A STUDY ON SERUM URIC ACID LEVELS IN TYPE 2 DIABETES PATIENTS AND ITS ASSOCIATION WITH CARDIOVASCULAR
DISEASE
DISSERTATION SUBMITTED TO THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY, CHENNAI In partial fulfilment of the requirements for the degree of
M.D. BRANCH – I (GENERAL MEDICINE)
REG NO 201711355
BONAFIDE CERTIFICATE
This is to certify that the dissertation entitled “A STUDY ON SERUM URIC ACID LEVELS IN TYPE 2 DIABETES PATIENTS AND ITS ASSOCIATION WITH CARDIOVASCULAR DISEASE” submitted by Dr.C.ARJUNAN., to the Tamilnadu Dr. M.G.R Medical University, Chennai, in partial fulfillment of the requirement for the award of M.D. Degree Branch – I (General Medicine) is a bonafide research work carried out by her under direct supervision & guidance.
Professor & Head of the Department, Department of General Medicine
Unit Chief,
Department of General Medicine
CERTIFICATE BY THE DEAN
I hereby certify that this dissertation entitled “A STUDY ON SERUM URIC ACID LEVELS IN TYPE 2 DIABETES PATIENTS AND ITS ASSOCIATION WITH CARDIOVASCULAR DISEASE” is a record of work done by Dr.C.ARJUNAN. , in the Department of General Medicine, Tirunelveli Medical College, Tirunelveli, during her postgraduate degree course period from 2017- 2020. This work has not formed the basis for previous award of any degree.
Date :
Place : TIRUNELVELI
The DEAN
Tirunelveli Medical College, Tirunelveli - 627011.
DECLARATION
I solemnly declare that the dissertation entitled “A STUDY ON SERUM URIC ACID LEVELS IN TYPE 2 DIABETES PATIENTS AND ITS ASSOCIATION WITH CARDIOVASCULAR DISEASE” is done by me at Tirunelveli Medical College Hospital, Tirunelveli Under the guidance and supervision of Prof.Dr.M.MOHAMED RAFI. M.D, the dissertation is submitted to The Tamilnadu Dr. M.G.R. Medical University towards the partial fulfilment of requirements for the award of M.D.
Degree (Branch I) in General Medicine.
Place: Tirunelveli Date:
Dr.C.ARJUNAN REG NO 201711355 Postgraduate Student,
CERTIFICATE – II
This is to certify that this dissertation work entitled “A STUDY ON SERUM URIC ACID LEVELS IN TYPE 2 DIABETES PATIENTS AND ITS ASSOCIATION WITH CARDIOVASCULAR DISEASE”
of the candidate Dr.C.ARJUNAN with registration Number 201711353 for the award of M.D. Degree in the branch of GENERAL MEDICINE (I). I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion page and result shows 16 percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal.
ACKNOWLEDGEMENT
I wish to express my heartfelt gratitude to our Dean Prof.Dr. S. M. Kannan M.S., MCh., Tirunelveli Medical College for
allowing me to do the study in this institution.
I would like to express my humble thanks to our professor & Head of the Department Prof. Dr. M. Ravichandran M.D., Department of General Medicine.
I express my sincere thanks to my renowned teacher and my guide Dr.M..MOHAMED RAFI M.D., Professor, Department of General Medicine, Tirunelveli Medical College for his guidance, valuable suggestions and constant encouragement throughout the study.
I express my sincere thanks to my former professor, Dr.S.Arumugapandian @ Mohan, M.D.,, for his constant support, encouragement and suggestions which helped me greatly to expedite this dissertation .
I am greatly obliged to Dr.RAVI EDWIN M.D, D.M
I would like to thank my parents, my beloved spouse Dr.S.P. Hari Sudha. for their support and motivation.
I thank all my patients who participated in this study for their extreme patience and kind co-operation.
.
CONTENT
S.NO TITLE PAGE.NO
1. INTRODUCTION 1
2. AIM AND OBJECTIVES OF THE STUDY 5
3. REVIEW OF LITERATURE 6
4. MATERIALS AND METHODS 51
5. RESULTS 53
6. DISCUSSION 66
8. CONCLUSION 73
9. BIBILIOGRAPHY ANNEXURE PERFORMA CONSENT FORM MASTER CHART
INTRODUCTION
Coronary heart disease and hypertension both are a global health epidemic. Age-specific events related to CHD have fallen dramatically in the last few decades, the overall frequency has risen as populations age and patients survive the initial coronary or cardiovascular event. The Centers for Disease Control and Prevention estimates that life expectancy in America might be increased by 7 years if CHD and its obstacles were eradicated. The most common cause of death worldwide is increase death from coronary vascular events and its most implicated factor responsible for this is lifestyle changes in developing countries .
Global Burden of Disease (GBD) Study described that in 1990 there were 5.2 million deaths from coronary heart diseases in economically developed countries and 9.1 million deaths from the similar causes in developing countries.1 The prevalence of cardiovascular diseases in India increased from 1.2% in 1960 to 9.9% in 1995 in city populations, and in rural populations the risk is significantly doubled.
The burden of the cardiovascular disease is same in developing
Left ventricular failure is the single most important predictor of mortality following STEMI. In 1967, Killip and Kimball recommended a prognostic classification scheme on the basis of the existence and severity of rales detected in patients presenting with STEMI.
Despite overall improvement in death rate in each class, compared with data detected during the original development of the classification scheme, the classification scheme remains useful today, as showed by data from large MI trials of STEMI patients. Killip classification is a potent independent predictor of all-cause death in patients with non–ST-elevation acute coronary syndromes.
There has been growing interest in the link between serum uric acid levels, xanthine oxidoreductase, and cardiovascular disease. Xanthine oxidoreductase exists in two forms, xanthine oxidase and xanthine dehydrogenase. Both of these enzymes are responsible for metabolizing uric acid from hypoxanthine and xanthine.
Preceding studies have reported that a high concentration of uric acid is a strong marker of an adverse prognosis of moderate to severe heart failure and coronary vascular disease. Uric acid may be raised in
Xanthine oxidase and oxidative stress as imitated by uric acid may form a cycle that promotes severe heart failure.
Adenosine produced locally by vascular smooth muscle in cardiac tissue is rapidly despoiled by the endothelium to uric acid, which undergoes rapid efflux to the vascular lumen due to low intracellular pH and negative membrane potential. Xanthine oxidase activity and uric acid synthesis are augmented in vivo under ischemic conditions, and therefore higher serum uric acid may act as a marker of underlying tissue ischemia.
In the human coronary circulation, hypoxia, caused by transient coronary artery occlusion, leads to an increase in the local circulating concentration of uric acid.
