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
Open accessAbstract
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)
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
α-Glucosidase inhibitors do not increase insulin sensitization.
“Whereas, it should be noted that they do not increase insulin sensitization (190)”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [190]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Heart Rate Variability: Standards of Measurement, Physiological Interpretation, and Clinical Use
Electrophysiology, T. F. O. T. E. S. O. C. T. N. A. (1996) · Circulation · doi:10.1161/01.cir.93.5.1043 · Cited by 17,159 · see citing works
Heart rate variability: Standards of measurement, physiological interpretation, and clinical use
Malik, M., Bigger, J. T., Camm, A. J., Kleiger, R. E., Malliani, A., Moss, A. J., & Schwartz, P. J. (1996) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a014868 · Cited by 15,289 · see citing works
Chiasson, J.-L., Josse, R. G., Gomis, R., Hanefeld, M., Karasik, A., Laakso, M., & for The STOP-NIDDM Trial Research Group (2003) · JAMA · doi:10.1001/jama.290.4.486 · Cited by 1,624 · see citing works
Ceriello, A., Esposito, K., Piconi, L., Ihnat, M. A., Thorpe, J. E., Testa, R., Boemi, M., & Giugliano, D. (2008) · Diabetes · doi:10.2337/db08-0063 · Cited by 1,310 · see citing works
Mean Amplitude of Glycemic Excursions, a Measure of Diabetic Instability
Service, F. J., Molnar, G. D., Rosevear, J. W., Ackerman, E., Gatewood, L. C., & Taylor, W. F. (1970) · Diabetes · doi:10.2337/diab.19.9.644 · Cited by 1,039 · see citing works
Kosiborod, M., Rathore, S. S., Inzucchi, S. E., Masoudi, F. A., Wang, Y., Havranek, E. P., & Krumholz, H. M. (2005) · Circulation · doi:10.1161/circulationaha.104.517839 · Cited by 666 · see citing works
Hanefeld, M. (2004) · European Heart Journal · doi:10.1016/s0195-668x(03)00468-8 · Cited by 641 · see citing works
Goto, A., Arah, O. A., Goto, M., Terauchi, Y., & Noda, M. (2013) · BMJ · doi:10.1136/bmj.f4533 · Cited by 492 · see citing works
Chow, E., Bernjak, A., Williams, S., Fawdry, R. A., Hibbert, S., Freeman, J., Sheridan, P. J., & Heller, S. R. (2014) · Diabetes · doi:10.2337/db13-0468 · Cited by 403 · see citing works
Kosiborod, M., Inzucchi, S. E., Krumholz, H. M., Xiao, L., Jones, P. G., Fiske, S., Masoudi, F. A., Marso, S. P., & Spertus, J. A. (2008) · Circulation · doi:10.1161/circulationaha.107.740498 · Cited by 385 · see citing works
Svensson, A.-M., McGuire, D. K., Abrahamsson, P., & Dellborg, M. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi230 · Cited by 310 · see citing works
Guidelines for Rehabilitation in Patients With Cardiovascular Disease (JCS 2012)
JCS Joint Working Group (2014) · Circulation Journal · doi:10.1253/circj.cj-66-0094 · Cited by 284 · see citing works
Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation
Reno, C. M., Daphna-Iken, D., Chen, Y. S., VanderWeele, J., Jethi, K., & Fisher, S. J. (2013) · Diabetes · doi:10.2337/db13-0216 · Cited by 159 · see citing works
Jun, J. E., Jin, S., Baek, J.-H., Oh, S. W., Hur, K. Y., Lee, M., Lee, M., & Kim, J. H. (2015) · Cardiovascular Diabetology · doi:10.1186/s12933-015-0233-0 · Cited by 111 · see citing works
Guidelines for Rehabilitation in Patients With Cardiovascular Disease (JCS 2012):– Digest Version –
JCSJointWorkingGroup (2014) · Circulation · Cited by 104 · see citing works
Mellbin, L., Malmberg, K., Waldenström, A. P., Wedel, H., Rydén, L., & for the DIGAMI 2 investigators (2008) · Heart · doi:10.1136/hrt.2008.152835 · Cited by 85 · see citing works
