Clinical Briefs

By Louis Kuritzky, MD

TZDs and HF in People with Type 2 Diabetes

Thiazolidinediones (TZDs) offer numerous potential benefits in diabetic patients, including improved insulin-stimulated glucose disposal, decreased insulin resistance, and favorable lipid effects. One of the well-recognized adverse effects of TZDs is an increase in plasma volume, reflected by a decrease in hematocrit, weight gain, and edema. Although case reports of an association between TZDs and heart failure have been reported, no published study has specifically examined this issue.

Relying on a large health insurance claims database, Delea and colleagues compared data from type 2 diabetic patients receiving TZDs (n = 5441) with control subjects (n = 28,103) based upon observational data accrued August 1997-March 2001.

During the follow-up period, subjects receiving TZDs were more than 1½ times more likely to experience heart failure than control subjects (2.3% incidence vs 1.4%). This translates into an approximately 60% greater relative risk of heart failure for diabetics treated with TZDs than controls. On the other hand, having received a prescription for metformin in the 3 months before initiation of the observation period was associated with a lesser risk of heart failure, hence "antidiabetic treatment" per se cannot be held culpable.

Previous warnings have cautioned specifically about the combination of insulin with TZDs, indicating an increased risk of heart failure; in this study, however, no discernible difference in risk of heart failure between TZDs with, or without, insulin was seen.

Delea TE, et al. Diabetes Care. 2003;26:2983-2989.

Exercise Plus Behavioral Management in Patients with AD

Although Alzheimer’s disease (AD) prompts clinicians to immediately address cognitive function, there is much less awareness of AD effect upon physical conditioning. AD patients have been found to be at greater risk of falls, fractures, rapid decline in mobility, and undernutrition. Pilot studies of exercise programs for AD patients have been promising, with benefits extending beyond simple conditioning to include favorable effects upon depression.

Home-based caregivers, for whom little guidance has been available about optimum techniques for exercise and behavioral management, provide much of the care for AD. This study randomized AD patients (n = 153) to traditional community care or an active exercise and behavioral management program. The active treatment group (patient and caregiver) received 12 sessions lasting 1 hour with instruction about exercise, strength training, balance, and flexibility, with a goal of at least 30 minutes of moderate intensity exercise daily. Supervised instruction occurred for 3 months, after which the patient and caregiver were "on their own"’ for an additional 24 months.

When compared to persons who received "routine" care, at 3 months time there was a significant difference in the SF-36 (quality of life evaluation) and depression scores in favor of active treatment. Indeed, while improvements in scores were seen amongst the active treatment group, declines in scores were seen for traditional care. At 24 months, there were still significant differences

between the 2 groups. Teri et al conclude that the robust and enduring benefits of a simple exercise program, when coupled with behavioral management skills for caregivers, are achievable for AD patients and merit consideration by clinicians.

Teri L, et al. JAMA. 2003;290:2015-2022.

Spironolactone in Resistant HBP

A commonly accepted definition of resistant hypertension (r-HTN) is failure to obtain blood pressure control (ie, < 140/90) with 3 or more different classes of antihypertensive medication. As many as 30% of hypertensive patients may fall into this category; for instance, in the recently completed ALLHAT trial, 34% of subjects, despite intensive multidrug treatment, failed to achieve goal BP.

In the past, use of aldosterone antagonists like spironolactone (SPL) was often reserved for cases of aldosteronism, or in persons plagued with persistent hypokalemia. Doses that may lead to an unacceptable adverse effect profile (100-400 mg/d) were not uncommonly used in such circumstance. Whether more modest doses of SPL (12.5-50 mg/d) might prove effective in r-HTN was the subject of this study.

At 6 months of treatment with SPL, the mean reduction in BP was 25/12 mm Hg. Although subjects who ultimately were determined to have aldosteronism required a higher dose of SPL than persons with low plasma renin, there was no statistically significant difference in efficacy between these subgroups. Similarly, there was no white vs black ethnic disparity in efficacy. The adverse effects profile included 4% incidence of breast tenderness, 7% incidence of worsening renal function, and 3% incidence of hyperkalemia.

It is encouraging that an inexpensive medication (available generically) is generally well tolerated and can provide substantial improvements in BP for persons already on multidrug therapy.

Nishizaka MK, et al. Am J Hypertens. 2003;16:925-930.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.