Significance of Glycemic Variability in Diabetes Mellitus

Kusunoki, Yoshiki; Konishi, Kosuke; Tsunoda, Taku; Koyama, Hidenori

doi:10.2169/internalmedicine.8424-21

Cited by 40Diabetes Management and ResearchDiabetes Treatment and ManagementHyperglycemia and glycemic control in critically ill and hospitalized patients

Significance of Glycemic Variability in Diabetes Mellitus

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Kusunoki, Yoshiki, Konishi, Kosuke, Tsunoda, Taku, Koyama, Hidenori·2022·Internal Medicine

DOI 10.2169/internalmedicine.8424-21PMC PMC8866772

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Abstract

The goal of diabetes treatment is to maintain good glycemic control, prevent the development and progression of diabetic complications, and ensure the same quality of life and life expectancy as healthy people. Hemoglobin A1c (HbA1c) is used as an index of glycemic control, but strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and cardiovascular death. Glycemic variability (GV), such as excessive hyperglycemia and hypoglycemia, is associated with diabetic vascular complications and has been recognized as an important index of glycemic control. Here, we reviewed the definition and evaluated the clinical usefulness of GV, and its relationship with diabetic complications and therapeutic strategies to reduce GV.

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Glycaemic variability complicates both the achievement of recommended glycated hemoglobin (HbA1c) and time in range (TIR) targets.
“It also complicates both the achievement of recommended glycated hemoglobin (HbA1c) and time in range (TIR) targets [101, 102].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [102]
The ‘Time in range (TIR)’ section (page unavailable) identifies TIR as a clinical target and reports that it correlates with glycaemic variability. The Introduction (page unavailable) says strict HbA1c-based control can carry risks. Neither passage establishes that glycaemic variability makes the recommended HbA1c and TIR targets harder to achieve. (LLM, conf=0.76)
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Šoupal, J., Škrha, J., Fajmon, M., Horová, E., Mráz, M., Škrha, J., & Prázný, M. (2014) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2013.0205 · Cited by 120 · see citing works
Prognostic Significance of Long-term HbA1c Variability for All-Cause Mortality in the ACCORD Trial
Sheng, C., Tian, J., Miao, Y., Cheng, Y., Yang, Y., Reaven, P. D., Bloomgarden, Z. T., & Ning, G. (2020) · Diabetes Care · doi:10.2337/dc19-2589 · Cited by 114 · see citing works
Beyond HbA1c: comparing glycemic variability and glycemic indices in predicting hypoglycemia in type 1 and type 2 diabetes
Rama Chandran, S., Tay, W. L., Lye, W. K., Lim, L. L., Ratnasingam, J., Tan, A. T. B., & S.L. Gardner, D. (2018) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2017.0388 · Cited by 114 · see citing works
Glycemic Variability: Risk Factors, Assessment, and Control
Kovatchev, B. P. (2019) · Journal of Diabetes Science and Technology · doi:10.1177/1932296819826111 · Cited by 111 · see citing works
HbA1c variability is associated with microalbuminuria development in type 2 diabetes: a 7-year prospective cohort study
Hsu, C., Chang, H., Huang, M., Hwang, S., Yang, Y., Lee, Y. S., Shin, S. J., & Tai, T. Y. (2012) · Diabetologia · doi:10.1007/s00125-012-2700-4 · Cited by 110 · see citing works
Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study
Nishimura, R., Tanaka, Y., Koiwai, K., Inoue, K., Hach, T., Salsali, A., Lund, S. S., & Broedl, U. C. (2015) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0169-9 · Cited by 109 · see citing works
The application of simple metrics in the assessment of glycaemic variability
Monnier, L., Colette, C., & Owens, D. R. (2018) · Diabetes & Metabolism · doi:10.1016/j.diabet.2018.02.008 · Cited by 106 · see citing works
Association Between Continuous Glucose Monitoring-Derived Time in Range, Other Core Metrics, and Albuminuria in Type 2 Diabetes
