Type New Diabetes
Marjorie Lazoff, MD
Emergency Medicine
Philadelphia, Pennsylvania
Medical Editor
Medical Computing Today

accepted for publication in Medical Computing Today September 1999
Originally published in the October 1999 issue of Medical Software Reviews

Background - Controversies: Dx/Screening - Gestational DM - Troglitazone - Organizations - Med Sites - EBM - Future - Summary

Keeping up with the past decade's many changes in diabetes classification, diagnosis, management, and medications -- and the proliferation of new investigational treatments and patient aids -- challenges most physicians and practitioners. Medical Web sites are an excellent source for health professionals looking to keep current but, not surprisingly, locating quality clinical information on diabetes is frustrating and time-consuming.

The Web is bursting with all kinds of general diabetes information for students, physicians, and patients. This NetView concentrates instead on changes in management, new therapies, and other controversial issues that have been hotly debated over the past two years. Most of the information was found, not on organization or professional medical sites, but within our old standbys, the top medical journals. Among these issues, the most important clinically are the latest diagnostic and screening recommendations for general and subtypes of diabetes, and the use of troglitazone. The article continues with other information on advanced clinical diabetes, primarily from non-journal medical sites, and concludes with resources for ongoing monitoring.

Diabetes mellitus (DM) is one of our most ubiquitous chronic diseases, affecting up to 5% of the U.S. population -- over 15 million Americans -- and an estimated 100 million people worldwide. With our aging population, more sedentary lifestyles, and increasing obesity, the prevalence of type 2 (insulin resistant, formerly non-insulin dependent) diabetes, which accounts for 90% of DM, has increased dramatically over the past decades, and some predict its numbers will double within the next 20 years.

DCCT's 1993 landmark study demonstrated that excellent blood sugar control in type 1 diabetics delays the onset and progression of microvascular complications, without finding increased neuropsychiatric sequelae from hypoglycemia. This definitively pushed the management pendulum away from generous blood sugar limits towards tight, stable, long-term control of blood sugar for all diabetics. Supporting this management philosophy are recent studies suggesting a similar relationship in type 2 diabetes, and possibly even for macrovascular complications. But for many reasons good control remains elusive for the majority of diabetics, and DM is still a major contributor to the development of cardiovascular disease, adult-onset blindness, lower extremity amputation, and renal failure.

Sections Background

Plenty of basic review materials are available on line. As luck (and marketing strategy) would have it, Harrison's Online has posted its chapter on Diabetes and all updates gratis. Praxis Press's PraxisMD has four chapters within its CP Medicine text, the most general on Diabetes Mellitus and Hypoglycemia; search too its GenRx drug database using the keyword "diabetes," and its Field Reports for two article updates (pathogenesis of the diabetic kidney and herbal medicine). Members of Physicians' Online will find four concise summaries on diabetes within its Outlines of Clinical Medicine.

Epidemiology and risk factors are summarized in BMJ's September 12, 1998, editorial Diabetes: A time for excitement and concern and in an April 18, 1998, review article Recent Advances in Diabetes. For a review of primary care/clinical information in text and slide format, see NDEI's Diabetes Data, as described below. Finally, UCSF's Diabetes Primary Care Guidelines, lists many excellent online resources, among them top organizations' clinical practice guidelines.

Sections Controversies

A Medline search on "diabetes" brings up several areas of hot research, clinical trials, and debate. Among them, new diagnosis/screening criteria, gestational diabetes, and troglitazone (Rezulin) are particularly important clinically.

Sections New Diagnosis/Screening Criteria

The American Diabetes Association (ADA) 1997 revised criteria de-emphasize the role of the oral glucose tolerance test (OGTT) in screening and epidemiologic studies, and lower the diagnostic threshold to include an eight-hour fasting plasma glucose (FPG) of 126 rather than 140 mg/dl. These criteria also advocate a more aggressive screening protocol starting at age forty-five, or younger in the presence of diabetes risk factors, and recommend managing patients with asymptomatic glucose abnormalities. Also, insulin resistant patients with normal levels of glycated hemoglobin (HbA1c) but an FPG over 110 mg/dl may benefit from active intervention to reduce their cardiac risk factors. (Although no studies at present demonstrate benefit with reduction of cardiac risk factors, patients with insulin resistance are at increased risk of developing macrovascular complications.) The ADA's goal is to identify individuals at risk of developing diabetes before microvascular changes take place.

The controversy surrounding the ADA criteria vs. the UK-supported World Health Organization (WHO) criteria --whose provisional 1998 report still advocates the OGTT and does not recommend the ADA's aggressive screening protocol -- has fueled studies and editorials on both sides of the Atlantic. Evidence-based medicine, cost-analysis, and the risks/benefits of broadly defining diagnoses and prevention strategies figure prominently in the debate. Importantly, several studies suggest that the OGTT and the FPG each miss up to a third of diabetics. Many experts conclude that prospective data are needed to evaluate whether the WHO or ADA criteria best identify individuals at risk of developing microvascular complications and cardiovascular disease, and at what point clinical intervention is appropriate.

