Uric Acid

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ASSOCIATION OF SERUM URIC ACID WITH DIABETES

MELLITUS IN DISTRICT NOWSHERA KPK


Muhammad Bilal Khattak1, Zahid Irfan Marwat2, Shah Nawaz2, Saqib Malik3, Muhammad Nadeem4,
Alamzeb jadoon5

ABSTRACT
Objectives: To compare the level of uric acid in diabetic and non-diabetic populations of District Nowshera
Methods: This Cross-sectional observational study was conducted in Department of Biochemistry Nowshera Medical
College & Qazi Hussain Ahmed Medical Complex Nowshera from January-December 2018. Both male and female pa-
tients from 24-65 years were included in this study. Nearly one hundred samples were collected from selected patients
for further investigation of serum Uric Acid and Blood glucose level.
Results: The number of cases having no diabetes were 77% out of which 59% of the patient had normal uric acid
while 18% of the patient had abnormal uric acid. The number of cases having diabetes was 23% out of which 17% of
the patients had normal uric acid while 6% of the patients had abnormal uric acid.
Conclusion: 6 percent Diabetics patients of Nowshera District had abnormal uric acid while 18 percent of Non-Diabetics
patients had abnormal uric acid in our present study.
Key words: Hyperuricemia, gout, Hyperglycemia ,Hypoglycemia ,Diabetic ketoacidosis

INTRODUCTION X-Ray studies in gouty crystals show that the


keto-oxygen in the second position of the purine struc-
Uric acid (C5H4N4O3) is a heterocyclic, purine ture has an hydroxyl group and the two nitrogen atoms
derivative bicyclic compound, consists of carbon, which share the ionic charge2.
nitrogen, oxygen, and hydrogen. It is a diprotic acid
(pKa1=5.4 and pKa2=10.3)1. It forms ions and salts It was first isolated from renal stones in 1776.
like urates and acid urates like ammonium acid urate. In 1882, Ivan Horbaczewski claimed to synthesized it
It is a product of purine nucleotides metabolism. It high from urea hydrogen peroxide, trichlorolactic acid, and
concentration causes gout and is associated with other its amide and glycine. However, Eduard Hoffmann
medical conditions including diabetes and the formation contradicted Ivan methods that this preparation with
of renal stones. glycine dose does not give a trace of uric acid. Rather,
trichlorolacetamide forms some uric acid. Hence, Hoff-
Uric acid So, in alkaline solution and high pH, it mann appeared the first one to synthesize uric acid3.
forms the dually charged full urate ion. in the presence
of carbonic acid or biological pH, it forms the singly Diabetes mellitus, a multifactorial endocrine
charged hydrogen or acid urate ion.due to its weak disorder is defined as high fasting blood glucose level
second ionization property, the full urate salts tend to caused by a relative or absolute deficiency in insulin.
hydrolyze back into hydrogen urate salts and free base One of the leading cause of adult blindness, amputation,
at neutral pH. renal failure, nerve damage, heart attacks, and strokes.
1
Department of Medicine Khyber Girls Medical Col- Type 1 Diabetes Mellitus is is due to an absolute
lege,Hayatabad medical complex Peshawar insulin deficiency caused by autoimmune destruction of
2
Department of Biochemistry Nowshera Medical Col- β cells of the pancreas. In this, activated T-lymphocytes
lege, Nowshera attack the islets of Langerhans, and as time passes,
3
Department of Medicine Ayub Medical College, Ayub the β cells population vanishes. However, the patient
Teaching Hospital Abbottabad becomes symptomatic abruptly when 80-90% of β cells
4
Department of Emergency Medicine Lady Reading depleted. At the point, the pancreas can not fulfill the
Hospital, Peshawar insulin requirement, and exogenous insulin therapy is
5
Department of Physiology Nowshera Medical College, required to restore metabolic control of glucose regu-
Nowshera lation. β cells destruction requires both a stimulus from
......................................................................................... the environment (such as a viral infection) and a genetic
Address for correspondence: determinant monozygotic (identical) twins, if one sib-
Prof Dr. Zahid Irfan Marwat ling develops Type 1 diabetes mellitus, the other twin
Department Biochemistry, Nowshera Medical College, has only 30 – 50% chance of developing the disease.
Nowshera However, in Type 2 disease, the genetic influence is
E-mail: [email protected] stronger, and in virtually all monozygotic twinships, the
Contact # 0300-9112880

