Expert consensus on diabetes mellitus after solid organ transplantation in adults / 器官移植

Post-transplant diabetes mellitus (PTDM) is a common endocrine and metabolic disorder after adult solid organ transplant (SOT), affecting 10% to 40% of recipients. PTDM has been associated with increased mortality, heightened risk of infections, graft-related complications and cardiovascular diseases, all of which seriously threaten the quality of life and long-term survival of recipients. According to recent studies and the domestic healthcare system, this consensus provides a comprehensive overview of the epidemiology, risk factors, pathogenesis, screening and diagnosis, treatments, prevention strategies, cardiovascular risk factor management and microvascular complications associated with PTDM, in order to further standardize the diagnosis and treatment of PTDM. The objective is to standardize the comprehensive management of PTDM with the aim of enhancing the long-term quality of life and clinical outcomes for SOT recipients.

Desenvolvimento e validação de método analítico por CLAE para determinação simultânea de atorvastatina, losartana e metformina em formulações farmacêuticas magistrais

Objetivos: Desenvolver e validar um método analítico para a análise simultânea de atorvastatina (ATO), losartana (LOS) e metformina (MTF) em formulações farmacêuticas magistrais por CLAE. Método: O método foi desenvolvido empregando o cromatógrafo a líquido modelo Dionex® Ultimate 3000, acoplado ao detector de arranjo de diodos (DAD) e a validação se deu conforme compêndios de validação internacional e nacional. Os seguintes parâmetros foram analisados: linearidade, precisão, exatidão, robustez, seletividade, LD e LQ. A separação cromatográfica foi realizada na coluna Sigma-Aldrich® C18, fase móvel MeOH:H2O (78:22 v/v), pH 3,0 e vazão de 0,3 mL-min-1, modo isocrático. As detecções foram realizadas nos comprimentos de onda de 225 nm (LOS), 236 nm (MTF) e 246 nm (ATO). Resultados: O método foi linear, com coeficientes de correlação linear (r)> 0,99 para todos os fármacos, preciso (DPR entre medidas < 2 %), exato (recuperação entre 98-102 %). As variações propostas no estudo de robustez não tiveram influência significativa nos resultados, exceto a coluna cromatográfica. O método foi seletivo, pois os excipientes não interferiram nas análises. A sensibilidade do método foi demonstrada através da determinação teórica dos LD e LQ. Conclusão: Os resultados obtidos sugerem que o método cromatográfico desenvolvido e validado nessa pesquisa poderá ser empregado nas análises de rotina dos laboratórios de controle de qualidade de medicamentos contendo esses fármacos de forma isolada ou combinados em formulações farmacêuticas de uso oral.

SUMMARY Aims: To develop and validate an analytical method for the simultaneous analysis of atorvastatin (ATO), losartan (LOS), and metformin (MTF) in pharmaceutical compounding by HPLC. Method: The method was developed using a liquid chromatograph model Dionex® Ultimate 3000, coupled to a diode array detector (DAD), and validation was carried out according to international and national validation compendiums. The following parameters were analyzed: linearity, precision, accuracy, robustness, selectivity, LD, and LQ. Chromatographic separation was performed on a Sigma-Aldrich® C18 column, mobile phase MeOH:H2O (78:22 v/v), pH 3.0, and flow rate of 0.3 mL-min-1, isocratic mode. Detections were performed at 225 nm (LOS), 236 nm (MTF), and 246 nm (ATO) wavelengths. Results: The method was linear, with linear correlation coefficients (r)> 0.99 for all drugs, precise (DPR between measurements < 2 %), accurate recovery (between 98-102 %). The variations proposed in the robustness study had no significant influence on the results, except for the chromatographic column. The method was selective, as the excipients did not interfere in the analyses. The sensitivity of the method was demonstrated through the theoretical determination of LD and LQ. Conclusion: The results obtained suggest that the chromatographic method developed and validated in this research can be used in the routine analyzes of quality control laboratories of drugs containing these drugs alone or combined in pharmaceutical formulations for oral use.

