Evidence map›Paper›PMID 35867128›Full record

ArticleDiabetologia2022

Assessment of the bi-directional relationship between blood mitochondrial DNA copy number and type 2 diabetes mellitus: a multivariable-adjusted regression and Mendelian randomisation study.

Wenyi Wang, Jiao Luo, Ko Willems van Dijk, Sara Hägg, Felix Grassmann, Leen M T Hart, Diana van Heemst, Raymond Noordam

Open access · hybridAbstract read
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In one paragraph

Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Wenyi WangDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands. w.wang1@lumc.nl.
Jiao LuoDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Ko Willems van DijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Sara HäggDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Felix GrassmannDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Leen M T HartDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
Diana van HeemstDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Leiden University Medical Center · NLKarolinska Institutet · SE

Funding

Medical Research Council MC_PC_17228Medical Research Council MC_QA137853
6 · The paper itself

Abstract

aims/hypothesisMitochondrial dysfunction, which can be approximated by blood mitochondrial DNA copy number (mtDNA-CN), has been implicated in the pathogenesis of type 2 diabetes mellitus. Thus far, however, insights from prospective cohort studies and Mendelian randomisation (MR) analyses on this relationship are limited. We assessed the association between blood mtDNA-CN and incident type 2 diabetes using multivariable-adjusted regression analyses, and the associations between blood mtDNA-CN and type 2 diabetes and BMI using bi-directional MR.

methodsMultivariable-adjusted Cox proportional hazard models were used to estimate the association between blood mtDNA-CN and incident type 2 diabetes in 285,967 unrelated European individuals from UK Biobank free of type 2 diabetes at baseline. Additionally, a cross-sectional analysis was performed to investigate the association between blood mtDNA-CN and BMI. We also assessed the potentially causal relationship between blood mtDNA-CN and type 2 diabetes (N=898,130 from DIAGRAM, N=215,654 from FinnGen) and BMI (N=681,275 from GIANT) using bi-directional two-sample MR.

resultsDuring a median follow-up of 11.87 years, 15,111 participants developed type 2 diabetes. Participants with a higher level of blood mtDNA-CN are at lower risk of developing type 2 diabetes (HR 0.90 [95% CI 0.89, 0.92]). After additional adjustment for BMI and other confounders, these results attenuated moderately and remained present. The multivariable-adjusted cross-sectional analyses showed that higher blood mtDNA-CN was associated with lower BMI (-0.12 [95% CI -0.14, -0.10]) kg/m CONCLUSIONS/

interpretationThe results from the present study indicate that the observed association between low blood mtDNA-CN and higher risk of type 2 diabetes is likely not causal.

Indexed as

Diabetes Mellitus, Type 2DNA, MitochondrialCross-Sectional StudiesDNA Copy Number VariationsHumansMitochondriaProspective StudiesDNA, MitochondrialMendelian randomisationMitochondrial DNA copy numberProspective analysesType 2 diabetes mellitus

Identifiers

PMID35867128
PMCPMC9477915
OpenAlexW4286447741

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.