Yoo, J. H., Choi, M. S., Ahn, J., Park, S. W., Kim, Y., Hur, K. Y., Jin, S., Kim, G., & Kim, J. H. (2020) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2019.0499 · Cited by 102 · see citing works
Variability in HbA1c , blood pressure, lipid parameters and serum uric acid, and risk of development of chronic kidney disease in type 2 diabetes
Ceriello, A., Cosmo, S. D., Rossi, M. C., Lucisano, G., Genovese, S., Pontremoli, R., Fioretto, P., Giorda, C. B., Pacilli, A., Viazzi, F. C., et al. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12976 · Cited by 100 · see citing works
Continuous Glucose Monitoring and Insulin Informed Advisory System with Automated Titration and Dosing of Insulin Reduces Glucose Variability in Type 1 Diabetes Mellitus
Breton, M. D., Patek, S. D., Lv, D., Schertz, E. M., Robic, J., Pinnata, J., Kollar, L. L., Barnett, C. L., WAKEMAN, C. A., Oliveri, M. C., et al. (2018) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2018.0079 · Cited by 98 · see citing works
HbA1c Variability as an Independent Risk Factor for Diabetic Retinopathy in Type 1 Diabetes: A German/Austrian Multicenter Analysis on 35,891 Patients
Hermann, J. M., Hammes, H., Rami-Merhar, B. M., Rosenbauer, J., Schütt, M., Siegel, E. G., Holl, R. W., & on behalf of the DPV Initiative the German BMBF Competence Network Diabetes Mellitus (2014) · PLoS ONE · doi:10.1371/journal.pone.0091137 · Cited by 95 · see citing works
The Effect of Canagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, on Glycemic End Points Assessed by Continuous Glucose Monitoring and Patient-Reported Outcomes Among People With Type 1 Diabetes
Rodbard, H. W., Peters, A. L., Slee, A., Cao, A., Traina, S. B., & Alba, M. (2017) · Diabetes Care · doi:10.2337/dc16-1353 · Cited by 94 · see citing works
New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese adults with type 1 diabetes using basal and mealtime insulin: glucose control and hypoglycaemia in a randomized controlled trial ( EDITION JP 1)
Matsuhisa, M., Koyama, M., Cheng, X., Takahashi, Y., Riddle, M. C., Bolli, G. B., Hirose, T., & on behalf of the EDITION JP 1 study group (2015) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12619 · Cited by 85 · see citing works
Glycemic variability assessed by continuous glucose monitoring and the risk of diabetic retinopathy in latent autoimmune diabetes of the adult and type 2 diabetes
Lu, J., Ma, X., Zhang, L., Mo, Y., Ying, L., Lu, W., Zhu, W., Bao, Y., & Zhou, J. (2018) · Journal of Diabetes Investigation · doi:10.1111/jdi.12957 · Cited by 83 · see citing works
Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin for type 1 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials
Yamada, T., Shojima, N., Noma, H., Yamauchi, T., & Kadowaki, T. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13260 · Cited by 81 · see citing works
Effects of Dapagliflozin on 24-Hour Glycemic Control in Patients with Type 2 Diabetes: A Randomized Controlled Trial
Henry, R. R., Strange, P., Zhou, R., Pettus, J., Shi, L., Zhuplatov, S. B., Mansfield, T. A., Klein, D. J., & Katz, A. (2018) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2018.0052 · Cited by 79 · see citing works
Simultaneous GLP-1 and Insulin Administration Acutely Enhances Their Vasodilatory, Antiinflammatory, and Antioxidant Action in Type 2 Diabetes
Ceriello, A., Novials, A., Canivell, S., Sala, L. L., Pujadas, G., Esposito, K., Testa, R., Bucciarelli, L. G., Rondinelli, M., & Genovese, S. (2014) · Diabetes Care · doi:10.2337/dc13-2618 · Cited by 78 · see citing works
Visit‐to‐Visit Variability of Fasting Plasma Glucose and the Risk of Cardiovascular Disease and All‐Cause Mortality in the General Population
Wang, A., Liu, X., Xu, J., Han, X., Su, Z., Chen, S., Zhang, N., Wu, S., Wang, Y., & Wang, Y. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006757 · Cited by 78 · see citing works
Glucose variability does not contribute to the development of peripheral and autonomic neuropathy in type 1 diabetes: data from the DCCT