Mesa 3: Efectos cardiovasculares de fármacos antidiabéticos / Table 3: Cardiovascular effects of anti-diabetic drugs

Los eventos cardiovasculares representan la mayor complicación de la diabetes. La evidencia sugiere que la metformina mejora los resultados cardiovasculares en pacientes con diabetes, especialmente en el United Kingdom Prospective Diabetes Study (UKPDS) y otros estudios posteriores, por distintos mecanismos. Hay pocos estudios de seguridad cardiovascular para sulfonilureas aunque no tendrían un perfil seguro a este nivel. La gliclazida parece ser la de mejor performance de las drogas de este grupo. Algo similar ocurre con las meglitinidas, para las cuales los datos indican que no aumentarían el riesgo pero tampoco mejorarían la incidencia de eventos cardiovasculares. Las tiazolidinedionas son las drogas más cuestionadas, aunque los estudios y metaanálisis son contradictorios no habría dudas que aumentan el riesgo de insuficiencia cardíaca. Los inhibidores de la DPPIV mostraron resultados neutros a excepción de saxagliptina que aumentaría el riesgo de internación por insuficiencia cardíaca. Existen datos convincentes que los inhibidores de los receptores SGLT-2 a nivel renal y los análogos del GLP-1 intestinal tienen efectos positivos a nivel cardiovascular, con algunas diferencias entre los integrantes de esta familia. En cuanto a las insulinas, los estudios sugieren que tanto los análogos lentos como rápidos tendrían un mejor perfil cardiovascular, ligado principalmente a la menor incidencia de hipoglucemias severas, que insulina NPH y regular respectivamente.

Cardiovascular events represent the greatest complication of diabetes. Evidence suggests that metformin improves CV outcomes in patients with diabetes, especially in the United Kingdom Prospective Diabetes Study (UKPDS) and other subsequent studies, by different mechanisms. There are few cardiovascular safety studies for sulfonylureas although they would not have a safe profile at this level. Gliclazide appears to be the best performing drug in this group. Something similar occurs with meglitinides for which the data indicates that they would not increase the risk but neither would they improve the incidence of cardiovascular events. Thiazolidinediones are the most questioned drugs, although the studies and meta-analyzes are contradictory, there would be no doubt that they increase the risk of heart failure. DPPIV inhibitors showed neutral results except for saxagliptin, which would increase the risk of hospitalization for heart failure. There is convincing data that SGLT-2 receptor inhibitors at the renal level and intestinal GLP-1 analogues have positive effects at the cardiovascular level with some differences between the members of these families. Regarding insulins, studies suggest that both slow and fast analogues would have a better cardiovascular profile, mainly linked to the lower incidence of severe hypoglycemia, than NPH and regular insulin, respectively

Efectos nefrológicos de los SGLT2. ¿Qué sabemos hasta ahora? / Nephrological effects of SGLT2. What do we know so far?

Resumen: La prevalencia de diabetes mellitus tipo 2 ha crecido de manera significativa, longitudinal y continua a lo largo de los años. Se infiere que el número de adultos con nefropatía diabética también aumentará. Por consiguiente, la nefropatía diabética conserva sustancial importancia en la salud global y existe gran necesidad de minimizar la morbilidad de este padecimiento. Los inhibidores del cotransportador de sodio-glucosa 2 (SGLT2) son la clase farmacológica incorporada más recientemente a los recursos terapéuticos de antidiabéticos orales. Su acción se basa en el bloqueo de los cotransportadores SGLT2 sodio-glucosa que se encuentran en la membrana luminal de las células del túbulo contorneado proximal. Reducen las tasas de hiper-glucemia en pacientes con diabetes mellitus tipo 2 al disminuir la reabsorción renal de glucosa, aumentando así la excreción urinaria de glucosa. Se han demostrado reducciones significativas en hemoglobina glucosilada (HbA1c), junto con disminución de glucosa sérica en ayuno y posprandial en pacientes con diabetes mellitus tipo 2. Aunque la eficacia de los inhibidores de SGLT2 se ve afectada por la función renal, se han realizado subanálisis que evidencian que los inhibidores SGLT2, incluso en el contexto de insuficiencia renal grado 3b o 4, tienen efectos neutros en HbA1c, pero mejoran los parámetros bioquímicos y disminuyen el peso. El objetivo de este artículo es revisar la bibliografía disponible en la actualidad de los efectos renales de los inhibidores de SGLT2.

