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

Ashley Choi, PharmD Candidate 2016, Mercer University College of Pharmacy

Diabetes is a complex, chronic endocrine disease that necessitates intensive ongoing medical care, according to the American Diabetes Association’s (ADA’s) “Standards of Medical Care in Diabetes” guidelines. As part of the initial evaluation and diabetes management planning, the guidelines recommend to assess common comorbid conditions that may complicate diabetes management.  Due to comorbidities and concurrent conditions, this may induce clinical challenges to polypharmacy, general symptoms, and complexity of care, per ADA guidelines.1

The “Standards of Medical Care in Diabetes” guidelines suggests a comprehensive plan to reduce cardiovascular risks since patients with diabetes also have an increased risk of cardiovascular disease (CVD).  According to the guidelines, CVD is the main cause of morbidity and mortality in patients with diabetes.1  The American Heart Association’s (AHA’s) scientific statement also states that patients with type 1 diabetes (T1DM) have two- to 10 fold higher rates of coronary heart disease and death compared to a non-diabetic population since multiple CVD risk factors exist in T1DM.2

For the hyperglycemia management in T1DM patients, insulin is suggested as the optimal therapy by different guidelines. 1,3  The “Consensus Evidence-based Guidelines for Use of Insulin Pump Therapy in the Management of Diabetes as per Indian Clinical Practice” states that benefits of intensified insulin therapy (IIT) produces good glycemic control achievement and reduction of complication risks in diabetes. For the IIT, the guideline considered insulin administration in forms of multiple daily injections (MDI) or using an external insulin delivery device such as a continuous subcutaneous insulin infusion (CSII) pump.3

Per the “Consensus Evidence-based Guidelines for Use of Insulin Pump Therapy in the Management of Diabetes as per Indian Clinical Practice,” CSII is a small programmable pump augmented with a fine tube introduced to a soft plastic cannula. It is considered to be the most refined and accurate insulin delivery aiming the mimicry of endogenous insulin delivery profile.  The CSII programs the multiple various basal rates of infusion based on individual lifestyle per guidelines. The pump can also be programmed to deliver a bolus insulin dose during meals in order to cover the excess carbohydrate ingestion.3

Title: Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18,168 people with type 1 diabetes: observational study4
Design Observational study; (N = 18,168)
Objective The primary aim of the study was to investigate the long term effects of insulin pump therapy on cardiovascular mortality in people with type 1 diabetes mellitus (T1DM).
Study Groups Patients with T1DM entered in the Swedish National Diabetes Register for whom data were available:

(1)  Subjects using insulin pump therapy/PUMP (n = 2,441)

(2)  Subjects using multiple daily insulin injections/MDIs (n = 15,727)

Methods Clinical characteristics for all subjects were obtained at baseline.  A history of cardiovascular disease was also defined. They were monitored throughout the study until death or the first incident or until December 31, 2012.  Hazard ratios were then estimated based on the Cox regression analysis for the outcomes.
Duration Baseline appointment from 2005 through 2007 with follow-up until December 31, 2012 (subjects were followed for an average of 6.8 years)
Primary Outcome Measure Hazard ratios for the cardiovascular disease and mortality:

(1)  Fatal or non-fatal coronary heart disease

(2)  Fatal or non-fatal cardiovascular disease

(3)  Fatal cardiovascular disease

(4)  Total mortality

Baseline Characteristics Standardized differences between the two groups were clearly below 10% for all baseline characteristics
Results Major endpoints Hazard ratio
(95% CI)
p-value
Fatal or non-fatal coronary heart disease
MDIs 1.0 0.05
Pump 0.81 (0.66 to1.01)
Fatal or non-fatal cardiovascular disease
MDIs 1.0 0.2
Pump 0.88 (0.73 to1.06)
Fatal cardiovascular disease
MDIs 1.0 0.005
Pump 0.58 (0.40 to 0.85)
Total mortality
MDIs 1.0 0.007
Pump 0.73 (0.58 to 0.92)
Adverse Events Not reported
Study Author Conclusions Treatment with an insulin pump was associated with a considerable reduction in risk of fatal cardiovascular disease and all-cause mortality.  Whether the results reflect the physiological consequences of insulin pump treatment, the clinical management that pump users receive, or the educational aspects of having the pump remains elusive.

Although no considerable benefit of insulin pump was observed for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease in the same participants, this study revealed a reduction of 42% for fatal cardiovascular disease (coronary heart disease or stroke), 27% for all-cause mortality, and 45% for fatal coronary heart disease (as secondary endpoints) by using insulin pump therapy among T1DM patients.  The study had a large number of participants and well balanced covariates between two groups to reduce the risk of bias.  However, the study was limited in information regarding (1) any strong unmeasured risk factor for coronary heart disease that is likely to be severely unbalanced between those using pump and injections, and (2) the duration of insulin pump treatment before study baseline analyses.  Further study is suggested to state a lower risk of coronary heart disease or cardiovascular disease without reasonable doubt.4

References

  1. AmericanDiabetes  Standards of medical care in diabetes–2015. Diabetes Care 2015 Jan;38 Suppl 1:S1-98.
  2. Maahs DM, Daniels SR, De ferranti SD, et al. Cardiovascular disease risk factors in youth with diabetes mellitus: a scientific statement from the American Heart Association. Circulation. 2014;130(17):1532-58.
  3. Kesavadev J, Jain SM, Muruganathan A, Das AK. Consensus evidence-based guidelines for use of insulin pump therapy in the management of diabetes as per Indian clinical practice. J Assoc Physicians India. 2014;62(7 Suppl):34-41.
  4. Steineck I, Cederholm J, Eliasson B, et al. Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18,168 people with type 1 diabetes: observational study. BMJ. 2015 Jun 22;350:h3234.
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