According to the Japanese Acute Coronary Syndrome Study , there was a close correlation between serum uric acid level and Killip classification in patients of acute myocardial infarction. Patients who developed short-term opposing events had high uric acid concentrations.
Elevated serum uric acid concentration has been found to be closely associated with Metabolic and other related syndromes. The
decreased renal blood flow and resultant increased urate reabsorption, although this association is not completely understood.
We undertook this study to note the levels of serum uric acid in type 2 diabetes patients with Acute Myocardial Infarction, to correlate the blood uric acid levels with Killip Classification, to study the role of serum uric acid as a marker of short-term mortality in coronary heart disease, to study the relation between serum uric acid and cardiac and Cpk-MB in acute myocardial infarction, and to study the relation between serum uric acid and Systemic Hypertension & Diabetes Mellitus in coronary heart disease.
AIM AND OBJECTIVES
To identify the level of serum uric acid in type 2 diabetes mellitus
To identify whether any association exist between age ,sex, anthropometric measurements(BMI,WHR), hypertension, dyslipidemia, duration of diabetes, smoking and coronary artery disease with serum uric acid levels.
REVIEW OF LITERATURE
Ischemic heart disease (IHD) is a condition in which there is an inadequate supply of blood and oxygen to a portion of the myocardium; it typically occurs when there is an imbalance between myocardial oxygen supply and demand. The most common cause of myocardial ischemia is atherosclerotic disease of an epicardial coronary artery (or arteries) sufficient to cause a regional reduction in myocardial blood flow and inadequate perfusion of the myocardium supplied by the involved coronary artery.
By reducing the lumen of the coronary arteries, atherosclerosis limits appropriate increases in perfusion when the demand for flow is augmented, as occurs during exertion or excitement. When the luminal reduction is severe, myocardial perfusion in the basal state is reduced. Epicardial coronary arteries are the major site of atherosclerotic disease. The major risk factors for atherosclerosis [high levels of plasma low-density lipoprotein (LDL), low plasma high-density lipoprotein (HDL), cigarette smoking, hypertension, and diabetes mellitus disturb the
formation, and abnormal interactions between blood cells, especially monocytes and platelets, and the activated vascular endothelium.
Functional changes in the vascular milieu ultimately result in the subintimal collections of fat, smooth muscle cells, fibroblasts, and intercellular matrix that define the atherosclerotic plaque. This process develops at irregular rates in different segments of the epicardial coronary tree and leads eventually to segmental reductions in cross-sectional area. The atherosclerotic plaques associated with a total thrombotic occlusion of an epicardial coronary artery, located in infarct-related vessels, are generally more complex and irregular than those in vessels not associated with STEMI. Histologic studies of these lesions often reveal plaque rupture or erosion.
Atherosclerotic plaques considered prone to disruption overexpress enzymes that degrade components of the plaque extracellular matrix. Activated macrophages and mast cells abundant at the site of plaque disruption in patients who died of STEMI can elaborate these proteinases. In addition to these structural aspects of vulnerable or high-
margin of the fibrous cap near an adjacent, less involved segment of the coronary artery wall (shoulder region of plaque).
A number of key physiologic variables such as systolic blood pressure, heart rate, blood viscosity, endogenous tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor type 1 (PAI-1) levels, plasma cortisol levels, and plasma epinephrine levels exhibit circadian and seasonal variations and increase at times of stress. These factors act in concert to heighten propensity to plaque disruption and coronary thrombosis, yielding the clustering of STEMI in the early morning hours, especially in the winter and after natural disasters.
The most common major mechanical complications of Acute STEMI include cardiogenic shock, right ventricular infarction, acute mitral regurgitation, ventricular septum rupture, and free wall rupture.
The electrical complications include Bradyarrhythmias (viz. sinus bradycardia, second-degree atrioventricular block, complete heart block, bundle-branch block), Tachyarrhythmias (viz. sinus tachycardia, atrial fibrillation, accelerated idioventricular rhythm, ventricular tachycardia,
with cardiogenic shock. It is important to exclude mechanical complications because primary therapy of such lesions usually requires immediate operative treatment, with intervening support of the circulation by intra-aortic balloon counterpulsation.
Cardiogenic shock is the most severe clinical expression of left ventricular failure and is associated with extensive damage to the left ventricular myocardium in more than 80% of STEMI patients in whom it occurs; the remainder have a mechanical defect such as ventricular septal or papillary muscle rupture or predominant right ventricular infarction. In the past, cardiogenic shock was reported to occur in up to of patients with STEMI, but estimates from recent large trials and observational databases report an incidence in the range of 5% to 8%.
LV failure is the most common cause of cardiogenic shock complicating acute MI. Left ventricular dysfunction is the single most important predictor of mortality following STEMI Other causes of cardiogenic shock in patients with STEMI include mechanical defects such as rupture of the ventricular septum, a papillary muscle, or free wall with
mortality of approximately 80%. The prospective SHOCK Trial Registry identified LV failure as the etiology of shock in 79% of patients. LV failure in acute MI varies widely in terms of pathophysiology and severity. Mild-to-severe pulmonary congestion may occur alone or in association with depressed stroke volume (SV) and cardiac output. At the severe end of the spectrum of pump failure, cardiogenic shock is a state of severe tissue hypoperfusion caused by cardiac dysfunction. Diastolic or systolic dysfunction may predominate.
After acute coronary occlusion, LV systolic and diastolic function changes over minutes, hours, and weeks. Superimposed fixed or transient MR, recurrent ischemia, or reinfarction may have a major effect. Compliance of the infarct zone evolves over time , and stunned myocardium may recover function. Elevations in LV filling pressures resulting from systolic or diastolic dysfunction may reduce the pressure gradient that maintains coronary blood flow and thereby initiate a cycle of hypoperfusion and worsening LV dysfunction.
In 1967, Killip and Kimball proposed a prognostic classification scheme on the basis of the presence and severity of rales detected in patients presenting with STEMI. Class I patients are free of rales and a third heart sound. Class II patients have rales but only to a mild to moderate degree (<50% of lung fields)., and they may or may not have an S. Patients in Class III have rales in more than half of each lung field and frequently have pulmonary edema. Finally, Class IV patients are in cardiogenic shock. Despite overall improvement in mortality rate in each class, compared with data observed during the original development of the
The Killip classification can be used as a method to stratify patients and predict clinical outcomes. When this classification was established in 1967, the expected hospital mortality rate of patients in these classes was as follows: class I, 0–5%; class II, 10–20%; class III, 35–45%; and class IV, 85–95%. With advances in management, the mortality rate in each class has fallen, perhaps by as much as one-third to one-half. With modern therapy, the mortality of those in cardiogenic shock has improved from 83% to approximately 50%.
