Genetic study supports causal effect of resting heart rate on type 2 diabetes risk
medwireNews: Researchers have used Mendelian randomization analysis to demonstrate a shared etiology between resting heart rate (RHR) and the risk for type 2 diabetes.
Liming Liang (Harvard TH Chan School of Public Health, Boston, Massachusetts, USA) and team found each 10 beats/minute increase in RHR to be responsible for a 12% increase in the risk for type 2 diabetes.
There was also a causal effect in the reverse direction, with type 2 diabetes adding an additional estimated 0.32 beats/minute to RHR, they report in the Journal of the American College of Cardiology.
Patricia Munroe (Queen Mary University of London, UK) and co-authors of a linked editorial describe the research as “a very ﬁrst step” in understanding these complex relationships, adding that “[t]he bidirectional causality especially raises questions, and further validation will be necessary before beginning to address any clinical implications of the work.”
The researchers used data from 428,250 people in the UK Biobank who were not using beta blockers to identify 437 genetic variants that were significantly associated with RHR, 327 of which had not been previously reported.
The team compared these genetic data with summary statistics from the DIAGRAM Consortium, which provided data from 74,124 people with type 2 diabetes and 824,006 without who participated in 32 genome-wide association studies.
This showed significant genetic correlation between RHR and type 2 diabetes, and also between RHR and six of eight metabolic parameters studied, namely, fasting insulin, fasting glucose, waist-to-hip ratio, BMI, triglycerides, and high-density lipoprotein (HDL) cholesterol.
Levels of these metabolic indices increased as RHR did, with the exception of HDL cholesterol, which fell. Total and low-density lipoprotein cholesterol were not associated with RHR.
In addition to being causally related to diabetes, RHR was also associated with waist-to-hip ratio, and vice versa, but other metabolic parameters were only associated in the reverse direction, eg, higher fasting glucose had a significant causal effect on higher RHR, but the reverse was not true.
The researchers identified seven genes that independently affected both RHR and the risk for type 2 diabetes, and so likely to play a role in the etiology of both processes. These were SMARCAD1, RP11-53O19.3, CTC-498M16.4, PDE8B, AKTIP, KDM4B, and TSHZ3.
The functions of these genes suggest a role for telomere function, epigenetic regulation of energy metabolism, and vascular endothelial aging in the etiology of RHR and type 2 diabetes, say Liang and team.
Munroe and co-authors note in their editorial that functional studies of these shared genes may yield useful knowledge, and the “promise of potential drug intervention” based on such research is “alluring.”
But they caution that lifelong genetic exposure as assessed in Mendelian randomization studies “may not translate to short- to medium-term intervention from pharmacological therapy in reducing [type 2 diabetes] risk.”
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