Abstract Prevalence of type 2 diabetes has increased significantly. It is inferred that the number of adults with diabetic nephropathy will also increase. Therefore, diabetic nephropathy will gain importance in global health and there is a need to minimize morbidity associated to this disease. Sodium-glucose transporter type 2 (SGLT2) inhibitors are the latest pharmacologic class of oral antidiabetics. They act upon the inhibition of SGLT2 co-transporters located in the luminal membrane of cells in the proximal convoluted tubule. Significant reductions in glycated haemoglobin levels, along with lower fasting glucose levels have been associated to SGLT2 inhibitors. Efficacy of SGLT2 inhibitors is affected with kidney failure, nonetheless, a subgroup study showed that SGLT2 inhibitors administered in the context of kidney failure (KDIGO stage 3b or 4) have neutral effects over HbA1C levels, but positive effects over other biochemical parameters and weight loss. The objective of this article is to review literature of renal effects of SGLT2 inhibitors.

Influence of type 2 diabetes treatment on patients with non-alcoholic fatty liver disease / 中国实用内科杂志

Non-alcoholic fatty liver disease(NAFLD), the incidence of which grows rapidly, has become the main cause of abnormal liver enzymes in healthy individuals. By now, no clear consensus has been reached on the treatment due to the multi-factorial pathogenesis of NAFLD. It has been indicated by a lot of studies that there is a close association between the pathogenesis, treatment and prognosis of non-alcoholic fatty liver disease and type 2 diabetes. So some measures of type 2 diabetes, including lifestyle intervention, medication and bariatric surgery, have been gradually used for NAFLD patients. This article introduces and summarizes the above-mentioned treatment for nonalcoholic fatty liver disease.

Normoglucemiantes orales y riesgo cardiovascular / Oral glucose-lowering drugs and cardiovascular risk

Resumen Introducción: la enfermedad cardiovascular es la principal causa de muerte en el mundo, así como la primera causa de morbilidad y mortalidad en pacientes con diabetes mellitus; por tanto, es importante conocer los diferentes medicamentos que existen hoy para el manejo de la diabetes mellitus y sus efectos, tanto positivos como negativos a nivel cardiovascular. De ahí que las diferentes sociedades y asociaciones científicas del mundo hayan emitido la recomendación de que todos los medicamentos para el tratamiento de la diabetes mellitus tipo 2 deben ser evaluados y certificados como seguros a nivel cardiovascular. Metodología: se hizo una búsqueda ampliada de la literatura existente acerca de los antidiabéticos actuales y sus efectos cardiovasculares. Resultados: existen diferentes tipos de medicamentos que se han relacionado con disminución o aumento del riesgo cardiovascular. En la actualidad hay evidencia que relaciona la metformina (biguanida), la empagliflozina (inhibidor del cotransportador sodio- glucosa 2) y la liraglutide (análogo de péptido similar al glucagón) con menos muerte cardiovascular y eventos cardiovasculares en pacientes con enfermedad cardiovascular establecida. Conclusión: los pacientes con enfermedad cardiovascular conocida pueden tener un beneficio adicional seleccionando medicamentos hipoglucemiantes con un mejor perfil de seguridad cardiovascular.

Abstract Introduction: Cardiovascular disease is the main cause of death worldwide, as well as the first cause of morbidity and mortality in patients with diabetes mellitus. For these reasons it is important to know the different drugs currently available to manage diabetes mellitus and their positive and negative effects at cardiovascular level. Hence, different scientific societies and associations of the world have issued the recommendation that all drugs for the treatment of type 2 diabetes mellitus must be evaluated and certified as safe at cardiovascular level. Methodology: An extensive search was carried out on the existing literature on current antidiabetic drugs and their cardiovascular effects. Results: There are different types of drugs that are associated with a decrease or increase in cardiovascular risk. Currently, there is evidence that associated metformin (biguanide), empagliflozin (sodium-glucose cotransporter 2 inhibitor), and liraglutide (a glucagon-like peptide analogue), with less cardiovascular deaths and cardiovascular events in patients with established cardiovascular disease. Conclusion: Patients with known cardiovascular disease may have an additional benefit in selecting glucose-lowering drugs with a better cardiovascular safety profile.

