TY - JOUR
T1 - Greater daily glucose variability and lower time in range assessed with continuous glucose monitoring are associated with greater aortic stiffness
T2 - The Maastricht Study
AU - Foreman, Yuri D.
AU - van Doorn, William P. T. M.
AU - Schaper, Nicolaas C.
AU - van Greevenbroek, Marleen M. J.
AU - van der Kallen, Carla J. H.
AU - Henry, Ronald M. A.
AU - Koster, Annemarie
AU - Eussen, Simone J. P. M.
AU - Wesselius, Anke
AU - Reesink, Koen D.
AU - Schram, Miranda T.
AU - Dagnelie, Pieter C.
AU - Kroon, Abraham A.
AU - Brouwers, Martijn C. G. J.
AU - Stehouwer, Coen D. A.
N1 - Funding Information:
The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs (grant 31O.041), Stichting De Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), School for Cardiovascular Diseases (CARIM, Maastricht, the Netherlands), School for Public Health and Primary Care (CAPHRI, Maastricht, the Netherlands), School for Nutrition and Translational Research in Metabolism (NUTRIM, Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), Health Foundation Limburg (Maastricht, the Netherlands), and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands), Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands), and Medtronic (Tolochenaz, Switzerland). The funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.
Funding Information:
The authors are grateful to the participants of The Maastricht Study and to all research personnel involved. In addition, The Regional Association of General Practitioners (Zorg in Ontwikkeling [ZIO]) is gratefully acknowledged for enabling The Maastricht Study to invite individuals with type 2 diabetes based on their electronic health records. NCS, RMAH, and MCGJB were supported by Medtronic (External Research Program). Medtronic did not direct design, conduct or outcomes of this study. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/8
Y1 - 2021/8
N2 - Aims CVD is the main cause of morbidity and mortality in individuals with diabetes. It is currently unclear whether daily glucose variability contributes to CVD. Therefore, we investigated whether glucose variability is associated with arterial measures that are considered important in CVD pathogenesis.Methods We included participants of The Maastricht Study, an observational population-based cohort, who underwent at least 48 h of continuous glucose monitoring (CGM) (n = 853; age: 59.9 +/- 8.6 years; 49% women, 23% type 2 diabetes). We studied the cross-sectional associations of two glucose variability indices (CGM-assessed SD [SDCGM] and CGM-assessed CV [CVCGM]) and time in range (TIRCGM) with carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient, carotid intima-media thickness, ankle-brachial index and circumferential wall stress via multiple linear regression.Results Higher SDCGM was associated with higher cf-PWV after adjusting for demographics, cardiovascular risk factors and lifestyle factors (regression coefficient [B] per 1 mmol/l SDCGM [and corresponding 95% CI]: 0.413 m/s [0.147, 0.679], p = 0.002). In the model additionally adjusted for CGM-assessed mean sensor glucose (MSG(CGM)), SDCGM and MSG(CGM) contributed similarly to cf-PWV (respective standardised regression coefficients [st.beta s] and 95% CIs of 0.065 [-0.018, 0.167], p = 0.160; and 0.059 [-0.043, 0.164], p = 0.272). In the fully adjusted models, both higher CVCGM (B [95% CI] per 10% CVCGM: 0.303 m/s [0.046, 0.559], p = 0.021) and lower TIRCGM (B [95% CI] per 10% TIRCGM: -0.145 m/s [-0.252, -0.038] p = 0.008) were statistically significantly associated with higher cf-PWV. Such consistent associations were not observed for the other arterial measures.Conclusions Our findings show that greater daily glucose variability and lower TIRCGM are associated with greater aortic stiffness (cf-PWV) but not with other arterial measures. If corroborated in prospective studies, these results support the development of therapeutic agents that target both daily glucose variability and TIRCGM to prevent CVD.
AB - Aims CVD is the main cause of morbidity and mortality in individuals with diabetes. It is currently unclear whether daily glucose variability contributes to CVD. Therefore, we investigated whether glucose variability is associated with arterial measures that are considered important in CVD pathogenesis.Methods We included participants of The Maastricht Study, an observational population-based cohort, who underwent at least 48 h of continuous glucose monitoring (CGM) (n = 853; age: 59.9 +/- 8.6 years; 49% women, 23% type 2 diabetes). We studied the cross-sectional associations of two glucose variability indices (CGM-assessed SD [SDCGM] and CGM-assessed CV [CVCGM]) and time in range (TIRCGM) with carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient, carotid intima-media thickness, ankle-brachial index and circumferential wall stress via multiple linear regression.Results Higher SDCGM was associated with higher cf-PWV after adjusting for demographics, cardiovascular risk factors and lifestyle factors (regression coefficient [B] per 1 mmol/l SDCGM [and corresponding 95% CI]: 0.413 m/s [0.147, 0.679], p = 0.002). In the model additionally adjusted for CGM-assessed mean sensor glucose (MSG(CGM)), SDCGM and MSG(CGM) contributed similarly to cf-PWV (respective standardised regression coefficients [st.beta s] and 95% CIs of 0.065 [-0.018, 0.167], p = 0.160; and 0.059 [-0.043, 0.164], p = 0.272). In the fully adjusted models, both higher CVCGM (B [95% CI] per 10% CVCGM: 0.303 m/s [0.046, 0.559], p = 0.021) and lower TIRCGM (B [95% CI] per 10% TIRCGM: -0.145 m/s [-0.252, -0.038] p = 0.008) were statistically significantly associated with higher cf-PWV. Such consistent associations were not observed for the other arterial measures.Conclusions Our findings show that greater daily glucose variability and lower TIRCGM are associated with greater aortic stiffness (cf-PWV) but not with other arterial measures. If corroborated in prospective studies, these results support the development of therapeutic agents that target both daily glucose variability and TIRCGM to prevent CVD.
KW - Arterial stiffness
KW - Continuous glucosemonitoring
KW - Glucose variability
KW - Time in range
KW - ALL-CAUSE MORTALITY
KW - ARTERIAL STIFFNESS
KW - GLYCEMIC VARIABILITY
KW - DIABETIC COMPLICATIONS
KW - MYOCARDIAL-INFARCTION
KW - COGNITIVE PERFORMANCE
KW - CARDIOVASCULAR RISK
KW - OXIDATIVE STRESS
KW - INDIVIDUALS
KW - MECHANISMS
U2 - 10.1007/s00125-021-05474-8
DO - 10.1007/s00125-021-05474-8
M3 - Article
C2 - 33991193
SN - 0012-186X
VL - 64
SP - 1880
EP - 1892
JO - Diabetologia
JF - Diabetologia
IS - 8
ER -