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Objective:To evaluate the effect of short-term very low-calorie restriction(VLCR) on glycemic control in overweight/obese patients with type 2 diabetes, and to explore mechanisms through identifying markers of gut microbiota.Methods:This trial was conducted in 14 adult overweight/obese patients with type 2 diabetes. They received VLCR for 9 days in the hospital(calorie intake 300-600 kcal/d). Before and after VLCR, body weight(BW), waist circumference(WC), blood pressure(BP), and heart rate(HR) were measured, and body mass index(BMI) was calculated according to their height and weight. Fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), fasting insulin(FINS), triglycerides(TG), total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), and low-density lipoprotein-cholesterol(LDL-C) were determined, and yielded the homeostasis model assessment for insulin resistance(HOMA-IR). Additional lab tests such as liver and kidney function and electrolytes were performed. The estimated glomerular filtration rate(eGFR) was calculated to evaluate renal function. All data were analyzed using the SPSS Sample Power software. Feces samples were collected before and after VLCR. Fecal samples were tested for microbial diversity using 16S rDNA technology. Professional software was used to analyze the differences of gut microbiota in feces before and after VLCR.Results:After 9 days of VLCR, BW, BMI, WC, BP, HR, FBG, 2hPBG, FINS, HOMA-IR, alkaline phosphatase, TG, and blood urea nitrogen of 14 overweight/obese patients with type 2 diabetes were significantly reduced( P<0.05). No effect was seen on serum alanine aminotransferase, aspartate amino transferase, gamma glutamyl transferase, TC, HDL-C, LDL-C, creatinine, eGFR, uric acid, albumin, calcium, and phosphorus( P>0.05). The gut microbiota diversity did not differ before and after VLCR. The abundance of Bacteroidetes increased significantly, and the Firmicutes/Bacteroidetes ratio decreased from 11.79 to 4.20. Between groups analysis showed the abundance of Parabacteroides distasonis increased significantly after VLCR. Conclusion:VLCR can improve body weight and glucose and lipid metabolism in overweight/obese patients with type 2 diabetes, with no serious adverse events. Parabacteroides distasonis may be a marker of VLCR.
ABSTRACT
The metabolic syndrome (MS) is one of the major risk factors for cardiovascular disease.The pathogenesis of MS is not fully understood.In addition to insulin resistance and central obesity,some other factors such as resting heart rate are also thought to play certain roles.The primary strategy of the intervention is still relying on lifestyle modification including healthy dietary habits.
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Diabetic retinopathy is a highly specific vascular complication of both type 1 and type 2 diabetes.NF-?B can be triggered by oxidative stress and controls several programs of gene expression,the majority of which participate in the host inflammation and immune response.Evidence has accumulated that NF-?B is involved in the development of diabetic retinopathy.NF-?B activation induced by diabetes is associated with the apoptosis found in the pericyte,leukocyte-endothelial interaction,capillary basement membrane thickening,neovascularization and formation of epiretinal membranes.Inhibition of(NF-?B) activation has been suggested as a treatment strategy in diabetic retinopathy.
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Objective:Activation of the transcription factor nuclear factor-kappaB (NF-?B) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short activation of NF-?B , we observed a long-lasting activation of NF-?B and iNOS in the kidneys of diabetic rats. Methods:Sprague-Dawley rats were randomly divided into control group and diabetic group. The pathological changes in the kidneys of diabetic rats were observed at 1, 3 and 6 months respectively. The activity of NF-?B and iNOS was detected by immunohistochemistry. Results:The change of histopathology was severer at 6 months than at 3 months and 1 month in the kidneys of diabetic rats. A comparable increase in NF-?B p65 antigen was observed in the kidney cells especialy in vascular endothelial cells of diabetic rats, and the expression of iNOS in renal tissues of diabetic rats was higher than that of normal control. Conclusion:NF-?B and iNOS may play an important role in the pathoge-neis of diabetic rats, and the expression of them may be considered as a predictor of progressive renal in- jury in diabetic rats.
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Objective:To study the express levels of transcription factor nuclear factor-?B in diabetic rat retina. Methods: Sprague-Dawley rats were randomly divided into control groups of 1, 3 and 6 months, diabetic groupsof 1, 3 and 6 months, respectively. Diabetic model of rat was induced by injecting streptozotocin (STZ). The retinal morphology was observed in paraffin slide by microscope. The expression of NF-?B was detected by immunohistochemistry and electrophoretic mobility shift assay. Results: Histopathological changes were detected at 3 and 6 months. The changes were severer at 3 months than at 6 months. Activation of retinal NF-?B was detected by electrophoretic mobility shift assay and immunohistochemistry at 1 month, and the NF-?B remained activated at 3 and 6 months in diabetic rats. Conclusion: NF-?B is activated in retina in diabetes before histopathological changes can be seen, and remains activated for the duration when the retinopathy is developing.
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AIM:To investigate the expression of nuclear factor-?B(NF-?B),inducable nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2)in diabetic myocardium.METHODS:Thirty SD rats were randomly divided into control and experimental groups.Diabetes was induced by a single intraperitoneal injection of STZ.The weight,blood glucose level and heart weight index(HWI)were measured 24 weeks after injection.The myocardial NF-?B,iNOS and COX-2 were stained at the same time.Furthermore,NF-?B activation in myocardium was investigated by electrophoretic mobility shift assay(EMSA).RESULTS:(1)Compared to the normal rats,the NF-?B-positive cells in the myocardium in diabetic rats significantly increased.(2)NF-?B activation in myocardium by EMSA was significantly higher in the diabetic rats than that in the normal rats.(3)The iNOS was not expressed in normal rat myocardium and was significantly expressed in the diabetic rat myocardium.(4)The COX-2 was rarely expressed in normal rat myocardium and was significantly expressed in the diabetic rat myocardium.CONCLUSION:The expressions of NF-?B,iNOS and COX-2 are significantly enhanced in the diabetic myocardium.