Prevalence of Skin Changes in Diabetes Mellitus and its Correlation with Internal Diseases: A Single Center Observational Study

Abstract

Background and Aim:

This single-center observational cross-sectional study has been done in an attempt to find out the prevalence of various skin manifestations in diabetes patients (DM) and their correlation with diabetes control and complications.

Materials and Methods:

Skin manifestations present over 12 months among those attend diabetes clinic were included in the study. Apart from demographic data and type, patients were also screened for micro vascular complications and control of diabetes over last 3 months.

Results and Discussion:

Sixty (n = 60) diabetes patisents (Type 1 DM, 9 patients and Type 2 DM 51 patients) have been found to have various skin lesions. Thirty-one (51.67%) patients presented with infectious conditions, vascular complications were present in 21 (35%) and dermatomes belonging to the miscellaneous group were present in 50 (83.33%) patients. Pyoderma, diabetic dermopathy, and pruritus without skin lesions were found to be most common manifestations in infective, vascular and miscellaneous group, respectively. Higher level of HB1_AC was found in patient with diabetic bulla (10.5 ± 0), scleredema (9.75 ± 0.77), lichen planus (9.3 ± 1.6), and acanthosis nigricans (9.15 ± 0.89). Patients with psoriasis and vitiligo had statistically significant lower level of glycosylated hemoglobin (P =< 0.001 and 0.03, respectively). However, no association of any kind of skin manifestation with DM with other microangiopathic complications was found in this study.

What was known?

Skin manifestations in diabetes are very common and a frequent subject of study though often neglected in clinical grounds.

Introduction

Diabetes mellitus (DM) is a metabolic disease characterized by relative or absolute insulin deficiency. The metabolic abnormality in DM results in gross defect in protein, carbohydrate and fat metabolism.[1] Presently DM affects individuals of all ages and in all socio-economic segments of the population. The International Diabetes Federation (IDF) estimated the total number of diabetic subjects to be around 40.9 million in India and this is further set to raise to 69.9 million by the year 2025.[2] WHO suggests that the number of diabetic subjects would increase to 80 million by the year 2030 in India.[3] Skin lesions are frequently observed in diabetic patients and about 30% of diabetics have cutaneous disorders.[4]

There are many proposed patho-mechanism for skin involvement in DM, which includes abnormal carbohydrate metabolism, other altered metabolic pathways, atherosclerosis, microangiopathy, neuron degeneration and impaired host immune mechanism.[5] Some studies revealed the correlation of skin manifestation of DM with microangiopathic complications.[6,7] However, a large-scale study in Indian population aiming at finding out the correlation of the skin manifestations with internal complication of DM is lacking till date.

There is also paucity of studies in this Eastern India to find out the prevalence of various types of skin changes among the diabetic individuals; hence, this study is an attempt to fill this lacunae. Moreover, this study also aims at searching the relationship of skin changes with microangiopathic complications of DM, so as to use them as early marker of the internal complications.

Materials and Methods

This observational study was a collaborative effort of Department of Dermatology and Endocrinology of a tertiary care hospital in Eastern India. All patients attending the Diabetes clinic of the institute (held twice a week) were evaluated for the presence of any skin lesion over a period of 12 months. Diabetes was diagnosed as per the criteria laid down by National Diabetes Data Group and World Health Organization, if any two of the following criteria were present: Symptom of DM and random plasma glucose ≥200 mg/dl or fasting blood sugar (8 hours) ≥126 mg/dl or 2 hours plasma glucose (75 mg) ≥200 mg/dl during an oral glucose tolerance test.[8]

Detail evaluation of demographic profile and clinical manifestations were carried out. Emphasis was given to assess the micro vascular complications (i.e. nephropathy, neuropathy, and retinopathy) and relevant investigations were done. Neuropathy was diagnosed by nerve conduction velocity test (NCV) and criteria detailed by Foster.[9] Nephropathy was diagnosed if microalbuminuria is present excluding other contributing factors. Assessment of diabetic retinopathy was done by opinion of ophthalmologist. The glycemic control was evaluated by measuring the glycosylated hemoglobin (Hb1_AC).

