Skip to main content
SpringerLink
Log in

Prognostic significance of reverse dipping status on lower limb event in type 2 diabetic patients without peripheral arterial disease

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Aims

We assessed reverse dipping influence on the risk of lower limb events in type 2 diabetic patients without peripheral arterial disease.

Methods

Patients with type 2 diabetes addressed for cardiovascular risk stratification in our university hospital from 2008 to 2012 underwent 24 h blood pressure monitoring. Patients with a prior history of limb revascularization or with a stenosis > 50% of the legs were excluded. Reverse dipping was defined as a greater night-versus day-time systolic blood pressure. The endpoint was the first occurrence of lower limb revascularization or limb amputation. Hazard ratios (HRs) and 95% confidence intervals were calculated using the Cox model.

Results

Two hundred and eighty-one patients were included. During a median follow-up of 9.4 [7.7–10.6] years, 20 lower limb events and 45 all-cause deaths were observed. Thirty-five patients were reverse dippers. The reverse dipping status was associated with lower limb events when considering all-cause death as a competitive risk, (HR 3.61 [1.16–11.2], P = 0.026). Reverse dipping, HbA1C and proteinuria were independently associated with lower limb outcome in a multivariable analysis (respectively HR 4.09 [1.29–12.9], P = 0.017, HR 1.30 [1.04–1.63], P = 0.022 and HR 1.06 [1.02–1.11], P = 0.001).

Conclusions

Reverse dipping status is independently associated with worse limb outcome in type 2 diabetic patients.

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

References

  1. Williams R, Karuranga S, Malanda B et al (2020) Global and regional estimates and projections of diabetes related health expenditure: results from the international diabetes federation diabetes atlas. Diabetes Res Clin Pract. https://doi.org/10.1016/j.diabres.2020.108072

    Article  PubMed  Google Scholar 

  2. Soriano LC, Gerry F, Fowkes R, Johansson S, Allum AM, Rodriguez LAG (2017) Cardiovascular outcomes for patients with symptomatic peripheral artery disease: a cohort study in the health improvement network (THIN) in the UK. Eur J Prev Cardiol 24(18):1927–1937. https://doi.org/10.1177/2047487317736824

    Article  Google Scholar 

  3. Adler AI, Stevens RJ, Neil A, Stratton IM, Boulton AJIM, Holman RR (2002) UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. Diabetes Care 25(5):894–899. https://doi.org/10.2337/diacare.25.5.894

    Article  PubMed  Google Scholar 

  4. Mohammedi K, Woodward M, Hirakawa Y et al (2016) Microvascular and macrovascular disease and risk for major peripheral arterial disease in patients with type 2 diabetes. Diabetes Care 39(10):1796–1803. https://doi.org/10.2337/dc16-0588

    Article  CAS  PubMed  Google Scholar 

  5. Cardoso CRL, Melo JV, Santos TRM, Leite NC, Salles GF (2021) Traditional and non-traditional risk factors for peripheral artery disease development/progression in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study. Cardiovasc Diabetol. https://doi.org/10.1186/s12933-021-01249-y

    Article  PubMed  PubMed Central  Google Scholar 

  6. Potier L, Roussel R, Velho G et al (2019) Lower limb events in individuals with type 2 diabetes: evidence for an increased risk associated with diuretic use. Diabetologia. https://doi.org/10.1007/s00125-019-4835-z

    Article  PubMed  Google Scholar 

  7. Erkens JA, Klungel OH, Stolk RP, Spoelstra JA, Grobbee DE, Leufkens HG (2004) Antihypertensive drug therapy and the risk of lower extremity amputations in pharmacologically treated type 2 diabetes patients. Pharmacoepidemiol Drug Saf. https://doi.org/10.1002/pds.932

    Article  PubMed  Google Scholar 

  8. Itoga NK, Tawfik DS, Lee CK, Maruyama S, Leeper NJ, Chang TI (2018) Association of blood pressure measurements with peripheral artery disease events. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.118.033348

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hansen TW, Li Y, Boggia J, Thijs L, Richart T, Staessen JA (2011) Predictive role of the nighttime blood pressure. Hypertension. https://doi.org/10.1161/HYPERTENSIONAHA.109.133900

