|Year : 2020 | Volume
| Issue : 1 | Page : 28-33
Nail fold capillaroscopic changes in patients with type 2 diabetes mellitus: An observational, comparative study
Deepak Jakhar1, Chander Grover1, Archana Singal1, Gopal Krushna Das2, SV Madhu3
1 Department of Dermatology and STD, University College of Medical Sciences and GTB Hospital, New Delhi, India
2 Department of Ophthalmology, University College of Medical Sciences and GTB Hospital, New Delhi, India
3 Department of Medicine, University College of Medical Sciences and GTB Hospital, New Delhi, India
|Date of Submission||01-Dec-2019|
|Date of Acceptance||23-Dec-2019|
|Date of Web Publication||12-Feb-2020|
Dr. Chander Grover
420-B, Pocket 2, Mayur Vihar, Phase 1, New Delhi - 110 091
Source of Support: None, Conflict of Interest: None
Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease affecting microvascular circulation causing complications such as retinopathy, nephropathy, and neuropathy. Nail fold capillaroscopy (NFC) is an in vivo study of microvascular circulation. Aim: The aim of this study is to describe and quantify NFC changes in type 2 diabetics. Materials and Methods: NFC was done for all 10 fingernails for 96 patients with T2DM (as per the American Diabetes Association criteria) and 40 healthy controls. The diabetics were further subdivided into two groups: those with microvascular complications (Group 1, n = 46) and those without any (Group 2, n = 50). Results: Demographic profile was comparable in both the groups. Overall, 80.2% (77/96) of the patients with T2DM showed NFC changes as compared to 12.5% of the healthy controls. Unique morphological alterations in T2DM were angulated and receding capillaries. Mean capillary density was overall reduced, especially in Group 1 (6.57 ± 1.02 capillary/mm) as compared to Group 2 (7.03 ± 1.09 capillary/mm) (P = 0.67). Overall, 89.13% of Group 1 patients had NFC changes as compared to 72% in Group 2 (P = 0.035). Specific morphological changes were also significantly more common in Group 1 than Group 2, including tortuosity (P = 0.035), meandering capillaries (P = 0.004), capillary dropouts (P = 0.012), and bizarre capillaries (P = 0.002). Limitations: A larger sample size study with different demographic populations could have provided a broader picture of NFC changes in T2DM. Conclusion: Our study suggests that NFC changes are correlated with microvascular complications in type 2 diabetics, possibly helping in noninvasive identification of patients at risk.
Keywords: Angulated capillaries, microangiopathy, nail fold capillaroscopy, receding capillaries, retinopathy
|How to cite this article:|
Jakhar D, Grover C, Singal A, Das GK, Madhu S V. Nail fold capillaroscopic changes in patients with type 2 diabetes mellitus: An observational, comparative study. Indian J Med Spec 2020;11:28-33
|How to cite this URL:|
Jakhar D, Grover C, Singal A, Das GK, Madhu S V. Nail fold capillaroscopic changes in patients with type 2 diabetes mellitus: An observational, comparative study. Indian J Med Spec [serial online] 2020 [cited 2020 May 26];11:28-33. Available from: http://www.ijms.in/text.asp?2020/11/1/28/278093
| Introduction|| |
Nail fold capillaroscopy (NFC) is an established method for in vivo assessment of microvascular circulation and architecture in the proximal nail fold (PNF), especially in connective tissue diseases (CTDs) such as systemic sclerosis.,, It aids in the diagnosis and management of CTDs in a simple, noninvasive yet effective way. However, NFC is still insufficiently applied to diseases other than CTDs, which affect the microvascular circulation.,
Type 2 diabetes mellitus (T2DM) is a metabolic disorder known to affect the microvasculature. Long-term microvascular complications in the form of retinopathy, neuropathy, and nephropathy develop in a sizeable number of patients, at some stage of their disease process., As compared to studies evaluating the retinal microvascular changes in diabetics, very little is known regarding the NFC features of these patients.,, With the fast-growing diabetic population all over the world in general and India in particular, there is a need for an early diagnosis and management of patients at risk, so as to prevent and postpone the future development of microvascular complications.