Etiological classification of diabetes mellitus :-
Type 1 (ß-cell destruction, usually leading to absolute insulin deficiency)
A. Immune-mediated B. Idiopathic
Type 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly insulin secretory defect with insulin resistance).
Other specific types of diabetes:
A. Genetic defects of ß cell function characterized by mutations in:
1. Hepatocyte nuclear transcription factor (HNF) 4a (MODY 1).
2. Glucokinase (MODY 2).
3. HNF-1a (MODY 3).
4. Insulin promoter factor-1 (IPF-1; MODY 4).
5. HNF-1ß (MODY 5).
6. NeuroD1 (MODY 6).
B. Genetic defects in insulin action 1. Type A insulin resistance 2. Leperchaunism
3. Rabson-Mendenhall syndrome 4. Lipodystrophy syndromes
C. Diseases of endocrine pancreas Pancreatitis, pancreatectomy, Neoplasia, cystic fibrosis, Hemochromatosis, fibrocalculous pancreatopathy, mutations in carboxyl ester lipase.
D. Endocrinopathies - Acromegaly, Cushings syndrome, glucagonoma, Pheochromocytoma, hyperthyroidism, Somatostatinoma, aldosteronoma.
E. Drug- or chemical induced - Vacor, pentamidine, nicotinic acid, glucocorticoids, thyroid hormone, Diazoxide, β-adrenergic agonists, thiazides, phenytoin, α- interferon, protease Inhibitors, clozapine.
H. Other genetic syndromes sometimes associated with diabetes ? Down's syndrome; Klinefelter's syndrome, Turner's syndrome, Wolfram's syndrome, Friedreich's ataxia, Huntington's chorea, Laurence-Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-Willi syndrome.
IV. Gestational diabetes mellitus (GDM). Epidemiology of diabetes:
DIABETES – A WORLD HEALTH PROBLEM
It is interesting to reflect that in the first edition of the IDF Diabetes Atlas, released in 2000, the estimated global diabetes prevalence was 151 million. Now the estimated diabetes prevalence for 2010 has risen to 285 million, representing 6.4% of the world’s adult population, with a prediction that by 2030 the number of people with diabetes will have risen to 438 million. Far from being a disease of higher income nations, diabetes is very much a disease associated with poverty, with the major burden borne by the low- and middle-income countries and disproportionately affecting the lower socio-economic groups.
There were an estimated 40 million persons with diabetes in India in 2007 and this number is predicted to rise to almost 70 million people by 2025(30).
TYPE 2 DIABETES MELLITUS
Type 2 diabetes is the most common form of diabetes. It is characterized by disorders of insulin action and insulin secretion, either of which may be the predominant feature. Although the specific aetiology of this form of diabetes is not known, autoimmune destruction of the β-cells does not occur. Most patients with type 2 diabetes are obese when they develop diabetes, and obesity aggravates the insulin resistance. The risk of developing Type 2 diabetes increases with age, obesity, and physical inactivity. Type 2 Diabetes shows strong familial aggregation, so that persons with a parent or sibling with the disease are at increased risk, as are individuals with obesity, hypertension, or dyslipidemia and women with a history of gestational diabetes. Persons of Native American, Polynesian or Micronesian, Asian-Indian, Hispanic, or African-American descent are at higher risk than persons of European origin. Although the disease is most commonly seen in adults, the age of onset tends to be earlier in persons of non-European origin. The disease can occur at any age and is now seen in children and adolescents.
According to ADA 2008 guidelines:
2—Criteria for the diagnosis of diabetes:
1. FPG -126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.*
OR
2. Symptoms of hyperglycaemia and casual plasma glucose -200 mg/dl (11.1mmol/l).
Casual is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycaemia include polyuria, polydipsia, and unexplained weight loss.
OR
3. 2-h plasma glucose -200 mg/dl (11.1 mmol/l) during an OGTT.
The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water*
IMPAIRED GLUCOSE TOLERANCE (IGT)
IGT is a stage of impaired glucose regulation that is present in individuals whose glucose tolerance is above the conventional normal range but lower than the level considered diagnostic of diabetes
It cannot be defined on the basis of fasting glucose concentrations;
an OGTT is needed to categorize such individuals. Persons with IGT do have a high risk of developing diabetes, although not all do so (9 ). Some revert to normal glucose tolerance, and others continue to have IGT for many years. Persons with IGT have a greater risk than persons of similar age with normal glucose tolerance of developing arterial disease (10), but they rarely develop the more specific micro vascular complications of diabetes, such as retinopathy or nephropathy, unless they develop diabetes . *In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeat testing on a different day .
IMPAIRED FASTING GLUCOSE (IFG)
IFG is also a stage of impaired glucose homeostasis. This category was introduced in the 1997 ADA and 1999 WHO classifications to include individuals whose fasting glucose levels were above normal but below those diagnostic for diabetes
Individuals with fasting plasma glucose concentrations of 100 to 125 mg/dL are now considered to have IFG (12). If an OGTT is performed, some of these individuals will have IGT and some may have diabetes (2 hours post load plasma glucose concentration ≥200 mg/dL. Consequently, it is prudent, and recommended by WHO, that such individuals, if possible, have an OGTT to exclude diabetes.
Pathogenesis of Type 2 Diabetes mellitus:
Genetic factors:
The contribution of genetic factors to the development of insulinresistance, impaired insulin secretion, and type 2 diabetes has been known for many years .Supporting evidence includes the familial clustering ofthese traits ,the higher concordance rate of type 2 diabetes in monozygotic versus dizygotic twins , and the high prevalence of type2 diabetes in certain ethnic groups. It is estimated that between 25% and70%
of the occurrence of type 2 Diabetes can be attributed to genetic factors .Studies of the patterns of inheritance indicate that multiple genes probably are involved, although their number and relative contributions are uncertain .
Beta cell dysfunction:
The distinctive β-cell defect in type 2 diabetes is the loss of the first phase of glucose-induced insulin secretion. The second phase is also impaired but to a lesser degree. Subsequent investigation showed that this defect was fully established by the time the fasting glucose level reached
Insulin resistance:
The term insulin resistance generally refers to resistance to the metabolic effects of insulin, including the suppressive effects of insulin on endogenous glucose production, the stimulatory effects of insulin on peripheral (predominantly skeletal muscle) glucose uptake and glycogen synthesis, and the inhibitory effects of insulin on adipose tissue lipolysis. It is generally accepted that insulin resistance plays a major role in the development of type 2 diabetes. Because currently an estimated 170 million people worldwide have Type 2 Diabetes, this is clearly an important association .Indeed, prospective studies have revealed that insulin resistance predates the onset of type 2 Diabetes by 10 to 20 years and is the best clinical predictor of subsequent development of type 2 Diabetes .
