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ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 1  |  Page : 89-93

Effect of obesity on YKL-40 serum level to evaluate its role as an independent marker in type 2 diabetic nephropathy


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Internal Medicine, Ministry of Health, Tanta, Egypt

Date of Submission14-Oct-2018
Date of Decision18-Nov-2018
Date of Acceptance25-Nov-2018
Date of Web Publication25-Mar-2020

Correspondence Address:
Fady W. T. Morkos
Department of Internal Medicine, Ministry of Health, Tanta
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_331_18

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  Abstract 

Objective
The objective of this study was to evaluate the serum YKL-40 level as an independent marker in patients with type 2 diabetic nephropathy (DN).
Background
DN is a microvascular complication of type 2 diabetes mellitus. The association of YKL 40 serum level with obesity and type 2 DN has not been adequately studied.
Patients and methods
This study was conducted on 75patients with type 2 DN(25 obese with type 2 DN,25 nonobese patients with type 2 DN,and25 obese without diabetes) fromJuly 2017 to February 2018. Full history, physical examination, serum urea, serum creatinine, estimated glomerular filtration rate (eGFR), glycated hemoglobin 1c (HbA1c), serum YKL-40, urinary albumin/creatinine ratio (ACR) and abdominal ultrasonography were done.
Results
There was no significant difference among the three groups regarding sex (P = 0.527), drug taking (P = 1.0), age (P = 0.149), and serum urea (P = 0.496), whereas there was a highly significant difference among all groups regarding BMI, YKL 40 serum level, ACR, HbA1c, eGFR, and serum creatinine level (P = 0.001 for all). YKL-40 level was significantly positively correlated with BMI, creatinine level, ACR, and HbA1c and in a negative correlation with eGFR in all groups.
Conclusion
YKL-40 significantly correlates with biochemical renal parameters like ACR, creatinine, and eGFR; glycemic parameter, HbA1c; and obesity measure, BMI. Our study suggests that YKL-40 can be a marker of microvascular complications such as DN but not an independent marker owing to positive affection of obesity on its serum level.

Keywords: diabetic nephropathy, obesity, type 2 diabetics, YKL-40


How to cite this article:
Korany MA, Nouh MZ, Omar TA, Morkos FW. Effect of obesity on YKL-40 serum level to evaluate its role as an independent marker in type 2 diabetic nephropathy. Menoufia Med J 2020;33:89-93

How to cite this URL:
Korany MA, Nouh MZ, Omar TA, Morkos FW. Effect of obesity on YKL-40 serum level to evaluate its role as an independent marker in type 2 diabetic nephropathy. Menoufia Med J [serial online] 2020 [cited 2020 Aug 15];33:89-93. Available from: http://www.mmj.eg.net/text.asp?2020/33/1/89/281302




  Introduction Top


YKL-40 is a substance that may be found in higher-than-normal amounts in the blood of patients with certain types of cancer and inflammatory diseases[1]. It is a type of glycoprotein, and its name is derived from its three N-terminal amino acids, tyrosine (y), lysine (K) and leucine (L), and its molecular mass of 40 kDa[2]. Inflammation, fibrosis, solid carcinoma, asthma, and extracellular tissue remodeling are associated with its pattern of expression, but main biological function of YKL-40 is unclear and it does not have a specific receptor[3],[4]. Approximately 415 million people had diabetes worldwide, with type 2 diabetes mellitus (T2DM) making up ~90% of the cases. This represents 8.3% of the adult population, with equal rates in both women and men[5]. Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, progressive decline in the glomerular filtration rate, and elevated arterial blood pressure. It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes, and it is the most common cause of end-stage kidney disease[6].

Obesity has a strong relationship with T2DM and is a major cause of increase in its prevalence[7]. The global prevalence of T2DM has more than doubled in the past 30 years and is predicted to continue to rise at an alarming rate[8]. Until now, there is no evidence of association between YKL-40 and DN and obesity. The aim of this study was to evaluate the serum YKL 40 level as an independent marker in patients with type 2 DN and effect of obesity on its serum level at Internal Medicine Department, Menoufia University Hospital.


