VALENZUELA MEDICAL CENTER

Padrigal Street, Karuhatan, Valenzuela City

Department of Internal Medicine

In Partial Fulfillment of the Requirements for Training in Internal Medicine

Prevalence of Hyperuricemia among Filipino Diabetic Patients Admitted at Valenzuela

Medical Center January 2019 to December 2019

Submitted by:

MAHALLA MAE M. SANTIAGO, M.D.

Internal Medicine Resident

Principal Investigator

IMELDA DIGNA ANTONIO MD, FPCP, FPSEDM

Co-Investigator

JOHANNA FELICITY PANGANIBAN, FPCP

Co-Author
 CHAPTER I

INTRODUCTION

Uric acid (UA) is the final breakdown product of purine compounds. It is generated in

the liver, and mainly excreted by the kidneys (65–75%) and the gastrointestinal tract (25–35%) .

Hyperuricemia (HUA) is widely known to cause gout which is the most common inflammatory

27
arthritis characterized by painful disabling acute attacks. Hyperuricemia is also associated

with the precursors of cardiovascular diseases, including hypertension, metabolic syndrome,

and coronary artery disease, as well as with closely related vascular diseases such as

cerebrovascular disease, vascular dementia, preeclampsia, and kidney disease 29.

However, recent evidence suggests an emerging association between HUA and in

developing type 2 diabetes mellitus (T2DM). T2DM, a major lifestyle disease, has become a

global burden, according to ADA, 10.4% of Filipinos are affected yearly with more than 640

million adults expected to be affected by the disease by 2040.

Recent studies show that hyperuricemia causes a series of pathophysiological changes

through inflammation, oxidative stress, vascular endothelial injury that contribute to the

development of diabetes and its complication. However It is still debated if serum uric acid can

be used as a monitoring parameters for developing typed 2 dm and the progression of

complications. 27

According to a study about ethnic variations in serum uric acid by Healey et al. the mean

serum uric acid among Filipino is significantly higher than the other races. It has been
postulated that the cause of hyperuricemia among Filipinos is due to decrease in uric acid (UA)

excretion due to the inability of the kidneys to compensate for the increased purine load. 26

Most studies have been made between the relationship of uric acid and diabetes in

other races like European, American and Bangladesh which revealed a significant relationship

between high serum uric acid and diabetes.

If serum uric acid is much higher among Filipino people than other races, there is higher

risk to develop or progression of diabetes. However, limited data and sparse research on the

prevalence of hyperuricemia among Filipinos with diabetes. This leaves room for further

investigation which may possibly influence future management and strategies to decrease the

progression and improve outcomes of patients with diabetes.

SIGNIFICANCE OF THE STUDY:

The prevalence of diabetes in the Philippines is increasing. Rapid urbanization results in

increasing dependence on electronic gadgets, cultural preferences for a traditional diet of

refined sugar, including white rice, bread, highly processed foods and sedentary lifestyle

contribute significantly to this rise. 29 Hyperuricemia may be one of contributary factors in the

progression of diabetes. It is also observed that Filipino people have increased serum uric acid

levels, as compared to other races.

However, diabetes care in the Philippines is challenged with regards to the patients

resources, government support, and economics. The monitoring and prevention of increasing

serum uric acid of patients not only improve the outcome of diabetes but it can also lessen the

burden of disease. Thus by prevention of hyperuricemia we also prevent progression of

diabetes and its complications hence reducing the expenses of daily medications. This study

maybe significant by increasing the awareness of the Filipino people in the early treatment and

prevention of hyperuricemia as one of the risk factors in developing diabetes.

OBJECTIVES:

General:

To determine the prevalence of hyperuricemia in diabetic Filipino patients admitted at

Valenzuela Medical Center.

Specific:

1. To create a clinical profile in patients with diabetes admitted at Valenzuela Medical

Center.

2. To correlate the incidence of increased serum uric acid with the duration of

diabetes.

