A LOW-PROTEIN DIET IMPROVES INSULIN SENSITIVITY OF ENDOGENOUS GLUCOSE-PRODUCTION IN PREDIALYTIC UREMIC PATIENTS

A low-protein, low-phosphorus diet (LPD) has been shown to improve ins ulin 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-H-2(2)]glucose to assess the insulin sensitivity of endogenous gluc ose production (EGP). Eight nondialyzed uremic patients were studied b efore and after 3 mo on an LPD providing 0.3 g/kg protein, 5-7 mg P/kg , and 146 W/kg (67% of energy as carbohydrates and 30% as lipids) per day, supplemented with ketoanalog amino acids. Postabsorptive plasma g lucose 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) be fore 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 lo wer 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 < 0.0 5). 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 sensit ivity of this parameter. This beneficial influence takes place at a ph ysiologic level of hyperinsulinemia, and it probably plays an importan t role in the better glucose tolerance that has been reported in uremi c patients on an LPD. An abnormal insulin sensitivity of EGP may parti cipate in the disturbances of glucose metabolism in chronic renal fail ure.