  Patients and Methods Top


This study was conducted in Internal Medicine Department, Menoufia University Hospital, for 8 months from July 2017 to February 2018, on 75 patients, who were divided into three groups: group A includes 25 obese patients with type 2 DN, group B includes 25 nonobese patients with type 2 DN, and group C includes 25 obese patients without diabetes.

Ethical consideration

The study was approved by the Ethical Committee of Faculty of Medicine, Menoufia University, and an informed consent was obtained from all patients before the study was commenced.

Exclusion criteria

The following were the exclusion criteria: a previous history of clinical microvascular or cardiac heart disease, history of malignancy, patients with primary hypertension, alcoholics, patients with active urinary tract infection, patients with other renal diseases, patients with active inflammatory disorders, and patients with liver failure.

All cases were subjected to the following: complete history including personal, present, past, and family history such as, age, relative consanguinity, and drug history, and clinical examination, including general such as anthropometric measurements, involving height, weight, and BMI, and local, involving cardiovascular system, central nervous system, abdominal, and chest.

Investigations: kidney functions

Blood urea and serum creatinine were assessed using the open system autoanalyzer synchron CX5 (Beckman Coulter Inc., Fullerton, California, USA)[9]. Glycated hemoglobin Alc (HbA1c) was produced by a nonenzymatic reaction between glucose and the terminal valine of the B-chain of the hemoglobin molecule[10]. Urinary albumin/creatinine ratio (ACR) was estimated by Beckman Microalbumin test kit on Synchron CX9 autoanalyzer Beckman, wherein normoalbuminuria is less than 30 mg albumin/g creatinine[11]. Estimated glomerular filtration rate (eGFR) in this study was estimated using Cockcroft–Gault formula, which in turn estimates glomerular filtration rate in ml/min. This formula expects weight to be measured in kg and creatinine to be measured in mg/dl. The resulting value is multiplied by a constant of 0.85 if the patient is female. Creatinine clearance={[(l × 40 − age)×weight]/(72 × serum creatinine)} × 0.85 (if female)[11]. Ultrasonography was done to exclude other renal diseases and hepatic patients. Serum YKL-40 level was determined by enzyme-linked immunosorbent assay (ELISA) (Molecular Devices, Sunnyvale, California, USA)[12].

Methods

A venous blood sample (8.1 ml) was withdrawn from each individual under aseptic conditions using sterile disposable syringe and then dispensed into two tubes: 4.1 ml of blood was delivered into a tube containing K-EDTA for HbA1c, and 4 ml of blood was delivered into a plain tube in which serum was separated by centrifugation on 3000 rpm for 10 min and used for assessment of renal function (urea and creatinine) and YKL-40 (by ELISA).

Urine sample

A morning urine sample and a second voided morning sample were cleanly collected. Samples contaminated with blood were excluded. Samples were centrifuged at 3000 rpm for 10 min before analysis to remove any cells or debris. This was used for estimation of ACR and for urine analysis.

Human chitinase-3-like protein 1 (YKL-40/CHI3L1; Molecular Devices) was estimated using ELISA. The median serum concentration of YKL-40 in healthy adults is 43 μg/l[1].

Test principle

The kit uses a double-antibody sandwich-ELISA to assay the level of human chitinase-3-like protein 1 (YKL-40/CHI3L1) in samples.

Summary of the procedures

Preparation of reagents, samples, and standards was done. Then the prepared samples and standards were placed in separated plates, and antibodies labeled with enzyme were added and left to react for 60 min at 37°C. The plates were washed five times. Then chromogen solutions A and B were added and left to react for 10 min at 37°C. Stop solution was added, and the optical density value was measured within 10 min, followed by calculations.

