To evaluate the relative value of glycosylated serum proteins (GSPs) versus glycosylated hemoglobin (HbA1c) in assessing glycemic control in diabetes mellitus, we performed regular monitoring of GSPs and HbA1c in 30 subjects with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) who performed frequent self-glucose monitoring. Analysis of the relationship between patterns of glycemic control and GSPs and HbA1c demonstrated that subjects with IDDM and NIDDM appeared similar when the more traditional indicators of glycemic control such as mean blood glucose level (166.9 +/- 20.9 v 177.4 +/- 39.6 mg/dL) or HbA1c (83.57 +/- 12.8 v 80.24 +/- 15.7 mmol hydroxymethyl furfuraldehyde [HMF]/mol hemoglobin [Hgb]) were used. However, when GSP levels or the standard deviation of mean glucose levels (SDMG) were used to assess glycemic control, higher levels were found in subjects with IDDM (52 +/- 10.3 mg/g protein and 28.59 +/- 7.60 mg/dL) versus NIDDM (44.6 +/- 15.2 mg/g protein and 21.6 +/- 15.9 mg/dL). Using multivariate analysis, GSPs were predictive of SDMG (P = .046), whereas HbA1c added no significant further information (P = .27). Our results suggest that GSPs may be more sensitive than HbA1c assay to the greater fluctuations in blood glucose levels generally associated with IDDM.