Epigenetic modifications such as DNA methylation, histone post-translational modifications, non-coding RNA are reversible, heritable alterations which are induced by environmental stimuli. Major risk factors of diabetes and diabetic complications including hyperglycemia, oxidative stress and advanced glycation end products, can lead to abnormal epigenetic modifications in retinal vascular endothelial cells and retinal pigment epithelium cells. Epigenetic mechanisms are involved in the pathogenesis of macular edema and neovascularization of diabetic retinopathy (DR), as well as diabetic metabolic memory. The heritable nature of epigenetic marks also playsakey role in familial diabetes mellitus. Further elucidation of epigenetic mechanisms in DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
Objective To systematically review the effectiveness and safety of autologous implantation of stem cells for diabetic peripheral neuropathy (DPN). Methods Randomized controlled trials on relevant studies were retrieved in databases including CBM (1978-2011.6), CNKI (1979-2011.6), MEDLINE (1950-2011.6), PubMed (1950-2011.6), EMbase (1970-2011.6) and The Cochrane Library (Issue 3, 2011). References of the included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assess the methodological quality of the included studies. Then, meta-analysis was performed using RevMan 5.0 software.Results Four RCTs involving 68 patients (136 limbs) were included, most of which were low in methodological quality. The results of meta-analysis indicated that, autologous stem cell therapy improved or even eliminated DPN symptoms including pain, numbness, and cold sensation in the limbs, intermittent limping, and rest pain. Compared with the routine therapy, autologous stem cell therapy improved tibial sensory nerve conduction velocity (MD=5.75, 95%CI 3.86 to 7.64, Plt;0.000 01), tibial motor nerve conduction velocity (MD=4.04, 95%CI 0.90 to 7.18, P=0.001), sural sensory nerve conduction velocity (MD=7.47, 95%CI 4.00 to 10.94, Plt;0.000 1), and sural motor nerve conduction velocity (MD=3.38, 95%CI 0.07 to 7.58, P=0.05), with no adverse reaction reported. Conclusion Current evidence shows that, autologous stem cell therapy is effective in treating DPN. Due to the lack of high quality studies, more high quality RCTs are needed to verify the above conclusion.
Objective To investigate the use of oral anti-diabetic drugs and sugar blood control situation in advanced aged patient with diabetic mellitus in a community health centre in order to provide references for rational drug use. Methods A cross-sectional survey about oral anti-diabetic drugs was carried out in senile diabetic patients who visited the community health centre and established complete health documents voluntarily from February 2012 to February 2013. Results There were 176 cases of advanced aged patients with type 2 diabetic mellitus, of which, 107 cases were female and 69 cases were male, whose age ranged from 80 to 94. Among 176 cases, there were 107 (60.80%) patients with type 2 diabetic mellitus combined with hypertension, chronic heart diseases, and stoke; 155 had oral anti-diabetic drugs (88.06%). 67.19% of patients who took one oral anti-diabetic drug chose α-glycosidase inhibitors, followed by sulfonylurea. 53.73% of patients who received combination therapy chose glycosidase inhibitors and sulfonylurea. For the treatment of anti-diabetic drugs, 73.68% of patients met the criteria (fasting blood sugar: no more than 8.0 mmol/L), with control rates of 73.56% for α-glycosidase inhibitors and 72.58% for sulfonylurea. More than half of the patients could not be evaluated for their glycosylated hemoglobin levels were not tested. Conclusion Doctors working in community health centres should choose oral anti-diabetic drugs according to patients’ own conditions when treating advanced aged patients with diabetic mellitus in order to avoid adverse reaction such as hypoglycemia. Glycosidase inhibitors are the mostly used drug in the community health centre because it is safe with less adverse reaction when used in senile people and it could ideally control their blood sugara.
Objective To assess the effectiveness of intensive versus routine education on diabetes mellitus for preventing diabetic foot ulcer. Methods We electronically searched CENTRAL (Issue 1, 2013), PubMed (1978-2013), EMbase (1978-2013), VIP (1989-2013) and WanFang Data (1980-2013), hand-searched correlated proceedings and retrieved the references of included studies, for the randomized controlled trials on intensive versus routine education on diabetes mellitus for preventing diabetic foot ulcer all over the world. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 software. Results Twelve trials involving 1 841 patients were finally included. The results of meta-analysis showed that: a) the incidence of diabetic foot ulcer in the intensive education group was lower than the routine group, with a significant difference (RR=0.51, 95%CI 0.30 to 0.84, P=0.008); b) two groups were alike in the amputation rate, with no significant difference (OR=0.54, 95%CI 0.17 to 1.67, P=0.28); and c) the score of knowledge on diabetes mellitus was higher in the intensive education group than in the routine education group, with a significant difference (MD=7.32, 95%CI 3.57 to 11.06, P=0.000 1). Conclusion Current evidence shows that: compared with routine education, intensive education could reduce the incidence of diabetic foot ulcer effectively. However, the above conclusion should be verified by conducting more high quality studies.
