Endocrinol Metab.  2022 Apr;37(2):243-248. 10.3803/EnM.2021.1337.

The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes

• Oh TJ
• Song H
• Koh Y
• Choi SH

• KMID: 2529216
• DOI: http://doi.org/10.3803/EnM.2021.1337

Abstract

Background
Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to be associated with increased cardiovascular disease, aging and insulin resistance. Despite the debate of causal contribution of CHIP on metabolic diseases, we want to explore whether CHIP is related to diabetic peripheral neuropathy (DPN).
Methods
This study analyzed the prevalence of CHIP in patients with type 2 diabetes classified according to DPN status. Logistic regression analysis was used to evaluate the association between CHIP and DPN.
Results
CHIP was more prevalent in subjects without DPN than those with DPN (19.9% vs. 8.8%, respectively; P=0.013). Individuals having any CHIP, or DNA methyltransferase 3A (DNMT3A) CHIP were less likely to have any abnormality shown in DPN test; the adjusted odds ratio were 0.85 (95% confidence interval [CI], 0.73 to 1.00) and 0.70 (95% CI, 0.56 to 0.89), respectively. Interestingly, DNMT3A CHIP showed the negative association, but Tet methylcytosine dioxygenase 2 (TET2) CHIP showed the positive association with abnormal feet electrochemical skin conductance level.
Conclusion
On the contrary to expectations, CHIP was negatively associated with DPN. Functional linking between the mutation in hematopoietic cells and DPN, and the opposite role of DNMT3A and TET2 should be investigated.

Keyword

Diabetic neuropathies; Clonal hematopoiesis; Risk factors

Figure

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  Fig. 1. Adjusted odds ratio (OR) (95% confidence interval [CI]) for the associations between clonal hematopoiesis and the presence of abnormalities in diabetic peripheral neuropathy (DPN). (A) All clonal hematopoiesis, (B) DNMT3A clonal hematopoiesis, and (C) TET2 clonal hematopoiesis. The OR was adjusted for body mass index, hemoglobin A1c, and high-density lipoprotein cholesterol levels, and estimated glomerular filtration rate. CH, clonal hematopoiesis; MNSI-Q, Michigan Neuropathy Screening Instrument-questionnaire; MNSI-PE, Michigan Neuropathy Screening Instrument-physical examination; MF, monofilament test; ESC, electrochemical skin conductance; DNMT3A, DNA methyltransferase 3A; TET2, Tet methylcytosine dioxygenase 2.

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