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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.

Diabetic Microvascular Complications: The Role Of The Family Physician In Diagnosis And Management

To provide primary care physicians with the most recent developments regarding the
diagnosis and treatment of diabetic microvascular complications.

This activity is designed for primary care physicians. No prerequisites required.

The Johns Hopkins University School of Medicine takes responsibility for the content,
quality, and scientific integrity of this CME activity. At the conclusion of this activity,
participants should be able to:

  • Understand the basic pathophysiology underlying diabetic microvascular complications.
  • Develop strategies for the early detection and treatment of diabetic retinopathy.
  • Review the various methods of screening for and diagnosing diabetic peripheral
    neuropathy (DPN), as well as therapeutic options for DPN management.
  • Develop an understanding of the importance of screening and of treatment options in diabetic nephropathy.
  • Compare current reactive and symptomatic treatment modalities to new pathway-
    specific targeted treatments for diabetic microvascular complications.
  • Establish the family physician as an integral member of an interdisciplinary team of
    specialists including ophthalmologists, neurologists, and nephrologists.

The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Johns Hopkins University School of Medicine designates this educational activity for
a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award.
Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity:  2 hours.

Release date: April 15, 2005. Expiration date: April 15, 2007.

The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Eli Lilly and Company.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Directors and Participating Faculty reported the following:


Neil Brooks, MD
Medical Director
Vernon Manor Health Care Center
Vernon, Connecticut
Dr Brook reports serving as a consultant to Eli Lilly and company, EyeTel Imaging, Inc, and Sepracor Inc.

Simeon Margolis, MD, PhD
Department of Medicine
Division of Endocrinology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Margolis reports having no significant financial or advisory relationship with corporate organizations related to this activity.


Mohamed G. Atta, MD
Assistant Professor of Medicine
Division of Nephrology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Atta reports serving as a consultant to Ortho Biotech Products, LP and Scios Inc; and receiving honoraria from Amgen Inc, Eli Lilly and Company, Ortho Biotech Products, LP, Pfizer Inc, Scantibodies Laboratory, Inc, and Scios Inc.

Vera Bril, MD, PhD, FRCP
Professor of Medicine
Division of Neurology
Toronto General Hospital
University Health Network
University of Toronto
Toronto, Ontario, Canada
Dr Bril reports receiving grants/research support, serving as a consultant to, and receiving honoraria from Eli Lilly and Company.

Ronald Klein, MD, MPH
Department of Ophthalmology and Visual Sciences
University of Wisconsin Medical School
Madison, Wisconsin
Dr Klein reports serving as a consultant to and receiving honoraria from AstraZeneca LP and Eli Lilly and Company.

Notice: The audience is advised that an article in this CME activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Bril—carbamazepine, epalrestat, fidarestat, gabapentin, oxycodone, ranirestat, ruboxistaurin, topiramate, tramadol.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Diabetic Microvascular Complications: The Role Of The Family Physician In Diagnosis And Management
Simeon Margolis, MD, PhD* and Neil Brooks, MD 

Diabetes is the most common cause of blindness, kidney failure, and amputation in the United States.1 Several recent studies have demonstrated the significant impact of diabetic microvascular complications (DMCs). A recent report by the US Centers for Disease Control and Prevention found that diabetes is associated with a greatly elevated risk of retinopathy and other diseases of the eye, including visual impairment, cataracts, and glaucoma.2 Another recent study found that the incidence of sight-threatening retinopathy over a 3-year period in patients with type 2 diabetes was 3.9%.3 The incidence of lower-extremity diseases among persons with diabetes (including peripheral arterial disease and diabetic peripheral neuropathy [DPN]) is approximately double the incidence among the general population.4 Persons with diabetes are also much more likely than the general population to suffer from chronic painful peripheral neuropathy.5 Among patients with chronic kidney disease, a diagnosis of diabetes predicts a significantly increased likelihood of death from kidney disease within 5 years.6 A recent statement from the American Heart Association noted that patients with chronic kidney disease (including chronic kidney disease associated with diabetes) should be considered to be in the Òhighest risk group' for subsequent cardiovascular disease.7

The likelihood of diabetic microvascular complications is closely related to the control of blood glucose. The incidence of DMCs is generally low for individuals with glycosylated hemoglobin A1c (HbA1c) values below 6%,8 and pharmacologic treatment to aggressively lower HbA1c values significantly reduces the risk of a number of diabetic microvascular complications, including retinopathy, neuropathy, and nephropathy.9 However, even patients who receive intensive therapy exhibit a gradual increase in HbA1c concentration over time, and most patients are not able to maintain HbA1c values below 6% after 7 to 10 years even with intensive treatment.9 New treatment strategies are currently being developed to prevent the progression of the microvascular complications of diabetes. These new approaches include interrupting metabolic pathways that produce tissue-damaging oxygen free radicals, improving blood flow, and stimulating the regeneration of injured nerves.

This monograph provides an update on diabetic microvascular complications. Simeon Margolis, MD, PhD provides an overview of DMCs—DPN, diabetic retinopathy (DR), and diabetic nephropathy. He also reviews the results of prospective clinical trials that have examined the effects of tight glucose control and the modification of other risk factors on clinical outcomes among patients with diabetes. Although control of blood glucose is clearly important for reducing the risk of diabetes complications, clinicians also need to consider other factors such as body weight, smoking, exercise, blood pressure, and lipids. Vera Bril, MD, PhD, FRCP, describes the pathophysiology, detection, and management of DPN. DPN is very common among patients with type 1 and type 2 diabetes, and is an important early step in the sequence of events that eventually culminates in lower-limb infection and amputation. Emerging therapeutic strategies that use novel mechanisms of drug action to slow the progression of diabetic microvascular complications are also reviewed. Ronald Klein, MD, MPH, describes epidemiologic studies and prospective clinical trials that have examined the progression of DR and the effects of intensive blood glucose control on DR and other eye diseases. Mohamed G. Atta, MD, discusses the progression of nephropathy in patients with diabetes, the relationship between microalbuminuria and other manifestations of vascular disease, and the effects of risk factor modification on the progression of diabetic nephropathy.

1. Reusch JE. Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose? J Clin Invest. 2003;112(7):986-988.
2. Centers for Disease Control and Prevention (CDC). Prevalence of visual impairment and selected eye diseases among persons aged ³ 50 years with and without diabetes-United States, 2002. MMWR Morb Mortal Wlky Rep. 2004;53(45):1069-1071.
3. Younis N, Broadbent DM, Vora JP, Harding SP, Liverpool Diabetic Eye Study. Incidence of sight-threatening retinopathy
 in patients with type 2 diabetes in the Liverpool Diabetic Eye Study: a cohort study. Lancet. 2003;361(9353):195-200.
4. Gregg EW, Sorlie P, Paulose-Ram R, et al. Prevalence of lower-extremity disease in the US adult population (40 years of age with and without diabetes: 1999-2000 national health and nutrition examination survey. Diabetes Care. 2004;27(7):1591-1597.
5. Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med. 2004;21(9):976-982.
6. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164(6):659-663.
7. Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108(17):2154-2169.
8. Stratton IM, Adler AI, Neil HAW, et al. Association of glycaemia with macrovascular and microvascular complications of type diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412.
9. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853. Erratum in: Lancet. 1999;354(9178):602.

*Professor, Department of Medicine, Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Medical Director, Vernon Manor Health Care Center, Vernon, Connecticut.
Address correspondence to: Simeon Margolis, MD, PhD, 1830 E. Monument St, Room 336, Baltimore, MD 21205. E-mail:

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