Skeletal Fragility in Type 2 Diabetes Mellitus

Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.

Medicinal properties of Ocotea bullata stem bark extracts: phytochemical constituents, antioxidant and anti-inflammatory activity, cytotoxicity and inhibition of carbohydrate-metabolizing enzymes / 中西医结合学报

<p><b>OBJECTIVE</b>This study evaluates the phytochemical constituents, antioxidant and anti-inflammatory activity, cytotoxicity, and inhibitory activity against carbohydrate metabolism of extracts from Ocotea bullata stem bark.</p><p><b>METHODS</b>Hexane, ethyl acetate, methanol and water were used to extract the air-dried sample. The phytochemical investigation and antioxidant assays were carried out on the extracts using standard procedures. The antidiabetic and anti-inflammatory potentials were evaluated using α-amylase, α-glucosidase and 5-lipoxygenase enzymes respectively. Vero cells were employed to determine the cytotoxicity of the extracts.</p><p><b>RESULTS</b>The ethyl acetate extract showed higher phenolic contents (8.97 mg/g gallic acid) while methanol displayed higher flavonoid (36.06 mg/g quercetin) and flavonol (153.44 mg/g rutin) contents than other extracts. Hexane extract had the greatest capacity to scavenge 1,1-diphenyl-2-picryl-hydrazyl (0.19 mg/mL), hydroxyl (25.77 mg/mL) and 2,2-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (0.07 mg/mL) radicals, while ethyl acetate extract exhibited stronger inhibition (P < 0.05) against superoxide anion (0.41 mg/mL) and ferric ion-reducing power (2.36 mg/mL) compared to other extracts and standards. Aqueous extract (27.02 mg/mL) exhibited strong metal-chelating activity (P < 0.05) compared to other extracts and gallic acid. The aqueous extract demonstrated the greatest inhibition of α-glucosidase (1.45 mg/mL) and α-amylase (2.43 mg/mL) compared to other extracts and acarbose. There were no significant differences (P < 0.05) in half-maximum inhibitory concentration (IC) values of all tested extracts and indomethacin in the inhibition of 5-lipoxygenase activity. The aqueous extract was nontoxic to Vero cells with an ICvalue of 0.38 mg/mL.</p><p><b>CONCLUSION</b>O. bullata stem bark contains active phytochemicals with diverse pharmacological potentials that could be beneficial in managing diabetes and inflammation.</p>

Developing and Evaluating a Drug Information Leaflet of Antidiabetics for Senior Citizens; Employing Performance-based User-testing

OBJECTIVE: The study purpose was to develop a drug information leaflet for the elderly and to evaluate it with performance-based user-testing. METHODS: We performed a stratified randomized controlled trial. We recruited 62 elderly patients with age of 65 or above who were taking antidiabetic medications at the point of participating and excluded those who suffered illiteracy. We randomly allocated them into the intervention group with a leaflet for the elderly and the control group with a leaflet for the general public. Main outcome measures were to ‘be able to find information’ and to ‘be able to understand information.’ We measured outcome variables by employing performance-based user-testing and analyzed data to find any differences between two groups with t-tests, chi-squared tests or Fisher's exact tests accordingly. RESULTS: More participants in the intervention group understood how to store their medications than those in the control group (intervention group 93% vs. control group 70%; p=0.02). There were no significant differences in other information items between two groups. Mostly ‘being able to understand information’ was lower than ‘being able to find information.’ The gaps between two outcome variables were about 10% in the intervention group and about 18% in the control group. The lowest understanding was observed in information relating to drug names and their potential adverse events. CONCLUSION: Without providing personalized drug information, it might be hard for the elderly to improve their drug knowledge even with leaflets that were developed specifically for the elderly.

