Gout

Recent studies have examined the relationship between gout and lead exposure, looked at hyperuricemia as a risk factor for diabetes, and addressed the starting does of allopurinol.

Acceptable Lead Levels Still Associated with Gout

People with blood lead levels that are considered in the normal range may still be linked to an increased risk of gout, a new study suggests.

Among many severe medical conditions it may cause, toxic lead exposure has long been known to interfere with the kidneys’ ability to excrete uric acid from the body, thus causing hyperuricemia and gout. The lead level range considered acceptable in adults is 25 mcg/dL or less, but many developed countries, including the United States, aim to cut that level much lower, and the average in this country is 3 mcg/dL. This study, which was published in August 2012 in the Annals of Internal Medicine, enrolled more than 6000 Americans 40 years and older. Their blood lead levels were measured, and they were interviewed about their health and lifestyle. What the researchers found was participants began to have an increased risk of gout at levels at or above 1.2 mcg/dL, way below the average in the United States. The risk increased with higher levels of lead.

The study has 2 major ramifications. First, if a patient has no other risk factors for gout, such as obesity and poor diet, the clinician may consider taking a blood lead level to see if it is elevated. High blood lead levels may be due to cigarette smoke, inhalation of lead-containing dust, exposure to lead-based paint, or drinking of water from lead-based pipes. Avoiding these exposures to lead may help improve gout. Second, this study suggests that the level that is considered acceptable for lead may be too high—and should be revised. The authors mention that the Centers for Disease Control and Prevention have previously lowered the acceptable lead level for children from 10 to 5 mcg/dL, and it may need to be lowered even more in the general population as well.

Scientists Propose Safe Starting Dose of Allopurinol

Higher doses of the commonly used drug allopurinal to treat gout is associated with an increased risk for allopurinal hypersensitivity syndrome (AHS), according to a study published in the August 2012 issue of Arthritis & Rheumatism.

According to current dosing guidelines, ≥300 mg/day of allopurinal may be associated with AHS, especially in patients with impaired hepatic function. Investigators looked at 54 AHS cases and 157 controls. Ninety-one percent of AHS patients and 36% of the controls received a starting dose of ≥1.5 mg per unit of estimated glomerular filtration rate (GFR).

The researchers concluded that a starting dosage of ≥1.5 mg per GFR reduces a patient’s risk of developing AHR. “In patients who tolerate allopurinol, the dose can be gradually increased to achieve the target serum urate level,” the researchers, led by Lisa K. Stamp, PhD, associate professor at the University of Otago and Fellow of the Royal Australasian College of Physicians, wrote.

Hyperuricemia May Predict Diabetes

Hyperuricemia may be an independent risk factor for diabetes and prediabetes, a new study suggests.

The study, published in the American Journal of Epidemiology in August 2012, analyzed 15-year followup data on 5012 participants in 4 US cities who were aged 18 to 30 years and diabetes-free at the time of enrollment. The authors found that during the follow-up period from 1986 to 2001, the incidence rates of diabetes and prediabetes (insulin resistance and impaired fasting glucose) were higher among those with greater serum urate concentrations. The authors concluded that hyperuricemia in the mid-twenties is an independent marker for predicting diabetes and prediabetes among young adults in the subsequent 15 years.

Obesity is a common risk marker for type 2 diabetes, but many people who develop type 2 diabetes are not obese, the authors write, so there must be other independent risk factors. Hyperuricemia may be one risk factor, and the link between hyperuricemia and diabetes is currently under investigation. Researchers believe that an increased blood level of uric acid may lead to insulin resistance. Also, hyperuricemia can cause reduced nitric oxide levels, which can also cause insulin resistance.

The study suggests that determining hyperuricemia in a patient may be an important first step in identifying if that patient will develop diabetes in the future. Proper interventions may be instituted in these patients to avoid the development of diabetes and prediabetes.

About the Author

Michael C. Wisotsky, PharmD, RPh, practices in Shrewsbury, New Jersey.