Latest guidelines on lipid management recommend statins as the first-line therapy. Because limited evidence is available on cardiovascular outcomes with varying statin-nonstatin combinations, recommendation levels for these regimens have been weak. However, a recent trial has demonstrated the additive effect of the statin-ezetimibe combination. The statin-fibrate combination has shown an effect in certain subgroups and on diabetic microangiopathy. Recent trials using the statin-niacin combination have been largely negative, whereas the statin-omega-3 fatty acids combination demonstrated a positive effect only in one study. Identifying the benefits and limitations of each combination is important for the best possible management of patients.
Diabetic Angiopathies ; Drug Therapy* ; Ezetimibe ; Fatty Acids ; Fibric Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Niacin

Blood Circulation ; drug effects ; physiology ; Diabetic Angiopathies ; therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional

Diabetes Mellitus ; drug therapy ; Diabetic Angiopathies ; drug therapy ; Diagnosis, Differential ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Hypoglycemic Agents ; therapeutic use ; Medicine, Chinese Traditional ; Phytotherapy

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Prescriptions ; Drug Combinations ; Diabetic Angiopathies/drug therapy* ; Data Mining ; Diabetes Mellitus/drug therapy*

BACKGROUNDDiabetic macrovascular complications are important causes of cardiovascular and cerebrovascular diseases and also one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Phlorizin has been reported to be effective in reducing the blood glucose level in diabetic mellitus, while little is known about its effects on vascular complications. This study aimed to observe the effects of phlorizin on the aorta of diabetes db/db mice and explore its mechanism.

METHODSDiabetic db/db mice (n = 16) and age-matched db/m mice (n = 8) were divided into three groups: normal control group (CC group, db/m mice, n = 8), untreated diabetic group (DM group, db/db mice, n = 8) and diabetic group treated by phlorizin (DMT group, db/db mice, n = 8). Phlorizin (20 mg/kg body weight) was given in normal saline solution intragastrically for 10 weeks. Animals were weighed weekly. At the 10th weekend, all mice were fasted overnight and then sacrificed. Fasting blood was collected, and the aortas were dissected. The blood samples were analyzed for fasting blood glucose (FBG), serum advanced glycation end products (AGEs), malondialdehyde (MDA) and superoxide dismutase (SOD) activity, the aortic ultrastructure was studied.

RESULTSThe weight and serum concentration of FBG, AGEs, and MDA in the DM group were higher than that in the CC group (P < 0.01), and they were significantly lower in the DMT group (P < 0.05). Serum SOD activity was lower than that in the CC group (P < 0.01), and it is significantly higher in the DMT group (P < 0.05). The severity of aorta damage in the DMT group was less than that in the DM group.

CONCLUSIONSPhlorizin protected the db/db mice from diabetic macrovascular complications, attributed to the decreasing of blood glucose and AGEs level, and its antioxidant potential. This study may provide a new natural medicine for treating diabetic macrovascular complications.

Animals ; Aorta, Thoracic ; pathology ; Blood Glucose ; analysis ; Diabetic Angiopathies ; drug therapy ; pathology ; Glycation End Products, Advanced ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phlorhizin ; therapeutic use ; Superoxide Dismutase ; metabolism

OBJECTIVEAs an endogenous antioxidant, taurine could retard the development of diabetic cardiovascular complications. Whereas, whether TAU has a protective effect on diabetic vascular endothelium in young patients is still unclear. This study aimed to investigate the protective effect of taurine on early vascular endothelial dysfunction and its possible mechanism by detecting the changes of oxLDL/LOX-1 system in young STZ-induced diabetic rats. Doing so, the authors expect to find an effective approach in clinical practice to the prevention and treatment of diabetic vascular complication.