The October 15, 1998, issue of American Family Physician includes Diagnosis and classification of diabetes mellitus: new criteria, a well-written review article that covers the ADA's new classification, diagnosis and screening recommendations, and use of HbA1c. Two accompanying editorials supplement this article. The first is strongly critical of the new ADA diagnosis and screening recommendations as not being evidence-based, or supported by major medical associations (such as the AAFP); those who subscribe to The Lancet can search on line for additional studies showing the limitations of the new ADA recommendations. The second AAFP editorial supports the new changes as more clinically relevant.

BMJ has placed on line its full text paper from the frequently referenced 1998 DECODE Study Group that reanalyzes the European epidemiologic data given the new diagnostic criteria for diabetes. See too the related editorial, and letters.

Aggressive screening and treatment is the subject of a recent editorial, More Evidence, from ADA's Clinical Diabetes. The editorial in the December 12, 1998, issue of BMJ is in support of early screening as recommended by the ADA. In fact, last year the CDC recommended screening at age 25 -- two decades earlier than even the ADA recommends -- based upon cost analysis and decreased morbidity.

Sections Gestational Diabetes

The ADA, in its 1998 position paper on gestational diabetes, now joins the American College of Obstetricians and Gynecologists and the U.S. Preventive Services Task Force in recommending a more cost-effective selective screening. The selection is based on age greater than twenty-five years or presence of risk factors, and screening is performed during the 24th-28th gestational week. The ADA also disagrees with the WHO on which OGTT to use.

The Nov. 27, 1997, issue of NEJM has a softly critical editorial accompanying a study supporting this selective screening for gestational diabetes, the abstract of which is online gratis. Arguments for universal screening and selective screening are presented in BMJ's Education and Debate articles from its September 20, 1997, issue.

Sections Troglitazone

Thiazolidinedione derivatives such as troglitazone act on PPAR receptors to reduce peripheral resistance to insulin, and so theoretically correct not just hyperglycemia but also hyperinsulinemia, hyperlipidemia, and hypertriglyceridemia, potentially affecting the development of the micro- and macrovascular complications. But as a result of 130 worldwide reports of liver dysfunctions, including six unanticipated deaths, troglitazone was withdrawn in Britain several months after its introduction in Fall 1997, and its approval has been delayed in many countries.

The FDA, reviewing the same data, decided that the benefits of treatment outweigh the risks, provided that patients are monitored frequently for signs of liver injury. Abstracts of two studies, one comparing the efficacy and metabolism of metformin and troglitazone and a second on troglitazone appear in the March 26, 1998, issue of NEJM. The accompanying full text editorial details troglitazone's mechanism of action, and summarizes its benefits and risks.

The FDA review of rosiglitazone and pioglitazone discusses these two recently approved drugs with a biochemical profile similar to troglitazone. From June 1999, see the latest FDA label changes that responds to ongoing data on potential liver damage. The FDA has dropped troglitazone's indication as first line agent and has increased the frequency of recommended monitoring.

Sections Organizations

The American Diabetes Association Web site is primarily for patients, although physicians will appreciate access to ADA's position papers, practice guidelines, reviews, and consensus statements. This section was updated in 1999, and references are linked to PubMed citations and abstracts. Its controversial Diagnosis and classification of diabetes mellitus as discussed above, is on line. While the ADA is not the definitive advisory agency, its conservative and patient-oriented recommendations have strong impact on the diabetic community. Health professionals can also access information about ADA research projects and opportunities, and press-release type news items.

Like ADA's site, NIDDK's Fact Sheet on Diabetes is designed for patients, though at the bottom of the page are two hefty documents on statistics. There are also links to online resources and organizations. The CDC Diabetes and Public Health Resource, another patient oriented site, contains Diabetes Surveillance, 1997 in full text PDF format. Likewise, the WHO Diabetes Page has epidemiological information and a list of dated references. (Without access to WHO Policy System search engine, I could not determine if clinical reports were on line as well.)

Although the American Association of Clinical Endocrinology is a specialty organization, its Diagnosing diabetes mellitus: do we need new criteria? is more appropriate for general practitioners. See too Diabetic foot management: does the shoe fit?. Both contain information from within the past two years.

The National Diabetes Education Incentive (NDEI) on type 2 diabetes is designed for endocrinologists, diabetologists, primary care physicians, and other healthcare professionals. Site content, developed by a national panel of academic physicians, is sponsored by the Professional Postgraduate Services division of Physicians World Communications Group. The site has a very nice News section that archives old items, and a Diabetes Data section full of basic clinical information as noted above.