3. To determine the level of fbs and hemoglobin a1c in correlation with serum uric acid

level.
 CHAPTER II

REVIEW OF LITERATURE

Hyperuricemia was defined as the circulating uric acid levels of more than 5.7mg/dl for

women and 7.0 mg/dl for men. Changes in the uric acid content in body fluids can reflect the

state of metabolism, immunity, and other functions of the human body. If the body produces

too much uric acid or the excretion mechanism is degraded, the body will retain excessive uric

acid.

Increased uric acid levels in the blood promoted the expression of interleukin-1β (IL-1β),

interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α) and CRP production. In human studies,

serum UA was positively associated with TNF-α, interleukin-6 and C-reactive protein in healthy

people.234 In diabetes, increase serum uric acid can lead to inflammation production of TNF, IL-

6, IL-B and CRP, oxidative stress via production of reactive oxygen species, endothelial

dysfunction by reduction of endothelial NO bioavailability, inhibition of insulin pathways by

ectonu- cleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) . With addition effect of

thrombus formation via increase platelet adhesion and activation of RAAS pathway may lead to

diabetic chronic complications.1

In hypertension, uric acid inhibits proliferation and migration of endothelial cells and NO

secretion. UA can react with NO to form 6-aminouracil, UA- dependent ROS reacts with NO to

form peroxynitrite, and UA can hold back L-arginine uptake and stimulate L-arginine

degradation. 9As a result of the effects of hyperglycemia and neurohormonal activation, UA

levels are independently associated with endothelial dysfunction in animals and humans,

thereby promoting hypertension.10

In the study entitled “Assessment of the relationship between serum uric acid and

glucose levels in healthy, prediabetic and diabetic individuals in Bangladeshi population.” The

prevalence of hyperuricemia was 18.4% with a higher percentage in the non-diabetic and pre

diabetic groups compared to the diabetic group. Younger participants in the non-diabetic group

had a higher level of SUA compared to older age participants in the prediabetic and diabetic

groups (p<0.001). Baseline characteristics of the study subjects revealed that male participants

often had a higher level of SUA compared to female individuals irrespective of glycemic status.

in diabetic individuals, SUA levels were significantly lower than in the healthy and prediabetic

individuals and showed an inverse association with FBG concentration. SUA levels were higher

in non-diabetic individuals, but a decreasing trend was observed in prediabetic and diabetic

individuals. This finding supports the hypothesis that SUA might be involved in the early stages

of metabolic imbalance leading to prediabetes and to a lesser extent in the advanced stages of

diabetes is diagnosed. So, SUA might be a determinant in altered glucose metabolism but not a

potential predictor of diabetes in the Bangladeshi population. 22

In a prospective study of Serum Uric Acid Levels and the Risk of Type 2 Diabetes of two

generations of the Framingham Heart Study, it is found that higher levels of serum uric acid

were associated with an increasing risk of developing type 2 diabetes. Specifically, for every

mg/dL increase in serum uric acid level, the risk of type 2 diabetes was increased by 20% in the

original cohort and 15% in the offspring cohort. These associations persisted in both genders
and were independent of other known risk factors of type 2 diabetes, including age, BMI,

alcohol consumption, smoking, physical activity level, hypertension, and levels of glucose,

cholesterol, creatinine and triglycerides. Overall, these findings provide prospective evidence

that individuals with higher serum uric acid, including younger adults, are at an increased future

risk of type 2 diabetes independent of other known risk factors. 23

In a cross sectional study of the prevalence and determinants of hyperuricemia in type

2 DM found that duration of DM >10 years, obesity, increase diastolic blood pressure, family

history of CVD and alcohol drinking were significantly associated with hyperuricemia. Disparity

in the prevalence might be explained by different population profiles, such as dietary habits,

geographical/environmental factors, genetic factors, sample size, study design and the use of

different cut off values.24

In another cross sectional study about the Prevalence and determinants of

hyperuricemia in type 2 diabetes mellitus patients with central obesity in Guangdong Province

in China It is found that the overall prevalence of hyperuricemia was 32.6%, and was

significantly higher in women than in men. The prevalence of hyperuricemia increased with

increasing BMI in both sexes and was significantly higher in women than in men. The

prevalence of hyperuricemia in patients with HbA1c <7% was significantly higher than in

patients with HbA1c ≥7%. The prevalence of hyperuricemia in patients with hypertension was

significantly higher than in patients without hypertension. The prevalence of hyperuricemia in

patients with dyslipidemia was also significantly higher than in patients without dyslipidemia
results revealed that the presence of hyperuricemia was significantly associated with women,

high BMI and waist circumference, high TC and TG, low HDL-cholesterol, and low eGFR. 25

