SummaryBackground-Metformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown. We aimed to investigate whether metformin treatment (added to titrated insulin therapy) reduced atherosclerosis, as measured by progression of common carotid artery intima-media thickness (cIMT), in adults with type 1 diabetes at increased risk for cardiovascular disease.

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.

Objective: To examine mortality from all causes and from cardiovascular disease (CVD), and CVD hospitalisation rate for a decentralised Aboriginal community in the Northern Territory. Design and participants: For a community‐based cohort of 296 people aged 15 years or older screened in 1995, we reviewed hospital and primary health care records and death certificates for the period up to December 2004 (2800 person‐years of follow‐up). Main outcome measures: Mortality from all causes and CVD, and hospitalisation with CVD coded as a primary cause of admission; comparison with prior trends (1988 to 1995) in CVD risk factor prevalence for the community, and with NT‐specific Indigenous mortality and hospitalisation rates. Results: Mortality in the cohort was 964/100 000 person‐years, significantly lower than that of the NT Indigenous population (standardised mortality ratio [SMR], 0.62; 95% CI, 0.42–0.89). CVD mortality was 358/100 000 person‐years for people aged 25 years or older (SMR, 0.52; 95% CI, 0.23–1.02). Hospitalisation with CVD as a primary cause was 13/1000 person‐years for the cohort, compared with 33/1000 person‐years for the NT Indigenous population. Conclusion: Contributors to lower than expected morbidity and mortality are likely to include the nature of primary health care services, which provide regular outreach to outstation communities, as well as the decentralised mode of outstation living (with its attendant benefits for physical activity, diet and limited access to alcohol), and social factors, including connectedness to culture, family and land, and opportunities for self‐determination.