Introduction: Exogenous insulin therapy has been the mainstay of treatment for those with uncontrolled type 2 diabetes; however, recent literature has pointed to a lack of risk reduction for cardiovascular disease (CVD). We sought to determine the association between insulin use and major adverse cardiovascular events (MACE) among older adults with type 2 diabetes with a long-term follow-up.

Methods: A cohort of 1,084 participants >50 years with type 2 diabetes from the National Health and Nutrition Examination Survey-III (1988-1994) was followed for an average 22.4 years through 2015. Subjects were divided into two groups: 1) those using insulin therapy and 2) those using oral medications only. The primary outcome was major adverse cardiovascular events (MACE), a combination of self-reported myocardial infarction, stroke, or CVD mortality. We used multivariable logistic regression, adjusting for HbA1c, demographic, metabolic, and inflammatory factors and accounting for the survey design.

Results: Among the participants, 227 (21%) regularly used insulin. Those using insulin were of similar age, more likely to be male, have similar BMI, waist circumference, blood pressure, and lipids, have higher HbA1c (8.2% vs. 7.3%, p<0.01), and have significantly higher serum insulin levels (mean[SD]: 51.1[4.2] vs. 18.5[0.7], p<0.001). Those taking insulin had nearly twice the adjusted odds of MACE relative to those only taking oral agents (aOR [95% CI]: 1.89 [1.11, 3.24]). When assessing individual conditions, those taking insulin had significantly increased odds of stroke, but not MI or CVD mortality (aOR [95% CI]: stroke = 3.69 [1.26, 10.78], MI = 1.41 [0.75, 2.65], CVD mortality = 1.19 [0.69, 2.06]). There was no significant dose-dependent association between insulin use and MACE.

Conclusion: Long-term insulin use may be associated with increased stroke, although no dose-dependent association was present. Increased care and assessment may be warranted in patients taking insulin.


A. Visaria: None. T. Dharamdasani: None. K. Wickramasinghe: None. D. Lo: None. R. Malhotra: None.

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