Stephen H. Schneider, MD, professor, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, UMDNJ-Robert Wood Johnson Medical School
A Multifaceted Approach to Diabetes Research
iabetes mellitus has become the number one public health problem facing the U.S. today. We are involved with several other departments at Robert Wood Johnson Medical School in approaching the problem of diabetes mellitus from a number of different perspectives. Research is in progress on novel drug therapies, such as inhaled insulin, and recently discovered new hormones from the gut. One group with a very high incidence of diabetes is the Asian Indian population. We are studying the pre-diabetic state in some of these individuals living in Central New Jersey to better understand the course of the disease and to find ways to prevent or delay the onset of clinical diabetes. In cooperation with other institutions around the country, we are studying the effectiveness of various interventions in managed care settings aimed at the prevention and treatment of diabetes mellitus and its major complication,
premature coronary artery disease. We are participating in a large multi-institutional study on the effects of exercise and weight loss on diabetes mellitus. In particular, we are interested in abnormalities of sex hormones that frequently accompany diabetes and are in the process of defining their importance as a marker for diabetic complications and a contributor to the disease. Finally, we have a number of interesting cooperative studies looking at the effects of air pollution on the metabolic abnormalities of diabetes in fat tissue and on the regulation of blood flow in diabetic blood vessels.
The number of individuals with diabetes in this country is quickly approaching somewhere between 20 and 30 million. Diabetes mellitus remains the number one cause of blindness, non-traumatic limb amputation, kidney failure, and is a major contributor to premature coronary artery
disease. The rapidly rising incidence of this disease is tightly linked to the increasing prevalence of obesity and an inactive lifestyle in the general
population. In addition, type 2 diabetes and its precursor, the so-called metabolic syndrome, are much more common in ethnic groups that compose an increasing percentage of our population, such as individuals from the Indian subcontinent and Hispanic patients with a Native American background. Addressing the problem of type 2 diabetes mellitus requires a multifaceted approach including basic science, development of new pharmacologic agents, public health measures, and new and more effective approaches to prevention and health care delivery.
We are continuing our cooperation with the pharmaceutical industry in New Jersey to study new pharmacologic agents that impact on diabetes and its complications. We have been active in the development of inhaled insulin as an alternative to insulin injections in the treatment of diabetes. We have also taken part in studies of the effects of the incretins, gut hormones that affect beta cell function, on blood glucose metabolism and beta cell preservation, and we are studying new medications for the treatment of painful diabetic neuropathy. As mentioned, the prevalence of type 2 diabetes mellitus and its associated
vascular complications are much more common in the large and rapidly growing population in this country from the Indian subcontinent, many of whom have settled in Central Jersey. Many years prior to the development of overt diabetes, individuals at risk develop an insulin resistant state associated with a clustering of cardiovascular risk factors known as the metabolic syndrome. Under the direction of Dr. Louis Amoroso, we have been engaged in an ongoing study of the Asian Indian population in Central Jersey. Previous criteria for identifying these patients have been established in populations consisting primarily of European immigrants and it is becoming apparent that our current criteria are inadequate for assessing risk in other ethnic groups, such as Asian Indians who develop the syndrome in the face of much less obesity. By examining this population at different ages, we hope to get insights into how to identify individuals at risk for developing the metabolic syndrome and progressing to diabetes, and what interventions may be useful in preventing them from going on to develop disease.
Modern treatment of diabetes mellitus provides remarkable protection against the development of its devastating complications. Despite this, an incredibly high portion of the patient population is not taking advantage of readily available preventive measures. The reasons for this are quite complex and include socioeconomic issues, lack of resources, and a generally poor understanding of how to implement current therapeutic guidelines. For the past seven years we have been active participants in a large multicenter study of delivery of care to patients with diabetes in various managed-care organizations across the country, which is known as TRIAD. This joint study involves input from a number of components of the University and is under the overall direction of Dr. Norman Lasser. A number of important observations have been made from these studies, which will have a major impact on how healthcare for patients with diabetes is delivered in the future. Interestingly, an emphasis on what are called processes, such as ensuring that blood pressure, and lipid and glucose measurements are done on a regular basis have had surprisingly little impact in and of themselves on outcomes in terms of risk factor reduction. Currently we are investigating the various barriers to treatment intensification that seem to underlie this apparent paradox.
Individuals at a high risk for type 2 diabetes can now be readily identified using simple clinical criteria and studies show that the onset of diabetes can be prevented or delayed for long periods by simple and relatively inexpensive interventions. Nevertheless, programs are not in place to identify such patients and intervention programs are also lacking. We are initiating a program to see if the Internet can be used for the self-identification of those individuals at risk and for the initiation of an effective preventive intervention.
Abnormalities in diabetes mellitus occur not only in relation to insulin, glucose and lipid metabolism, but also involve other hormonal regulatory systems. The reproductive system and its associated sex steroids are often abnormal in patients with diabetes mellitus and their roles in the course of the disease are not clearly understood. Erectile dysfunction occurs in more than 50% of men with diabetes mellitus. Initially thought to be hormonal in genesis, it is now recognized as an early marker of more generalized endothelial dysfunction and may predict coronary events. Abnormalities of sex steroid metabolism are complex in diabetes. In women, a high level of male sex hormones, often associated with the “polycystic ovary syndrome,” has proven to be a marker of insulin resistance and a major risk factor for the development of type 2 diabetes. In men with diabetes, low levels of testosterone have been found and this may contribute to increased coronary risk. As part of a multi-center study on the effects of exercise and weight reduction on type 2 diabetes known as the LOOKAHEAD study, we are heading up a special sub-study of the relationship between erectile dysfunction and vascular disease and the implications of abnormalities in sex steroid levels in patients with type 2 diabetes. By examining in more detail the relationships between these hormonal changes and the development of cardiovascular risk factors and events, we hope to better understand the potential diagnostic and therapeutic implications of these two seemingly distinct hormonal systems.
Another area where a multidisciplinary approach to diabetes is underway is the study of how air pollution may affect vascular and metabolic processes related to diabetes mellitus. As noted elsewhere in this issue, the division of endocrinology is working closely with Howard Kipen, MD, MPH, and his team to study effects of pollution on vascular reactivity. We are also looking at the epidemiology of pollution, diabetes, and obesity in the population at large, and will soon be starting studies on the effects of pollution on adipose tissue metabolism and insulin resistance.
Stephen H. Schneider was born in Neptune, New Jersey, and graduated from Boston University and Boston University Medical School. He has been at Robert Wood Johnson Medical School since 1978, where he is currently a professor of medicine in the Division of Endocrinology, Metabolism, and Nutrition. His research has focused on diabetes and exercise, diabetes and atherosclerosis, and exercise physiology and obesity.