Plasma advanced glycation endproduct, methylglyoxal-derived hydroimidazolone is elevated in young, complication-free patients with Type 1 diabetes.
OBJECTIVE
Elevated advanced glycation endproducts (AGEs) are implicated in diabetic complications. Methylglyoxal-derived hydroimidazolone (MG-H) is one of the most abundant AGEs in vivo. Our objective was to develop a time-saving, specific method to measure free MG-H in plasma and determine its levels in complication-free young individuals with Type 1 diabetes (T1DM). The relationship of plasma free MG-H to hemoglobin A1C (A1C) and plasma methylglyoxal levels was also determined.


METHODS
A solid phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, and free plasma MG-H levels were measured in 40 T1DM patients (DM group), aged 6-21 years, and 11 non-diabetics (ND group), 6-22 years. Methylglyoxal was measured using LC-MS/MS and A1C by a Tosoh G7 high-performance liquid chromatograph.


RESULTS
Our method showed high recovery, sensitivity and short run-time. Plasma free MG-H (nmol/L) was higher (p<0.001) in the DM group (1318+/-569; mean+/-standard deviation) as compared to the ND group (583+/-419). Within the DM group, plasma free MG-H did not correlate with plasma methylglyoxal or A1C.


CONCLUSIONS
Our LC-MS/MS method to measure free MG-H in plasma may be useful for future clinical application. The increased levels of free MG-H observed in individuals with TIDM are not merely the result of short term changes in glucose or methylglyoxal, but may reflect long-term alterations to tissue proteins.
Han
Yingchun
Y
Division of Biochemical Pathology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Randell
Edward
E
Vasdev
Sudesh
S
Gill
Vicki
V
Curran
Matthew
M
Newhook
Leigh Anne
LA
Grant
Marie
M
Hagerty
Donna
D
Schneider
Celine
C
D000293:Adolescent; D002648:Child; D002853:Chromatography, Liquid; D048909:Diabetes Complications; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D017127:Glycation End Products, Advanced; D007093:Imidazoles; C117197:imidazolone