Objective To assess the efficacy of Tongxinluo for diabetic kidney disease. Methods we conducted a systematic review of randomized controlled trials (RCTs) in which Tongxinluo was used to treat diabetic kidney disease. And we screened relevant studies according to predefined inclusion and exclusion criteria, evaluated the quality of the included studies, and performed meta-analyses by using The Cochrane Collaboration’s Revman 5.0 software. Results A total of 11 RCTs were enrolled in the review. The results of meta-analysis showed that Tongxinluo was better on attenuating 24 hour urinary protein,BUN and UAER; Tongxinluo was not superior to no treatment on the improvement of Scr and Ccr; Tongxinluo was better than no treatment on the Regulation of blood lipids, such as TC, TG, LDL-C. However, Tongxinluo might have similar effects on the improvement of HDL-C; Tongxinluo was better than no treatment on the improvement of FBG, but xuezhikang was not superior to no treatment on the improvement of P2BG and HbA1c. Tongxinluo was better than no treatment in decreasing plasma endothelin (ET). No significant adverse effects or Allergic reactions were reported. Conclusion The evidence currently available shows that Tongxinluo has some effect and is relatively safe in treating patients with diabetic kidney disease.Due to a high risk of selection bias and detection bias in the included studies, the evidence is insufficient to determine the effect of Tongxinluo. Further large-scale trials are required to define the role of xuezhikang in the treatment of DKD.
Objective To make individualized evidence-based treatment for patients with diabetic peripheral neuropathy. Methods Based on the clinical questions we raised, evidence was collected and critically assessed. Patients’ preferences was also taken into consideration in the decision-making treatment. Results 157 studies were retrieved and finally 15 randomized controlled trials, 14 systematic reviews and meta-analyses, and 1 clinical guidelines were considered eligible. The evidence indicated that the first step in management of patients with diabetic peripheral neuropathy should aim for stable and optimal glycemic control; there was no statistically significant difference between aldose reductase inhibitors and placebo in the treatment of diabetic polyneuropathy, the same to nerve growth factor; alpha-lipoic acid is superior to placebo in reducing symptoms of diabetic peripheral neuropathy; 5-hydroxytryptamine and norepinephrine uptake inhibitor, tricyclic antidepressants and anticonvulsants might alleviate the pain in patients with diabetic peripheral neuropathy; vitamin B and capsaicin cream are is effective and safe in the management of diabetic peripheral neuropathic pain. The individualized treatment plans were developed based on the available evidence. After 3 month of treatment, the blood sugar returned to normal and symptoms were alleviated. Conclusion The treatment efficacy in diabetic peripheral neuropathy has been improved by determining an individulized treatment plan according to evidence-based methods.
Objective To evaluate the effectiveness and safety of spironolactone for diabetic nephropathy. Methods We electronically searched CENTRAL (issue 3, 2008), MEDLINE (1950 to August 2008), EMbase (1984 to August 2008), CNKI (1994 to September 2008), and VIP (1989 to August 2008). We also checked the reference lists of all papers identified for further trials. Randomized controlled trials (RCTs) and quasi-RCTs were identified and analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions. Results Three RCTs were included. Meta-analysis was not performed due to heterogeneity. Trials showed that spironolactone might decrease urinary albumin excretion, but could scarcely play an important role on kidney function and blood pressure. Conclusion Affirmative assessment cannot be made about the effectiveness and safety of spironolactone for diabetic nephropathy according to the limited existing trials. Large-scale, high-quality RCTs are needed to confirm or refuse the available evidence.
Objective To assess the effectiveness of xuezhikang for treating diabetic kidney disease. Methods We searched the Cochrane Central Register of Controlled Trials (Issue 3, 2008), MEDLINE (1980 to September 2008), EMbase (1980 to September 2008), CBMdisc (1990 to September 2008), and CNKI (1994 to September 2008). We also hand searched relevant journals and conference proceedings. Randomized controlled trials (RCTs) in which xuezhikang was used to treat diabetic kidney disease were collected. Then we screened the retrieved studies according to predefined inclusion and exclusion criteria, evaluated the quality of included studies, and performed metaanalyses by using The Cochrane Collaboration’s RevMan 4.2 software. Results Nine RCTs were included. Meta-analyses showed that xuezhikang was superior to routine treatment in decreasing 24-hour urinary protein (WMD –0.87, 95%CI –1.34 to –0.41), microalbuminuria (WMD –115.39, 95%CI –127.63 to –103.15), and urinary albumin excretion rate (WMD – 65.46, 95%CI –68.87 to –62.12); but xuezhikang had similar effects in reducing serum creatinine compared with routine treatment (WMD –5.42, 95%CI –11.06 to 0.21). Moreover, xuezhikang was more effective in regulating blood lipids, including TC (WMD –1.71, 95%CI –2.39 to –1.03), TG (WMD –0.96, 95%CI –1.46 to –0.46), LDL-C (WMD –1.01, 95%CI –1.64 to –0.38), and HDL-C (WMD 0.22, 95%CI 0.09 to 0.36). Xuezhikang was not superior to routine treatment in improving fasting blood sugar (WMD -0.01, 95%CI -0.49 to 0.47), but was more effective in improving 2 h-BS (WMD –1.10, 95%CI –1.35 to –0.85) and HbA1c (WMD –0.41, 95%CI –0.56 to –0.27). No significant adverse effects or allergic reactions were reported. Conclusions The evidence currently available shows that xuezhikang may decrease 24-hour urinary protein, microalbuminuria, serum creatinine, regulate blood lipids, and adjust blood glucose. Due to a high risk of selection bias and detection bias in the included studies, the evidence is insufficient to determine the effect of xuezhikang. Further large-scale trials are required to define the role of xuezhikang in the treatment of diabetic kidney disease.
