Correlation of Serum Uric Acid Levels with Certain Anthropometric Parameters in Prediabetic and Drug-naive Diabetic Subjects

Abstract

Introduction:

Uric acid is produced during the metabolism of nucleotide and adenosine triphosphate and contains the final product of human purine metabolism. It acts both as an antioxidant and pro-inflammatory marker and has a positive association with visceral fat in overweight subjects. The aim of the present study is to find an association of uric acid level with certain anthropometric parameters in subjects having type 2 diabetes.

Materials and Methods:

The study included 124 urban drug-naive diabetic Indian subjects above 18 years of age from the general population of the city of North India. Uric acid concentrations were estimated by the uricase method. Fasting plasma glucose (FPG) concentrations were estimated by the glucose oxidase-peroxidase method. Anthropometric measurements and information on lifestyle factors and disease history were collected through in-person meeting.

Results:

All participants of the study subjects had a body mass index (BMI) of more than 23.5. BMI, waist-to-hip ratio (WHR), waist-to-height ratio, waist circumference, neck circumference, weight, age, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index were positively correlated with the serum uric acid level. The correlation of weight, BMI, SAD, and WHR was statistically significant.

Conclusion:

We found that serum uric acid level increases as body fat content increases. Statistical data show remarkable results for a significant correlation of uric acid level with BMI, WHR, SAD, and FPG. Hypertrophy occurs as a result of inflammatory processes and oxidative stress when the supply of energy starts to exceed the storage capacity of adipocytes, as a result, adipokines such as interleukin (IL)-1, IL-6, and tumor-necrosis factor-alpha are released more frequently which lead to low-grade chronic inflammation. Uric acid levels are much lean toward visceral obesity than overall body fat content.

INTRODUCTION

Metabolic syndrome (MetS) is a significant medical entity and one of the principle difficulties of current clinical practice influencing the outcome of other comorbidities. The International Diabetes Federation suggested that one-fourth of the world’s grown-up population has MetS and the predominance of MetS in the National Health and Nutrition Examination Survey was 5% among the subjects of normal weight, 22% among the overweight, and 60% among the obese.[1]

The World Health Organization (WHO) recommends the use of waist/hip ratio, diabetes mellitus (DM) type 2 or insulin resistance, microalbuminuria, hypertension, and triglycerides (TG) for diagnosis MetS.[2]

Compared to other fatty tissues in the body, adipose tissue presents in the abdomen which is more metabolically active and contains much more number of residing macrophages.[3] Abdominal adiposity adds on to inflammatory processes and oxidative stress, which are the key precursors of complications such as insulin resistance, hypertension, and hyperlipidemia which eventually lead to MetS.[4,5]

Oxidative stress is conventionally characterized as an occasion coming about because of the intensity of imbalance among oxidant and antioxidant factors[6,7] created in a setting of oxidation-reducing factors. Since the age and the activity of these substances rely upon this oxidation-decreasing system, researchers presently utilize the expression “imbalance of oxidation-reduction system” to present the oxidative stress.[8,9]

Antioxidant system, including enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and nonenzymatic substrates such as ferritin, transferrin, bilirubin, ceruloplasmin, and carrier of albumin low molecular weight, such as uric acid and lipoic acid controls oxidative stress.[10]

Antioxidants can trap free radicals produced by the metabolism of cellular products or exogenous sources through the reduction by hydrogen ions of these particles, breaking the continuous reactions, which ceases action on lipids, amino acids in proteins, bonds of the polyunsaturated fats, and DNA bases, preventing lesion formation and loss of cell integrity.[11] Another function of antioxidants is the defense system, which acts in the DNA repair brought about by free radicals, a cycle identified with the expulsion of the damaged DNA molecule and repair of damaged cell membranes.[12]

Uric acid, once seen as an inactive metabolic final result of purine catabolism, has been as of late implicated in various long-term illness states, including arterial blood pressure, metabolic condition, diabetes, nonalcoholic fatty liver disorders, and chronic renal disorders. Raised uric acid may end up being one of the more significant remediable problematic factors for metabolic and cardiovascular disorders.[13]

