New Approaches to Diabetes Disease Control, Insulin Delivery, and Monitoring

Abstract

Some of the most dangerous outcomes of either form of diabetes are those related to long-term complications, including kidney damage, or diabetic nephropathy. Over time, small blood vessels inside the kidneys can become damaged and reduce the body’s ability to filter toxins from the blood. Damaged kidneys leak a protein, albumin, into the urine. Detection of even small albumin levels, microalbuminuria, is one of the earliest signs of kidney problems, and also one that is not always noticeable in the earliest stages of the disease. Left untreated, the damage worsens until the kidneys fail, a condition called end-stage renal disease (ESRD). Because of the serious long-term consequences of kidney damage, in mid-November, 2004 the International Society of Nephrology urged national health bodies around the world to proactively implement albuminuria screening with the goal of preventing further kidney function deterioration in diabetics and others with kidney disease. Currently, the American Diabetes Association recommends that people diagnosed with type 2 diabetes be tested for microalbuminuria at the time they are diagnosed and every year thereafter. Those with type 1 diabetes should be tested 5 years after diagnosis and every year thereafter. About 21% and 28% of people with type 1 and 2 diabetes, respectively, have detectable levels of microalbuminaria by age 15.New York, NY-based AusAm Biotechnologies, founded in 2000, has developed a new type of diagnostic test to better detect extremely low levels of albuminuria. The FDA approved the company’s Accumin diagnostic test in August 2003 as the first test to measure total intact urinary albumin. The technology is based on the work of Wayne Comper, Ph.D., DSc, of Monash University, Australia. “The problem with conventional tests for urine albumin is that they can miss intact albumin that does not react with the antibodies used in making these tests. As a result, conventional urine testing is subject to a potentially large false negative rate for microalbuminuria,” says Mr. James McCullough, AusAm’s CEO. “It was derived from raising antibodies to serum albumin. Dr. Comper recognized that as the serum albumin passes through the kidney and out through the urine, it can undergo a slight conformational change rendering it unreactive to conventional serum-derived albumin antibodies. In other words, intact albumin that is invisible to conventional antibodies—which is in all the major manufacturers’ platforms and dipsticks—ends up unrecognized in the urine.” In the clinical tests that Dr. Comper and colleagues performed, conventional tests generated a 33% false negative rate for microalbuminuria when they were compared with Accumin.“In May 2004, we published that we can detect microalbuminuria up to 12 years earlier than radioimmunoassay, which is the most sensitive of the conventional urine tests,” says McCullough, “But on average, it is really about 3 years earlier.” The key, claims McCullough, is that the antibody used in the test was raised to urine albumin. “After doing 2D electrophoresis and HPLC, we discovered this whole population of intact albumin which was unrecognizable by the conventional antibodies in all the major immunoassays around the world,” says McCullough.The test is done in combination with a test for creatinine, a protein excreted by the muscles. The results are reported as a ratio of microalbumin/creatinine. “If you are above 30 mg of albumin per gram of creatinine, you are said to be microalbuminuria positive,” explains McCullough. “We can pick up as low as 3–4 mg albumin per gram of creatinine.”“We are platform agnostic,” says McCullough. “The FDA-approved Accumin quantitative test is currently done with chromatography. But we are in the process now of working with several analyzer companies to place the technology in high-throughput immunochemical devices.” In 2005, AusAm hopes to roll out a dipstick version of the technology to bring it even closer to the point of care.