ABSTRACT
Para la gestión en salud, fortalecer la Atención Primaria como estrategia es un desafío. Esto implica coordinar los esfuerzos entre los distintos niveles de atención. En el caso de Argentina, la organización del sistema de salud divide las responsabilidades sobre cada nivel de atención en distintas jurisdicciones, quedando el primer nivel en la órbita de los municipios. En el caso de Córdoba, este escenario es particularmente complejo, ya que la descentralización del primer nivel de atención trajo consecuencias adversas, dificultando la integración de información sanitaria producida en los municipios. El Ministerio de Salud de la Provincia ha desarrollado una herramienta de monitoreo (el Monitor Sanitario) que construye indicadores de evaluación aprovechando los datos reportados por 754 efectores de salud públicos al programa Sumar. Estos indicadores se organizan por líneas de cuidado, y ya se encuentran en marcha los tableros que muestran los resultados para la línea de cuidado de personas gestantes y la de cuidado de personas con diabetes. La medición periódica de los desempeños por municipio de estas líneas se asocia a un pago por desempeño. Consideramos que esta experiencia permite mostrar la integración de esfuerzos para impactar en los tres componentes del sistema: en el modelo de atención (por definir priorización de cuidados y estimular la proactividad), en el modelo de financiamiento (al indicar las posibilidades de reporte al programa Sumar y al establecer un pago por resultados) y en el modelo de gestión (al orientar las gestiones locales a los resultados) (AU)
For health management, strengthening Primary Care as a strategy is a challenge. This implies coordinating efforts between the different levels of health care. In the case of Argentina, the health system assigns the responsibilities for each level of care to different jurisdictions, leaving the primary level of care in the orbit of the local governments. In the case of Córdoba, this scenario is particularly complex, considering the decentralization of the primary level of care brought adverse consequences, making it difficult to integrate health information produced in local governments.The Ministry of Health of the Province has developed a monitoring tool (the Health Monitor) that builds evaluation indicators taking advantage of the data reported by 754 public health effectors to Sumar program. These indicators are organized by lines of care, and there are two boards that already shows the results for pregnancy care and for people with diabetes. The periodic measurement of the performance of each local government in these lines is associated with a payment for performance.This experience shows how the integration of efforts impacts on the three components of the system: in the care model (by defining care prioritization and stimulating proactivity), in the financing model (by indicating the possibilities of reporting to Sumar program and establishing a payment for results) and in the management model (by directing local managements to results) (AU)
Subject(s)
Humans , Female , Pregnancy , Outcome and Process Assessment, Health Care , Primary Health Care/organization & administration , Health Management , Health Information Systems , Healthcare Financing , Argentina , Prenatal Care , Quality Indicators, Health Care , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapyABSTRACT
ABSTRACT The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI −0.66 to −0.59) and body weight by 0.60 kg (95% CI −0.64 to −0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.
Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic use , Blood , Body Weight , Brazil , Glycated Hemoglobin/analysis , Randomized Controlled Trials as Topic , Canagliflozin/therapeutic useABSTRACT
Clinical expertise, patient preference, and the best evidence are the three elements of evidence-based medicine. Based on high-level and high-quality evidence, qualitative and quantitative analysis of the prescribing decisions of physicians is beneficial to improving clinical efficacy. A mature methodological system is available for the retrieval, analysis, summary, evaluation, and recommendation of the evidence, but there are still few studies on physicians' prescribing decisions. How to analyze the trend of physicians' prescribing decisions based on the priority ranking in addition and subtraction of prescriptions? Analytic hierarchy process(AHP) is a method for decision making, which arranges the elements of the decision problem into overall goal, criteria, and operational sub-criteria, and uses the matrix eigenvector method to solve the problem. This study aims to analyze the priority of physicians' prescribing decisions for diabetes mellitus with deficiency of both Qi and Yin based on AHP. To be specific, a database of diabetes mellitus cases with deficiency of both Qi and Yin was established and AHP was used to yield the priority ranking of Chinese patent medicine prescriptions in specific clinical scenarios. In the selected cases of diabetes mellitus with deficiency of both Qi and Yin, Xiaoke Pills was the best prescription for the treatment of type 2 diabetes mellitus(deficiency of both Qi and Yin)(normalized=0.388), followed by Liuwei Dihuang Pills(normalized=0.269), Qishen Capsules(normalized=0.230), and Shengmai Injection(normalized=0.113). According to the analysis the available data, for type 2 diabetes mellitus(deficiency of both Qi and Yin), Xiaoke Pills was the most effective prescription in specific scenarios. When the physicians' prescribing decisions are consistent with the evidence, quantitative analysis of physicians' cognition will boost the evidence-based medical decision-making. However, the research results are also affected by the quality of literature, evidence level and priority, which are thus have some limitations. It is recommended that further small data research based on individual cases be carried out to lay a evidence-based basis for the clinical decision-making of type 2 diabetes mellitus.
