Barrett syndrome

Hardly an issue of any primary care medical journal, including this issue of American Family Physician, can be opened without encountering an article on type 2 diabetes, dyslipidemia, or hypertension. Furthermore, newspapers and television news shows are replete with reports about the epidemic of obesity and consequent diabetes in the U.S. population. It is rare to see type 2 diabetes, dyslipidemia, obesity, or hypertension in isolation. The evidence suggests that these four conditions (and others) frequently coexist in what was described by Reaven in 1988 as syndrome X, now known as the metabolic syndrome. (1) An article (2) in JAMA placed the prevalence of metabolic syndrome in the United States at 24 percent--and the prevalence appears to be increasing.

There is general agreement that insulin resistance is the underlying cause of metabolic syndrome. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes), hypertriglyceridemia, hypertension, polycystic ovary syndrome, hypercoagulability, and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke, and myriad end-organ diseases. Conversely, treatment and consequent improvement of insulin resistance have been shown to result in better outcomes in virtually all of these conditions.

Government and medical organizations have focused a great deal of attention on the diagnosis and treatment of the various components of metabolic syndrome such as type 2 diabetes, hypertension, obesity, dyslipidemias, and their associated comorbidities. More recently, investigators have begun to focus on understanding the underlying causes of these conditions, and attention is starting to shift toward screening and prevention. Unfortunately, because of the previous lack of good data, organizations such as the American Diabetes Association (ADA) (3) and the U.S. Preventive Services Task Force (USPSTF) (4) disagree about the appropriateness of screening the general population for diabetes, and about what constitutes a "susceptible" population. The ADA recommends screening men and women 45 years and older for impaired fasting glucose or impaired glucose tolerance and considering screening younger patients with an elevated body mass index. The USPSTF does not recommend routine screening of asymptomatic adults.

The current recommendations for the management of hypertension, type 2 diabetes, obesity and dyslipidemias aim primarily at screening and treating each problem separately. Beyond lifestyle changes, few measures have been available for addressing the root problem--insulin resistance. Recently, however, evidence has started to surface about the usefulness of pharmacologic interventions.

Perhaps the most significant challenge in the prevention of metabolic syndrome is the lack of a diagnostic test. To diagnose the syndrome, the physician has to rely on clinical observations and a high index of suspicion. Unfortunately, by the time signs are detected, the damage often has been done.

There also is no simple, clinically applicable test for insulin resistance. Use of the hyperinsulinemic clamp, a laboratory technique used to quantify insulin resistance, is cumbersome and expensive. Measurement of insulin levels is not reliable because of poor specificity. Some interesting correlations have been found between insulin resistance and plasma levels of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, (5) but clinical applicability remains an issue.

Although we cannot screen for insulin resistance, we have the ability to identify key components of the metabolic syndrome and to provide interventions long before end-organ damage is evident. Regular screening of lipid levels, blood pressure, and blood glucose levels in susceptible patients is key to early identification of the syndrome. Methods for evaluating dyslipidemia and hypertension are readily available to physicians. The evaluation of glucose abnormalities is more challenging. By the time hyperglycemia develops, hyperinsulinemia has been present and causing damage for years.

In this issue of AFP, Rao and associates (6) present a reasonable, practical clinical approach to identifying patients before they develop overt diabetes and its complications. Data from the Diabetes Prevention Study show that lifestyle modifications and pharmacologic therapy can prevent the development of type 2 diabetes. (7) When one fourth of the general U.S. population is at risk for developing a preventable condition, a more aggressive approach is warranted.

The role of the family physician is clear. Patients at risk for type 2 diabetes will not present to an endocrinologist, a cardiologist, or any other subspecialist until symptoms appear. Therefore, the family physician must be vigilant and intervene early enough to make a difference.

REFERENCES

(1.) Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607.

(2.) Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among U.S. adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287:356-9.

(3.) American Diabetes Association and National Institute of Diabetes, Digestive and Kidney Diseases. The prevention or delay of type 2 diabetes [correction published in Diabetes Care 2002;25:947]. Diabetes Care 2002;25:742-9.

(4.) U.S Preventive Services Task Force. Guide to clinical preventive services: report of the U.S. Preventive Services Task Force. 2d & 3d eds. Alexandria, Va.: International Medical Pub., 2002.

(5.) Stuhlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 2002;287:1420-6.

(6.) Rao SS, Disraeli P, McGregor T. Impaired glucose tolerance and impaired fasting glucose. Am Fam Physician 2004;69:1429-36,1439-40.

(7.) Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.

IGNACIO DE ARTOLA, JR., M.D. Keck School of Medicine, University of Southern California Los Angeles, California

Ignacio de Artola, Jr., M.D., is assistant professor of clinical family medicine at Keck School of Medicine, University of Southern California, Los Angeles.

Address correspondence to Ignacio de Artola, Jr., M.D., USC Department of Family Medicine, 1420 San Pablo St., PMB-B205, Los Angeles, CA 90033 (e-mail: deartola@usc.edu). Reprints are not available from the author.

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