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Metabolic inflexibility is a common feature of impaired fasting glycaemia and impaired glucose tolerance

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Abstract

Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation. Impaired metabolic flexibility is related to insulin resistance and type 2 diabetes, but whether metabolic flexibility is impaired in individuals with the pre-diabetic states isolated impaired fasting glycaemia (i-IFG) and isolated impaired glucose tolerance (i-IGT) is unknown. Using the gold standard euglycaemic hyperinsulinaemic clamp technique combined with indirect calorimetry, we measured peripheral insulin sensitivity, lipid and glucose oxidation, and thus metabolic flexibility in 66 individuals with normal glucose tolerance (NGT, n = 20), i-IFG (n = 18) and i-IGT (n = 28). During insulin stimulation, individuals with i-IGT displayed reduced insulin sensitivity including reduced glucose oxidation. Interestingly, those with i-IFG exhibited reduced glucose oxidation and a slightly elevated lipid oxidation rate during insulin infusion despite having normal total peripheral glucose disposal. Thus, metabolic flexibility was significantly reduced in individuals with both i-IFG and i-IGT even after adjustment for BMI and insulin sensitivity. The data indicate that metabolic inflexibility may precede the development of overt peripheral insulin resistance in pre-diabetic individuals. However, prospective studies are needed to confirm this notion.

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Acknowledgments

The authors wish to thank Marianne Modest and Lars Sander Koch for their expert technical assistance. Likewise, the participants who took part in the study are thanked for their important contributions. The study was supported by the Danish Agency for Science, Technology, and Innovation.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Steno Diabetes Center, Niels Steensens Vej 2, 2820, Gentofte, Denmark

    Kristine Færch & Allan Vaag

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  1. Kristine Færch
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  2. Allan Vaag
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Correspondence to Kristine Færch.

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Færch, K., Vaag, A. Metabolic inflexibility is a common feature of impaired fasting glycaemia and impaired glucose tolerance. Acta Diabetol 48, 349–353 (2011). https://doi.org/10.1007/s00592-010-0245-x

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  • DOI: https://doi.org/10.1007/s00592-010-0245-x

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