Subject(s)
Analytic Hierarchy Process , China , Diabetes Mellitus, Type 2/drug therapy , Drug Prescriptions , Humans , Medicine, Chinese Traditional , Nonprescription Drugs/therapeutic use , Qi , Syndrome , Yin Deficiency/drug therapyABSTRACT
This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1β(IL-1β) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.
Subject(s)
Animals , Diabetes Mellitus, Type 2/drug therapy , Gastrointestinal Microbiome , Inflammation/drug therapy , Insulin , Powders , RatsABSTRACT
Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world's adult population is about 20%-25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects.
Subject(s)
Curcuma , Curcumin/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Humans , Metabolic Syndrome/drug therapy , Plant Extracts/therapeutic use , RhizomeABSTRACT
Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/therapeutic use , Glucagon-Like Peptides , Humans , Hypoglycemic Agents/therapeutic use , Motivation , Obesity/drug therapyABSTRACT
This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.
Subject(s)
Aged , Blood Pressure , China/epidemiology , Cholesterol, LDL/therapeutic use , Cross-Sectional Studies , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin/analysis , Humans , Male , Middle AgedABSTRACT
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na+/H+ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.
Subject(s)
Animals , Diabetes Mellitus , Diabetes Mellitus, Type 2/drug therapy , Glucose , Humans , Mice , Myocardial Infarction/metabolism , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Ventricular RemodelingABSTRACT
Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.
Subject(s)
Blood Platelets , Diabetes Mellitus, Type 2/drug therapy , Humans , Hyperglycemia/complications , Insulin Resistance , Obesity/complicationsABSTRACT
Hepatocellular carcinoma is one of the most common malignant tumors in the world. Although there are many options for the treatment of hepatocellular carcinoma, such as surgical resection, interventional therapy, radiotherapy, chemotherapy, targeted therapy and liver transplantation, the poor therapeutic effect seriously reduces the quality of life for patients and also increases the social and economic burden. Metformin is originally used as the first-line drug for type 2 diabetes, but it has been found to play a certain effect in the prevention and treatment of malignant tumor. The potential roles of metformin against hepatocellular carcinoma, such as regulation of the microenvironment, proliferation signal pathway, metabolism, invasion and metastasis, apoptosis, autophagy, and epigenetics of hepatoma cells. It provides a new choice for the prevention and treatment of hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular/prevention & control , Cell Line, Tumor , Cell Proliferation , Diabetes Mellitus, Type 2/drug therapy , Humans , Liver Neoplasms/prevention & control , Metformin/therapeutic use , Quality of Life , Tumor MicroenvironmentABSTRACT
OBJECTIVE@#To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial.@*METHODS@#A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored.@*RESULTS@#Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000).@*CONCLUSION@#SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Subject(s)
Alkaloids , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Double-Blind Method , Glycated Hemoglobin , Humans , Hypoglycemic Agents/therapeutic use , Morus , Tablets/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE@#To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM).@*METHODS@#PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.@*RESULTS@#Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD -6.46 mg/dL, 95% CI -11.95 to -0.98; moderate-quality evidence) and HOMA-IR (MD -1.23, 95% CI -2.16 to -0.31; low-quality evidence), but comparable changes in HbA1c (MD -0.39%, 95% CI -0.84 to 1.61; very-low-quality evidence), 2hBG (MD -4.99 mg/dL, 95% CI -20.74 to 10.76; low-quality evidence), and FINS (MD -1.32 µIU/mL, 95% CI -3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild.@*CONCLUSIONS@#The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Trial registration No. CRD42018115639).
