Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity

Diabetes, Obesity and Metabolism, 05/11/2012

Knop F et al. – These findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin–resistant state have normal glucose tolerance (NGT).


  • Four hour 50-g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35-41) kg/m2].
  • Eight obese subjects with NGT [BMI: 33 (35-38) kg/m2].
  • Eight lean patients with T2DM [BMI: 24 (22-25) kg/m2].
  • Eight lean healthy subjects [BMI: 23 (20-25) kg/m2].


  • The incretin effect was significantly (p < 0.05) reduced in patients with T2DM {obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p < 0.05).
  • Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects.

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