The oral glucose tolerance test-derived incremental glucose peak is associated with greater arterial stiffness and maladaptive arterial remodeling: The Maastricht Study

Abstract

Background: Daily glucose variability may contribute to vascular complication development irrespective of mean glucose values. The incremental glucose peak (IGP) during an oral glucose tolerance test (OGTT) can be used as a proxy of glucose variability. We investigated the association of IGP with arterial stiffness, arterial remodeling, and microvascular function, independent of HbA_1c and other confounders.

Methods: IGP was calculated as the peak minus baseline plasma glucose value during a seven-point OGTT in 2758 participants (age: 60 ± 8 years; 48% women) of The Maastricht Study, an observational population-based cohort. We assessed the cross-sectional associations between IGP and arterial stiffness (carotid-femoral pulse wave velocity [cf-PWV], carotid distensibility coefficient [carDC]), arterial remodeling (carotid intima-media thickness [cIMT]; mean [CWS_mean] and pulsatile [CWS_puls] circumferential wall stress), and microvascular function (retinal arteriolar average dilatation; heat-induced skin hyperemia) via multiple linear regression with adjustment for age, sex, HbA_1c, cardiovascular risk factors, lifestyle factors, and medication use.

Results: Higher IGP was independently associated with higher cf-PWV (regression coefficient [B]: 0.054 m/s [0.020; 0.089]) and with higher CWS_mean (B: 0.227 kPa [0.008; 0.446]). IGP was not independently associated with carDC (B: - 0.026 10^-3/kPa [- 0.112; 0.060]), cIMT (B: - 2.745 µm [- 5.736; 0.245]), CWS_puls (B: 0.108 kPa [- 0.054; 0.270]), retinal arteriolar average dilatation (B: - 0.022% [- 0.087; 0.043]), or heat-induced skin hyperemia (B: - 1.380% [- 22.273; 19.513]).

Conclusions: IGP was independently associated with aortic stiffness and maladaptive carotid remodeling, but not with carotid stiffness, cIMT, and microvascular function measures. Future studies should investigate whether glucose variability is associated with cardiovascular disease.

Keywords: Arterial remodeling; Arterial stiffness; Glucose metabolism status; Glucose variability; Oral glucose tolerance test.

Fig. 1

Flowchart of the IGP study population selection process. OGTT oral glucose tolerance test, IGP incremental glucose peak, cf-PWV carotid-femoral pulse wave velocity, carDC carotid distensibility coefficient, cIMT carotid intima-media thickness, CWS_mean mean circumferential wall stress, CWS_puls pulsatile circumferential wall stress

Fig. 2

Multivariable-adjusted associations of incremental glucose peak (IGP) and arterial stiffness and arterial remodeling. Regression coefficients (B) indicate the mean difference (95% confidence interval) associated with 1 unit (mmol/L) increase of IGP. The panels depict the a associations between IGP and carotid-femoral pulse wave velocity (cf-PWV); b associations between IGP and carotid distensibility coefficient (carDC); c associations between IGP and carotid intima-media thickness (cIMT); d associations between IGP and mean circumferential wall stress (CWS_mean); e associations between IGP and pulsatile circumferential wall stress (CWS_puls). Model 1: crude. Model 2: additionally adjusted for age and sex. Model 3: additionally adjusted for HbA_1c. Model 4: additionally adjusted for mean arterial pressure and mean heart rate (cf-PWV), mean arterial pressure (carDC, CWS_puls), office systolic blood pressure (cIMT) or carotid pulse pressure (CWS_mean). Model 5: additionally adjusted for body mass index, smoking status, physical activity, Mediterranean diet score, use of antihypertensive and lipid-modifying drugs, fasting triglycerides, and total-to-HDL cholesterol levels