Acquired factors:
Beta cell cytotoxic chemical/ virus.
Autoimmunity.
Ageing, obesity.
Risk factors for Type2 Diabetes mellitus:
Family history of diabetes
Obesity
Sedentary lifestyle
IFG/ IGT
History of GDM• Systemic hypertension( >140/90 mm hg)
HDL<35 mg/dl, TGL> 250 mg/dl
Polycystic ovarian disease
History of vascular disease
(Source: adopted from ADA 2004).
Complications of Diabetes mellitus (DM):
Acute Complications of DM
Diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) are acute complications of diabetes. DKA was formerly considered a hallmark of type 1 DM, but it also occurs in individuals wholack immunologic features of type 1 DM and who can subsequently
Chronic Complications of DM
The chronic complications of DM affect many organ systems and are responsible for the majority of morbidity and mortality associated with the disease. Chronic complications can be divided into vascular and nonvascular complications. The vascular complications of DM are further subdivided into micro vascular (retinopathy, neuropathy, nephropathy) and macro vascular complications [coronary artery disease(CAD), peripheral arterial disease (PAD), cerebrovascular disease]. Nonvascular complications include problems such as gastro paresis, infections, and skin changes. Long-standing diabetes may be associated with hearing loss.
Evidence implicating a causative role for chronic hyperglycaemia in the development of macro vascular complications is less conclusive.
However, coronaryheart disease events and mortality are two to four times greater in patients with type 2DM. These events correlate with fasting and postprandial plasma glucose levels as wellas with the A1C. Other factors (dyslipidemia and hypertension) also play important roles in macro vascular complications.
METABOLIC SYNDROME
The metabolic syndrome (syndrome X, insulin resistance syndrome) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovasculardisease (CVD) and diabetes mellitus (DM). The criteria for the metabolic syndromehave evolved since the original definition by the World Health Organization in 1998,reflecting growing clinical evidence and analysis by a variety of consensus conferences and professional organizations. The major features of the metabolic syndrome includecentral obesity, hypertriglyceridemia, low HDL cholesterol, hyperglycaemia, and hypertension
NCEP: ATPIII 2001 Three or more of the following:
• Central obesity: Waist circumference >102 cm (M), >88 cm (F).
• Hypertriglyceridemia: Triglycerides>150 mg/dL or specific medication.
• Low HDL cholesterol: <40 mg/dL and <50 mg/dL for men and women respectively, or specific medication.
• Hypertension: Blood pressure > 130 mm systolic or > 85 mm diastolic or specific medication.
• Fasting plasma glucose >100 mg/dL or specific medication or previously diagnosed type 2 diabetes.
Two or more of the following:
Fasting triglycerides >150 mg/dL or specific medication.
HDL cholesterol <40 mg/dL and <50 mg/dL for men and women, respectively, or specific medication.
Blood pressure >130 systolic or >85 mm diastolic or previous diagnosis or specific medication.
Epidemiology
Prevalence of the metabolic syndrome varies across the globe, in part reflectingthe age and ethnicity of the populations studied and the diagnostic criteria applied. In general, the prevalence of metabolic syndrome increases with age. The highest recorded .prevalence worldwide is in Native Americans, with nearly 60% of women ages 45–49and 45% of men ages 45–49 meeting National Cholesterol Education Program, Adult Treatment Panel III (NCEP:ATPIII) criteria.
Pathophysiology of the metabolic syndrome:
Free fatty acids (FFAs) are released in abundance from an expanded adiposetissue mass. In the liver, FFAs result in an increased production of glucose, triglyceridesand secretion of very low density lipoproteins (VLDLs). Associated lipid/lipoprotein abnormalities include reductions in high-density lipoprotein (HDL) cholesterol and an increased density of low-density lipoproteins (LDLs). FFAs also reduce insulinsensitivity in muscle by inhibiting insulin-mediated glucose uptake. Associated defectsinclude a reduction in glucose partitioning to glycogen and increased lipid accumulation in triglyceride (TG). Increase in circulating glucose and to some extent FFA, increase inpancreatic insulin secretion, resulting in hyperinsulinemia. Hyperinsulinemia may resultin enhanced sodium reabsorption and increased sympathetic nervous system (SNS) activity and contribute to the hypertension, as might increase levels of circulating FFAs.
The proinflammatory state is superimposed and contributory to the insulin resistance produced by excessive FFAs. The enhanced secretion of interleukin 6 (IL-6) and tumour necrosis factor (TNF-alpha) produced by
and FFAs also increase the hepatic production of fibrinogen and adipocyteproduction of plasminogen activator inhibitor 1 (PAI-1), resulting in a prothromboticstate. Higher levels of circulating cytokines also stimulate the hepatic production of Creactive protein (CRP). Reduced production of the anti-inflammatory and insulin sensitizing cytokine adiponectin are also associated with the metabolic syndrome.
Associated Diseases
Cardiovascular Disease
The relative risk for new-onset CVD in patients with the metabolic syndrome, in the absence of diabetes, averages between 1.5- and threefold. In an 8-year follow up of middle-aged men and women in the Framingham Offspring Study (FOS), the population attributable risk for patients with the metabolic syndrome to develop CVD was 34% in men and 16% in women.
Ischemic stroke.
Peripheral vascular disease.
Type 2 Diabetes
Increases in:
ApoB and C III.
Uric acid- Hyperuricemia reflects defects in insulin action on the renal tubular reabsorption of uric acid.
Prothrombotic factors (fibrinogen, plasminogen activator inhibitor 1) • Serum viscosity.
Asymmetric dimethylarginine, homocysteine, white blood cell count, proinflammatory cytokines, CRP.
Microalbuminuria.
Non-alcoholic fatty liver disease (NAFLD) and/or non-alcoholic steatohepatitis (NASH).
Polycystic ovarian disease (PCOS).
Obstructive sleep apnoea (OSA).
OBESITY
Obesity is defined as a state of excessive adipose tissue mass and is best viewed as a syndrome or group of diseases rather than as a singledisease entity. The importance of this state derives from its high prevalence in our society and its association with serious morbidity, not the least ofwhich is a marked increase in the prevalence of type 2 diabetes.BMI is calculated by determining weight in kilograms and dividing by the height in meters squared. This measurement has been used to definefour classes of body weight. A BMI of
< than 18.5 is considered underweight.
