Skip to main content

Advertisement

SpringerLink
Log in

Association of time in range with lower extremity atherosclerotic disease in type 2 diabetes mellitus: a prospective cohort study

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Time in range (TIR) has surfaced as a key continuous glucose monitoring (CGM)—derived metric, which was linked to diabetes-related outcomes. We aimed to investigate the association of TIR with the risk of lower extremity atherosclerotic disease (LEAD) among patients with type 2 diabetes.

Methods

A total of 1351 adult patients with type 2 diabetes were prospectively recruited from a single center in Shanghai, China. TIR was obtained from CGM data at baseline. LEAD was measured with color Doppler ultrasonography. Cox proportion hazard regression analysis was used to assess the association between TIR and the risk of incident/progressive LEAD.

Results

During a median follow-up of 7.4 years, 450 participants developed incident/progressive LEAD. The multivariable-adjusted hazard ratios (HRs) for incident/progressive LEAD across different levels of TIR ( > 85%, 71~85%, 51~70%, and ≤50%) were 1.00, 1.15 (95% confidence interval [CI] 0.87–1.52), 1.37 (95% CI 1.04–1.80) and 1.46 (95% CI 1.10–1.94) (P for trend = 0.004), respectively. With each 10% decrease in TIR, the multivariable-adjusted risk of incident/progressive LEAD increased by 7% (95% CI 1.02–1.11). Similar results were found in the association between TIR and incident LEAD as the secondary outcome (P for trend < 0.001).

Conclusions

The current study found an inverse association of TIR with the risk of LEAD among patients with type 2 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Restrictions apply to the availability of data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. Data are however available from the authors upon reasonable request.

References

  1. M.I. Maiorino, S. Signoriello, A. Maio, P. Chiodini, G. Bellastella, L. Scappaticcio, M. Longo, D. Giugliano, K. Esposito, Effects of continuous glucose monitoring on metrics of glycemic control in diabetes: a systematic review with meta-analysis of randomized controlled trials. Diabetes Care 43(5), 1146–1156 (2020)

    Article  CAS  Google Scholar 

  2. J. Bolinder, R. Antuna, P. Geelhoed-Duijvestijn, J. Kröger, R. Weitgasser, Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial. Lancet 388(10057), 2254–2263 (2016)

    Article  Google Scholar 

  3. R.W. Beck, T. Riddlesworth, K. Ruedy, A. Ahmann, R. Bergenstal, S. Haller, C. Kollman, D. Kruger, J.B. McGill, W. Polonsky, E. Toschi, H. Wolpert, D. Price, Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial. Jama 317(4), 371–378 (2017)

    Article  CAS  Google Scholar 

  4. T. Haak, H. Hanaire, R. Ajjan, N. Hermanns, J.P. Riveline, G. Rayman, Flash glucose-sensing technology as a replacement for blood glucose monitoring for the management of insulin-treated type 2 diabetes: a multicenter, open-label randomized controlled trial. Diabetes Ther. 8(1), 55–73 (2017)

    Article  CAS  Google Scholar 

  5. G. Grunberger, J. Sherr, M. Allende, T. Blevins, B. Bode, Y. Handelsman, R. Hellman, R. Lajara, V.L. Roberts, D. Rodbard, C. Stec, J. Unger, American Association of Clinical Endocrinology Clinical Practice Guideline: the use of advanced technology in the management of persons with diabetes mellitus. Endocr. Pr. 27(6), 505–537 (2021)

    Article  Google Scholar 

  6. Xie P., Deng B., Zhang X., Li Y., Du C., Rui S., Deng W., Boey J., Armstrong D.G., Ma Y., Deng W. Time in range in relation to amputation and all-cause mortality in hospitalised patients with diabetic foot ulcers. Diabetes Metab. Res. Rev. 38(2), e3498 (2021)

  7. K. Kristensen, L.E. Ögge, V. Sengpiel, K. Kjölhede, A. Dotevall, A. Elfvin, F.K. Knop, N. Wiberg, A. Katsarou, N. Shaat, L. Kristensen, K. Berntorp, Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies. Diabetologia 62(7), 1143–1153 (2019)

    Article  CAS  Google Scholar 

  8. C.B. Olivier, H. Mulder, W.R. Hiatt, W.S. Jones, F.G.R. Fowkes, F.W. Rockhold, J.S. Berger, I. Baumgartner, P. Held, B.G. Katona, L. Norgren, J. Blomster, M.R. Patel, K.W. Mahaffey, Incidence, characteristics, and outcomes of myocardial infarction in patients with peripheral artery disease: insights from the EUCLID trial. JAMA Cardiol. 4(1), 7–15 (2019)

    Article  Google Scholar 

  9. J.A. Barnes, M.A. Eid, M.A. Creager, P.P. Goodney, Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease. Arterioscler Thromb. Vasc. Biol. 40(8), 1808–1817 (2020)