In a prospective cohort study done by S. P Juraschek et al. between the temporal

relationship of uric acid and diabetes. the study concluded that a higher uric acid

concentrations is associated with greater risk of diabetes. They also found that while elevated

uric acid concentrations were associated with increased risk of diabetes, after diagnosis of

diabetes, uric acid concentrations declined. The decline in uric acid level was strongly

associated with duration of diabetes with the greatest reduction in uric acid was observed

among participants with a diabetes duration of 7.2–9.0 years. It is possible that lifestyle

changes or medication use subsequent to a diabetes diagnosis alters uric acid production;

however, the ongoing alterations in metabolism due to the chronic effects of diabetes cannot

be ruled out. 26

Increase serum uric acid appears to have negative effects on the progression and

development of diabetes via inflammation, oxidative stress, endothelial dysfunction and insulin

inhibiting pathways. The studies mentioned would conclude that increase serum uric acid can

lead to the development and progression of diabetes.

 CHAPTER III

RESEARCH DESIGN AND METHODOLOGY:

This is a hospital-based chart review study which was conducted in Valenzuela Medical

Center located in Padrigal St. Karuhatan Valenzuela City. We will review the charts of the

patient with known diabetes from January 2019 to December 2019.

The admission data will be collected using a program called iHOMIS, the hospital's

automated electronic medical record screening program. This program contains the data of all

patients admitted to the Valenzuela medical center internal medicine unit between January 1,

2019 and December 31, 2019. Data such as sex, age, admission and discharge dates. A chart

review of these patients will be done and the following data will be gathered: duration of

diabetes, serum UA level, documented complications, hba1c levels, fbs, lipid profile and

medications used. Data collected will be plotted on a spreadsheet.

The investigator will be constructing a descriptive research using cross sectional data for

the year 2019. The population for this study will be comprised of diabetes patients admitted at
Valenzuela Medical Center from January 1 to December 31, 2019. The said population will then

be evaluated whether or not the patient is qualified for the inclusion criteria of this study. Then

necessary values for the variables required in this study will be tabulated.

Inclusion Criteria :

Diabetic Filipino patients Admitted at Valenzuela medical center from January 2019 to

December 2019, aged 30 years old and above.

Exclusion Criteria :

1. Patients of known gouty arthritis, RA, Osteoarthritis, Reactive Arthritis, Infective Arthritis

2. Patients with serum creatinine > 1.5 mg/dl or GFR < 60 mL/min/1.73 m2

3. Patients known with liver disorders by history or with increase transaminases.

4. Patients who are suffering from connective tissue disorders.

5. Patients with cancer and patients on corticosteroids.

SAMPLE SIZE
 The investigator will be using the simplified formula in determining the sample size

(Yamane, 1967) using a 95% confidence level with a 0.05 margin of error will be assumed. The

formula is as follows:

N
n=
1+ Ne 2

where n – sample size

N – population size

e – margin of error

Computation:

447
n=
1+ 447( 0.05)2
= 211.10

The ideal sample size for this study is approximately 211 patients. However, after checking the

inclusion-exclusion criterion, only 197 patients qualified for this study. The investigator used a

Convenience sampling method in choosing the participants for this study.

STATISCAL TESTS

The investigator will be computing for descriptive measures for each

variable in this study. For categorical variables, frequencies and percentages will be calculated

while mean and standard deviation will be calculated for numeric and continuous variables. The

Chi Square Test for Independence will be used to identify the relationship between variables as

well as the Pearson correlation coefficient to determine the corresponding degree of

correlation. The software that will be used for this study are Microsoft Excel and SPSS

(Statistical Package for Social Sciences).