Siegelaar, S. E., Kilpatrick, E. S., Rigby, A. S., Atkin, S. L., Hoekstra, J. B. L., & DeVries, J. H. (2009) · Diabetologia · doi:10.1007/s00125-009-1473-x · Cited by 74 · see citing works
Improved Postprandial Glycemic Control with Faster-Acting Insulin Aspart in Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion
Bode, B. W., Johnson, J. A., Hyveled, L., Tamer, S. C., & Demissie, M. (2017) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2016.0350 · Cited by 72 · see citing works
HbA1c variability is associated with an increased risk of retinopathy requiring laser treatment in type 1 diabetes
on behalf of the FinnDiane Study Group, Hietala, K., Wadén, J., Forsblom, C. M., Harjutsalo, V., Kytö, J., Summanen, P. A., & Groop, P. (2013) · Diabetologia · doi:10.1007/s00125-012-2816-6 · Cited by 70 · see citing works
The effects of 2 weeks of interval vs continuous walking training on glycaemic control and whole-body oxidative stress in individuals with type 2 diabetes: a controlled, randomised, crossover trial
Karstoft, K., Clark, M. A., Jakobsen, I., Müller, I. A., Pedersen, B. K., Solomon, T. P. J., & Ried‐Larsen, M. (2016) · Diabetologia · doi:10.1007/s00125-016-4170-6 · Cited by 67 · see citing works
The impact of food order on postprandial glycaemic excursions in prediabetes
Shukla, A. P., Dickison, M., Coughlin, N., Karan, A., Mauer, E., Truong, W., Casper, A., Emiliano, A. B., Kumar, R. B., Saunders, K. H., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13503 · Cited by 66 · cited 1× · see citing works
“and exercise therapies are useful for GV suppression (82, 83); however, drug therapy is also quite effective.”
Background
Association of time in range, as assessed by continuous glucose monitoring, with painful diabetic polyneuropathy
Yang, J., Yang, X., Zhao, D., Wang, X., Wei, W., & Yuan, H. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13394 · Cited by 63 · see citing works
Associations between continuous glucose monitoring-derived metrics and arterial stiffness in Japanese patients with type 2 diabetes
Wakasugi, S., Mita, T., Katakami, N., Okada, Y., Yoshii, H., Osonoi, T., Kuribayashi, N., Taneda, Y., Kojima, Y., Gosho, M., et al. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01194-2 · Cited by 58 · see citing works
Association of glycaemic variability evaluated by continuous glucose monitoring with diabetic peripheral neuropathy in type 2 diabetic patients
Hu, Y.-M., Zhao, L.-H., Zhang, X.-L., Cai, H.-L., Huang, H.-Y., Xu, F., Chen, T., Wang, X.-Q., Guo, A.-S., Li, J.-A., et al. (2018) · Endocrine · doi:10.1007/s12020-018-1546-z · Cited by 57 · see citing works
Glucose variability and the risks of stroke, myocardial infarction, and all-cause mortality in individuals with diabetes: retrospective cohort study
Lee, D. Y., Han, K., Park, S. H., Yu, J. H., Seo, J. A., Kim, N. H., Yoo, H. J., Kim, S. G., Choi, K. M., Baik, S. H., et al. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01134-0 · Cited by 57 · see citing works
Visit-to-Visit Glucose Variability Predicts the Development of End-Stage Renal Disease in Type 2 Diabetes
Yang, Y.-F., Li, T., Li, C., Liu, C.-S., Lin, W., Yang, S.-Y., Chiang, J., Huang, C.-C., Sung, F., & Lin, C. (2015) · Medicine · doi:10.1097/md.0000000000001804 · Cited by 56 · see citing works
Greater daily glucose variability and lower time in range assessed with continuous glucose monitoring are associated with greater aortic stiffness: The Maastricht Study
Foreman, Y. D., van Doorn, W. P. T. M., Schaper, N. C., van Greevenbroek, M. M. J., Kallen, C., Henry, R. M. A., Koster, A., Eussen, S. J. P. M., Wesselius, A., Reesink, K. D., et al. (2021) · Diabetologia · doi:10.1007/s00125-021-05474-8 · Cited by 51 · see citing works
A Comparative Study of the Effects of a Dipeptidyl Peptidase-IV Inhibitor and Sulfonylurea on Glucose Variability in Patients with Type 2 Diabetes with Inadequate Glycemic Control on Metformin
Kim, H., Shin, J.-A., Lee, S., Kim, E.-S., Cho, J., Son, H., & Yoon, K. (2013) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2013.0038 · Cited by 50 · see citing works
