Effects of metformin plus gliclazide versus metformin plus glimepiride on cardiovascular risk factors in patients with type 2 diabetes mellitus

High blood glucose level, lipid profile disturbances and plasma homocysteine [Hey] are important risk factors for cardiovascular diseases in patients with type 2 diabetes. This study was conducted to evaluate and compare effects of glimepiride/metformin combination versus gliclazide/metformin combination on cardiovascular risk factors in type-2 diabetes mellitus [T2DM] patients. One hundred and eighty T2DM patients were randomly allocated for treatment with placebo [control], metformin [500mg twice daily], glimepiride [3mg once daily], gliclazide [80mg once daily], metformin plus glimepiride or metformin plus gliclazide for 3 months. We evaluated plasma levels of glucose [PG], glycated hemoglobin [HbAlC], Hey, vitamin B12, folic acid and lipid profile before treatment and 3 months post treatment. Compared to metformin treated patients, glimepiride plus metformin induced significant reductions in: fasting plasma glucose, postprandial PG level, HbAlC % and Hey level. Conversely, plasma folic acid and vitamin B12 were significantly increased. The levels of total cholesterol and triglyceride were significantly decreased; low-density lipoprotein was markedly decreased, whereas high-density lipoprotein was significantly increased and hence risk ratio was significantly decreased. Similar results but with lower values were obtained using combination of metformin plus gliclazide on glycemic control only. Combination of glimepiride with metformin was superior to gliclazide plus metformin in alleviating the cardiovascular risk factors in type 2 diabetes mellitus patients

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA1 levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.

Simultaneous determination of pioglitazone and glimepiride in bulk drug and pharmaceutical dosage from by RP-HPLC METHOD

A simple, fast, and precise reverse phase, isocratic HPLC method was developed for the separation and quantification of pioglitazone and glimepiride in bulk drug and pharmaceutical dosage form. The quantification was carried out using Inertsil ODS [250 x 4.6 mm, 5micro] column and mobile phase comprised of acetonitrile and ammonium acetate [pH 4.5; 20mM] in proportion of 60:40 [v/v]. The flow rate was 1.0 ml/min and the effluent was monitored at 230 nm. The retention time of pioglitazone and glimepiride were 7.0 +/- 0.1 and 10.2 +/- 0.1 min respectively. The method was validated in terms of linearity, precision, accuracy, and specificity, limit of detection and limit of quantitation. Linearity of pioglitazone and glimepiride were in the range of 2.0 to 200.0microg/ml and 0.5-50microg/ml respectively. The percentage recoveries of both the drugs were 99.85% and 102.06% for pioglitazone and glimepiride respectively from the tablet formulation. The proposed method is suitable for simultaneous determination of pioglitazone and glimepiride in pharmaceutical dosage form and bulk drug

The effect of the glyphosate, 2,4-D, atrazine e nicosulfuron herbicides upon the Edaphic collembola (Arthropoda: Ellipura) in a no tillage system

The use of herbicides is a common and intensive practice in no tillage systems. The herbicides can influence, directly or indirectly, the population of edaphic arthropods. Collembola is a group that functions as a bio-indicator of soil conditions. The degree of abundance and diversity of Collembola provides the level of soil disturbance provoked by agricultural practices. This experiment was designed to compare the influence of herbicides on the population fluctuation of Collembola in a no-till soil preparation system. The work was conducted in a non irrigated no-till area at the Núcleo Experimental de Ciências Agrárias of the Universidade Federal de Mato Grosso do Sul (UFMS), Campus de Dourados, in soil planted with corn as a surface covering, during the period of December, 2002 to December, 2003. The data were analyzed according to a completely randomized model, in a split plot design. The plots received four types of herbicides: glyphosate, atrazine, 2,4-D and nicosulfuron. A fifth plot did not receive any herbicide (control), for a total of five treatment types. The sub plots were represented by their collection times (10, 20, 30 and 40 days after the herbicide applications). Both the type of herbicide and the time of data sampling influenced the Collembola population fluctuaction. The treatments with atrazine and 2,4-D caused the most reduction of the population of Collembola, depending on the time of application.

