5 Early development of a predictive tool of ‘type-2 diabetes associated cardiovascular risk’ using malondialdehyde changes in the skin

<h3></h3> Levels of Malondialdehyde (MDA), the lipid peroxidation end product, have been shown to be significantly elevated in type 2 diabetes (T2D), and considered to be indicative of underlying microvascular complications.^{1 2} Predicting cardiovascular risk in skin, could be a convenient early biomarker to inform effective disease management.³ This pilot study explored whether changes to experimental conditions mimicking diabetes (IL-6 and increased glucose) would induce changes in MDA using a skin model. Mouse skin from C57/Bl6 mice was obtained from the University of Manchester. The tissue was shaved and small pieces of approximately 50mg were dissected and weighed. Samples were incubated for 24 hours in 3pg/mL or 9pg/mL IL-6, or 5.5mmol/L and 20mmol/L glucose, reflecting normal and pathophysiological levels in both cases. Non-treated tissue was used as control. MDA was measured using the Malondialdehyde (MDA) Colorimetric Assay Kit (TBA Method) (Elabscience®). In both IL-6 and glucose experiments, there was a significant increase in MDA detected compared with untreated control (p&lt;0.05, n=3). Furthermore, this was significantly increased at 9pg/mL compared with 3pg/mL IL-6 and at 20mmol/L versus 5.5mmol/L glucose. The increase in MDA was significantly reduced when samples were co-incubated with Superoxide dismutase (SOD) (3pg/mL: p&lt;0.001, n=3 and 9pg/mL: p&lt;0.001, n=3), though MDA levels were still significantly greater in the 9pg/ml IL-6 + SOD treated group than those observed at 0 and 3pg/mL in the presence of SOD. These very early data are a proof of principle for developing an effective and personalised predictive tool for cardiovascular risk. Further studies determining relevance to chronic T2D and the clinical situation are required. <h3>References</h3> Priyanka B, Prashanta B, Madhusnata D. Lipid peroxidation: a biomarker of oxidative stress in type 2 diabetes mellitus. [(accessed on 15 July 2022)];Malays. <i>J. Med. Res.</i> 2018;<b>2</b>:61–66. Mahreen R, Mohsin M, Nasreen Z, Siraj M, Ishaq M. Significantly increased levels of serum malonaldehyde in type 2 diabetics with myocardial infarction. <i>Int. J. Diabetes Dev. Ctries.</i> 2010;<b>30</b>:49–51. Lutgers HL, <i>et al</i>. Skin autofluorescence provides additional information to the UK prospective diabetes study (UKPDS) risk score for the estimation of cardiovascular prognosis in Type 2 diabetes mellitus. <i>Diabetologia</i> 2009;<b>52</b>:789–797. 1308-9.