Hyperglycemia Is the Main Mediator of Prediabetes- and Type 2 Diabetes–Associated Impairment of Microvascular Function: The Maastricht Study
- Ben M. Sörensen1,2,
- Alfons J.H.M. Houben1,2,
- Tos T.J.M. Berendschot3,
- Jan S.A.G. Schouten3,
- Abraham A. Kroon1,2,
- Carla J.H. van der Kallen1,2,
- Ronald M.A. Henry1,2,4,
- Annemarie Koster5,6,
- Koen D. Reesink1,7,
- Pieter C. Dagnelie1,5,8,
- Nicolaas C. Schaper1,2,5,
- Casper G. Schalkwijk1,2,
- Miranda T. Schram1,2,4 and
- Coen D.A. Stehouwer1,2⇑
- 1School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands
- 2Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands
- 3University Clinic for Ophthalmology, Maastricht University Medical Center+, Maastricht, the Netherlands
- 4Heart and Vascular Center, Maastricht University Medical Center+, Maastricht, the Netherlands
- 5Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
- 6Department of Social Medicine, Maastricht University, Maastricht, the Netherlands
- 7Department of Biomedical Engineering, Maastricht University, Maastricht, the Netherlands
- 8Department of Epidemiology, Maastricht University, Maastricht, the Netherlands
- Corresponding author: Coen D.A. Stehouwer, cda.stehouwer{at}mumc.nl.
Article Figures & Tables
Tables
- Table 1
General characteristics and retinal and skin measures for the retinal study population according to glucose metabolism status
Characteristics NGM (n = 1,040) Prediabetes (n = 276) T2D (n = 475) Age (years) 58.0 ± 8.2 61.5 ± 7.2 62.9 ± 7.6 Women 596 (57.3) 130 (47.1) 147 (30.9) Diabetes duration (years)* — — 6.0 (3.0–12.0) Diabetes medication use Any type — — 359 (75.6) Insulin — — 86 (18.1) Oral glucose-lowering medication — — 338 (71.2) BMI (kg/m2) 25.5 ± 3.4 27.5 ± 4.0 29.5 ± 4.5 Waist circumference (cm) Men 96.3 ± 9.1 101.6 ± 9.4 106.7 ± 11.6 Women 85.6 ± 9.7 92.7 ± 12.1 100.9 ± 13.6 Smoking Never/former/current, n 409/502/116 75/161/33 136/264/62 Never/former/current, % 39.8/48.9/11.3 27.9/59.9/12.3 29.4/57.1/13.4 History of cardiovascular disease 116 (11.4) 30 (11.2) 118 (25.8) eGFR (mL/min/1.73 m2) 89.9 ± 13.0 87.2 ± 14.0 85.3 ± 17.2 eGFR <60 mL/min/1.73 m2 18 (1.7) 10 (3.6) 45 (9.5) (Micro)albuminuria† 47 (4.6) 15 (5.4) 77 (16.2) Retinopathy 1 (0.1) 1 (0.4) 18 (3.9) Composite indices of potential mediators‡ Markers of hyperglycemia HbA1c (%)‡ 5.4 ± 0.4 5.7 ± 0.4 6.8 ± 0.9 HbA1c (mmol/mol) 35.8 ± 3.7 38.4 ± 4.5 50.6 ± 9.9 Fasting glucose (mmol/L)‡ 5.2 ± 0.4 5.9 ± 0.6 7.7 ± 1.7 2-h postload glucose (mmol/L)‡§ 5.4 ± 1.1 8.2 ± 1.7 14.2 ± 3.9 Skin autofluorescence (AU)‡ 2.3 ± 0.5 2.4 ± 0.5 2.6 ± 0.6 Markers