Forum Two: Unanswered Research Questions about Metabolic Control in Non-Insulin-dependent Diabetes Mellitus

The overwhelming choice for the most important research question to ask about metabolic control in noninsulin-dependent diabetes mellitus (NIDDM) was whether glucose control prevents or delays the progression of macrovascular disease in persons with NIDDM. The conference group recognized that a definitive answer, supported by well-controlled clinical trial evidence, was lacking. Associated questions were also raised, including the following: - Should there be the same goals for glucose control in all groups with NIDDM, such as elderly persons, different ethnic groups, and obese persons? - Should goals be modified for those with clinical vascular disease? - Are there different therapeutic goals and strategies at different stages of the disease, for example, at the time of first diagnosis as compared with later in the course of diabetes? - Would short-term, controlled studies of intensive as compared with standard glycemic regulation in an acute hyperglycemic syndrome such as the perioperative period of coronary artery bypass surgery in patients with NIDDM be of value? - Is it possible to identify specific levels of blood glucose (or of hemoglobin A1c) that could alter the benefit/risk ratio of intensive glycemic management? The second major question concerned the relative benefits and risks of glucose control as compared with intensive regulation of other vascular risk factors (for example, lipid profiles, hypertension, and obesity and insulin resistance) in NIDDM. In discussion, we recognized that more basic research into these risk factors as well as studies in less recognized areas such as vascular biology, thrombosis, and the coagulation system were needed to help identify other risk factors and potential therapeutic approaches. It was agreed that clarification of the exact role of aspirin therapy is needed. The value of surrogate vascular end points such as microalbuminuria and noninvasive techniques to assess macrovascular disease should be explored. Standardization of research methods, especially those for glycated hemoglobin, is needed. As in the first question, the need for studies of preventive approaches at different stages of NIDDM as well as in different populations with the disease was recognized because the approaches and results of intensive management may differ. Finally, the answer to the following question is badly needed: Will increased exogenous insulin necessary to achieve improved metabolic control have a detrimental effect on the incidence of macrovascular disease in those patients who require such therapy? The third major area needing research is in health services models of comprehensive management of patients with NIDDM. We recognized that currently there is a great resistance to intensive glycemic management in these patients among primary care health professionals and that studies to establish improved mechanisms to address this problem are clearly indicated. The growth of managed care networks is likely to make this need even more pressing. As a corollary, it was suggested that studies of methods to motivate primary care physicians to use comprehensive management, including glycemic control, are needed. The fourth major question asked which methods were best to reduce insulin resistance in patients with NIDDM. It was recognized that more research on the pathophysiology of obesity and insulin resistance is needed to address this issue. Improved means of enhancing a patient's adherence to diet and exercise programs should be established, and more research is needed on community-based approaches to exercise and weight reduction in various populations with NIDDM. Attention to the relative risks and benefits of weight control in these patients is indicated, as are new studies on the behavioral aspects of nutrition therapy. Exercise as either a replacement for, or an adjunct to, weight control is encouraged, and new studies in the relative value of exercise as compared with diet therapy are suggested. Finally, the value of primary prevention trials with persons at high risk for developing NIDDM was recognized. The fifth research question dealt with identifying the genetic markers that may predict who is most susceptible to vascular complications in NIDDM. Identification of high-risk persons by genetic markers could lead to tailored, comprehensive preventive approaches at early stages of disease. As a corollary, and in recognition that excellent data from the Diabetes Control and Complications Trial on insulin-dependent diabetes mellitus (IDDM) may not be readily transferrable to the general population of patients with NIDDM, it was suggested that better means of differentiating between IDDM and NIDDM in patients, particularly young adults, are needed. The sixth major question, identified late in the discussion but rated highly by many, concerned the reasons for the apparent loss of protection against macrovascular disease in premenopausal women with NIDDM. This clinical fact has been supported by several studies but has received little research attention as to pathogenic mechanisms. If these mechanisms were understood, new strategies of prevention or therapy, or both, for women with NIDDM could emerge. Thus, six broad areas of research needs were identified from the original twelve identified by the nominal group process. Increased focus on these areas should help to answer the primary question: What are the unanswered research questions regarding intensification of metabolic control in NIDDM? Dr. Clark: Regenstrief Health Center, 1001 W. Tenth Street, 5th Floor, Indianapolis, IN 46202.