Research Article Relationship of Hyperglycaemia, Hypoglycaemia, and Glucose Variability to Atherosclerotic Disease in Type 2 Diabetes Caroline Jane Magri , 1,2 Dillon Mintoff , 3 Liberato Camilleri , 4 Robert G. Xuereb, 2 Joseph Galea, 5 and Stephen Fava 5 1 Department of Cardiology, Mater Dei Hospital and University of Malta, Msida, Malta 2 Department of Cardiology, Mater Dei Hospital, Msida, Malta 3 Mater Dei Hospital, Msida, Malta 4 Statistics & Operations Research, Faculty of Science, University of Malta, Msida, Malta 5 Mater Dei Hospital and University of Malta, Msida, Malta Correspondence should be addressed to Stephen Fava; stephen.fava@um.edu.mt Received 2 January 2018; Revised 1 June 2018; Accepted 24 June 2018; Published 22 July 2018 Academic Editor: Andrea Flex Copyright © 2018 Caroline Jane Magri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Type 2 diabetes mellitus (T2DM) is known to be associated with increased cardiovascular risk. The aim of this study was therefore to investigate the independent effects of hyperglycaemia, hypoglycaemia, and glucose variability on microvascular and macrovascular disease in T2DM. Methods. Subjects with T2DM of <10 years duration and on stable antiglycaemic treatment underwent carotid intima-media thickness (CIMT), ankle-brachial index (ABI), albumin-creatinine ratio (ACR), and HbA 1c measurement, as well as 72-hour continuous glucose monitoring. Macrovascular disease was defined as one or more of the following: history of ischaemic heart disease (IHD), cerebrovascular accident (CVA), ABI < 0.9, or abnormal CIMT. Results. The study population comprised 121 subjects with T2DM (89 males : 32 females). The mean age was 62.6 years, and the mean DM duration was 3.7 years. Macrovascular disease was present in 71 patients (58.7%). In multivariate logistic regression analysis, body surface area (BSA) (OR 18.88 (95% CI 2.20–156.69), p =0 006) and duration of blood glucose (BG) < 3.9 mmol/L (OR 1.12 (95% CI 1.014–1.228), p =0 024) were independent predictors of macrovascular disease. BSA (OR 12.6 (95% CI 1.70–93.54), p =0 013) and duration of BG < 3.9 mmol/L (OR 1.09 (95% CI 1.003–1.187), p =0 041) were independent predictors of abnormal CIMT. Area under the curve for BG > 7.8 mmol/L (β = 15.83, p =0 005) was the sole independent predictor of albuminuria in generalised linear regression. Conclusions. This study demonstrates that hypoglycaemia is associated with the occurrence of atherosclerotic disease while hyperglycaemia is associated with microvascular disease in a Caucasian population with T2DM of recent duration. 1. Introduction Diabetes is known to be associated with both microvascular and macrovascular disease [1]. Whilst good glycaemic con- trol has been consistently shown to reduce microvascular dis- ease, most intervention studies have failed to document a reduction in macrovascular disease outcomes [2, 3]. One possible explanation for this discrepancy is the det- rimental effect of hypoglycaemia. Östgren and colleagues have recently reported a U-shaped relationship of HbA 1c with cardiovascular events, including mortality [4]. A recent meta-analysis has also confirmed that hypoglycaemia is associated with a twofold increased risk of cardiovascular dis- ease in type 2 diabetes [5]. Furthermore, both hyperglycae- mia and hypoglycaemia following acute coronary syndrome have been associated with increased mortality [6, 7] The tra- ditional explanations of these observations are the proar- rhythmogenic effect of hypoglycaemia as a consequence of catecholamine release and QTc prolongation [8, 9] and the unavailability of an energy substrate to the myocardium dur- ing hypoglycaemia leading to an ischaemia equivalent [10]. However, the increased mortality extends beyond the hypo- glycaemic episode itself. Although a hypoglycaemic episode is known to predict future ones [11], this is unlikely to be Hindawi Journal of Diabetes Research Volume 2018, Article ID 7464320, 9 pages https://doi.org/10.1155/2018/7464320