A study on adiponectin, uric acid, and C-reactive protein in prediabetic and diabetic subjects

Rachna Sharma; Pallavi Anand; Shrawan Kumar

doi:10.4103/bjhs.bjhs_34_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 7 | Issue : 1 | Page : 89-93

A study on adiponectin, uric acid, and C-reactive protein in prediabetic and diabetic subjects

Rachna Sharma¹, Pallavi Anand¹, Shrawan Kumar²
¹ Department of Biochemistry, Rama Medical College, Hospital and Research Centre, Kanpur, Uttar Pradesh, India
² Department of Medicine, Rama Medical College and Hospital, Kanpur, Uttar Pradesh, India

Date of Submission	22-Apr-2021
Date of Decision	31-Jul-2021
Date of Acceptance	26-Aug-2021
Date of Web Publication	27-Jun-2022

Correspondence Address:
Dr. Rachna Sharma
Department of Biochemistry, Rama Medical College, Hospital and Research Centre, Kanpur, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/bjhs.bjhs_34_21

Abstract

BACKGROUND: Diabetes and prediabetes are always on the rise over the past decade, but little is known about the development of type 2 diabetes mellitus dysfunction in young adults. The study was conducted in prediabetic and diabetic patients in order to belong to an anti-inflammatory hormone adiponectin and pro-inflammatory marker uric acid (UA) in these patients and also to determine the role of these markers in future cardiovascular disease (CVD) risk.
MATERIALS AND METHODS: This case–control study was conducted at Rama Medical College and Hospital, Kanpur. Out of 400 participants recruited, 140 subjects were control, 140 were prediabetics, and the remaining 120 were controlled. The detailed history of the patients regarding age, gender, height, weight, and family history regarding obesity and other chronic illnesses was taken. Patients with medical complications or diseases and conditions that may affect levels of inflammatory markers were excluded from the study. The data analysis was done using SPSS 16 and the results were presented as mean ± standard deviation where P < 0.05 has been considered as statistically significant.
RESULTS: The adiponectin level was found significantly decreased and C-reactive protein and UA levels were increased in both study groups (prediabetes and diabetes) while comparison was done with control group. Similarly, basic parameters including waist/hip ratio, body mass index, glycated hemoglobin, and fasting blood glucose were increased.
CONCLUSION: The study showed that prediabetes and diabetes are diseases of inflammatory origin with a high level of pro-inflammatory molecules. These medications are not only potent risk factors for prediabetes and diabetes but also mediate significant future CVD risk in these patients.

Keywords: Adiponectin, C-reactive protein, diabetes mellitus, prediabetic, uric acid

How to cite this article:
Sharma R, Anand P, Kumar S. A study on adiponectin, uric acid, and C-reactive protein in prediabetic and diabetic subjects. BLDE Univ J Health Sci 2022;7:89-93

How to cite this URL:
Sharma R, Anand P, Kumar S. A study on adiponectin, uric acid, and C-reactive protein in prediabetic and diabetic subjects. BLDE Univ J Health Sci [serial online] 2022 [cited 2023 Jun 3];7:89-93. Available from: https://www.bldeujournalhs.in/text.asp?2022/7/1/89/348270

On the basis of various studies conducted among diabetic subjects, it is clear that it is an inflammatory disorder.^[1] Since numerous studies in the last few years have indicated the persistence of low-grade inflammation in prediabetes that increases the future risk of diabetes and associated complications, there is an urge for better understanding of inflammatory mechanisms fundamental to progression from prediabetes to diabetes. In this context, it is worth to identify and investigate novel markers of inflammation that might indicate different stages of diabetes and illuminate the associated pathophysiology, thereby aiding the clinicians to target the high-risk groups. The normoglycemic individual experiences a stage of latent hyperglycemia, i.e., prediabetic phase before developing disease. Developments of phases from normoglycemia, to prediabetic and further to diabetic state, are all manifested by insulin resistance status. And this is hallmark of the inflammatory response. Uric acid (UA) is purine catabolic Product, is synthesized in vivo from glutamate and 5-phosphoribosyl pyrophosphate.^[2] several epidemiological studies have implicated strong influence of UA in several conditions such as insulin resistance, obesity, hypertension, metabolic syndrome, diabetes, and renal diseases.^[2] Raised level of UA level has also been seen in prediabetic subjects and the offspring of diabetes patients too. Current few studies have shown the important role of UA in immune activation and thereby release of cytokines.^[3] These molecules potentially mediate both endothelial dysfunction and phase of inflammation and oxidative stress in metabolic syndrome. A higher level of UA may pose individuals with higher risk of diabetes as per literature search.^[4] Antioxidant and pro-oxidant role of UA is well studied and established.^[5] Raised UA level has also been reported to show its effect on pancreatic B-cell apoptosis through activating several signal transduction pathways.^[6] The study was planned in prediabetic and diabetic patients in order to pertain an anti-inflammatory hormone adiponectin and pro-inflammatory marker UA in these patients and also to determine the role of these markers in future cardiovascular disease (CVD) risk.

