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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2024

Open Access 01-12-2024 | Type 2 Diabetes | Research

Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study

Authors: Rachel A. Warren, Michael P. Bancks, Allie S. Carew, Andrew P. Levy, John Sapp, Judy Bahnson, Cora E. Lewis, Eric B. Rimm, Mark A. Espeland, Leah E. Cahill

Published in: Cardiovascular Diabetology | Issue 1/2024

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Abstract

Background

Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes.

Methods

Haptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration.

Results

1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78–1.17) or with (0.89, 0.68–1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups.

Conclusions

Hp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.
Appendix
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Metadata
Title
Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study
Authors
Rachel A. Warren
Michael P. Bancks
Allie S. Carew
Andrew P. Levy
John Sapp
Judy Bahnson
Cora E. Lewis
Eric B. Rimm
Mark A. Espeland
Leah E. Cahill
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-024-02164-8

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