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.

Rosiglitazone and CV Risk

The recent indication in an article by Nissen, et al (N Engl J Med. 2007;356:2457-2471) that rosiglitazone (ROSI) might actually increase cardiovascular (CV) risk was met with surprise and dismay by many clinicians and their patients alike. Even though subsequent commentary on the newly-identified risk profile suggested that such conclusions should be considered "preliminary," because CV disease is the predominant cause of death in diabetics—in disproportion to the general population—providers continue to experience consternation.

In an attempt to provide clarification, Home, et al provide data from the RECORD trial (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes), which although not yet completed, offers almost 4 years of followup on over 4,000 diabetics.

In RECORD, subjects not achieving adequate control of diabetes on either metformin or sulfonylurea monotherapy were assigned to combine the two (n = 2,227), or add ROSI (n = 2,220). The primary endpoint of the trial is hospitalization or death from any cause.

In this interim analysis, there was no statistically significant difference between the groups for CV mortality, MI, or all-cause mortality. The safety monitoring board of this trial, fully cognizant of the Nissen publication, did not feel that, based upon these prospective data, there is any safety concern sufficient to stop the trial. More conclusive information will be available at close of trial.

Home PD, et al. N Engl J Med. 2007;357:28-38.

Aldosteronism is a Frequent Cause of Resistant Hypertension in Diabetics

Hypertension (HTN) is substantially more common in diabetics than in the general population. This is of particular concern since cardiovascular disease is also disproportionately the cause of death in persons with diabetes. Most diabetics have essential hypertension, but it is reasonable to suspect that resistant hypertension (defined as BP >140/90 despite at least 3 antihypertensive agents) in this population is sometimes caused by primary hyperaldosteronism (PHA). This report provides details about the prevalence of PHA in diabetics with resistant HTN.

The study population was comprised of diabetics with resistant HTN, who were allowed to continue their medications during the study. Persons already receiving aldosterone antagonists (ie, aldosterone, eplerenone) were excluded from the trial.

Screening lab data included a plasma aldosterone-to-renin ratio, which if abnormal, was followed by a salt loading test. PHA was considered confirmed if the 24-hr urine aldosterone on day 3 of salt loading was > 12 mcg, or if plasma aldosterone was > 5 ng/dL after a 4-hr IV saline load.

Ultimately, 14% of diabetics with resistant HTN were confirmed to have PHA. The authors suggest that screening for PHA is appropriate in the specific group of diabetics with resistant HTN.

Umpierrez GE, et al. Diabetes Care. 2007;30(7):1699-1703.

Hydroxychloroquine is Associated with Less Diabetes in RA

Although rheumatoid arthritis (RA) immediately prompts consideration of joint disease and subsequent disabilities, lesser recognized is that persons with RA also suffer a disproportionate burden of cardiovascular disease. OF course, when a patient with RA develops diabetes, their CV risk is greatly magnified.

The antimalarials, of which hydroxychloroquine (HCQ) is an example, have been shown to improve insulin sensitivity and enhance insulin secretion. Indeed, hypoglycemia is a recognized adverse effect of antimalarials. Recently, a cluster of trials with medication, diet, and exercise have indicated that diabetes may be prevented by pharmacotherapies such as metformin, thiazolidinediones, and acarbose. The purpose of this publication by Wasko, et al was to compare the incidence of new onset diabetes in RA patients treated with HCQ (n = 1,808) vs those on other regimens (n = 3,097) over an observation period of 21 years.

The incidence of new onset diabetes was 5.2/1000 patient-years in persons who received HCQ, compared to 8.9/1000 patient-years in the comparison group (p = < 0.001). Longer HCQ use was associated with greater risk reductions. Although newer diseasemodifying therapies for RA provide excellent therapeutic results, this advantage of hydroxychloroquine may prove to be very attractive for persons identified as high-risk for diabetes.

Wasko MCM, et al. JAMA. 2007;298(2):187-193.