Chronic oscillating glucose challenges disarrange innate immune homeostasis to potentiate the variation of neutrophil-lymphocyte ratio in rats with or without hidden diabetes mellitus

• Published in: Diabetes, metabolic syndrome and obesity Vol. 11; pp. 277 - 288
• Main Authors: Yang, Gaoxiong, Yan, Rui, Tong, Huanjun, Zhang, Jitai, Chen, Bin, Xue, Xiangyang, Wang, Jue, Chu, Maoping, Jin, Shengwei, Li, Ming
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Antioxidants (Nutrients); Apoptosis; Blood glucose; Care and treatment; Control; Development and progression; Diabetes; Diabetes mellitus; Genetic aspects; Glucose; Glucose tolerance test; Health aspects; High definition television; Homeostasis; Hospitals; Hyperglycemia; Hypotheses; Immunohistochemistry; Immunology; Inflammation; innate immune; Lymphocytes; Neutrophil/lymphocyte ratio; Neutrophils; Original Research; oscillating glucose level; Oxidative stress; Pancreas; rat; Reactive oxygen species; Urine; China; innate immune; rat; neutrophil–lymphocyte ratio; diabetes; oscillating glucose level
• ISSN: 1178-7007; 1178-7007
• DOI: 10.2147/DMSO.S160301

The neutrophil-lymphocyte ratio (NLR) has been considered as an inflammatory marker in various disorders, but it is not clear whether the NLR is also elevated with hidden diabetes (HD), which is normal in fasting blood glucose (FBG) but abnormal in the oral glucose tolerance test (OGTT). An HD animal model for 27 days and an animal model with oscillating glucose (OG) for 7 days were applied on adult female Sprague-Dawley rats. OGTT, leukogram analysis, histology, and immunohistochemistry were carried out. In HD rats, the percentage of neutrophils increased but the percentage of lymphocytes decreased; hence, the NLR rose relative to sham. This may be a result of the OG levels often experienced by diabetic subjects, as normal rats given OG (6 g/kg/6 h) for 7 days had significantly reduced lymphocyte numbers and increased NLR compared with the values before and 1 h after oral glucose administration during OGTT. Glucose-induced disarrangement of partitions of circulating immune cells and NLR was involved in the increase in oxidative stress, as these changes were totally blocked by the antioxidant glutathione (GSH). GSH (50 mg/kg/6 h) totally blocked the glucose-induced alterations in lymphocyte and NLR values. HD associated with elevation of NLR values may be partly attributed to a homeostasis disorder of the innate inflammatory state, caused by oscillating hyperglycemia. Acute high glucose administration produced a significant decrease in lymphocyte number. OG administration potentiated this effect and increased the NLR value, which was blocked by GSH, suggesting that reactive oxygen species play a critical role in maintaining lymphocyte numbers.