Therapeutic effect of QQL prescription on type 2 diabetic rats / 中国病理生理杂志

AIM:To investigate the therapeutic effect of Qingqianliu ( QQL) antidiabetic prescription , contai-ning Cyclocarya paliurus, on type 2 diabetic rats.METHODS: Ten rats were randomly chosen as normal control group , and other rats were used to establish diabetic rat models by high-fat diet feeding plus streptocin intraperitoneal injection . Successfully modeling rats were randomly divided into high (300 mg· kg -1· d-1), medium (150 mg· kg-1· d-1) and low (75 mg· kg-1· d-1) doses of QQL treatment groups, and model control group (10 rats in each group).The rats re-ceived daily treatment for 6 weeks.Meanwhile, the therapeutic effect of QQL on these type 2 diabetic rats were evaluated via the body weight , the levels of serum glucose , insulin and glycosylated hemoglobin , the glucose tolerance , the pathologi-cal changes of pancreatic islands , antioxidative indexes and inflammaory factors .RESULTS:Compared with model control group, the body weight, serum insulin, glucose tolerance, serum SOD and serum GSH were increased , the serum glucose, glycosylated hemoglobin , MDA, IL-1βand TNF-αwere decreased , and the pathological changes of pancreatic islands were improved in type 2 diabetic rats with QQL treatment at high and low doses (P<0.05 or P<0.01).CONCLUSION:The QQL reduces the blood glucose , improves the glucose tolerance , and attenuates the damage of pancreatic islands .Its me-chanism may be related to antioxidative and anti-inflammatory effects .

Therapeutic effect of QQL prescription on type 2 diabetic rats / 中国病理生理杂志

AIM:To investigate the therapeutic effect of Qingqianliu ( QQL) antidiabetic prescription , contai-ning Cyclocarya paliurus, on type 2 diabetic rats.METHODS: Ten rats were randomly chosen as normal control group , and other rats were used to establish diabetic rat models by high-fat diet feeding plus streptocin intraperitoneal injection . Successfully modeling rats were randomly divided into high (300 mg· kg -1· d-1), medium (150 mg· kg-1· d-1) and low (75 mg· kg-1· d-1) doses of QQL treatment groups, and model control group (10 rats in each group).The rats re-ceived daily treatment for 6 weeks.Meanwhile, the therapeutic effect of QQL on these type 2 diabetic rats were evaluated via the body weight , the levels of serum glucose , insulin and glycosylated hemoglobin , the glucose tolerance , the pathologi-cal changes of pancreatic islands , antioxidative indexes and inflammaory factors .RESULTS:Compared with model control group, the body weight, serum insulin, glucose tolerance, serum SOD and serum GSH were increased , the serum glucose, glycosylated hemoglobin , MDA, IL-1βand TNF-αwere decreased , and the pathological changes of pancreatic islands were improved in type 2 diabetic rats with QQL treatment at high and low doses (P<0.05 or P<0.01).CONCLUSION:The QQL reduces the blood glucose , improves the glucose tolerance , and attenuates the damage of pancreatic islands .Its me-chanism may be related to antioxidative and anti-inflammatory effects .

Increased glucose metabolism and alpha-glucosidase inhibition in Cordyceps militaris water extract-treated HepG2 cells

BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS: Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha (HNF-1α), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta (GSK-3β) expression levels. The α-glucosidase inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS: CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through HNF-1α expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and GSK-3β, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of α-glucosidase inhibitory activity than that from acarbose. CONCLUSION: CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.

Effect of Methanolic Extract of Passiflora foetida on Glucose Kinetics in Alloxan-induced Diabetic Mice.

