Project Summary/Abstract –
The goal of this proposal is to validate glycated CD59 (GCD59) in human urine as a novel diabetes
biomarker. The validation of urine GCD59 as a diabetes biomarker will be conducted across several
hyperglycemic conditions including pregnancy-induced glucose intolerance/gestational diabetes. The proposal
is highly translational and addresses major Public Health priorities because: 1) women with pregnancy-
induced glucose intolerance and their fetus are at an increased risk of adverse clinical outcomes and perinatal
complications, 2) the frequency of pregnancy-induced glucose intolerance is increasing at alarming rates, 3)
appropriate treatment reduces the associated risks for the mother and newborn, and 4) glucose load tests,
currently the gold standard identifying pregnancy-induced glucose intolerance, are expensive, time consuming,
non-physiologic and unpleasant, have poor reproducibility on repeat testing. These facts highlight why
there is agreement that a simpler, shorter, easier-to-use, cost-effective, sensitive and specific test would be a
much better tool to screen for pregnancy-induced glucose intolerance. Similar considerations apply to the
general field diabetes in the general population, whose frequency is also increasing at alarming, almost
epidemic, rates.
The applicants have 1) discovered that human CD59 is inactivated by glycation, 2) provided evidence for a
link between the complement system and the pathogenesis of the complications of diabetes, and 3)
developed key reagents and established specific and sensitive assays that allows quantification of GCD59
in blood. With this assay, we have conducted several published studies including ≈4,000 subjects with
diabetes, pre-diabetes or gestational diabetes. Based on the robust preliminary data from these studies and
available resources, we now propose the highly focused aim of assessing the clinical utility of urine GCD59
as a simple, easy-to-use test for screening and diagnosis of diabetes, pre-diabetes and gestational diabetes.
All necessary tools and expertise to accomplish our aims are available in the laboratory of the applicant and
expert collaborators, including monoclonal antibodies specific for GCD59 and assay calibrators, access to
urine and plasma samples from a large and diverse population of individuals seeking medical care at
the two main Partner’s Healthcare Hospitals, diagnostic tools, equipment and expertise necessary to
conduct all studies proposed in the application.
Successful accomplishment of our aim will provide a clinically useful and independent biomarker that could
simplify the screening, diagnosis and management of conditions characterized by hyperglycemia.