Statistical analysis

Results were tabulated and statistically analyzed by using a personal computer using Microsoft Excel 2016 and SPSS, version 2 (SPSS Inc., Chicago, Illinois, USA). Statistical analysis was done as follows: descriptive, for example, percentage (%), mean, and SD, and analytical, which includes χ2-test, Student's t-test, Mann–Whitney test, one-way analysis of variance test, Kruskal–Wallis test, and Pearson's correlation coefficient (r). A value of P less than 0.05 was considered statistically significant.


  Results Top


This study included 39 (52%) males (13, 15, and 11 in groups A, B and C, respectively) and 36 (48%) females (12, 10, and 14 in groups A, B, and C, respectively). In this study, the numbers of patients on oral hypoglycemic drugs were 15 in group A and 15 in group B, whereas there were 10 patients on insulin in group A and 10 patients on insulin in group B. There was no significant difference among the three groups regarding sex (P > 0.05) and drug taking (P = 1.00) [Table 1].
Table 1: Comparison between the studied groups regarding sex and drug taking

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In this study, the mean age was 57 ± 12.5 years in group A (obese patients with DN), 61.88 ± 5.88 years in group B (no-obese patients with DN), and 58.04 ± 7.91 years in group C (obese patients). There was no significant difference between three groups regarding age (P > 0.05). Regarding BMI, the mean in group A was 34.08 ± 2.43, in the group B was 22.00 ± 1.61, and in the group C was 32.44. The mean YKL-40 level in group A was 285.80 ± 67.26, in group B was 121.84 ± 36.54, and in group C was 45.68 ± 4.92. The mean range of ACR in group A was 440.48 ± 175.07, in group B was 154.56 ± 74.00, and in group C was 24.08 ± 4.36. The mean HbA1c in group A was 7.42 ± 0.73, in group B was 7.89 ± 0.94, and in group C was 5.40 ± 0.26. The mean eGFR in group A was 65.98 ± 16.68, in group B was 44.83 ± 9.15, and in C group was 101.64 ± 25. There was a highly significant difference among all groups regarding BMI, YKL-40 level, ACR, HbA1c level, and eGFR (P = 0.001 for all), whereas there were no significant differences between all groups regarding urea level (P = 0.496). However, there was a highly significant difference between all groups regarding creatinine level (P = 0.001) [Table 2].
Table 2: Comparison between the studied groups (obese + diabetic nephropathy, diabetic nephropathy, and obese) regarding age, BMI, YKL 40, albumin-creatinine ratio, glycated hemoglobin 1c, and renal function

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Moreover, this study shows that YKL-40 level was significantly positively correlated with BMI (P = 0.001, 0.005, and 0.001, respectively), creatinine level (P = 0.002, 0.001, and 0.035), ACR (P = 0.001, 0.001, and 0.001, respectively), and HbA1c (P = 0.001, 0.001, and 0.001, respectively), and negatively correlated with eGFR (P = 0.031, 0.001, and 0.038, respectively) in group A (obese patients with DN), group B (nonobese patients with DN), and group C (obese patients) [Table 3].
Table 3: Pearson's correlation (r) between YKL-40 and other parameters in the studied groups

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  Discussion Top


This study found a significant association between serum YKL-40 level and obesity (P < 0.05). In agreement with this study, Abdelaal et al.[8] conducted their study on 60 patients classified equally into three groups, with 20 patients each, according to their BMI, as overweight having BMI of 25–29.9 kg/m2, obese having BMI of 30–34.9 kg/m2, and morbid obese having BMI of at least 35 kg/m2. They found a positive correlation between YKL-40 level and BMI. In addition, Hempen et al.[13] conducted their study on 17 patients of morbid obesity and found a significant association between serum YKL-40 level and obesity and proved that YKL-40 is elevated in morbidly obese patients and declines after weight loss. A study conducted by Thomsen et al.[14] on 324 nondiabetic relatives to patients with T2DM showed that fasting serum YKL-40 levels were positively associated with measures of obesity and dyslipidemia, especially with measures of waist, and waist–hip ratio, but not with BMI. Moreover, many studies have shown that serum levels of YKL-40 in diabetic patients are higher than in a control group. Rathcke et al.[15] proved that YKL-40 had a correlation with type 1 DN and suggested a role of YKL-40 in the occurrence of microvascular complications during renal vascular damage. Thus, they considered that YKL-40 might be useful as an independent marker[15],[16].