Glucose Variables in Type 1 Diabetes Studies With Dapagliflozin: Pooled Analysis of Continuous Glucose Monitoring Data From DEPICT-1 and -2
Mathieu, C., Dandona, P., Phillip, M., Oron, T., Lind, M., Hansen, L., THOREN, F. A., Xu, J., Langkilde, A. M., & on behalf of the DEPICT-1 and DEPICT-2 Investigators (2019) · Diabetes Care · doi:10.2337/dc18-1983 · Cited by 48 · see citing works
Associations between continuous glucose monitoring-derived metrics and diabetic retinopathy and albuminuria in patients with type 2 diabetes
Wakasugi, S., Mita, T., Katakami, N., Okada, Y., Yoshii, H., Osonoi, T., Nishida, K., Shiraiwa, T., Torimoto, K., Kurozumi, A., et al. (2021) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2020-001923 · Cited by 47 · see citing works
Continuous glucose monitoring in patients with type 2 diabetes treated with glucagon‐like peptide‐1 receptor agonist dulaglutide in combination with prandial insulin lispro: an AWARD ‐4 substudy
JENDLE, J. H., Testa, M. A., Martin, S., Jiang, H. H., & Miličević, Z. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12705 · Cited by 47 · see citing works
Variability of fasting plasma glucose increased risks of diabetic polyneuropathy in T2DM
Yang, C., Li, C.-I., Liu, C.-S., Lin, W., Hwang, K.-L., Yang, S.-Y., Li, T., & Lin, C. (2017) · Neurology · doi:10.1212/wnl.0000000000003682 · Cited by 44 · see citing works
Fasting plasma glucose variability levels and risk of adverse outcomes among patients with type 2 diabetes: A systematic review and meta-analysis
Zhao, Q., Zhou, F., Zhang, Y., Zhou, X., & Ying, C. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.12.010 · Cited by 43 · see citing works
Poststroke glycemic variability increased recurrent cardiovascular events in diabetic patients
Yoon, J., Sunwoo, J., Kim, J. S., Roh, H., Ahn, M., Woo, H., & Lee, K. B. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.11.014 · Cited by 40 · see citing works
Relationships between time in range, glycemic variability including hypoglycemia and types of diabetes therapy in Japanese patients with type 2 diabetes mellitus: Hyogo Diabetes Hypoglycemia Cognition Complications study
Kuroda, N., Kusunoki, Y., Osugi, K., Ohigashi, M., Azuma, D., Ikeda, H., Makino, S., Otsuka, A., Tamada, D., Watanabe, N., et al. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13336 · Cited by 36 · see citing works
Self-citation
Fasting plasma glucose variability and HbA1c are associated with peripheral artery disease risk in type 2 diabetes
Yang, C., Lin, C., Li, C., Liu, C.-S., Lin, C., Hwang, K.-L., Yang, S.-Y., & Li, T. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0978-y · Cited by 35 · see citing works
A meta‐analysis of rate ratios for nocturnal confirmed hypoglycaemia with insulin degludec vs. insulin glargine using different definitions for hypoglycaemia
Heller, S. R., Mathieu, C., Kapur, R., Wolden, M. L., & Zinman, B. (2015) · Diabetic Medicine · doi:10.1111/dme.13002 · Cited by 34 · see citing works
Ultra-Rapid Lispro Improves Postprandial Glucose Control and Time in Range in Type 1 Diabetes Compared to Lispro: PRONTO-T1D Continuous Glucose Monitoring Substudy
Małecki, M., Cao, D., Liu, R., Hardy, T., Bode, B., Bergenstal, R., & Bue-Valleskey, J. (2020) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2020.0129 · Cited by 30 · see citing works
Antiobesity pharmacotherapy in the management of Type 2 diabetes
Scheen, A. J., & Lef�bvre, P. J. (2000) · Diabetes/Metabolism Research and Reviews · doi:10.1002/(sici)1520-7560(200003/04)16:2 · Cited by 29 · see citing works
Effects of Switching from Insulin Glargine or Detemir to Insulin Degludec in Patients with Type 1 Diabetes Mellitus
Kusunoki, Y., Katsuno, T., Miyakoshi, K., Ikawa, T., Nakae, R., Ochi, F., Tokuda, M., Akagami, T., Murai, K., Miuchi, M., et al. (2013) · Diabetes Therapy · doi:10.1007/s13300-013-0048-5 · Cited by 28 · see citing works
Self-citation
Association of time in range with hemoglobin A1c, glycated albumin and 1,5‐anhydro‐ d ‐glucitol
