Haffner D, Nissel R, Wühl E, Schaefer F, Bettendorf M, Tönshoff B, Mehls O
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Pediatr Res. 1998 Feb;43(2):209-15. doi: 10.1203/00006450-199802000-00009.
To evaluate the metabolic effects of long-term treatment with recombinant human (rh) GH in short children with chronic renal failure (CRF), annual oral glucose tolerance tests (oGTT) during rhGH therapy for up to 5 y in 53 prepubertal children with CRF on conservative treatment, dialysis, and after renal transplantation were compared with that of 12 age-matched children treated with rhGH for idiopathic short stature. At the start of rhGH treatment, fasting values of glucose, insulin, glycosylated Hb A (HbA1C), triglycerides, cholesterol, glucose, and insulin responses during oGTT were significantly elevated in all patient groups compared with control subjects (p < 0.001). In the total population, fasting and 2-h postprandial glucose concentrations were inversely correlated with GFR and positively with age and methylprednisolone dosage in transplanted patients. Fasting insulin levels were positively correlated with body mass index and inversely with GFR. RhGH treatment was not associated with a change in fasting or stimulated glucose concentrations in any treatment group throughout the observation period. In contrast, serum insulin levels increased during the first treatment year in all groups, resulting in a more marked elevation of integrated insulin levels in transplant (1402 +/- 179 pM) and dialysis (1025 +/- 114 pM) patients compared with conservatively treated patients (829 +/- 94 pM), and control subjects (719 +/- 89 pM) (p < 0.01). Hyperinsulinemia persisted in all treatment groups for up to 5 y of follow-up. In conclusion, age, renal function, and obesity are the major independent predictors of glucose tolerance in children with CRF. Long-term rhGH treatment does not affect glucose tolerance, but aggravates the preexisting hyperinsulinemia in children with end-stage renal disease. In concert with the dyslipidemia of uremia, the rhGH-promoted hyperinsulinemia may contribute to the long-term risk for premature atherosclerosis in patients with childhood onset CRF.
为评估重组人生长激素（rhGH）长期治疗对慢性肾功能衰竭（CRF）矮小儿童的代谢影响，对53例青春期前接受保守治疗、透析及肾移植的CRF患儿在rhGH治疗长达5年期间每年进行的口服葡萄糖耐量试验（oGTT），与12例因特发性矮小接受rhGH治疗的年龄匹配儿童进行比较。在rhGH治疗开始时，与对照组相比，所有患者组的空腹血糖、胰岛素、糖化血红蛋白A（HbA1C）、甘油三酯、胆固醇水平以及oGTT期间的血糖和胰岛素反应均显著升高（p<0.001）。在总体人群中，空腹及餐后2小时血糖浓度与移植患者的肾小球滤过率（GFR）呈负相关，与年龄及甲泼尼龙剂量呈正相关。空腹胰岛素水平与体重指数呈正相关，与GFR呈负相关。在整个观察期内，rhGH治疗在任何治疗组中均未导致空腹或刺激后血糖浓度发生变化。相反，所有组在治疗的第一年血清胰岛素水平均升高，导致移植患者（1402±179 pM）和透析患者（1025±114 pM）的胰岛素积分水平升高幅度比保守治疗患者（829±94 pM）和对照组（719±89 pM）更为显著（p<0.01）。高胰岛素血症在所有治疗组中持续长达5年的随访期。总之，年龄、肾功能和肥胖是CRF患儿糖耐量的主要独立预测因素。长期rhGH治疗不影响糖耐量，但会加重终末期肾病患儿已有的高胰岛素血症。与尿毒症的血脂异常共同作用，rhGH促进的高胰岛素血症可能会增加儿童期起病的CRF患者发生过早动脉粥样硬化的长期风险。