Research Design:

Collection Information of
Database of patients in
IHomis

Inclusion Criteria : Exclusion Criteria :

Diabetic Filipino patients Admitted at 1. Patients of known gouty arthritis, RA,

Valenzuela medical center from Osteoarthritis, Reactive Arthritis, Infective
January 2019 to December 2019, aged Arthritis
Data gathering and creation of clinical profile

Analysis of data
gathered

Formulation of
conclusion

ETHICAL CONSIDERATION

The researcher will consider several ethical standards in the investigation prior to

collecting information about patients. All personal information of patients will remain

anonymous. The information declared in the study will be strictly confidential. In this
case, the records of patients will be presented in a summarized result and not

representation of individual reports.

CHAPTER IV

RESULTS AND DISCUSSION

Diagnostic Checking

Normality Test for Continuous Variables

Before the investigator can use statistical tests, normality assumptions regarding

the sample data must be satisfied in order to generate reliable results.

Duration of Diabetes (in years) Uric Acid Level

Hemoglobin a1c Fasting Blood Sugar

 All of the graphs above show that the values cluster around the diagonal line
indicating that the variables in this study are approximately, normally distributed. Thus, the test
for independence can be applied.

Table 1. Clinical Profile

Variables Minimum Maximum Mean Std. Deviation

AGE 24.0 87.0 58.046 12.6650
CBC 0.1300 0.6020 0.378128 0.0782714
CREA 8.00 130.40 71.6999 21.89166
DURATION(years) 0.01 30.00 6.4129 5.60964
FBS 3.16 28.05 10.8009 5.07535
HBA1C 4.70 16.40 8.9252 2.65991
HDL 0.19 2.22 1.0319 0.37368
LDL 0.380 7.780 2.76780 1.284713
TAG 0.35 10.59 1.5630 1.21687
TOTAL CHOLE 0.77 10.13 4.5186 1.58209
URIC ACID
0.114 0.760 0.40905 0.112355
LEVEL

For this study, the mean age of diabetic patients is 58 years old. The mean number of years a
patient has Diabetes is approximately 6 years. The mean uric acid level, fasting blood sugar and
hemoglobin a1c are 0.41 mmol/L, 10.8 mmol/L, and 8.93 mmol/L, respectively. Note that the
mean uric level is approximately within the normal range while the mean HBA1C and FBS are
above the normal range of a person.
 Sex Frequency
Male 98
Female 99
Notable Comorbidities Frequency
Hypertension 147
Pulmonary Tuberculosis 18
Bronchial Asthma 13
Coronary Artery Disease 8
Notable Treatments Frequency
Metformin 88
Insulin 27
Glicazide 16

Table 2. Chi Square Test for Independence

Uric Acid Level * Duration Crosstabulation

DURATION

< 5 YRS 5 TO 10 YRS > 10 YRS Total

UA LEVEL HIGH 63 46 9 118

NORMAL 30 17 10 57

LOW 18 2 2 22
Total 111 65 21 197

The uric acid level is grouped into three (LOW, NORMAL, HIGH) as well as the duration of
diabetes mellitus in order to perform a Chi Square test for independence. It is evident that
hyperuricemia is more common to those diabetic patients who had the condition at an early stage
(less than 5 years) at 63. Conversely, the longer the person has diabetes, the lower the uric acid
level is.

Chi-Square Tests

Value df p-value

Pearson Chi-Square 11.725 4 0.020

Likelihood Ratio 12.602 4 0.013
N of Valid Cases 197
As mentioned earlier in Chapter 3, the investigator used a 95% confidence level having a 5%
level of significance. Since the p-value of 0.02 is less than the level of significance, there is
sufficient evidence to say that the uric acid level and the duration of diabetes mellitus a patient
has are related to one another.

