Effect of Brassica rapa var. rapifera on Insulin Resistance and Inflammatory Analysis of Visceral Adipose Tissue of Obese Wistar Rats Under Glucolipotoxicity Condition / Efecto de Brassica rapa var. rapifera sobre la Resistencia a la Insulina y el Análisis Inflamatorio del Tejido Adiposo Visceral de Ratas Wistar Obesas en Condiciones de Glucolipotoxicidad

SUMMARY: Obesity-related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the effect of nutritional stress induced by a high-fat and high-sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high-fat (10 %) high-sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti-diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.

La fisiopatología relacionadas con la obesidad, como la resistencia a la insulina y el síndrome metabólico, muestran un riesgo notablemente mayor de diabetes tipo 2 y enfermedad cardiovascular aterosclerótica. Este riesgo parece estar relacionado con alteraciones en la función del tejido adiposo, lo que lleva a una inflamación crónica y a la desregulación de los factores derivados de los adipocitos. Brassica rapa se ha utilizado en la medicina tradicional para el tratamiento de varias enfermedades, incluida la diabetes. Este estudio tuvo como objetivo investigar el efecto del estrés nutricional inducido por una dieta rica en grasas y sacarosa sobre la fisiopatología del tejido adiposo visceral y el efecto terapéutico de Brassica rapa en ratas Wistar macho. Sometimos a ratas experimentales a una dieta rica en grasas (10 %) y alta en sacarosa (20 %)/por día durante 11 meses y las tratamos durante 20 días con extracto acuoso de Br (AEBr) a 200 mg/kg al final del experimento. En el momento del sacrificio, monitoreamos los parámetros bioquímicos plasmáticos y tisulares, así como la morfohistopatología del tejido adiposo visceral. Encontramos parámetros metabólicos corregidos por AEBr y marcadores inflamatorios en tejido adiposo visceral homogeneizado y reducción de hipertrofia, hiperplasia y gotitas de lípidos. Estos resultados sugieren que AEBr mejora el efecto antidiabético, antiinflamatorio y protector sobre la morfología del tejido adiposo en la diabetes tipo 2 y la obesidad.

Cultivo versus metagenómica para la identificación bacteriana en pacientes con osteomielitis de pie diabético: una revisión sistemática / Culture and metagenomics as bacterial identification methods in patients with diabetic foot ulcers: a systematic review

BACKGROUND: Diabetic foot osteomyelitis (DFO) is a serious complication of infected ulcers in a diabetic patient. The identification of the infecting microorganisms is generally by culture, which causes a bias. Recently, metagenomics has been used for microbial identification. AIM: To systematically review the scientific literature related to DFO in the last 10 years to evaluate if culture and metagenomics are complementary. MATERIAL AND METHODS: To carry out the systematic review, PRISMA and Rayyan were used for the selection of studies, using three databases, using the keywords diabetes, osteomyelitis, culture and microbiome. Articles in English or Spanish were included, containing information related to bacterial identification in DFO. Characteristics of the technique, patients and frequency of bacterial appearance were collected. RESULTS: Twenty six articles were included, 19 used culture and 7 metagenomics. The patients were predominantly men (68%), with an average age of 61 years, 83% had type 2 diabetes and comorbidities, mainly vascular and neuropathy. The Families with the highest frequency of appearance using the culture technique were Enterobacteriaceae (29.3%) and Staphylococcaceae(28.3%) and with metagenomics Peptoniphilaceae (22.1%) and Staphylococcaceae (9.4%). Peptoniphilaceae were not identified in culture, although they were frequently identified by metagenomics. Methicillin- resistant Staphylococcus aureus, regularly identified by culture, was not identified using metagenomics. CONCLUSIONS: Comparing results, there is a certain complementarity between microbiological culture and sequencing to identify bacteria present in DFO.

Associação entre a adesão terapêutica e o controle glicêmico de pacientes com Diabetes Mellitus tipo 2 / Association between therapeutic adherence and glycemic control in patients with type 2 diabetes mellitus

