Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational studyBMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h3234 (Published 22 June 2015) Cite this as: BMJ 2015;350:h3234
- Isabelle Steineck, physician1,
- Jan Cederholm, associate professor2,
- Björn Eliasson, adjunct professor of medicine, senior consultant3,
- Araz Rawshani, physician4,
- Katarina Eeg-Olofsson, physician3,
- Ann-Marie Svensson, research nurse4,
- Björn Zethelius, associate professor5, scientific director6,
- Tarik Avdic, medical student4,
- Mona Landin-Olsson, adjunct professor of medicine, senior consultant7,
- Johan Jendle, associate professor, senior consultant8,
- Soffia Gudbjörnsdóttir, associate professor34
- the Swedish National Diabetes Register
- 1Department of Endocrinology, Aarhus University Hospital, Aarhus Denmark
- 2Department of Public Health and Caring Sciences/Family and Preventive Medicine, Uppsala University, Uppsala, Sweden
- 3Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
- 4National Diabetes Register, Centre of Registers, Gothenburg, Sweden
- 5Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
- 6Medical Products Agency, Uppsala, Sweden
- 7Department of Clinical Science, Lund University, Lund, Sweden
- 8Faculty of Health Sciences and Medicine, Örebro University, Örebro, Sweden
- Correspondence to: I Steineck
- Accepted 11 June 2015
Objective To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes.
Design Observational study.
Setting Swedish National Diabetes Register, Sweden 2005-12.
Participants 18 168 people with type 1 diabetes, 2441 using insulin pump therapy and 15 727 using multiple daily insulin injections.
Main outcome measures Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases.
Results Follow-up was for a mean of 6.8 years until December 2012, with 114 135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association.
Conclusion Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections.
We thank all regional Swedish National Diabetes Register coordinators, contributing nurses, physicians, and patients who contributed to the success of this study. The Swedish Society of Diabetology and the Swedish Diabetes Association, a patient advocacy group, support the Swedish National Diabetes Register. The results and views expressed in the study represent those of the authors and not necessarily those of the Swedish Medical Products Agency, at which one of the authors (BZ) is employed. The study was presented at the 50th European Association for the Study of Diabetes (EASD) Annual Meeting, Vienna, Austria, September 2014.
Contributors: IS, JC, and SG researched the data; IS and JC performed the statistical analyses; IS, JC, and SG wrote the article, contributed to the discussion, and reviewed and edited the article. BE, AR, KE-O, A-MS, BZ, TA, ML-O, and JJ contributed to the discussion and reviewed and edited the article. SG is guarantor.
Funding: This study received funding from the European Association for the study of diabetes. The Swedish National Diabetes Register is funded by the Swedish Association of Local Authorities and Regions.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: KE-O has received fees from Sanofi and Novo Nordisk for lectures outside the submitted work; ML-O lectures about diabetology and has been paid by different pharmaceutical companies.
Ethical approval: The study was approved by the regional ethical review board at the University of Gothenburg. All individuals with diabetes give their informed consent before being entered.
Data sharing: No additional data available, but data from this study are available on request.
Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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