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Clonal hematopoiesis as a novel risk factor for type 2 diabetes mellitus in patients with hypercholesterolemia
Min Joo Kim1,2, Han Song3, Youngil Koh2,3
1Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.
Insights
Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of developing type 2 diabetes, particularly when combined with high LDL cholesterol. This finding highlights a synergistic effect between CHIP and hyper-LDL cholesterolemia in diabetes development.
Area of Science:
- Hematology
- Endocrinology
- Cardiovascular Science
Background:
- Clonal hematopoiesis of indeterminate potential (CHIP) is linked to cardiovascular disease.
- Previous research suggests a potential connection between CHIP and diabetes.
- This study investigates the association between CHIP and the development of type 2 diabetes.
Purpose of the Study:
- To determine if CHIP is associated with an increased risk of new-onset type 2 diabetes.
- To explore the interaction between CHIP and LDL cholesterol levels in diabetes risk.
Main Methods:
- A cohort of 4,047 participants aged 40 years or older without diabetes was studied.
- Targeted gene sequencing was used to identify CHIP in peripheral blood cells.
- New-onset type 2 diabetes incidence was monitored during a median follow-up of 5.1 years.
Main Results:
- CHIP was identified in 15.7% of the subjects.
- New-onset diabetes occurred more frequently in CHIP carriers (11.8%) compared to non-carriers (9.1%).
- CHIP significantly increased diabetes risk in individuals with hyper-LDL cholesterolemia (HR 1.64), but not in those without it. The combined risk for CHIP and hyper-LDL cholesterolemia was substantially elevated (HR 2.05).
Conclusions:
- CHIP is a significant risk factor for new-onset type 2 diabetes.
- The risk is particularly pronounced in individuals with high LDL cholesterol, indicating a synergistic effect.
- These findings underscore the importance of considering CHIP and lipid profiles in diabetes risk assessment.
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.
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