In this study, there was a positive association between serum YKL-40 and type 2 DN regarding ACR in urine samples (P < 0.05) in the three studied groups, which was in agreement with Røndbjerg et al.[17], who conducted their study on 105 patients with T2DM: 49 with normoalbuminuria (urine albumin/creatinine <2.5 mg/mmol), 35 with persistent microalbuminuria (2.5–25 mg/mmol), and 21 with persistent microalbuminuria/DN (>25 mg/mmol). The control group consisted of 20 healthy individuals. They concluded that YKL-40 levels were elevated in patients with T2DM with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. Another study by Paarivalavan et al.[18] showed the role of plasma and urinary YKL 40 in early diagnosis of nephropathy in T2DM patients. They conducted their study on 20 (T2DM) patients in the age group of 35–60 years, who were compared with age-matched 20 healthy controls. They found that both plasma and urine YKL-40 levels were significantly higher in patients with T2DM. Besides, YKL-40 positively and significantly correlated with important measured renal parameters, which is in agreement with our study, except that our study also found a significant correlation with obesity index or what is called BMI with serum level of YKL-40. The study by Han et al.[16] also proved a significant correlation between the level of YKL-40 and urinary albumin, which is in agreement with our study, but they differed from our study also in that we found a significant correlation between YKL-40 serum level and BMI.

In this study, there was a positive correlation between YKL-40 serum level and ACR and HbA1c, which is in agreement with Han et al.[16]. This study found a positive correlation with serum YKL-40 level and creatinine level, which is in agreement with Paarivalavan et al.[18]. This study also found a highly significant difference among the three groups according to eGFR (P = 0.001) and a negative significant correlation with YKL-40 in the three groups (P = 0.031, 0.001, and 0.038, respectively), which is in agreement with Paarivalavan et al.[18] who conducted their study on 110 patients, but was against the study by Røndbjerg et al.[17] who conducted their study on 105 patients with T2DM. YKL-40 positively and significantly correlates with measured biochemical renal parameters like ACR and creatinine and also with HbA1c but negatively correlates with eGFR. This proves the fact that YKL-40 can be assumed as a marker in DN, but serum YKL-40 level was also positively significantly correlated with BMI. These results may be owing to the fact that obesity is accompanied by a low-grade inflammatory condition through an increase of macrophage infiltration in adipose tissues, which represents the source of many of the circulating inflammatory molecules and suggest that YKL-40 plays a role in obesity-related inflammation[19]. Previous studies have suggested that the visceral adipose tissue could be an important source of released YKL-40 in obesity, and as YKL-40 is known to regulate other inflammatory markers, for example, increase the expression of monocyte chemoattractant protein-1 in alveolar macrophages of patients with chronic obstructive pulmonary disease, it is possible that YKL-40 plays a role in orchestrating the inflammatory response originating from the visceral adipose tissue[20].


  Conclusion Top


YKL-40 significantly correlates with biochemical renal parameters like ACR, creatinine, and eGFR; with glycemic parameter HbA1c; and also with the obesity measure BMI. Our study suggests that YKL-40 can be a marker of microvascular complications such as DN but not an independent marker owing to positive affection of obesity on its serum level, so this study recommends keeping in mind obesity degree while using YKL-40 as an inflammatory marker for detection of DN as it affects its serum level.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Thomsen S, Gjesing A, Steint B. Associations of the inflammatory marker YKL-40 with measures of obesity and dyslipidaemia in individuals at high risk of type 2 diabetes. PLoS ONE 2015; 3:45–53.  Back to cited text no. 14
    
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