Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study

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.

[1]  J. Shaw,et al.  Glycemic control and excess mortality in type 1 diabetes. , 2015, The New England journal of medicine.

[2]  C. Pipper,et al.  Nationwide reduction in the frequency of severe hypoglycemia by half , 2015, Acta Diabetologica.

[3]  S. Gudbjörnsdottir,et al.  Diabetes care--improvement through measurement. , 2014, Diabetes research and clinical practice.

[4]  W. Herman,et al.  Severe Hypoglycemia and Mortality After Cardiovascular Events for Type 1 Diabetic Patients in Sweden , 2014, Diabetes Care.

[5]  Steven G. Heeringa,et al.  Multiple Imputation of Missing Data Using SAS , 2014 .

[6]  Alan Bernjak,et al.  Risk of Cardiac Arrhythmias During Hypoglycemia in Patients With Type 2 Diabetes and Cardiovascular Risk , 2014, Diabetes.

[7]  P. Wiklund,et al.  Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes , 2014, BMJ : British Medical Journal.

[8]  M. Hanefeld,et al.  Relationship Between Hypoglycemic Episodes and Ventricular Arrhythmias in Patients With Type 2 Diabetes and Cardiovascular Diseases: Silent Hypoglycemias and Silent Arrhythmias , 2014, Diabetes Care.

[9]  J. Sandall,et al.  What happens when patients know more than their doctors? Experiences of health interactions after diabetes patient education: a qualitative patient-led study , 2013, BMJ Open.

[10]  S. Yusuf,et al.  Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial. , 2013, European heart journal.

[11]  O. Rolandsson,et al.  Aspirin treatment and risk of first incident cardiovascular diseases in patients with type 2 diabetes: an observational study from the Swedish National Diabetes Register , 2013, BMJ Open.

[12]  F. Montorsi,et al.  Comparison of mortality outcomes after radical prostatectomy versus radiotherapy in patients with localized prostate cancer: A population‐based analysis , 2012, International journal of urology : official journal of the Japanese Urological Association.

[13]  G. Bruno,et al.  Severe Hypoglycemia and Cardiovascular Disease Incidence in Type 1 Diabetes , 2012, Diabetes Care.

[14]  C. Castell,et al.  Hypoglycaemia and cardiovascular disease in Type 1 Diabetes. Results from the Catalan National Public Health registry on insulin pump therapy. , 2012, Diabetes research and clinical practice.

[15]  J. Pickup,et al.  Insulin-pump therapy for type 1 diabetes mellitus. , 2012, The New England journal of medicine.

[16]  Masataka Nakano,et al.  Acute Coronary Events , 2012, Circulation.

[17]  E. Bass,et al.  Comparative Effectiveness and Safety of Methods of Insulin Delivery and Glucose Monitoring for Diabetes Mellitus A Systematic Review and Meta-analysis , 2012 .

[18]  S. Gudbjörnsdottir,et al.  A new model for 5‐year risk of cardiovascular disease in Type 1 diabetes; from the Swedish National Diabetes Register (NDR) , 2011, Diabetic medicine : a journal of the British Diabetic Association.

[19]  M. Rosenqvist,et al.  Association of candesartan vs losartan with all-cause mortality in patients with heart failure. , 2011, JAMA.

[20]  George Dailey,et al.  Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. , 2010, The New England journal of medicine.

[21]  P. Nilsson,et al.  Glycemic Control and Cardiovascular Disease in 7,454 Patients With Type 1 Diabetes , 2010, Diabetes Care.

[22]  Douglas E. Faries,et al.  Analysis of Observational Health Care Data Using SAS , 2010 .

[23]  Matthew Page,et al.  Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. , 2010, The Cochrane database of systematic reviews.

[24]  N. Marchionni,et al.  Continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 1 diabetes: a meta-analysis , 2010, Acta Diabetologica.

[25]  N. Sattar,et al.  Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials , 2009, The Lancet.

[26]  Yogish C Kudva,et al.  Clinical review: Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections. , 2009, The Journal of clinical endocrinology and metabolism.

[27]  Grant D. Huang,et al.  Glucose control and vascular complications in veterans with type 2 diabetes. , 2009, The New England journal of medicine.

[28]  Medical Advisory Secretariat.  Continuous Subcutaneous Insulin Infusion (CSII) Pumps for Type 1 and Type 2 Adult Diabetic Populations: An Evidence-Based Analysis. , 2009, Ontario health technology assessment series.

[29]  R. Little,et al.  Statistical methods for monitoring the relationship between the IFCC reference measurement procedure for hemoglobin A1c and the designated comparison methods in the United States, Japan, and Sweden. , 2008, Clinical chemistry.

[30]  A J Sutton,et al.  Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta‐analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion , 2008, Diabetic medicine : a journal of the British Diabetic Association.

[31]  A. Berghold,et al.  Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis , 2008, Diabetologia.

[32]  Peter C Austin,et al.  A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study , 2007, Statistics in medicine.

[33]  B. Zinman,et al.  Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. , 2005, The New England journal of medicine.

[34]  L. Råstam,et al.  Comparison of different procedures to identify probable cases of myocardial infarction and stroke in two Swedish prospective cohort studies using local and national routine registers , 2000, European Journal of Epidemiology.

[35]  Björn Eliasson,et al.  The National Diabetes Register in Sweden: an implementation of the St. Vincent Declaration for Quality Improvement in Diabetes Care. , 2003, Diabetes care.

[36]  T. Erlinger,et al.  Safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes. , 2003, Diabetes care.

[37]  E. Casiglia,et al.  Continuous subcutaneous insulin infusion (CSII) in the Veneto region: efficacy, acceptability and quality of life , 2002, Diabetic medicine : a journal of the British Diabetic Association.

[38]  R. D'Agostino.  Adjustment Methods: Propensity Score Methods for Bias Reduction in the Comparison of a Treatment to a Non‐Randomized Control Group , 2005 .

[39]  R. Kronmal,et al.  Assessing the sensitivity of regression results to unmeasured confounders in observational studies. , 1998, Biometrics.

[40]  Hypoglycemia in the Diabetes Control and Complications Trial , 1997, Diabetes.

[41]  P. Davidson,et al.  Reduction in Severe Hypoglycemia With Long-Term Continuous Subcutaneous Insulin Infusion in Type I Diabetes , 1996, Diabetes Care.

[42]  H. Tunstall-Pedoe,et al.  Myocardial Infarction and Coronary Deaths in the World Health Organization MONICA Project: Registration Procedures, Event Rates, and Case‐Fatality Rates in 38 Populations From 21 Countries in Four Continents , 1994, Circulation.