For the purpose of the study we had divided the skin manifestations due to DM in three different categories:

• Cutaneous infections due to immune alterations like bacterial, viral and fungal infections

• symptoms due to vascular abnormalities and

• miscellaneous conditions, where etio-pathogenesis could not be explained by vascular or infective complications.

Data were statistically described in terms of range, median, mean ± standard deviation (±SD), as appropriate. The continuous variable data were analyzed using the t-test and the categorical data were analyzed using the Chi-square test. Medcalc statistical software^® version 9.6.4.0 (http://www.medcalc.be) was used for statistical analysis and a P ≤ 0.05 was considered statistically significant.

Results

Among 200 patients who attended the diabetes clinic over the 6 month period, 60 patients (9 of them had type 1 DM and 51 had type 2 DM) had skin changes. Demographic profiles of the patients are represented in Table 1. The mean age and BMI were significantly high in the Type 2 DM compared to Type 1 DM (P < 0.001 and P = 0.002, respectively). We found no significant gender difference or significant difference in blood sugar level or glycosylated hemoglobin (Hb1_AC) among Type 1 and Type 2 DM patients.

Table 1.

Demographic profile of study population

Thirty-one (51.67%) patients presented with infectious conditions, vascular complications were present in 21 (35%) and dermatomes belonging to the miscellaneous group as per our study protocol were present in 50 (83.33%) patients.

Among the infectious complications pyoderma [Figure 1] was the most common complication (n = 14, 23%), followed by onychomycosis and genital candidiasis [Figure 2] (n = 4, 6.67% each) being most common among the infectious complications.

Figure 1.

Severe pyoderma in a long-standing uncontrolled diabetes patient

Figure 2.

Extensive genital candidiasis

Among the vascular complications, diabetic dermopathy was the most common cutaneous microangiopathic complication (n = 13, 21.6%) followed by wet gangrene which was present only in two cases.

Among the miscellaneous complications pruritus without skin lesions was most common (n = 8, 13.33%), [Figure 3] followed by acanthosis nigricans (n = 7, 11.67%), xanthelasma palpebrarum (n = 6, 10% of study populations), skin tag (n = 5, 8.3% of study populations), maculopapular rash and PPD (n = 4, 6.67% of study populations), lipodystropy and vililigo (n = 3,5% of study populations) porokeratoses, ichthyosis and xerosis, lichen planus, limited joint mobility psoriasis and scleroderma (n = 2, 3.33% of study populations). Diabetic bulla was found in only one patient.

Figure 3.

Prurigo as a result of pruritus

Regarding age at presentation, wet gangrene (32.5 ± 7.77 years), pruritus (35.37 ± 16.61 years) and ichthysis and xerosis (38 ± 48.08 years) were found to arise at an early age in our study population. Genital candidiasis (62.25 ± 2.21 years) and onychomycosis (64 ± 6.73 years) were found to be significantly associated with those patients presenting at advancing age (P = 0.0357 and P = 0.0147, respectively).

Higher level of HB1_AC was found in patient with diabetic bulla (10.5 ± 0), scleredema (9.75 ± 0.77), lichen planus (9.3 ± 1.6), acanthosis nigricans (9.15 ± 0.89). Patients with psoriasis and vitiligo had statistically significant lower level of glycosylated hemoglobin (P =< 0.001 and 0.03, respectively). Table 2 represents relationship of microangiopathic complications of DM (retinopathy, nephropathy and neuropathy) with skin changes. No statistically significant associations of any of the cutaneous manifestations with DM control were found.

Table 2.

Relation of various skin diseases with micro vascular complications

Discussion

DM is a common condition. International Diabetes Federation (IDF) estimated the total number of diabetic subjects to be around 40.9 million in India and this is further set to raise to 69.9 million by the year 2025.[2] Almost all diabetic patients eventually develop skin complications. Most of the time a patient is unaware that his skin condition is due to diabetes. So the exact data of prevalence of skin changes among the diabetic patients is difficult to obtain. Various studies reported 7.6% to 30%[4,10,11] study carried out by Yosipovitch et al. found prevalence of skin manifestations among the Type 1 DM population is as high as 71%.[12] In our study a wide variation of prevalence of skin changes of diabetic population may be due to lack of knowledge and attitude of the diabetic patients towards their skin problem. In fact, an institution-based cross-sectional study in this eastern part of the world carried out by Hussain et al.[13] found that in most of the cases the person is not concern that their skin condition is due to DM and even in more than in 50% of the treating physician fails to inform the complications.

