Abstract:
Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.
摘要:
椎板炎是马足的常见和疼痛病症,并且大约90%的病例与胰岛素失调(ID)相关,所述胰岛素失调是常见的内分泌紊乱马代谢综合征(EMS)的主要特征,并且发生在具有垂体间壁功能障碍的动物的子集中。EMS的其他特征包括肥胖,脂肪因子(特别是脂联素和瘦素)和高甘油三酯血症的循环浓度改变。肥胖,ID,低脂联素血症,高瘦素血症和血浆脂质谱改变也是人类代谢综合征(HMS)和高血糖症的特征.钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是一类新型的口服降血糖药物,可与生活方式的改变结合使用HMS。SGLT2受体负责发生在近曲小管中的90%的肾葡萄糖重吸收。因此,这些药物通过抑制肾小球滤液的葡萄糖重吸收来增加尿葡萄糖排泄,从而导致尿卡路里损失,从而导致体重减轻和ID改善。高血糖症,低脂联素血症和高瘦素血症。没有许可的兽药可用于治疗马的ID和预防胰岛素相关的椎板炎。因此,最近有人主张使用SGLT2i控制马高胰岛素血症,目的是改善相关活动性椎板炎的恢复或预防未来的椎板炎.有少数已发表的研究报告SGLT2icanagliflozin的使用,ertugliflozin和velagliflozin有助于马ID的管理。然而,所使用的剂量在很大程度上是从人体研究中推断出来的,而对物种特异性变异的考虑有限。此外,对马和人类的身份证之间的根本差异的评估有限,特别是大多数患有ID的马保持高胰岛素血症但血糖正常的事实,这可能不能解释这些药物的有益作用。需要进一步研究与治疗相关的高甘油三酯血症的潜在有害作用,以及SGLT2i疗法对马中脂肪因子循环浓度的影响。