↓ Skip to main content

A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes

Overview of attention for article published in Nature, June 2014
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (86th percentile)

Citations

dimensions_citation
336 Dimensions

Readers on

mendeley
413 Mendeley
citeulike
3 CiteULike
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes
Published in
Nature, June 2014
DOI 10.1038/nature13425
Pubmed ID
Authors

Ida Moltke, Niels Grarup, Marit E. Jørgensen, Peter Bjerregaard, Jonas T. Treebak, Matteo Fumagalli, Thorfinn S. Korneliussen, Marianne A. Andersen, Thomas S. Nielsen, Nikolaj T. Krarup, Anette P. Gjesing, Juleen R. Zierath, Allan Linneberg, Xueli Wu, Guangqing Sun, Xin Jin, Jumana Al-Aama, Jun Wang, Knut Borch-Johnsen, Oluf Pedersen, Rasmus Nielsen, Anders Albrechtsen, Torben Hansen

Abstract

The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose (β = 3.8 mmol l(-1), P = 2.5 × 10(-35)) and serum insulin (β = 165 pmol l(-1), P = 1.5 × 10(-20)) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (β = -0.18 mmol l(-1), P = 1.1 × 10(-6)) and fasting serum insulin (β = -8.3 pmol l(-1), P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6 × 10(-24)). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (β = 0.43 mmol l(-1), P = 5.3 × 10(-5)). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.

X Demographics

X Demographics

The data shown below were collected from the profiles of 168 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 413 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 5 1%
Denmark 3 <1%
France 2 <1%
Sweden 1 <1%
South Africa 1 <1%
Mexico 1 <1%
Brazil 1 <1%
Spain 1 <1%
Canada 1 <1%
Other 0 0%
Unknown 397 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 98 24%
Student > Ph. D. Student 81 20%
Student > Bachelor 47 11%
Student > Master 45 11%
Professor > Associate Professor 18 4%
Other 61 15%
Unknown 63 15%
Readers by discipline Count As %
Agricultural and Biological Sciences 121 29%
Biochemistry, Genetics and Molecular Biology 89 22%
Medicine and Dentistry 58 14%
Immunology and Microbiology 8 2%
Sports and Recreations 6 1%
Other 52 13%
Unknown 79 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 200. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 January 2023.
All research outputs
#198,609
of 25,519,924 outputs
Outputs from Nature
#11,872
of 98,138 outputs
Outputs of similar age
#1,513
of 243,177 outputs
Outputs of similar age from Nature
#134
of 1,012 outputs
Altmetric has tracked 25,519,924 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 98,138 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.6. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 243,177 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 1,012 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.