Impaired postprandial regulation of insulin-like growth factor binding protein-1 in children with chronic renal failure.
Patients with chronic renal failure (CRF) have elevated plasma levels of insulin-like growth factor-1 (IGFBP-1). We sought to determine the dynamics of plasma IGFBP-1 in response to an endogenous insulin pulse during an oral glucose tolerance test (oGTT) in 12 prepubertal children with advanced CRF [glomerular filtration rate (GFR) 12.5 +/- 4 mL/min/1.73 m2] and in 9 age-, gender-, and body size-matched controls with normal renal function. Glucose and insulin responses to oGTT were significantly elevated in CRF (P < 0.01), indicating decreased sensitivity to the hypoglycemic action of insulin. Fasting plasma IGFBP-1 levels in CRF (235 +/- 40 ng/mL) were 2.5-fold increased compared with controls (94 +/- 11.6 ng/mL, P < 0.0001). In controls, plasma IGFBP-1 levels rapidly decreased with time by 52%, to a level of 45 +/- 6.7 ng/mL 180 min after the oral glucose load. In contrast, plasma IGFBP-1 levels in CRF patients slowly decreased with time by 25%, to a level of 176 +/- 28 ng/mL (P < 0.001 vs. controls) 180 min after the oral glucose load. For the group as a whole, the percent decrease in IGFBP-1 at 180 min was positively correlated with GFR (r = 0.85, P < 0.0001). Plasma GH concentrations were not statistically different at baseline, but showed a paradoxical increase in CRF patients thereafter. Plasma IGF-I concentrations at baseline were comparable in CRF patients and controls and similarly decreased by about 10% (P < 0.01) after the oral glucose load. In summary, our study shows that the decline of plasma IGFBP-1 in response to an oral glucose load is impaired in children with CRF despite increased insulin levels. This impaired postprandial decline of plasma IGFBP-1 might interfere with glucose homeostasis by blocking insulin-like activity of free IGFs in vivo and thereby contribute to glucose intolerance in uremia.
Haffner
D
D
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Blum
W F
WF
Heinrich
U
U
Mehls
O
O
Tönshoff
B
B
D000284:Administration, Oral; D002648:Child; D004435:Eating / Q000502:physiology*; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000502:physiology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D009994:Osmolar Concentration; D012016:Reference Values
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D019382:Human Growth Hormone