Saito, I., Hitsumoto, S., Maruyama, K., Nishida, W., Eguchi, E., Kato, T., Kawamura, R., Takata, Y., Onuma, H., Osawa, H., et al. (2015) · Journal of Epidemiology · doi:10.2188/jea.je20140254 · Cited by 77 · see citing works
Koivikko, M. L., Salmela, P. I., Airaksinen, J. K. E., Tapanainen, J. S., Ruokonen, A., Mäkikallio, T. H., & Huikuri, H. V. (2005) · Diabetes · doi:10.2337/diabetes.54.3.744 · Cited by 59 · see citing works
The proarrhythmic effect of hypoglycemia: evidence for increased risk from ischemia and bradycardia
Nordin, C. (2013) · Acta Diabetologica · doi:10.1007/s00592-013-0528-0 · Cited by 58 · see citing works
Kurajoh, M., Koyama, H., Kadoya, M., Naka, M., Miyoshi, A., Kanzaki, A., Kakutani‐Hatayama, M., Okazaki, H., Shoji, T., Moriwaki, Y., et al. (2015) · Cardiovascular Diabetology · doi:10.1186/s12933-015-0280-6 · Cited by 49 · see citing works
Lee, S. A., Cho, S. J., Jeong, M. H., Kim, Y., Kim, C. J., Cho, M., Kim, H.-S., Ahn, Y., Koh, G., Lee, J. M., et al. (2014) · Diabetes Care · doi:10.2337/dc13-2856 · Cited by 45 · see citing works
Meyer, M. L., Gotman, N., Soliman, E. Z., Whitsel, E. A., Arens, R., Cai, J., Daviglus, M. L., Denes, P., González, H. M., Moreiras, J. J., et al. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0364-y · Cited by 40 · see citing works
Hermanns, N., Schumann, B., Kulzer, B., & Haak, T. (2014) · Journal of Diabetes Science and Technology · doi:10.1177/1932296814524105 · Cited by 39 · see citing works
Shimabukuro, M., Higa, M., Yamakawa, K., Masuzaki, H., & Sata, M. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.05.109 · Cited by 39 · see citing works
Self-citationSvensson, M. K. E., Lindmark, S., Wiklund, U., Rask, P., Karlsson, M., Myrin, J., Kullberg, J., Johansson, L. O. M., & Eriksson, J. W. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0411-8 · Cited by 38 · see citing works
Kishimoto, M., & Noda, M. (2011) · Cardiovascular Diabetology · doi:10.1186/1475-2840-10-115 · Cited by 30 · see citing works
Saito, I., Maruyama, K., Nishida, W., Eguchi, E., Kato, T., Hitsumoto, S., Kawamura, R., Takata, Y., Onuma, H., Osawa, H., et al. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv096.284 · Cited by 29 · see citing works
Li, F.-F., Xu, X., Fu, L., Su, X., Wu, J.-D., Lu, C., Ye, L., & Ma, J. (2015) · International Journal of Endocrinology · doi:10.1155/2015/903524 · Cited by 28 · see citing works
Kitano, D., Chiku, M., Li, Y., Okumura, Y., Fukamachi, D., Takayama, T., Hiro, T., Saito, S., & Hirayama, A. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-92 · Cited by 25 · see citing works
Resting Heart Rate in First Year Survivors of Myocardial Infarction and Long-term Mortality
Jabre, P., Roger, V. L., Weston, S. A., Adnet, F., Jiang, R., Vivien, B., Empana, J. P., & Jouven, X. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.07.017 · Cited by 18 · see citing works
Smits, M. M., Tonneijck, L., Muskiet, M. H. A., Hoekstra, T., Kramer, M. H. H., Diamant, M., & van Raalte, D. H. (2016) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2016.12.011 · Cited by 16 · see citing works
Vascular Glucose Sensor Symposium
Joseph, J. I., Torjman, M. C., & Strasma, P. J. (2015) · Journal of Diabetes Science and Technology · doi:10.1177/1932296815587938 · Cited by 11 · see citing works
Matsuura, K., Mori, Y., Nakamura, A., Yokoyama, J., & Utsunomiya, K. (2012) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2011.0188 · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
From pre-diabetes to diabetes: diagnosis, treatments and translational research
Khan, R., Chua, Z., Tan, J., Yang, Y., Liao, Z., & Zhao, Y. (2019) · Medicina · doi:10.3390/medicina55090546 · Cited by 484 · see citing works
Treatment strategies against diabetes: Success so far and challenges ahead.