    Article  PubMed  Google Scholar 

  10. Cuspidi C, Sala C, Tadic M et al (2017) Clinical and prognostic significance of a reverse dipping pattern on ambulatory monitoring: an updated review. J Clin Hypertens. https://doi.org/10.1111/jch.13023

    Article  Google Scholar 

  11. Sprynger M, Rigo F, Moonen M et al (2018) Focus on echovascular imaging assessment of arterial disease: complement to the ESC guidelines (PARTIM 1) in collaboration with the working group on aorta and peripheral vascular diseases. Eur Heart J Cardiovasc Imaging. https://doi.org/10.1093/ehjci/jey103

    Article  PubMed  Google Scholar 

  12. Humphries MD, Brunson A, Li CS, Melnikow J, Romano PS (2016) Amputation trends for patients with lower extremity ulcers due to diabetes and peripheral artery disease using statewide data. J Vasc Surg. https://doi.org/10.1016/j.jvs.2016.06.096

    Article  PubMed  PubMed Central  Google Scholar 

  13. Paul SK, Bhatt DL, Montvida O (2016) The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium-glucose cotransporter type-2 inhibitors: real-world study. Eur Heart J. https://doi.org/10.1093/eurheartj/ehaa956

    Article  Google Scholar 

  14. Su D, Guo Q, Gao Y et al (2016) The relationship between red blood cell distribution width and blood pressure abnormal dipping in patients with essential hypertension: a cross-sectional study. BMJ Open. https://doi.org/10.1136/bmjopen-2015-010456

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ayala DE, Moyá A, Crespo JJ et al (2013) Circadian pattern of ambulatory blood pressure in hypertensive patients with and without type 2 diabetes. Chronobiol Int. https://doi.org/10.3109/07420528.2012.701489

    Article  PubMed  Google Scholar 

  16. Eguchi K, Ishikawa J, Hoshide S et al (2009) Night time blood pressure variability is a strong predictor for cardiovascular events in patients with type 2 diabetes. Am J Hypertens. https://doi.org/10.1038/ajh.2008.294

    Article  PubMed  Google Scholar 

  17. Bouhanick B, Bongard V, Amar J, Bousquel S, Chamontin B (2008) Prognostic value of nocturnal blood pressure and reverse-dipping status on the occurrence of cardiovascular events in hypertensive diabetic patients. Diabetes Metab. https://doi.org/10.1016/j.diabet.2008.05.005

    Article  PubMed  Google Scholar 

  18. Matsushita K, Ballew SH, Coresh J, Arima H, Ärnlöv J, Cirillo M et al (2017) Chronic kidney disease prognosis consortium measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. https://doi.org/10.1016/S2213-8587(17)30183-3

    Article  PubMed  PubMed Central  Google Scholar 

  19. Han J, Gao Y, Guo Q et al (2016) Cross-sectional study on the relationship between the level of serum cystatin C and blood pressure reverse dipping in hypertensive patients. BMJ Open. https://doi.org/10.1136/bmjopen-2016-011166

    Article  PubMed  PubMed Central  Google Scholar 

  20. Uzu T, Kimura G (1999) Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation. https://doi.org/10.1161/01.cir.100.15.1635

    Article  PubMed  Google Scholar 

  21. Spallone V, Ziegler D, Freeman R et al (2011) Toronto consensus panel on diabetic neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. https://doi.org/10.1002/dmrr.1239

    Article  PubMed  Google Scholar 

  22. Spallone V, Bernardi L, Ricordi L et al (1993) Relationship between the circadian rhythms of blood pressure and sympathovagal balance in diabetic autonomic neuropathy. Diabetes. https://doi.org/10.2337/diab.42.12.1745

    Article  PubMed  Google Scholar 

  23. Cuspidi C, Tadic M, Sala C, Gherbesi E, Grassi G, Mancia G (2019) Blood pressure non-dipping and obstructive sleep apnea syndrome: a meta-analysis. J Clin Med. https://doi.org/10.3390/jcm8091367

    Article  PubMed  PubMed Central  Google Scholar 

  24. Marinakis AG, Vyssoulis GP, Michaelides AP, Karpanou EA, Cokkinos DV, Toutouzas PK (2003) Impact of abnormal nocturnal blood pressure fall on vascular function. Am J Hypertens. https://doi.org/10.1016/s0895-7061(02)03262-4

