Glycemic variability in continuous glucose monitoring is inversely associated with baroreflex sensitivity in type 2 diabetes: a preliminary report

Abstract

BackgroundIt is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy. The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring (CGM).MethodsThis was a multicenter, prospective, open-label clinical trial. A total of 102 patients with type 2 diabetes were consecutively recruited for this study. GV was assessed by measuring the standard deviation (SD), glucose coefficient of variation (CV), and the mean amplitude of glycemic excursions (MAGE) during CGM. The BRS was analyzed from electrocardiogram and blood pressure recordings using the sequence method on the first day of hospitalization.ResultsA total of 94 patients (mean diabetes duration 9.7 ± 9.6 years, mean HbA1c 61.0 ± 16.8 mmol/mol [7.7 ± 1.5%]) were analyzed. In the univariate analysis, CGM-SD (r = − 0.375, p = 0.000), CGM-CV (r = − 0.386, p = 0.000), and MAGE (r = − 0.395, p = 0.000) were inversely related to BRS. In addition to GV, the level of BRS correlated with the coefficient of variation in the R–R intervals (CVR-R) (r = 0.520, p = 0.000), heart rate (HR) (r = − 0.310, p = 0.002), cardio-ankle vascular index (CAVI) (r = − 0.326, p = 0.001), age (r = − 0.519, p = 0.000), and estimated glomerular filtration rate (eGFR) (r = 0.276, p = 0.007). Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS. These findings remained after adjusting the BRS for age, sex, hypertension, dyslipidemia, HR, eGFR, CAVI, and CGM-mean glucose. Additionally, BRS was divided according to quartiles of the duration of diabetes (Q1–4). BRS decreased after a 2-year duration of diabetes independently of age and sex.ConclusionsGV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients. Measurement of BRS may have the potential to predict CV events in consideration of GV.Trial registration UMIN Clinical Trials Registry UMIN000025964, 28/02/2017Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0683-2) contains supplementary material, which is available to authorized users.

Clinical Implications of Baroreflex Sensitivity in Type 2 Diabetes

“…In fact, we recently reported that in patients with T2DM, there was an association of increased shortterm GV assessed by continuous glucose monitoring with reduced BRS, independently of blood glucose levels. 31) Furthermore, we reported that long-term GV represented by visit-to-visit HbA1c variability over a 2-year period, which is an independent risk factor for CV events, [55][56][57][58] was inversely related to BRS independently of mean HbA1c in patients with T2DM. 59) Details of the mechanism for reduced BRS in patients with T2DM are not yet fully understood.…”

“…[28][29][30] Recently, we reported that the cardio-ankle vascular index, an indicator of arteriosclerosis, was independently associated with BRS. 31) In a carotid bulb containing highly concentrated baroreceptors, increased intima-media thickness was also reportedly associated with reduced BRS. 32) CLINICAL IMPLICATIONS OF BAROREFLEX SENSITIVITY…”

Improved glucose homeostasis in male obese Zucker rats coincides with enhanced baroreflexes and activation of the nucleus tractus solitarius

“…Similarly, in the absence of diabetes, a prediabetic level of fasting blood glucose (Ͼ100 mg/dl) is a better predictor of impaired HR variability and HR turbulence than any other attribute of metabolic syndrome (5). Furthermore, in patients with type 2 diabetes the variability of blood glucose has a highly significant inverse relationship with baroreflex sensitivity (58).…”

Continuous glucose monitoring defined glucose variability is associated with cardiovascular autonomic neuropathy in type 1 diabetes

“…4,5 In addition, CAN was the strongest predictor for mortality during a 7-year follow-up in people with type 1 diabetes compared with traditional cardiovascular risk factors. 6 Several recent studies indicated that glycaemic variability (GV) is associated with CAN independent of mean glucose in poorly controlled 7,8 and newly diagnosed 9 type 2 diabetes. However, most previous studies on the association between continuous glucose monitoring (CGM)-defined GV and CAN have been conducted in patients with type 2 diabetes, [7][8][9] without dedicated analysis in adults with type 1 diabetes.…”