Accumulation of Advanced Glycation Endproducts is Associated with Macrovascular Complications and Mortality, and Glycaemic Control with Microvascular Complications in Type 2 Diabetes Mellitus

Yozgatli, K. (Kadir) (2015) Accumulation of Advanced Glycation Endproducts is Associated with Macrovascular Complications and Mortality, and Glycaemic Control with Microvascular Complications in Type 2 Diabetes Mellitus. thesis, Medicine.

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Abstract

Background The UK Prospective Diabetes Study (UKPDS) showed in the nineties that glycaemic control (HbA1c) can predict vascular complications in type 2 diabetes mellitus (T2DM). More recently, the role of Advanced Glycation Endproducts (AGEs) accumulation in the development of cardiovascular complications in T2DM is increasingly acknowledged. The DCCT Trial showed that accumulation of AGEs from skin biopsies can predict vascular complications in type 1 diabetes mellitus. Nowadays, tissue AGEs can be measured non-invasively with the use of Skin Auto Fluorescence (SAF) properties and the AGE-Reader. The primary aim of this study was to evaluate the associations between SAF and the development of both macrovascular complications and microvascular complications in secondary care patients with T2DM. Our secondary aim was to compare these results with the UKPDS risk score calculations. Methods and results A prospective cohort study of 514 T2DM patients (mean age 69±11 years, T2DM duration 18 years) from five Dutch hospitals was performed. Clinical status was assessed from April 2007 till January 2015. After a median follow-up of 5.1 (IQR 4.3-5.9) years, 79 (15%) patients died and 49 (9%) were lost to follow-up. 189 (37%) patients developed a macrovascular complication and 133 (26%) patients a microvascular complication. Tertiles of SAF were significantly associated with the development of macrovascular complications in Kaplan-Meier analysis (logrank p=0.003) but not for microvascular complications. However, tertiles of HbA1c were not associated with macrovascular complications, but only for the development of microvascular complications (logrank p=0.022). Cox regression analysis for SAF gave a hazard ratio (HR) of 1.53 (95%CI 1.24-1.89), p=0.0007 per unit (SAF) increase in the development of macrovascular complications. After correction for the UKPDS risk score the HR stayed significant: HR 1.28 (1.03-1.60), p=0.026. For HbA1c and microvascular complications a crude HR 1.20 (1.06-1.36), p=0.004 was found. The HR did not change after correction for the UKPDS score: HR 1.20 (1.06-1.36), p=0.004. Conclusion This study shows after 5-years of follow-up that accumulation of AGEs is associated with the development of macrovascular complications in patients with T2DM. Furthermore, glycaemic control (HbA1c) is associated with the development of microvascular complications.

Item Type:	Thesis (Thesis)
Supervisor name:	Smit, Prof. Dr .A.J. and Department of Vascular Medicine University Medical Centre Gr
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:04
Last Modified:	25 Jun 2020 11:04
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2394

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