Cochran Elaine, Young Janice Ryan, Sebring Nancy, DePaoli Alex, Oral Elif Arioglu, Gorden Phillip
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Endocrinol Metab. 2004 Apr;89(4):1548-54. doi: 10.1210/jc.2003-031952.
Recombinant methionyl human leptin (r-metHuLeptin) therapy has shown clear efficacy in the treatment of severe insulin resistance associated with lipodystrophy syndromes and low leptin levels. We treated two siblings with Rabson-Mendenhall syndrome (severe insulin resistance and presumed insulin receptor mutations). The brother and sister, aged 13 and 11 yr, respectively, had severe acanthosis nigricans, insulin resistance, and diabetes. Both were taking 2000 mg metformin and 2 mg rosiglitazone daily; the brother was also taking 300 U regular insulin daily. In contrast to our lipoatrophic patients treated with r-metHuLeptin, these two patients had a higher percent body fat and low-normal fasting triglycerides [42 mg/dl (0.37 mmol/liter), male sibling, and 33 mg/dl (0.47 mmol/liter), female sibling]. The siblings were treated with r-metHuLeptin therapy for 10 months and demonstrated a 40-60% decrease in fasting serum glucose and insulin levels and improved glycosylated hemoglobin. There was corresponding improvement in glucose and insulin tolerance during leptin therapy. This is the first report of a partial, but significant, effect of r-metHuLeptin administration in patients with extreme insulin resistance with a presumed insulin receptor mutation and low serum triglyceride levels.
重组甲硫氨酰人瘦素（r-metHuLeptin）疗法已在治疗与脂肪营养不良综合征和低瘦素水平相关的严重胰岛素抵抗方面显示出明确疗效。我们对两名患有拉布森-门登霍尔综合征（严重胰岛素抵抗且推测存在胰岛素受体突变）的兄弟姐妹进行了治疗。这对兄妹分别为13岁和11岁，均患有严重的黑棘皮病、胰岛素抵抗和糖尿病。两人均每日服用2000毫克二甲双胍和2毫克罗格列酮；哥哥还每日注射300单位常规胰岛素。与接受r-metHuLeptin治疗的脂肪萎缩患者不同，这两名患者的体脂百分比更高，空腹甘油三酯水平处于低正常范围[男性兄妹为42毫克/分升（0.37毫摩尔/升），女性兄妹为33毫克/分升（0.47毫摩尔/升）]。这两名患者接受r-metHuLeptin治疗10个月后，空腹血糖和胰岛素水平下降了40% - 60%，糖化血红蛋白得到改善。在瘦素治疗期间，葡萄糖和胰岛素耐受性也有相应改善。这是关于r-metHuLeptin给药对推测存在胰岛素受体突变且血清甘油三酯水平低的极端胰岛素抵抗患者产生部分但显著效果的首份报告。
