www.mamcjms.in/preprintarticle.asp?id=350639
Key Messages: Morphological patterns such as tortuosity, giant capillaries, and decreased capillary density in nail fold capillaries are more common in diabetics. These changes are even more pronounced in the presence of other microvascular complications (diabetic retinopathy). Large-scale studies can establish a characteristic pattern for diabetic nail fold capillary changes and their association with diabetic nephropathy and macrovascular disease.
| Introduction|| |
Diabetes is a heterogeneous disorder characterized by a state of hyperglycemia. It is one of the leading causes of morbidity and mortality worldwide. Complications of diabetes are mostly responsible for morbidity and mortality associated with the disease. Among these, microvascular complications (retinopathy, neuropathy, and nephropathy) are specific to diabetes and one of the important causes of morbidity and mortality.
Microvascular changes in diabetes can be assessed by ophthalmoscopy but it requires a lot of training and dexterity and involves a certain degree of discomfort for the patient. Video capillaroscope to assess nail fold capillaries has not been used frequently in diabetes.,
Nail fold capillaroscopy (NFC) is mainly used in the assessment of connective tissue disorders such as systemic sclerosis, inflammatory myositis, and Raynaud phenomenon. Typical nail fold capillary changes are seen in these diseases. But NFC in diabetes is not used routinely. In the last few years, some studies on nail fold capillary changes in diabetes have been published, but no specific pattern of nail fold capillary changes could be established in diabetes.
We planned this study to look for the presence of NFC abnormalities among diabetic patients and to correlate the presence of these abnormalities with diabetic retinopathy (DR) changes. The objective was to assess NFC as a viable tool for the assessment of microvascular changes in diabetic patients.
| Material and Methods|| |
The objectives of this study were the following:
1. To study the nail fold capillary abnormalities in patients with diabetes mellitus
3. To determine whether nail fold capillary abnormalities among patients with type 2 diabetes are associated with DR
It was an observational, cross-sectional study conducted on 50 diabetic patients, who were recruited from the diabetes OPD during their regular visits. The enrolment of subjects in the study was done after informed consent and in accordance with the principles of the declaration of Helsinki on ethical principles for medical research involving human subjects. Ethics clearance was obtained from the Institutional Ethics Committee.
All consenting adult patients with diabetes mellitus, according to the American Diabetes Association criteria (fasting plasma glucose of ≥126 mg/dL or an HbA1c of ≥6.5%, as measured on two separate occasions), were included.
- History of Raynaud phenomenon or connective tissue disease
- Use of drugs such as glucocorticoids and oral contraceptives
- Occupations with a risk of microtrauma to nails and cuticles of fingers (e.g., farmer, manual laborer, and gardener)
- Active liver disease
- Current pregnancy
- Active infection
- Overt current or past cerebrovascular and/or cardiovascular disease
- Any skin disease precluding the use of NFC.
History and examination for diabetic retinopathy
A detailed history was taken to document the onset of diabetes, duration, major clinical events, level of glycemic control, and treatment. Direct ophthalmoscopy was done by a trained ophthalmologist to look for the presence of DR. Glycosylated hemoglobin was tested using nephelometry in whole blood.
Nail fold video capillaroscopy
After resting the patient for 20 minutes in a room at a temperature of 20 to 24 degrees Celsius, immersion oil was applied to the nail fold of all participants for better visualization. Capillaroscopy was done on four fingers (index and middle fingers of both hands) of all participants at ×200 magnification with a capillaroscopy device [Figure 1] by a trained physician and two images (1 × 1 mm in size) from the middle of the nail fold in each finger were recorded and evaluated. Thus, a total of eight images were obtained and recorded on the video capillaroscopy device for each patient.
The nail fold capillary images were assessed for capillary distribution, density, and morphology according to the Maricq criteria modified by Bergman et al.
Descriptive statistics were presented as frequency, percentage (%), median (minimum–maximum), and mean ± standard deviation. Fisher exact test and Pearson chi-square test were used to assess relationships between categorical variables. The difference between the two groups was tested using the Mann–Whitney U test and Student t test, where appropriate. A value of <0.05 was considered to be statistically significant. All analyses were performed using SPSS version 22.0.
| Results|| |
Demographic and baseline clinical characteristics
Fifty patients with diabetes were included in the study. All of them had type 2 diabetes, except one (type 1 diabetes). Out of these 50 patients, 27 were female while 23 were male. The majority of patients (40%) in this study were between 51 to 60 years, 26% were between 41 and 50 years, 24% were below 40 years, and only 10% were older than 60 years [Table 1]. The mean age of patients was 49.5 ± 10.6 years (range 15–65 years).