Khursheed, R., Singh, S. K., Wadhwa, S., Kapoor, B., Gulati, M., Kumar, R., Ramanunny, A. K., Awasthi, A., & Dua, K. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172625 · Cited by 239 · see citing works
Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments
Wang, M., Tan, Y., Shi, Y., Wang, X., Liao, Z., & Wei, P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00568 · Cited by 231 · see citing works
Pharmacotherapy of type 2 diabetes: An update
Upadhyay, J., Pοlyzos, S. A., Perakakis, N., Thakkar, B., Paschou, S. Α., Katsiki, N., UNDERWOOD, P. C., Park, K., Seufert, J., Kang, E. S., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.08.010 · Cited by 190 · see citing works
Takahashi, H., Iwahashi, N., Kirigaya, J., Kataoka, S., Minamimoto, Y., Gohbara, M., Abe, T., Okada, K., Matsuzawa, Y., Konishi, M., et al. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0761-5 · Cited by 86 · see citing works
He, H., Zheng, S.-W., Xie, Y., Wang, Z., Jiao, S., Yang, F.-R., Li, X.-X., Li, J., & Sun, Y. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02146-w · Cited by 81 · see citing works
Cheng, S., Shen, H., Han, Y., Han, S., & Lu, Y. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02462-1 · Cited by 72 · see citing works
Yin, Y., Jin, J., Li, Y., Sun, P., Wang, H., & Wang, X. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00774 · Cited by 65 · see citing works
Zhou, Z., Ye, F., Lei, L., Zhou, S., & Zhao, G. (2022) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2022.02.016 · Cited by 61 · see citing works
Progression of cardiovascular autonomic neuropathy and cardiovascular disease in type 2 diabetes
Yun, J., Park, Y., Cha, S., Ahn, Y., & Ko, S. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0752-6 · Cited by 52 · see citing works
Matsutani, D., Sakamoto, M., Iuchi, H., Minato, S., Suzuki, H., Kayama, Y., Takeda, N., Horiuchi, R., & Utsunomiya, K. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0683-2 · Cited by 52 · see citing works
Chan, C.-W., Yu, C.-L., Lin, J., Hsieh, Y., Lin, C., Hung, C.-Y., Li, C.-H., Liao, Y., Lo, C., Huang, J., et al. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0663-6 · Cited by 52 · see citing works
Glucose Variability and Coronary Artery Disease
Xia, J., & Yin, C. (2018) · Heart Lung and Circulation · doi:10.1016/j.hlc.2018.10.019 · Cited by 42 · see citing works
Kim, H., & Hyun, C. (2022) · Molecules · doi:10.3390/molecules28010115 · Cited by 29 · see citing works
Xia, J., Hu, S., Xu, J., Hao, H., Yin, C., & Xu, D. (2018) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2018-0220 · Cited by 23 · see citing works
Alsaidan, A. A., Al-Kuraishy, H. M., Al-Gareeb, A. I., Alexiou, A. T., Papadakis, M., Alsayed, K. A., Saad, . M., & Batiha, G. E. (2023) · Immunity Inflammation and Disease · doi:10.1002/iid3.798 · Cited by 21 · see citing works
Shi, F., Shen, L., Yue, J., Ma, J., Gu, Z., Li, H., & Lin, H. (2021) · Pharmacology Research & Perspectives · doi:10.1002/prp2.725 · Cited by 14 · see citing works
He, H., Xie, Y., Wang, Z., Li, J., Zheng, S.-W., Li, X.-X., Jiao, S., Yang, F.-R., & Sun, Y. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111595 · Cited by 13 · see citing works
Li, Z., Zhao, L., Yu, L., & Yang, J. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00777 · Cited by 13 · see citing works
Dimova, R. B., Chakarova, N. Y., Grozeva, G. G., & Tankova, T. I. (2020) · Diabetes and Vascular Disease Research · doi:10.1177/1479164120958619 · Cited by 12 · see citing works
(2020) · Biointerface Research in Applied Chemistry · doi:10.33263/briac112.96299637 · Cited by 12 · see citing works
Zhong, L., Yang, J., Syed, J. N., Zhang, Y., Tian, Y., & Fu, X. (2025) · Aging and Disease · doi:10.14336/ad.2024.1477 · Cited by 10 · see citing works
Wei, Y., & Xu, W. (2019) · Future Cardiology · doi:10.2217/fca-2018-0062 · Cited by 9 · see citing works
Evans, A. J., & Li, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212464 · Cited by 7 · see citing works
