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Muscle ATP defect in diabetes-prone offspring

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

Source

Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of insulin-resistant offspring of type 2 diabetic parents

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

doi.org/10.1371/journal.pmed.0020233Read the full paper ↗232 citationscc by

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.

What they did

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.

What they found

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

The limits

What it doesn't show

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

Key terms

Insulin resistance
Reduced tissue response to insulin, a precursor state for type 2 diabetes.
ATP synthesis
Mitochondrial production of ATP measured here as muscle flux.
Hyperinsulinemic-euglycemic clamp
Gold-standard method holding glucose steady while infusing insulin.
31P MRS
Magnetic resonance spectroscopy of phosphorus metabolites in vivo.
IR offspring
Insulin-resistant children/grandchildren of people with type 2 diabetes.
IMCL
Intramyocellular lipid content linked to mitochondrial and insulin phenotypes.

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IR offspring ATP response to insulin was about:

Common questions

Who were IR offspring?

Seven lean healthy young adults with multi-generation type 2 diabetes family history.

What was the key ATP finding?

Insulin stimulated ATP flux ~90% in controls vs ~5% in IR offspring.

Why is this clinically relevant?

Suggests mitochondrial ATP defects appear early in diabetes pathogenesis.

Was this an animal study?

No—human volunteers studied with clamps and MRS.

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