Choroidal thickness in relation to urinary albumin excretion rate in type 2 diabetes mellitus without retinopathy

Background To evaluate choroidal thickness (CT) in diabetic patients without diabetic retinopathy (DR) in relation to the urinary albumin excretion rate (UAER). Methods This is a prospective case-control study that included a consecutive sample of 120 patients with type 2 diabetes without clinically evident DR and a group of 60 matched healthy controls. Diabetic patients were included in two groups according to their UAER (normoalbuminuria and microalbuminuria). Complete ophthalmological examination was performed followed by optical coherence tomography (SD-OCT) for retinal and choroidal assessment. Twenty-four-hour urine samples were collected for UAER and blood samples for HbA1c and serum creatinine were obtained. Results The study included 180 eyes from 180 subjects in three groups. Patients with higher levels of albuminuria had a thinner choroid than normal controls, with decremental thinning as albuminuria progressed. Diabetics with normoalbuminuria showed no significant differences from controls. Choroidal thickness showed a significant moderate negative correlation with UAER (r = − 0.58, p < 0.001). Multiple regression analyses for diabetic patients with microalbuminuria demonstrated that UAER is the most important determinant of subfoveal choroidal thickness (SFCT) (p < 0.001). Conclusions Decreased CT was significantly correlated with UAER in diabetic patients without retinopathy and otherwise normal kidney functions. This decrease in thickness might be a predictor of DR.

Protective Effects of Bariatric Surgery on Kidney Functions by Inhibiting Oxidative Stress Responses Through Activating PPARα in Rats With Diabetes

ObjectiveThe aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats.MethodsWe established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague–Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal–jejunal bypass (DJB) surgery group. The food intake and body weight of rats were monitored and the glucose tolerance test (OGTT) test was performed every 2 weeks. The glomerular filtration rate (GFR) and urinary albumin excretion rate (UAFR) were measured to assess renal function. Hematoxylin–eosin (H&amp;E), periodic acid–Schiff (PAS), and Masson staining were used to evaluate renal histopathological changes. TUNEL assay was performed to detect cell apoptosis. The expressions of oxidative stress factors and inflammatory factors in the renal tissues of rats were detected by ELISA. The expressions of PPARα, reactive oxygen species (ROS), and NF-κB were detected by immunofluorescence. For in vitro experiment, HK2 cells cultured with high glucose were treated with PPARα agonist, PPARα antagonist, and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) agonist. The expressions of AMPK/PPARα/NF-κB signaling pathway-related proteins were detected by Western blot.ResultsBariatric surgery improved the glucose tolerance of DN rats. The GFR was decreased, the promotion of urinary albumin excretion rate (UAER) was inhibited, and the renal injury was alleviated. The extracellular matrix fraction was decreased and the renal function was improved. Meanwhile, bariatric surgery activates PPARα, inhibits ROS release, reduces oxidative stress injury, and reduces renal cell apoptosis. In vitro experiment results showed that the AMPK activator could activate PPARα, downregulate NF-κB, and inhibit inflammatory response. The phosphorylation of AMPK was inhibited by PPARα antagonism.ConclusionBariatric surgery can activate PPARα, inhibit oxidative stress injury, and improve glucose metabolism and renal function in DN rats.

The expression of POMC and AgRP in brain and kidney tissues at different stages of diabetic nephropathy rats

Objective To explore the changes of proopiomelanocortin (POMC) and Agouti-Related Peptide (AgRP) expression in brain and kidney tissues under insulin intervention at different stages of diabetic nephropathy (DN) rats. Methods The male Sprague-Dawley (SD) rats of DN were treated with high-fat diet for 8 weeks and induced by intraperitoneally injection of streptozotocin (30 mg/kg) for one time. Then DN rats were also injected insulin subcutaneously at 2–5 U/(kg·24 h) from initiation of the streptozotocin. Kidney tissue, blood sample, and 24 h-urine were collected to detect the ratio of kidney/body weight, blood glucose and 24-h urinary albumin excretion rate at different stages (4, 8, 12, and 16 weeks). Immunohistochemistry assay was used to measure the expression of POMC and AgRP at different stages of DN rats. Results The DN rats were established successfully. With the progression of DN, blood glucose, 24-h urinary albumin excretion rate and kidney body weight ratio increased significantly, while decreased when insulin was injected. Immunohistochemistry showed that the expression levels of POMC were decreased gradually in brain and kidney tissues. Conversely, the expression of AgRP in kidney was highest at week 8 and then decreased gradually. The effect of insulin on normalizing POMC and AgRP expression in brain and renal tissues was also observed in DKD rats. Conclusion With the progression of DN, the expression of POMC and AgRP in kidney tissues was observed at different stages of disease, and their expressions were significantly normalized by insulin. The mechanism of in situ expression of POMC and AGRP in kidney to the progression of DN needs further investigations.