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

Yuri D. Foreman (Corresponding author), Martijn C.G.J. Brouwers, Tos T.J.M. Berendschot, Martien C.J.M. van Dongen, Simone J.P.M. Eussen, Marleen M.J. van Greevenbroek, Ronald M.A. Henry, Alfons J.H.M. Houben, Carla J.H. van der Kallen, Abraham A. Kroon, Koen D. Reesink, Miranda T. Schram, Nicolaas C. Schaper, Coen D.A. Stehouwer

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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 HbA1c 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 [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. Results: Higher 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]). 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.

Original languageEnglish
Article number152
Number of pages12
JournalCardiovascular Diabetology
Volume18
Issue number1
DOIs
Publication statusPublished - 14 Nov 2019

Funding

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), Care and Public Health Research Institute (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).

Keywords

  • Arterial remodeling
  • Arterial stiffness
  • Glucose metabolism status
  • Glucose variability
  • Oral glucose tolerance test

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