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FORA

Forum One: Current Recommendations about Intensification of Metabolic Control in Non-Insulin-dependent Diabetes Mellitus

right arrow Robert R. Henry, MD, and Saul Genuth, MD

1 January 1996 | Volume 124 Issue 1 Part 2 | Pages 175-177

Purpose: To review issues about intensive management of non–insulin-dependent diabetes mellitus (NIDDM) and to formulate recommendations for goals and general approaches to implementation of intensive management.

Method: A panel of clinical scientists and practitioners specializing in diabetes initially used a formal nominal process to identify the points of agreement on major issues. These points were further refined in a general conference discussion.

Conclusions: 1) On the basis of data from intervention trials in IDDM that prove that intensive glycemic control reduces microvascular and neuropathic complications, coupled with epidemiologic and basic scientific data that support the strong likelihood of a similar benefit in NIDDM, the goal of treatment in NIDDM should be near-normal glycemia [glycohemoglobin level no higher than 1.0% above the upper normal limit]; 2) glycemic targets should be adjusted individually according to clinical factors such as increased risk for hypoglycemia, advanced age, or reduced life expectancy from comorbid conditions; 3) some degree of comprehensive and repetitive instruction about diet and exercise and the use of blood glucose self-monitoring for all patients is essential to achieve the chosen targets; 4) intensive management of hyperglycemia should be instituted early and should initially emphasize diet and exercise therapy; staged introduction of oral hypoglycemic agents and finally insulin regimens of increasing complexity are recommended as needed to achieve glycemic targets; 5) comprehensive care must also include aggressive attempts to reduce cardiovascular risk factors [particularly hypertension, smoking, dyslipidemia, and obesity] as well as prevention of nephropathy and neuropathy; 6) the complex interaction among treatment regimens for hyperglycemia, dyslipidemia, obesity, and hypertension ideally requires a team approach, using a physician, diabetes educator, nurse, dietitian, and other health professionals; health insurers should make these resources available to generalists who currently care for most diabetic patients.


Forum One was charged with preparing recommendations for conference discussion about what should constitute intensive management of non–insulin-dependent diabetes mellitus (NIDDM) and how this management should best be implemented. This article summarizes the goals of intensive management and the general approach to achieving those goals that were agreed on by most participants in the conference.

Goals of management should be similar to those stated in the American Diabetes Association standards of care [1] currently being advocated for management of insulin-dependent diabetes mellitus (IDDM) based on the Diabetes Control and Complications Trial (DCCT) results [2].

The first issue addressed was whether intensification of therapy to lower glucose levels was warranted in NIDDM and, if so, to what extent based on the prevailing state of knowledge. Considerations included not only information on the potential benefits of near-normal to normal glycemic control but the possible advantages of reducing cardiovascular risk factors such as hypertension, dyslipidemia, and smoking. At the present time, no direct evidence exists that normoglycemia in NIDDM has specific advantages over lesser degrees of glycemic control in relation to microvascular or macrovascular complications. All interventional clinical trial data on glycemic control to date is derived from studies of IDDM, the most notable data being from the DCCT and the Swedish Diabetes Intervention Study [2, 3]. Application of these data to NIDDM is inferential and suggestive at best. However, because a large body of epidemiologic and basic scientific data also exists that supports a relation between microvascular disease and hyperglycemia in NIDDM similar to that in IDDM [4], the general consensus was that glycemic goals similar to those currently advocated by the American Diabetes Association [1] Table 1 would be prudent and should be strived for, when possible. It was agreed that any substantial reduction in glycemia was worthwhile and the closer to normal the blood glucose level became, the greater were the benefits. A suggested generalization of the glycemic treatment target for NIDDM was a glycated hemoglobin level less than 1.0 percentage point above the upper limit of normal.


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Table 1. Target Levels of Glucose Control in NIDDM*

 


Goals and methods of treatment should be individually adjusted
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The conference participants recognized that the recommendation for intensive treatment of hyperglycemia requires individualization because this level of aggressive management is inappropriate in certain circumstances, for example, situations in which the patient is unable or unwilling to comply with the prescribed treatment regimen, the risk for or from hypoglycemia is excessive, or concomitant diseases are present that would adversely influence the risk/benefit ratio or substantially shorten life expectancy. Examples of such patients include the very old or those with significant dementia, those with malignancies not responsive to various therapies, those who have already developed renal failure, and those with advanced cardiovascular disease manifested by stroke, multiple myocardial infarctions, severe congestive heart failure, or major amputations. Under such circumstances, the primary care provider should still try to achieve the best glycemic control possible using the simplest regimen with the least possible risk.


