Abstract
BackgroundDaily 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 HbA1c and other confounders.MethodsIGP 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 [CWSmean] and pulsatile [CWSpuls] circumferential wall stress), and microvascular function (retinal arteriolar average dilatation; heat-induced skin hyperemia) via multiple linear regression with adjustment for age, sex, HbA1c, cardiovascular risk factors, lifestyle factors, and medication use.ResultsHigher IGP was independently associated with higher cf-PWV (regression coefficient [B]: 0.054 m/s [0.020; 0.089]) and with higher CWSmean (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]), CWSpuls (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]).ConclusionsIGP 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.
Highlights
Glucose variability may contribute to vascular complication development irrespective of mean glucose values
In view of the aforementioned, we investigated, in a large population-based cohort, whether incremental glucose peak (IGP) is associated with arterial stiffness, arterial remodeling, and microvascular function, independent of HbA1c
Some participants had incomplete data on the seven-point oral glucose tolerance test (OGTT), either because of missing glucose samples (n = 368) or an OGTT contraindication (n = 238; i.e. insulin use or plasma glucose levels > 11.0 mmol/L before initiation of the OGTT), resulting in a study population of 2804 individuals. Those with missing glucose samples were generally comparable to the final study population (Additional file 1: Table S1); as expected, those with an OGTT contraindication differed statistically significantly from the carotid-femoral pulse wave velocity, carDC carotid distensibility coefficient, cIMT carotid intima-media thickness, CWSmean mean circumferential wall stress, CWSpuls pulsatile circumferential wall stress final study population with regard to almost all characteristics (Additional file 1: Table S1)
Summary
Glucose variability may contribute to vascular complication development irrespective of mean glucose values. Foreman et al Cardiovasc Diabetol (2019) 18:152 hyperglycemia and endothelial dysfunction are considered to be bidirectionally related, potentially entering a vicious cycle that could lead to microvascular complications [6]. Of note, these pathophysiologic processes have been shown to already occur in the prediabetic state [7, 8]. Glucose variability could play a role in vascular complication development irrespective of mean glucose values [10]. While relatively small observational studies have found conflicting results regarding the association between glucose variability and classic diabetic complications [11,12,13], experimental studies have shown that greater glucose variability can be harmful independent of mean glucose values [14, 15]
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