|Year : 2023 | Volume
| Issue : 4 | Page : 366-371
|Desnutrin as a biomarker for insulin resistance in patients with vitiligo vulgaris
Mohammed Abu El-Hamd1, Ahmed Sedky2, Asmaa B Mahmoud1, Wafaa M Abd El-Magid1
1 From the Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt
|Date of Web Publication||31-Aug-2023|
Mohammed Abu El-Hamd
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag University Street, Sohag City, Sohag - 82524
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Vitiligo is a common depigmented skin disorder characterised by the selective destruction of melanocytes. Aims and Objectives: This study aimed to assess serum desnutrin and its association with insulin resistance in patients with vitiligo vulgaris. Materials and Methods: This study was a cross-sectional case-control study. It included 45 patients with vitiligo vulgaris and 45 age- and sex-matched healthy controls. Patients were subjected to complete general and cutaneous evaluations. All participants were subjected to the assay of fasting blood glucose (FBG), cholesterol, triglyceride, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), fasting serum insulin and serum desnutrin. Homeostasis Model Assessment + insulin resistance (HOMA + IR) was calculated for all participants. Results: There were statistically significant differences between the patients with vitiligo vulgaris and healthy controls regarding HDL, FBG, fasting insulin, HOMA-IR, and serum desnutrin (P < 0.001). Desnutrin levels were negatively correlated with FBS, LDL, VLDL, fasting insulin, and HOMA-IR (P < 0.05). Unlikely, the level of desnutrin had a positive, non-significant correlation with HDL (rho = 0.17, P = 0.059). Conclusion: This study concluded that in patients with vitiligo vulgaris, as a result of increased serum levels of glucose and insulin, the serum desnutrin was suppressed, perhaps contributing to hyperlipidaemia and IR. So, low serum desnutrin could be a biomarker for IR in patients with vitiligo vulgaris. A multidisciplinary approach is essential for the early detection of diabetes mellitus, IR and hyperlipidemia among patients with vitiligo vulgaris to avoid cardiovascular and metabolic complications.
Keywords: Desnutrin, insulin resistance, vitiligo
|How to cite this article:|
El-Hamd MA, Sedky A, Mahmoud AB, Abd El-Magid WM. Desnutrin as a biomarker for insulin resistance in patients with vitiligo vulgaris. Indian J Dermatol 2023;68:366-71
|How to cite this URL:|
El-Hamd MA, Sedky A, Mahmoud AB, Abd El-Magid WM. Desnutrin as a biomarker for insulin resistance in patients with vitiligo vulgaris. Indian J Dermatol [serial online] 2023 [cited 2023 Sep 24];68:366-71. Available from: https://www.e-ijd.org/text.asp?2023/68/4/366/384852
| Introduction|| |
Vitiligo is a depigmented skin disorder characterised by the selective destruction of melanocytes. The etiopathogenesis of vitiligo is multifactorial. It is considered an autoimmune disorder, connected with genetic and environmental precipitating factors jointly with metabolic, oxidative stress and cell-detachment abnormalities. It is present in 0.5–2% of the population. There is great evidence that vitiligo is not only affecting the skin but also has several systemic presentations. It may also be associated with metabolic abnormalities like glucose intolerance and lipid abnormalities, all of which can emphasise the systemic nature of this disease. It has been reported that melanocytes, particularly those present in the adipose tissues, can prevent metabolic syndrome through their capability to reduce inflammation and oxidative damage.
Desnutrin is a member of the family of proteins that can organise adipose tissue lipolysis. It is temporarily activated by fasting and reduced by refeeding. Desnutrin/adipose triglyceride lipase (ATGL) is dominantly expressed in adipose tissues and displays high substrate, especially for triacylglycerol (TAG).,
Desnutrin has been known to act as the main lipase catalysing the hydrolysis of TAG in adipose tissues. TAG accumulation due to desnutrin ablation activates adipocyte hypertrophy. The overexpression of desnutrin causes decreased adipocyte TAG content and decreased diet-induced obesity. Moreover, desnutrin-mediated lipolysis stimulates fatty acid oxidation and re-esterification within adipocytes. Whomsoever, adipose tissue lipolysis is changed, TAG is stored, and free fatty acids are enhanced. This could result in numerous metabolic disorders such as insulin resistance (IR), type 2 diabetes, hypertension, obesity and cardiovascular disorders.,,
Patients with vitiligo vulgaris are more likely to experience increased serum levels of glucose and insulin, which may suppress the serum desnutrin, perhaps contributing to IR. Therefore, this study aimed to assess serum desnutrin and its association with IR in patients with vitiligo vulgaris.
| Materials and Methods|| |
Study design and patient enrolment
This study was a cross-sectional case-control study. It included 45 patients with vitiligo vulgaris and 45 age- and sex-matched healthy controls. Patients were recruited from the Outpatient Clinics of Dermatology at Faculty of Medicine, Sohag University, Upper Egypt between August 2020 and August 2021.