Sections Medical Sites

Once registered, follow the link on the home page of Medscape to the American Diabetes Association 59th Scientific Session. Medscape-employed physicians report on over a dozen presentations from this mid June 1999 conference. CME credit is available, and although most content is purely textual some feature or include audio interviews. Medscape's convention reporting is one of the site's best features, and this Session is one of the best online resources on current diabetic research and management for primary practitioners. (NDEI and PharmInfoNet have posted summaries of this Session's major presentations and Conference Highlights, respectively.)

Medscape's Diabetes and Endocrinology site includes other news, and journal and CME articles, such as a review highly supportive of thiazolidinediones (one of which advertises on the site). Journal Scan summarizes recent articles from JAMA, NEJM, and Journal of Clinical Endocrinology and Metabolism.

Registrants of Cyberounds will find a readable, practice-oriented interpretation of the new ADA recommendations in Eli Ipps, M.B., BCh's multi-part case discussion on type 2, MODY, and gestational diabetes. The work is timely, despite the title's reference to "NIDDM" instead of "type 2."

SilverPlatter's MD Opinions is a FAQ list of controversies, difficulties, and new clinical information for primary physicians, with an editorial panel of physicians headed by Mark Garber, MD, providing expert opinion alongside member submissions. Unfortunately, What are the current criteria for diagnosing diabetes mellitus? is given superficial treatment by a laboratory specialist and primary care practitioner. Glib statements such as "Fasting plasma glucose is really where it's at now for making a diagnosis of diabetes" ignore the legitimate controversy discussed above. I wish Dr. Graber had followed Cyberounds' practical review as an example, rather than writing a pedestrian paragraph on HbA1c. Although much of MD Opinion's database is not recent, this particular question is dated August 1999.

Sections Evidence-Based Medicine

Several meta-analyses and reviews reaching predictable conclusions are on line. For example, Cochrane Diabetes Group lists abstracts of several systematic reviews. The July 10, 1999, issue of BMJ reviews the evidence supporting glucose control. Again, evidence supporting long term benefits of glucose control in type 2 diabetes is presented in the January/February 1999 issue of Evidence-based Medicine, and evidence supporting Metformin in the January/February 1999 issue of ACP Journal Club.

A NetView favorite, the University of British Columbia's Therapeutics Letter, reviews Type 2 Diabetes and Treatment of Type 2 Diabetes. Troglitazone is not approved in Canada.

EBM fans will appreciate the Canadian Medical Association's 1998 Clinical Practice Guidelines which, based largely on cost-efficacy rather than clinical evidence, follow the ADA recommendations.

Sections For the Next Millennium

The July 9, 1998 issue of NEJM reports on research conducted on type 1 diabetes demonstrating reversal of lesions of diabetic nephropathy after pancreatic transplantation. The abstract and accompanying full text editorial provide a nice review of this promising but still experimental procedure. A recent BMJ editorial recommends dual pancreatic/kidney transplants for patients with uncomplicated type 1 diabetic with chronic renal failure.

Aggressive research in genetics and molecular biology is beginning to pay off in many clinical (and business) arenas. For example, March 13, 1999's BMJ News reports on a McGill University team that discovered a gene associated with obesity and type 2 diabetes, promising that drugs inhibiting this gene may some day be developed.

An article from the July 22/29, 1998, issue of JAMA reviews not-yet-available non-invasive means of monitoring blood glucose such as infrared radiation spectroscopy, polarized light rotation, and minimally invasive devices that analyze the interstitial fluid secretions harvested from the skin. More recently, NDEI has a page of new glucose monitoring devices in various stages of the FDA approval system.

Finally, visitors may be interested in Computer-Prompted Diabetes Care, a multifaceted software program from Israel described in the October/November 1998 issue of Effective Clinical Practice. (FYI: an extensive listing of diabetes software (http://www.mendosa.com/software.htm), many with reviews, is maintained by Rick Mendosa, a business, high tech, and medical writer, as part of his huge labor-of-love online diabetes resource list for patients.)

Sections Summary

With the arguable exceptions of Current Practice, Medscape, and Cyberounds, professional online medical sites provide little more than pedantic content. No one seems to be fully using Web technology to serve clinicians' need for sophisticated and timely information.

Health professionals who require ongoing updates might consider a weekly automated Medline service that is topic-specific, such as JADE or AMEDEO. Also, consider bookmarking NDEI'sNewsWatch and Literature Alert, both updated monthly with archives, and/or Medscape's Diabetes and Endocrinology. Finally, PharmInfoNet's Diabetes Information Center maintains a gathering of newsy articles, drug reviews, and conference highlights.

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