African Journal of Biotechnology Vol. 10(6), pp. 996-998, 7 February, 2011 Available online at http://www.academicjournals.org/AJB DOI: 10.5897/AJB10.1930 ISSN 16845315 2011 Academic Journals

Short Communication

Obesity and the risk of hyperuricemia in Gadap Town, Karachi

Muhammad Akram1, H.M.Asif2, Khan Usmanghani1, Naveed Akhtar2, Qaiser Jabeen2, Asadullah Madni2, Tariq saeed3, Riazur Rehman2, Khalil Ahmed2 and S.M. Ali Shah2

1Shifa ul Mulk Memorial Hospital, Hamdard University, Karachi, Pakistan.

2Faculty of Pharmacy and Alternative Medicine, Islamia University of Bahawalpur.

3University College of Pharmacy, Punjab University, Lahore, Pakistan.

Accepted 30 December, 2010

Obesity is a known risk factor for hyperuricemia. However, the effect of the interaction between obesity and hyperuricemia is not well understood. Previous study has shown a relationship between hyperuricemia and obesity, but the evidence from prospective studies of an association between obesity and uric acid risk is limited. We prospectively evaluated the association between obesity and the incidence of uric acid in obese individuals.In a population-based cohort, obesity and weight gain was found to be strongly associated with hyperuricemia. Additionally, all patients who developed hyperuricemia were obese at baseline. Obesity is a risk factor for hyperuricemia and may be useful for prediction of incident gout in individuals. Keywords: Lipids, cardiology, hypertension.

INTRODUCTION Hyperuricemia Uric acid is the end product of purine metabolism. Syn-thesis of uric acid occurs in liver. Gout is an abnormality of uric acid metabolism that results in the deposition of sodium urate crystals in joints, soft tissues and urinary tract. Gout may be caused by impaired excretion of uric acid or overproduction of uric acid. An abnormality in handling uric acid can cause attacks of painful arthritis (gout attack), kidney stones and blockage of the kidney-filtering tubules with uric acid crystals, leading to kidney failure. On the other hand, some people may only develop elevated blood uric acid levels (hyperuricemia) without having manifestations of gout, such as arthritis or kidney problems. The state of elevated levels of uric acid in the blood without symptoms is referred to as asympto-matic hyperuricemia. Asymptomatic hyperuricemia may ultimately result to disease conditions like gout and kidney stone. Gouty arthritis is typically an extremely painful attack with a rapid onset of joint inflammation. The *Corresponding author. E-mail: makram_0451@hotmail.com. Tel: 92-021-6440083. Fax: 92-021-6440079.

joint inflammation is precipitated by deposits of uric acid crystals in the joint fluid (sensorial fluid) and joint lining (synovial lining). Intense joint inflammation occurs as the immune system reacts, causing white blood cells to engulf the uric acid crystals and chemical messengers of inflammation to be released, and this leads to pain, heat and redness of the joint tissues. As gout progresses, the attacks of gouty arthritis typically occur more frequently and often in additional joints (Garg et al., 2005).

It is estimated that approximately 15 out of every 1,000 male between 35 and 45 years of age have hyperuri-cemia. Hyperuricemia afflicts an estimate of 840 out of 100,000 people. Men tend to have higher uric acid levels than women. International prevalence of hyperuricemia is 0.3%. Hyperuricemia has a 90% male predominance. Fairly substantial proportion of patients with hyperuri-cemia (10 to 20%) has a family history of hyperuricemia (McCarty, 1994). Causes of hyperuricemia and gout

Gout occurs as a result of excess uric acid (urate) in the

blood and tissues. It occurs due to impaired excretion of uric acid from the kidney. Impaired excretion of uric acid has primary and secondary causes. Primary cause is idiopathic. Secondary cause includes chronic renal disease, drug therapy, hypertension, lead toxicity, pri-mary hyperparathyroidism, hypothyroidism, increased lactic acid production and glucose 6 phosphatase deficiency. Over production of uric acid causes idiopathic (primary) gout, increased purine synthesis de novo due to hypoxanthine guanine phosphoribosyl transferase reduction (an x linked inborn error causing the lesh nyhan syndrome) and phosphoribosyl-pyrophosphate synthe-tase over activity. Gout is a common joint disease which affects over five times more men than women. It is rare in children. In men, it can occur any time after puberty, whereas in women it is uncommon before the meno-pause. In about 10% of such cases, there is a family history of the disorder. People who are overweight, have high blood pressure, eat diets rich in protein and drink large quantities of alcohol have an increased risk of developing gout (Shiraishi and Une, 2009). Signs and symptoms of hyperuricemia that leads to gout

Gout usually affects the large joint of the big toe, but it can occur in the feet, ankles, knees, hands and wrists. The pain is likely to be most severe within the first 12 to 24 h after it begins. After the most severe pain subsides, joint comfort may last from a few days to a few weeks. Later attacks are likely to last longer and affect more joints. The affected joint or joints become swollen, tender and red. Most often, symptoms first start in one joint. Symptoms can also occur in other parts, if more than one joint is affected. Multiple joints are affected in only 10 to 20% of first attacks. The most frequently affected joints are the foot, ankle, knee, wrist, elbow and hand. The pain usually occurs in joints of one side of the body and it is usually, in the lower legs and feet. An untreated attack will typically peak 24 to 48 h after the first appearance of symptoms, and subside after 5 to 7 days. However, some attacks last only for hours, while others persist as long as several weeks (Brule et al., 1992). It also affects the elbow, shoulder, wrist and metacarpophalangeal joints. The cascade of pathologic events leads to acute inflam-mation of the joint or soft tissue. Hyperuricemia can also result in uric acid nephrolithiasis and possible nephro-pathy if uric acid accumulates in the renal interstitium and tubules. Acute attacks can be precipitated by several factors such as increased alcohol consumption (espe-cially beer), trauma, use of diuretics, dehydration, cyclo-sporine, diet (organ meat, shellfish) and any drug that can lead to sudden changes (increase or decrease) in urate levels, such as hypouricemic agents (Beutler and Schumacher, 1994). When urate accumulates in a super-saturated medium, it can be deposited in soft tissues or bones and form a tophus. Tophi can be present in the