Patients with vitiligo vulgaris of both sexes and an age of 18 years or more were accessed for eligibility to participate in the current study.
Patients with segmental vitiligo, children less than 18 years old, obese, known to be diabetic or hypertensive and pregnant or lactating women, at the time of recruitment, were also excluded from this study.
All the included patients were subjected to the following clinical assessments:
- Patients' data included age, sex, education, occupation, residence, marital status and special habits of medical importance.
- The history of vitiligo included the duration of the disease (years), disease activity (expansion of existing lesions or appearance of new lesions), previous treatment of vitiligo and family history of vitiligo.
- The general examination included weight in kilograms (kg), height in metres (m) and body mass index (BMI). The latter was calculated by dividing body weight (kg) by the square of height (m2).
- Dermatological examination included Fitzpatrick's skin phototype, anatomical site, extension and activity of vitiligo.
- The extension of vitiligo was assessed by the Vitiligo Area Scoring Index. Also, the activity of vitiligo was assessed by the Vitiligo Disease Activity Score.
All the included patients and healthy controls were subjected to the following laboratory assessments:
Five millilitres of venous blood were taken from each participant under aseptic conditions, and by using sterile disposable gloves, the blood samples were allowed to clot at room temperature for 30 minutes and then centrifuged at a speed of 2000–3000 rpm for 15 minutes. The supernatants were collected, and the serum was divided into three aliquots:
- The first one was used for the assessment of fasting blood glucose (FBG), cholesterol, triglyceride (TG), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), which were assessed using the Cobas C 311 Chemistry Analyser System (Roch Diagnostic GmbH, Indianopolis, IN, USA).
- The second one was used for the assessment of fasting serum insulin level using the Architect il000SR system (Abbott Laboratories, Diagnostic Division, Abbott Park, IL).
IR was calculated using the Homeostasis Model Assessment + insulin resistance (HOMA + IR), which was calculated by fasting glucose level (mg/dl) × fasting insulin level (mU/ml)/405. Early IR: HOMA-IR ≤2.9; significant IR: HOMA-IR >2.9.
- The third one was used for assessment of desnutrin by quantitative sandwich ELISA technique using desnutrin human ELISA kit catalogue no: SG-10503 (using ELISA Thermo Fisher Scientific Multiscan EX Microplate Reader, OY, FI-O1621, Vanta, Finland).
This study was approved by the Scientific Research and Ethical Committee at Faculty of Medicine, Sohag University. The study has been conducted following the Declaration of Helsinki. Informed written consent was obtained from participants.
Sample size calculation
The sample size was prospectively calculated with an expected effect size of 0.6, a 95% confidence interval and 80% power for the sample size was 45 patients.
Data were analysed using IBM SPSS Statistics for Windows version 20.0. Quantitative data were expressed as mean ± stander deviation or median and interquartile range. Qualitative data were expressed as numbers and percentages. The data were tested for normality using the Shapiro–Wilk test and normality plots. The non-parametric Mann–Whitney test was used for data that were not normally distributed. The Chi-square (χ2) test was used for the comparison of qualitative variables. Pearson Correlation/Spearman Rank correlation analysis was used to test the association between variables as appropriate. A 5% level was chosen as a level of significance in all statistical tests used in the study.
| Results|| |
This study included 45 patients with vitiligo vulgaris and 45 healthy control subjects. There were no statistically significant differences between the patients with vitiligo vulgaris and healthy control subjects regarding age, gender, weight, height and BMI (P > 0.05) [Table 1].
|Table 1: Comparison between the patients and controls regarding age, gender, weight, height and BMI|
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The clinical characteristics of vitiligo patients are shown in [Table 2].
There was a statistically significant lower value of HDL among patients with vitiligo vulgaris than healthy control subjects (P = 0.015), while there were no statistically significant differences between the patients and controls regarding cholesterol, TG, LDL, and VLDL (P > 0.05) [Table 3].
|Table 3: Comparison between the patients and controls regarding lipid profile|
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There were statistically significant higher values of FBG, fasting insulin and HOMA-IR among patients with vitiligo vulgaris than healthy control subjects (P < 0.001). There were statistically significant lower values of desnutrin among patients with vitiligo vulgaris than healthy control subjects (P < 0.001) [Table 4]. Of 34 (75.56%) patients with vitiligo vulgaris and HOMA-IR, 16 (35.56%) had significant IR and 18 (40%) had early IR [Table 5].
