Glycosylated serum protein levels assayed with highly sensitive immunoradiometric assay accurately reflect glycemic control of diabetic patients.
OBJECTIVE
To develop a sensitive and reliable immunoreadiometric assay to measure glycosylated lysine residues on serum proteins (GSP) and to evaluate its efficacy in monitoring glycemic control.


METHODS
The effect of acute and chronic in vitro and in vivo changes in glucose levels on GSP concentration was evaluated. GSP determinations from insulin-dependent diabetic (IDDM) patients, non-insulin-dependent diabetic (NIDDM) patients, and control subjects were correlated with other indices of glycemic control.


RESULTS
The GSP levels were unaffected by acute glucose changes after food or intravenous glucose administration but increased during storage at -20 degrees C due to in vitro glycosylation by endogenous glucose. Immediate acidification of the serum prevented this, permitting long-term storage despite high ambient glucose levels. In randomly selected diabetic patients, 96% of GSP values were greater than the mean +3SD of nondiabetic control subjects. In diabetic patients, GSP levels correlated with mean plasma glucose concentrations (Kendall correlation statistics 0.47, P less than 0.001), fasting plasma glucose levels (Kendall statistics 0.42, P less than 0.001), and glycosylated hemoglobin (GHb, Kendall statistics 0.30, P less than 0.005). Induction of near-normal glycemia in poorly controlled NIDDM patients reduced GSP levels with a slope consistent with a half time of disappearance of 4.7 +/- 0.4 days. GSP levels remained elevated in 6 of 10 well-controlled NIDDM patients, despite normal GHb concentrations. Chronic hypoglycemic states, like pregnancy and hyperinsulinemic hypoglycemia, were associated with significantly low GSP levels.


CONCLUSIONS
We describe a reproducible and sensitive immunoradiometric assay for GSP that closely reflects the degree of glycemic control in diabetic patients. Further studies are needed to determine whether this assay may be useful in screening for glucose intolerance or gestational diabetes.
Gordon
A
A
Hubert Humphrey Institute for Experimental Medicine, Hebrew University School of Medicine, Jerusalem, Israel.
Glaser
B
B
Wald
M
M
Del Rio
G
G
Della Casa
L
L
Gross
J
J
Cerasi
E
E
D001786:Blood Glucose / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis*; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting; D006023:Glycoproteins; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods; D012016:Reference Values; D000093422:Glycated Serum Proteins
D001786:Blood Glucose; D001798:Blood Proteins; D006023:Glycoproteins; D000093422:Glycated Serum Proteins