Prediabetes is a glucose homeostasis disorder described by impairment of glucose tolerance or impairment of fasting glucose.[14] Prediabetes can thus be viewed as a significant reversible stage that could prompt the incidence of type 2 DM, and early distinguishing proof of prediabetes may add to the reduced incidence of type 2 DM.[15]

The presence of chronic and low-grade inflammation in obesity is also seen in many chronic illnesses such as type 2 diabetes, hypertension, atherosclerosis, fatty liver, cancer, asthma, and sleep apnea. During inflammation, there is an increase in the number of white blood cells and/or the level of pro-inflammatory cytokines in circulation as well as within the tissues.[16]

MATERIALS AND METHODS

The study included 124 Indian subjects above 18 years of age from the general population of the city of North India who were diabetic or prediabetic. Subjects were not taking any medication regularly, as stated by them. Dietary history, occupational history, marital status, personal history, and family history were taken in person with each subject. Subjects were not on any long-term medication. All anthropometric parameters were measured following standard protocols. Patients suffering from type 1 diabetes, any known endocrinal, renal or nutritional disorder, any known anatomical deformity which can interfere with anthropometric data, pregnancy, known subjects with gout are excluded from study.

Anthropometry

Subjects aged 18–60 years from the Outpatient Department of Medicine Department were included. Informed consent form was filled out by each subject for biochemical and anthropometric analysis. Weight and height were measured according to techniques proposed by Jelliffe 1966.[17] Weight was measured on the portable scale without heavy clothing. The measurement was done after the bladder has been emptied and before a meal. The balance was placed on a hard, flat surface, and checked and adjusted for zero balance before each measurement. Body weight was recorded to the nearest 0.1 kg. Height was measured by rigid stadiometer to the nearest centimeter while barefoot with minimal clothing so that posture could be clearly seen. Body mass index (BMI) was calculated according to formulae. BMI = weight/height² expressed in kilogram per meter square. Hip circumference was measured at the widest circumference over the great trochanter.

Waist circumference (WC) was measured with a flexible and inelastic measuring tape, according to the WHO’s recommendation with the subject standing, after a regular expiration, to the nearest centimeter midway between the lowest rib and the iliac crest. Sagittal abdominal diameter (SAD) was recorded with the subject in the supine position and with bent knees and with a standardized sliding beam caliper at the highest point of the abdomen. Skinfold thickness was measured by the Harpenden skinfold caliper. The skinfold was grasped between the thumb and index finger approximately 2.0 cm above the measurement mark (site of the skinfold to be measured would be marked with a marker). The skinfold was pulled away from the subject’s body to separate the fat from the underlying muscle. The caliper jaws were placed perpendicular to the length of the fold and the handle of the calipers will be released to apply full tension on the fold, and this position was held for approximately 3 s. It was critical to wait roughly 3 s before attempting to read the skinfold measurement. During this time, the needle on the caliper dial was settled into a final position that represents the true thickness of the fold. The caliper dial was read at eye level to prevent measurement error due to parallax. The thickness was measured to the nearest tenth of a millimeter (0.1 mm).[17] Neck circumference (NC) was measured to the nearest 0.1 cm just below the laryngeal prominence (Adam’s apple) perpendicular to the long axis of the neck with the subject standing upright and shoulders relaxed using flexible measuring tape.[18]

Body roundness index (BRI) was calculated by the formula BRI = 364.2–365.5× (1-[WC/2 π]²/[0.5 × height]²)¹/².[19] Waist-to-hip ratio and waist-to-height ratio (WHtR) were also calculated.

Estimation of biochemical parameters

All aseptic precautions were taken during procedure.