of blood pressure Ambulatory 24-h SBP (mmHg)‡ 117.3 ± 11.1 120.1 ± 11.9 122.4 ± 11.7 Ambulatory 24-h DBP (mmHg)‡ 73.6 ± 7.2 74.5 ± 7.3 73.0 ± 7.0 Antihypertensive medication use‡ 226 (21.7) 113 (40.9) 333 (70.1) Markers of lipid profile Total-to-HDL cholesterol ratio 3.5 ± 1.1 3.9 ± 1.3 3.7 ± 1.1 LDL cholesterol (mmol/L) 3.3 ± 0.9 3.3 ± 1.1 2.4 ± 0.9 Total cholesterol (mmol/L)‡ 5.6 ± 1.0 5.5 ± 1.2 4.4 ± 1.1 HDL cholesterol (mmol/L)‡ 1.7 ± 0.5 1.5 ± 0.4 1.3 ± 0.4 Triglycerides (mmol/L)‡ 1.2 ± 0.6 1.6 ± 1.0 1.8 ± 0.9 Lipid-modifying medication use‡ 178 (17.1) 93 (33.7) 350 (73.7) Markers of insulin resistance HOMA2-IRInsulin (AU)‡ 1.3 ± 0.7 1.9 ± 1.1 2.4 ± 1.4 HOMA2-IRC-peptide (AU)‡ 1.3 ± 0.5 1.7 ± 0.7 2.1 ± 0.9 Markers of low-grade inflammation hs-CRP (mg/L)‡ 1.1 (0.6–2.2) 1.8 (0.8–3.5) 1.5 (0.7–3.3) Serum amyloid A (mg/L)‡ 3.0 (1.9–5.0) 3.6 (2.3–5.7) 3.5 (2.2–6.0) Soluble ICAM-1 (ng/mL)‡ 338.6 ± 80.2 365.8 ± 103.2 383.8 ± 115.9 Interleukin-6 (pg/mL)‡ 0.5 (0.4–0.8) 0.6 (0.4–0.9) 0.8 (0.6–1.1) Interleukin-8 (pg/mL)‡ 3.7 (3.0–4.6) 4.3 (3.3–5.3) 4.8 (4.0–6.1) Tumor necrosis factor-α (pg/mL)‡ 2.1 (1.8–2.4) 2.2 (1.9–2.6) 2.5 (2.1–2.9) Markers of arterial stiffness Carotid-femoral pulse wave velocity (m/s)‡ 8.4 ± 1.7 9.2 ± 2.1 9.9 ± 2.3 Carotid distensibility coefficient (103/kPa)‡ 15.1 ± 5.2 13.7 ± 4.8 13.3 ± 4.9 Microvascular outcomes Baseline arteriolar diameter (MU) 115.3 ± 15.3 114.8 ± 15.9 116.0 ± 15.9 Arteriolar average dilation (%) Mean ± SD 3.4 ± 2.8 3.1 ± 2.8 2.4 ± 2.7 Median [interquartile range] 3.0 (1.1–5.3) 2.8 (0.8–5.0) 1.6 (0.4–3.9) Baseline skin blood flow (PU)‖ 10.8 ± 6.4 11.7 ± 7.2 11.0 ± 5.7 Skin hyperemic response (%)‖ Mean ± SD 1,252.6 ± 813.4 1,107.4 ± 710.8 941.7 ± 701.1 Median [interquartile range] 1,104.0 (668.7–1,656.9) 1,006.9 (604.9–1,536.9) 821.2 (479.0–1,209.8) Data are reported as mean ± SD, median [interquartile range], or number (%) as appropriate. AU, arbitrary units; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HOMA2-IR, HOMA of insulin resistance; ICAM, intercellular adhesion molecule; MU, measurement units; PU, perfusion units; SBP, systolic blood pressure.
↵* Available in 313 individuals with type 2 diabetes.
↵† (Micro)albuminuria was defined as a urinary albumin excretion of >30 mg per 24 h.
↵‡ Indicates that the individual marker is part of the corresponding composite index.
↵§ Available in 389 individuals with T2D, as the oral glucose tolerance test was not performed in individuals who were on insulin treatment.
↵‖ Heat-induced skin hyperemia measures were available in a different subset of n = 1,281.