Materials and Methods

Our study was a case–control study which was approved by the Ethical Committee of Rama Medical College and Hospital Kanpur, UP, India. Out of 400 participants recruited, 140 subjects were control, 140 were prediabetics, and the remaining 120 were controlled. Detailed history of the patients regarding age, gender, height, weight, and family history regarding obesity and other chronic illnesses was taken. Patients suffering from any medical complications or diseases or any other conditions that may affect levels of inflammatory markers were not considered in the study. Blood samples from the recruited study subjects were collected and the separated serum or plasma was used for biochemical analysis. All the parameters including routine (fasting blood glucose [FBG] and glycated hemoglobin [HbA1c]) and inflammatory parameters (adiponectin, UA, and C-reactive protein [CRP]) were analyzed appropriately using standard kits. The anthropometric variables included in the present study were body mass index (BMI) and waist/hip ratio (WHR):

BMI = weight (kg)/height (m)²
WHR = waist circumference (cm)/hip circumference (cm).

Venous blood was withdrawn by venipuncture of antecubital vein after overnight fasting and distributed among fluoride for glucose, EDTA for HbA1c and plain vacutainer for UA, CRP, and adiponectin respectively.

The samples were centrifuged at 3000 rpm for 15 min to separate plasma or serum and were preserved at 80° centigrade temperature until the day of estimation. Serum glucose was measured with glucose oxidase–peroxidase method (using ERBA glucose kit, Transasia Bio-Medicals Pvt. Ltd., South Sikkim, India).

Plasma levels of adiponectin were measured immunochemically in our clinical biochemistry laboratory, using commercial ELISA kit. The total adiponectin assay (Qayee-bio Shanghai ELISA kit using Tulip Liza Quant Elisa Reader with Washer, Shanghai) captured all the multimeric forms of circulating adiponectin, with a sensitivity of 0.78 ng/mL and within-batch and between-batch coefficients of variation of 1.8% and 6.2%, respectively. HbA1c was measured with ion-exchange resin method using Tulip HbA1c kit (Coral Clinical Systems, Goa, India), and CRP was estimated immunoturbidimetrically by standardized ERBA CRP kit (Transasia Bio-Medicals Pvt. Ltd., South Sikkim, India). UA was estimated by uricase–peroxidase method using ERBA UA kit (Transasia Bio-Medicals Pvt. Ltd., South Sikkim, India) in our clinical biochemistry laboratory.

The anthropometric parameters such as weight and height were taken in the standing position with bare feet, eyes looking forward, and back leaning straight against the wall. BMI was calculated and derived as kg/m² and classified according to the World Health Organization (January 10, 2004).^[7]

The data analysis was done using by a statistical program for social science (SPSS) version 16, IBM Corp., Chicago, USA, 2008 and the results were calculated as mean ± standard deviation where P < 0.05 has been taken as statistically significant. The comparison of assayed parameters among control and prediabetic groups, control and diabetic groups, and prediabetic and diabetic groups was done by Student's t-test (unpaired). To determine the association, Pearson's correlation test was applied.

Results

In this study, the adiponectin level was significantly decreased and CRP and UA levels were significantly increased in both the groups (prediabetes and diabetes) as compared to the control group. Similarly, basic parameters including WHR, BMI, HbA1c, and FBG were increased. In the study, cardiac risk indices were also estimated and significantly high risk was documented in the patient group with profoundly raised levels in the diabetic group [Table 1] and [Table 2]. Regarding correlation analysis, adiponectin in both the prediabetic and diabetic groups correlated inversely with CRP (r/p = −0.32/<0.001, 0.6/<0.001) and UA (r/p = −0.14/0.09, −0.2/0.024), respectively. Similarly significant differences were found among high BMI, HbA1c, FBG in diabetics as compared to prediabetic group. Similarly, the indices for cardiac risk as cardiac risk ratio, A1, AC, and AIP showed inverse association to adiponectin (r/p = −0.31/<0.001, −0.29/<0.001, −0.29/<0.001, −0.29/<0.001 in prediabetic group; −0.45/<0.001 and − 0.41/<0.001, −0.45/<0.001 and − 0.49/<0.001 in diabetes, respectively) and the linear association with CRP (r/p = 0.24/0.004, 0.22/0.008, 0.24/0.004 and 0.19/0.22 in prediabetes and 0.71/<0.001, 0.67/<0.001, 0.71/<0.59/<0.001) in diabetes, respectively, UA (r/p = 0.13/0.119, 0.12/0.15, 0.13/0.119 and 0.1/0.231 in prediabetes; 0.29/<0.001, 0.28/<0.001, 0.29/<0.001 and 0.22/0.013 in diabetes, respectively).