Akram et al. 997 helices of the ears, extensor areas of the limbs, pressure areas such as the finger pads, and over the Achilles tendons. Occasionally, they are not seen on physical examination but are noted on x-ray films as cystic or mass like lesions. In general, a tophus on radiographic films is radiolucent, but when it occurs over a calcified nodule, it may be seen as radio opaque (Chung et al., 1997). Urate nephropathy is the result of the deposition of monosodium urate crystals in the renal interstitial tissue. Uric acid nephropathy is caused by the deposition of uric acid crystals in the collecting tubules, renal pelvis or the ureter and results in impaired urine flow. Calcium oxalate urolithiasis also occurs in hyperuricemic patients. Uric acid urolithiasis (uric acid kidney stones) accounts for approximately 10% of all urinary calculi (stones) in the US (Pearle et al., 2005).

Diagnosis

The serum urate level is usually raised but it is important to appreciate that this does not prove the diagnosis because asymptomatic hyperuricemia is very common. However, possible synovial fluid should be aspirated and examined under polarizing light. Joint radiographs are seldom useful in establishing the diagnosis. Although they may show characteristic punched out erosion asso-ciated with the soft tissue swelling of urate tophi, occasionally flecked with calcium, the diagnosis will be clinically apparent in such patients and in others the ero-sions may be indistinguishable from those seen in various forms of inflammatory arthritis (Martinez et al., 1988).

Treatment of hyperuricemia that leads to gout

Serum uric acid concentrations may be reduced with non pharmacologic therapy. Useful dietary and lifestyle changes include weight reduction, decreased alcohol ingestion, decreased consumption of foods with a high purine content and control of hyperlipidemia and hyper-tension. Used alone, however, these measures will probably not reduce serum uric acid levels to normal, which is the treatment goal for the prevention of acute gout attacks. Symptomatic hyperuricemia usually re-quires medication. Lowering the blood concentration of uric acid may permit any existing crystals of uric acid to be gradually dissolved into the blood, from where the dissolved uric acid can be excreted. Maintaining a lower blood concentration of uric acid, should similarly reduce the formation of new crystals. Most medications often used to treat hyperuricemia are of two kinds: xanthine oxidase inhibitors and uricosurics. Xanthine oxidase inhibitors decrease the production of uric acid, by interfering with xanthine oxidase. Uricosurics increase the excretion of uric acid, by reducing the reabsorption of uric acid once the kidneys have filtered it out of the blood. Some of these medications are used as indicated; others are used off-label. Several other kinds of medications

998 Afr. J. Biotechnol. have potential for use in treating hyperuricemia. For people receiving hemodialysis, it can significantly reduce serum uric acid (Shrestha et al., 1994; Garg et al., 1993; Ohno et al., 2009; Scott and Higgens, 1992; Akram, 2009). MATERIALS AND METHODS

The evaluations of parameters like body mass index and serum uric acid were conducted at Shifa-ul-Mulk Memorial Hospital, for Eastern Medicine, Hamdard University. The patients were registered in the general O.P.D and hospitalized in the clinical Research ward of the Hospital. All the patients selected for the study, were thoroughly examined and clinical history was recorded.

We conducted a community-based prospective cohort study of 3000 participants (age range, 35 to 70 years) living in Gadap Town, who were found to be free of uric acid and cardiovascular disease during baseline assessment at study entry in 2005. During a median 5 year follow-up, 560 participants developed hyperuricemia.

RESULTS

Prevalence of hyperuricemia was seen in obese individuals. During a median 5 year follow-up, out of 3000 obese participants, 560 developed hyperuricemia. Preva-lence of Hyperuricemia is seen in obese individuals. Of the 3000 individuals with serum urate measurements, all were free of hyperuricemia. Additionally, 560 participants (18%) developed hyperuricemia over five years of follow-up. At baseline, all of the individuals who developed hyperuricemia were obese.

DISCUSSION

Many diseases and complication are associated with obesity. Hyperuricemia is one of these conditions. Our study showed positive association between obesity and serum uric acid level (p < 0.05). Serum uric acid is not only associated with obesity but it is also positively and significantly associated with many other clinical con-ditions, e.g. diabetes mellitus, hypertension and ischemic heart disease. Although these conditions are also associated with obesity, serum uric acid is independently associated with all these conditions. So it can be inferred that obese patients, who are also hyperuricemic, suffer more commonly from diabetes mellitus, hypertension and ischemic heart disease when compared with patients who are obese but not hyperuricemic. Increased levels of serum uric acid also increase morbidity and mortality in these patients. It is recommended that serum uric acid should be routinely measured in all obese and overweight patients in order to prevent or at least delay compli-cations due to raised serum uric acid. Serum uric acid is also a reliable indicator for the pre-metabolic syndrome in obese patients. Mechanism by which serum uric acid is increased in obese patients is not known but it has been

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