26 KJMS January - April, 2020, Vol. 13, No.1


disease eventually develops in both individuals. subjects were taken. Diabetes was defined according
to the guidelines of the American Diabetes Association
Type 2 diabetes develops gradually without promi-
(fasting serum glucose ≥126 mg/dL, random serum
nent symptoms and is often detected by routine screen-
glucose ≥200 mg/dL). The age group selected for the
ing tests. However, many Type 2 diabetes patients have
study was 35-70 years.
symptoms of polyuria and polydipsia. Type 2 diabetes
patients have an abnormality of both, insulin resistance Type 2 diabetes mellitus with complications were
as well as β cells dysfunction. Although, initially, insulin excluded from the study: those with blood and renal
is produced and do not require its therapy to sustain life, disorders, patients with a history of gout or on antihy-
but eventually be required to control hyperglycemia and pertensive drugs, On long-term diuretics and steroids,
keep a normal level of HbA1C in 90% 0f patients. The antimetabolite and chemotherapy drugs, hypertension,
metabolic variations in Type 2 are milder than of Type 1 arthritis, myocardial infarction or Hepatic disorders,
because the absolute deficiency of insulin secretion in Peripheral vascular disease, cerebrovascular disease,
Type 1 diabetes leads to life-threatening ketoacidosis. pulmonary tuberculosis, Renal transplant patients,
Both types‘ Diagnosis is based most commonly on Pregnancy and lactating mothers were excluded.
the presence of hyperglycemia that is, a fasting blood
Data were analyzed using SPSS statistical
glucose concentration of equal to or greater than
software (version 22, SPSS). Data were expressed as
126mg/dl. Pathogenesis does not involve viruses or
mean±SD. Student’s t-test was used to compare and
autoimmune antibodies. An acute complication of Type
asses the significance between groups. P-value < 0.05
2 in the elderly is a hyperglycemic hyperosmolar state
was considered statistically significant.
characterized by severe hyperglycemia and dehydration
and altered mental status4. Following steps were followed in serum uric acid es-
timation:
Since early 20s, The association of hyperurice-
mia with diabetes has been known, but the hypothesis • Three test tubes were taken and marked as T.S
that hyperuricemia is a risk factor for diabetes is still and B.
controversial. In fact, hyperuricemia was postulated to
be the result of insulin resistance rather than its pre- • 1 ml Reagent was added in all three test tubes 1
cursor5. However, many studies concluded that high ml each.
serum uric acid has a strong association with risk of • 10 micro liter Serum was added in T marked tube.
type 2 diabetes, independent of obesity, hypertension
and, dyslipidemia. It has also been presumed in the • 10 micro liters’ standard solution was added in S
development of diabetic nephropathy. Although some tube
studies have demon¬strated the role of Uric Acid in the • 10 micro liter distilled water was added in B tube
progression of pre-diabetes to dia¬betes, conflicting
data exist about the uric acid levels in Type 2 DM, which • All three tubes were mixed and incubated at the
are associated with risk factors and complications. body temperature (37 C) for 5 min.
Thus, the role of Uric Acid in the pathogenesis and the • Reading of absorbance against the reagent
development of diabetic complications are debatable. blank obtained on the Spectrophotometer at 546nm
Therefore, this study aimed to look for any association wavelength.
of serum uric acid with Diabetes Mellitus, while keep-
ing the standard relevant clinical, biochemical and the • Readings were calibrated with the slandered/
anthropometric data. calibrator.
• Calculations were done according to the standard
MATERIALS AND METHODS
formula.
This is a Cross-sectional observational study
Uric acid [mg/dl] = Absorbance of sample
was conducted in Population of Nowshera District KPK
×6 Absorbance of standard
during the period January-December 2018. Nearly one
hundred samples were collected from Qazi Hussain Following steps were followed in blood glucose esti-
Ahmed Medical Complex on simple convenient meth- mation:
od. A blood sample was drawn and brought to the
Department of Biochemistry Laboratory of Nowshera • Three test tubes were taken and marked as T, S,
Medical College Nowshera for further investigation of and B.
serum Uric Acid and Blood glucose level. Serum uric • 1 ml reagent was added in all three test tubes 1
acid was estimated by enzymatic (uricase) method. ml each.
Their ages, smoking habits, physical status, and • 10 micro liter serums were added in T marked
health conditions were recorded using a questionnaire. tube.
The study protocol was approved from the same insti-
tution ethical committee board. Informed consent of the • 10 micro liter slandered solution was added in S