Ohigashi, M., Osugi, K., Kusunoki, Y., Washio, K., Matsutani, S., Tsunoda, T., Matsuo, T., Konishi, K., Katsuno, T., Namba, M., et al. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13437 · Cited by 28 · see citing works
Self-citation
Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin
Kusunoki, Y., Katsuno, T., Myojin, M., Miyakoshi, K., Ikawa, T., Matsuo, T., Ochi, F., Tokuda, M., Murai, K., Miuchi, M., et al. (2012) · Endocrine Journal · doi:10.1507/endocrj.ej12-0290 · Cited by 25 · see citing works
Self-citation
Association of Sitagliptin with cardiovascular outcome in diabetic patients: a nationwide cohort study
Yang, T., Liaw, Y., Huang, J., Chang, H., Chang, K.-W., & Ueng, K. (2015) · Acta Diabetologica · doi:10.1007/s00592-015-0817-x · Cited by 25 · see citing works
Lower risk of severe hypoglycaemia with insulin glargine 300 U/ <scp>mL</scp> versus glargine 100 U/ <scp>mL</scp> in participants with type 1 diabetes: A <scp>meta‐analysis</scp> of <scp>6‐month</scp> phase 3 clinical trials
Danne, T., Matsuhisa, M., Sussebach, C., Goyeau, H., Lauand, F., Niemoeller, E., & Bolli, G. B. (2020) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14109 · Cited by 25 · see citing works
Effects of insulin degludec and insulin glargine <scp>U300</scp> on glycaemic stability in individuals with type 1 diabetes: A multicentre, randomized controlled crossover study
Miura, H., Sakaguchi, K., Otowa‐Suematsu, N., Yamada, T., So, A., Komada, H., Okada, Y., Hirota, Y., Tamori, Y., & Ogawa, W. (2020) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14161 · Cited by 25 · see citing works
Effectiveness of insulin glargine U-300 versus insulin glargine U-100 on nocturnal hypoglycemia and glycemic control in type 1 and type 2 diabetes: a systematic review and meta-analysis
Díez‐Fernández, A., Cavero‐Redondo, I., Moreno-Fernández, J., Pozuelo‐Carrascosa, D. P., Garrido‐Miguel, M., & Martínez‐Vizcaíno, V. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1258-0 · Cited by 23 · see citing works
Evaluation of blood glucose fluctuation in Japanese patients with type 1 diabetes mellitus by self-monitoring of blood glucose and continuous glucose monitoring
Kusunoki, Y., Katsuno, T., Nakae, R., Watanabe, K., Akagami, T., Ochi, F., Tokuda, M., Murai, K., Miuchi, M., Miyagawa, J., et al. (2015) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2015.01.040 · Cited by 21 · see citing works
Self-citation
A Randomized Pilot Study of the Effect of Trelagliptin and Alogliptin on Glycemic Variability in Patients with Type 2 Diabetes
Nishimura, R., Osonoi, T., Koike, Y., Miyata, K., & Shimasaki, Y. (2019) · Advances in Therapy · doi:10.1007/s12325-019-01097-z · Cited by 20 · see citing works
A randomized controlled trial to compare the effects of sulphonylurea gliclazide MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic variability and control measured by continuous glucose monitoring (CGM) in Brazilian women with type 2 diabetes
Vianna, A. G. D., de Lacerda, C. S., Pechmann, L. M., Polesel, M. G., Marino, E. C., & Faria‐Neto, J. R. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.03.035 · Cited by 17 · see citing works
Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin
楠, 宜. (2013) · Medical Entomology and Zoology · Cited by 15 · see citing works
Lixisenatide reduces glycaemic variability in insulin‐treated patients with type 2 diabetes
Umpierrez, G. E., O'Neal, D. N., DIGENIO, A. G., Goldenberg, R., Hernández-Triana, E., Lin, J., Park, C., Renard, É., & Kovatchev, B. P. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12930 · Cited by 13 · see citing works
Effects of Teneligliptin on HbA1c levels, Continuous Glucose Monitoring-Derived Time in Range and Glycemic Variability in Elderly Patients with T2DM (TEDDY Study)
Bae, J. C., Kwak, S. H., Kim, H. J., Kim, S.-Y., Hwang, Y., Suh, S., Hyun, B. J., Cha, J. E., Won, J. C., & Kim, J. H. (2021) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2021.0016 · Cited by 12 · see citing works
Glycemic Variability: The Danger of a Physiologically Stable Metric
Battelino, T., & Dovč, K. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa486 · Cited by 9 · see citing works

