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Aims In addition to hyperglycaemia, glycaemic variability seems to be associated with poor outcomes after acute myocardial infarction. This study explored the impact of glycaemic variability in diabetic Wistar rats subjected to myocardial ischaemia/reperfusion. Methods Animals with streptozotocin-induced diabetes received insulin either to maintain stable hyperglycaemia (Dh group) or to generate glycaemic variability (Dv). After experimental myocardial ischaemia/reperfusion was surgically induced, 7T cardiac magnetic resonance imaging (CMR) was performed at weeks 1 (w1) and 3 (w3). Results Twenty-six rats were randomized [sham group (S): n = 5; control group (C): n = 7; Dh group: n = 6; and Dv group: n = 8]. The mean amplitude of glucose reflecting glycaemic variability was higher in the Dv than in the Dh group (9.1 ± 2.7 mmol/L vs 5.9 ± 1.9 mmol/L; P < 0.05). CMR assessment at w3 revealed ventricular enlargement in both Dh and Dv groups compared with the C and S groups (end-diastolic volume: 1.60 ± 0.22 and 1.36 ± 0.30 mL/kg compared with 1.11 ± 0.13 and 0.87 ± 0.11 mL/kg, respectively; P < 0.05). Circumferential strain was altered between w1 and w3 in the remote area only in the Dv group, resulting in a lower value in this group than in the S, C and Dh groups (−0.11 ± 0.01 vs −0.17 ± 0.05, −0.15 ± 0.03 and −0.16 ± 0.03, respectively; P < 0.05). In addition, at w3, oedema was also higher in the remote area in the Dv than in the C group (18.3 ± 4.9 ms vs 14.5 ± 1.7 ms, respectively; P < 0.05). Conclusion In the context of experimental myocardial ischaemia/reperfusion, our results suggest that glycaemic variability might have a potentially deleterious impact on myocardial outcomes beyond the classical glucose metrics. [ABSTRACT FROM AUTHOR]

Background/aim The number of diabetic people never ceased to increase over the last decades. Cardiovascular (CV) disease is the primary cause of death in diabetic patients. Many studies have investigated the effects of glycemic variability on CV events, and some of these proposed glycemic variability as one of the factors associated with CV disease. Simple models can be used to investigate molecular mechanisms involved. The aim of this study was to investigate the impact of glucose fluctuations on cellular and mitochondrial functions in HL-1 cardiac cell line. Methods/results HL-1 cells were subjected to a 12 hours treatment. This treatment consisted in a several glucose concentrations exposure: 2 mM (low glucose [LG]), 5 mM (normal glucose [NG]), and 25 mM (high glucose [HG]). A fourth condition consisted in glucose fluctuations, every two hours, between 2 and 25 mM (intermittent high glucose [IHG]). After treatment, cells were harvested and several cellular and mitochondrial mechanisms were tested. We measured the oxygen consumption on permeabilized cells using polarography, with different substrates. IHG and HG conditions significantly enhance oxygen consumption compared with LG condition. We also evaluated activation of p38 and Akt proteins by Western blot. IHG significantly increased p38 and Akt phosphorylation compared with LG and NG conditions, respectively. Mitochondrial membrane potential was also determined, using a mitochondria specific fluorescent probe, TMRE. Mitochondrial membrane potential was significantly increased for IHG condition compared to LG and NG. Conclusion These data indicate that glucose fluctuations increase both p38 and Akt activation in HL-1 cells. Oxygen consumption and mitochondrial membrane potential were also increased for cells treated with IHG. Further studies to explore the cellular and mitochondrial mechanisms involved are required, particularly oxidative stress and cell death. [ABSTRACT FROM AUTHOR]