East: Dr. Yamada opened with a historical perspective of changes in lifestyle and in prevalence of diabetes in Japan. The remainder of his talk focused on The Japan Diabetes Complications Study, a large-scale, prospective study designed to understand the epidemiology of diabetes and cardiovascular disease in Japan better and to improve the medical management of adults with type 2 diabetes.


West: Dr. Nesto used recently published material as a basis for explaining why diabetic patients have a poorer outcome after acute coronary events than patients without diabetes. He concluded by presenting molecular targets for pharmacologic and other interventions in the treatment of diabetic patients.

East: Dr. Yamada opened with a historical perspective of changes in the past 50 years in Japan in lifestyle and in the prevalence of diabetes mellitus. He noted significant changes in diet (increase in fat from 7.5% to 26.4%, with drop in carbohydrates from 80.0% to 57.6%) and daily activity, with a trend toward a more sedentary lifestyle. During the same time frame, the prevalence of type 2 diabetes has increased more than 20-fold, to a prevalence of roughly 10% of adults over age 40 years.

The Japan Diabetes Complications Study is the first large-scale, prospective study to focus on the Japanese diabetic population: It enrolled more than 2,000 patients previously diagnosed with type 2 disease and randomized them (in April 1996) to conventional care or to intensive intervention. The groups are comparable in baseline characteristics; he noted that their average body mass index of 23.1 is significantly lower than the average value in the West. After 3 years, only one parameter, HbA1c level, has a statistically significant difference, and that difference (7.70 for conventional group versus 7.53 for the intervention group) is small.

Acute coronary events and strokes are the macroangiopathic endpoints. After 4 years, 44 patients had coronary events and 40 had strokes. The frequencies of both are significantly higher than those for non-diabetic Japanese adults. There was a gender differential for heart disease (male greater than female), but none for stroke. Dr. Yamada noted that frequencies of heart diseases are much lower than those in the West. For instance, the incidence of coronary events is less than one third of that cited in most Western studies. He noted that a study of Hiroshima University showed that Japanese living in Hawaii had coronary disease similar to that of Hawaiian Caucasians rather than that of people living in Japan. He noted that this supports the importance of environmental factors such as nutrition in development and progression of atherosclerosis.

Analysis of the results from the first 4 years of endpoint data show that the most important risk factors for coronary disease are LDL cholesterol and HbA1c, with systolic blood pressure and fasting insulin level most important for stroke. The study reviewers recommend maintenance of LDL less than 140mg/dl, ideally less than 100mg/dl, and maintenance of systolic pressure less than 150mm/Hg, and ideally less than 130mm/Hg.

Dr. Yamada concluded with a re-emphasis on the difference in incidence of coronary disease between Japanese and Western diabetics as evidence that lifestyle, and thus lifestyle interventions, have direct impact on atherosclerotic heart disease.

West: Dr. Nesto noted that many studies have found that diabetic patients have poorer outcomes after acute coronary events than patients without diabetes and that this phenomenon has triggered an explosion in physician interest. The goal of his talk was to present what is known about coronary disease in patients with diabetes or impaired glucose tolerance and what avenues research is taking to develop better medical care for this population.

The prevalence of diabetes in the United States has climbed from 4.7% in 1990 to greater than 6% in 1998, an increase of more than 60%. Thus, this population (as in Japan) is large and growing in size.

Dr. Nesto emphasized that recent studies have concluded that diabetes is equivalent to coronary disease. One study showed that in 2 years of follow-up, diabetic patients with a coronary event matched the survival curve for non-diabetic persons who had a previous coronary event. New, unpublished data from the GUSTO2B trial substantiates that diabetic patients have poor outcomes that do not seem to depend on factors seen in other patients. Prognosis for diabetic patients was poor regardless of infarct size or whether the infarction showed ST elevation or not. Patients who demonstrated impaired glucose tolerance but were not diagnosed with diabetes had a prognosis similar to that of patients with overt diabetes.

Next, he discussed an autopsy series on more than 1,000 individuals 15-34 years of age with elevated HbA1c (8%) that was designed to study the development and progression of atherosclerosis. Investigators found that there was a significant prevalence of atherosclerosis in this group. Roughly 45% of subjects had 5% or more of their right coronary arteries covered in fatty streaks, and 16% had the same extent covered with raised, atherosclerotic plaques. Clearly, atherosclerosis begins and progresses years before diabetes is diagnosed.

A recent study of angiographic results for diabetic patients shows that this group tends to show a wide extent of atherosclerotic involvement but with mild to moderate disease (with many lesions showing less than 25% stenosis). The profile of extensive disease that does not slowly progress to near complete occlusion places these people at higher risk that a thrombotic or embolic event will precipitate acute myocardial infarction.

Dr. Nesto then made the transition to discussion of what is physiologically different in diabetic persons with atherosclerosis. For instance, he cited studies indicating that C-reactive protein levels, a marker for inflammation, are higher in people with type 2 diabetes of greater than 10 years' duration. Elevated levels indicate a potentially prothrombotic state and are a risk factor for both stroke and myocardial infarction.

Another area in which diabetic patients are qualitatively different lies in neuropathy. Investigators who conducted positron emission scans of diabetic subjects and non-diabetic subjects with previous myocardial infarction found that the pattern of autonomic neuropathy shown by diabetic persons without a previous infarction was quite close to that of non-diabetic patients with a previous myocardial infarction.

Dr. Nesto stated that even after adjustment for all known risk factors related to atherosclerosis, diabetic patients have a doubled mortality rate after infarction compared with non-diabetic patients. He hypothesized that prothrombotic states, autonomic neuropathy, or both, along with as yet undefined physiologic differences, may account for this difference in prognosis. As we learn more about the physiology of persons with diabetes, we can develop appropriate interventions.

He concluded by noting that roughly 50% of patients without history of diabetes who have presented to him in the cath lab have either an impaired glucose tolerance or diagnostic diabetes when screening is done. He reminded physicians to view coronary patients as possible diabetic patients, too.