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Diabetes

Muscle ATP defect in diabetes-prone offspring

Petersen KF, Dufour S, Shulman GI · PLoS medicine · 2005

Open access · cc by · source: Europe PMC

Lean insulin-resistant offspring of type 2 diabetic parents showed blunted insulin-stimulated muscle ATP synthesis versus matched controls.

Study at a glance

Design
Other — Clamp + 31P MRS group comparison of IR offspring vs controls; no randomized intervention
N
N=14 · 7 IR offspring vs 7 controls, from the paper’s “What Did the Researchers Do and Find?” section in the stored full text
Population
Young lean sedentary adults with or without parental type 2 diabetes history
Outcome
Insulin-stimulated muscle ATP synthesis and phosphate transport (31P MRS)

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

Insulin raised muscle ATP flux ~90% in controls but only ~5% in IR offspring, supporting early mitochondrial dysfunction before overt diabetes.

Methodology

Healthy lean sedentary IR offspring with family diabetes history and matched controls underwent hyperinsulinemic-euglycemic clamps with 31P MRS of muscle ATP synthesis and phosphate transport.

Limitations

Whether fixing ATP synthesis prevents diabetes, and findings may not generalize beyond young lean high-risk offspring.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • QualifiesDiabetes Careconcept

    TXNIP rises with impaired glucose handling and tracks lower muscle glucose uptake.

    In human muscle physiology work, TXNIP is reciprocally regulated by insulin and glucose, elevated in T2DM/prediabetes, and inversely related to glucose uptake—pointing to a molecular brake on peripheral glucose disposal.

    Scope note — related mechanism — mitochondrial ATP flux defect, not TXNIP regulation

    Limits the claim's scope: a different population, assay, or outcome.

  • SupportsDiabetes Careconcept

    Insulin barely raises muscle ATP synthesis in insulin-resistant offspring of parents with diabetes.

    In insulin-resistant offspring of parents with type 2 diabetes, insulin raised muscle ATP synthesis flux only ~5% versus ~90% in controls—evidence of early mitochondrial dysfunction before overt diabetes.

    Evidence for the claim as stated.

  • SupportsDiabetes Careconcept

    Muscle mechanism studies, night-shift incidence, GDM sequelae, T2D complication associations, and a T1D app trial all sit under diabetes care but answer different estimands. They are complementary scopes, not interchangeable results.

    Evidence for the claim as stated.

  • QualifiesInsulin resistanceconcept

    TXNIP rises with impaired glucose handling and tracks lower muscle glucose uptake.

    In human muscle physiology work, TXNIP is reciprocally regulated by insulin and glucose, elevated in T2DM/prediabetes, and inversely related to insulin-stimulated glucose uptake—pointing to a molecular brake on peripheral disposal.

    Scope note — related IR phenotype — mitochondrial ATP flux, not TXNIP transcript regulation

    Limits the claim's scope: a different population, assay, or outcome.

  • SupportsInsulin resistanceconcept

    Insulin barely raises muscle ATP synthesis in insulin-resistant offspring of parents with diabetes.

    In insulin-resistant offspring of parents with type 2 diabetes, insulin raised muscle ATP synthesis flux only ~5% versus ~90% in controls—evidence of early mitochondrial dysfunction before overt diabetes.

    Evidence for the claim as stated.

  • QualifiesInsulin resistanceconcept

    Gut microbiota composition associates with metabolites and metabolic-syndrome traits.

    In middle-aged men, gut microbiota composition was associated with plasma metabolites and metabolic-syndrome–related traits, placing the microbiome beside—not instead of—insulin-resistance physiology.

    Scope note — different system — stool microbiota vs clamp/MRS muscle energetics

    Limits the claim's scope: a different population, assay, or outcome.

  • SupportsInsulin resistanceconcept

    Microbiome–metabolite associations in METSIM men and clamp/MRS insulin-resistance phenotypes share metabolic-syndrome territory while measuring different exposures and outcomes.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

History

When this study was placed

Dated entries from the concept change log — when this paper was added or removed as support, challenge, or qualifier on a claim.

  1. 2026-09-14

    Placed as a scope qualifier on Diabetes Care

    In human muscle physiology work, TXNIP is reciprocally regulated by insulin and glucose, elevated in T2DM/prediabetes, and inversely related to glucose uptake—pointing to a molecular brake on peripheral glucose disposal.

  2. 2026-09-14

    Placed as supporting evidence on Diabetes Care

    In insulin-resistant offspring of parents with type 2 diabetes, insulin raised muscle ATP synthesis flux only ~5% versus ~90% in controls—evidence of early mitochondrial dysfunction before overt diabetes.

  3. 2026-09-14

    Placed as supporting evidence on Diabetes Care

    Muscle mechanism studies, night-shift incidence, GDM sequelae, T2D complication associations, and a T1D app trial all sit under diabetes care but answer different estimands. They are complementary scopes, not interchangeable results.

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Same topic cluster — not a recommendation engine.