March 2009
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Undiagnosed Diabetes Equals Undiagnosed CVD: A Call for More Effective Diabetes Screening
Three major causes of undiagnosed diabetes are a lack of access to health care, ineffective screening strategies and practices, and suboptimal screening methods.
By Saleh A. Aldasouqi, MD, FACE, FACP; Ved V. Gossain, MD, FACE, FACP; and Randie R. Little, PhD
Diabetes mellitus has become an epidemic1 in the United States, with more than 24 million Americans having the disease at present2 and worldwide, diabetes is a pandemic.2 Due to its devastating complications, type 2 diabetes has caused serious health and economic problems globally.2 Nevertheless, a sizable proportion of diabetes remains undiagnosed. Data from the United States3-6 and the United Kingdom7 estimate this proportion to range from 25% to 33%. Of the four types of diabetes (type 1, type 2, gestational, and secondary), type 2 diabetes represents the bulk of the diabetic burden.8
Prediabetes1,2,9-10 and the metabolic syndrome11 have also increased in prevalence in the United States—26%9,10 and 25%,11 respectively. It has been reported that prediabetes will ultimately convert into type 2 diabetes in about 70% of cases.1 Worse than the data on undiagnosed type 2 diabetes, recent data reported much higher rates of undiagnosed (self-reported) prediabetes, as high as 85%.10
CVD AND DIABETES
The associations between cardiovascular disease (CVD) and type 2 diabetes5,9,12-17 and prediabetes1,2,9,17 are well established. Compared to microangiopathic complications (eg, retinopathy), CVD is the macroangiopathic form of chronic diabetes complications that comprises generalized atherosclerosis, coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease. At the time of diagnosis of type 2 diabetes, more than 50% of patients already have preexisting CAD.13
This close association stems not particularly from hyperglycemia (which contributes ultimately to CVD by means of protein glycation of the vessels)—but from the associated metabolic syndrome also known as insulin resistance syndrome. In addition to hyperglycemia, the remaining components of the metabolic syndrome (hypertension, elevated triglycerides, low HDL, and obesity) are established risk factors for CVD.17 Therefore, treatment that is focused only on controlling hyperglycemia does not significantly alter the risk of CVD in patients with type 2 diabetes. Instead, a multifactorial approach addressing all of these components is the most cost-effective approach in the quest for effective management of type 2 diabetes and its complications.14
Epidemiological data have shown that 75% to 80% of patients with type 2 diabetes die from atherosclerosis and CVD12,13 and two-thirds die as the result of the manifestations of CAD.12 Direct detrimental effects of type 2 diabetes in regard to CVD include increased immediate and 1-year mortality after myocardial infarction (MI) by two-fold; increased risk of heart failure after MI; 70% increase in mortality after acute coronary syndrome and non–ST-elevation MI; and increased risk of sudden death, atrial fibrillation, and ventricular fibrillation.12
MORE EFFECTIVE DIAGNOSIS
It can be appreciated that missing a diagnosis of diabetes translates to a large extent into missing a diagnosis of CVD that already exists in some form in many undiagnosed patients. Because CVD is among the top-ranked human killers, efforts should be maximized toward more effective and timely detection of diabetes and prediabetes. This is especially logical because screening for diabetes and prediabetes is simple and accurate15 and because effective diabetes treatment is achievable.14 Furthermore, diabetes prevention studies have shown that early identification and treatment of prediabetes (by lifestyle modifications or simple medications) have the potential to reduce or delay the progression to overt type 2 diabetes and related CVD.1,2
This argument translates into more effective diabetes screening. To tackle this challenge, the first question to ask is: Why is diabetes undiagnosed in 20% to 30% of the population? We believe that there are three major causes of undiagnosed diabetes: (1) lack of access to health care (ie, lack of medical insurance); (2) ineffective screening strategies and practices; and (3) suboptimal screening methods.
ACCESS TO CARE
Regarding lack of access to health care, Zhang et al evaluated the National Health And Nutrition Examination Survey (1999–2004). They found that 42% of uninsured Americans had undiagnosed diabetes, as compared with 26% of the insured.5 The solution to this big socioeconomic problem requires big national efforts, which cannot be covered in this short review. With over one-quarter of the insured Americans5 still having undiagnosed diabetes (62% of Zhang's sample), however, the remaining two causes of undiagnosed diabetes appear to play a more important role.