18.5 - 24.9 is considered normal.
25.0 - 29.9 is considered overweight or preobese.
> 30 is considered in the obese category.
class I (BMI, 30 to 39.9)
class II (BMI, 40 to 49.9)
class III (BMI, >50).
The definition of obesity can be refined on the basis of the
to lower-body fat(i.e., buttocks and leg) or subcutaneous abdominal fat (34, 35). Abdominal fat, typically evident on physical examination, can be estimated by determiningthe waist-to-hip circumference ratio (with a ratio
>0.72 considered abnormal), or more accurately quantified by dual-energy x-ray absorptiometry (DEXA) scanning or computed tomography.
An important predictor of the morbidity and mortality associated withobesity is the quantity of visceral fat. A rough index of the relative amounts of visceral and abdominal fat is the waist-to-hip ratio. The alternative patterns of body-fat distribution have been described as pear shaped (low waist-to-hip ratio) and apple shaped (higher waist-to-hip ratio). When the waist-to-hip ratio is less than 0.8, the relative risk of morbidities associatedwith obesity is lower than when the waist-to-hip ratio is greater than 1.0.Hence, the metabolic syndrome, which is a clustering of obesity and other cardiovascular risk factors, is more likely to be associated with visceral obesity.
.PATHOLOGIC CONSEQUENCES OF OBESITY:
• Diabetes
The increased risk for type 2 diabetes in individuals with obesity is considerable. (In persons aged 20 to 44, obesity is associated with a fourfold increase in the relative risk of diabetes. Potential candidate substances produced by fat that may cause insulin resistance include tumournecrosis factor and other cytokines, such as interleukin-6, and resist in and adiponectin.
• Cardiovascular Disease
Obesity is an independent risk factor for cardiovascular disease ,including
• Pulmonary disease:
• The increased metabolic rate in obese subjects increases O2 consumptionand CO2 production, and these changes result in increased minuteventilation. In subjects with marked obesity, the compliance of the chestwall is reduced, the work of breathing is increased, and the respiratory reserve volume and vital capacity are reduced
• Gallstones.
Increased incidence of cholesterol gallstones (41)
• Cancer: The relative risk of liver cancer was almost 2-fold higher inmen with a BMI of 30.0 to 34.9. In men with a BMI higher than 35,the risk of stomach cancer was increased 1.94-fold, that of kidney cancer was increased 1.7-fold, and that of oesophageal cancer was increased 1.6-fold over the risk in normal-weight individuals. Inwomen with a BMI greater than 35, the relative risk of cancer of theuterus was 2.8, of cancer of the cervix was 3.8, and of breast cancer was 1.7
Hyperinsulinemia.
Major cardiovascular risk factors indicated in JNC-7 report are:
• Hypertension
• Smoking
• Obesity
• Physical inactivity
• Diabetes mellitus
• Dyslipidemia
• Microalbuminuria or estimated GFR< 60ml/mt o Age> 55 for men,
o >65 for women
• Family history of premature cardiovascular disease o <55 for men
o <65 for women.
Uric Acid in Disease
Uric acid is the final breakdown product of purine degradation in humans. Urates, the ionized forms of uric acid, predominate in plasma extracellular fluid and synovial fluid, with 98% existing as monosodium urate at pH 7.4. Although purine nucleotides are synthesized and degraded in all tissues, urate is produced only in tissues that contain xanthine oxidase, primarily the liver and small intestine. Urate production varies with the purine content of the diet and the rates of purine biosynthesis, degradation, and salvage. Normally, two-thirds to three- fourths of urate is excreted by the kidneys, and most of the remainder is eliminated through the intestines.
Urate is produced by the conversion of a very soluble molecule, hypoxanthine, to the less soluble xanthine, which in turn is converted to the very insoluble uric acid by progressive purine ring oxidations catalyzed by the enzyme xanthine oxidase. Xanthine oxidase is present in several organs, but most activity occurs in the liver and intestines.
Hyperuricemia may be classified in relation to the underlying pathophysiology, i.e., whether it results from increased production, decreased excretion, or a combination of the two. The most recognized complication of hyperuricemia is gouty arthritis.
Hyperuricemia also causes several renal problems: (1) nephrolithiasis; (2) urate nephropathy, a rare cause of renal insufficiency attributed to monosodium urate crystal deposition in the renal interstitium; and (3) uric acid nephropathy, a reversible cause of acute renal failure resulting from deposition of large amounts of uric acid crystals in the renal collecting ducts, pelvis, and ureters.
Previous studies have reported that a high concentration of uric acid (UA) is a strong marker of an unfavourable prognosis of moderate to
Xanthine oxidase and oxidative stress as reflected by UA may form a vicious cycle that promotes severe heart failure.
Many studies suggest that serum uric acid may exert a negative effect on cardiovascular disease by stimulating inflammation, which is clearly involved in the pathogenesis of coronary vascular disease.
Elevated serum uric acid is highly predictive of death in patients with cardiac failure or coronary vascular disease and of cardiovascular events in patients. High UA has been indicated as a risk factor for myocardial infarction and as an independent prognostic factor of poorer outcomes (occurrence of AMI, fatal AMI, sudden death, all-cause mortality) in patients with verified CAD. It has also theorized that hyperuricemia might be elaborate in chronic cardiac failure and metabolic syndrome.
Experimental studies have revealed a uric acid link to endothelial dysfunction, platelet adhesiveness, and platelet aggregation.
Uric acid has been found to promote low-density lipoprotein (LDL) oxidation in vitro, a key step in the progression of atherosclerosis, and these effects are inhibited by vitamin C indicating an important interaction between aqueous anti- oxidants. Uric acid can also stimulate granulocyte adherence to the endothelium, and peroxide and superoxide free radical liberation. Therefore uric acid may have a deleterious effect on the endothelium through leukocyte activation and, interestingly, a consistent relationship has been noted between elevated serum uric acid
There has been growing interest in the link between uric acid levels, xanthine oxidoreductase, and CVD. Xanthine oxidoreductase occurs in two forms, xanthine oxidase and xanthine dehydrogenase. Both of these enzymes are accountable for processing uric acid from hypoxanthine and xanthine.
Xanthine oxidoreductase is also an important source of reactive oxygen species in the cardiovascular system. Through this role, it has been linked with hypertension, endothelial dysfunction, and congestive heart failure.
Uric acid as a indicator of subclinical ischemia
Adenosine is produced and released by cardiac and vascular myocytes. Binding to specific adenosine receptors causes relaxation of vascular smooth muscle and arteriolar vasodilatation. It makes a minor contribution to normal resting endothelial tone, since competitive antagonism at the adenosine receptor by methylxanthines, such as theophylline, reduce blood flow response to ischemia in the forearm vascular bed.