Subject(s)
Acupuncture Therapy/methods , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/adverse effects , Insulin Resistance , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE@#To investigate the protective effects of modified Linggui Zhugan Decoction (, MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus (T2DM) rats.@*METHODS@#Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2DM (ob-T2DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M, 9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups, 10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance (IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or Akt)/the mammalian target of rapamycin (mTOR)-ribosome protein subunit 6 kinase 1 (S6K1 )/AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α) pathways were also studied.@*RESULTS@#MLZD dose-dependently reduced fasting blood glucose, fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2DM rats (P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2DM rats after 4-week treatment (P<0.05 or P<0.01). Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6 (P<0.05 or P<0.01). MLZD regulated the PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways and restored the tissue structure of liver and pancreas (P<0.05 or P<0.01).@*CONCLUSIONS@#MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Animals , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2/drug therapy , Glycolipids , Inflammation , Obesity/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , TOR Serine-Threonine Kinases/metabolismABSTRACT
Immune checkpoint inhibitors (ICIs) have become an important means of cancer treatment, and their application in the clinic is becoming more and more widespread. The adverse reactions caused by ICIs are gradually recognized. Among them, immunotherapy-related diabetes is a rare adverse reaction and type 1 diabetes mellitusis common. With the wide application of ICIs combined with chemotherapy in lung cancer patients, patients with type 2 diabetes mellitus have gradually been discovered during the treatment. However, the effect of continued use of ICIs maintenance therapy on blood glucose and ICIs treatment process in these patients is still unclear. This article reports two cases of type 2 diabetes mellitus induced by immune checkpoint inhibitor combined with chemotherapy, one of whom converted to type 1 diabetes mellitus, in order to increase the understanding of immunotherapy-related diabetes. .
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Humans , Immune Checkpoint Inhibitors , Immunotherapy/adverse effects , Lung Neoplasms/therapy , Molecular Targeted TherapyABSTRACT
Objective: To investigate whether the selective cyclooxygenase-2 enzyme inhibitors celecoxib has protective effect on the liver of rats with type 2 diabetes mellitus (T2DM) combined with nonalcoholic steatohepatitis (NASH) via inhibiting the expression of Rho/ROCK pathway. Methods: Forty male SD rats were randomly divided into four groups: type 2 diabetes mellitus combined with nonalcoholic steatohepatitis (T2DM-NASH) group, T2DM-NASH + celecoxib group, control group, and control+celecoxib group. The T2DM-NASH and T2DM-NASH + celecoxib groups were fed with high-sugar and fat diet, and the control group and control + celecoxib group were fed with basal diet (25 kJ/kg). Four weeks later, streptozotocin (STZ, 30 mg/kg) was intraperitoneally injected into the NASH group and T2DM-NASH + celecoxib group to induce T2DM model, and the control group and control + celecoxib group were intraperitoneally injected with isovolumic citric acid-sodium citrate buffer. Four weeks after STZ injection, the T2DM-NASH + celecoxib group and the control + celecoxib group were gavaged with celecoxib (10 mg·kg·d) dissolved in normal saline for 4 weeks, and the remaining two groups of rats were gavaged with isovolumic normal saline for 4 weeks. Animals were sacrificed at the end of the 12- weeks, and the liver tissue was collected. Liver pathological changes were observed by HE staining. The expressions of RhoA, RhoA, ROCK1 and ROCK2 proteins in liver were detected by immunohistochemistry and western blot. The expressional condition of RhoA, ROCK1 and ROCK2 mRNA in liver were detected by real-time quantitative PCR. The differences were compared between protein and mRNA expression among the groups by analysis of variance and t-test. Results: Compared with the control group and the control + celecoxib group, the liver tissue of the T2DM-NASH group and the T2DM-NASH + celecoxib group had severe steatosis, and there was partial inflammatory cell infiltration under the light microscope. The expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were significantly increased (P < 0.05) in each liver tissue, while liver steatosis was reduced to certain extent in T2DM-NASH + celecoxib group than T2DM-NASH group, and the expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were decreased in each liver tissue of T2DM-NASH group (P < 0.05). Conclusion: The selective cyclooxygenase-2 enzyme inhibitors celecoxib has a protective effect on the liver of rats with T2DM-NASH, and its effect may be achieved by inhibiting the expression of Rho/ROCK pathway.