With an increasing availability of high-quality dermatoscopes which can reliably detect capillary morphological changes, it seems possible that capillary microvascular changes can be evaluated faster and more reliably. The present study attempts to describe and quantify the NFC changes in T2DM to assess whether it may have a role in detecting or monitoring changes in microvascular circulation in an easier manner.
| Materials and Methods|| |
The study was conducted in the outpatient departments of dermatology, internal medicine, and ophthalmology at a tertiary care center. The institutional ethical committee approved the study protocol. Adults (>18 years of age) diagnosed with T2DM, based on the American Diabetes Association criteria and consenting to the study protocol, were included. Forty age- and sex-matched healthy controls were also included in the study. Patients with hypertension or smoking, nail unit infections, onychophagia, onychotillomania, trauma to the nail unit, or frostbite; patients with known CTD or on drugs affecting peripheral circulation; and pregnant and lactating females were excluded. A detailed history, clinical examination including nail examination, and relevant investigations were recorded on a predesigned proforma. All patients were evaluated thoroughly for the presence of microvascular complications in the form of retinopathy, neuropathy, and nephropathy. Based on this, they were divided into Group 1 (with one or more microvascular complication) and Group 2 (those without any microvascular complication).
For all the study participants, a detailed NFC was done for all 10 fingernails, using a Universal Serial Bus (USB) dermatoscope (Dino-Lite AM413ZTDigital Microscope; New Taipei City, Taiwan; polarizing 20-220x). The patients were made to sit at an ambient temperature for 15 min, with hands kept on a dull, nonretractile surface, at the level of the heart. Linkage fluid was applied to the PNF before NFC to enhance the visualization of capillaries. NFC was done, first at a low magnification (×50) for global visualization of capillaries in the entire PNF and then at a higher magnification (×200) for individual capillary architectural change. Images were taken by a single observer and were interpreted by two independent observers.
Both quantitative and qualitative parameters pertaining to nail fold capillaries were evaluated. The quantitative parameter recorded was mean capillary density (MCD), reflecting the number of distal-most capillary loops per millimeter. It was recorded from images from the fourth and fifth fingers of both the hands (total of four nail folds). The center of the PNF was marked near the cuticle with an ultra-thin marker pen, and then, two images (at high magnification) were captured on either side of the marked point. These images were analyzed with the calibration software of the USB dermatoscope, counting the distal-most capillary loops visible over 2 mm length on either side of the marked point, giving us the total number of capillaries over a 4-mm length in an individual finger. The average of the four fingers (right and left fourth and fifth fingers) thus yielded the MCD/millimeter for that individual. The fourth and fifth fingers were chosen because previous studies have shown them to have maximum capillary visibility.,
Qualitative morphological alterations in capillary loops were carefully visualized in all the fingers. The presence of tortuous capillaries (capillary limb curled but not crossing over); meandering capillaries (limbs crossed upon themselves several times); dilated and giant capillaries (width of the capillary >2 times or >10 times the normal, respectively); neoangiogenesis/bushy capillaries (small, multiple buds originating from the distal loop); microhemorrhages; capillary dropouts; avascular areas (absence of two or more adjacent capillaries from the distal-most row); and bizarre capillaries (atypical morphology not conforming to the predefined morphologies) was recorded.,, The visibility of subpapillary plexus was also recorded. The degree of capillary loss was evaluated on the scale proposed by Lee et al. A careful analysis was done to record any new findings as well.
The data recorded were statistically analyzed using SPSS v20 (IBM SPSS Statistics for windows, version 20.0. Armonk, NY: IBM Corp). Continuous variables were expressed as mean ± standard deviation, whereas categorical variables were expressed as frequencies in percentages. The student's t-test and Fisher's exact test were used to compare data. P< 0.05 was considered statistically significant.
| Results|| |
A total of 96 patients diagnosed with T2DM (divided into two groups: Group 1 [n = 46] with microvascular complication and Group 2 [n = 50] without microvascular complications) were evaluated. The baseline characteristics of the two groups are summarized in [Table 1].
|Table 1: Baseline characteristics of Group 1 (type 2 diabetics with microvascular complications) and Group 2 (type 2 diabetics without microvascular complications)|
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In Group 1, 15 patients had diabetic retinopathy, 19 had peripheral neuropathy, 7 had nephropathy, 4 had retinopathy with nephropathy, and one patient had all five microvascular complications. The MCD recorded for T2DM patients (n = 96) was 6.81 ± 1.08 capillaries/mm as compared to 7.67 ± 1.72 capillaries/mm. The MCD in Group 1 (n = 46) was 6.57 ± 1.02 capillaries/mm, while for Group 2 (n = 50), it was slightly higher (7.03 ± 1.09 capillaries/mm). The difference was, however, not statistically significant (P = 0.67). The qualitative capillary changes in healthy controls were tortuosity (12.5%), meandering capillary (10%), microhemorrhages (7.5%), and capillary dilation (7.5%). The qualitative capillary changes in T2DM were seen as tortuous capillaries (80.2%), meandering capillaries (63.5%), capillary dilation (33.3%), microhemorrhages (32.3%), and evidence of neoangiogenesis (31.2%) [Figure 1]a and [Figure 1]b. The difference in the NFC between the healthy controls and T2DM patients was statistically significant (P = 0.01).
