Letters to the Editor

Preventing the Progression of Diabetes Mellitus

TO THE EDITOR: I enjoyed the review article1 on impaired glucose tolerance in the April 15, 2004, issue of American Family Physician. I felt that the section summarizing lifestyle and pharmacologic interventions to prevent the development of diabetes was especially important for practicing physicians.

Of particular importance, the authors cited the TRIPOD (TRoglitazone In the Prevention Of Diabetes) study,2,3 a double-blind, placebo-controlled study 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 out the most startling aspect of this study that may have profound implications for the prevention of diabetes in patients at risk.

Although the TRIPOD study ended when the U.S. Food and Drug Administration withdrew troglitazone from the market, the investigators continued to track the progression to diabetes in all women in the study who had received placebo and those who had received troglitazone. Annual incidence rates of progression to diabetes were 21.2 percent in the group who had been taking placebo but were only 3.1 percent in the group who had been taking the thiazolidinedione agent, troglitazone (P = 0.03). This persistent protection from progression to diabetes suggested that the drug had fundamentally altered the underlying metabolic natural history that leads to diabetes rather than simply masking the deterioration by 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 by 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 only the central metabolic mediator of the clinical overlap in atherosclerotic disease and insulin resistance but also the singular therapeutic target for medicines to reduce, 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 study may have helped to unearth the central mediator of insulin resistance and atherosclerotic vascular disease: PPARs. Further patient-oriented outcome research may move this discovery into the hands of physicians and provide us with the ability to prevent the development of the primary diseases that end the lives of the majority of our patients.

BRIAN V. REAMY, COL, MC, USAF

Department of Family Medicine
Uniformed Services University
4301 Jones Bridge Rd
Bethesda, MD 20814

REFERENCES

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

Clarifications on Patients Presenting with Jaundice

to the editor: I read with great interest the review on "Jaundice in the Adult Patient,”1 by Drs. Roche and Kobos in the January 15, 2004, issue of American Family Physician. I think it is an easy to read and well-organized review; however, it contained certain inaccuracies.

The authors state, "Abdominal pain is the most common presenting symptom in patients with pancreatic or biliary tract cancers.”1 In fact, the most common presentation in patients with pancreatic cancer is jaundice (72 percent of patients versus 36 percent of patients with abdominal pain).2 Furthermore, by the time patients present with abdominal pain, they usually have unresectable tumors.3

In the paragraph discussing posthepatic causes of jaundice, the authors estimate that cholangiocarcinoma "is associated with an approximately 50 percent survival rate.”1 This survival rate is too optimistic, because it is well known that cholangiocarcinoma is usually associated with a very poor prognosis. Cholangiocarcinoma is almost always a fatal malignancy, primarily because it usually is diagnosed at a late stage (similar to pancreatic cancer).4

Finally, in their discussion of serum testing, the authors report that hemolysis "is indicated by the presence of fractured red blood cells (schistocytes) and increased reticulocytes on the smear.” I would like to clarify that schistocytes are seen only in microangiopathic hemolysis (disseminated intravascular coagulopathy, thrombocytopenic purpura), which is a subset of the hemolytic anemia family, but not present in all forms of hemolytic anemia, and with intravascular prostheses.

MOUSSA F. YAZBECK, M.D.

St. Edward Mercy Medical Center
North Logan Mercy Hospital
500 E. Academy
Paris, AR 72855

REFERENCES

EDITOR'S NOTE: This letter was sent to the authors of "Jaundice in the Adult Patient,” who declined to reply.

Send letters to Jay Siwek, M.D., Editor, American Family Physician, 11400 Tomahawk Creek Pkwy., Leawood, KS 66211-2672; fax: 913-906-6080; e-mail: afplet@aafp.org.

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