Introduction
According to world health organization diabetes is going to be the 7th leading cause of mortality in 2030. International Diabetes Federation report estimated that 642 million people would be affected by diabetes at the end of the year 2040. Diabetes mellitus is having multiple risk factors and is one of the silent killers of the middle to old aged people in the entire world. It is a metabolic disorder having hyperglycemia associated with dysregulation of lipid and protein metabolism. There are several types of diabetes, out of which type 2 diabetes is because of progressive insulin secretion defect on the background of insulin resistance. In today’s scenario, India considered as the diabetes capital of the world. India scores the second-highest number of cases of diabetes in the world after China during the year 2015.1 Several independent risk factors are associated with the causation of type 2 diabetes. Among them, prominent risk factors are ageing, increased body mass index, lack of exercise etc. Studies show that elevated uric acid levels in the blood might play as an independent biochemical risk factor for the causation of type 2 diabetes. Uric acid is the end product of the breakdown of purine metabolism. Serum uric acid levels differ as to age increases. In adults, the content of uric acid increases steadily and varies with body weight, height, and alcohol intake.2, 3
Metabolic disorders of purine like gout have a strong positive correlation with insulin resistance that leads to the causation of type 2 diabetes.4 Studies have shown that hyperuricemia is associated with the causation of diabetes and obesity.5 Bhole V et al. conducted a prospective study consisted of two generations of the Framingham Heart Study. They concluded that higher levels of serum uric acid were associated with an increased risk of developing type 2DM. Specifically, for every mg/dL increase in serum uric acid level, the risk of type 2 DM increased by 20% in the original cohort (n=4,883) and 15% in the offspring cohort (n=4,292). These associations persisted in both genders and were independent of other known risk factors of type 2 DM including age, BMI, alcohol consumption, smoking, physical activity level, hypertension, and levels of glucose, cholesterol, creatinine and triglycerides.4
Few studies show that reduced clearance of uric acid is associated with hyperinsulinemia that causes insulin resistance in type 2 diabetes. A positive correlation between uric acid and fasting blood glucose levels leads to the causation of type 2 diabetes. Furthermore, certain studies indicate that uric acid functions as pro-oxidant & antioxidant according to their concentration levels. Blood uric acid has a role of pro-oxidant properties that causes oxidative stress in the cells and results in the resistance of the cells to the insulin. Studies showed hyperuricemia is associated with excess risk for development of type 2 diabetes.6, 7, 8 Whether the hyperuricemia causes type 2 diabetes, or is it one of the complications of diabetes? Therefore the study is done to know the association of blood uric acid with the duration (2-10 years) of diabetes in people with type 2 diabetes only with no other morbidities and any complications.
Materials and Methods
Study setting
The present study conducted at GSL Medical College, Rajamahendravaram, Andhra Pradesh.
Study participants
Fifty type 2 diabetic patients (10 men & 5 women) randomly selected from the medicine outpatient department of GSL hospital for this pilot study.9
Inclusion criteria
Type 2 diabetics
Fasting blood glucose reports within one week (>110mg/dL
The age group for more than 40 years
Both genders included (10 males & 5 females
Duration of diabetes: 2-10 years
BMI: 19-25 Kg/m2
They were taking hypoglycemic drugs regularly or irregularly
Willing to participate voluntarily
Exclusion criteria
History of CVS, Respiratory, GIT, Renal & CNS disorders
History of endocrine & metabolic disorders like type 1DM, GOUT
Overweight & obese
Smokers
Alcoholics
Any complications of type 2 diabetes
Pregnancy & lactation
Menstrual disorders
Personal, family & diet history from the patients recorded. General physical examination, height (cms), weight (kgs), BMI (Kg/m2), vitals and systemic examinations performed to rule out the exclusion criteria. Overweight, obese & hypertensive excluded from the study, which could affect uric acid and insulin resistance in type 2 diabetics. Specific instructions were given to the patients about 8 hour overnight fasting. Collection of the venous blood samples under aseptic precaution at Central Laboratory of the Hospital done. A biochemical investigation like Uricase method (Peroxidase) employed for the estimation of serum uric acid (SUA) levels in the patients. Uricase method: Uric acid in the blood serum utilizes peroxidase system added with several oxygen acceptors to form a chromogen that develops a colour. By using colourimeter absorbance of the intensity measured at 440 nanometer.10
Results
Table 1 show the Pearson correlation of SUA with the duration of diabetes in years of type 2 diabetes. The result showed that a positive correlation present between SUA and duration of type 2 diabetes is statistically significant. As the duration of diabetes increases than there is an increase in the serum uric acid concentration in type 2 diabetes patients. SUA in the type 2 diabetes patients was 7.8 ± 1.7 (mean ± SD) stating that they were suffering from hyperuricemia. Hyperuricemia is termed as >7.0 mg/dL in males and > 6.0 mg/dL in females.11 Out of fifteen, eleven of them were suffering from hyperuricemia (73%). Average uric acid level elevated from 6.88 ± 0.95 in people with the duration of diabetes 2 to 6 years to 7.61 ± 3.16 in people with the duration of diabetes 7 to 10 years shown in the Table 2.
Discussion
Blood uric acid acts as an independent risk factor for developing insulin resistance, obesity & even hypertension showed in the previous literature. A positive correlation between SUA & the duration of diabetes in type 2 diabetic patients shown in Table 1. Similar results obtained from the study done by Rao TMV & Vanukuri NK12 on type 2 diabetes patients in India. But in their study exclusion of overweight, obesity & hypertension not done, which acts as a confounding factor to cause hyperuricemia.
Hyperuricemia can cause dysfunction of endothelial cells and reduced secretion of nitric oxide, that causes insulin resistance & type 2 diabetes.13 Studies done on fructose-induced hyperuricemia rats leading to insulin resistance & development of the metabolic syndrome. Hyperuricemia treated by taking hypouricemic drugs.14 Some studies showed elevated serum acid levels might cause prediabetes status at the renal level. Hyperinsulinemia with prediabetes can decrease renal excretion of uric acid, as insulin can stimulate the urate-anion exchanger and the sodium-dependent anion co-transporter in brush border membranes of the proximal renal tubule and increase renal urate reabsorption.15, 16, 17, 18, 19
Strength of the present study: a simple, cost-effective test like uric acid is used, which can guide to diagnose the impaired glucose tolerance leading to insulin resistance. The uric acid level can also guide as a marker of cardiovascular disease, which is the most frequent cause of mortality in diabetes mellitus. The limitations of the present study include small sample size, other biochemical parameters which support the type 2 diabetes-like serum triglycerides, cholesterol, blood urea, serum creatinine, insulin levels, leptin and other inflammatory mediators like C reactive protein levels not assessed.20 The patients were on hypoglycemic drug treatment which could have reduced insulin resistance and hence hyperuricemia.
Conclusions
The present study has shown a positive correlation existing between SUA & duration of diabetes in the type 2 diabetics. Further large sample study with other investigations like insulin, leptin levels should be assessed to know the strength of this positive association. From this study, we conclude that by reducing the uric acid levels with medications can help in preventing the occurrence of insulin resistance leading to type 2 diabetes mellitus and its complications.
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