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. 2023 Jun 28:11:1181879.
doi: 10.3389/fpubh.2023.1181879. eCollection 2023.

Clonal hematopoiesis as a novel risk factor for type 2 diabetes mellitus in patients with hypercholesterolemia

Min Joo Kim #  1   2 , Han Song #  3 , Youngil Koh  2   3 , Heesun Lee  1   2 , Hyo Eun Park  1   2 , Sung Hee Choi  2   4 , Ji Won Yoon  1   2 , Su-Yeon Choi  1   2
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Clonal hematopoiesis as a novel risk factor for type 2 diabetes mellitus in patients with hypercholesterolemia

Min Joo Kim et al. Front Public Health. .

Abstract

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with atherosclerosis and cardiovascular disease. It has been suggested that CHIP may be related to diabetes, so we investigated the association between CHIP and new-onset type 2 diabetes.

Methods: This study included 4,047 subjects aged >=40 years without diabetes. To detect CHIP, targeted gene sequencing of genomic DNA from peripheral blood cells was performed. The incidence of new-onset type 2 diabetes during the follow-up period was evaluated.

Results: Of the total subjects, 635 (15.7%) had CHIP. During the median follow-up of 5.1 years, the incidence of new-onset diabetes was significantly higher in CHIP carriers than in subjects without CHIP (11.8% vs. 9.1%, p = 0.039). In a univariate analysis, CHIP significantly increased the risk of new-onset diabetes (HR 1.32, 95% CI 1.02-1.70, p = 0.034), but in a multivariate analysis, it was not significant. The CHIP-related risk of new onset diabetes differed according to LDL cholesterol level. In the hyper-LDL cholesterolemia group, CHIP significantly increased the risk of diabetes (HR 1.64, 95% CI 1.09-2.47, p = 0.018), but it did not increase the risk in the non-hyper-LDL cholesterolemia group. The subjects with CHIP and hyper-LDL-cholesterolemia had approximately twice the risk of diabetes than subjects without CHIP and with low LDL cholesterol (HR 2.05, 95% CI 1.40-3.00, p < 0.001).

Conclusion: The presence of CHIP was a significant risk factor for new-onset type 2 diabetes, especially in subjects with high LDL cholesterol. These results show the synergism between CHIP and high LDL cholesterol as a high-risk factor for diabetes.

Keywords: LDL cholesterol; clonal hematopoiesis; diabetes mellitus; hematopoiesis; hypercholesterolemia.

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Conflict of interest statement

HS and YK are shareholders of Genome Opinion, Inc. The content of this study has been applied as a patent by HS and S-YC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Risk of new-onset type 2 diabetes according to the presence of CHIP. Kaplan–Meier curves were plotted for all subjects (total group) (n = 4,047) (A) subjects with low LDL cholesterol levels (non-hyperLDLC group) (B), and subjects with high LDL cholesterol levels (hyperLDLC group) (C). The multivariate Cox regression model was analyzed adjusting for age, sex, BMI, and family history of diabetes in the total group, non-hyperLDLC group, and hyperLDLC group (D).
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