Three Days Low-carbohydrate/High-fat Diet Increases Insulin Clearance in Non-obese Healthy Men

Abstract

　It has been reported that 1-wk overfeeding impairs insulin sensitivity and elevates insulin level, and the latter is partly induced by impaired metabolic clearance rate of insulin (MCRI). Thus, MCRI is considered as a regulatory factor to maintain euglycemia during short term dietary change. However, the effect of low-carbohydrate/high-fat (LCHF) diet on MCRI has not been elucidated.

　To clarify the effect of 3-day LCHF diet, we studied 48 non-obese healthy men (BMI; 22.6±2.5 kg/m²). Each subject consumed a 3-day control diet, which was followed by a 3-day eucaloric LCHF diet (20% carbohydrate, 20% protein, 60% fat). After the completion of both diet protocols, we performed hyperinsulinemic euglycemic clamp (insulin infusion rate (IIR) =100 mU/m² per min) to evaluate glucose infusion rate (GIR) and MCRI, calculated as a ratio of IIR to steady state serum insulin (SS_SI). The 3-day LCHF diet increased MCRI (497.4±1.4 ml/min per m² to 540.1±85.0 ml/min per m², p<0.05); however, the individual changes were highly variable. To further investigate the role of MCRI, we divided the subject into high-responder (HR) and low-responder (LR) based on the median %change of MCRI by LCHF diet. At baseline, HR group showed higher GIR level compared with LR group (13.0±1.9 vs. 11.8±2.0 mg/kg FFM per min, p<0.05), while MCRI and SS_SI levels were comparable. After LCHF diet, MCRI was increased (481.9±58.8 to 582.5±90.8 ml/min per m², p<0.001) and SSSI was decreased (210.2±23.3 μU/ml to 175.1±23.5 μU/ml, p<0.001) in HR group, but those were not altered in LR group. In parallel with decreased SS_SI, GIR was decreased in HR group (from 13.0±1.9 to 11.7±2.4 mg/kg FFM per min, p=0.003) after LCHF diet, but not in LR group.

　In conclusion, MCRI was increased after 3-day LCHF diet; however, the effect was highly variable. The decreased GIR after LCHF diet in HR group may be partly due to decreased SSSI and contribute to maintain euglycemia during low-carbohydrate availability in insulin sensitive subjects.