Zhang, D., Tu, H., Hu, W., Duan, B., Zimmerman, M. C., & Li, Y. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.871852 · Cited by 6 · see citing works
Significance of day-to-day glucose variability in patients after acute coronary syndrome
Miyoshi, M., Uzui, H., Shimizu, T., Aiki, T., Shiomi, Y., Nodera, M., Ikeda, H., Tama, N., Hasegawa, K., Morishita, T., et al. (2021) · BMC Cardiovascular Disorders · doi:10.1186/s12872-021-02303-z · Cited by 6 · see citing works
Xie, Y.-Y., Chen, H., Wang, Z., He, H., Xu, Y., Liu, L., & Zheng, J.-G. (2025) · Angiology · doi:10.1177/00033197251333216 · Cited by 6 · see citing works
Li, A., & Zhang, F. (2025) · World Journal of Diabetes · doi:10.4239/wjd.v16.i10.110722 · Cited by 3 · see citing works
Hossain, M. A., Shamim, M., Islam, M. A., Shourav, S. M. Y., Hosen, M. R., Fariha, F. M., Alam, S., & Karim, M. R. (2026) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-026-10643-6 · Cited by 2 · see citing works
Oh, T. J., & Choi, S. H. (2019) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0148 · Cited by 2 · see citing works
Glycemic variability and diabetic cardiac autonomic neuropathy
Serhiyenko, A. A., Tsaryk, T. V., Pavlovskiy, Y., & Serhiyenko, V. A. (2024) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.20.4.2024.1398 · Cited by 1 · see citing works
Meng, K., Yang, S., He, X., Luo, W., He, L., & He, D. (2025) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2025.111694
Zhou, J., Deng, X., Zhou, P., Luo, X., Li, H., & Fan, X. (2025) · BMC Geriatrics · doi:10.1186/s12877-025-06499-z
He, H.-M., Zheng, S.-W., Xie, Y.-Y., Wang, Z., Jiao, S.-Q., Yang, F., Li, X.-X., Li, J., & Sun, Y.-H. (2024) · Figshare · doi:10.6084/m9.figshare.25200738
Chan, C.-W., Yu, C.-L., Lin, J.-C., Hsieh, Y., Lin, C.-C., Hung, C.-Y., Li, C.-H., Liao, Y.-C., Lo, C.-P., Huang, J.-L., et al. (2018) · Figshare · doi:10.6084/m9.figshare.5821893
He, H.-M., Zheng, S.-W., Xie, Y., Wang, Z., Jiao, S.-Q., Yang, F., Li, X.-X., Li, J., & Sun, Y.-H. (2024) · Figshare · doi:10.6084/m9.figshare.26679341
He, H.-M., Zheng, S.-W., Xie, Y.-Y., Wang, Z., Jiao, S.-Q., Yang, F., Li, X.-X., Li, J., & Sun, Y.-H. (2024) · Figshare · doi:10.6084/m9.figshare.25200647
Daharia, A., Thakur, A. S., & Dewangan, L. (2026) · Russian Journal of General Chemistry · doi:10.1134/s1070363225608130
- Authors
- Shimabukuro, M., Tanaka, A., Sata, M., Dai, K., Shibata, Y., Inoue, Y., Ikenaga, H., Kishimoto, S., Ogasawara, K., Takashima, A., Niki, T., Arasaki, O., Oshiro, K., Mori, Y., Ishihara, M., Node, K., & Study, O. B. O. T. C. O. T. E. O. M. O. G. M. I. A. C. S. (.
- Affiliations
- Fukushima Medical University (JP)
- Saga University (JP)
- Tokushima University (JP)
- Miyazaki Medical Association Hospital (JP)
- Tomishiro Central Hospital (JP)
- Jikei University School of Medicine (JP)
- Hyogo Medical University (JP)
- Corresponding author
- Node, Koichi
- ORCID
- Venue
- Cardiovascular Diabetology
- Published
- 2017-07-06
- Volume
- 16
- Issue
- 1
- Pages
- 86-86
- ISSN
- 1475-2840 (ISSN-L)
- PMC
- PMC5501494
- OpenAlex
- W2725327820
- Cited by
- 38
- References
- 35
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 8 · 2017: 1
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cardiovascular Diabetology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Society for the Promotion of Science (16H05299, 16K01823)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- miglitol, alpha-glucosidase inhibitors, type 2 diabetes, acute coronary syndrome, glucose fluctuations, heart rate variability, sympathetic activity, continuous glucose monitoring, autonomic dysfunction, glycemic variability, cardiac autonomic function, LF/HF ratio, Holter electrocardiography
- MeSH terms
- Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucose, Heart Rate, Humans, Hypoglycemic Agents, Male, Middle Aged, Treatment Outcome, 1-Deoxynojirimycin, Acute Coronary Syndrome, Glycoside Hydrolase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review