Association of Glycation Gap With Mortality and Vascular Complications in Diabetes

Abstract

OBJECTIVEThe “glycation gap” (G-gap), an essentially unproven concept, is an empiric measure of disagreement between HbA1c and fructosamine, the two indirect estimates of glycemic control. Its association with demographic features and key clinical outcomes in individuals with diabetes is uncertain.RESEARCH DESIGN AND METHODSThe G-gap was calculated as the difference between measured HbA1c and a fructosamine-derived standardized predicted HbA1c in 3,182 individuals with diabetes. The G-gap’s associations with demographics and clinical outcomes (retinopathy, nephropathy, macrovascular disease, and mortality) were determined.RESULTSDemographics varied significantly with G-gap for age, sex, ethnic status, smoking status, type and duration of diabetes, insulin use, and obesity. A positive G-gap was associated with retinopathy (odds ratio 1.24 [95% CI 1.01–1.52], P = 0.039), nephropathy (1.55 [1.23–1.95], P < 0.001), and, in a subset, macrovascular disease (1.91 [1.18–3.09], P = 0.008). In Cox regression analysis, the G-gap had a “U”-shaped quadratic relationship with mortality, with both negative G-gap (1.96 [1.50–2.55], P < 0.001) and positive G-gap (2.02 [1.57–2.60], P < 0.001) being associated with a significantly higher mortality.CONCLUSIONSWe confirm published associations of G-gap with retinopathy and nephropathy. We newly demonstrate a relationship with macrovascular and mortality outcomes and potential links to distinct subpopulations of diabetes.

Association between hemoglobin glycation index and hepatic steatosis in non-diabetic individuals

“…Hempe et al [18] and McCarter et al [21] have observed that a higher HGI level, calculated using self-glucose monitoring data to predict the value of HbA1c, is associated with a greater risk of developing nephropathy and retinopathy in patients with type 1 diabetes. Several studies have demonstrated a positive association between micro-and macrovascular complications of type 2 diabetes and glycation gap, an analogue measure of the discordance between the observed and the predicted levels of HbA1c, calculated as HGI except that fructosamine concentrations replace blood glucose levels in the formula used to calculate predicted HbA1c [34][35][36][37]. An increased HGI level, calculated using fasting plasma glucose concentration to predict HbA1c value, has been recently shown to identify a subgroup of the ACCORD population with a greater risk of diabetic complications, hypoglycemia and total mortality [22].…”

The Hemoglobin Glycation Index Identifies Subpopulations With Harms or Benefits From Intensive Treatment in the ACCORD Trial

“…The glycation gap developed by Cohen et al ( 5 ) is calculated in exactly the same way as HGI except fructosamine replaces directly measured glucose for obtaining a predicted HbA 1c . Several studies have shown that patients with type 2 diabetes with a high glycation gap have greater risk for microvascular or macrovascular complications ( 5 , 10 , 13 , 14 ). HGI and the glycation gap are strongly positively correlated, which suggests they reflect the same biological phenomenon ( 15 ).…”

The Glucose Measurement Industry and Hemoglobin A1c

“…Some medical investigators state these glycation gaps are associated with increased diabetic morbidity and mortality. 13 …”