Candler Toby, McGregor David, Narayan Kruthika, Moudiotis Chris, Burren Christine P
Department of Paediatric Endocrinology, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
Medical Research Council The Gambia at London School of Hygiene and Tropical Medicine, London, UK.
J Pediatr Endocrinol Metab. 2020 Jul 28;33(7):951-955. doi: 10.1515/jpem-2019-0389.
Objectives Prader-Willi Syndrome (PWS) is characterised by hyperphagia often leading to obesity; a known risk factor for insulin resistance and type 2 (T2) diabetes. We present a prepubertal girl with PWS who developed diabetes. Case presentation Our case was diagnosed with PWS in infancy following investigation for profound central hypotonia and feeding difficulties. She commenced growth hormone (GH) aged 8 years for short stature and treatment improved linear growth. At age 12 years, she presented with polydipsia, polyuria and vulvovaginitis. She was overweight (BMI SDS +1.43). Diabetes was diagnosed (Blood glucose = 24.2 mmol/L, HbA1c = 121 mmol/mol or 13.2%). She was not acidotic and had negative blood ketones. Autoantibodies typical of type 1 diabetes were negative. She was initially treated with basal bolus insulin regime. GH was discontinued 3 months later due to concerns regarding GH-induced insulin resistance. Off GH, insulin requirements reduced to zero, allowing Metformin monotherapy. However off GH, she reported significant lethargy with static growth and increased weight. Combinations of Metformin with differing insulin regimes did not improve glucose levels. Liraglutide (GLP-1 agonist) and Metformin did not improve glucose levels nor her weight. Liraglutide and Empaglifozin (SGLT-2 inhibitor) therapy used in combination were well tolerated and demonstrated rapid normalisation of blood glucose and improvement in her HbA1c to within target (48 mmol/mol) which was sustained after 6 months of treatment. Conclusions Newer treatments for type 2 diabetes (e. g. GLP-1 agonists or SGLT-2 inhibitors) offer potential treatment options for those with diabetes and PWS when conventional treatments are ineffective.
目标普拉德-威利综合征（PWS）的特征是食欲亢进，常导致肥胖，而肥胖是胰岛素抵抗和2型（T2）糖尿病的已知危险因素。我们报告一名患有PWS的青春期前女孩患了糖尿病。病例报告我们的病例在婴儿期因严重的中枢性肌张力低下和喂养困难接受检查后被诊断为PWS。她8岁时因身材矮小开始使用生长激素（GH），治疗改善了线性生长。12岁时，她出现多饮、多尿和外阴炎。她超重（BMI SDS +1.43）。诊断为糖尿病（血糖 = 24.2 mmol/L，糖化血红蛋白 = 121 mmol/mol或13.2%）。她没有酸中毒，血酮阴性。1型糖尿病典型的自身抗体为阴性。她最初接受基础大剂量胰岛素治疗方案。3个月后，由于担心GH诱导的胰岛素抵抗，停用了GH。停用GH后，胰岛素需求量降至零，可进行二甲双胍单药治疗。然而，停用GH后，她报告有明显的嗜睡，生长停滞且体重增加。二甲双胍与不同胰岛素治疗方案联合使用并未改善血糖水平。利拉鲁肽（GLP-1激动剂）和二甲双胍并未改善血糖水平和她的体重。联合使用利拉鲁肽和恩格列净（SGLT-2抑制剂）治疗耐受性良好，血糖迅速恢复正常，糖化血红蛋白改善至目标范围内（48 mmol/mol），治疗6个月后仍保持这一效果。结论当传统治疗无效时，2型糖尿病的新型治疗方法（如GLP-1激动剂或SGLT-2抑制剂）为患有糖尿病和PWS的患者提供了潜在的治疗选择。
