The role of reactive metabolites in diabetic complications

Can methylglyoxal predict the onset of diabetes complications?

Aim and purpose
In this project, we investigate the role of methylglyoxal (MG) – a highly reactive physiological metabolite –  and MG-derived, advanced glycation end products (MG-AGEs) in the development of micro- and macrovascular diabetic complications. We aim to assess the value of MG information for the prediction of diabetes complications and hope to gain insight into whether the pathophysiological mechanisms involving MG and MG-AGEs provide a basis for novel therapeutic approaches.

Design and method
The project will be based on blood samples from the ADDITION-Denmark study), a systematic, high-risk screening strategy for type 2 diabetes in general practice with subsequent waves of data collection, including a randomised, multi-factorial intervention1. The study entails lab analyses of samples from the two intervention arms (routine care vs intensive treatment), including a total of 1533 individuals with screen detected type 2 diabetes. We will analyse samples from baseline and 5-yr followup, allowing analyses of changes in MG and MG-AGE levels and the associations with complications e.g. nephropathy and neuropathy. Whereas previous MG investigations have been performed on either animal models or in small scale human studies, the present study will combine lab analyses at a high throughput level with detailed clinical information.

Target group
The clinical setting of this study will enable a direct assessment of the clinical utility of our findings. Ultimately,  the study may help determine which patients are at high risk of developing complications.

Expected outcome
The epidemiological scale of the study and the use of a cluster randomised design based in general practice will enable a direct translation of our findings to the real-life setting of population-wide general practice-based diabetes screening and tailored prevention.
The knowledge we generate about the mechanisms driving the earliest stages of diabetes and its complications will allow us to identify new potential targets for individualised prevention and treatment of type 2 diabetes and associated complications.
We expect to publish the first results from this study in early to mid 2014.

Sidst opdateret 18-08-2015

Troels Mygind Jensen
PhD student
Clinical Epidemiolgy Research
The ADDITION study website

Griffin SJ, Borch-Johnsen K, Davies MJ et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet 2011;378(9786):156-167