PreventAGE now provides precise measurement of Advanced Glycation and Oxidation Products for your Research Program

Dear Investigator,

PreventAGE Health Care is pleased to be the first to offer analyses of a unique set of advanced glycation and oxidation products to you as an academic or commercial researcher.

Our precision diagnostic tests will be useful as you seek to understand mechanistic pathways resulting in diabetic complications, and will provide you with important predictive information on risk and potential targets for new therapies. This analytical service will allow you the opportunity to apply these assays to multiple research applications, in multiple fields.

Our overarching objective is to fundamentally improve the care of patients with diabetes and thereby improve their outcomes, including quality of life, health status, and longevity.  We believe that our diagnostic assays will fill an essential, yet currently unmet, need and will lead to the fulfillment of our slogan "Know your risk, Change your outcome!".

We are excited about the potential for our unique services in multiple areas of clinical investigation, and welcome inquiries to discuss application to your projects.

Sincerely,

Paul J. Beisswenger MD, Chief Scientific Officer, PreventAGE Healthcare

 

Glycation/Oxidation Pathways Play a major Role in the development of Diabetic Complications:

The vascular complications of Diabetes are major health problems in the US and in the developed world, involving all ethnic populations. 

One of the most important processes associated with the cellular dysfunction associated with hyperglycemia is nonenzymatic glycation, which has gained increasing acceptance as a significant mechanism contributing to the vascular damage associated with diabetes [1-4]. This process initially involves spontaneous reactions between ubiquitous reducing sugars, and amines, while its extent depends only on the nature and concentration of the reactants. It initially involves the formation of early glycation products (EGPs) including Amadori Products and highly reactive a dicarbonyl compounds (methylglyoxal (MG) and others), which in turn undergo a complex series of chemical reactions that lead to the formation of advanced glycation end products (AGEs) [5-6]. Glucose induced oxidative stress is also initiated in diabetes and can produce direct tissue damage or lead to activation of all of the major pathways that produce diabetic complications [7-10].

 

We Now Provide Assays to Measure Specific AGEs and Oxidation Products

Until recently, our knowledge of the full spectrum of AGEs and oxidation products formed in diabetes has been limited, but using Liquid chromatography, triple quaudrupole mass spectrometric methods (LC-MS/MS) we can now precisely measure 6 specific AGEs and 4 stable oxidation products. The structural formulae of these products, which range in molecular weight from 161.2 to 378.4 D are shown in figure 1. These AGEs reflect and integrate the activity of distinct precursor glycation and oxidative pathways, and provide new tools to assess the impact of increased production, or decreased detoxification, of these products over time. We have developed new analytical methods, which can quantify multiple AGEs and OPs on substantially shortened runs, allowing 28,000 analyses per year for each instrument acquired.

 

Figure 1. Structural Formulae of AGEs and oxidation End Products

 

The magnitude of increase in AGEs and Oxidation Products in diabetes

Utilizing these assays, we have shown that the highest in vivo AGEs quantitatively are arginine derived end products, which increase up to 9 fold in plasma, and 15 fold in urine in diabetes [11,12], while we have also recently shown that urinary and plasma levels of MetSO increase five-fold in diabetes relative to controls.

 

Methylylglyoxal (MG) can predict Individual susceptibility to the development of diabetic nephropathy

It is well recognized that individuals with diabetes show widely varying susceptibility to the development of debilitating vascular complications [13-15]. Thus a substantial subset (20-25%) of those with diabetes develop diabetic nephropathy despite reasonable glycemic control while others never develop them in spite of long-term hyperglycemia [16, 17]. We have previously shown in several study populations that those with higher levels of a dicarbonyls and oxidative stress have a greater propensity to accelerated diabetic nephropathy [8, 18, 19]. The concurrent increases in dicarbonyl and oxidative stress seen in our human translational studies are consistent with Brownlee’s [20] proposed unifying hypothesis of diabetes complications.  Biomarkers that reflect these pathways could therefore identify those at greatest risk of diabetic nephropathy.

 

Methylglyoxal derived AGEs predict diabetic nephropathy

As shown in our recent manuscript [21] we have demonstrated that three plasma AGE biomarkers, two of which are end products of MG, predict development of biopsy proven early diabetic nephropathy [27]. Although these AGEs reflect different chemical processes than HbA1C, these biomarkers together have additive predictive value concurrently with it.

 

PreventAGE has confirmatory outcome studies underway

These findings suggest that the specific AGEs that we found to be predictive for diabetic nephropathy have a high potential as biomarkers for the inherent propensity for developing other diabetic complications. We are currently investigating other areas where AGEs and oxidative processes may play important roles, and where measurement in clinical settings may be useful in predicting and preventing progressive degenerative processes.

We believe that the development of new biomarkers for prediction of diabetic complications will shift the treatment paradigms for diabetes. The development of diagnostic tests that predict early complications before symptoms are visible is a valuable research tool and will allow individualized treatment yielding more positive results, healthier patients, and lower health care costs. Additionally, enhanced understanding of the roles that AGEs and OPs play as biomarkers will open doors to future research on the role that they play in creating complications.

PreventAGE's goal is to create assays that will provide important predictive information to researchers, doctors and patients with diabetes, allowing them to establish treatment plans that assure better and more cost effective outcomes.

We are excited about the potential for our unique services in multiple areas of clinical investigation, and welcome inquiries to discuss application to your projects.

 

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