Coppey Lawrence, Davidson Eric, Shevalye Hanna, Obrosov Alexander, Torres Michael, Yorek Mark A
Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Department of Veterans Affairs, Iowa City Health Care System, Iowa City, IA, USA.
Diabetes Metab Syndr Obes. 2020 Apr 24;13:1367-1384. doi: 10.2147/DMSO.S247571. eCollection 2020.
To determine whether cornea nerve fiber density and/or corneal function are valid markers for early detection and treatment of peripheral neuropathy in rats modeling prediabetes and type 2 diabetes.
High-fat feeding combined without or with low-dose streptozotocin was used to create rat models for prediabetes and type 2 diabetes that were longitudinally studied for loss of structure and function of sensory nerves in the cornea and skin as well as nerve conduction velocity and vascular reactivity of epineurial arterioles. There were three time points examined in each of the three conditions with 12 rats per group. The latest time point (24 weeks of high-fat diet with or without 16 weeks of hyperglycemia) was used to examine reversibility of neuro and vascular pathology following 16 weeks of treatment with menhaden oil, a natural source of long-chain omega-3 polyunsaturated fatty acids. The number of rats in the intervention study ranged from 6 to 17.
Our longitudinal study demonstrated that vascular and neural dysfunction associated with obesity or type 2 diabetes occur early and are progressive. Decrease in cornea nerve fiber length and function were valid markers of disease in both the pre-diabetic and diabetic rat models and were more sensitive than decrease in intraepidermal nerve fiber density of the skin and thermal nociception of the hindpaw. Late intervention with menhaden oil significantly reversed both vascular and peripheral nerve damage induced by chronic obesity or type 2 diabetes.
These studies provide support for examination of corneal structure and function as an early marker of peripheral neuropathy in prediabetes and type 2 diabetes. Furthermore, we demonstrate that omega-3 polyunsaturated fatty acids derived from fish oil are an effective treatment for peripheral neuropathy that occurs with chronic obesity or type 2 diabetes.
确定在糖尿病前期和2型糖尿病大鼠模型中，角膜神经纤维密度和/或角膜功能是否为早期检测和治疗周围神经病变的有效标志物。
采用高脂喂养联合或不联合低剂量链脲佐菌素的方法建立糖尿病前期和2型糖尿病大鼠模型，纵向研究角膜和皮肤感觉神经的结构和功能丧失，以及神经外膜小动脉的神经传导速度和血管反应性。在三种条件下，每组12只大鼠，共检查三个时间点。使用最新的时间点（高脂饮食24周，伴或不伴16周高血糖）来检查用富含长链ω-3多不饱和脂肪酸的天然来源的鲱鱼油治疗16周后神经和血管病变的可逆性。干预研究中的大鼠数量为6至17只。
我们的纵向研究表明，与肥胖或2型糖尿病相关的血管和神经功能障碍出现早且呈进行性。角膜神经纤维长度和功能的降低是糖尿病前期和糖尿病大鼠模型中疾病的有效标志物，比皮肤表皮内神经纤维密度的降低和后爪热痛觉更敏感。后期用鲱鱼油干预可显著逆转慢性肥胖或2型糖尿病所致的血管和周围神经损伤。
这些研究支持将角膜结构和功能检查作为糖尿病前期和2型糖尿病周围神经病变的早期标志物。此外，我们证明源自鱼油的ω-3多不饱和脂肪酸是治疗慢性肥胖或2型糖尿病伴发的周围神经病变的有效方法。