|Figure 1: (a and b) Nail fold capillaroscopy showing meandering and tor tuous capillaries (a); dilated capillary and meandering capillaries (b) (Dino-Lite AM413ZT; polarizing view; ×200)|
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In addition to these qualitative features which have been mentioned in other diseases and in previous studies, two peculiar NFC features were noted in T2DM patients. These were receding capillaries (59.4%) and angulated capillaries (42.7%). Receding capillaries [Figure 2]a were seen as individual capillaries maintaining their position in the distal-most row but presenting slightly proximal to the distal-most loops. They probably gave an impression that the capillary had receded backward but had yet not dropped out. Angulated capillaries [Figure 2]b were a special type of tortuous capillary where one or both the arms of the distal capillary loop were seen to bend at an angle. The various qualitative parameters and their comparison between the two groups are shown in [Table 2].
|Figure 2: (a) Receding capillaries visualized as individual capillaries which maintain their position in the distal-most rows but present slightly proximal to the distal-most capillary loops (Dino-Lite AM413ZT; polarizing view; ×200). (b) Angulated capillary visualized as a special type of tortuous capillary where one or both the arms of the distal capillary loop were seen to bend at an angle (Dino-Lite AM413ZT; polarizing view; ×200)|
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|Table 2: Comparative analysis of qualitative nail fold capillaroscopy features observed between diabetics with and without microvascular complications|
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Further subgroup analysis was also done. Group 2 patients (n = 50) were analyzed on the basis of their hemoglobin A1c (HbA1c) levels (>7.0 or < 7.0%) reflecting their glycemic control. The comparison between subgroups with poor or good glycemic control is depicted in [Table 3]. Morphological changes in capillaries were more commonly seen in those with poor glycemic control; however, the results were not consistent and neither were the differences statistically significant. Comparative analysis of NFC features between patients with retinopathy and those with other microangiopathies was also not different statistically [Table 4].
|Table 3: Comparative analysis of qualitative nail fold capillaroscopy features based on hemoglobin A1c levels in diabetics without microvascular complications (n=50)|
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|Table 4: Comparative analysis of nail fold capillaroscopy features in diabetics with retinopathy as compared to those with other microvascular complications (n=46)|
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| Discussion|| |
T2DM is a complex chronic disease prevalent worldwide, becoming even more common with lifestyle changes. The disorder is known to affect microcirculation, leading to micro- and macrovascular complications, which are responsible for much of the morbidity and mortality associated with the disease. The involvement of the microvascular system has been documented in visualized microvascular beds, especially the retina; however, the changes can also be detected and monitored in the nail fold capillaries which are horizontally oriented in the PNF., We used a USB videodermatoscope to study changes in these nail fold capillaries.
The MCD for diabetics (6.81 ± 1.08 capillaries/mm) was slightly lower than the healthy controls (7.67 ± 1.72 capillaries/mm). The expected range of MCD among the healthy controls is 7–14 capillaries/mm.,,,,,, The same is subject to ethnic variations as well, with an Indian study reporting MCD in healthy controls as 8.7 capillaries/mm. Barchetta et al. reported that 10.7% of patients of type 2 diabetics have a MCD <8 capillaries/mm.
