Accumulation of advanced glycation end products is associated with macrovascular events and glycaemic control with microvascular complications in Type 2 diabetes mellitus

AimThe United Kingdom Prospective Diabetes Study (UKPDS) study showed that glycaemic control (HbA(1c)) can predict vascular complications in Type 2 diabetes mellitus. The Diabetes Control and Complications Trial (DCCT) study showed that accumulation of advanced glycation end products (AGEs) from skin biopsies predicts vascular complications in Type 1 diabetes. Previously, we showed that tissue AGEs can be measured non-invasively using skin autofluorescence (SAF). The aim of this study was to compare the predictive value of HbA(1c) and SAF for new macrovascular events and microvascular complications in people with Type2 diabetes. MethodsA prospective cohort study of 563 participants, median age 64years [interquartile range (IQR) 57-72], diabetes duration of 13years, from five Dutch hospitals was performed. ResultsAfter a median follow-up of 5.1 (IQR 4.3-5.9)years, 79 (15%) participants had died and 49 (9%) were lost to follow-up. Some 133 (26%) developed a microvascular complication and 189 (37%) a macrovascular event. Tertiles of HbA(1c) were significantly associated with development of microvascular complications (log rank P=0.022), but not with macrovascular events. Tertiles of SAF were significantly associated with macrovascular events (log rank P=0.003). Cox regression analysis showed SAF was associated with macrovascular events: crude hazard ratio (HR) 1.53 (P<0.001) per unit increase, HR 1.28 (P=0.03) after correction for UKPDS score. HbA(1c) was predictive for microvascular complications: crude HR 1.20 (P=0.004), HR 1.20 (P=0.004) after correction for UKPDS score. ConclusionThis study shows that tissue accumulation of AGEs, assessed by SAF, is associated with development of macrovascular events in people with Type2 diabetes, whereas HbA(1c) is associated with the development of microvascular complications.