α-Glucosidase inhibitor miglitol attenuates glucose fluctuation, heart rate variability and sympathetic activity in patients with type 2 diabetes and acute coronary syndrome: a multicenter randomized controlled (MACS) study - PubMed (original) (raw)

Randomized Controlled Trial

doi: 10.1186/s12933-017-0571-1.

Atsushi Tanaka 3, Masataka Sata 4, Kazuoki Dai 5, Yoshisato Shibata 6, Yohei Inoue 3 6, Hiroki Ikenaga 5, Shinji Kishimoto 5, Kozue Ogasawara 4, Akira Takashima 4, Toshiyuki Niki 4, Osamu Arasaki 7, Koichi Oshiro 8, Yutaka Mori 9, Masaharu Ishihara 10, Koichi Node 11; Collaborators on the Effect of Miglitol on Glucose Metabolism in Acute Coronary Syndrome (MACS) Study

Affiliations

Randomized Controlled Trial

α-Glucosidase inhibitor miglitol attenuates glucose fluctuation, heart rate variability and sympathetic activity in patients with type 2 diabetes and acute coronary syndrome: a multicenter randomized controlled (MACS) study

Michio Shimabukuro et al. Cardiovasc Diabetol. 2017.

Abstract

Background: Little is known about clinical associations between glucose fluctuations including hypoglycemia, heart rate variability (HRV), and the activity of the sympathetic nervous system (SNS) in patients with acute phase of acute coronary syndrome (ACS). This pilot study aimed to evaluate the short-term effects of glucose fluctuations on HRV and SNS activity in type 2 diabetes mellitus (T2DM) patients with recent ACS. We also examined the effect of suppressing glucose fluctuations with miglitol on these variables.

Methods: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group comparative study included 39 T2DM patients with recent ACS, who were randomly assigned to either a miglitol group (n = 19) or a control group (n = 20). After initial 24-h Holter electrocardiogram (ECG) (Day 1), miglitol was commenced and another 24-h Holter ECG (Day 2) was recorded. In addition, continuous glucose monitoring (CGM) was performed throughout the Holter ECG.

Results: Although frequent episodes of subclinical hypoglycemia (≤4.44 mmo/L) during CGM were observed on Day 1 in the both groups (35% of patients in the control group and 31% in the miglitol group), glucose fluctuations were decreased and the minimum glucose level was increased with substantial reduction in the episodes of subclinical hypoglycemia to 7.7% in the miglitol group on Day 2. Holter ECG showed that the mean and maximum heart rate and mean LF/HF were increased on Day 2 in the control group, and these increases were attenuated by miglitol. When divided 24-h time periods into day-time (0700-1800 h), night-time (1800-0000 h), and bed-time (0000-0700 h), we found increased SNS activity during day-time, increased maximum heart rate during night-time, and glucose fluctuations during bed-time, which were attenuated by miglitol treatment.

Conclusions: In T2DM patients with recent ACS, glucose fluctuations with subclinical hypoglycemia were associated with alterations of HRV and SNS activity, which were mitigated by miglitol, suggesting that these pathological relationships may be a residual therapeutic target in such patients. Trial registration Unique Trial Number, UMIN000005874 ( https://upload.umin.ac.jp/cgi-open-bin/ctr\_e/ctr\_view.cgi?recptno=R000006929 ).

Keywords: Acute coronary syndrome; Glucose fluctuation; Heart rate variability; Hypoglycemia; Miglitol; Sympathetic nervous system activity; Type 2 diabetes.

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Figures

Fig. 1

Fig. 1

Study outline. ACS acute coronary syndrome

Fig. 2

Fig. 2

Participants’ flow

Fig. 3

Fig. 3

Continuous glucose monitoring. a, b Mean variations in 24-h blood glucose measured by a continuous glucose monitoring system in control and miglitol groups. Lines represent mean (solid) ± SD (dotted) of blood glucose levels on Day 1 (black) and Day 2 (blue or red) in a control (n = 17) and b miglitol (n = 13) groups. To see daily variations of glucose levels, we divided time periods into 0700–1800 h (day-time), 1800–0000 h (night-time), and 0000–0700 h (bed-time). Patients took a standard regimen of breakfast, lunch, and supper. The peaks after lunch and supper on Day 2 in the miglitol group (red arrow, Fig. 3b) are indicated by red arrows. c, d Levels of mean glucose, minimum (min) glucose, maximum (max) glucose, ∆glucose, SD glucose, and MAGE during 24-h in the control and miglitol groups. Boxes represent mean ± SD, and whiskers represent min to max during 24-h on Day 1 and Day 2 in c control (n = 17) and d miglitol (n = 13) groups

Fig. 4

Fig. 4

Impact of miglitol on glucose fluctuation, heart rate variability, and sympathetic nervous activity. a–d Plots of 24-h blood glucose measured by a continuous monitoring system in control and miglitol-treated patients. Lines indicate blood glucose levels on Day 1 and Day 2 in (a, c) control (n = 17) and (B, D) miglitol (n = 13) groups. To see daily variations of glucose levels, we divided time periods into 0700–1800 h (day-time), 1800–0000 h (night-time), and 0000–0700 h (bed-time). Patients took a standard regimen of breakfast, lunch and supper. The percentage values indicate the proportions of patients with episodes of glucose ≤4.44 mmol/L throughout the day, indicated by blue lines on the figures. e, f Mean variations in 24-h heart rate (HR) in the control and miglitol groups. Lines represent mean (solid) ± SD (dotted) of mean heart rate measured by Holter electrocardiography on Day 1 (black) and Day 2 (blue or red) in e control (n = 18) and f miglitol (n = 17) groups. To see daily variations of heart rate, we divided time periods into 0700–1800 h (day-time), 1800–0000 h (night-time), and 0000–0700 h (bed-time)

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