No plantio direto o uso de herbicidas é uma prática comum e intensiva, que influencia direta ou indiretamente a população de artrópodes da mesofauna edáfica. O grau de abundância e diversidade de Collembola comumente é indicado para comprovar a extensão de distúrbios de várias práticas agrícolas, pois esse grupo serve como bioindicador das condições do solo. Esta pesquisa teve como objetivo comparar a influência de alguns herbicidas na flutuação populacional de Collembola, em solo sob o sistema de plantio direto. O trabalho foi realizado em uma área de plantio direto de sequeiro, do Núcleo Experimental de Ciências Agrárias da Universidade Federal de Mato Grosso do Sul (UFMS), Campus de Dourados, em latossolo roxo distroférrico com cobertura de milho, durante os meses de outubro de 2002 a janeiro de 2003. Os dados obtidos foram analisados segundo o modelo inteiramente casualizado constituído de tratamentos dispostos no esquema de parcelas subdivididas, onde as parcelas são representadas por uma testemunha mais quatro herbicidas: glifosate, atrazina, 2,4-D e nicosulfuron (totalizando cinco tratamentos) e as subparcelas pelas épocas de cada coleta (10, 20, 30 e 40 dias após aplicação dos herbicidas). Tanto os herbicidas testados quanto as épocas de coleta influenciaram a população de Collembola. Dependente do período de degradação dos herbicidas no solo, os tratamentos com 2,4-D, Atrazina, foram os que mais influenciaram a abundância de Collembola reduzindo sua população.

Study on the effect of oral hypoglycaemic agents on arterial stiffness among Malays with type II diabetes mellitus

To determine the effect of two regimens of oral hypoglycaemic agents: sulphonylurea monotherapy and metformin in combination with sulphonylurea on arterial stiffness. A case control study was conducted at the Family Medicine and Diabetic Clinic, HUSM from May 2004 until May 2005. Sixty subjects receiving sulphonylurea alone and ninety subjects on combination therapy with metformin participated in this study. A simple random sampling method using a draw lot was used to select 51 subjects for each group. Augmentation index [AI] was measured using the Sphygmocor apparatus and all measurements were performed by the investigators after an earlier validation study. The mean augmentation index measurements were analyzed. The mean AI values of diabetic subjects treated with sulphonylurea monotherapy and a combination with metformin were 140.51 +/- 11.42 vs 140.14 +/- 12.86, p= 0.877. AI values were significantly higher in females compared with males [143.23 +/- 10.60 vs 135.82 +/- 13.01, 95% CI: -12.07, -2.73, p = 0.002]. Duration of diabetes [in years] was significantly less [3.46 +/- 3.16 vs 5.41 +/- 3.66, p = 0.005] for sulphonylurea monotherapy patients compared with combination therapy patients. This study shows that sulphonylurea monotherapy and metformin in combination with sulphonylurea have similar effects on arterial stiffness in type 2 diabetes subjects. Diabetes is associated with a greater arterial stiffness in women compared with men

Gatifloxacin induced abnormalities in glucose homeostasis in a patient on glimepiride.

Gatifloxacin, a commonly prescribed antimicrobial can produce profound hypoglycemia and disturbances in glucose homeostasis especially in diabetes patients on sulphonylureas. Also new onset disturbances in glucose homeostasis can occur in patients who were unaffected by the previous use of gatifloxacin. Therefore it is suggested that gatifloxacin is better avoided in patients with diabetes and in the elderly.

Involvement of potassium channels in hypoglycemic effect of sertraline.