|Table 4: Comparison between the two study groups regarding FBG, fasting insulin, HOMA + IR and desnutrin|
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|Table 5: Comparison between the two study groups regarding patterns of the IR|
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The level of desnutrin showed a negative high-moderate correlation with FBS (r = -0.44, P < 0.001). Likewise, the desnutrin level showed a negative moderate correlation with LDL and VLDL (r = -0.22 and -0.26, respectively), and this was statistically significant (P = 0.021 and 0.007). Notably, there was a high moderate and a high negative significant correlation between desnutrin level, fasting insulin and HOMA + IR (rho = -0.58 and -0.63. P < 0.001). On the other hand, there were negative mild non-significant correlations between desnutrin level and both cholesterol and total TG (rho = -0.13 and -0.18, P = 0.112 and 0.050). Unlikely, the level of desnutrin had a positive non-significant correlation with HDL (rho = 0.17, P = 0.059) [Table 6].
|Table 6: Correlations between desnutrin and laboratory parameters among vitiligo patients|
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| Discussion|| |
Vitiligo is an acquired disease in which progressive patchy loss of pigmentation of the skin, overlying hair and mucous membranes results from the local destruction of melanocytes at the affected sites. The destruction of melanocytes in vitiligo patients appears to have an autoimmune groundwork, resulting from a combination of genetic and environmental precipitating factors. Vitiligo is epidemiologically connected with other autoimmune diseases. Mahajan et al. found that the incidence of vitiligo was higher in non-insulin-dependent diabetic patients compared with healthy controls. Also, Vijayasingam et al. found a 3.3% incidence of vitiligo in diabetic patients. On the other hand, the incidence of diabetes was higher in patients with vitiligo compared with the general population.,,
The current study reported that there were statistically significant higher values of FBG, fasting insulin and HOMA + IR among patients with vitiligo vulgaris than healthy control subjects; these findings were in agreement with Karadag et al., who found that patients with vitiligo had higher insulin levels and IR than healthy control subjects.
Also, this study found that 34 (75.56%) patients with vitiligo vulgaris had HOMA-IR; (16 (35.56%) had significant IR, and 18 (40%) had early IR). Of the control subjects, no significant IR was reported, and 17 (37.78%) had early IR.
Tumour necrosis factor-alpha, interleukin-1 (IL-1), IL-6 and IL-6 are the main pro-inflammatory cytokines that could play an important role in the pathogenesis of vitiligo. Also, these cytokines are linked with IR, atherosclerosis and several metabolic complications.,,
Without diabetes, IR is a serious risk factor for cardiovascular disorders with early mortality. IR activates glucose transport in adipose tissues and skeletal muscles, which is one of the earliest defects reported with IR. Overtly, hyperglycemia occurs when enhanced insulin secretion no longer compensates for IR.
This study found that there was a statistically significant lower value of HDL among patients with vitiligo vulgaris than healthy control subjects, while there were no statistically significant differences between the patients and controls regarding cholesterol, TG, LDL and VLDL. Whereas Karadag et al. found that there were significantly lower HDL levels and a higher LDL/HDL ratio among patients with vitiligo than healthy control subjects. Pietrzak et al. reported that girls with vitiligo had significantly lower HDL values and higher LDL values than those of healthy controls. In this study, the values of cholesterol, TG, LDL, and VLDL among patients with vitiligo vulgaris were not significantly higher than healthy control subjects, which could be explained by early evaluations of these patients.
The serum desnutrin levels were influenced by some cutaneous diseases like acne and psoriasis., It has been reported that the development and progression, but not the severity, of acne vulgaris among susceptible individuals might be influenced by the serum desnutrin level. Serum desnutrin levels among psoriatic patients were lower than those of the control participants.
To the best of our knowledge, no previous research has assessed serum desnutrin levels and their association with IR in patients with vitiligo vulgaris. The current study revealed significantly lower serum desnutrin levels in patients with vitiligo vulgaris when compared with healthy control subjects. Also, desnutrin levels were negatively correlated with FBS, LDL, VLDL, fasting insulin and HOMA + IR. Unlikely, the level of desnutrin had a positive, non-significant correlation with HDL.
It has been reported that insulin is a strong anti-lipolytic hormone that can inhibit postprandial lipolysis. Desnutrin is inhibited by insulin secretion and enhanced lipolysis due to extended fasting. Suppression of desnutrin lipase activity by insulin has been recorded as a contributing factor in the development of obesity, hyperlipidaemia and IR.
However, this study requires more verification in large-scale clinically controlled studies to precisely evaluate the serum levels of desnutrin and the expression of desnutrin in vitiligo and non-vitiligo tissue. Also, future research comparing serum levels of desnutrin among vitiligo patients with or without metabolic syndrome is recommended. Further randomised clinical studies are needed to assess the genetic polymorphism of desnutrin genes.
This study concluded that in patients with vitiligo vulgaris, as a result of increased serum levels of glucose and insulin, the serum desnutrin was suppressed, perhaps contributing to hyperlipidaemia and IR. So, low serum desnutrin could be a biomarker for IR in patients with vitiligo vulgaris. A multidisciplinary approach is essential for the early detection of diabetes mellitus, IR, and hyperlipidemia among patients with vitiligo vulgaris to avoid cardiovascular and metabolic complications.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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