Various study reported age of presentation of Type 2 DM patients with skin manifestation is between 5^th to 6^th decade.[10,13,14] Age of presentation of Type 2 DM of our study populations is 51.21 ± 10.38 which matches with previous study findings. Among the patients presented with skin manifestations 15% was Type 1 and 85% Type 2 DM. Study carried out by Cvitanovi et al.[11] had almost similar finding. The occurrence of lower incidence of skin changes among type 1 DM might be due to lower disease burden of Type 1 DM patients as compared to Type 2 DM patients.

The prevalence of different types of skin changes varies considerably in different studies. A south Indian study revealed that infectious complications are most common complications. Fungal infection was the most common infectious complication. Among the other complications, 2(2.27%) had xanthelasma palpebrarum, 1(1.14%) had pruritus without any skin lesions, 2 patients had diabetic dermopaty and 1(1.14%) had diabetic bulla. Polyneuropathy and diabetic ulcer was noted in one patient each. Miscellaneous conditions like vitiligo, lichen planus, drug reactions, lichen simplex, pustular bacterid, atopic dermatitis, eczema, psoriasis, skin tag and pemphigus vulgaris were noted in 20 patients altogether. Pruritus was the most common skin symptom.[10] Another Indian Study carrier out by Mahajan et al.[15] in North India found infectious complication was most common. On the other hand, a Croatian-based study showed diabetic dermopathy was the most common cutaneous manifestation (32, 14%). The second common was skin infections associated with DM and were found in 16.47% patient which is much lower than Eastern studies. Third group represented diabetic complications, and was found in 11 patients (13, 10%) and the most common changes were ulcers in 4(4,76%) patients and xerosis in 4(4, 76%) patients.[11] Another western study among the populations of Type 1 DM reported xerosis as the most common skin manifestation. That study found that ichthyosiform skin changes of the shins, scleroderma-like skin changes, tinea pedis, and dry scaly palms were detected in 48 vs. 7%, 39 vs. 0%, 32 vs. 7%, and 21 vs. 0.8% of the patients and control subjects, respectively.[12]

Considering individual types infectious complications are the most common complication in our study which matches the findings of the other studies of this eastern part of the world. However, our study found pyoderma as the most common cutaneous manifestation, while other study found mycosis as the most common skin findings. Our study also revealed statistically significantly higher occurrence of onychomycosis and genital candidiasis among the diabetic populations with increasing age.

Diabetic dermopathic was found to be the most common microangiopathic cutaneous complication. We also found statistically significant lower level of Hb_1Ac among the patients with vitiligo and psoriasis. This may be due to patients with psoriasis and vitiligo becomes more stringent regarding their diabetic control.

Regarding association of DM with other microangiopathic complications our study did not found any association of any kind of skin manifestations with DM. On the other hand, the study carried out by Mahajan et al.[15] found higher percentage of retinopathy (58.3%) and neuropathy (25%) among the patient with vasculopathic complication of DM. Another study carried out by Sawhney et al.[16] found though not statistically significant, dermopathy was more commonly associated with retinopathy (33.3% compared to only 13.7% who did not have dermopathy.). Goyal et al.[17] reported xerosis is predominant findings in hundred diabetic patients in Indian background. Ragunatha et al. found signs of insulin resistance, acrochordon (26.2%), and acanthosis nigricans (5%) as the most common presentation in 500 Indian diabetic cohorts.[18] But association of microangiopathic complications with skin lesions is not documented in any large-scale studies. Our study failed to reveal any association in this regard. More large-scale study involving more number of study populations may reveal this association in future.

What is new?

• Uncontrolled DM or higher HB1AC is associated with diabetic bulla, scleredema, lichen planus and signs of insulin resistance.

• No association with any kind of skin manifestations and microangiopathic complications though often cited as an etiopathogenic factor was found in this observational study.