Intermittent hyperglycemia, characterized by fluctuations in blood glucose levels, has been proposed as a stronger driver of vascular damage than sustained hyperglycemia. This project aims to investigate its role in the development of atherosclerosis. We will use low-density lipoprotein receptor-deficient (Ldlr-/-) mice, a well-established model of atherosclerosis, maintained on a cholesterol-enriched diet to promote lesion formation. To mimic clinical glycemic variability, mice will receive drinking water supplemented with fructose and glucose either continuously or discontinuously, generating sustained versus intermittent hyperglycemia, respectively. We will monitor metabolic parameters, inflammatory markers, and gut microbiota composition to assess systemic and intestinal responses. Atherosclerotic burden will be quantified by histological and morphometric analyses of the aortic root and en face preparations of the aorta.
We hypothesize that intermittent hyperglycemia will exacerbate systemic inflammation and accelerate atherosclerotic lesion development compared with continuous exposure, potentially through enhanced oxidative stress and microbiota dysbiosis. This study will provide mechanistic insights into how glycemic fluctuations influence cardiovascular risk, with implications for the management of diabetic patients.

Paris postdoc seminar series