Short Communication

Acta Diabetologica

, Volume 48, Issue 4, pp 349-353

First online:

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

  • Kristine FærchAffiliated withSteno Diabetes Center Email author 
  • , Allan VaagAffiliated withSteno Diabetes Center

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


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.


Insulin resistance Impaired fasting glycaemia Impaired glucose tolerance Metabolic flexibility Glucose oxidation Lipid oxidation Non-esterified fatty acids Non-oxidative glucose metabolism