Evidence map›Paper›PMID 23287371›Full record

ArticleJournal of the American College of Cardiology2013

Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance.

Steen Larsen, Nis Stride, Martin Hey-Mogensen, Christina N Hansen, Lia E Bang, Henning Bundgaard, Lars B Nielsen, Jørn W Helge, Flemming Dela

3 registry-linked trialsAbstract read
PubMed Publisher
In one paragraph

Article in Journal of the American College of Cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
14.7field-weighted citation impact, top 1% 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02255682 phase4completedstarted 2015, after this paper: background citation

Living With Statins - The Impact of Cholesterol Lowering Drugs on Health, Lifestyle and Well-being

Ran2015Enrolled35Registered outcomes5Posted comparisons0ConditionsCardiovascular Disease, Diabetes MellitusArmsQ10, simvastatin
Open the trial in the graph
NCT02796378 phase4unknown statusstarted 2016, after this paper: background citation

Living With Statins - The Impact of Cholesterol Lowering Drugs on Health, Lifestyle and Well-being

Ran2016Enrolled30Registered outcomes5Posted comparisons0ConditionsCardiovascular Disease, Diabetes MellitusArmsTraining+Simvastatin-placebo+Q10-placebo, Training+Simvastatin+Q10, Training+Simvastatin+Q10-placebo
Open the trial in the graph
NCT02250677 completednot on this mapstarted 2014, after this paper: background citation

LIFESTAT - Living With Statins, a Cross Sectional Study on the Impact of Cholesterol Lowering Drugs on Health, Lifestyle and Well-being

TypeobservationalSponsorUniversity of CopenhagenRan2014 to 2016Enrolled75ConditionsCardiovascular Disease, Diabetes Mellitus
3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.

  1. Pooled it
  2. Statins Are Associated With Increased Insulin Resistance and Secretion.Arteriosclerosis, thrombosis, and vascular biology · 2021 · on this map
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  8. Evidence for metabolic aberrations in asymptomatic persons with type 2 diabetes after initiation of simvastatin therapy.Translational research : the journal of laboratory and clinical medicine · 2015
    Trial
  9. Review
  10. Article
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  16. Association of statins with peak oxygen consumption in 4,941 adults: A cross-sectional study.International journal of cardiology. Heart & vasculature · 2024
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  18. Article
  19. Article
  20. Review

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Steen LarsenCenter for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. stelar@sund.ku.dk
Nis Stride
Martin Hey-Mogensen
Christina N Hansen
Lia E Bang
Henning Bundgaard
Lars B Nielsen
Jørn W Helge
Flemming Dela
University of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesGlucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9).

backgroundA prevalent side effect of statin therapy is muscle pain, and yet the basic mechanism behind it remains unknown. We hypothesize that a statin-induced reduction in muscle Q(10) may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism.

methodsPlasma glucose and insulin concentrations were measured during an oral glucose tolerance test. Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers by high-resolution respirometry in a cross-sectional design. Mitochondrial content (estimated by citrate synthase [CS] activity, cardiolipin content, and voltage-dependent anion channel [VDAC] content) as well as Q(10) content was determined.

resultsSimvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q(10) content was reduced (p = 0.05), whereas mitochondrial content was similar between the groups. OXPHOS capacity was comparable between groups when complex I- and complex II-linked substrates were used alone, but when complex I + II-linked substrates were used (eliciting convergent electron input into the Q intersection [maximal ex vivo OXPHOS capacity]), a decreased (p < 0.01) capacity was observed in the patients compared with the control subjects.

conclusionsThese simvastatin-treated patients were glucose intolerant. A decreased Q(10) content was accompanied by a decreased maximal OXPHOS capacity in the simvastatin-treated patients. It is plausible that this finding partly explains the muscle pain and exercise intolerance that many patients experience with their statin treatment.

Indexed as

Blood GlucoseCase-Control StudiesCell RespirationElectron TransportElectron Transport Complex IElectron Transport Complex IIGlucose IntoleranceGlucose Tolerance TestHumansHydroxymethylglutaryl-CoA Reductase InhibitorsInsulin ResistanceMaleMiddle AgedMitochondria, MuscleMuscle Fibers, SkeletalMuscle, SkeletalBlood Glucosecoenzyme Q10Electron Transport Complex IElectron Transport Complex IIHydroxymethylglutaryl-CoA Reductase InhibitorsSimvastatinUbiquinone

Identifiers

PMID23287371
OpenAlexW2216733834

What OpenQuestion holds

Texttitle and abstract
Read underepoch 390

Registered trials

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.