Markers of Glucagon Resistance Improve With Reductions in Hepatic Steatosis and Body Weight in Type 2 Diabetes

型糖尿病患者胰高血糖素抵抗标志物随着肝脏脂肪变性和体重的减少而改善

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作者:Sasha A S Kjeldsen, Mads N Thomsen, Mads J Skytte, Amirsalar Samkani, Michael M Richter, Jan Frystyk, Faidon Magkos, Elizaveta Hansen, Henrik S Thomsen, Jens J Holst, Sten Madsbad, Steen B Haugaard, Thure Krarup, Nicolai J Wewer Albrechtsen

Conclusion

Improvements in glucagon resistance may depend on body weight loss in patients with type 2 diabetes.

Methods

A post hoc analysis was conducted from 2 previously published randomized controlled trials. We investigated the effect of weight maintenance (study 1: isocaloric feeding) or weight loss (study 2: hypocaloric feeding), both of which induced reductions in hepatic steatosis, on markers of glucagon sensitivity, including the glucagon-alanine index measured using a validated enzyme-linked immunosorbent assay and metabolomics in 94 individuals (n = 28 in study 1; n = 66 in study 2). Individuals with overweight or obesity with type 2 diabetes were randomly assigned to a 6-week conventional diabetes (CD) or carbohydrate-reduced high-protein (CRHP) diet within both isocaloric and hypocaloric feeding-interventions.

Objective

This work aimed to investigate the dependency of body weight loss following a reduction in hepatic steatosis on markers of glucagon resistance in type 2 diabetes.

Results

By design, weight loss was greater after hypocaloric compared to isocaloric feeding, but both diets caused similar reductions in hepatic steatosis, allowing us to investigate the effect of reducing hepatic steatosis with or without a clinically relevant weight loss on markers of glucagon resistance. The glucagon-alanine index improved following hypocaloric, but not isocaloric, feeding, independently of macronutrient composition.

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