Introdução: A adesão ao tratamento no diabetes mellitus é fundamental para o controle metabólico, prevenção de complicações, melhoria e manutenção da qualidade de vida. Objetivo: Avaliar a associação entre a adesão ao tratamento farmacológico e o controle glicêmico de pacientes diabéticos tipo 2 e investigar fatores associados a essas condições. Método: Estudo transversal com pacientes ≥ 18 anos com diabetes mellitus tipo 2, atendidos em um serviço privado de endocrinologia, em uso de antidiabéticos orais há pelo menos 6 meses e com dosagem de hemoglobina glicada (HbA1c) de no máximo 12 meses. Foram utilizados a MMAS-8 (Morisky Medication Adherence Scale) e um questionário com dados sociodemográficos e clínicos. Resultados apresentados em razão de prevalência (RP) e intervalo de confiança (IC) 95%, ajustados por regressão logística pelo método enter. O nível de significância estatística adotado foi de 5%. Resultados: Participaram do estudo 134 pacientes, com média de 56,7 ± 12,9 anos, sendo 58,2% mulheres. A adesão terapêutica foi demonstrada por 78,4% dos pacientes, havendo associação positiva com a escolaridade e negativa em relação à idade e ao tempo de diagnóstico. O controle glicêmico foi verificado por 68,7%, não havendo diferença estatisticamente significativa em relação a sexo, idade, raça, escolaridade e tempo de diagnóstico. Entre os pacientes considerados aderentes, 77,1% apresentaram controle adequado da glicemia, enquanto entre pacientes considerados não aderentes, 37,9% foram considerados controlados (p<0,001). Conclusão: A adesão ao tratamento farmacológico esteve associada ao controle glicêmico em pacientes com diabetes tipo 2, acompanhados em consultório privado de endocrinologia.

Introduction: Treatment adherence in diabetes mellitus is essential for metabolic control, complication prevention, quality of life improvement and maintenance. Objective: To assess the association between adherence with pharmacological treatment and glycemic control in patients with type 2 diabetes and investigate factors associated with these conditions. Method: This is a cross-sectional study with patients ≥ 18 years old with type 2 diabetes mellitus, treated at a private endocrinology service, using oral antidiabetics for at least 6 months and with a glycated hemoglobin (HbA1c) measurement for a maximum of 12 months. The MMAS-8 (Morisky Medication Adherence Scale) and a questionnaire with sociodemographic and clinical data were used. Results presented as prevalence ratio (PR) and 95% confidence interval (CI), adjusted by logistic regression using the enter method. The level of statistical significance adopted was 5%. Results: A total of 134 patients participated in the study, with a mean age of 56.7 ± 12.9 years, 58.2% of whom were women. Therapeutic adherence was demonstrated by 78.4% of patients, with a positive association with education and a negative association with age and time since diagnosis. Glycemic control was verified by 68.7%, with no statistically significant difference in relation to sex, age, race, education and time since diagnosis. Among patients considered adherent, 77.1% had adequate glycemic control, while among patients considered non-adherent, 37.9% were considered controlled (p<0.001). Conclusion: Pharmacological treatment adherence was associated with glycemic control in patients with type 2 diabetes followed up in a private endocrinology office.

Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort / 中西医结合学报

OBJECTIVE@#The main aim of this study is to investigate whether acupuncture could be an effective complementary treatment for reducing the risk of macrovascular complications in diabetic patients currently taking antidiabetic medications using a nationwide population-based database.@*METHODS@#We conducted a retrospective cohort study to assess the efficacy of acupuncture on cardiovascular complications in diabetic patients using data from patients between 40 and 79 years of age, newly diagnosed with diabetes between 2003 and 2006, found in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea. From the data, we identified 21,232 diabetic patients who were taking antidiabetic medication between 2003 and 2006. The selected patients were divided into two groups-those who received acupuncture at least three times and those who received no acupuncture (non-acupuncture) in the year following their diagnosis of diabetes. After 1:1 propensity score matching (PSM), each group had 3350 patients, and the observation ceased at the occurrence of a major adverse cardiovascular event (MACE), which was defined as either myocardial infarction, stroke, or death due to cardiovascular cause.@*RESULTS@#After PSM, the acupuncture group had a lower incidence of MACE (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81-0.94; P = 0.0003) and all-cause mortality (HR: 0.77; 95% CI: 0.70-0.84; P < 0.0001) than the non-acupuncture group; the HRs for stroke-related mortality (HR: 0.75; 95% CI: 0.56-1.00; P = 0.0485), ischemic heart disease mortality (HR: 0.53; 95% CI: 0.34-0.84; P = 0.006) and circulatory system disease mortality (HR: 0.67; 95% CI: 0.55-0.82; P < 0.0001) were lower in the acupuncture group than in the non-acupuncture group in the secondary analysis.@*CONCLUSION@#Our results indicate that diabetic patients receiving acupuncture treatment might have a lower risk of MACE, all-cause mortality and cardiovascular mortality. This population-based retrospective study suggests beneficial effects of acupuncture in preventing macrovascular complications associated with diabetes. These findings call for further prospective cohort or experimental studies on acupuncture treatment for cardiovascular complications of diabetes. Please cite this article as: Jung H, Won T, Kim GY, Jang J, Yeo S, Lim S. Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort. J Integr Med. 2023; 21(2): 176-183.