    Article  CAS  Google Scholar 

  10. M.H. Criqui, V. Aboyans, Epidemiology of peripheral artery disease. Circ. Res 116(9), 1509–1526 (2015)

    Article  CAS  Google Scholar 

  11. V. Aboyans, J.B. Ricco, M.E.L. Bartelink, M. Björck, M. Brodmann, T. Cohnert, J.P. Collet, M. Czerny, M. De Carlo, S. Debus, C. Espinola-Klein, T. Kahan, S. Kownator, L. Mazzolai, A.R. Naylor, M. Roffi, J. Röther, M. Sprynger, M. Tendera, G. Tepe, M. Venermo, C. Vlachopoulos, I. Desormais, 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur. Heart J. 39(9), 763–816 (2018)

    Article  Google Scholar 

  12. K.G. Alberti, P.Z. Zimmet, Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med 15(7), 539–553 (1998)

    Article  CAS  Google Scholar 

  13. J. Lu, X. Ma, J. Zhou, L. Zhang, Y. Mo, L. Ying, W. Lu, W. Zhu, Y. Bao, R.A. Vigersky, W. Jia, Association of time in range, as assessed by continuous glucose monitoring, with diabetic retinopathy in type 2 diabetes. Diabetes Care 41(11), 2370–2376 (2018)

    Article  CAS  Google Scholar 

  14. A.S. Levey, L.A. Stevens, C.H. Schmid, Y.L. Zhang, A.F. Castro 3rd, H.I. Feldman, J.W. Kusek, P. Eggers, F. Van Lente, T. Greene, J. Coresh, A new equation to estimate glomerular filtration rate. Ann. Intern Med 150(9), 604–612 (2009)

    Article  Google Scholar 

  15. X. He, J. Su, X. Ma, W. Lu, W. Zhu, Y. Wang, Y. Bao, J. Zhou, The association between serum growth differentiation factor 15 levels and lower extremity atherosclerotic disease is independent of body mass index in type 2 diabetes. Cardiovasc. Diabetol. 19(1), 40–40 (2020)

    Article  CAS  Google Scholar 

  16. P.J. Touboul, M.G. Hennerici, S. Meairs, H. Adams, P. Amarenco, N. Bornstein, L. Csiba, M. Desvarieux, S. Ebrahim, R. Hernandez Hernandez, M. Jaff, S. Kownator, T. Naqvi, P. Prati, T. Rundek, M. Sitzer, U. Schminke, J.C. Tardif, A. Taylor, E. Vicaut, K.S. Woo, Mannheim carotid intima-media thickness and plaque consensus (2004–2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc. Dis. 34(4), 290–296 (2012)

    Article  Google Scholar 

  17. R.W. Beck, R.M. Bergenstal, T.D. Riddlesworth, C. Kollman, Z. Li, A.S. Brown, K.L. Close, Validation of time in range as an outcome measure for diabetes clinical trials. Diabetes Care 42(3), 400–405 (2019)

    Article  CAS  Google Scholar 

  18. El Malahi A., Van Elsen M., Charleer S., Dirinck E., Ledeganck K., Keymeulen B., Crenier L., Radermecker R., Taes Y., Vercammen C., Nobels F., Mathieu C., Gillard P., De Block C. Relationship between time in range, glycemic variability, HbA1c and complications in adults with type 1 diabetes mellitus. J. Clin. Endocrinol. Metab. 107(2), E570-E581 (2021)

  19. Mayeda L., Katz R., Ahmad I., Bansal N., Batacchi Z., Hirsch I.B., Robinson N., Trence D.L., Zelnick L., de Boer I.H. Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease. BMJ Open Diabetes Res. Care 8(1), e000991 (2020)

  20. J.H. Yoo, M.S. Choi, J. Ahn, S.W. Park, Y. Kim, K.Y. Hur, S.M. Jin, G. Kim, J.H. Kim, Association between continuous glucose monitoring-derived time in range, other core metrics, and albuminuria in type 2 diabetes. Diabetes Technol. Ther. 22(10), 768–776 (2020)

    Article  CAS  Google Scholar 

  21. Q. Guo, P. Zang, S. Xu, W. Song, Z. Zhang, C. Liu, Z. Guo, J. Chen, B. Lu, P. Gu, J. Shao, Time in range, as a novel metric of glycemic control, is reversely associated with presence of diabetic cardiovascular autonomic neuropathy independent of hba1c in chinese type 2 diabetes. J. Diabetes Res 2020, 5817074 (2020)