A small area around the vein (preferably antecubital vein) was cleaned with rectified spirit and with the help of a disposable syringe, 3 mL venous blood sample will be collected only once. This sample was then transferred to plain (serum) vial (3 mL) and fluoride vial. Then, the sample was further analyzed for the estimation of uric acid and blood glucose. Enzymatic colorimetric method is used for the estimation of uric acid.[20] Glucose (monoreagent) (glucose oxidase-peroxidase method) is used for the estimation of blood glucose.[21]

RESULTS

All participants of the study subjects have fasting plasma glucose (FPG) more than 100 mg/dL. Pearson correlation was done using Microsoft Excel for statistical analysis. BMI, waist-to-hip ratio (WHR), WHtR, WC, NC, weight, age, SAD, skinfold thickness, BRI, and FPG were positively correlated with the serum uric acid level. Correlation of weight, BMI, SAD, and WHR was statistically significant with P < 0.05. Physical activity, height, and hip circumference were inversely correlated with serum uric acid levels [Table 1 and Figure 1].

Table 1.

Pearson’s correlation between serum uric acid with other parameters

Parameter	R	P
Serum uric acid versus age	0.068	0.46
Serum uric acid versus height	−0.029	0.75
Serum uric acid versus weight	0.308	0.0005
Serum uric acid versus BMI	0.39	0.00005
Serum uric acid versus NC	0.059	0.510
Serum uric acid versus WC	0.099	0.28
Serum uric acid versus HC	−0.07	0.44
Serum uric acid versus SAD	0.275	0.002
Serum uric acid versus SFT	0.085	0.3460
Serum uric acid versus WHR	0.332	0.00016
Serum uric acid versus WHtR	0.1117	0.2166
Serum uric acid versus BRI	0.109	0.227
Serum uric acid versus FPG	0.299	0.001

FPG=Fasting plasma glucose, BMI=Body mass index, NC=Neck circumference, WC=Waist circumference, SAD=Sagittal abdominal diameter, SFT=Skinfold thickness, WHR=Waist-to-hip ratio, WHtR=Waist-to-height ratio, BRI=Body roundness index, HC=Hip circumference

Figure 1.

Graph showing mean values of anthropometric and biochemical parameters. FPG = Fasting plasma glucose, BMI = Body mass index, NC = Neck circumference, WC = Waist circumference, SAD = Sagittal abdominal diameter, SFT = Skinfold thickness, WHR = Waist-to-hip ratio, WHtR = Waist-to-height ratio, BRI = Body roundness index, HC = Hip circumference

DISCUSSION

In the present study, we found that serum uric acid level increases as body fat content increases. Statistical data show remarkable results for a significant correlation of uric acid level with BMI, WHR, and SAD and FPG.

Hypertrophy occurs as a result of inflammatory processes and oxidative stress when the supply of energy starts to exceed the storage capacity of adipocytes.[22] As a result, adipokines such as interleukin (IL)-1, IL-6, and tumornecrosis factor-alpha (TNF-α) are released more frequently which lead to low-grade chronic inflammation that starts in adipose tissue and finally reaches the circulation and other organs.[23,24]

Most mammals and fowls will store their abundance of fat in their fat tissue, yet in addition, in their liver and serum TG, regularly in relationship with the advancement of insulin resistance and raised arterial pressure.[25] While the fundamental components engaged in adipose tissue metabolism include different hereditary and other elements, ongoing researches recommend a role for DNA metabolism, where activation of adenosine monophosphate (AMP) deaminase advances fat metabolism and insulin resistance, though stimulation of AMP-initiated protein kinase started fat catabolism and diminishes gluconeogenesis. A key factor that seems to advance fat stockpiling is the AMP deaminase residues, uric acid.[26,27]