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Sorted by citations

Comparison of admission glycemic variability and glycosylated hemoglobin in predicting major adverse cardiac events among type 2 diabetes patients with heart failure following acute ST-segment elevation myocardial infarction
Yang, X., Su, G., Zhang, T., Yang, H., Tao, H., Du, X., & Dong, J. (2024) · Journal of Translational Internal Medicine · doi:10.2478/jtim-2024-0006 · Cited by 25 · see citing works
“[5,6] Historically, HbA1c has been served as the primary indicator for assessing glycemic control and utilized in primary and secondary prevention of coronary heart disease.”
Background
Causal associations between HbA1c and multiple diseases unveiled through a Mendelian randomization phenome-wide association study in East Asian populations
Han, L., Xu, S., Chen, R., Zheng, Z., Ding, Y., Wu, Z., Li, S., He, B., & Bao, M. (2025) · Medicine · doi:10.1097/md.0000000000041861 · Cited by 19 · see citing works
“[71] 73–76] A study based on the Korean KoGES cohort (≥50 years old; 1972 age-related cataracts [ARC] cases and 38,290 healthy controls) investigated the association between metabolic syndrome and its components with ARC.”
Glycaemic variability and risk of adverse cardiovascular events in acute coronary syndrome
Zhang, L., Li, F., Liu, H., Zhang, Z., Yang, F., Qian, L., & Wang, R. (2022) · Diabetes and Vascular Disease Research · doi:10.1177/14791641221137736 · Cited by 18 · see citing works
“Many studies had evaluated whether GV was directly related to the occurrence and adverse prognosis of ACS patients.(6,34,35) A recent metaanalysis showed that there was a negative association between GV and myocardial infarction.”
BackgroundMethod
Time in Range, Time in Tight Range, and Average Glucose Relationships Are Modulated by Glycemic Variability: Identification of a Glucose Distribution Model Connecting Glycemic Parameters Using Real-World Data
Xu, Y., Dunn, T. C., Bergenstal, R. M., Cheng, A., Dabiri, Y., & Ajjan, R. (2024) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2023.0564 · Cited by 18 · see citing works
“We have also demonstrated a strong relationship between TBR and CV, which has been documented before, 9,24 but our data are now able to more accurately deﬁne this association.”
Influential
Glucose profiles in obstructive sleep apnea and type 2 diabetes mellitus
Aurora, R. N., Gaynanova, I., Patel, P. S., & Punjabi, N. M. (2022) · Sleep Medicine · doi:10.1016/j.sleep.2022.04.007 · Cited by 16 · see citing works
Weight-neutral early time-restricted eating improves glycemic variation and time in range without changes in inflammatory markers
Bruno, J., Walker, J. M., Nasserifar, S., Upadhyay, D., Ronning, A., Vanegas, S. M., Popp, C. J., Barua, S., & Alemán, J. O. (2024) · iScience · doi:10.1016/j.isci.2024.111501 · Cited by 14 · see citing works
“35 This may more accurately assess dysregulation of glucose homeostasis than HbA1c or OGTT, the current gold standards for assessing glycemic control.”
To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study
Lazăr, S., Ioniță, I., Reurean‐Pintilei, D., Timar, R. Z., Luca, S. A., & Timar, B. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13020450 · Cited by 13 · see citing works
“On the other hand, it is known that a high GV represents a major burden in achieving the target values of the traditional glycemic control parameter [30].”
Background
Association between brain imaging biomarkers and continuous glucose monitoring-derived glycemic control indices in Japanese patients with type 2 diabetes mellitus
Inoue, C., Kusunoki, Y., Ohigashi, M., Osugi, K., Kitajima, K., Takagi, A., Inoue, M., Yagi, C., Tsunoda, T., Kakutani, M., et al. (2024) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2023-003744 · Cited by 10 · see citing works
“Statistical analyses were conducted using the BellCurve software V.4.04 (Social Survey Research Information, Tokyo, Japan).”
MethodInfluentialSelf-citation
Bridging the Gap: A Literature Review of Advancements in Obesity and Diabetes Mellitus Management
Pop, G. N., Manole, F., Buleu, F., Motofelea, A., Bircea, S., Popa, D., Motofelea, N., & Pirvu, C. (2024) · Applied Sciences · doi:10.3390/app14156565 · Cited by 8 · see citing works
