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Comorbidity affects the relationship between glycemic control and cardiovascular outcomes in diabetes: a cohort study
Sheldon Greenfield1, John Billimek, Fabio Pellegrini
1University of California Irvine, Irvine, California, USA. sgreenfi@uci.edu
Insights
Intensive glucose control (HbA1c <7%) benefits cardiovascular health in type 2 diabetes patients with low comorbidity. High comorbidity patients show diminished cardiovascular benefits from intensive glycemic control.
Area of Science:
- Endocrinology
- Cardiology
- Diabetes Management
Background:
- Mixed results exist on intensive glucose-lowering therapy's cardiovascular benefits in type 2 diabetes.
- Comorbidity is a significant factor in managing diabetes and its complications.
Purpose of the Study:
- To investigate if achieving specific hemoglobin A1c (HbA1c) targets (≤6.5% or ≤7.0%) offers different cardiovascular benefits based on patient comorbidity levels.
- To assess the impact of baseline glycemic control on cardiovascular events in type 2 diabetes patients with varying comorbidity burdens.
Main Methods:
- A 5-year longitudinal observational study involving 2613 type 2 diabetes patients from Italian clinics.
- Patients were stratified into high and low-to-moderate comorbidity groups using the Total Illness Burden Index (TIBI).
- Outcomes measured included total mortality and incident cardiovascular events, with hazard ratios adjusted for age and sex.
Main Results:
- Achieving HbA1c ≤6.5% at baseline was linked to reduced cardiovascular events in patients with low-to-moderate comorbidity (HR 0.60), but not in those with high comorbidity (HR 0.92).
- Similarly, HbA1c ≤7.0% at baseline predicted fewer cardiovascular events in the low-to-moderate comorbidity group (HR 0.61), with no significant benefit in the high comorbidity group (HR 0.88).
- Statistical analysis indicated a significant interaction between comorbidity level and HbA1c targets for cardiovascular event reduction.
Conclusions:
- Intensive blood glucose control may offer reduced cardiovascular benefits for type 2 diabetes patients with high comorbidity.
- Comorbidity assessment is crucial for personalizing glucose-lowering therapy strategies to optimize cardiovascular outcomes.
- Further research is needed to confirm these findings due to the observational nature and limitations of the study.
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.
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