Diabetes presents a clinical condition in which insulin is not utilized normally, resulting in impaired levels of blood glucose. Increased levels of glucose diffuse into red blood cells, reacting irreversibly with the hemoglobin inside the cells and producing glycosylated hemoglobin, or HbA1C.

The diagnostic test for HbA1C provides a measurement that is not affected by short-term changes in glucose levels, but instead reflects glucose levels over a period of time. The HbA1C average daily blood glucose levels over a 3-month period are: 6% (120 mg/dl, considered good), 8% (180mg/dl, fair), 10% (240mg/dl, caution), and 13% (330 mg/dl, dangerous).

The HbA1C test is useful for monitoring if done every 3 to 6 months, depending on the degree of accuracy that is required.

Companies involved in diagnostics are engaged in intense competition to produce the most accurate, comprehensive, and efficient assays for HbA1C testing. A look at four of these companies gives us a profile of developments in the year ahead.

New Hemoglobin Control

Quantimetrix Corp, Redondo Beach, Calif, has developed GlycoHemosure, a glycosylated Hemoglobin (A1C) control. This human serum-based control is supplied in a liquid format requiring no reconstitution and has an 18-month frozen closed-vial stability. A quality control program is now available for a wide range of testing including clinical labs as well as point-of-care and physician office labs.

GlycoHemosure is a basic blood chemistry control for the verification of HbA1C. GlycoHemosure is compatible with instruments such as the Bayer DCA 2000, Cobas Integra, Dimension, Hitachi, Primus CLC 330/385, and Synchron. The control is available as a two-level set consisting of four 2-ml bottles.

Increased levels of glycosylated hemoglobin can be monitored using GlycoHemosure. Additionally, circulating levels of VLDL, LDL, and HDL can be separated and quantified using the Lipoprint System developed by Quantimetrix.

Direct Assay Streamlines Testing

Quantimetrix’s GlycoHemosure

Pointe Scientific, Canton, Mich, while not technically a clinical lab, is a manufacturer that introduced the breakthrough single-channel, direct HbA1C assay that has been adopted by many labs.

A novel approach when it first appeared 4 years ago, the direct assay foregoes steps traditionally used in HbA1C tests on general chemistry analyzers. Although it shares the characteristic of being an immunoturbidometric assay, the Pointe Scientific HbA1C test does not require the manual step that has to be performed by the more traditional approach to prepare the blood sample for the analyzer, which is then followed by two assays: one to measure the total hemoglobin and a second to measure the specific HbA1C concentration. Instead, the direct assay runs a whole blood sample on just one channel and gets the equivalent result of the two-channel procedure while using only one channel.

Advantages of the direct assay single-channel system, according to Bill Walters, the company’s VP and director of technical operations, include the potential for full automation, which most two-channel systems do not have, plus “greater precision, less work, and lower cost.” The accuracy of Pointe Scientific’s HbA1C assay is certified through the NGSP certification program, Walters says.

Nonetheless, Walters adds, there is still plenty of competition in the industry because, he says, “There are about half a dozen entirely different methods of measuring glycosylated hemoglobin.” Included among these is the High Pressure Liquid Chromatography assay, often considered the gold standard in HbA1C testing.

Quantimetrix’s Lipoprint System

Walters is confident, however, that for testing done on clinical lab general chemistry analyzers, the direct single-channel assay will continue to be the leader in HbA1C testing, and has in fact become the product leader at Pointe Scientific.

TCG Reduces Morbidity

At Nova Biomedical, Waltham, Mass, there is a recent emphasis on better glycemic control for diabetic as well as nondiabetic patients. As reported by Howard Deahr, VP of marketing, “Labs and clinicians are partnering to implement new patient care protocols for improved glycemic control of diabetic and nondiabetic patients. Hyperglycemia occurs frequently in hospitalized patients with and without diabetes. Evidence that hyperglycemia causes poor clinical outcome has led to the need for improved recognition and treatment of hyperglycemia in the hospital setting. Stricter control of hyperglycemia is bringing the lab and clinical staff together to implement new protocols such as tight glycemic control (TGC). These protocols have been shown to reduce morbidity and mortality for critical care and surgical patients by 30% or more.”