In the study, 17 out of 50 patients had DR. The mean duration of diabetes among the patients was 6.6 ± 4.7 years (range: 6 months to 25 years) and the mean HbA1c was 7.79 ± 1.12 % (range: 6.1–11.2%). On further analysis, the mean duration of diabetes was more in patients with DR as compared to those without DR (10.1 ± 5.3 years versus 4.8 ± 3.2 years; P < 0.0001) [Table 2]. Similarly, the mean HbA1c level was higher in patients with DR as compared to those without DR (8.46 ± 1.05 % versus 7.44 ± 1.0%; P < 0.001) [Table 2].
|Table 2 Comparison of baseline clinical characteristics of patients with and without DR|
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Nail fold capillaroscopy findings
Capillary length, capillary density, and various morphological patterns were assessed. These parameters were compared between patients with DR and patients without DR [Table 3].
|Table 3 Comparison of capillaroscopic parameters of patients with and without DR|
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In the study, various morphological patterns [Figure 2]a-g were seen but the most frequent morphological alterations were tortuous capillaries (56%), giant capillaries (46%), and cross-linked capillaries (44%). Other morphological patterns such as avascular areas (9%), hemorrhages (12%), bushy capillaries (8%), and neo-angiogenesis (4%) were also seen [Table 3]. When the individual morphological pattern was compared in patients with DR versus those without DR, statistically significant differences [Table 3] were seen for giant capillaries (P < 0.0001), tortuous capillaries (P < 0.0001), and avascular areas (P < 0.05).
|Figure 2 (a) Normal nailfold capillary pattern, (b-g) Various abnormalities in nailfold capillaries.|
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In the study, the mean capillary length (87.6 ± 39.8 μm) in diabetics was less than the normal capillary length (92–295 μm). On further analysis, the mean capillary length was significantly shorter among patients with DR (67.06 ± 26.28 μm) than patients without DR (98.18 ± 41.78 μm) (P = 0.007) [Table 3]. The mean capillary density among diabetic patients in the study was 10.48 ± 2.84 capillaries/μm. On further analysis, mean capillary density was significantly lesser among patients with DR than patients without DR (8.35 ± 2.23 versus 11.58 ± 2.5 capillaries/μm) (P < 0.0001) [Table 3].
| Discussion|| |
The aim of this study was to look for nail fold capillary changes in diabetes patients and correlate those changes with the presence of DR.
The most frequent morphological alterations in our study were tortuous capillaries (56%), giant capillaries (46%), and cross-linked capillaries (44%). Similar alterations were also seen in other studies. In a study by Bakirci et al., a greater number of tortuous (78.1%) and cross-linked capillaries (98.4%) were seen. A study by Pazos-Moura et al. showed that nail fold capillary changes were seen more among type 2 diabetes than type 1 diabetes patients. In this study, prominent morphological alterations were increased tortuosity and decreased capillary density. In contrast, a study by Barchetta et al. showed more capillary alterations among type 1 diabetes as compared to type 2 diabetes patients. Morphological patterns seen in this study were decreased capillary density, edema, ectasias, and increased diameter. A characteristic nail fold capillary pattern described by Maldonado et al. consists of avascular areas, ectasias, and tortuous and cross-linked capillaries. Tortuosity and angiogenesis were the most frequent morphological alterations in a study conducted by Rajaei et al. Few other studies also showed decreased capillary density along with dilated and tortuous patterns., It may be inferred that NFC abnormalities are found in diabetic patients (both type 1 and type 2), though a typical pattern is not evident.
In our study, the mean capillary length and capillary density were decreased as compared to normal values. Although decreased capillary density has been seen in many studies, capillary length has not been detailed.
A handful of studies on nail fold capillary changes in diabetes are available in the literature and even fewer have compared these changes with the presence and absence of DR. In our study, we compared these nail fold capillary changes with the presence and absence of DR and few patterns showed significant results. Giant and tortuous capillaries were seen more frequently in DR patients as compared to patients without DR. Similarly, capillary length and capillary density were significantly reduced in patients with DR versus those without DR. In a similar study conducted by Uyar et al., few morphological patterns (tortuosity, bushy capillary, neoformation, and ectasias) showed significant differences when compared between patients with and without DR. All this evidence leads us to believe (since patients with DR were found to have higher HbA1c and longer duration of diabetes) that NFC abnormalities are found commonly among those diabetics who have poor glycemic control and longer duration of diabetes. Thus, it is proposed that detection and monitoring of NFC abnormalities may serve as a useful and simple surrogate marker of diabetic microangiopathy in other systemic vascular beds such as glomeruli and retina.
Our study has some limitations too. The sample size was small and there was no control group of healthy people since NFC abnormalities have been documented in healthy people too. But this issue has been addressed by other studies that have conclusively demonstrated that NFC abnormalities are significantly different and more frequent among diabetics than in the healthy population. More important information could have been studied by a prospective follow-up of diabetic patients and evaluating NFC changes over time. Further, the correlation of NFC morphologic alterations with microalbuminuria, C reactive protein, kidney function, and markers of macrovascular disease will tell us the utility of assessing NFC changes among diabetic patients.
| Conclusion|| |
Morphological alterations of nail fold capillaries are seen in diabetes. Various studies have shown different patterns, and no characteristic pattern for diabetes is yet seen as in scleroderma. But few morphological alterations such as tortuosity, giant capillaries, and decreased capillary density are frequently seen in diabetics. These changes are even more pronounced in the presence of other microvascular complications such as DR. Larger, prospective studies are needed to establish a characteristic pattern and progression of nail fold capillary abnormalities in diabetes. The ultimate objective is to detect microvascular changes in diabetics earlier with this easy and noninvasive method of nail fold video capillaroscopy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]