METHODSix-week-old rats were divided randomly into normal control (CN group, n=8), diabetes mellitus group (DM group, n=8) and taurine supplement group (DM+TAU group, n=8). Diabetes was induced in the rats by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) and after the onset of diabetes, the rats in DM+TAU group were given free access to drinking water containing 1% taurine. At the end of 4 weeks, blood glucose, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), oxidized low density lipoprotein (oxLDL) and sICAM-1 levels were determined, meanwhile LOX-1 and ICAM-1 expression on abdominal aortas were examined by immunostaining, Western blotting and reverse transcription PCR, respectively. The results were quantified by densitometry.

RESULTCompared to normal control, in STZ-induced diabetic rats, the levels of serum TC, TG, LDL, oxLDL and sICAM-1 were all increased (P<0.01 for all), meanwhile LOX-1 and ICAM-1 expression (protein and mRNA) in the endothelium layers of abdominal aortas were also markedly enhanced (P<0.01 for all); while in taurine supplemented rats, the levels of serum TG (0.64+/-0.12 vs. 0.97+/-0.18), TC (0.82+/-0.18 vs. 1.01+/-0.23), oxLDL (3.1+/-0.6 vs. 4.2+/-0.6), sICAM-1 (108.3+/-18.0 vs. 130.7+/-17.4), expression of LOX-1 and ICAM-1 protein (1.02+/-0.19 vs. 2.60+/-0.33, 1.21+/-0.22 vs. 2.98+/-0.31) as well as mRNA (0.45+/-0.09 vs. 0.96+/-0.15, 0.50+/-0.07 vs. 0.87+/-0.16) were all markedly lower than those of untreated diabetic rats (P<0.05 for all). Also, the level of LOX-1 protein expression was positively correlated with levels of serum oxLDL (r=0.922, P=0.001), sICAM-1 (r=0.753, P=0.031) and ICAM-1 expression on abdominal aorta (r=0.849, P=0.008).

CONCLUSIONVascular endothelial dysfunction was present in early stage of young diabetic rats and taurine supplement could protect against this early endothelial dysfunction by its antioxidation to inhibit the role of oxLDL/LOX-1 system in young rats with diabetes mellitus.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetic Angiopathies ; prevention & control ; Endothelium, Vascular ; metabolism ; Male ; Oxidative Stress ; Rats ; Rats, Wistar ; Taurine ; therapeutic use

BACKGROUNDThere is no agreement as to whether intensive glucose control in type 2 diabetes can reduce the incidence of macrovascular events in these patients. We performed a meta-analysis comparing intensive glucose control or conventional glucose control in randomized controlled trials.

METHODSDatabases including MEDLINE, EMBASE, and Cochrane controlled trials register, the Cochrane Library, and Science Citation Index were searched to find relevant trials. Outcome measures were the incidence of major macrovascular events.

RESULTSSix trials involving 28 065 patients were included. Analysis suggested that there was an obviously decreased incidence of major macrovascular events in patients having intensive glucose treatment vs. controls (RR 0.92; 95%CI 0.87, 0.98; P = 0.005). However, intensive glycemia control strategies in type 2 diabetes showed no significant impact on the incidence of death from any cause compared with conventional glycemia control strategies, intensive 14.7%, controls 12.0% (RR 0.95; 95%CI 0.80, 1.12; P = 0.55), as well as on the incidence of cardiovascular death, intensive 3.7%, controls 3.6% (RR 1.10, 95%CI 0.79, 1.53; P = 0.57).

CONCLUSIONSControl of glycemia to normal (or near normal levels) in type 2 diabetes appears to be effective in reducing the incidence of major macrovascular events, but there were no significant differences of either the mortality from any cause or from cardiovascular death between the two glycemia-control strategies.

Blood Glucose ; analysis ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; mortality ; Diabetic Angiopathies ; prevention & control ; Glycated Hemoglobin A ; analysis ; Humans ; Randomized Controlled Trials as Topic

OBJECTIVETo verify the clinical efficacy of Chinese drugs for benefiting-qi, activating-blood, dissolving phlegm and removing-toxin (CDs) Combined with Conventional Treatment on post-operative vascular restenosis in patients with diabetic lower extremity arterial disease (DLEAD) underwent percutaneous transluminal angioplasty (PTA).