KJMS January - April, 2020, Vol. 13, No.1 27


tube the relationship of Abnormal Uric Acid with Diabetic and
Non-diabetic patients.
• 10 micro liter distilled water was added in B tube
The numbers of cases having no diabetes were
• All three tubes were mixed.
77% out of which 59% of the patient had normal uric
• Incubated at 37oC for 10 minutes. acid while 18% of the patient had abnormal uric acid.
The number of cases having diabetes was 23% out of
• Reading of absorbance against the reagent which 17% of the patients had normal uric acid while
blank obtained on the spectrophotometer at 546nm 6% of the patients had abnormal uric acid
wavelength.
Uric acid is the end product of the purine me-
• Readings were calibrated with the standard/ tabolism in humans. IN urin acid production, The final
calibrator. two reactions i.e. the conversion of hypoxanthine to
• Calculations were done according to the standard xanthine and then to uric acid, are catalyzed by the
formula. enzyme xanthine oxidoreductase, this enzyme persists
in 2 inter-convertible forms, xanthine dehydrogenase or
Glucose [mg/dl] = Absorbance of sample × 100 xanthine oxidase. The xanthine oxidase utilizes molec-
Absorbance of standard ular oxygen as an electron acceptor and it generates a
superoxide anion and other Reactive Oxygen Species
RESULTS (ROS), thus favoring an antioxidant pro-oxidant urate
redox shuttle6,7. Uric Acid is also a physiological free
A blood sample of 100 selected patients was radical scavenger and one of the major contributors
taken from patients visiting Qazi Hussain Ahmed Med- of the plasma antioxidant capacity8. Thus, Uric Acid
ical Complex Nowshera and brought to Department of
Biochemistry Laboratory of Nowshera Medical College Table 1: Descriptive Statistics
Nowshera to determine the Uric Acid and fasting and
random blood glucose level and to know the relation- N Mini- Maxi- Mean Std.
ship of Abnormal Uric Acid with Diabetic and Non-dia- mum mum Devia-
betic patients. tion
Mean age of the patients was 43.89±10-412 Age (in 100 24 65 43.89 10.412
ranging from 24 to 65 years and mean Uric Acid was years)
5.628±1.069 ranging from 4.00 to 8.90 and mean blood Diabe- 100 89 443 150.55 78.106
glucose was 150.55±78.60 ranging from 89 to 443 as tes
shown in Table 1.
Uric 100 4.00 8.90 5.6280 1.06951
According to the frequency of gender of the pa- Acid
tients, Male patients were 39% while the Female patients
were 61% out of 100 patients as shown in Table 2. Table 2: Frequency of Gender of the Patients
According to the frequency of diabetic patients,
Frequency Percent
24% patients had abnormal uric acid while the other
76% were normal uric acid out of the total 100 patients Male 39 39.0
as shown in Table 3. Female 61 61.0
According to the history of Diabetic patients, 77% Total 100 100.0
were non-diabetic patients, and 23% were diabetic out
of the total 100 patients as shown in Table 4. Table 3: Frequency of Uric Acid Patients
According to the cross tabulation, the number of Frequency Percent
cases having no diabetes were 77% out of which 59% of
the patient had normal uric acid while 18% of the patient Normal 76 76.0
had abnormal uric acid. The number of cases having Abnormal 24 24.0
diabetes was 23% out of which 17% of the patients had Total 100 100.0
normal uric acid while 6% of the patients had abnormal
uric acid as shown in Table 5. Table 4: Frequency of Diabetic Patients
DISCUSSION Frequency Percent
A blood sample of 100 selected patients were Normal 77 77.0
collected from patients visiting Qazi Hussain Ahmed
High 23 23.0
Medical Complex Blood to determine the Uric Acid and
fasting and random blood glucose level and to know Total 100 100.0

28 KJMS January - April, 2020, Vol. 13, No.1


Table 5: Cross Tabulation of Uric Acid with Diabetes
Uric Acid Group Total
Normal Abnormal
Normal Percentage 59 18 77
59.0% 18.0% 77.0%
High Percentage 17 6 23
17.0% 6.0% 23.0%
Total 76 24 100
76.0% 24.0% 100.0%
Chi-Square 0.789
Pearson's R 0.792

impairs the endogenous antioxidant defense system12.


Due to increased oxidative stress, local antioxidants are
depleted and resulting in reducing the total antioxidant
pool of the body13. Many studies have revealed the as-
sociation of hypouricemia with Type 2 DM14,15. A positive
relationship has been explained between glycosuria and
uricosuria16.
Further, a higher degree of hyper-glycemia was
observed to be associated with an increased rate of
uric acid clearance and lowering of the plasma uric acid
levels17. Hypo-uricaemia and the tubular transport of uric
acid have been thoroughly reviewed18. A greater urate
clearance due to marked-up glomerular hyper-filtration
which is a result of an abnormality in the tubular urate
handling has been reported19.

CONCLUSION
According to our study regarding the history
of Diabetic patients, 77% were non-diabetic patients,
and 23% were diabetic out of the total 100 patients as
shown in Table 4. According to the cross tabulation,
the number of cases having no diabetes were 77% out
of which 59% of the patient had normal uric acid while
18% of the patient had abnormal uric acid.

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