Integrated care teams in primary care improve clinical outcomes and care processes in patients with non-communicable diseases

INTRODUCTION@#Primary care physicians face the increasing burden of managing multimorbidities in an ageing population. Implementing an integrated care team (ICT) with defined roles and accountability to share consultation tasks is an emerging care model to address this issue. This study compared outcomes with ICT versus usual care for patients with multimorbidities in primary care.@*METHODS@#Data was retrospectively extracted from the electronic medical records (EMRs) of consecutive adult Asian patients empanelled to ICT and those in UC at a typical primary care clinic (polyclinic) in eastern Singapore in 2018. The study population had hypertension, and/or hyperlipidaemia and/or type 2 diabetes mellitus (T2DM). Clinical outcomes included the proportion of patients (ICT vs. UC) who attained their treatment goals after 12 months. Process outcomes included the proportion of patients who completed annual diabetic eye and foot screenings, where applicable.@*RESULTS@#Data from 3,302 EMRs (ICT = 1,723, UC = 1,579) from January 2016 to September 2017 was analysed. The ICT cohort was more likely to achieve treatment goals for systolic blood pressure (SBP) (adjusted odds ratio [AOR] = 1.52, 95% confidence interval [CI] = 1.38-1.68), low-density lipoprotein cholesterol (AOR = 1.72, 95% CI = 1.49-1.99), and glycated haemoglobin (AOR = 1.28, 95% CI = 1.09-1.51). The ICT group had higher uptake of diabetic retinal screening (89.1% vs. 83.0%, P < 0.001) and foot screening (85.2% vs. 77.9%, P < 0.001).@*CONCLUSION@#The ICT model yielded better clinical and process outcomes than UC, with more patients attaining treatment goals.

Insulinas análogas de ação prolongada comparadas à insulina NPH para tratamento de diabetes mellitus tipo 2 em adultos: revisão rápida / Long-acting basal insulin analogues compared to nph insulin for type 2 diabetes mellitus in adults: rapid review

Tecnologia: Insulinas análogas de liberação prolongada versus insulina NPH (protamina neutra de Hagedorn). Indicação: Tratamento de adultos com diabetes mellitus tipo 2. Pergunta: Há diferenças de efeito nos principais desfechos de eficácia e segurança entre insulinas análogas de liberação prolongada versus insulina NPH no tratamento de pacientes com DM2? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada e incluída uma revisão sistemática. Conclusão: As insulinas análogas (glargina e detemir) não demonstraram superioridade nos desfechos de eficácia e segurança quando comparadas à insulina NPH, não demonstraram redução significativa em relação à mortalidade por todas as causas e complicações secundárias ao DM2. Quando comparadas à insulina NPH, foi observado redução na hipoglicemia confirmada e hipoglicemia noturna a favor das insulinas análogas e na hipoglicemia grave a favor da insulina detemir

Technology: Long-acting insulin analogues versus NPH insulin (human isophane insulin). Indication: Treatment of adults with type 2 diabetes mellitus. Question: Are there effect differences in key efficacy and safety outcomes between long-acting insulin analogues versus NPH insulin in the treatment of DM2 patients? Methods: Rapid review of evidence (overview) of systematic reviews, with a bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: A systematic review was selected and included. Conclusion: Analog insulins (glargine and detemir) did not demonstrate superiority in efficacy and safety outcomes when compared to NPH insulin, did not demonstrate a significant reduction in all-cause mortality and complications secondary to DM2. When compared to NPH insulin, a reduction in confirmed hypoglycemia and nocturnal hypoglycemia in favor of analogue insulins and in severe hypoglycemia in favor of insulin detemir was observed

Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.

Effectiveness and safety of Shexiang Baoxin Pill (MUSKARDIA) in patients with stable coronary artery disease and concomitant diabetes mellitus: a subgroup analysis of a randomized clinical trial / 中华医学杂志(英文版)

BACKGROUND@#Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM).@*METHODS@#This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty.@*RESULTS@#MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95).@*CONCLUSION@#As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM.@*TRIAL REGISTRATION@#ChiCTR.org.cn, ChiCTR-TRC-12003513.