Background: This study investigated the hypoglycemic potential of methanolic extract of Passiflora foetida (PF) in alloxan-induced diabetic albino mice. Diabetes is a metabolic disease characterized with high blood sugar levels over a prolonged period. Discovery of a new drug will greatly reduce the mortality and morbidity associated with the disease. Methods: Diabetes was induced in albino mice by administration of 150 mg/kg body weight (b.w.) alloxan. Different concentrations of the methanolic extract of PF was prepared and administered orally to groups of alloxan-induced diabetic mice. Blood glucose was determine at different time point over 4 hrs. Results: The extract reduced blood glucose levels in diabetic mice significantly (P<0.001) and the kinetic parameters such as, area under glucose concentration time curve (AUC0-4hG) (P<0.05), glucose mean residence time (MRTG), glucose t1/2G were significantly lower (<0.05) in PF treated groups when compared with the control groups. The rate of glucose clearance (CLG) was high in the group treated with the extract. Conclusion: The results of this study indicate presence of hypoglycemic constituent in the plant.

How Essential the Anti-diabetic Medications in Chinese Hospitals? / 中国药房

OBJECTIVE:To analyze the treatment of anti-diabetics medicines and use of essential medicines in Chinese hospi-tal,and provide evidence for developing medicine policy,preventing and treating diabetes. METHODS:Data about annual con-sumption from 2012 to 2014 were extracted from the IMS CHPA database to analyze the object medicines of the target drugs with top 60% consumption volume of oral anti-diabetics and insulins,and the proportion of consumption volume and consumption amount in insulin,its analogues and three generations of insulin by 2 administration mode in Chinese hospital. RESULTS & CON-CLUSIONS:Acarbose tablet manufactured by Beijing Bayer HealthCare Co.,Ltd. and Metformin tablet manufactured by Shanghai Squibb Pharmaceutical Co.,Ltd. had occupied the top 2 of volume consumption in Chinese hospitals,totally accounting for 25%-26%. The 60% volume consumption of insulins and its analogues concentrated on one cheap local animal insulin(volume ac-counting for 13%-16% and amount accounting for 1%)and those imported or joint venture-made the second and third generation of insulins and analogues administrated by pen/cartridge. No matter insulins or oral anti-diabetics,the top consumption was listed as National Essential Medicine System,but none was recommended by WHO. Multi-pharmas dominate the Chinese anti-diabetic mar-ket through introducing new combined formulations and new dosage forms. WHO non-listed anti-diabetics have beautiful sales in Chinese hospitals,while traditional cheap medications for the general public grew slowly and with low profits. Chinese hospitals generally consumed more expensive new generations and original research manufacturers of anti-diabetics. As a lower middle in-come country that just established a universal coverage of basic health insurance,China still has a huge population with very limit-ed benefit package. Efficient use of limited health resources is essential for a successful health reform and a sustainable development of the health system in China.

Diabetes mellitus: Novas perspectivas terapêuticas / Diabetes Mellitus: new perspectives therapeutic

O diabetes mellitus tipo 2 (DM2) apresenta alta prevalência, com aumento inclusive em crianças e adolescentes. A importância de um estrito controle glicêmico pode ser comprovada com a redução das complicações crônicas microvasculares. Já em relação à redução da doença macrovascular, principal causa de mortalidade nestes pacientes, são fundamentais o controle da glicemia, bem como de outros fatores de risco cardiovasculares, tais como hipertensão arterial, dislipidemia, peso, e a manutenção de hábitos saudáveis de vida. Temos vários medicamentos para o tratamento do DM2, sendo que a metformina é ainda a droga de primeira escolha, devido ao seu baixo custo e eficácia comprovada...

Type 2 diabetes mellitus (DM2) is highly prevalent and is increasing even in children and adolescents. The importance of strict glycemic control can be proven to reduce chronic microvascular complications. Regarding the reduction of macrovascular disease, the leading cause of mortality in these patients, it is essential tight glycemic control, as well as other cardiovascular risk factors, such as arterial hypertension, dyslipidemia, weight control, and maintaining healthy lifestyles. We have a lot of drugs for the treatment of DM2, and metformin is still the drug of first choice due to its low cost and proven effectiveness...

SGLT-2 inhibitors: The glucosuric antidiabetics.

