By Lisa Fratt

 Advances in the diagnosis and management of diabetes have a number of implications for laboratory technologists. Many of the advances promise to meet the dual health care mantra of improved clinical care and controlled or reduced costs. For example, AusAm markets a new assay that can better predict diabetic complications—-specifically kidney disease. The current version is geared to larger reference sites, but the company plans a high-throughput immunochemical assay appropriate across the health care spectrum. And Kronus Inc markets assays for investigational use only that may improve identification of type 1 diabetes in high-risk populations. Finally, LifeScan provides IT solutions to facilitate implementation of Tight Glycemic Controls (TGC), a practice recommended by the American Association of Clinical Endocrinologists (AACE).

Raising the Bar on Identification
The gold standard for serological measurement of antibodies for type 1 diabetes is to identify pancreatic islet cell antibodies (ICA) via the immunofluorescence test (IFA). There are, however, a number of drawbacks to the method. The test relies on individual interpretation of the signal strength to indicate the presence of cytoplasmic islet cell antibodies. While the IFA test is useful, especially when read over time by a well-trained technologist, it is a semiquantitative measurement of the antibodies.

Kronus offers a way to potentially improve prediction and identification of individuals at risk of type 1 diabetes. There are more than 30 distinct autoantibodies associated with the immune process in type 1 diabetes, with three of the autoantibodies correlating with a high predictive value and improved sensitivity and specificity for the disease in individuals predisposed to type 1 diabetes: glutamic acid decarboxylase (GAD), IA-2, and insulin. These early markers are usually present and measurable several years prior to the clinical onset of disease, potentially enabling a more proactive, educational approach to the management of diabetes.

Kronus markets three investigational-use-only tests kits to assess the autoimmune process and improve sensitivity, specificity, and positive predictive value. Kronus President and CEO Christopher Viele says, “Antibodies to GAD offer the greatest overall sensitivity, but the ability to test for antibodies to the presence of all three autoantigens potentially gives physicians the ability to capture a larger number of high-risk individuals who may progress to clinically overt disease.” And because the test kits can be used to measure the markers over time, the combined results can provide clinicians with vital information about the autoimmune progression of diabetes.

The tests consist of standard radioimmunoassay kits classified as manual, high-complexity assays according to CLIA, which precludes some laboratories from offering the tests. Indeed, in order to offer the test, a lab must have a refrigerated centrifuge, a gamma counter to read the signal, or a spectrophotometer. Kronus sells kits in radioimmunoassay (RAA) format for all three autoantibodies and ELISA kits for GAD and IA-2.

Islet Antibodies and Their Use in Predicting Type 1 Diabetes

When Positive for: Sensitivity Overt Disease
(within 5 years)
GAD Ab 90% 52%
GAD Ab and IA-2 Ab 62% 86%
GAD Ab, IA-2 Ab, and insulin (IAA)   52% 100%
ICA (via IFA) 74% 51%

Adapted from Verge, et al. Diabetes. 1996;45:926-933.

Improving Inpatient Diabetes Management
Brian Murphy, marketing director of LifeScan Inc, repeats an inevitable truism of modern health care. “Historically, it has been difficult to reconcile clinical and financial outcomes; the two always seem to be at odds with each other.” Tight glycemic controls (TGC) is one of the exceptions to the rule. TGC entails tight management of glucose levels of higher risk patients within specified ranges.

“This is a real opportunity for the lab to lead an initiative that has incredible patient outcomes,” Murphy says. For example, recent studies link TGC with a 57% reduction in mortality and a reduction of almost 4 days in the average hospital stay.

Implementing TGC is a significant undertaking that requires more time on the part of point of care coordinators, nurses, and laboratorians. With TGC, the nursing staff has additional testing to perform, and the lab must collate and analyze the additional data from the bedside.

According to Murphy, the lab often leads the charge in implementing TGC, which entails securing buy-in from nursing, administration, and surgical staff. LifeScan provides tools to facilitate adoption and implementation and to educate key stakeholders. The company’s Diabetes Informatics products leverage information technology to transform blood glucose results into actionable data. Diabetes Informatics can help administrators evaluate various TGC protocols or measure the effectiveness of TGC in various patient populations. The most common approach for hospitals is to first implement TGC in the ICU and then transition into the medical surgical wards. LifeScan’s DataLink Data Management System features embedded TGC reporting to allow facilities to monitor and flag TGC patients. A large number of sites use the system to implement and evaluate TGC programs.

