Comorbidity affects the relationship between glycemic control and cardiovascular outcomes in diabetes: a cohort study.

ABSTRACT

BACKGROUND: Recent studies have shown mixed results regarding the effectiveness of intensive glucose-lowering therapy in reducing risk for cardiovascular events. OBJECTIVE: To determine whether attaining hemoglobin A(1c) (HbA(1c)) targets of 6.5% or less or 7.0% or less for glycemic control at baseline provides differential benefits for patients with high versus low-to-moderate levels of comorbidity. DESIGN: 5-year longitudinal observational study of patients with type 2 diabetes. Patients were categorized into high and low-to-moderate comorbidity subgroups by using the Total Illness Burden Index (TIBI), a validated patient-reported measure of comorbidity. SETTING: 101 diabetes outpatient clinics and 103 general practitioners' clinics in Italy. PATIENTS 2613 (83%) of 3074 patients with type 2 diabetes, sampled randomly from diabetes outpatient clinic rosters and recruited consecutively from general practitioners' clinics, who completed the baseline questionnaire. MEASUREMENTS TIBI score, total mortality, and incident cardiovascular events. Hazard ratios (HRs) were adjusted for age and sex. RESULTS: Attaining an HbA(1c) level of 6.5% or less at baseline was associated with lower 5-year incidence of cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.60 [95% CI, 0.42 to 0.85]; P = 0.005) but not in the high comorbidity subgroup (adjusted HR, 0.92 [CI, 0.68 to 1.25]; P = 0.61; P for subgroup by HbA(1c) interaction = 0.048). Similarly, attaining a baseline HbA(1c) level of 7.0% predicted fewer cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.61 (CI, 0.44 to 0.83; P = 0.001) but not in the high comorbidity subgroup (adjusted HR, 0.88 [CI, 0.66 to 1.17]; P = 0.38; P for subgroup by HbA(1c) interaction = 0.093). LIMITATIONS: The observational nature of the study does not allow causal inference. The length of the data collection period was limited. Information on clinical management was not available. CONCLUSION: Patients with the high levels of comorbidity common in type 2 diabetes may receive diminished cardiovascular benefit from intensive blood glucose control. Comorbidity should be considered when tailoring glucose-lowering therapy in patients with type 2 diabetes. PRIMARY FUNDING SOURCE Pfizer of Italy.