Smoking and progression of diabetic nephropathy in patients with type 1 diabetes
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To evaluate the effect of cumulative smoking on the development of diabetic nephropathy.
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.
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.
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.
KeywordsType 1 diabetes Diabetic nephropathy Microalbuminuria Macroalbuminuria End-stage renal disease Smoking Smoking cessation
Urinary albumin excretion rate
Estimated glomerular filtration rate
Estimated glucose disposal rate
End-stage renal disease
Finnish Diabetic Nephropathy Study
The authors would like to acknowledge all physicians and nurses at each FinnDiane Center participating in patient recruitment and characterization (see online supplement).
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.
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.
Compliance with ethical standards
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.
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 was obtained from all patients for being included in the study.
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