To address the issue of ineffective diabetes screening practices, Tabaei et al18 undertook a community-based screening program based on the American Diabetes Association (ADA) screening guidelines. The study (n=3,031) results were very disappointing (significant high rates of false positives and false negatives) and showed an extreme failure rate of detection of undiagnosed diabetes (<1%) despite systematic follow-up.
The aforementioned study was sponsored by the Michigan Department of Community Health Diabetes Control Program, which subsequently opted to drastically revise the diabetes screening strategy.18 Needless to say, similar national and statewide educational campaigns geared toward primary care health providers regarding the importance of effective diabetes screening are warranted to improve diabetes screening strategies.
SUBOPTIMAL SCREENING TESTS
Finally, we believe that the last but not least important cause of undiagnosed diabetes is related to the suboptimal diagnostic tests for diabetes, which are based solely on direct glucose measurements, namely fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT)—currently recommended19 by the ADA and adopted almost globally. Many experts suggest that there are significant deficiencies in these diagnostic criteria,20-26 with FPG missing a significant proportion of patients with diabetes (33% to 50%) due to undesirable sensitivity20,21,26 and OGTT being regarded as cumbersome, inconvenient, and not well reproducible.20-24,26 Furthermore, both FPG and OGTT require fasting and need to be repeated in the absence of unequivocal symptoms for purposes of verification.
Therefore, given the drawbacks of the current diabetes screening tests, the search for alternative screening tools to improve early diabetes detection is warranted. We believe that A1C, which has been extensively evaluated and has proven to be a promising diabetes screening tool in type 2 diabetes,6,20-23,25,26 should be routinely used in diabetes screening, as an adjunct/or alternative to FPG, and that OGTT should be limited to special and difficult situations. The validity of A1C in gestational diabetes is still controversial.24
A1C cutoff values recommended for screening have not been identified or standardized, but the upper limit of normal—6.0%—seems like a reasonable option. Saudek et al recommend 6.0% as a trigger for active screening and 6.5% as a diagnostic cutoff.6 Although major health organizations such as the World Health Organization, the ADA, and the American Association of Clinical Endocrinologists do not recommend A1C in screening, other organizations and other investigators have, including:
- A recommendation by the Japanese Diabetes Association.27
- A report published by Waugh et al28 that can be retrieved from the UK National Health Services National Institute of Health Research (www.ncchta.org).
- A report published by an expert panel of US academic diabetes specialists led by Saudek et al.6
- A report published by the US Preventive Services Task Force (USPST).15 In this recent report about diabetes screening, it was not specifically recommended by the USPSTF to utilize A1C in screening, but it was stated in the report that "three tests have been used to screen for diabetes: FPG, OGTT, and A1C."
In conclusion, we believe that adding A1C in the screening tests as an adjunct to FPG and OGTT will improve the detection of diabetes and potentially detect CVD at an early stage when primary prevention measures can be more efficacious.
Saleh A. Aldasouqi, MD, FACE, FACP, is Clinical Associate Professor, Michigan State University College of Human Medicine, and in the Department of Medicine, Saint Francis Medical Center, Cape Girardeau, Mo. He may be reached at saldasouqi@pol.net; phone: 573-339-8718; or fax: 573-339-9543.
Ved V. Gossain, MD, FACE, FACP, is the Swartz Professor of Medicine and Chief of Endocrinology in the Department of Medicine, Michigan State University College of Human Medicine. He may be reached at ved.gossain@ht.msu.edu; phone: 517-353-3730; or fax: 517-353-1326.
Randie R. Little, PhD, is Associate Professor at the University of Missouri School of Medicine, Departments of Pathology and Anatomical Sciences and Child Health, Coordinator, National Glycohemoglobin Standardization Program Network, and Codirector Diabetes Diagnostic Laboratory. She may be reached at LittleR@health.missouri.edu; phone: 573-882-1257; or fax: 573-884-8823.
Drs. Aldasouqi and Gossain have received research support from Metrika (Sunnyvale, CA) during an investigator-initiated study to evaluate the company's portable A1C analyzer A1C-Now (the study was published elsewhere). The research support was in the form of providing meters and strips for testing purposes and did not include any monetary or similar compensation. The writing of this manuscript was not shared with Metrika. The interest of the authors in advocating A1C for diabetes screening long anteceded this association.
The authors thank Faith Crutscheon, Saint Francis Medical Center Medical Library, Cape Girardeau, Mo., for assistance in references retrieval.
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