Table 1: Basic parameters among control, prediabetic, and diabetic groups

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Table 2: Correlation among adiponectin, C-reactive protein, and uric acid in prediabetes, diabetes, and control subjects

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Discussion

Diabetes mellitus, one of the important health issues of 21^st century, affecting millions of life is mainly attributed to physical inactivity, stress, changes in living habit.

According to the different studies conducted in India, central obesity is the stronger predictor of diabetes and its risks compared to general obesity. Previous studies have suggested that Asian Indians have a high tendency of abdominal fat accumulation, thereby contributing to high risk and prevalence of diabetes. Obesity may trigger metabolic changes in the body that stimulate adipose tissue to release a higher amount of glycerol, fatty acids, and hormones which can lead to insulin resistance that in combination with pancreatic β-cell dysfunction disturb the blood glucose homeostasis.^[8] Over 60%–90% of diabetic population is obese showing obesity as a major diabetic risk factor.^[9]

Over 60%–90% of diabetic population is obese showing obesity as a major diabetic risk factor. Basic parameters including BMI, WHR, FBG, and HbA1c were evaluated between different groups and found to be significantly raised prediabetic and diabetic groups (>0.05 in both the groups). The outcome of the study was in support of previous studies done. Adela and Banerjee also reported raised FBG in subjects compared to controls.^[10] Similarly also documented significantly high BMI, HbA1c, FBG, differences were more significant in diabetics as compared to prediabetic group.^[11],[12]

Adiponectin is an anti-inflammatory adipokine. The level of adiponectin was apparently less in both the groups (prediabetes and diabetes) in comparison to the healthy control group. Supporting evidence shows significantly low adiponectin level in prediabetic and hyperglycemic group as compared to normoglycemic group.^[11] Further supporting studies also show significant differences in adiponectin level in both the subject groups as compared to control group.^[13,14]According to Maggio CA et al. (2003) adiponectin has been found as one of the important factors predicting prediabetes.^[15] The protective role of adiponectin against hyperglycemia can be correlated with its insulin-sensitizing effects.^[16] Mechanistic approaches demonstrate that adiponectin stimulates AMP-dependent protein kinases^[17] and thereby triggers insulin sensitivity by enhancing glucose cellular uptake and fatty acid oxidation in the liver. According to Okada-Iwabu et al., oral supplementation of AdipoR agonist can serve as a promising therapeutic option for insulin resistance and diabetes.^[18]

CRP is the most common acute-phase inflammatory marker generated by the liver. Several observational studies have demonstrated well diabetes incidence and association with CRP. The results of our study have been found in alliance with many others who showed orderly increase of CRP levels from control group to prediabetic and to diabetic group.^[19] Consistent results were also observed in the studies of Sabanayagam C et. al and Muilwijk M et al. , who showed high CRP level in prediabetic group^[20],[21] though fewer studies have focused on ethnic variations with regard to association of CRP with prediabetes.^[22] The elaborated mechanism that links hyperglycemia with CRP level may be explained in parts with insulin resistance.^[23] UA has been reported to serve as a marker for blood glucose metabolic alterations.^[2] This study documented significantly high UA concentration in diabetic subjects (with respect to the prediabetic, diabetic, and control groups). A study conducted has been reported similar results.^[24] The level of UA has been found progressively increased from control group to IFG to hyperglycemic group, thereby highlighting the significance of UA in the pathogenesis of diabetes. Number of other workers also reported similar results.^[25] Some studies suggested, though UA level is low in diabetes, raises again due to renal insufficiency associated with Diabetes.^[26] A possible mechanism of such variations in UA level may be due to reduced synthesis and altered excretion of uric acid and increased consumption as an antioxidant.^[26]

As per correlation analysis, all the basic parameters were significantly and inversely correlated with adiponectin. These reports were analogous with many researches including reported significant inverse correlation of adiponectin with HbA1c and BMI, but the correlation was insignificant in the case of age, diabetes duration, and insulin and glucose level.^{[27],[28],[29]}

Conclusion

The study showed that prediabetes and diabetes are diseases of inflammatory origin with high level of pro-inflammatory molecules. These mediators are not only potent risk factors to prediabetes and diabetes but also mediate significant future CVD risk in these patients. Therefore, earlier screening of high-risk individuals is suggested so as to prevent the onset of diabetes development.

Acknowledgment

We would like to thank the Department of Biochemistry, Rama Medical College, Hospital and Research Centre, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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