Insulin-glucose infusion given before hemodialysis increases IGF-I in type 2 diabetes patients with chronic kidney disease.

OBJECTIVE: Hemodialysis is associated with catabolism and one contributing factor could be decreased bioavailable IGF-I. The aim of this investigation was to study the response of IGF-I and IGFBP-1 to a euglycemic hyperinsulinemic clamp before hemodialysis in type 2 diabetes (T2D) with chronic kidney disease on hemodialysis (CKD5D). Stage 5 (Stages 0-5 according to renal function) indicates a GFR less than 15 mL/min/1.73 m², D indicates hemodialysis. The response was compared with that in type 1 diabetes (T1D) with normal renal function. DESIGN: Five overnight fasted patients with T2D with CKD5D were subjected to an insulin infusion (1.6 mU/kg/h) for 4 h after which they had lunch followed by a four hour hemodialysis session. The results were compared with results from a previous study in seven T1D patients with normal renal function who had received a similar clamp the same insulin dose with the addition of an initial bolus dose. Blood samples were drawn at 15 to 30 min intervals for analysis of IGFBP-1, IGF-I and insulin and at 5 min intervals to determine blood glucose. RESULTS: There was no significant change between pre- and postdialysis values of IGF-I but there was a significant 29% increase (p<0.05) at the end of hemodialysis compared with the basal levels before insulin infusion in the T2D patients with CKD5D. The fasting mean levels of IGFBP-1 were increased in both T1D with normal renal function (geometric mean: 216 µg/l, range 169-275 µg/l) and in T2D with CKD5D (geometric mean: 112 µg/l , range 78-162 µg/l, p=0.15 compared with T1D patients) in spite of a high mean insulin level (32±5 mU/l). Insulin caused a similar decrease (p<0.05 all groups) in IGFBP-1 mean levels for the first 90 min in the T2D patients with CKD5D (73±7% of basal IGFBP-1 values) and the T1D patients (69±6%) with normal renal function. After 90 min there was a blunted response in the T2D patients with CKD5D whereas IGFBP-1 in the T1D patients with normal renal function continued to decline. After hemodialysis the IGFBP-1 serum levels increased compared with the levels at the end of insulin infusion but the predialysis values remained significantly lower than before the insulin infusion. CONCLUSION: Type 2 diabetes patients with chronic kidney disease requiring hemodialysis (CKD5D) have a high mean basal level of IGFBP-1 in spite of increased insulin levels. The first 90 min response of IGFBP-1 to insulin infusion is similar in T2D patients with CKD5D and T1D patients with normal renal function. After 90 min of insulin infusion a blunted decrease in IGFBP-1 was seen in T2D patients with CKD5D compared with type \1 diabetes with normal renal function. Insulin infusion before hemodialysis reduced the earlier reported increase in IGFBP-1 and increased IGF-I levels. Insulin infusion before dialysis in patients with CKD5D should be further studied since it could contribute to an anabolic effect with more bioavaialable IGF-I thus reducing the catabolic effect of hemodialysis.

Growth hormone treatment in hemodialysis patients--a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Renal failure and hemodialysis (HD) affect the anabolic growth hormone (GH)-insulin-like growth factor (IGF) axis. A positive correlation between serum IGF-I and normalized protein catabolic rate (PCRn) in HD patients has been reported, and the aim of this study was to assess the metabolic impact of recombinant human (rh)GH in these patients. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled study, rhGH was given to 35 HD patients for 8 weeks: 0.025 IU/kg/day for 1 week, increasing to 0.05 IU/kg/day. Patients with diabetes, malignancy or clinical signs of infection and those receiving steroid treatment were excluded. RESULTS: All patients completed the study. Side-effects were rare and equally distributed between the two groups. Post-treatment, serum IGF-I and IGF-I standard deviation score (IGF-I SD) increased in the rhGH group compared to the placebo group: 283+/-33 vs 151+/-16 mg/l (p = 0.001) and 1.8+/-0.6 vs -0.2+/-0.6 (p = 0.002), respectively. IGF binding protein-3 was higher in the rhGH group compared to the placebo group: 5859+/-285 vs 4369+/-321 mg/l (p = 0.002). PCRn was significantly higher in the rhGH group compared to the placebo group: 1.09+/-0.06 vs 0.90+/-0.06 g/kg/day (p = 0.029). No differences were found in body weight, serum albumin or leptin between the two groups. There was no change in C-reactive protein (CRP) in the rhGH group compared to the placebo group: 17.4+/-9.0 vs 12.3+/-4.6 mg/l (p = NS). When the patients were subgrouped according to the CRP level (< or > 10 mg/1), the effect on PCRn persisted only in rhGH-treated subjects with a normal CRP level: 1.10+/-0.08 vs 0.81+/-0.09 g/kg/day (p = 0.025). CONCLUSION: Treatment of HD patients with rhGH at a moderate dose causes augmentation of PCRn which is considered to indicate a higher dietary protein intake. The anabolic effect of rhGH seems to be abolished by subclinical inflammation.