Effect of 21 days administration of sertraline (30 mg/kg, po) in streptozotocin (55 mg/kg, ip) induced diabetic and non-diabetic rats produced hypoglycemia in diabetic and non-diabetic rats. Pinacidil (1mg/kg, po), when co-administered with sertraline or glimepiride antagonized the decrease in glucose levels in diabetic rats. Pinacidil (10(-6)-10(-3) M) produced dose dependent relaxation (EC50-1.58 x 10(-5) M). Neither sertraline nor glimepiride had any effect on the resting tension of ileum preparation. Both sertraline and glimepiride antagonized competitively the pinacidil-induced relaxation. The pA2 values of sertraline and glimepiride reversal of pinacidil-induced relaxation were 5.5 and 6.2 respectively. These studies suggest the involvement of K+ channels in hypoglyceimic effects of sertraline.

Effect of glurenorm on immunohistochemical changes in pancreatic beta cells of rats in experimental diabetes.

Immunohistochemical localization of islets of Langerhans of streptozotocin (65 mg/kg, ip) induced diabetic + glurenorm (10 mg/kg, po) treated female albino rats revealed increase in number of beta cells and insulin immunoreactivity of beta cells. The results suggest that glurenorm can cause the stimulation of beta cells of endocrine pancreas in diabetic rats.

Diabetes Mellitus tipo 2 / Type 2 diabetes mellitus

Atualizaçäo no tratamento do diabetes mellitus tipo 2: dieta, exercícios, novas drogas, importancia da associaçäo de medicamentos para o controle adequado e prevençäo de complicaçöes crônicas.(au)

The role of diminished beta cell reserve and insulin resistance in secondary sulfonylurea failure of type 2 diabetes mellitus.

INTRODUCTION: The correction of hyperglycemia by insulin treatment has been shown to ameliorate beta cell function and insulin sensitivity in SU failure patients, and there also appears to have disparity between tests of beta cell function among these patients. The objectives of this study were to determine beta cell secretory reserve and insulin resistance of secondary SU failure type 2 diabetic patients who had fairly good glycemic control compared with those who were SU responsive and the disparity of beta cell responses to glucose and non-glucose stimuli were examined in these two groups. SUBJECTS AND METHOD: Eight secondary SU failure, insulin-treated and 11 SU responsive type 2 diabetic patients who were matched for age, degree of obesity, duration of diabetes as well as HbAlc were studied. Intravenous glucagon and oral glucose tolerance tests (OGTT) as well as short intravenous insulin tolerance test using arterialized venous blood were randomly performed on separate occasions to assess beta cell secretory reserve and insulin sensitivity, respectively. RESULTS: Basal (0.37+/-0.05 (SEM) vs 0.80+/-0.14 nmol/l; p=0.02) and stimulated c-peptide levels (0.66+0.08 vs 1.16+/-0.14 nmol/l; p=0.007) after glucagon as well as basal (0.46+/-0.06 vs 0.73+/-0.10 nmol/l; p=0.046) and maximal c-peptide responses (1.41+/-0.14 vs 1.97+/-0.14 nmol/l; p=0.021) to glucose stimulation were significantly lower in SU failure than SU responsive patients. However, the incremental changes of c-peptide over basal after glucagon (0.29+/-0.06 vs 0.37+/-0.09 nmol/l) and glucose (AUC: 36.9+/-7.6 vs 47.9+/-4.5 nmol/l/h) were not different between both groups. There were strong positive relationships between basal and stimulated c-peptide responses to glucagon (r=0.818; p=0.002) and glucose (r=0.85; p=0.001) in SU responsive patients but these relationships were not as strong in SU failure patients (r=0.682; p=0.062 and r=0.41; p=NS, respectively). Insulin sensitivity did not differ between the two groups. CONCLUSION: This study demonstrated that decreased basal, but not stimulated, insulin secretion was possibly a major factor associated with secondary SU failure in type 2 diabetic patients. With comparable glycemic control, there was no disparate beta cell responses to glucose and glucagon in patients with or without secondary SU failure.

