Rigalleau V, Blanchetier V, Combe C, Guillot C, Deleris G, Aubertin J, Aparicio M, Gin H
Service de Nutrition-Diabétologie, Hôpital Haut-Lévêque, Pessac, France.
Am J Clin Nutr. 1997 May;65(5):1512-6. doi: 10.1093/ajcn/65.5.1512.
A low-protein, low-phosphorus diet (LPD) has been shown to improve insulin sensitivity in uremic patients; however, this improvement has not been studied at low physiologic concentrations of plasma insulin, and the metabolic pathways concerned with this improvement have not been located. We used the glucose clamp technique at a low (0.25 mU.kg-1.min-1) level of hyperinsulinemia associated with the infusion of D[6,6-2H2] glucose to assess the insulin sensitivity of endogenous glucose production (EGP). Eight nondialyzed uremic patients were studied before and after 3 mo on an LPD providing 0.3 g/kg protein, 5-7 mg P/kg, and 146 kJ/kg (67% of energy as carbohydrates and 30% as lipids) per day, supplemented with ketoanalog amino acids. Postabsorptive plasma glucose and insulin declined after 3 mo of the diet (plasma glucose: 5.0 +/- 0.1 mmol/L before compared with 4.7 +/- 0.1 mmol/L after the LPD, P < 0.05; plasma insulin: 82.4 +/- 20.7 pmol/L before compared with 48.8 +/- 6.0 pmol/L after, P < 0.05). Postabsorptive glucose turnover rates did not change with the diet (2.06 +/- 0.14 mg.kg-1.min-1 before compared with 2.11 +/- 0.17 mg.kg-1.min-1 after LPD; NS). The insulin metabolic clearance rate was enhanced after the diet, so a lower level of hyperinsulinemia was obtained during the clamp (168.8 +/- 28.1 pmol/L before compared with 115.2 +/- 14.7 pmol/L after; P < 0.05). However, EGP was more easily inhibited after the diet (0.90 +/- 0.31 mg.kg-1.min-1 before compared with 0.30 +/- 0.17 mg.kg-1.min-1 after; P < 0.05), providing evidence of an improved insulin sensitivity of this parameter. This beneficial influence takes place at a physiologic level of hyperinsulinemia, and it probably plays an important role in the better glucose tolerance that has been reported in uremic patients on an LPD. An abnormal insulin sensitivity of EGP may participate in the disturbances of glucose metabolism in chronic renal failure.
低蛋白、低磷饮食（LPD）已被证明可改善尿毒症患者的胰岛素敏感性；然而，尚未在低生理浓度的血浆胰岛素水平下研究这种改善情况，且与这种改善相关的代谢途径也未明确。我们采用葡萄糖钳夹技术，在与输注D[6,6-2H2]葡萄糖相关的低水平（0.25 mU·kg-1·min-1）高胰岛素血症状态下，评估内源性葡萄糖生成（EGP）的胰岛素敏感性。对8例未透析的尿毒症患者在接受LPD饮食3个月前后进行了研究，该饮食每天提供0.3 g/kg蛋白质、5 - 7 mg P/kg以及146 kJ/kg（67%的能量来自碳水化合物，30%来自脂质），并补充酮类似物氨基酸。饮食3个月后，空腹血浆葡萄糖和胰岛素水平下降（空腹血浆葡萄糖：饮食前为5.0±0.1 mmol/L，LPD饮食后为4.7±0.1 mmol/L，P<0.05；血浆胰岛素：饮食前为82.4±20.7 pmol/L，饮食后为48.8±6.0 pmol/L，P<0.05）。空腹葡萄糖周转率未随饮食改变（饮食前为2.06±0.14 mg·kg-1·min-1，LPD饮食后为2.11±0.17 mg·kg-1·min-1；无显著性差异）。饮食后胰岛素代谢清除率提高，因此在钳夹期间获得了较低水平的高胰岛素血症（饮食前为168.8±28.1 pmol/L，饮食后为115.2±14.7 pmol/L；P<0.05）。然而，饮食后EGP更易被抑制（饮食前为0.90±0.31 mg·kg-1·min-1，饮食后为0.30±0.17 mg·kg-1·min-1；P<0.05），这证明该参数的胰岛素敏感性得到了改善。这种有益影响发生在高胰岛素血症的生理水平，并且可能在LPD饮食的尿毒症患者中所报道的更好的糖耐量中起重要作用。EGP异常的胰岛素敏感性可能参与慢性肾衰竭患者的糖代谢紊乱。