Hypoglycemic effect of electroacupuncture at "Tianshu" (ST 25) combined with metformin on rats with type 2 diabetes mellitus based on AMPK / 中国针灸

OBJECTIVE@#To observe the hypoglycemic effect of electroacupuncture (EA) at "Tianshu" (ST 25) combined with metformin on rats with type 2 diabetes mellitus (T2DM) as well as its effect on expression of adenosine monophosphate activated protein kinase (AMPK) in liver and pancreas.@*METHODS@#Thirty-six male SD rats were randomly divided into a blank group (6 rats) and a model establishing group (30 rats). The rats in the model establishing group were fed with high-fat diet and treated with intraperitoneal injection of low-dose streptozotocin (STZ) to establish T2DM model. The rats with successful model establishment were randomly divided into a model group, a control group, a metformin group, an EA group and a combination group, 6 rats in each group. The rats in the EA group were treated with EA at "Tianshu" (ST 25), dense-disperse wave, 2 Hz/15 Hz in frequency and 2 mA in current intensity, 20 min each time. The rats in the metformin group were treated with intragastric administration of metformin (190 mg/kg) dissolved in 0.9% sodium chloride solution (2 mL/kg). The rats in the combination group were treated with EA at "Tianshu" (ST 25) and intragastric administration of metformin. The rats in the control group were treated with intragastric administration of 0.9% sodium chloride solution with the same dose. All the treatments were given once a day for 5 weeks. After the intervention, the body mass and random blood glucose were detected; the serum insulin level was detected by ELISA; the expression of AMPK and phosphorylated adenosine monophosphate activated protein kinase (p-AMPK) in liver and pancreas was detected by Western blot method; the expression of protein gene product 9.5 (PGP9.5) was detected by immunofluorescence.@*RESULTS@#①Compared with the blank group, the body mass in the model group was decreased (P<0.05); compared with the model group, the body mass in the EA group and the combination group was decreased (P<0.05); the body mass in the EA group and the combination group was lower than the metformin group (P<0.05). Compared with the blank group, the random blood glucose in the model group was increased (P<0.01); compared with the model group, the random blood glucose in the metformin group, the EA group and the combination group was decreased (P<0.01). The random blood glucose in the combination group was lower than the metformin group and the EA group (P<0.05). ②Compared with the blank group, the insulin level in the model group was decreased (P<0.05); compared with the model group, the insulin level in the metformin group, the EA group and the combination group was all increased (P<0.05). The insulin level in the combination group was higher than the metformin group and the EA group (P<0.05). ③Compared with the blank group, the protein expression of AMPK and p-AMPK in liver tissue was decreased (P<0.05), and the protein expression of AMPK and p-AMPK in pancreatic tissue was increased (P<0.05) in the model group. Compared with the model group, the protein expression of AMPK and p-AMPK in liver tissue in the metformin group, the EA group and the combination group was increased (P<0.05, P<0.01); the protein expression of AMPK in pancreatic tissue in the metformin group was increased (P<0.05); the protein expression of AMPK in pancreatic tissue in the EA group and the combination group was decreased (P<0.05); the protein expression of p-AMPK in pancreatic tissue in the metformin group, the EA group and the combination group was decreased (P<0.05). The protein expression of AMPK and p-AMPK in liver tissue in the combination group was higher than that in the metformin group and the EA group (P<0.05); the protein expression of AMPK in pancreatic tissue in the EA group and the combination group was less than that in the metformin group (P<0.05), and the expression of p-AMPK protein in pancreatic tissue in the combination group was less than that in the metformin group and the EA group (P<0.05). ④Compared with the blank group, the expression of PGP9.5 in pancreatic tissue in the model group was increased (P<0.01); compared with the model group, the expression of PGP9.5 in pancreatic tissue in the metformin group, the EA group and the combination group was decreased (P<0.05, P<0.01). The expression of PGP9.5 in pancreatic tissue in the EA group was lower than the metformin group and the combination group (P<0.05).@*CONCLUSION@#Electroacupuncture at "Tianshu" (ST 25) could promote the effect of metformin on activating AMPK in liver tissue of T2DM rats, improve the negative effect of metformin on AMPK in pancreatic tissue, and enhance the hypoglycemic effect of metformin. The mechanism may be related to the inhibition of pancreatic intrinsic nervous system.