Continuous glucose monitoring‐derived time in range is associated with changes in cognitive function test scores in Japanese patients with type 2 diabetes mellitus
Inoue, M., Kusunoki, Y., Ohigashi, M., Osugi, K., Inoue, C., Otsuka, A., Azuma, D., Ikeda, H., Tamada, D., Inagaki, T., et al. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16511 · Cited by 9 · see citing works
“14 Cerebral small vascular disease (SVD) is a microvascular disease or syndrome of the brain commonly seen in older people, with representative lesions including white matter lesions, lacunar infarction, subcortical infarction and cerebral microhemorrhage.”
Self-citation
Personal and Social‐Built Environmental Factors of Glucose Variability Among Multiethnic Groups of Adults With Type 2 Diabetes: Research Protocol Using Ecological Momentary Assessment, Continuous Glucose Monitoring, and Actigraphy
Nam, S., Jeon, S., Ash, G. I., WEINZIMER, S. A., Dunton, G. F., Parekh, N., Grey, M. J., Chen, K., Lee, M., Sajdlowska, A., et al. (2024) · Research in Nursing & Health · doi:10.1002/nur.22420 · Cited by 9 · see citing works
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“Newer studies highlight the importance of glycemic variability, as a risk predictor for micro-and macro-angiopathies in patients with DM [26,27].”
Background
Predictive Value of Glycemic Variability and HDL-C for Secondary Persistent Inflammatory Immunosuppressed Catabolic Syndrome in Patients with Sepsis
Yao, J., Chen, K., Tong, H., & Liu, R. (2023) · Journal of Inflammation Research · doi:10.2147/jir.s433895 · Cited by 6 · see citing works
“14 Stress hyperglycemia is a common clinical phenomenon in sepsis at early stage, but high GV at late stage may reflect an overall response to treatment.”
Background
Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study
Inaishi, J., Saisho, Y., Watanabe, Y., Tsuchiya, T., Sasaki, H., Masaoka, T., & Itoh, H. (2022) · BMC Endocrine Disorders · doi:10.1186/s12902-022-00932-9 · Cited by 6 · see citing works
“The definitions and interpretation of each index were described in previous reports [8, 9] and recent review [10].”
Background
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“20,21 25–27 The mechanism responsible is suspected to be an increased activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase resulting in excessive production of reactive oxygen species, oxidative DNA damage and decreased superoxide dismutase activity.”
Background
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“Alongside HbA1c, GV has become a widely recognized indicator of glucose control [34,35].”
Background
Employing an Artificial Intelligence Platform to Enhance Treatment Responses to GLP-1 Agonists by Utilizing Metabolic Variability Signatures Based on the Constrained Disorder Principle
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Self-citation
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Background
Factors Associated with Blood Glucose Fluctuations in Patients with Type 2 Diabetes: A Retrospective Observational Study Using Continuous Glucose Monitoring
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Background
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Authors: Kusunoki, Y., Konishi, K., Tsunoda, T., & Koyama, H.
Affiliations: Hyogo Medical University (JP)
ORCID: Kusunoki, Yoshiki
Konishi, Kosuke
Koyama, Hidenori
Venue: Internal Medicine
Publisher: Japanese Society of Internal Medicine
Published: 2022-02-01
Volume: 61
Issue: 3
Pages: 281-290
ISSN: 0918-2918 (ISSN-L)
1349-7235
DOI: 10.2169/internalmedicine.8424-21
PMC: PMC8866772
OpenAlex: W3200775034
Cited by: 40
References: 130
Citations by year: 2026: 10 · 2025: 10 · 2024: 11 · 2023: 5 · 2022: 4
FWCI: 3.73
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: cc-by-nc-nd
Locations: Internal Medicine (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Keywords: glycemic variability, diabetes mellitus, glycemic control, HbA1c, hypoglycemia, hyperglycemia, diabetic vascular complications, cardiovascular mortality
MeSH terms: Blood Glucose, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Glycated Hemoglobin, Humans, Quality of Life

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Significance of Glycemic Variability in Diabetes Mellitus

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