Despite availability of a number of oral antidiabetics, a sizeable population of diabetics remains uncontrolled. Thus there is growing need of new group of drugs for diabetic control. Understanding renal conservation of glucose by efficient reabsorption through sodium glucose cotransporter-2 (SGLT-2) has paved way for development of an entirely new group of drugs, the SGLT-2 inhibitors. These glucosuric antidiabetic agents have shown promise in early clinical studies. Canagliflozin is recently approved for use in diabetes alone or along with other antidiabetics. Other highly selective inhibitors undergoing various stages of clinical developments are dapagliflozin, sergliflozin, remogliflozin, ipragliflozin, empagliflozin, luseogliflozin, tofogliflozin and desoxyrhaponticin. KGA-2727 (pyrazole-O-glucoside) is the first selective SGLT-1 inhibitor undergoing intense preclinical testing. There are safety issues associated with this group like urogenital infections (fungal), weight loss, initial osmotic diuresis and increased incidence of cardiovascular events. The long term safety remains to be established. Despite these limitations, SGLT-2 inhibition offers a unique target for achieving adequate control of diabetes in adults.

Evaluation of Anti-diabetic and Liver Enzymes Activity of Aqueous Extracts of Moringa oleifera and Bridelia ferruginea Leaves in Alloxan Induced Diabetic Albino Rats.

To evaluate anti-diabetic and liver enzymes activities of aqueous extracts of Moringa oleifera and Bridelia ferruginea leaves in alloxan induced diabetic albino rats. Study design: Diabetes was induced in three groups of rats, one group was not treated while two groups were treated orally with M. oleifera and B. ferruginea extracts at 200, 400 and 800 mg/kg body weight of rats twice for 1 week respectively. One group was not induced and received distilled water only. The anti-diabetic and liver enzymes activities were determined from blood glucose and transaminases activities of the rats. Place and Duration of Study: Department of Biochemistry Ebonyi State University, Abakaliki, Nigeria, September, 2012. Methodology: Twenty-four albino rats were grouped into A, B, C and D group. Group C and D were further subdivided into C1, C2, C3, D1, D2 and D3, respectively. Diabetes was induced in all the groups, except group A (positive control). Group B (negative control) was not treated while group C and D were treated with aqueous extracts of M. oleifera and B. ferruginea leaves, which were administered orally to the animals twice daily for 1 week at varying concentrations of 200, 400 and 800 mg/kg body weights. The glucose and liver enzymes levels were determined using glucometeric and spectrophotometric methods. Results: The results revealed that there was significant reductions (P < 0.05) in glucose level in rats treated with aqueous extract of B. ferruginea than M. oleifera treated rats. There were no significant reduction (P> 0.05) in Alkaline phosphatase level between the controls and the treated groups, except at 200 mg/kg dose in which Alkaline phosphatase level was high in rats treated with M. oleifera extract. There were significant reduction (P< 0.05) in Alanine aminotransaminase level in rats treated with both M. oleifera and B. ferruginea in comparison to the negative control while there was significant increase (P < 0.05) when compared to the positive control except at 200 mg/kg dose where there was decrease in Alanine aminotransaminase level in both plant extracts. Also there was a significant decrease (P < 0.05) in AST level in rats treated with M. oleifera when compared to controls while there was significant increase (P< 0.05) in Aspartate aminotransaminase level in rats treated with B. ferruginea except at 200 mg/kg where there was decrease when compared to the controls. Conclusion: These suggest that both extracts can be used in ethno-medicine for the management of diabetes mellitus.

Novas perspectivas de tratamento medicamentoso do diabetes mellitus / New prospects for drug treatment of diabetes mellitus

O diabetes mellitus tipo 2 (DM2) apresenta alta prevalência, com aumento inclusive em crianças e adolescentes. A importância de um estrito controle glicêmico pode ser comprovada com a redução das complicações crônicas microvasculares. Já em relação à redução da doença macrovascular, principal causa de mortalidade nestes pacientes, são fundamentais o controle da glicemia, bem como de outros fatores de risco cardiovasculares, tais como hipertensão arterial, dislipidemia, peso, e a manutenção de hábitos saudáveis de vida. Temos vários medicamentos para o tratamento do DM2, sendo que a metformina é ainda a droga de primeira escolha, devido ao seu baixo custo e eficácia comprovada.

