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Smoking and progression of diabetic nephropathy in patients with type 1 diabetes

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Abstract

Aims

To evaluate the effect of cumulative smoking on the development of diabetic nephropathy.

Methods

Study included 3613 patients with type 1 diabetes, participating in the Finnish Diabetic Nephropathy Study. The 12-year cumulative risk of microalbuminuria, macroalbuminuria and end-stage renal disease (ESRD) was estimated for current, ex- and nonsmokers. Cox regression analyses, with multivariable adjustments for other risk factors for diabetic nephropathy, were used to evaluate the risk at different stages of diabetic nephropathy based on the cumulative amount of smoking in pack-years.

Results

The 12-year cumulative risk of microalbuminuria was 18.9 % (95 % CI 14.6–23.0, P < 0.0001) for current smokers and 15.1 % (10.3–19.6, P = 0.087) for ex-smokers, compared with 10.0 % (7.8–12.1) for nonsmokers. The corresponding risks of macroalbuminuria were 14.4 % (95 % CI 10.8–17.9, P < 0.0001), 6.1 % (3.5–8.6, P = 0.082) and 4.7 % (3.0–6.4), respectively. The 12-year cumulative risk of ESRD was 10.3 % (95 % CI 8.4–12.4, P < 0.0001) for current smokers and 10.0 % (7.9–12.3, P < 0.0001) for ex-smokers, compared with 5.6 % (4.6–6.7) for nonsmokers. In the current smokers, one pack-year increased the risk of macroalbuminuria with a HR of 1.025 (1.010–1.041) and the risk of ESRD with a HR of 1.014 (1.001–1.026) compared with nonsmokers, in the fully adjusted model. In the ex-smokers, the risk of macroalbuminuria and ESRD was no different from the risk in nonsmokers after multivariable adjustment.

Conclusions

Current smoking is a risk factor for the progression of diabetic nephropathy and the risk increases with the increasing dose of smoking. Ex-smokers seem to carry a similar risk of progression of diabetic nephropathy as nonsmokers.

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Abbreviations

UAER:

Urinary albumin excretion rate

eGFR:

Estimated glomerular filtration rate

eGDR:

Estimated glucose disposal rate

ESRD:

End-stage renal disease

FinnDiane:

Finnish Diabetic Nephropathy Study

IQR:

Interquartile range

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Acknowledgments

The authors would like to acknowledge all physicians and nurses at each FinnDiane Center participating in patient recruitment and characterization (see online supplement).

Funding

This research was supported by grants from the Folkhälsan Research Foundation, Academy of Finland (134379), Wilhelm and Else Stockmann Foundation, Diabetes Research Foundation, Liv och Hälsa Foundation, Finska Läkaresällskapet, NovoNordisk Foundation, Signe and Ane Gyllenberg Foundation and Päivikki and Sakari Sohlberg Foundation. The funding sources were not involved in the design or conduct of the study.

Author contribution

MF designed the study, carried out statistical analyses and wrote the manuscript. VH contributed to the design of the study, statistical analyses and aspects of the manuscript. CF contributed to the design of the study and critically revised the manuscript. LT, JW, NT and RL contributed to the collection of the data and critically revised the manuscript. P-HG contributed to the study design and edited and critically revised the manuscript. P-HG is the guarantor of this work, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final version of the manuscript for publication.

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Authors and Affiliations

  1. Folkhälsan Research Center, Folkhälsan Institute of Genetics, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland

    Maija Feodoroff, Valma Harjutsalo, Carol Forsblom, Lena Thorn, Johan Wadén, Nina Tolonen, Raija Lithovius & Per-Henrik Groop

  2. Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Maija Feodoroff, Valma Harjutsalo, Carol Forsblom, Lena Thorn, Johan Wadén, Nina Tolonen, Raija Lithovius & Per-Henrik Groop

  3. Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland

    Maija Feodoroff, Valma Harjutsalo, Carol Forsblom, Lena Thorn, Johan Wadén, Nina Tolonen, Raija Lithovius & Per-Henrik Groop

  4. Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland

    Valma Harjutsalo

  5. The Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia

    Per-Henrik Groop

Authors
  1. Maija Feodoroff
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  2. Valma Harjutsalo
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  3. Carol Forsblom
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  4. Lena Thorn
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  5. Johan Wadén
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  6. Nina Tolonen
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  7. Raija Lithovius
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  8. Per-Henrik Groop
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Corresponding author

Correspondence to Per-Henrik Groop.

Ethics declarations

Conflict of interest

P.-H. G. has received lecture honorariums from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Genzyme, Medscape, MSD, Novartis, Novo Nordisk and Sanofi. P.-H. G. is an advisory board member of Abbott, AbbVie, Boehringer Ingelheim, Cebix, Eli Lilly, Janssen, Medscape and Novartis. P.-H. G. has received investigator-initiated study grants from Eli Lilly and Roche. No other potential conflicts of interest relevant to this article were reported.

Ethical standard

The study was conducted in accordance with the Declaration of Helsinki and accepted by the Helsinki University Hospital Research Ethics Committee.

Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Additional information

Managed by Massimo Federici.

On behalf of the FinnDiane Study Group.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 23 kb)

Supplementary material 2 (DOCX 12 kb)

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Feodoroff, M., Harjutsalo, V., Forsblom, C. et al. Smoking and progression of diabetic nephropathy in patients with type 1 diabetes. Acta Diabetol 53, 525–533 (2016). https://doi.org/10.1007/s00592-015-0822-0

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  • DOI: https://doi.org/10.1007/s00592-015-0822-0

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