In Hypoxia and tissue ischemia, vascular adenosine synthesis and release are upregulated, causing suggestively increased circulating concentrations. Cardiac and visceral ischemia endorse generation of adenosine, which may serve as an vital regulatory mechanism for restoring blood flow and limiting the ischaemia.
Adenosine produced in vascular smooth muscle of cardiac tissue is rapidly degraded by the endothelium to uric acid, which in the presence of low ph and negative membrane potential undergoes rapid efflux in the vascular lumen .
temporary coronary artery occlusion, leads to an rise in the local circulating level of uric acid.
Study of tourniquet-induced lower limb exsanguination in patients undergoing surgery shows a five-fold increase in systemic vascular xanthine oxidase activity during reperfusion, and a significant elevation of serum uric acid, which persists for at least two hours.72 Others demonstrated deposits of urate crystals in the proliferated intima of arteries or in organized thrombi, and this, of course, represents one mechanism by which uric acid may participate in the process of vascular degeneration.
Emerging evidence suggests that there is an imbalance between free radical production and NO generation in HF (nitroso-redox imbalance). Within the heart, xanthine oxidase activity stimulates cardiac myocyte hypertrophy and apoptosis and impairs matrix structure. The underpinnings of these derangements can be linked not solely to oxidative stress but also to reduced NO generation. In this regard, xanthine oxidase interacts with NO signalling at numerous levels, including a direct protein- protein interaction with neuronal NO synthase (NOS1) in the sarcoplasmic reticulum. Deficiency or translocation of NOS1 away from
can blunt the Frank-Starling response in the heart, and it may be a mechanism of decreased heart function via hyperuricemia.
According to the chinese Acute Cardiovascular Study , there was a close association between serum uric acid level and Killip classification in patients of acute myocardial infarction. Patients who developed short-term opposing events had high uric acid level.
Bickel C et al reported that one mg/dL increase in serum uric acid levels was associated with a 26% increase in mortality.
Siniša Car et al. in their study found that higher serum uric acid determined on admission was associated with higher in-hospital mortality and thirty-day mortality and poorer long-
Yıldız et al and Nihat Kalay et al in their separate studies found that serum uric acid levels were higher in patients with Slow Coronary Flow compared to controls. Serum uric acid has also been suggested as a risk factor for occurrence and a predictor of poorer outcomes in acute stroke.
mortality in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study. Therefore, any drug interventions, such as therapy to decrease serum uric acid level in addition to coronary reperfusion, may have a favourable effect on mortality in patients who have Acute Myocardial Infarction.
Cardiovascular Conditions and Risk Factors Associated with Elevated Uric Acid
Hypertension and prehypertension, renal disease (including reduced glomerular filtration rate and microalbuminuria), metabolic syndrome (including abdominal obesity, hypertriglyceridemia, low level of high-density lipoprotein cholesterol, insulin resistance, impaired glucose tolerance, elevated leptin level), obstructive sleep apnea, vascular disease (carotid, peripheral, coronary artery), stroke and vascular dementia, preeclampsia, inflammation markers (C-reactive protein, plasminogen activator inhibitor type 1, soluble intercellular adhesion molecule type 1), endothelial dysfunction, oxidative stress, sex and race (postmenopausal women, blacks), and demographic (movement
Our study was done to note the levels of serum uric acid in acute myocardial infarction, to correlate serum uric acid levels with Killip classification and to note any relationship between serum uric acid level and mortality following acute myocardial infarction, to study the relation between serum uric acid and cardiac troponin and CK-MB in acute myocardial infarction, and to study the relation between serum uric acid and systemic hypertension & diabetes mellitus in acute myocardial infarction.
In the present study, we found a close relation between serum uric acid concentrations and hypertension,dyslipidimia,coronary artery disease in diabetic patients. High uric acid concentrations on admission were strongly associated with adverse clinical outcome in patients who had acute myocardial infarction.
METHODOLOGY
STUDY SETTING: This study was done at Tirunelveli Medical College Hospital,
STUDY DESIGN: Descriptive analytical study STUDY DURATION: 0ne year
STUDY SUBJECTS: Study will be conducted on 70 cases of type 2 diabetes mellitus patients.
INCLUSION CRITERIA :
Patients with type 2 diabetes mellitus(irrespective of glycemic status and duration of diabetes)
Patient age more than 40years Both sex were included
EXCLUSION CRITERIA : Patients with
Renal failure
PVD, CVD,PTB
Renal transplant patients
Pregnancy and lactating mothers DATA COLLECTION:
Based on the criteria, patients were selected, and proforma containing history, clinical examination and investigation was prepared.
Ethics committee approval was obtained before the start of the study by the Institutional Ethics Committee.
RESULTS
ANALYSIS RESULTS:
Descriptive Statistics
N Range Minimum Maximum Mean Std.
Deviation Variance
Age 70 29.0 41.0 70.0 55.886 8.0803 65.291
Blood Uric acid 70 3.6 5.5 9.1 7.240 .6834 .467
Blood Sugar 70 113.0 112.0 225.0 157.771 26.8761 722.324
BMI 70 6.91 23.60 30.51 26.9544 1.72964 2.992
WHR 70 .72 .78 1.50 .9447 .10670 .011
CPKMB 70 52.0 38.0 90.0 66.114 13.5877 184.624
TOTAL
CHOLESTRAL 70 96.0 144.0 240.0 180.543 25.9479 673.295
TGL 70 84.0 96.0 180.0 144.571 14.3704 206.509
LDL 70 54.0 38.0 92.0 47.943 7.9689 63.504
Valid N
TABLE 2
AGE AND SEX DISTRIBUTION Sex
Total Male Female
Agegroup
< 55 Years
Count 19 20 39
% within
Agegroup 48.7% 51.3% 100.0%
> 55 Years
Count 14 17 31
% within
Agegroup 45.2% 54.8% 100.0%
Total
Count 33 37 70
% within
Agegroup 47.1% 52.9% 100.0%
P value = 0.478
OUT OF 70 PATIENTS ,33 MALES AND 37 FEMALES, MAJORITY OF THE PATIENTS WERE FEMALES
TABLE 3
AGE WITH OBESITY DISTRIBUTION BMIgroup
Total Normal Obese
Agegroup
< 55 Years
Count 2 37 39
% within Agegroup
5.1% 94.9% 100.0%
> 55 Years
Count 7 24 31
% within Agegroup
22.6% 77.4% 100.0%
Total
Count 9 61 70
% within Agegroup
12.9% 87.1% 100.0%
P value = 0.030
AMONGST THE STUDIED GROUP OUT OF 39 PATIENTS <55 YEARS 95% HAD OBESITY AND OUT OF 31 PATIENTS >55 YEARS 77.4% HAD OBESITY
TABLE 4
HYPERTENSION DISTRIBUTION
P value = 0.031
Hypertension
Total
Yes No
Sex
Male
Count 13 20 33
% within
Sex 39.4% 60.6% 100.0%
Female
Count 19 18 37
% within
Sex 51.4% 48.6% 100.0%
Total
Count 32 38 70
% within
Sex 45.7% 54.3% 100.0%
AMONGST THE STUDIED MALES OUT OF 33 MALES,39.4% OF MALE HAD HYPERTENSION. AMONGST THE FEMALES OUT OF 37 ,51.4% OF FEMALES HAD HYPERTENSION.THAT IS 45.7% OF THIS STUDY HAD HYPERTENSION.