Uric Acid Level * Hemoglobin A1C Crosstabulation

HBA LEVEL

HIGH NORMAL LOW Total

UA LEVEL HIGH 96 22 0 118

NORMAL 45 12 0 57

LOW 5 1 16 22
Total 146 35 16 197

Based on this table, patients with higher hemoglobin a1c tend to have higher uric acid levels.

Chi-Square Tests

Value df p-value

Pearson Chi-Square 138.688a 4 0.000

Likelihood Ratio 85.392 4 .000
N of Valid Cases 197

Since the p-value is less than 0.05, there is also sufficient evidence to say that uric acid level is related with
hemoglobin a1c at 5% level of significance.

Uric Acid Level * FBS Crosstabulation

 FBS LEVEL

HIGH NORMAL LOW Total

UA LEVEL HIGH 99 16 3 118

NORMAL 43 13 1 57

LOW 4 0 18 22
Total 146 29 22 197

The higher FBS of patients tend to lead to a higher uric acid level as well.

Chi-Square Tests

Value df p-value

Pearson Chi-Square 127.419a 4 0.000

Likelihood Ratio 82.709 4 .000

N of Valid Cases 197

At 5% level of significance, there is also enough evidence to say that uric acid level and FBS are
related.

Uric Acid Level * AGE GROUP Crosstabulation

AGE GROUP Total

60 YRS AND
30-39 YRS 40-49 YRS 50-59 YRS UP

UA LEVEL HIGH 7 16 39 56 118

NORMAL 3 7 13 34 57

LOW 3 4 6 9 22
Total 13 27 58 99 197
As with age, diabetic patients who are already in their 60’s tend to have higher uric acid levels.

Chi-Square Tests

Value df p-value

Pearson Chi-Square 5.269a 6 0.510

Likelihood Ratio 4.890 6 .558
N of Valid Cases 197

Even if the contingency table shows a relationship between age and uric acid
level, at 5% level of significance, there is no sufficient evidence to say that age and uric acid
level are related to one another.

Table 3. Degree of Relationship

Pearson Correlation Uric Acid Level Relationship

Hemoglobin a1c 0.037 Weak direct relationship
FBS 0.114 Weak direct relationship
Duration (years) -0.005 Too weak inverse relationship
Triglycerides 0.110 Weak direct relationship
Age -0.139 Weak inverse relationship
HDL 0.016 Weak direct relationship
LDL 0.031 Weak direct relationship
Total Cholesterol 0.069 Weak direct relationship
CBC -0.063 Weak inverse relationship
Creatinine 0.190 Direct relationship

Even if the investigator had shown that a relationship exists between uric

acid levels and the duration a diabetic patient has the condition, the Pearson correlation

coefficient suggests a very weak inverse relationship at -0.005. This means, however,

that the longer a patient has a diabetes, the lower his/her uric acid level becomes. Both
the hemoglobin a1c and FBS show a weak direct relationship with the uric acid level of

a person. That is, as both increase, uric acid level tends to get higher as well. Of all the

factors considered in this study, creatinine has the highest degree of relationship with

hyperuricemia at 0.19. This suggests that as the creatinine level of a diabetic patient

increases, so is the uric acid level. This might suggest that creatinine level could

determine presence of hyperuricemia on diabetic patients.

 CHAPTER V

CONCLUSION AND RECOMMENDATION

After conducting this study, the investigator has shown that the uric acid level of

a diabetic patient is related to different factors. Hyperuricemia is found to have an

inverse, even though weak, relationship with the duration a diabetic patient has had the

condition. This is true for diabetic patients admitted at Valenzuela Medical Center from

January to December 2019. In addition, hyperuricemia is directly related with the

increasing levels of hemoglobin a1c and fasting blood sugar. This is quite interesting

since both factors determine if a person already has diabetes. Further study might be

done to verify if hyperuricemia can also be a sign that a person has diabetes already.

The investigator would also like to recommend further study regarding the relationship

of hypertension with hyperuricemia. It was found out that 44% of diabetic patients in this

study have hypertension and hyperuricemia at the same time. Possible relationships

might be present with these factors. Another insight from here is the effect of using

Metformin with hyperuricemia. In this study, it was found out that diabetic patients using

Metformin for treatment of their condition tend to have hyperuricemia (25% of the

patients).