Effects of plateau hypoxia on population pharmacokinetics and pharmacodynamics of metformin in patients with Type 2 diabetes / 中南大学学报(医学版)

OBJECTIVES@#Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM).@*METHODS@#A total of 85 patients with T2DM taking metformin tablets in the plateau group (n=32, altitude: 1 500 m) and control group (n=53, altitude: 3 800 m) were enrolled according to the inclusion and exclusion criteria, and 172 blood samples were collected in the plateau group and the control Group. A ultra-performance liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method was established to determine the blood concentration of metformin, and Phoenix NLME software was used to establish a model of pharmacokinetics of metformin in the Chinese T2DM population. The efficacy and serious adverse effects of metformin were compared between the 2 groups.@*RESULTS@#The population pharmacokinetic modeling results showed that plateau hypoxia and age were the main covariates for model building, and the pharmacokinetic parameters were significantly different between the plateau and control groups (all P<0.05), including distribution volume (V), clearance (CL), elimination rate constant (Ke), half-life(T1/2), area under the curve (AUC), time to reach maximum concentration (Tmax). Compared with the control group, AUC was increased by 23.5%, Tmax and T1/2 were prolonged by 35.8% and 11.7%, respectively, and CL was decreased by 31.9% in the plateau group. The pharmacodynamic results showed that the hypoglycaemic effect of T2DM patients in the plateau group was similar to that in the control group, the concentration of lactic acid was higher in the plateau group than that in the control group, and the risk of lactic acidosis was increased after taking metformin in the plateau population.@*CONCLUSIONS@#Metformin metabolism is slowed down in T2DM patients in the hypoxic environment of the plateau; the glucose-lowering effect of the plateau is similar, and the attainment rate is low, the possibility of having serious adverse effects of lactic acidosis is higher in T2DM patients on the plateau than on the control one. It is probably suggested that patients with T2DM on the plateau can achieve glucose lowering effect by extending the interval between medication doses and enhancing medication education to improve patient compliance.

Asiatic acid improves insulin secretion of β cells in type 2 diabetes through TNF- α/Mfn2 pathway / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg－1·d－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.

Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review / 中国中药杂志

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Los inhibidores SGLT2: una mirada al futuro del tratamiento de la insuficiencia cardiaca / Sodium-glucose cotransporter 2 inhibitors for the management of heart failure

Heart failure (HF) is a global health problem. There is a strong association h between HF and type 2 diabetes mellitus (DM2), with an increasing prevalence of patients having both conditions concomitantly. Sodium-glucose cotransporter 2 inhibitors (ISGLT2) significantly reduce cardiovascular events, including cardiovascular death. In this article we will focus on the current evidence about the effectiveness of these medications in adults with heart failure with reduced or preserved ejection fraction.

Monitor sanitario: experiencia de gestión y monitoreo de líneas de cuidado priorizadas en Córdoba / Health monitor: management and monitoring experience of prioritized lines of care in Córdoba

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)

Perfiles de hipoglicemiantes e insulinas en pacientes con diabetes mellitus tipo 2 y su efecto en control metabólico, hipoglicemia y otros efectos adversos / Profile of glucose lowering drug use in outpatients with type 2 diabetes mellitus

BACKGROUND: The use of glucose lowering agents with favorable weight profile is a growing practice in Diabetology. AIM: To characterize medication combinations in patients with type 2 Diabetes (T2D) and their effect on metabolic control. MATERIAL AND METHODS: Review of medical records of 249 outpatients with T2D with a median age of 66 years, cared for at a medical network. Clinical characteristics, glycated hemoglobin (HbA1c), details of Diabetes treatment (types of drugs or insulin), renal function, lipids and B12 vitamin levels were registered. RESULTS: The median disease duration was 16 years. The most recent HbA1c was 7.4%. No patient was using sulfonylureas, 45 were using Dipeptidyl peptidase 4 inhibitors, 113 were using Sodium-glucose Cotransporter-2 (SGLT2i) Inhibitors, 21 used Glucagon-like Peptide-1 Receptor Agonists (GLP1ra), 158 used basal insulin and 61 on basal plus bolus insulin. The use of SGLT2i or GLP1ra was associated with a metabolic control similar to those patients not using them, while patients on rapid insulin had a significantly worse metabolic control and a tendency to greater body mass index. The use of basal insulin and rapid insulin was significantly associated with more hypoglycemia events. CONCLUSIONS: The use of SGLT2i and GLP1ra in patients with T2D is associated with better metabolic control than rapid insulin with less risk of hypoglycemia. The use of these therapies should be prioritized in the future.

Dose-ranging effects of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis

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.

Effects of turmeric (Curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review / 中西医结合学报

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.

New practice in semaglutide on type-2 diabetes and obesity: clinical evidence and expectation / 医学前沿

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.

Effectiveness of quality of care for patients with type 2 diabetes in China: findings from the Shanghai Integration Model (SIM) / 医学前沿

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.

Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis

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.