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.


METHODS
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.


CONCLUSIONS
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.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. bjorn.lindgren@ki.se
Björn F
BF
Lindgren
Stefan H
SH
Jacobson
Kerstin
K
Brismar
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000628:therapy; D004334:Drug Administration Schedule; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage*; D007332:Insulin Infusion Systems; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008875:Middle Aged; D006435:Renal Dialysis / Q000379:methods; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D005947:Glucose