City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA
Address for correspondence: Samuel Rahbar, M.D., Ph.D., City of Hope National Medical Center and Beckman Research Institute, 1500 E. Duarte Road, Duarte, CA 91010. Voice: 626-256-4673 x 63131; fax: 626-301-8136. srahbar{at}coh.org
Glycated hemoglobins are minor components of human hemoglobin
(Hb). These are formed nonenzymatically by condensation of glucose
or other reducing sugars with
- and ß-chains of hemoglobin
A. The subfraction HbA
1c, a nonenzymatic glycation at the amino-terminal
valines of the ß-chain, was identified by the author
in the 1960s as a minor "abnormal fast-moving hemoglobin band"
in diabetic patients during routine screening for hemoglobin
variants. This finding later turned out to be an important biomolecular
marker with clinical and pathological applications. Measurement
of HbA
1c in diabetic patients is an established procedure for
evaluating long-term control of diabetes, and the introduction
of this measurement represents an outstanding contribution to
the quality of care of diabetic patients in this century. More
importantly, HbA
1c is the first example of
in vivo nonenzymatic
glycation of proteins, and its discovery opened new and still-growing
avenues of research on Maillard reactions in biological systems,
including the concept of advanced glycation/lipoxidation end
products (AGEs/ALEs) and the development of diabetic complications
and various diseases associated with aging. Although interest
in the Maillard reaction is growing rapidly, much remains to
be done in this field, including detection and characterization
of all
in vivo AGEs/ALEs, development and clinical applications
of AGE inhibitors and breakers, as well as investigations into
the possible roles of the Maillard reaction in regulatory biology
and carcinogenesis.