LifeScan, as well as other companies in the diabetes management market, are considering the next step. “Semicontinuous monitoring will be the next great advance in TGC,” Murphy says. “It will increase efficiency and patient comfort and capitalize on the benefits of telemetry.” An interim step toward this next big breakthrough is wireless monitoring. LifeScan’s current solutions provide near real-time data, and early next year the company plans to introduce a wireless offering to make real-time data transfer a reality.

 AusAm Biotechnologies has developed several products to detect excess albumin in urine.

Advances in Predicting Kidney Disease
An excess of albumin in urine, or microalbuminuria, is as or more predictive for potential kidney or cardiovascular disease than elevated blood pressure or cholesterol, with diabetics at increased risk for both conditions. Moreover, research shows that earlier detection of progression to kidney or heart disease correlates with better clinical outcomes and lower costs. The hitch comes in the form of conventional tests for measuring urinary albumin; all of the conventional immunoassays, from dipsticks to quantitative hospital analyzers, suffer from a high degree of variability and can generate 30%–40% false-negatives for microalbumin, says James McCullough, CEO of AusAm Biotechnologies. Essentially, intact albumin in urine comes in two forms, one of which has been rendered unrecognizable during kidney passage to conventional tests.

In August 2003, AusAm received FDA approval for its solution to this missed albumin. As a result, studies have shown Accumin can detect microalbuminuria up to 12 years earlier than conventional tests. On average, Accumin detects microalbuminuria 3 years earlier than other tests in type 1 diabetcs.

In addition to earlier detection of microalbuminuria, Accumin carries a number of other benefits. The test is reimbursable and uses existing Medicare and third-party payor reimbursement codes. Finally, the test is noninvasive; it does not require a blood draw.

Accumin works with AusAm’s High-Performance Liquid Chromatography (HPLC) equipment AccuChrom. The AccuChrom HPLC equipment physically separates and measures intact urinary albumin. Because the equipment is designed for large reference laboratories, hospital labs find it difficult to implement Accumin.

In the next year, AusAm plans to open up the hospital market with the introduction of Accumin on high-throughput immunochemical assays. The company plans to introduce an Accumin point-of-care dipstick that can be used to screen high-risk patients, including diabetics. This screening would allow physicians to send positive patients to a reference lab for confirmatory quantitative analysis.

Opportunities for Lab Leadership
in Diabetes Management

Jeffrey A. DuBois, PhD, vice president for Nova Biomedical, has his finger on the pulse of diabetes management. “We need to close the gap between the clinician treating the patient and the laboratory in terms of sharing test results. While we continue to work on improving the accuracy and precision of testing technology, one of the biggest challenges is integration and connectivity.”

 Jeffrey A. DuBois, PhD

There are occasional glimpses of the potential of the connected approach. For example, Nova Biomedical and Medtronics have developed the Paradigm Link Diabetes Management System, which consists of a meter connected directly to a pump for type 1 diabetics. DuBois says the technology reduces errors, increases patient convenience, and brings patient management one step closer to total integration.

“One of the reasons data integration is important is because we need more outcomes measurement,” DuBois says. “Until we can effectively integrate data from the patient population, the effectiveness of clinical therapies and outcomes for therapies is less than optimal. The sooner we can have more real-time information the easier it will be to conduct outcome and evidence-based studies.”

Ultimately, clinicians need real-time information and results to make decisions, and putting the right information in their hands hinges on connectivity. DuBois says, “There needs to be a paradigm shift—characterized by LIS companies focusing on point-of-care connectivity. The lab needs to be proactive in developing an integrated approach to diabetes management. One of the ways that laboratorians can support clinicians and enhance diabetes care and management is by implementing programs that facilitate data flow between the lab and the hospital floor.” In fact, as labs evaluate new assays, processes, and systems, one of the key criteria should be how well the solution facilitates connectivity and information flow.

DuBois sees other opportunities for laboratorians to help improve diabetes care and management. There is a significant gap in standardization of methods in the four communities where tests are performed: home testing (self-monitoring by finger stick and testing of capillary whole blood); bedside testing, which is similar to self-monitoring in the use of capillary whole blood; critical care testing devices (whole blood arterial and venous specimens); and central laboratory testing (normally serum/plasma-based analysis). According to DuBois, lab professionals can play a major role in educating clinicians and nurse practitioners about the validity of the various methods and the best approach to standardizing results obtained in the four segments. The National Institute of Standards and Technology (NIST) provides primary standards, but there are documented differences between whole blood venous, whole blood arterial, venous blood, plasma, serum, capillary whole blood, and interstitial fluid. These differences, in turn, indicate a need for clinicians and lab scientists to come together to standardize and further improve the quality and correlation of glucose testing, says DuBois.

Lisa Fratt is a contributing writer for Clinical Lab Products.