Impact of Glycemic and Blood Pressure Variability on Surrogate Measures of Cardiovascular Outcomes in Type 2 Diabetic Patients

Abstract

OBJECTIVE The effect of glycemic variability (GV) on cardiovascular risk has not been fully clarified in type 2 diabetes. We evaluated the effect of GV, blood pressure (BP), and oxidative stress on intima-media thickness (IMT), left ventricular mass index (LVMI), flow-mediated dilation (FMD), and sympathovagal balance (low frequency [LF]/high frequency [HF] ratio) in 26 type 2 diabetic patients (diabetes duration 4.41 ± 4.81 years; HbA1c 6.70 ± 1.25%) receiving diet and/or metformin treatment, with no hypotensive treatment or complications. RESEARCH DESIGN AND METHODS Continuous glucose monitoring (CGM) data were used to calculate mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA)-2, mean blood glucose (MBG), mean postprandial glucose excursion (MPPGE), and incremental area under the curve (IAUC). Blood pressure (BP), circadian rhythm, and urinary 15-F2t-isoprostane (8-iso-prostaglandin F2α [PGF2α]) were also evaluated. Subjects were divided into dipper (D) and nondipper (ND) groups according to ΔBP. RESULTS IMT and LVMI were increased in ND versus D (0.77 ± 0.08 vs. 0.68 ± 0.13 [P = 0.04] and 67 ± 14 vs. 55 ± 11 [P = 0.03], respectively). MBG, MAGE, and IAUC were significantly associated with LF/HF ratio at night (r = 0.50, P = 0.01; r = 0.40, P = 0.04; r = 0.41, P = 0.04, respectively), MPPGE was negatively associated with FMD (r = −0.45, P = 0.02), and CONGA-2 was positively associated with LVMI (r = 0.55, P = 0.006). The Δsystolic BP was negatively associated with IMT (r = −0.43, P = 0.03) and with LVMI (r = −0.52, P = 0.01). Urinary 8-iso-PGF2α was positively associated with LVMI (r = 0.68 P < 0.001). CONCLUSIONS An impaired GV and BP variability is associated with endothelial and cardiovascular damage in short-term diabetic patients with optimal metabolic control. Oxidative stress is the only independent predictor of increased LV mass and correlates with glucose and BP variability.