Tighter glycemic control protocols involving rapid adjustment of insulin have led to the need for frequent bedside glucose testing. Achieving the lower glucose levels of TGC without risk of hypoglycemia, however, requires new levels of accuracy, precision, and freedom from interferences that exceed the capability of today’s bedside glucose meters and strips. “These meters,” Deahr says, “were originally developed for self-monitoring of blood glucose levels in the adult, nonhospital diabetic population. Target glucose concentrations for patients in the hospital are much narrower. In addition many hospitalized patients have severe hematocrit abnormalities and are on multiple medications that interfere with these meters.”

According to Deahr, the glucose meters and strips in use today are subject to serious errors due to hematocrit interferences that are commonly found in hospitalized patients. As Deahr points out, “Abnormal hematocrit levels can cause glucose meter results to be erroneous by as much as 40%. Severe hematocrit abnormalities are extremely common among ICU, NICU, PICU, and surgical populations.”

Nova Biomedical’s StatStrip Glucose Meter

Nova Biomedical has developed a new technology multiwell glucose strip to measure and eliminate hematocrit and other interferences. “This new technology,” Deahr says, “brings a level of accuracy, precision, and patient safety to bedside testing that approaches the quality of testing performed in the central laboratory.” Nova’s StatStrip is the first glucose meter to measure and eliminate interferences from hematocrit and other interferences frequently encountered among hospitalized patients. One of the StatStrip’s four measuring wells measures and corrects for hematocrit interference. Another well is used to measure and eliminate interferences due to electrochemical substances such as uric acid and acetaminophen. StatStrip also eliminates interferences due to maltose, xylose, and galactose. “This new technology,” Deahr concludes, “allows hospitals to provide safe and accurate bedside glucose testing needed for strict glycemic control of hospitalized patients.”

Acquisitions Expand Testing Capacity

At global multi-industry giant Siemens, there is plenty of excitement in the medical division over recent acquisitions that have significantly augmented its diagnostic capabilities. The November 2007 acquisition of Dade Behring Holdings Inc, in particular, brought with it a new immunoassay platform, the Advia and Dimension Vista Intelligent Lab System, that provides clinical labs with a broad test menu including urinary albumin and enzymatic creatinin, both of which are crucial in monitoring diabetes. Testing for urinary albumin (known historically as micro-albumin) can indicate renal complications that may significantly impact the therapeutic process, while enzymatic creatinin gives very accurate measurements and is considered a state-of-the-art modality for monitoring diabetes.

According to Jim Donnelly, global VP of medical and clinical affairs for Siemens Healthcare Diagnostics, “Clearly, central labs have a role in diabetes diagnostics and monitoring. With the new platforms and informatics at our disposal, we now can offer laboratories advanced capabilities for testing of HbA1C, albumin, creatinin, and other metabolic and enzymatic indicators, all coming off of one automated instrument, the Advia fully integrated and automated chemistry analyzer.”

Siemens’ ADVIA Workcell® CDX

President and CEO of Siemens Medical Solutions, Erich R. Reinhardt, in commenting on the string of diagnostic acquisitions, says, “The acquisition of Dade Behring ideally complements our acquisitions of Diagnostic Product Corporation and Bayer Diagnostics. The implementation of integrated IT and clinical solutions from Siemens will help improve workflow efficiency throughout the healthcare enterprise … This will enable our customers to increase the quality of patient care while simultaneously reducing costs.”

Siemens is due to unveil a new HbA1C assay in 2008, debuting in Europe and at the same time submitting for FDA approval. Perhaps its most significant feature, as reported by Donnelly, is that “unlike traditional assays, our new assay can take a whole blood sample without any pretreatment and test it on a completely automated, walkaway system. Also, significantly, there is no interference from hemoglobin C or hemoglobin S.” Donnelly believes that not needing pretreatment, thus reducing time, labor, and costs, is a “great bonus for central laboratories when running diagnostic tests on a large, general chemistry platform.” He describes the forthcoming HbA1C assay as “next generation.”

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Regarding informatics systems, Donnelly explains that there are three levels: central link, which is part of diagnostics; lab information systems; and higher-level administrative systems. “The beauty of the informatics systems is that they’re capable of putting together reports, tracking and monitoring, and getting feedback to the physician so that he can educate his patient and give them the information they need so they can understand where they’re going with their case.”

Highlighting the importance of the acquisitions, Donnelly concludes, “Siemens’ intention is to look at diagnostics as very complementary to their other product lines. With the acquisition of Dade Behring, we have found ourselves in a position where we can satisfy practically every situation where diagnostics is needed. We can supply small labs and physicians’ offices for diabetic monitoring, all the way through to very large reference laboratories. We cover the spectrum now.”

Alan Ruskin is staff writer for CLP.