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

Abstract

BackgroundLittle 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.MethodsThis 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.ResultsAlthough 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.ConclusionsIn 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)Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0571-1) contains supplementary material, which is available to authorized users.

Glycemic variability determined with a continuous glucose monitoring system can predict prognosis after acute coronary syndrome

“…Recent investigations have demonstrated that glucagon-like peptide-1 (GLP-1) analogue inhibits oxidative injuries in vascular endothelial cells [ 28 ]. Another study suggested that the α-glucosidase inhibitor attenuated GV, heart rate variability, and sympathetic activity in ACS patients with type 2 DM [ 29 ]. According to the current study’s results, we emphasize that there is a possibility of improving prognosis by reducing GV via the use of CGM.…”

Head-to-Head Comparison of the Hypoglycemic Efficacy and Safety Between Dipeptidyl Peptidase-4 Inhibitors and α-Glucosidase Inhibitors in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

“…Thirdly, we found that despite of significant decreased FBG by DPP4 inhibitors compared with AGIs, treatment with DPP4 inhibitors also significantly decreased PPG as compared with AGIs in T2DM patients, which is not reported in previous meta-analysis (Cai et al, 2015). This is of clinical significance since AGIs are often considered as the OADs of choice to lower PPG because of its direct pharmacological action, which is to inhibit the absorption of carbohydrates during the meals (Liu and Ma, 2017; Shimabukuro et al, 2017). Based on our results, DPP4 inhibitors should be considered in patients with high PPG levels.…”

Progression of cardiovascular autonomic neuropathy and cardiovascular disease in type 2 diabetes

“…Serum average and variability of glycated albumin level, which represent the short-term (2–3 weeks) glycemic status, are significantly associated with the presence of CAN [ 20 ]. Shimabukuro et al demonstrated that short-term suppression of glycemic variability with α-glucosidase inhibitor can improve sympathetic nervous system activity and modify heart rate variability [ 21 ]. Jaiswal et al found that the prevalence of CAN in a young diabetes cohort was comparable to that reported in the adult diabetes population and that elevated triglyceride levels were the modifiable factors associated with CAN in this group [ 22 ].…”