    PubMed  PubMed Central  Google Scholar 

  22. M.Y. Kim, G. Kim, J.Y. Park, M.S. Choi, J.E. Jun, Y.B. Lee, S.M. Jin, K.Y. Hur, J.H. Kim, The association between continuous glucose monitoring-derived metrics and cardiovascular autonomic neuropathy in outpatients with type 2 diabetes. Diabetes Technol. Ther. 23(6), 434–442 (2021)

    Article  CAS  Google Scholar 

  23. J. Lu, X. Ma, Y. Shen, Q. Wu, R. Wang, L. Zhang, Y. Mo, W. Lu, W. Zhu, Y. Bao, R.A. Vigersky, W. Jia, J. Zhou, Time in range is associated with carotid intima-media thickness in type 2 diabetes. Diabetes Technol. Ther. 22(2), 72–78 (2020)

    Article  CAS  Google Scholar 

  24. E. Selvin, T.P. Erlinger, Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation 110(6), 738–743 (2004)

    Article  Google Scholar 

  25. C.P. Yang, C.C. Lin, C.I. Li, C.S. Liu, C.H. Lin, K.L. Hwang, S.Y. Yang, T.C. Li, Fasting plasma glucose variability and HbA1c are associated with peripheral artery disease risk in type 2 diabetes. Cardiovasc. Diabetol. 19(1), 4 (2020)

    Article  CAS  Google Scholar 

  26. Y. Shen, D. Dai, J. Lu, Y. Wang, W. Zhu, Y. Bao, G. Hu, J. Zhou, Visit-to-visit variability of glycated albumin was associated with incidence or progression of lower extremity atherosclerotic disease. Cardiovasc. Diabetol. 19(1), 211 (2020)

    Article  CAS  Google Scholar 

  27. C. Zhang, M. Tang, X. Lu, Y. Zhou, W. Zhao, Y. Liu, Y. Liu, X. Guo, Relationship of ankle-brachial index, vibration perception threshold, and current perception threshold to glycemic variability in type 2 diabetes. Medicine 99(12), e19374 (2020)

    Article  CAS  Google Scholar 

  28. A. Ceriello, K. Esposito, L. Piconi, M.A. Ihnat, J.E. Thorpe, R. Testa, M. Boemi, D. Giugliano, Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57(5), 1349–1354 (2008)

    Article  CAS  Google Scholar 

  29. R.W. Beck, R.M. Bergenstal, P. Cheng, C. Kollman, A.L. Carlson, M.L. Johnson, D. Rodbard, The relationships between time in range, hyperglycemia metrics, and HbA1c. J. Diabetes Sci. Technol. 13(4), 614–626 (2019)

    Article  Google Scholar 

  30. J. Lu, X. Ma, L. Zhang, Y. Mo, W. Lu, W. Zhu, Y. Bao, W. Jia, J. Zhou, Glycemic variability modifies the relationship between time in range and hemoglobin A1c estimated from continuous glucose monitoring: A preliminary study. Diabetes Res Clin. Pr. 161, 108032 (2020)

    Article  CAS  Google Scholar 

  31. T.W. Rooke, A.T. Hirsch, S. Misra, A.N. Sidawy, J.A. Beckman, L.K. Findeiss, J. Golzarian, H.L. Gornik, J.L. Halperin, M.R. Jaff, G.L. Moneta, J.W. Olin, J.C. Stanley, C.J. White, J.V. White, R.E. Zierler, 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 58(19), 2020–2045 (2011)

    Article  Google Scholar 

Download references

Acknowledgements

We appreciate all the involved doctors and nurses from Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, as well as all the patients who participated in this study.

Author contributions

J.Z. designed the study. Y.W., J.L. and J.N. collected the data. Y.W. cleaned the data. Y.W. and J.L. performed statistical analysis and wrote the draft of the manuscript. J.Z. rescanned and edited the manuscript. All authors read and approved the final manuscript.

Funding

This work was funded by the National Key Research and Development Program of China (2018YFC2001004), the Shanghai Municipal Education Commission‐Gaofeng Clinical Medicine Grant (20161430), and the Shanghai “Rising Stars of Medical Talent” Youth Development Program–Outstanding Youth Medical Talents.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, China

    Yaxin Wang, Jingyi Lu, Yun Shen, Jiaying Ni, Lei Zhang, Wei Lu, Wei Zhu, Yuqian Bao & Jian Zhou

Authors
  1. Yaxin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jingyi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yun Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiaying Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuqian Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jian Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Zhou.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval and consent to participate

The study and the analysis plan were approved by the Research Ethics Committees of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital. We have obtained informed consent from all participants.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

These authors contributed equally: Yaxin Wang, Jingyi Lu

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Lu, J., Shen, Y. et al. Association of time in range with lower extremity atherosclerotic disease in type 2 diabetes mellitus: a prospective cohort study. Endocrine 76, 593–600 (2022). https://doi.org/10.1007/s12020-022-03038-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-022-03038-3

Keywords

Search

Navigation