This study has shown that 59.9% of diabetic patients in Valenzuela Medical

Center have hyperuricemia. Other factors might need to be identified to understand how

related hyperuricemia is with diabetic patients’ behavior. This is enough to say that

hyperuricemia could lead to more serious illness for diabetic patients if ignored. This will
help all patients, not just those suffering from diabetes, in regulating uric acid levels to

lessen, if not totally prevent hyperuricemia.

Appendices:

Table 1: Patient’s Profile

Subject Characteristics
Age 30-39
40-49
50-59
60 and Above
Gender Male
Female
Co-morbids HTN, dyslipedemia

Table 2: Clinical Profile

Duration of Diabetes < 5 years

5-10 years
>10 years
Treatment regimen OHA
Insulin
none

Table 3: Laboratory Profile

Normal Values Result Interpretation

Uric Acid Level 0.100-0.400

mmol/L
HBa1c level >6.5
<6.5
4.40-6.40
FBS 3.85-6.40 mmol/L
Total Cholesterol 0.00-5.20 mmol/L
Triglycerides 0.40-2.30 mmol/L
HDL 1.15-1.56 mmol/L
LDL 1.70-4.60 mmol/L
GLOSSARY OF TERMS:

 Diabetes- is a group of metabolic disorders characterized by a high blood sugar level

over a prolonged period of time. With a fasting blood plasma glucose ≥126 mg/ dL, non-

fasting plasma glucose ≥200 mg/dL.

 Pre-Diabetes- is a component of the metabolic syndrome and is characterized by

elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. 

 Uric acid- is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with

the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as

ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine

nucleotides, and it is a normal component of urine.

 Hyperuricemia- is an abnormally high level of uric acid in the blood. In the pH conditions

of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid
 concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for

youth (under 18 years old) are defined as hyperuricemia.

 Hba1c- is a form of hemoglobin(Hb) that is chemically linked to a sugar. A1c is measured

primarily to determine the three-month average blood sugar level and can be used as a

diagnostic test for diabetes mellitus and as an assessment test for glycemic control in

people with diabetes. The test is limited to a three-month average because the average

lifespan of a red blood cell is four months. 

 GFR- glomerular filtration rate; Glomerular filtration rate (GFR) represents the flow of

plasma from the glomerulus into Bowman’s space over a specified period and is the

chief measure of kidney function.

 IHOMIS- The Integrated Hospital Operations and Management

Information System (iHOMIS) is a computer-based. information system developed by

the Department. of Health to support the hospital management for. effective and

quality health care by providing timely, relevant and reliable information.

 HDL- HDL (high-density lipoprotein), or “good” cholesterol, absorbs cholesterol and

carries it back to the liver. The liver then flushes it from the body. High levels

of HDL cholesterol can lower your risk for heart disease and stroke.
 LDL- LDL stands for low-density lipoproteins. It is sometimes called the "bad" cholesterol

because a high LDL level leads to a buildup of cholesterol in your arteries. HDL stands for

high-density lipoproteins.

 FBS- Fasting blood sugar test; A fasting blood sugar level less than 100 mg/dL (5.6

mmol/L) is normal. A fasting blood sugar level from 100 to 125 mg/dL (5.6 to 6.9

mmol/L) is considered prediabetes. If it's 126 mg/dL (7 mmol/L) or higher on two

separate tests, you have diabetes.

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Uric Acid, Hyperuricemia and Vascular Diseases Ming Jin 1,4, Fan Yang4,†, Irene Yang4,†, Ying Yin2,4,†, Jin Jun Luo3,4,
29

Hong Wang2,4, and Xiao-Feng Yang2,4,* 1Department of Pathology and Laboratory Medicine, Philadelphia, PA 19140
2Department of Pharmacology and Cardiovascular Research Center, Philadelphia, PA 19140 3Department of Neurology,
Philadelphia, PA 191404Temple University School of Medicine, Philadelphia, PA 19140