Proteomic and Metabolomic Approaches to Diagnose Diabetes and Pre-Diabetes

Environmental Health Perspectives, May 2004 | Go to article overview

Proteomic and Metabolomic Approaches to Diagnose Diabetes and Pre-Diabetes


More than 5 million adults in the United States have undiagnosed type 2 diabetes mellitus, and another 38 million with pre-diabetes are at increased risk for developing diabetes. The lack of a simple and reliable way to detect diabetes and pre-diabetes has hindered identification of these individuals and provision of effective therapies. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) encourages the application of proteomic and other novel technologies to develop new diagnostic tests and/or to identify new biomarkers for the diagnosis of pre-diabetes and/or diabetes that do not require fasting or glucose administration.

Diabetes is a metabolic disease characterized by hyperglycemia that in 2002 affected nearly 9% of U.S. adults. More than 90% of the people with diabetes have type 2 diabetes. The symptoms of type 2 diabetes develop gradually. Some people have no symptoms until after they develop complications, which could have been prevented or delayed with early diagnosis and effective treatment. Additionally, 38 million U.S. adults aged 40-74 have pre-diabetes. Pre-diabetes is defined as impaired fasting glucose or impaired glucose tolerance (http://www.diabetes.org/diabetes-prevention/ pre-diabetes.jsp). These individuals have glucose levels above normal but below the level needed for diagnosis of diabetes. They are at increased risk of cardiovascular disease compared to those with normal glucose tolerance, and are at substantial risk for developing diabetes.

Clinical trials have demonstrated effective interventions for preventing or delaying complications in those with diabetes and for preventing or delaying onset of diabetes in those with pre-diabetes. However, millions of Americans are not receiving effective therapy, in part due to the limitations of current methods of diagnosing diabetes and pre-diabetes. The oral glucose tolerance test (OGTT)--the gold standard for diagnosis of diabetes and pre-diabetes--is inconvenient, requires fasting, and is not highly reproducible. The fasting blood glucose is less burdensome but much less sensitive, particularly in older Americans, who have the highest prevalence of diabetes and pre-diabetes. The quantitation of hemoglobin A1c (a glycated form of hemoglobin) from blood has been widely used as a test for assessing the adequacy of glycemic control and risk of complications in diabetic patients, but this test is not sufficiently sensitive to detect the range of glucose values typically seen in pre-diabetes or new-onset type 2 diabetes. Furthermore, there are many variants of hemoglobin present in blood, particularly in minority populations that are disproportionately affected by diabetes, and this adds additional uncertainty to the use of this test.

A simplified, less burdensome approach to the diagnosis of diabetes and pre-diabetes would facilitate increased recognition and improved care of these conditions. Many proteins and other blood components may be modified in individuals with elevated blood glucose. Identification of these molecules or of identifiable correlates of hyperglycemia would facilitate development of potential new laboratory tests for diagnosis of diabetes and pre-diabetes. With this initiative, we are encouraging scientists with expertise in proteomics and metabolomics to develop new tests to detect pre-diabetes and diabetes that correlate with the results of the OGTT but do not require fasting or administration of glucose.

Proteomic and metabolomic approaches have been successfully used for studying complex biological problems and for the identification of disease markers. Recent developments indicate that these technologies could be used or appropriately modified for developing new methods to diagnose diabetes and pre-diabetes. For example, mass spectrometry has been successfully used for the identification and quantitation of large numbers of proteins from plasma. Similar studies were performed for quantifying large numbers of metabolites. …

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Proteomic and Metabolomic Approaches to Diagnose Diabetes and Pre-Diabetes
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