TABLE NO :5
DISTRIBUTION OF MYOCARDIAL INFARCTION MYOCARDIAL INFARCTION
Total ASMI AWMI ILMI IWMI JLWMI
Sex
Male
Count 8 23 1 1 0 33
% within
Sex 24.2% 69.7% 3.0% 3.0% 0.0% 100.0%
Female
Count 12 17 2 3 3 37
% within
Sex 32.4% 45.9% 5.4% 8.1% 8.1% 100.0%
Total
Count 20 40 3 4 3 70
% within
Sex 28.6% 57.1% 4.3% 5.7% 4.3% 100.0%
P value = 0.213
FROM THE STUDY WE CAN FIND THAT MAJORITY OF THE PATIENTS HAD ANTERIOR WALL MI ,NEXT IN COMMON WAS ASMI .AND THE PREVALENCE WAS MORE IN MALES.
TABLE 6
BMI DISTRIBUTION BMIgroup
Total Normal Obese
Sex
Male
Count 2 31 33
% within
Sex 6.1% 93.9% 100.0%
Female
Count 7 30 37
% within
Sex 18.9% 81.1% 100.0%
Total
Count 9 61 70
% within
Sex 12.9% 87.1% 100.0%
P value = 0.130
AMONST THE STUDIED MALES,93.9% OF MALES HAD BMI MORE THAN 25.IN FEMALES 81.1% HAD BMI MORE THAN 25.
Group Statistics
Sex N Mean Std.
Deviation
Std. Error
Mean Sig.
Blood Uric acid
Male 33 7.603 .5047 .0878 0.000
Female 37 6.916 .6635 .1091 Blood Sugar
Male 33 164.697 23.8910 4.1589 0.039 Female 37 151.595 28.1765 4.6322
BMI
Male 33 27.1061 1.43917 .25053 0.493 Female 37 26.8192 1.96292 .32270
WHR
Male 33 .9458 .07826 .01362 0.939
Female 37 .9438 .12796 .02104 CPKMB
Male 33 64.152 14.7651 2.5703 0.025 Female 37 67.865 12.3854 2.0361
TOTAL CHOLESTROL
Male 33 176.091 26.4520 4.6047 0.177 Female 37 184.514 25.1822 4.1399
TGL
Male 33 148.121 11.5346 2.0079 0.050 Female 37 141.405 15.9904 2.6288
LDL
Male 33 47.848 6.7367 1.1727 0.926
Female 37 48.027 9.0200 1.4829
Group Statistics
Agegroup N Mean Std.
Deviation
Std. Error
Mean Sig value Blood
Uric acid
< 55 Years 39 7.272 .7539 .1207 0.023
> 55 Years 31 7.200 .5927 .1065 Blood
Sugar
< 55 Years 39 150.333 28.3236 4.5354 0.008
> 55 Years 31 167.129 21.9723 3.9463 BMI
< 55 Years 39 27.3849 1.52102 .24356 0.030
> 55 Years 31 26.4129 1.84567 .33149 WHR
< 55 Years 39 .9721 .12813 .02052 0.005
> 55 Years 31 .9103 .05654 .01015 CPKMB
< 55 Years 39 64.667 14.1706 2.2691 0.281
> 55 Years 31 67.935 12.8113 2.3010 TOTAL
CHOLESTRA L
< 55 Years 39 179.410 26.8776 4.3039 0.535
> 55 Years 31 181.968 25.0951 4.5072 TGL
< 55 Years 39 146.538 12.8429 2.0565 0.193
> 55 Years 31 142.097 15.9590 2.8663 LDL
< 55 Years 39 47.128 6.0008 .9609 0.465
> 55 Years 31 48.968 9.9247 1.7825
DISCUSSION
Unlike many medical conditions that are common, disable, and kill, cardiovascular disease already the most common cause of death in the world, and expected to account for a growing proportion of all deaths—is almost entirely preventable. Socioeconomic factors and habits of society, including (1) a diet high in saturated fat, (2) sedentary living, and (3) smoking, are important underlying determinants of the population rate of coronary disease. There are strong, unconfounded relationships between several risk factors and CHD mortality and nonfatal myocardial infarction. Those with the strongest effect are (1) age, (2) country, and (3) presence of symptomatic or preclinical disease. Based on recent individual patient data meta-analysis, systolic blood pressure and cholesterol have a log-linear relation with CHD mortality, with no evidence of lower threshold at every age up to the ninth decade of life. A lower blood pressure is associated with a lower risk, whatever the starting level. The implications of this are profound: shifting the distribution of such a risk factor in the whole population by an apparently small amount has a major effect on population rates of disease, e.g. a 5-mmHg
We studied a total of 70 diabetic patients with acute myocardial infarction, of which 33 were males and 37 were females. Seventy patients were also evaluated for their baseline serum uric acid level. There Sarma P et al in their study of risk of coronary heart disease with raised serum uric acid reported that in 222 diabetic patients who had experienced myocardial infarction, 68.5% had serum uric acid levels above 6 mg/dl and 31.5% had normal serum uric acid. Thus, raised serum uric acid level may be associated with Coronary Heart Diseases. An epidemiological link between elevated serum uric acid and an increased cardiovascular risk has been recognized for many years. Observational studies show that serum uric acid concentrations are higher in patients with established coronary heart disease compared with healthy controls. However, hyperuricemia is also associated with possible confounding factors including elevated serum triglyceride and cholesterol concentrations, blood glucose, fasting and post-carbohydrate plasma insulin concentrations, waist-hip ratio and body mass index.
There are certain clinical clustering groups with increased cardiovascular risk, which have associated hyperuricemia.