METHODSFifty-six DLEAD patients underwent PTA of below-knee artery were assigned to the treatment group (32 patients) treated by basic therapy combined with CDs and the control group (24 patients) treated by basic therapy only. The changes in symptoms and signs, ankle/brachial index (ABI) and transcutaneous oxygen pressure (TCPO2) of affected limb, and blood flow (BF) in operated vessels checked with color Doppler examination were monitored and analyzed with SPSS software 16. 0.

RESULTSOverall effectiveness, including symptom score, ABI, TCPO2 and BF in patients after operation were all better in both groups significantly (P < 0.05), the improvements began to reveal in 3-6 months, and be stabilized in the treatment group, but declined gradually in the control group after then. So, the effective rate in the treatment group became significantly higher than that in the control group (75.00% vs. 41.67%, P < 0.01) at the end of the 6th month, meanwhile levels of ABI (0.65 +/- 0.12), TCPO2 (68.00 +/- 4.21 mm Hg), and BF (35.00 +/- 2.11 cm/s) in the former were better than those in the control group, respectively (0.44 +/- 0.12, 41.00 +/- 2.02 mm Hg and 21.00 +/- 1.85 cm/s, P < 0.05).

CONCLUSIONCDs shows definite effect in post-PTA prevention of vascular restenosis in DLEAD patients.

Aged ; Aged, 80 and over ; Angioplasty ; Arterial Occlusive Diseases ; drug therapy ; therapy ; Diabetes Mellitus, Type 2 ; physiopathology ; Diabetic Angiopathies ; drug therapy ; physiopathology ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Phytotherapy ; Secondary Prevention

BACKGROUND: Microvascular complications in type 2 diabetes (T2DM), including diabatic retinopathy (DR), diabetic kidney disease (DKD), diabetic peripheral neuropathy (DPN) are the leading causes of visual loss, end-stage renal disease or amputation, while the current therapies are still unsatisfactory. Chinese medicine (CM) has been widely used for treating diabetic mellitus. However, most of the previous studies focused on the single complication. The role of CM treatment in T2DM patients with 2 or multiple microvascular complications is not clear. OBJECTIVE: To appraise the curative effect of CM in T2DM patients with 2 or multiple microvascular complications, and to compare the effects of stationary treatment and individualized treatment in T2DM patients with microvascular complications. METHODS: This trial will be an 8-center, randomized, controlled study with 8 parallel groups. A total of 432 patients will be randomized to 8 groups: DR study group (32 cases) and a corresponding control group (32 cases), DR+DKD study group (64 cases) and a corresponding control group (64 cases), DR+DPN study group (64 cases) and a corresponding control group (64 cases), DR+DKD+DPN study group (56 cases) and a corresponding control group (56 cases). The control group will receive stationary treatment, and the study group will receive individualized treatment based on CM syndrome differentiation in addition to stationary treatment. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The outcomes will assess efficacy of treatment, improvement in CM symptoms, safety assessments, adherence to the treatment, and adverse events. CONCLUSION This study will provide evidence of evidence-based medicine for CM treatment in two or multiple microvascular complications caused by T2DM. (Registration No. ChiCTR-IPR-15007072).
Diabetes Mellitus, Type 2 ; complications ; drug therapy ; Diabetic Angiopathies ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Outcome Assessment (Health Care) ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated. RESULTS: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01). CONCLUSION CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.
Alkaloids ; pharmacology ; Animals ; Apoptosis ; drug effects ; Atherosclerosis ; Diabetes Mellitus, Experimental ; Diabetic Angiopathies ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; Male ; Ophiopogon ; chemistry ; Panax notoginseng ; chemistry ; Polysaccharides ; pharmacology ; Rabbits ; Saponins ; pharmacology