Objective To prepare nerve growth factor (NGF)-insulin composite gel and observe the effects of NGF-insulin composite gel on deep second degree scald wound healing in diabetic rats. Methods Carbomer 980, NGF (4 000 U), and insulin (800 U) were used to prepare the insulin gel, NGF gel, and NGF-insulin composite gel. The character of NGF-insulin composite gel was observed, and the in vitro drug release was tested. Seventy-five SPF Wistar male rats, weighing 200-250 g, were divided into 5 groups randomly, 15 rats each group: normal control group (group A), diabetes control group (group B), insulin gel treatment group (group C), NGF gel treatment group (group D), and NGF-insulin composite gel treatment group (group E). The type 1 diabetes rat model was established by intraperitoneal injection of Streptozotocin (55 mg/kg) in groups B, C, D, and E, while the rats in group A were injected with the same dose of citric acid and calcium citrate buffer. After modeling success, deep second degree scald wound on the back was made with constant temperature water bath box. Wounds were treated with carbomer blank gel in groups A and B, with insulin composite gel in group C, with NGF gel in group D, and with NGF-insulin composite gel in group E, once a day. At 3, 7, 11, 15, and 21 days after injury, the scald wound healing was observed and healing rate was calculated; the full-thickness skin specimens were harvested from 3 rats of each group for histological and immuohistochemical staining observation. Results The NGF-insulin composite gel was clear and transparent, and had good moisture retention capacity and adhesion; it was easy to apply and clean up. The drug release in vitro lasted more than 24 hours and maintained for 30 days. No rat died during the experiment. At 3 days after injury, wound area did not reduce in all groups; at 7, 11, 15, and 21 days, group E had the highest wound healing rate, and group B had the lowest; significant differences were found between group E and group B and when compared with the other groups (P lt; 0.05). HE staining showed that group E surpassed other groups in the growth of granulation tissue and collagen fiber. Immunohistochemical results showed that the CD34 and proliferating cell nuclear antigen (PCNA) expressed at 3 days, and the number of positive cells increased gradually with time; the microvessel density and PCNA expression were highest in group E and were lowest in group B, showing significant differences when compared with the other groups and between group E and group B (P lt; 0.05). Conclusion NGF-insulin composite gel can improve deep second degree scald wound healing in diabetic rats.
Objective To evaluate the efficacy and safety of Bismuth Subgallate/Borneol (SuileTM) (BSB) dressing in the treatment of diabetic foot ulcers. Method s A two-center, randomized controlled parallel-group comparison study was conducted. Between September 2005 and November 2006, 35 patients with nonhealing diabetic foot ulcer (Wagner 2-3 grade) were recruited and divided randomly into the test group (BSB group, n=25) and control group (IG group, n=10). There was no significant difference in general data between 2 groups (P gt; 0.05). Based on the comprehensive therapy of diabetic foot, ulcers were topically treated by SuileTM dressing and Intrasite gel in the BSB group and IG group, respectively. The ulcer area was measured once a week. Ulcer bleeding was observed and acceptance of the dressing was inquired each week. Results Of the patients, 22 patients in the BSB group and 8 in the IG group completed the clinical trial. Intention to treat (ITT) analysis indicated that the results were excellent in 19 (76%) cases, good in 3 cases (12%), fair in 1 case (4%), and poor in 2 cases (8%) in the BSB group. In the IG group, the results were excellent in 8 cases (80%) cases, fair in 1 case (10%), and poor in 1 case (10%). Per-protocol (PP) analysis showed that the results were excellent in 19 cases (86%) and good in 3 cases (14%) in the BSB group, and were excellent in 8 cases (100%) in the IG group. The results of ITT and PP analysis all showed no significant difference between 2 groups (P gt; 0.05). The change trend of ulcer areas in the BSB group was similar to that in the IG group. There was no significant difference in the hemostatic effect between 2 groups (P gt; 0.05) and the patients were more likely to accept BSB dressings. Conclusion BSB dressings is an effective, safe, and generally well-tolerated therapy dressing in the treatment of diabetic foot ulcers.