Required comprehensive care should include treatment of hyperglycemia, hypertension, and dyslipidemia as well as patient education and prevention of risks for retinopathy, nephropathy, neuropathy, and cardiovascular disease
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The basic level of care for diabetes should meet or exceed the standards recently adopted by the American Diabetes Association [1]. Non–insulin-dependent diabetes mellitus is a unique disorder, differing in many aspects from other chronic multisystem diseases. It is managed in large part by lifestyle modifications of diet and exercise. When necessary, oral hypoglycemic agents, insulin, or both may also be required in addition to medications for treatment of hypertension and dyslipidemia. Pharmacologic therapy requires continuous close medical supervision and education to be effective. The interaction between treatment methods is often complex and problematic to institute and monitor. The achievement of normal or near-normal glucose levels requires comprehensive training in self-management and monitoring of blood glucose levels. Continuing patient education and reinforcement are necessary to ensure that treatment goals are understood and that appropriate attention is given to meal planning, exercise, and therapeutic regimens. Home or self-monitoring of capillary blood glucose is one of the most important recent developments available to improve glycemic control. This technique enables the patient to be involved in self-management and understand the influence of therapy on blood glucose levels. Because home glucose monitoring facilitates glycemic control and reinforces adherence to therapy, consideration should be given to having all diabetic patients do such measurements. The frequency and pattern of home glucose monitoring should be appropriate to the therapeutic regimen being used and increase in complexity as treatment goes from diet and exercise therapy alone to several daily injections of insulin.

The death rate from coronary heart disease is markedly increased by the presence of diabetes when associated with hypertension, dyslipidemia, and smoking [5]. Therefore, it is vital to focus efforts on reducing cardiovascular risk factors as well as glycemia by optimizing blood pressure, lipoprotein levels, diet, and body weight. Unless contraindications exist, exercise should also be an integral component of the treatment program for diabetes. The highest priority should be given to reducing elevated blood pressure because strong evidence exists for its effectiveness in diabetic patients and because it also delays or reduces the risk for renal insufficiency [6, 7]. Another priority should be to encourage and assist patients to stop cigarette smoking, given the overall evidence of its adverse effects on cardiovascular and peripheral vascular events. No data exist from a randomized trial done specifically with diabetic patients to prove that treatment of dyslipidemia accompanying NIDDM is as beneficial as it now appears to be in nondiabetic patients. Nevertheless, from the available evidence, correction of abnormal low- and high-density lipoprotein cholesterol and triglyceride levels is recommended [8]. Reasonable target levels are specified in the American Diabetes Association standards of care [1]. Although diet and exercise regimens alone may not often result in complete normalization of cardiovascular risk factors, they are beneficial, and adherence should be constantly encouraged and reinforced because the response to subsequent institution of pharmacologic therapy will be enhanced. Drug treatment of hypertension and dyslipidemias should be introduced promptly when the response to diet and exercise therapy is inadequate.

To optimize management and delay or prevent the potentially devastating consequences of the complications [9], NIDDM is best managed by a comprehensive, multifaceted team approach, which involves active participation by the physician, nurse, diabetes educator, dietitian, and behavioral therapist. Effective management is time consuming and requires many expensive resources. However, a preventive approach with the expectancy of reduced complications is likely to be cost effective [10].


Progressive or staged treatment of hyperglycemia in NIDDM should be initiated at the earliest possible opportunity
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Management of NIDDM should follow a staged or stepped approach beginning with dietary modification and exercise therapy. Intensive management should be initiated from the time of diagnosis. When diet and exercise therapies are ineffective for maintaining plasma glucose levels within the glycemic objectives shown in Table 1, oral antidiabetic agents are usually instituted. Oral medication should not be used as a substitute for diet and exercise therapy, but as adjunctive therapy. The recent introduction of metformin into the American market adds an oral agent that can be used alone or combined with the sulfonylureas [11]. Insulin therapy should be reserved for patients in whom an adequate trial of diet, exercise, and oral antidiabetic agent therapies, according to the stepwise approach advocated by the American Diabetes Association [12], has failed to achieve appropriate control. Some insulin treatment regimens commonly used in NIDDM are reviewed in other articles in this supplement. The primary objective of insulin treatment should be to achieve the best possible glycemic control with the least risk for hypoglycemia using the simplest regimen. Thus, insulin treatment may progress from single injections of longer-acting insulins to multiple injections of long- and short-acting insulins similar to those required by patients with IDDM. Although the issue remains unsettled and somewhat controversial, no direct compelling evidence exists that exogenous insulin administration causes cardiovascular disease in NIDDM or IDDM.


