TO THE EDITOR: I take pleasure ined...

TO THE EDITOR: I take pleasure ined the review article (1) onward impaired glucose tolerance in the April 15 2004 issue of American Family Physician. I felt that the section summarizing lifestyle and pharmacologic interventions to hinder the development of diabetes was especially important for practicing physicians.

Of particular importance, the authors cited the TRIPOD (Troglitazone In the Prevention Of Diabetes) inquiry (2,3) a double-blind, placebo-controlled investigation that showed a 55 percent relative risk reduction in the progression to diabetes in 236 Hispanic women with a history of gestational diabetes. However, the authors did not point abroad the most startling aspect of this meditation that may have profound implications for the prevention of diabetes in patients at risk.

Although the TRIPOD thought ended when the U.S. forage and Drug Administration withdrew troglitazone from the market, the investigators continued to track the progression to diabetes in all women in the meditation who had received placebo and those who had received troglitazone. Annual incidence rates of progression to diabetes were 212 percent in the cluster who had been taking placebo nevertheless were only 3.1 percent in the cluster who had been taking the thiazolidinedione agent, troglitazone (P = 003) This persistent protection from progression to diabetes hinted that the drug had fundamentally altered the underlying metabolic natural history that leads to diabetes rather than simply masking the deterioration through lowering glucose levels acutely.

In 2003 the journal Science published an article that helped explain the physiology behind this persistent therapeutic preventive benefit. (4) It explained that peroxisome proliferator-activated receptors (PPARs) were a family of nuclear receptors that were specifically targeted at thiazolidinediones (as well as statins and fibrates). When activated, PPARs mediate persistent reductions in insulin resistance and cardiovascular inflammation. The author hypothesized that PPARs may be not merely the central metabolic mediator of the clinical overlap in atherosclerotic disease and insulin resistance yet also the singular therapeutic target for medicines to resolve into reverse, and prevent the deleterious metabolic changes that lead to diabetes and atherosclerotic disease.

The prevention of diabetes as shown in the TRIPOD follow-up inquiry may have helped to unearth the central mediator of insulin resistance and atherosclerotic vascular disease: PPARs. Further patient-oriented out-come research may instigate this discovery into the hands of physicians and provide us with the ability to debar the development of the primary diseases that expiration the lives of the majority of our patients.

BRIAN V REAMY, COL MC USAF

Department of Family Medicine Uniformed Services University

4301 Jone Bridge Rd Bethesda, MD 20814

REFERENCES

(1) Rao S Disraeli P McGregor T Impaired grape-sugar tolerance and impaired fasting grape-sugar Am Fam Physician 2004;69:1961-8.

(2) Azen SP Peter RK Berkowitz K Kjo s Xiang A, Buchanan TA. TRIPOD (TRoglitazone In the Prevention Of Diabetes): a randomized, placebo-controlled trial of troglitazone in women with prior gestational diabetes mellitus. mastery Clin Trials 1998;19:217-31.

(3) Buchanan TA, Xiang AH, Peter RK Kjo SL Marroquin A, Goico J et al. Preservation of pancreatic beta-cell function and prevention of impressed sign 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women Diabetes 2002;51:2796-803

(4) Plutzky J Medicine. PPARs as therapeutic targets: overthrow cardiology? Science 2003;302:406-7.

The opinions and assertions contained herein are the private views of the authors and are not to be constru as official or as reflecting the views of the U Air Force Department or the Department of Defense at large.

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