Subject(s)
Animals , Cyclooxygenase 2/therapeutic use , Cyclooxygenase 2 Inhibitors/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Liver , Male , Non-alcoholic Fatty Liver Disease/drug therapy , Rats , Rats, Sprague-DawleySubject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Cardiovascular Diseases/chemically induced , Stroke/chemically induced , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Heart Failure , Metformin/adverse effects , Myocardial Infarction/chemically induced , Sodium/therapeutic use , United States , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Medicare , Stroke/prevention & control , Stroke/epidemiology , Glucose/therapeutic use , Hypoglycemic Agents/adverse effects , Myocardial Infarction/prevention & control , Myocardial Infarction/epidemiologySubject(s)
Humans , Adult , Young Adult , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/drug therapy , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Randomized Controlled Trials as Topic , Diabetes Mellitus, Type 2/prevention & control , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/therapeutic use , Life Style , Metformin/therapeutic useABSTRACT
Acarbose is widely used as α-glucosidase inhibitor in the treatment of type Ⅱ diabetes. Actinoplanes sp. is used for industrial production of acarbose. As a secondary metabolite, the biosynthesis of acarbose is quite complex. In addition to acarbose, a few acarbose structural analogs are also accumulated in the culture broth of Actinoplanes sp., which are hard to remove. Due to lack of systemic understanding of the biosynthesis and regulation mechanisms of acarbose and its structural analogs, it is difficult to eliminate or reduce the biosynthesis of the structural analogs. Recently, the advances in omics technologies and molecular biology have facilitated the investigations of biosynthesis and regulatory mechanisms of acarbose and its structural analogs in Actinoplanes sp.. The genes involved in the biosynthesis of acarbose and its structural analogs and their regulatory mechanism have been extensively explored by using bioinformatics analysis, genetic manipulation and enzymatic characterization, which is summarized in this review.
Subject(s)
Acarbose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Genetic Techniques , HumansABSTRACT
Resumo O objetivo deste estudo foi analisar o uso e o acesso aos medicamentos para o diabetes mellitus tipo 2 em idosos atendidos na Estratégia Saúde da Família de Ribeirão Preto, São Paulo. Trata-se de um inquérito domiciliar de base populacional realizado com 338 idosos, em amostragem por conglomerados. Investigou-se a farmacoterapia do diabetes e o acesso por meio de um questionário estruturado em entrevistas face a face. O número de medicamentos usados no tratamento do diabetes variou de um a quatro. Observou-se o predomínio de antidiabéticos orais, sendo o uso de apenas metformina autorreferido por 37,9% dos idosos, e 9,8% usavam sulfonilureia isoladamente. No grupo de idosos com idade igual ou superior a 80 anos, percebeu-se maior frequência (38,9%) no uso de insulina do que nos outros grupos etários. O acesso total foi estimado em 96,4%, a forma de financiamento gratuita correspondeu a 78,1% e as farmácias do Sistema Único de Saúde foram os principais locais de provisão dos medicamentos (74,8%). A metformina foi o antidiabético oral mais usado pelos idosos, em conformidade com as atuais recomendações para o tratamento da doença. Contudo, verificou-se usos inapropriados, especificamente na utilização isolada de sulfonilureia. Além disso, evidenciou-se a importância do sistema público de saúde para o fornecimento dos medicamentos.
Abstract The objective of this study was to analyze the use and access to medications for type 2 diabetes among older people registered in the family health strategy in Ribeirão Preto, São Paulo. A population-based household survey was undertaken with 338 older adults selected using two-stage cluster sampling. Pharmacotherapy of diabetes and access to medications was investigated using a structured questionnaire administered by means of face-to-face interviews. The number of medicines used to treat diabetes ranged between 1 and 4. Respondents predominantly used only oral antidiabetic agents. The use of metformin and sulfonylureas on their own was reported by 37.9% and 9.8% of respondents, respectively. Frequency of insulin use was greatest in the 80 years and overage group (38.9%). The large majority of respondents (96.4%) had full access to medicines. Means of payment was "free of charge" in 78.1% of the respondents and public pharmacies were the main source of medication (74.8%). The most commonly used oral antidiabetic was metformin, which is consistent with current treatment guidelines. However, the findings show inappropriate medication use among older people, more specifically the use of sulfonylureas on their own. The findings of this study highlight the important role played by the public health service in providing medications for type 2 diabetes.
Subject(s)
Humans , Aged , Pharmacies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Brazil , Health Services Accessibility , Hypoglycemic AgentsABSTRACT
ABSTRACT Objective: To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers. Materials and methods: This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m2 and T2DM. Beinaglutide was administered for three months. Changes in body weight, fasting plasma glucose (FPG) level, 2 h postprandial plasma glucose (2h-PG) level, glycosylated hemoglobin (HbA1c) level, BMI and visceral and subcutaneous fat areas were measured at baseline and after three months of treatment. In addition, relevant inflammation/obesity cytokines and biomarkers were measured. Results: After three months, beinaglutide treatment led to significant changes, including in body weight, BMI, FPG level, HbA1c level, visceral and subcutaneous fat areas. In addition, serpin E1, leptin, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) also decreased significantly. The plasma protein concentrations of CRP (Log2 transformed) were found to be positively correlated with the percentage of weight loss (R = 0.514 and p-value = 0.021). Conclusion: Beinaglutide treatment resulted in weight loss, plasma glucose control and anti-inflammatory effects in patients with T2DM and overweight/obesity.