Non-diabetic patient groups with accelerated atherosclerosis,
T2DM patient groups with accelerated atherosclerosis,
Congestive heart failure patient groups with ischemic cardiomyopathy, metabolic syndrome patients,
Renal disease patient groups,
Hypertensive patient groups,
African American patient groups,
Patient groups taking diuretics,
Patient groups with excessive alcohol usage.
The four major factors in the metabolic syndrome are hyperinsulinemia, hypertension, hyperlipidemia, and hyperglycemia. Each member of this deadly quartet has been demonstrated to be an independent risk factor for CHD and capable of working together in a synergistic manner to accelerate both non-diabetic atherosclerosis and the atheroscleropathy associated with MS, PD, and T2DM.In a like manner,
manner resulting in the progression of accelerated atherosclerosis and arterial vessel wall remodelling along with the original players.
In this study serum uric acid levels in diabetes was examined. Uric acid as a marker of CAD in combination with other risk factors which includes Metabolic Syndrome components was examined. A control group consisting of non diabetics was also examined. Both the groups were age and sex matched. Uric acid levels and age were independent. Duration of the diabetes positively correlated with uric acid levels. Uric acid levels increase with increasing duration of diabetes and the association was statistically significant. Yoo et al. (2005) and Becker and Jolly (2006) reported that hyperglycemia was a remarkable risk factor for hyperuricemia. In a study of 3 681 Japanese adult, it was found that an elevation of serum uric acid concentration in males increased the risk of type 2 diabetes (Nakanishi et al., 2003). It was concluded that hyperuricemia was positively associated with hyperglycemia. In the present study males have higher uric acid level when compared to females.
The mean uric acid levels in males and females were 7.6±0.5 and 6.9±0.6
cm in females is abnormal. In this present study the mean serum uric acid levels inpatients with abnormal WHR and normal WHR were 6.91±1.31 and 6.55±1.11 respectively and the difference was statistically significant.
Hyperuricemia has been associated with increasing body mass index (BMI) in recent studies and are even apparent in the adolescent youth [92- 95] Leptin levels are elevated and associated with insulin resistance in MS and early T2DM. Bedir A et al. have recently discussed the role of leptin as possibly being a regulator of SUA concentrations in humans and even suggested that leptin might be one of the possible candidates for the missing link between obesity and hyperuricemia (76) In the present study uric acid levels were significantly elevated in patients with dyslipidemia.The intrinsic defects in GA3PDH and a loss of its responsiveness to insulin, by causing accumulation of glycolytic intermediates, may explain the association between insulin resistance, hyperuricemia, and hypertriglyceridemia.Two separate laboratories have demonstrated the development of systemic hypertension in a rat model of hyperuricemia developed with an uricase inhibitor(oxonic acid) after several weeks of treatment [97,98]. This hypertension was associated with
the NOS enzyme. Hypertension, neural nitric oxide synthase (nNOS) and renin changes were also prevented by maintaining uric acidlevels in the normal range with allopurinol or benziodarone (uricosuric). These above models have provided the first challenging evidence that uric acid may have a pathogenic role in the development of hypertension, vascular disease, and renal disease .
An epidemiological relationship between elevated serum uric acid and an increased cardiovascular risk has been recognized for decades.
Observational studies show that serum uric acid concentrations are higher in patients with established coronary heart disease compared with healthy controls.
Raised serum uric acid concentrations are also found in healthy offspring of parents with coronary artery disease, indicating a possible causal relationship. However, hyperuricemia is also associated with possible confounding factors including elevated serum triglyceride and cholesterol concentrations, blood glucose, fasting and post-carbohydrate plasma insulin concentrations, waist-hip ratio and body mass index. About
that the importance of uric acid may be independent of confounding risk factors.
Several studies have recommended that the relationship between elevated serum uric acid and cardiovascular risk does not persist after improving for other risk factors showed a significant association between elevated serum uric acid and fatal and non fatal coronary disease over a mean 16.8 years However, this relationship disappeared after correcting for other risk factors, particularly serum cholesterol concentration.
The Coronary Drug Project Research Group studied 2789 men, aged 30 to 64 years, and found that the association between increased cardiovascular risk and elevated serum uric acid concentration was not significant after consideration of other risk factors, and when thiazide diuretic use was considered .
In the present study serum uric acid positively correlated with duration of diabetes and cardiovascular risk factors like obesity (high BMI, abnormal waist hip ratio), hypertension, dyspidemia and the results were statistically significant.
CONCLUSION
Serum uric acid levels were significantly higher in diabetic population.
The serum uric acid level was independent of age and smoking status (in males).
Mean serum uric acid levels were high in males.
Significant positive correlation between serum uric acid levels and Body Mass
Index as well as Waist Hip Ratio was noted.
Elevated serum uric acid levels were significantly noted among those with
1. BMI>25,
2. WHR abnormality,
3. Dyslipidemia with high triglycerides, 4. Hypertension.
• Serum uric acid levels increased with increasing duration of diabetes.
SUMMARY
An epidemiological elevated serum uric acid and an increased cardiovascular risk has been recognized for many years. Observational studies show that serum uric acid concentrations are higher in patients with established coronary heart disease compared with healthy controls.
However, hyperuricemia is also associated with possible confounding factors including elevated serum triglyceride and cholesterol concentrations, blood glucose, fasting and post-carbohydrate plasma insulin concentrations, waist-hip ratio and body massindex. Diabetes mellitus is strongly associated with hyperuricemia. The present study was proposed to assess the uric acid status in patients with diabetes mellitus and to find its association with age, gender, BMI, WHR, smoking, dyslidemia, hypertension and CAD.
With rigid criteria patients were selected carefully and evaluated after gettinginstitutional, ethical clearance and informed consent.
Serum uric acid levels were significantly higher in the study group, BMI above 25 were seen in 87.1% of cases,
significant. Mean serum uric acid in males was high compared to females.
Smoking was not significantly associated with higher uric acid levels.
Patients with longer duration of diabetes also had elevated uric acid levels.Factors contributing to hyperuricemia in diabetes are:
• Hyperinsulinemia reduces urinary uric acid excretion and sodium excretion.
• Micro vascular disease in diabetes mellitus causes local tissue ischemia and decreased renal blood flow. Ischemia increases lactate production that blocks urate secretion in proximal tubules.
Meticulous control of blood sugar, hypertension, dyslipidemia, body weight and abdominal girth form an essential component of diabetes which will bring down uric acid levels. It is worth to explore uric acid levels in diabetic patients with other cardiovascular risk factors like obesity, dyspidemia, hypertension to detect early cardiovascular complications.
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