Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus
Tineke van de Weijer1, Lauren Marie Sparks, Esther Phielix
1Department of Human Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
Plos One
|February 19, 2013
Summary
Type 2 diabetes (T2D) involves mitochondrial dysfunction, impacting substrate utilization. Impaired mitochondrial function in T2D patients affects basal metabolism, while glucose disposal rate is key for insulin response and metabolic flexibility.
Area of Science:
- Metabolic physiology
- Endocrinology
- Molecular biology
Background:
- Type 2 diabetes (T2D) is linked to mitochondrial dysfunction, lipid accumulation, insulin resistance, and metabolic inflexibility.
- The precise interrelationships between these factors in T2D etiology remain under investigation.
Purpose of the Study:
- To investigate the interrelationships between mitochondrial function, lipid accumulation, insulin resistance, and metabolic inflexibility in T2D.
- To compare these metabolic parameters between T2D patients and obese normoglycemic controls.
Main Methods:
- Enrolled 49 male T2D patients and 54 male controls.
- Performed hyperinsulinemic-euglycemic clamp, indirect calorimetry, and muscle biopsy for intramyocellular lipid (IMCL) measurement.
- Assessed in vivo mitochondrial function via PCr recovery in a subset of participants.
Main Results:
- Mitochondrial function was reduced by 12.5% in T2D patients (p<0.01).
- Metabolic flexibility (ΔRER) was significantly lower in T2D patients (p<0.01).
- Mitochondrial function predicted basal substrate oxidation, while glucose disposal rate predicted insulin-stimulated substrate oxidation and metabolic flexibility.
Conclusions:
- Skeletal muscle mitochondrial dysfunction in T2D primarily affects basal substrate oxidation.
- Glucose disposal rate is a critical determinant of substrate utilization during insulin stimulation in T2D.
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