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.

Diabetes Prevention: 7 Ways to Leave Your Sugar

Impaired Fasting Glucose (IFG) and impaired glucose tolerance (IGT) appear to be the steps directly preceding the development of overt diabetes. Randomized clinical trials have demonstrated that several different interventions can reduce the development of diabetes for persons with IFG or IGT: acarbose, diet and exercise, or metformin. The thiazolidinedione troglitazone has also demonstrated efficacy, but was withdrawn from the market due to liver toxicity. Functional similarities between troglitazone and rosiglitazone (ROS) suggest that the latter should also be effective to prevent progression from IFG/IGT to frank diabetes, without the attendant risk of hepatic dysfunction.

The DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication)Trial randomized 5808 persons with either IGT or IFG (as determined by 75 g oral GTT) to ROS or placebo. Dosing of ROS was 4 mg/d × 2 months then 8 mg/d × 3 years.

ROS treatment reduced the composite primary end point (incident diabetes or death) by 60%, and the specific secondary end point of new onset diabetes by 62% (P < 0.0001 for each). Risk reduction was similar whether the subject entered the trial with IFG or IGT. Clinicians now have numerous evidence-based pathways from which to choose if they wish to intervene in persons with IFG or IGT to prevent diabetes.

The DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

Mortality Amongst Persons with Hepatitis B or Hepatitis C

Both hepatitis B (HEPb) and hepatitis C (HEPc) may progress to advanced liver disease, but little data have addressed the long-term mortality associated with these infections. The Notifiable Diseases Database of Australia provides an opportunity to retrospectively examine outcomes in persons with hepatitis.

During the 1990-2002 period, 117,547 persons were identified with HEPb or HEPc. Standardized mortality ratios were greatly magnified for death from liver disease in persons with either HEPb or HEPc, and risk was compounded when co-infected with both. For instance, persons with HEPb incurred a risk of liver-related death 12-fold greater than age-matched persons without HEPb; for HEPb/HEPc coinfection, risk was magnified 33-fold.

One (perhaps) surprising data point emerged from this study: in persons with HEPc, risk of dying from illicit drug-related causes was actually greater than liver-related causes. Because 80% of HEPc in Australia is acquired through intravenous drug use, continued substance abuse remains a problem whose mortality outweighs that of the HEPc disease process itself.

Amin J, et al. Lancet. 2006;368:938-945.

Medical Management of Kidney Stones

Kidney Stones (KST) are epidemiologically important in the United States, being responsible for almost 2 million annual office or emergency department visits in recent years. Small distal ureteral stones (< 5 mm) will spontaneously pass most of the time, but surgical treatment is sometimes required.

Calcium channel blockers (CCB) and alpha-blockers (ALB) have physiologically appealing activity that could enhance likelihood of stone expulsion: they decrease ureteral smooth muscle spasm, while allowing continued physiologic ureteral peristalsis.

Hollingsworth et al report upon a literature search of all randomized controlled trials (n = 417) of CCB or ALB to treat kidney stones (total patient n = 693). The pooled data indicate a 65% greater likelihood of stone passage in persons receiving CCBs or ALB than in persons treated with simple analgesia (eg, NSAIDs or other analgesics).

Most of the clinical trials employing CCB or ALB have been published in subspecialty literature. The authors suggest that the available evidence supports inclusion of medical therapy (alpha blockers or calcium channel blockers) to enhance likelihood of KST passage. Tamsulosin and nifedipine were the most commonly reported agents representative of ALB and CCB respectively. Because both classes of drugs have a high degree of familiarity to clinicians, and the adverse effect profiles are excellent, CCB/ALB treatment may reduce the need for surgical intervention in persons suffering KST and deserve consideration by primary care clinicians as appropriate medical therapy.

Hollingsworth JM, et al. Lancet. 2006;368:1171-1179.