Resources necessary to implement the above recommendations should be made available to the health care providers of patients with NIDDM
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In setting all the above recommendations, it was understood that most patients with NIDDM are currently being cared for by generalists and that the recommended level of care might be difficult for many health care providers to institute because of the need for extensive resources. Additional barriers to effective management might include the difficulty encountered by health personnel in keeping up with rapid advances in technology and knowledge related to diabetes management. Ongoing efforts to simplify and improve the delivery of new information in diabetes management were proposed. The proposed development of a National Diabetes Education Program (NDEP) to develop and foster information about diabetes treatment is a major step in this direction. At present, full implementation of intensive metabolic control as recommended may be restricted to those practices and institutions with adequate resources and to patients with adequate insurance. To overcome this limitation, it was emphasized that the relevant governmental and private-paying agencies responsible for health care to diabetic persons should recognize and fund sufficient resources to provide optimal care.

Dr. Henry: Veterans Affairs Medical Center, San Diego (V-111G), 3350 La Jolla Village Drive, San Diego, CA 92161.


Author and Article Information
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From the Department of Medicine, University of California, San Diego; the Veterans Affairs Medical Center, San Diego, California; the Department of Medicine, Case Western Reserve University, and Mt. Sinai Medical Center, Cleveland, Ohio.
Note: This article is one of a series of articles comprising an Annals of Internal Medicine supplement entitled "Risks and Benefits of Intensive Management in Non-Insulin-dependent Diabetes Mellitus: The Fifth Regenstrief Conference." To view a complete list of the articles included in this supplement, please view its Table of Contents.
Acknowledgments: The authors thank Drs. Charles Clark and Ted Ganiats for their constructive comments and advice.
Grant Support: By the Medical Research Service, Department of Veterans Affairs, the Veterans Affairs Medical Center, San Diego. California, and by the Saltzman Institute for Clinical Investigation, Mt. Sinai Medical Center, Cleveland, Ohio.
Requests for Reprints: Robert R. Henry, MD, Veterans Affairs Medical Center, San Diego (V-111G), 3350 La Jolla Village Drive, San Diego, CA 92161.
Current Author Addresses: Dr. Genuth: Chief, Endocrinology, Mt. Sinai Medical Center, One Mt. Sinai Drive, Cleveland, OH 44106-4198.


References
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1. American Diabetes Association. Standards of medical care for patients with diabetes mellitus Diabetes Care. 1994;17:616-23.

2. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus N Engl J Med. 1993;329:977-86.

3. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus N Engl J Med. 1993;329:304-9.

4. Genuth SM. The case for blood glucose control Adv Intern Med. 1995;40:573-623.

5. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial Diabetes Care. 1993;16:434-44.

6. Mogensen CE. Progression of nephropathy in long-term diabetics with proteinuria and effect of initial and anti-hypertensive treatment Scand J Clin Lab Invest. 1976;36:383-8.

7. Mogensen CE. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy Br Med J. 1982;285:685-8.

8. Bierman EL. George Lyman Duff Memorial Lecture. Atherogenesis in diabetes Arterioscler Thromb. 1992;12:647-56.

9. Clark CM, Lee DA. Prevention and treatment of the complications of diabetes mellitus N Engl J Med. 1995;332:1210-7.

10. Litzelman DK, Slemenda CW, Langefeld CD, Hays LM, Welch MA, Bild DE, et al. Reduction of lower extremity clinical abnormalities in patients with non–insulin-dependent diabetes mellitus. A randomized, controlled trial Ann Intern Med. 1993;119:36-41.

11. Hermann LS, Schersten B, Bitzen PO, Kjellstrom T, Lindgarde F, Melander A. Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study Diabetes Care. 1994;17:1100-9.

12. American Diabetes Association. Medical Management of Non-Insulin-Dependent (Type II) Diabetes. Third ed. Alexandria, Virginia: American Diabetes Association; 1994:26.


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