A raised serum uric acid is likewise a strong indicator for the presence of overweight and fatty liver.[28] From researches, uric acid has been appeared to raise TG in liver cells[29] and hyperuricemia likewise builds fatty substance levels in the liver of rats.[30] The component has been demonstrated to be intervened by intracellular and mitochondrial oxidative stress.[31] The oxidative stress is related to aconitase inhibition in the Krebs cycle that prompts citrate collection and the induction of adenosine triphosphate citrate lyase, bringing about raised fat synthesis, just as a hindrance of enoyl CoA hydratase results in disturbed beta fatty acid oxidation that is additionally potentiated by the hindrance of AMP-activated protein kinase (AMPK)-initiated protein kinase.[26,29]

The particular connection between instinctive fat tissue aggregation and insulin resistance keeps on being observed. Adiposity of visceral organs is related to amassing of the overabundance of lipid in the liver and results in cell-independent impedance in insulin signaling. Visceral fat tissue is additionally inclined to inflammatory cytokine release, which likewise adds to impedance in insulin signaling. The development of visceral fat tissue and overabundance of lipid gathering in the liver and muscle may result from restricted expandability of subcutaneous fat tissue because of the properties of its extracellular framework and limit with respect to growth of capillaries.[32]

Overall observations suggest that visceral adiposity is the key factor for hyperuricemia. Visceral adiposity leads to comparatively higher oxidative stress than other adipose components of the body. Hyperuricemia is remarkable indicator for visceral adiposity.

Inflammation hinders the insulin signaling activities in adipocytes and hepatocytes through many ways. The first is restraint of insulin receptor substrate-1 (IRS-1) and insulin receptor in the pathway of insulin signaling.[33,34] IRS-1 gets signals from insulin receptors in the pathway of insulin signaling. The second pathway is hindrance of peroxisome proliferator-activated receptor gamma (PPARγ) work.[34] PPARγ is a receptor present in the nucleus that drives lipid production and fat stocking in cells. Its movement is subject to ligands, which incorporate long-chain unsaturated fats and thiazolidinedione. Decrease of PPARγ action adds to insulin resistance. The third is to expand plasma-free fatty acids through lipolysis and blocking of TG production.[35] The three pathways involve in the inflammation process. These impacts are basically seen in fat tissue and liver.

In obesity, a few modifications added to the beginning of chronic type inflammation, e.g., endoplasmic reticulum stress, adiponectin decrease, raised leptin, death of adipocytes, macrophage invasion, and lipolysis.[16] Fat-tissue hypoxia has been proposed as a typical root for these progressions (192). Hypoxia may induce increase of pro-inflammatory cytokines in adipose tissue directly or indirectly. The rise of these cytokines in adipose tissue and circulation has been reported in many trials.[36,37] These cytokines incorporate IL-1, IL-6, TNF-α, monocyte chemotactic protein-1, and Plasminogen activator inhibitor-1 (PAI-1). These cytokines were initially utilized as a term for protein that causes signaling among white blood cells (T cells, B cells, and macrophages) by association with a particular plasma membrane receptor. They are unique in relation to hormones since they for the most part act in the paracrine fashion to direct cell multiplication, differentiation, catabolism, and anabolism. It is difficult to isolate cytokine from hormone as in many cases, e.g., leptin and adiponectin. Cytokine that is mainly created by adipocytes is known as adipokines. Functions of these cytokines are complicated in obesity which involves adipocytes inhibition,[38,39,40] initiation of angiogenesis, fuel activation, energy expenditure inhibition, and concealment of food consumption. These exercises are required for the control of metabolic balance in the body.[41,42,43,44,45]

Earlier studies also show that visceral adiposity is a key factor for increasing oxidative stress and uric acid level. Known mechanism of action of uric acid is to block AMPK and stimulate gluconeogenesis, and insulin-mediated nitric oxide release is blocked by uric acid, which is important for insulin action.

CONCLUSION

Study findings can be concluded that various anthropometric measurements have a pathophysiological relationship with uric acid and this relationship is further augmented in the metabolic condition of prediabetes and diabetes. Relationship between BMI, body weight, SAD, and FPG was found to be statistically significant with plasma uric acid level. This study suggested that the overburden of adipose tissue, especially visceral adiposity, has a key connection with plasma uric acid.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.