Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study [采用每日多剂胰岛素泵疗法的18168名1型糖尿病患者的心血管疾病死亡率：观察性研究]

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BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h3234 (Published 22 June 2015)
Cite this as: BMJ 2015;350:h3234

Authors
Isabelle Steineck, physician, Jan Cederholm, associate professor, Björn Eliasson, adjunct professor of medicine, senior consultant, Araz Rawshani, physician, Katarina Eeg-Olofsson, physician, Ann-Marie Svensson, research nurse, Björn Zethelius, associate professor, scientific director, Tarik Avdic, medical student, Mona Landin-Olsson, adjunct professor of medicine, senior consultant, Johan Jendle, associate professor, senior consultant, Soffia Gudbjörnsdóttir, associate professor the Swedish National Diabetes Register

Abstract
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.