Type 2 diabetes mellitus (DM2) is highly prevalent and is increasing even in children and adolescents. The importance of strict glycemic control can be proven to reduce chronic microvascular complications. Regarding the reduction of macrovascular disease, the leading cause of mortality in these patients, it is essential tight glycemic control, as well as other cardiovascular risk factors, such as arterial hypertension, dyslipidemia, weight control, and maintaining healthy lifestyles. We have a lot of drugs for the treatment of DM2, and metformin is still the drug of first choice due to its low cost and proven effectiveness.

Antidiabetic and antihyperlipidemic effects of Dillenia indica (L.) leaves extract / Efeitos antidiabético e anti-hiperlipidêmico de extratos de folhas de Dillenia (L. )

The present study was carried out to evaluate antidiabetic and antihyperlipidemic effects of Dillenia indica methanolic leaves extracts in streptozotocin induced diabetic Wistar rats by administering graded oral doses (250 and 500 mg/kg body weight) for 21 days. The extract showed significant antidiabetic activity (p<0.001). Furthermore, the decreased body weight of rats was significantly improved after extract treatments. Daily oral treatment with the extract for 21 days to diabetic rats, also resulted in significant reduction in serum cholesterol, triglycerides and serum transaminase levels but HDL-cholesterol level was found to be improved (p<0.001) as compared to the diabetic control group. The extract treatment also showed to enhance serum insulin level in diabetic rats as compared to the diabetic control group. In conclusion, D. indica leaf extract might be useful for diabetes mellitus management and other abnormalities associated with this metabolic disorder.

Realizou-se o presente estudo para avaliar os efeitos antidiabético e anti-hiperlipidêmico de extratos metanólicos de folhas de Dillenia indica em ratos wistar com diabetes induzido por estreptozotocina por meio da administração de doses orais (250 e 500 mg/kg de peso corporal) por 21 dias. O extrato mostrou atividade antidiabética significativa (p<0,001). Além disso, a diminuição do peso corporal dos ratos foi significativamente melhorada após o tratamento com os extratos. O tratamento com doses orais do extrato por 21 dias aos ratos diabéticos também resultou em redução significativa do colesterol, triglicerídios e níveis de transaminase séricos, mas o nível de HDL-colesterol foi melhorado (p<0,001), quando comparado ao grupo controle diabético. O tratamento com extrato também mostrou aumento do nível sérico de insulina em ratos diabéticos comparativamente ao grupo controle diabético. Em conclusão, o extrato de folha de D. indica poderia ser útil para o controle do diabetes mellitus e de outras anormalidades associadas a essa disfunção metabólica.

Evaluation of the Antidiabetic and Antilipaemic Activities of the Hydroalcoholic Extract of Phoenix Dactylifera Palm Leaves and Its Fractions in Alloxan-Induced Diabetic Rats

Background: The antidiabetic and antilipaemic effects of Phoenix dactylifera leaf extract (PDE) and its fractions were investigated in various rat models. Methods: Diabetes was induced in male Wistar rats by alloxan monohydrate. Diabetic animals were randomly divided into 8 groups (1 diabetic control and 7 treated groups). Diabetic control animals received saline (5 mL/kg) orally, whereas the treatment groups received different doses of PDE (100, 200, and 400 mg/kg), PDE fractions (50, 100, and 200 mg/kg), or glibenclamide (4 mg/kg) orally once a day for 14 days. Blood was withdrawn for glucose determination on the 1st, 6th, 10th, and 14th days. The rats were fasted overnight and then sacrificed on the 14th day; blood was collected for biochemical evaluation, including the levels of blood glucose, plasma insulin, serum triglyceride, and cholesterol. Results: Subacute administration of PDE or its fractions in alloxan-induced diabetic rats significantly reduced blood glucose (P < 0.01). Water intake, serum triglyceride, and cholesterol also decreased in treated animals compared with the control group (P < 0.01). Plasma insulin level increased in the treated groups relative to the control group (P < 0.01). Conclusion: The results suggested that PDE exhibits antidiabetic and antilipaemic effects in alloxan-induced diabetic rats.