Glycated Amadori Plasma Protein Levels Reflect Short-Term Diabetes Control

The level of Amadori-modified proteins — the intermediate products of glycation — may be useful for monitoring short-term glycemic control in patients with type 2 diabetes.

The authors explain that Amadori-modified proteins are intermediates on the pathway to formation of advanced glycation end products, which are implicated in many of the chronic complications of diabetes.

Dr. K. Sreekumaran Nair from the Mayo Clinic in Rochester, Minnesota, and colleagues investigated the level of Amadori-modified proteins in type 2 diabetic patients with poor glycemic control and the effects of short-term insulin treatment on glycation of these proteins.

Untreated diabetics had significantly higher glycation of albumin, fibrin, transferrin, and immunoglobulin heavy chain than did nondiabetics, the authors report.

All these glycated proteins showed significant reductions, ranging from 13% (immunoglobulin light chain) to 34.6% (fibrin), after 10 days of insulin treatment, the report indicates.

Additional investigation also revealed significant reductions in glycation for beta-fibrinogen precursor, hemopexin, vitamin D binding protein, and serine protease inhibitor after insulin treatment, the researchers note.

Eleven days of insulin treatment was accompanied by complete disappearance of glycated alpha-fibrinogen precursor, fibrinogen gamma-B chain precursor, and transferrin, the results indicate.

"The prevention of formation of Amadori products or the removal of these modified proteins is potentially the most effective way to interrupt the glycation cascade and prevent the potential pathological consequences of glycation," the investigators explain. The current study also demonstrated that this glycation is significantly reduced by 10 days of short-term intensive insulin treatment and examined this approach to identify molecules to use as a short-term index of glycemia.

"The current report shows the potential value of these newly identified plasma proteins for monitoring the effect of short-term glycemic changes in diabetic patients," the authors conclude.

"This approach may provide an opportunity for more focused investigations that may identify protein modifications responsible for pathogenesis of complications related to type 2 diabetes as well as to monitor insulin treatment," the researchers add.

HbA1c, an Amadori product, has been used extensively since the 1970s as an index of blood glucose control in clinical practice and research.. A correlation between glycated albumin, another Amadori-modified plasma protein, and diabetic nephropathy and other complications has been recently reported (23,24). The current study demonstrates that glycated albumin is increased in type 2 diabetic patients after 2 weeks of poor glycemic control.
Diabetes Care 2005;28:645-652

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FACT:
Insulin producing cells have now been found to exist outside the pancreas. They produce proinsulin, as do pancreas beta cells in the face of increased glucose and diabetes. Organs these cells have been found in include bone marrow, liver, adipose tissue, spleen and thymus. These cells, these tissues, react in many ways that may also be important in the course of the development of diabetes 1A (immune mediated) as well as having therapeutic potential for the reversal of diabetes 1.
Proc Natl Acad Sci USA 2004 2:101(8): 2458-63.