Relationship between time-varying achieved HbA1c and risk of coronary artery disease events among common haptoglobin phenotype groups with type 2 diabetes: the ADVANCE study
Authors' conclusion
The present ADVANCE analysis suggests that not having HbA1c ≥8.0%, rather than achieving HbA1c <7.0%, was found to be particularly important for CAD prevention among people with type 2 diabetes and the common Hp2-2 phenotype. While the subgroup analyses were likely underpowered, their inclusion is hypothesis generating and can be used in future meta-analyses to improve power and generalizability.
Study context
- Population
- People with T2D in the ADVANCE biomarker case-cohort study
- Participants
- 1,323 vs 2,069
- Comparison
- Time-varying achieved HbA1c <7.0% and ≥8.0% vs 7.0%-7.9%, by haptoglobin (Hp) phenotype
- Hp2-2n = 1,323
- non-Hp2-2n = 2,069
- Primary endpoint
- Incident CAD by achieved HbA1c (<7.0% or ≥8.0% vs 7.0%-7.9%), by Hp phenotype
- Follow-up
- Median 5.0 (IQR 4.5-5.3) years
Methodological detailscase-cohort, weighted multivariable-adjusted Cox regression, a priori stratifications by sex, race, previous cardiovascular disease (CVD) and T2D duration
- Case-cohort
- Weighted multivariable-adjusted Cox regression
- A priori stratifications by sex, race, previous CVD and T2D duration
Primary result
As reported in the abstract
CAD risk, HbA1c ≥8.0% vs 7.0%-7.9%, by Hp phenotype
| Group | HR | 95% CI | CI |
|---|---|---|---|
| Hp2-2 | 1.53 | 1.01 to 2.32 | |
| non-Hp2-2 | 1.26 | 0.89 to 1.77 |
HR
Hp2-21.53
non-Hp2-21.26
95% CI
Hp2-21.01 to 2.32
non-Hp2-2— not stated in the abstract
CI
Hp2-2— not stated in the abstract
non-Hp2-20.89 to 1.77
- Hp2-2 vs non-Hp2-2: P for interaction = 0.71
Further findings
CAD risk, HbA1c ≥8.0% vs <8.0%
P for interaction = 0.97
HR Hp2-2 1.59 · non-Hp2-2 1.39
CI Hp2-2 1.12 to 2.26 · non-Hp2-2 1.03 to 1.88
Higher CAD risk
| Outcome | Hp2-2 | non-Hp2-2 | P value |
|---|---|---|---|
| CAD risk, HbA1c ≥8.0% vs 7.0%-7.9%, excluding previous CVD at baseline | P for interaction = 0.03 | ||
| HR | 2.80 | — not stated in the abstract | |
| CI | 1.41 to 5.53 | — not stated in the abstract |
— not stated in the abstract
Mean HbA1c
- Mean HbA1c was similar in each phenotype group throughout the study
Original publication
Relationship between time-varying achieved HbA1c and risk of coronary artery disease events among common haptoglobin phenotype groups with type 2 diabetes: the ADVANCE study. BMJ Open Diabetes Res Care. Published 6 May 2025. doi:10.
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