J Shen1,2, K Reesink1,3, M Schram1,4,5,6, BE de Galan1,2,7, CG Schalkwijk1,2, MMJ van Greevenbroek1,2
1CARIM, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands. 2Department of Internal Medicine, Maastricht University Medical Center+ (MUMC+), Maastricht, the Netherlands. 3Department of Biomedical Engineering, Maastricht University, Maastricht, the Netherlands. 4Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. 5MheNS, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands. 6Heart and Vascular Center, Maastricht University Medical Center+ (MUMC+), Maastricht, Netherlands. 7Department of internal medicine, Radboud University Medical Center, Nijmegen, the Netherlands. E-mail: jie.shen@maastrichtuniversity.nl.
Background: Arterial stiffness may contribute to organ damage via potential reduced local metabolism, possibly resulting from microvascular damage in local tissues. The pancreas and in particular the islets and the beta cells therein are exposed to high blood flow and may, therefore, also be affected by arterial stiffness. However, few to no studies have related arterial stiffness to beta cell dysfunction.
Methods: In 2053 participants (60.0±8.0years, 50.2% male, 21.8% type 2 diabetes (T2D)), oral glucose tolerance tests were performed to generate beta cell function (BCF) measurements including C-peptidogenic indext0-30, overall insulin secretion index, beta cell glucose sensitivity, beta cell potentiation factor and beta cell rate sensitivity. An overall BCF score was calculated as the average of the five standardized BCF measurements followed by re-standardization. Arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV). BCF measurements and cfPWV were ln-transformed and standardized. Linear regression was used to assess the cross-sectional associations between cfPWV and BCF indices. Potential confounders included demographics, physical activity, diet, body mass index, insulin resistance, heart rate, and mean arterial pressure.
Results: In the fully adjusted models, cfPWV was inversely associated with overall BCF score (standardized β: -0.10 [95% CI -0.16; -0.05]). In line, cfPWV was inversely associated with C-peptidogenic indext0-30 (-0.06 [-0.12; -0.01]), overall insulin secretion index (-0.06 [-0.11; -0.01]), beta cell glucose sensitivity (-0.06 [-0.11; -0.00]), beta cell potentiation factor (-0.12 [-0.17; -0.07]), and with beta cell rate sensitivity (-0.04 [-0.09; 0.01]). Interaction analyses showed that glucose metabolism status did not modify these associations.
Discussion/Conclusion: In this middle-aged population, arterial stiffness, measured as cfPWV, was consistently associated with worse beta cell function. Thus, an increase in arterial stiffening may contribute to impaired (regulation of) synthesis and secretion of insulin and further to the risk of the development and progression of T2D.