Rose D Roderick, Clemmons David R
Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Growth Horm IGF Res. 2002 Dec;12(6):418-24. doi: 10.1016/s1096-6374(02)00083-7.
Growth hormone hypersecretion is a known cause of insulin resistance. This change in insulin sensitivity is believed to be mediated directly by growth hormone binding to its receptor. Five subjects ages 28-55 years who were participating in a clinical study that had been designed to assess the effects of a growth hormone receptor antagonist (Pegvisomant) on disease activity in acromegaly were evaluated to determine the role of growth hormone hypersecretion in inducing changes in insulin sensitivity. These subjects were treated with the 15-30 mg/day of Pegvisomant for periods ranging from 14 to 23 months. These doses were adequate to normalize IGF-I in four of the five subjects. The subjects were monitored to ensure that there were no significant changes in diet, exercise, or weight. Mean pretreatment IGF-I was 1104+/-277 ng/ml and decreased to a nadir of 355+/-157 ng/ml on treatment. After a 6-week withdrawal period, mean IGF-I had increased to 549+/-142 ng/ml. Fasting insulin was 35.2+/-16 uU/ml prior to treatment then decreased to a nadir of 19.9+/-14.6 uU/ml on treatment and then increased to 24.5+/-11.3 uU/ml. Fasting glucose decreased from 187+/-68 to 122+/-38 mg/dl and then increased to 159+/-41 mg/dl. Hemoglobin A(1)C decreased from 8.1+/-1.7 to 6.3+/-1.5%. Two subjects with overt type II diabetes had decreases in hemoglobin A(1)C from 8.3 to 5.9% and from 11.4 to 8.6%. These changes were associated with decreases in the amount of medication needed to control blood glucose. Weight remained stable throughout the study. The results show that the Pegvisomant is an effective agent for improving insulin resistance in subjects who have acromegaly and that this effect is independent of weight loss. The results suggest a potential role for Pevisomant in the treatment of insulin resistant states other than acromegaly.
生长激素分泌过多是胰岛素抵抗的一个已知原因。胰岛素敏感性的这种变化被认为是由生长激素与其受体结合直接介导的。对5名年龄在28至55岁之间、参与一项旨在评估生长激素受体拮抗剂（培维索孟）对肢端肥大症疾病活动影响的临床研究的受试者进行评估，以确定生长激素分泌过多在诱导胰岛素敏感性变化中的作用。这些受试者接受了每天15至30毫克的培维索孟治疗，治疗时间为14至23个月。这些剂量足以使5名受试者中的4名的胰岛素样生长因子-I（IGF-I）恢复正常。对受试者进行监测，以确保其饮食、运动或体重没有显著变化。治疗前IGF-I的平均值为1104±277纳克/毫升，治疗时降至最低点355±157纳克/毫升。经过6周的停药期后，IGF-I的平均值升至549±142纳克/毫升。治疗前空腹胰岛素为35.2±16微单位/毫升，治疗时降至最低点19.9±14.6微单位/毫升，然后升至24.5±11.3微单位/毫升。空腹血糖从187±68降至122±38毫克/分升，然后升至159±41毫克/分升。糖化血红蛋白A1C从8.1±1.7降至6.3±1.5%。两名明显的II型糖尿病受试者的糖化血红蛋白A1C分别从8.3降至5.9%以及从11.4降至8.6%。这些变化与控制血糖所需药物量的减少有关。在整个研究过程中体重保持稳定。结果表明，培维索孟是改善肢端肥大症患者胰岛素抵抗的有效药物，且这种作用与体重减轻无关。结果提示培维索孟在治疗除肢端肥大症以外的胰岛素抵抗状态方面可能具有潜在作用。