The most common qualitative capillary changes in healthy controls were tortuosity, meandering capillary, microhemorrhages, and capillary dilation. Similar observations have been made in the previous studies as well.,,,,,, The NFC changes were significantly higher (P = 0.01) in the T2DM patients. Tortuosity, meandering capillaries, capillary dilation, microhemorrhages, and evidence of neoangiogenesis were common NFC findings in T2DM patients. An interesting observation in these patients was the presence of receding capillaries (59.4%) and angulated capillaries (42.7%). The typical findings in T2DM may be attributed to the advanced glycation end-products (AGEs) which are known to be associated with the macro- and microvascular complications.,,, AGEs are a heterogeneous group of compounds formed by nonenzymatic glycation of proteins, lipids, or nucleic acids, known to affect endothelial cells and pericytes, resulting in impaired angiogenesis.,,, Apoptosis of retinal capillary pericytes and endothelial cells is one of the pathomechanisms resulting in the changes associated with diabetic retinopathy. The changes seen in the NFC of T2DM patients in PNF may be explained by the same mechanism. Since AGEs affect the vascular endothelial cell and pericytes (in turn affecting the capillary wall), the NFC features seen as changes in the capillary architecture tortuosity, meandering, receding, or angulated capillaries may be a result of this. On the other hand, NFC features of collagen vascular diseases, which are much more well known, possibly result due to a complex interplay between vascular endothelial growth factor, antiangiogenic factors (angiostatin, endostatin, tumstatin, and canstatin), and increased levels of hypoxia-induced factor, affecting not only the capillaries but also surrounding connective tissue matrix as well.,, Thus, NFC features are predominantly proliferative in early stages (capillary dilation, giant or bushy capillaries) and regressive in long-standing disease (such as capillary dropouts and avascular areas).
Barchetta et al. reported an abnormal capillary morphology in 67.8% of the 28 T2DM patients studied by them, as compared to 80.2% in our study. However, detailed specification of the specific morphological alterations was not reported in this study. We attempted to specify abnormal capillary morphologies in the form of tortuous, meandering, bushy and bizarre capillaries, angulated and receding capillaries. The frequency of microhemorrhages in their study (10.7% of the patients) was also lower than our observation (32.3%). The difference may be attributable to ethnic variation, other than the larger sample size and higher magnification used in our study.
Upon subgroup analysis, it was seen that patients with microvascular complications had a slightly lower MCD (6.57 ± 1.02 capillaries/mm) than those without (7.03 ± 1.09 capillaries/mm). A comparison of qualitative NFC changes in T2DM patients with and without microvascular changes showed that meandering capillaries (P = 0.004), bizarre capillaries (P = 0.002), capillary dropout (P = 0.012), and capillary tortuosity (P = 0.035) were significantly more common in diabetics with microvascular complications. For other NFC parameters, the differences were not statistically significant even though all alterations were seen more commonly in Group 1 including dilated capillaries (36.95% in Group 1 vs. 30% in Group 2), neoangiogenesis (36.95% vs. 26%), avascular areas (5.3% vs. 0%), microhemorrhages (34.78% vs. 30%), bushy capillaries (13.04% vs. 6%), and angulated capillaries (47.83% vs. 38%). Only, receding capillaries were slightly more commonly seen in diabetics without microvascular complications (60%) as compared to those with microvascular complications (58.70%), suggesting that this could be an early change in capillary morphology. However, this difference between the groups was not statistically significant. We could not find any previous study comparing the NFC features between these two groups.
Overall, patients with diabetic retinopathy (n = 15) were found to have NFC structural alterations more frequently, as compared to patients with other microangiopathies (n = 31); however, the difference was not statistically significant [Table 4]. This could be because of the smaller number of patients with diabetic retinopathy included in our study. In these patients, a comparison of NFC changes with changes seen on fundoscopy revealed that NFC showed more of regressional changes as compared to the retinal changes which were more proliferative in nature. The findings are consistent with a previous study.
HbA1c is an important marker of glycemic control for monitoring disease control in T2DM patients. A value of C.0% has been associated with possibility of the development of microvascular complication. Group 2 patients could be further analyzed on the basis of their HbA1c levels (>7.0 or <7.0%) to study the correlation of glycemic control on NFC. This comparison showed that variations in NFC parameters were not correlated with levels of glycemic control [Table 3]. This could possibly be because HbA1c reflects glycemic control over the past 3–4 months only, whereas morphological alterations in capillaries require a much longer time period to manifest. Furthermore, no correlation was found between the NFC changes and disease duration. These findings were in concordance with previous studies by Barchetta et al. and Pazos-Moura et al.,
A larger sample size including more patients in both the groups could also have enabled us to draw clearer conclusions.
| Conclusion|| |
NFC is a noninvasive, easy to perform, in vivo technique aiding detection of changes in the microvascular bed. Significant changes can be visualized in patients with T2DM, detected in higher frequency among patients with microvascular complications. Our results suggest that NFC could possibly be used as an adjunctive tool in diabetics for diagnosing or monitoring the microvascular complications. Further studies with larger sample sizes can help define its clinical utility.
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Conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]