We investigated whether glycation gap (G-Gap), an index of intracellular glycation of proteins, was associated with diabetes complications.
We measured concomitantly HbA 1c and fructosamine in 925 patients with type 2 diabetes to calculate the G-Gap, defined as the difference between measured HbA 1c, and fructosamine-based predicted HbA 1c. Patients were explored for retinopathy, nephropathy, peripheral neuropathy, cardiac autonomic neuropathy ( n = 512), and silent myocardial ischemia ( n = 506).
Macroproteinuria was the only complication that was associated with G-Gap (prevalence in the first, second, and third tertile of G-Gap: 2.9, 6.2, and 11.0%, respectively; P < 0.001). The G-Gap was higher in patients with macroproteinuria than in those without (1.06 ± 1.62 vs. 0.03 ± 1.30%; P < 0.0001). Because HbA 1c was associated with both G-Gap (HbA 1c 7.0 ± 1.4, 7.9 ± 1.4, and 10.1 ± 1.8% in the first, second, and third G-Gap tertile, respectively; P < 0.0001) and macroproteinuria (HbA 1c 8.8 ± 2.2% if macroproteinuria, 8.3 ± 2.0% if none; P < 0.05), and because it could have been a confounder, we matched 54 patients with macroproteinuria and 200 patients without for HbA 1c. Because macroproteinuria was associated with lower serum albumin and fructosamine levels, which might account for higher G-Gap, we calculated in this subpopulation albumin-indexed fructosamine and G-Gap; macroproteinuria was independently associated with male sex (odds ratio [OR] 3.2 [95% CI 1.5–6.7]; P < 0.01), hypertension (2.9 [1.1–7.5]; P < 0.05), and the third tertile of albumin-indexed G-Gap (2.3 [1.1–4.4]; P < 0.05) in multivariate analysis.