Insulin provision therapy and mortality in older adults with diabetes mellitus and stable ischemic heart disease: Insights from BARI-2D trial

Abstract

Importance: Optimal strategies for glucose control in very old adults with diabetes and stable ischemic heart disease (SIHD) are unclear.

Objective: To compare the effects of insulin provision (IP) therapy versus insulin sensitizing (IS) therapy for glycemic control in older (≥75years) and younger (<75years) adults with type II diabetes (DM) and SIHD.

Design, setting, and participants: Adults enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) were studied. The BARI 2D study population (all with type II DM and SIHD) was randomized twice: (1) between revascularization plus intensive medical therapy versus intensive medical therapy alone, and (2) between IP versus IS therapies. The primary endpoint was all-cause-mortality over five-year follow-up. In this substudy outcomes related to IP vs. IS are assessed in relation to age. Adults aged ≥75years who received IP versus IS are compared to those <75years who received IP versus IS. Multivariate Cox regression analysis was used to evaluate the effects of IP vs. IS on outcomes in the two age groups.

Results: 2368 subjects with SIHD and DM were enrolled in BARI 2D; 182 (8%) were ≥75years. Compared to younger subjects, the older cohort had lower BMI, higher diuretic use, worse kidney function, and increased history of heart failure. Within the older cohort, the IP and IS subgroups were similar in respect to baseline cardiovascular risk factors, medications, and coronary artery disease severity. During follow-up, the older subjects receiving IP therapy had higher cardiovascular mortality compared to those receiving IS therapy (16% vs. 11%, p=0.040). Using Cox proportional hazards analysis, the older IP subjects were at increased risk for all-cause-mortality (hazard ratio 1.89, CI 1.1-3.2, p=0.020). No mortality difference between IP and IS was observed in those <75years of age.

Conclusion and relevance: Among adults with diabetes and SIHD aged ≥75years, IP therapy may be associated with increased mortality compared to IS therapy. Additional studies are needed to further refine optimal treatment strategies for diabetes and SIHD in old age.

Keywords: BARI 2D; Diabetes mellitus; Elderly; Insulin; Ischemic heart disease.