Evidence mapPaperPMID 39109797Full record

Observational studyThe Journal of clinical endocrinology and metabolism2025

Insulin Sensitivity and Insulin Secretion in Adults With Friedreich's Ataxia: The Role of Skeletal Muscle.

Jaclyn Tamaroff, Sara Nguyen, Neil E Wilson, Darko Stefanovski, Rui Xiao, Theresa Scattergood, Christopher Capiola, Gayatri Maria Schur, Julia Dunn, Anna Dedio and 10 more

Registry-linked trialAbstract readObservational Study
In one paragraph

Observational study in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02920671 (Skeletal Muscle Oxidative Phosphorylation Capacity and Nutrient Homeostasis in Individuals With Primary), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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.

NCT02920671 completednot on this map

Skeletal Muscle Oxidative Phosphorylation Capacity and Nutrient Homeostasis in Individuals With Primary (Genetic) and Secondary (Obesity-related) Mitochondrial Impairment as Compared to Healthy, Normal-weight Individuals

TypeobservationalSponsorUniversity of PennsylvaniaRan2017 to 2024Enrolled45ConditionsMitochondrial Diseases, ObesityArmsTracer-enhanced oral glucose tolerance test (OGTT*), Muscle MRI, Dual energy x-ray absorptiometry (DXA), Questionnaires
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
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

20 authors.

Jaclyn TamaroffDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-3630-9937
Sara NguyenDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Neil E WilsonPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Darko StefanovskiNew Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA 19348, USA.
Rui XiaoDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Theresa ScattergoodPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher CapiolaDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Gayatri Maria SchurDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Julia DunnDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Anna DedioDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Kristin WadeDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Hardik ShahDepartment of Molecular Biology, Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Rohit SharmaDepartment of Molecular Biology, Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Vamsi K MoothaDepartment of Molecular Biology, Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Andrea KellyDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Kimberly Y LinPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
David R LynchPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Ravinder ReddyPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael R RickelsDivision of Endocrinology, Diabetes & Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Shana E McCormackDivision of Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-1143-4459

Funding

Univ of Pennsylvania Diabetes Endocrinology Res CTRP30DK019525 · UNIVERSITY OF PENNSYLVANIA · 1986 to 2025
$10.9M
Institutional Clinical and Translational Science AwardUL1TR001878 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$10.2M
Clinical and Translational Science AwardUL1TR001873 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$10.0M
NAD+ precursor supplementation with exercise training to improve aerobic capacity in Friedreich's AtaxiaR01HL149722 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI SHANA ERIN MCCORMACK · 2022 to 2024
$2.6M
The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/PennP50HD105354 · CHILDREN'S HOSP OF PHILADELPHIA · 2025 to 2025
$1.4M
High Spatial and Temporal Resolution MRI Mapping of Oxygen Consumption in HumansP41EB029460 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$1.1M
CHOP Friedreich's Ataxia Center of ExcellenceCHOP/Penn CHPSNational Institutes of Health (NIH) K23DK102659NCATS NIH HHS UL1 TR000003NCATS NIH HHS UL1TR000003NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR001878NHLBI NIH HHS R01 HL149722NIBIB NIH HHS P41 EB029460NICHD NIH HHS P50 HD105354NIDDK NIH HHS F32 DK128970NIDDK NIH HHS K23 DK102659NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R03 DK114491Non-NIHPenn Diabetes Research Center Radioimmunoassay and Biomarkers Core P30 DK19525
6 · The paper itself

Abstract

introductionFriedreich's ataxia (FRDA) is a multisystem disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM.

methodsCase-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer magnetic resonance imaging) were assessed.

resultsParticipants included 11 individuals with FRDA (4 female), median age 27 years (interquartile range 23, 39), body mass index 26.9 kg/m2 (24.1, 29.4), and 24 controls (11 female), 29 years (26, 39), 24.4 kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA [91 vs 83 mg/dL (5.0 vs 4.6 mmol/L), P < .05]. Individuals with FRDA had lower insulin sensitivity (whole-body insulin sensitivity index 2.8 vs 5.3, P < .01), higher postprandial insulin secretion (insulin secretory rate incremental area under the curve 30-180 minutes, 24 652 vs 17,858, P < .05), and more suppressed postprandial endogenous glucose production (-.9% vs 26.9% of fasting endogenous glucose production, P < .05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different.

conclusionLower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory and, when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.

Indexed as

Friedreich AtaxiaInsulinInsulin ResistanceInsulin SecretionMuscle, SkeletalAdultBlood GlucoseBody CompositionCase-Control StudiesFemaleGlucose Tolerance TestHumansMaleOxidative PhosphorylationYoung AdultBlood GlucoseInsulinFriedreich's ataxiainsulin secretioninsulin sensitivitymitochondriaphysical activityskeletal muscle

Identifiers

PMID39109797
PMCPMC11747682

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.