Automating Diabetes-Related Tests

The high-volume diabetes-related tests, namely glucose and glycated hemoglobin, have been available on automated chemistry instruments for many years. Insulin, C-peptide and urinary albumin ("microalbumin"), although not as frequently tested, continue to increase in volume with the growing number of diabetics. In fact, the World Health Organization has predicted that the worldwide population of diabetics will double by the year 2025 from the current number of approximately 150 million to 300 million.¹ As a result, diabetes-related testing will see a dramatic increase over the next few years. In spite of this projection, only recently have some of the lower volume tests, such as insulin, C-peptide and microalbumin, been consolidated onto automated platforms. Although not as commonly ordered as glucose and glycated hemoglobin, these three assays play an integral part in the diagnosis and management of diabetes.

Insulin and C-peptide concentrations are often evaluated following the diagnosis of diabetes. When insulin is produced by the b cells of the pancreas, C-peptide is released in equimolar amounts. Both C-peptide and insulin can then be used as indicators of pancreatic b-cell function.

In type 1 diabetes, the individual produces very little or no insulin at all. C-peptide and insulin determinations and their levels after glucose load or glucagon stimulation can be used to make this differential diagnosis.²

Type 2 diabetes is commonly associated with inadequate insulin production as well as insulin resistance-a condition in which the body does not properly respond to insulin for use in glucose cellular uptake. Treatment for this type of diabetes normally involves a combination of oral medication, diet regimen, and physical exercise. However, some type 2 diabetics eventually require insulin injections.³ To determine the best course of therapy, or to make modifications to an existing therapy, both insulin and C-peptide stimulation tests may be used to ascertain actual b-cell function.

C-peptide is also valuable when monitoring the b-cell function of type 2 diabetics during insulin therapy. Insulin production in these patients needs to be assessed periodically to determine if their insulin therapy needs modification. However, insulin assays cannot differentiate between endogenous and exogenous insulin. Also, some patients may develop anti-insulin antibodies that could potentially interfere with insulin immunoassays. By contrast, C-peptide assays are not affected by crossreactivity of exogenous insulin or anti-insulin antibodies and therefore allow the physician to monitor any changes in insulin production.²

A related utility of the insulin and C-peptide assays is for the differential diagnosis of fasting hypoglycemia. Insulinomas, which are tumors in the pancreas, persistently produce abnormally high levels of insulin and cause hypoglycemia. C-peptide levels are also elevated and therefore confirm the presence of an insulinoma. Factitious hypoglycemia, also associated with abnormally high levels of insulin, can be a result of inappropriate/ accidental insulin administration or even deliberate insulin overdose. However, C-peptide is not present in commercial preparations of insulin and therefore would not be elevated during fasting hypoglycemia.²

Diabetes is the most common cause of renal failure in the United States and one of the leading causes of renal failure worldwide. Microalbuminuria is a condition associated with the early stages of diabetic nephropathy. ("Microalbumin" is actually a misnomer. It is not small particles of albumin as the name might imply, but rather a slight to moderate increase over normal urinary albumin concentrations, at levels not quantifiable by classic biochemical techniques.) Before the development of sensitive immunoassays, albumin measurements provided information indicative only of kidney failure, which eventually requires dialysis or transplantation. The highly sensitive albumin immuno- assays are able to detect diabetes-related kidney disease in its early stages. This has led to therapies that are now able to slow progression of the disease. The National Academy of Clinical Biochemistry (NACB), following the recommendation of the American Diabetes Association (ADA), advises beginning annual microalbuminuria screening for pubertal or postpubertal subjects five years after diagnosis of type 1 diabetes and at the time of diagnosis of type 2 diabetes.⁴

Insulin, C-peptide, and urinary albumin (microalbumin) assays all play an important role in the management and monitoring of diabetes. As the prevalence of the disease increases, so will the demand for automated laboratory tests. Currently, DPC's IMMULITE/IMMULITE^® 1000 and IMMULITE^® 2000 are the only immunoassay systems that perform these three tests on a single, random access automated platform.

References

1. World Health Organization. Diabetes mellitus [fact sheet no. 138, revised April 2002]. http://www.who.int/inf-fs/en/fact138.html (accessed April 2003).

2. Bodlaender, P. Diabetes mellitus and the utility of insulin, C-peptide and urinary albumin assays [technical report ZB188]. Los Angeles: DPC; 1999.

3. WebMD Inc. WebMDHealth: Type 2 diabetes. http://my.webmd.com/content/healthwise/164/52034 (accessed April 2003).

4. Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48:436-72.