Objective: We studied if large artery stiffness is involved in type 2 diabetes pathogenesis. We also investigated the effect of genetic risk for type 2 diabetes in these associations and the causality. Research design and Methods: In the prospective population-based Rotterdam Study (n = 3,055; mean age, 67.2 years), markers of aortic and carotid stiffnesses and measures of arterial remodeling were assessed. Cox proportional hazard regression analysis estimated the associations between arterial stiffness measures with incident type 2 diabetes. We used 403 single nucleotide polymorphisms to calculate the genetic risk score (GRS) for type 2 diabetes. We adopted Mendelian randomization (MR) analysis to evaluate the causal associations. Results: Over a median follow-up of 14.0 years, higher carotid-femoral pulse wave velocity (hazard ratio,1.18; 95 %CI: 1.04–1.35), carotid distensibility coefficient (1.17; 1.04–1.32), and carotid intima-media thickness (1.15; 1.01–1.32) were independently associated with incident diabetes. The associations were stronger among individuals with a higher GRS for type 2 diabetes. MR analysis did not support the causality of the observed associations. Conclusions: Elevated arterial stiffness is independently associated with incident type 2 diabetes. For most arterial stiffness markers, the associations with incident type 2 diabetes were more robust in individuals with a higher GRS for diabetes.
|Journal||Diabetes Research and Clinical Practice|
|Publication status||Published - Feb 2023|
Bibliographical noteFunding Information:
This manuscript is part of a project that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 875534. This joint undertaking supports the European Union's Horizon 2020 research and innovation program and EFPIA and T1D Exchange, JDRF, and Obesity Action Coalition.
Erasmus MC and Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; Netherlands Genomics Initiative; Netherlands Ministry of Education, Culture and Science; Netherlands Ministry of Health, Welfare and Sports; European Commission; and Municipality of Rotterdam.
This study is embedded within the Rotterdam Study (RS), a prospective cohort study of the community-dwelling population aged 55 years and older in Rotterdam, the Netherlands. Briefly, in 1990 all inhabitants (n = 10,215) aged 55 years or over were invited; 7,983 invitees agreed to participate (RS-I). In 2000, 3,011 participants who had reached the age of 55 years (out of 4,472 invitees) were invited to participate in the second cohort (RS-II). There were no eligibility criteria to enter the Rotterdam Study apart from the minimum age and residential area based on postal codes. The Rotterdam Study has been approved by the Medical Ethics Committee of the Erasmus MC (registration number MEC 020.1015) and by the Dutch Ministry of Health, Welfare, and Sport (Population Screening Act WBO, license number 1071272-159521-PG). The Rotterdam Study entered into the Netherlands National Trial Register (NTR; https://www.trialregister.nl) and the WHO International Clinical Trials Registry Platform (ICTRP; https://www.who.int/ictrp/network/primary/en/) under shared catalog number NTR6831. 98 % of participants provided written informed consent to participate in the study and obtain their information from treating physicians. The complete design and rationale behind the Rotterdam Study have been described previously.
© 2023 The Author(s)