Glucose metabolism in chronic renal failure with reference to GH treatment of uremic children.
Growth retardation is a common feature in children with end-stage renal failure (ESRF). Medical management of renal insufficiency rarely normalizes growth and optimistic reports on the effect of rhGH treatment on growth velocity may presage more extensive use of rhGH in pediatric nephrology. Ample evidence has shown beneficial effects of GH replacement therapy in both childhood and adolescent hypopituitarism. However, the remarkably few side effects of treatment reported in these conditions cannot necessarily be extrapolated to children with ESRF. Uremia is associated with a wide range of metabolic and hormonal derangements including decreased glucose tolerance. This is mainly due to impaired insulin-stimulated glucose disposal in peripheral tissues and insufficient insulin-induced suppression of hepatic glucose production. Insulin-stimulated glucose uptake in skeletal muscle in ESRF is reduced by 30-50% as compared to that in healthy subjects, and a reduction may be detected even in subjects with a more moderate reduction in renal function (GFR around 25 ml/min). Dialysis therapy improves the disturbed insulin action significantly. The cause of the insulin resistance in ESRF is multifactorial. Impaired physical fitness, accumulation of uremic toxins, raised levels of GH and glucagon, metabolic acidosis, dyslipidemia and the medication applied may all contribute. If exogenous GH administration is added to the already marked uremic insulin resistance, insulin action may be severely disturbed and the secondary hyperinsulinism further magnified. However, frank diabetes mellitus does not develop unless the beta cells fail to meet the enhanced demands. This will probably occur only in patients with a beta-cell genotype pivotal for the phenotypic expression of non-insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
Schmitz
O
O
Department of Medicine M (Endocrinology and Diabetes), Kommunehospitalet, Aarhus, Denmark.
Orskov
L
L
Lund
S
S
Møller
N
N
Christiansen
J S
JS
Orskov
H
H
D002648:Child; D005947:Glucose / Q000378:metabolism*; D006130:Growth Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D013006:Growth Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014511:Uremia / Q000378:metabolism* / Q000503:physiopathology
D011994:Recombinant Proteins; D013006:Growth Hormone; D005947:Glucose