Greater daily glucose variability and lower time in range assessed with continuous glucose monitoring are associated with greater aortic stiffness: The Maastricht Study

• Published in: Diabetologia Vol. 64; no. 8; pp. 1880 - 1892
• Main Authors: Foreman, Yuri D., van Doorn, William P. T. M., Schaper, Nicolaas C., van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Henry, Ronald M. A., Koster, Annemarie, Eussen, Simone J. P. M., Wesselius, Anke, Reesink, Koen D., Schram, Miranda T., Dagnelie, Pieter C., Kroon, Abraham A., Brouwers, Martijn C. G. J., Stehouwer, Coen D. A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2021; Springer Nature B.V
• Subjects: Aged; Ankle; Aorta; Blood Glucose - metabolism; Blood Glucose Self-Monitoring; Blood Pressure - physiology; Cardiovascular disease; Cardiovascular diseases; Carotid Arteries - physiopathology; Cross-Sectional Studies; Demography; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetic Angiopathies - physiopathology; Disease management; Female; Glucose; Glucose monitoring; Health risks; Human Physiology; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Morbidity; Population studies; Prediabetic State - blood; Prospective Studies; Pulse Wave Analysis; Risk Assessment; Risk factors; Time Factors; Variability; Vascular Stiffness - physiology; Netherlands; Continuous glucose monitoring; Glucose variability; Arterial stiffness; Time in range
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-021-05474-8

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 [SD
CGM
] and CGM-assessed CV [CV
CGM
]) and time in range (TIR
CGM
) 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 SD
CGM
was associated with higher cf-PWV after adjusting for demographics, cardiovascular risk factors and lifestyle factors (regression coefficient [B] per 1 mmol/l SD
CGM
[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
), SD
CGM
and MSG
CGM
contributed similarly to cf-PWV (respective standardised regression coefficients [st.βs] 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 CV
CGM
(B [95% CI] per 10% CV
CGM
: 0.303 m/s [0.046, 0.559],
p
 = 0.021) and lower TIR
CGM
(B [95% CI] per 10% TIR
CGM
: −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 TIR
CGM
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 TIR
CGM
to prevent CVD.
Graphical abstract