Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Reconfirmation of the Death of Homocysteine

Source: Ebbing M, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: A randomized controlled trial. JAMA 2008;300:795-804.

Homocysteine (HCYS) has all the trappings of a first-rate cardiovascular risk factor: as strong an association with CVD endpoints as cholesterol, ease of identification, and simplicity of modulation. Trouble is, trials to date have been unable to show that reductions of homocysteine provide meaningful benefits to patients. Indeed, one recent commentary following a large double-blind interventional trial of HCYS for cardiovascular endpoints began with "The homocysteine hypothesis is dead ... ."

Apparently as undaunted as Mark Twain ("The reports of my death are greatly exaggerated ..."), Ebbing et al tested HCYS reduction through B vitamins after coronary angiography. The primary endpoint of the study was all-cause mortality, non-fatal stroke and MI, and hospitalization for unstable angina (composite).

The trial (n = 3096) was designed to follow patients for 4 years, but was stopped at 38 months due to information from another trial that had reported a possible negative effect of B vitamin intervention. B vitamins did reduce HCYS by approximately 30%, but failed to have any impact (positive or negative) upon endpoints. The HCYS hypothesis is still dead.

Incidentalomas in the Knee

Source: Englund M, et al. Incidental meniscal findings on knee MRI in middle-aged and elderly persons. N Engl J Med 2008;359:1108-1115.

One of the primary things that has stood in the way of definitive diagnosis of acute low back pain is the extraordinarily high rate of false-positive findings seen on plain films, CT, or MRI. Indeed some studies suggest that as many as half of healthy, asymptomatic individuals studied by MRI of the lumbar spine have findings consistent with disk pathology.

Little is known about the frequency of incidental findings seen in MRI of the knee, since studies generally investigate symptomatic individuals; subsequent radiographic findings, if they correlate with symptomatology, have been taken to support a causal relationship.

Englund et al performed an MRI of the right knee in 991 randomly selected adult subjects ages 50-90 in Massachusetts. Excluded subjects included those with rheumatoid arthritis, knee replacement, terminal illness, or non-ambulatory status.

The incidence of meniscal tears seen ranged from 19% in the youngest women (ages 50-59) to 56% in senior men (ages 70-90). Among the group with radiographic changes of osteoarthritis, the frequency of meniscal tears in symptomatic and asymptomatic individuals was similar (63% vs 60%, respectively). Overall, the majority of persons (60%) with meniscus tears confirmed by MRI had no symptoms referable to the knee. It appears that as with back MRI, incidental findings of pathology are frequent, and call into question an ironclad attribution of knee symptoms to positive findings on MRI.

Undiagnosed Diabetes in Obese Americans

Source: Wee CC, et al. Obesity and undiagnosed diabetes in the U.S. Diabetes Care 2008;31:1813-1815.

No clinician is surprised to see that diabetes often goes undiagnosed. Patients can persist with modest symptoms, or even asymptomatically, for protracted periods during the early stages of type 2 diabetes. The fact that literally half of type 2 diabetics have one or more of the traditional complications of diabetes (neuropathy, nephro-pathy, retinopathy, dermopathy) at the time of clinical diagnosis attests to the fact that diagnosis lags substantially behind disease onset.

Most type 2 diabetics are obese, and obesity provides an environment that promotes insulin resistance, a cardinal dysfunction in early diabetes and pre-diabetes. Hence, scrutiny of obese subjects provides a window of observation into a population felt to be at greater risk for developing diabetes. On the one hand, clinicians might think that the presence of obesity would prompt greater vigilance for diabetes; on the other hand, there is evidence that compared to the non-obese, obese individuals experience delays in receiving preventive care.

From the 1999-2004 NHANES data, it was determined that 9.8% of the population had diabetes (defined as BG > 126 mg/dL). Slightly more than one-fourth (28.1%) of persons with FBG > 126 mg/dL had not been diagnosed with diabetes. When parsed into BMI categories, normal weight individuals were less likely to have undiagnosed diabetes than overweight or obese persons (22.2% vs 32.5% vs 27.4%, respectively). Because more than one-half of undiagnosed diabetes is seen in overweight and obese individuals, enhanced vigilance is appropriate.