    Article  PubMed  Google Scholar 

  25. Shin JI, Grams ME, Coresh J, Chang AR, Matsushita K (2019) Proteinuria and risk of lower-extremity amputation in patients with peripheral artery disease. Diabetes Care. https://doi.org/10.2337/dc19-0764

    Article  PubMed  PubMed Central  Google Scholar 

  26. Salmon AH, Satchell SC (2012) Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J Pathol. https://doi.org/10.1002/path.3964

    Article  PubMed  Google Scholar 

  27. Marcovecchio ML, Patricelli L, Zito M et al (2006) Ambulatory blood pressure monitoring in obese children: role of insulin resistance. J Hypertens. https://doi.org/10.1097/HJH.0b013e328010918b

    Article  PubMed  Google Scholar 

  28. Di Pino A, DeFronzo RA (2019) Insulin resistance and atherosclerosis: implications for insulin-sensitizing agents. Endocr Rev. https://doi.org/10.1210/er.2018-00141

    Article  PubMed  PubMed Central  Google Scholar 

  29. Rossen NB, Knudsen ST, Fleischer J et al (2014) Targeting nocturnal hypertension in type 2 diabetes mellitus. Hypertension. https://doi.org/10.1161/HYPERTENSIONAHA.114.03958

    Article  PubMed  Google Scholar 

  30. Hermida RC, Crespo JJ, Domínguez-Sardiña M et al (2020) Hygia project investigators bedtime hypertension treatment improves cardiovascular risk reduction: the hygia chronotherapy trial. Eur Heart J. https://doi.org/10.1093/eurheartj/ehz754 (PMID: 31641769)

    Article  PubMed  Google Scholar 

  31. Montaigne D, Staels B (2018) Time to check the clock in cardiovascular research and medicine. Circ Res. https://doi.org/10.1161/CIRCRESAHA.118.313543

    Article  PubMed  Google Scholar 

Download references

Funding

Pr David Montaigne is supported by Grants from Agence Nationale pour la Recherche (ANR-10-LBEX-46, ANR TOMIS-Leukocyte: ANR-CE14-0003-01 and ANR CALMOS: ANR-18-CE17-0003-02), the Leducq Foundation LEAN Network 16CVD01 and the National Center for Precision Diabetic Medicine—PreciDIAB (ANR-18-IBHU-0001; 20001891/NP0025517; 2019_ESR_11).

Author information

Authors and Affiliations

  1. CHU Lille, Vascular Medicine and Hypertension Department, Institut Cœur Poumon, Boulevard Pr Leclercq, 59000, Lille, France

    Pascal Delsart, Guillaume Ledieu, Diane-Flore Eymard & Agathe Le Chevalier De Preville

  2. Endocrinology, Diabetology and Metabolism, CHU Lille, 59000, Lille, France

    Madleen Lemaitre, Anne Vambergue & Florence Baudoux

  3. Inserm U1011, CHU Lille, Institut Pasteur de Lille, EGID, Univ. Lille, 59000, Lille, France

    Sandro Ninni & David Montaigne

  4. Inserm U1167, CHU Lille, Institut Pasteur, Univ. Lille, 59000, Lille, France

    Christophe Bauters

  5. Inserm U1008, CHU Lille, 59000, Lille, France

    Jonathan Sobocinski

  6. CHU Lille, University of Lille, 59000, Lille, France

    Claire Mounier-Vehier

Authors
  1. Pascal Delsart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madleen Lemaitre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne Vambergue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandro Ninni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christophe Bauters
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guillaume Ledieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Diane-Flore Eymard
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Florence Baudoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Agathe Le Chevalier De Preville
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jonathan Sobocinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. David Montaigne
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Claire Mounier-Vehier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pascal Delsart.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

The study was conducted according to the guidelines of the declaration oh Helsinski. The present study was approved by the French national data protection commission (Commission Nationale de l’Informatique et des Libertés; reference: DEC 2015-9).

Informed consent

Each patient received a verbal explanation and an inform consent of the study’s objectives and a written information about the right to withdraw permission for the subsequent use of his or her personal data.

Additional information

Managed by Massimo Porta.

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Delsart, P., Lemaitre, M., Vambergue, A. et al. Prognostic significance of reverse dipping status on lower limb event in type 2 diabetic patients without peripheral arterial disease. Acta Diabetol 59, 843–850 (2022). https://doi.org/10.1007/s00592-022-01879-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-022-01879-y

Keywords

Search

Navigation