Serum Insulin, Proinsulin and Proinsulin/Insulin Ratio in Type 2 Diabetic Patients: As an Index of beta-Cell Function or Insulin Resistance

BACKGROUND: Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. METHODS: We compared serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and control subjects. We also investigated the relationship between serum insulin, proinsulin and proinsulin/insulin ratio and several biochemical markers which represent insulin resistance or beta cell function. RESULTS: Insulin, proinsulin and proinsulin/insulin ratio were significantly higher in type 2 DM than control(p < 0.001). In diabetic patients, total insulin level was correlated with urinary albumin excretion rates(r = 0.224, p = 0.025) and body mass index(r = 0.269, p = 0.014). Proinsulin level was correlated with fasting C-peptide(r = 0.43, p = 0.002), postprandial 2 hour blood glucose(r = 0.213, p = 0.05) and triglyceride(r = 0.28, p = 0.022). Proinsulin/insulin ratio was positively correlated with fasting C-peptide(r = 0.236, p = 0.031), fasting blood glucose (r = 0.264, p = 0.015), postprandial 2 hour blood glucose(r = 0.277, p = 0.001) and triglyceride(r = 0.428, p < 0.001). In control subjects, insulin level was correlated with triglyceride(r = 0.366, p = 0.002). Proinsulin/insulin ratio was correlated with age(r = 0.241, p = 0.044). CONCLUSION: The serum levels of insulin and proinsulin seem to be associated with several markers of insulin resistance. Whereas proinsulin/insulin ratio might represent beta cell function rather than insulin resistance. But more studies are needed to clarify the mechanisms of elevated proinsulin/insulin ratio in type 2 DM.

Tratamiento farmacológico de la diabetes mellitus tipo 2 / Drug theraphy for the treatment of type 2 diabetes mellitus

El tratamiento farmacológico para los pacientes con diabetes mellitus tipo 2 se encuentra en su estado más maduro, con una base racional, con el principal objetivo de la prevención de la morbilidad y la mortalidad, lo que se encuentra considerado como el distintivo más importante en esta enfermedad. El tratamiento de los pacientes con diabetes mellitus tipo 2 con dieta ocurre en 12 por ciento, con hipoglucemiantes orales en 48 por ciento, con insulina en 36 por ciento, y 4 por ciento tienen un tratamiento combinado de hipoglucemiantes orales e insulina. Durante los últimos años ha habido una gran proliferación de nuevos medicamentos para el tratamiento de los pacientes con diabetes mellitus tipo 2. Estos productos ofrecen diferentes mecanismos de acción, lo que hace importante la individualización del tratamiento. Al momento de prescribir un hipoglucemiante oral debemos tener presente los efectos colaterales y las contraindicaciones

Canais de potassio sensíveis ao ATP e a secreçäo de insulina: aspectos fisiopatológicos da hiperinsulinemia familiar / Potassium channels sensibles to ATP and insulin secretion: physiopathological aspects of the familial hyperinsulinism

Glicose provoca a secreçao de insulina através do aumento da relaçao ATP/ADP no citoplasma das células beta. Isto leva ao bloqueio de canais de K+ sensíveis ao ATP (KATP), reduçao da saída deste cátion da célula, despolarizaçao celular, ativaçao da permeabilidade ao Ca2+ sensível à voltagem, entrada e acúmulo deste cátion nas células e consequente secreçao de insulina. O canal KATP parece ser composto por duas unidades distintas; uma delas, denominada Kir6,2, constitui o canal propriamente dito, por onde fluem as correntes de K+. A outra é o receptor de sulfoniluréias (SUR1), que é provida de sítios de ligaçao para o referido fármaco, para ATP, MgADP e diazoxida, atuando como unidade regulatória. Neste artigo, fazemos uma breve revisao da fisiologia dos canais KATP, considerando também sua importância na fisiopatologia do processo secretório.

Agentes farmacológicos actuales en el tratamiento de la Diabetes Mellitus no Insulinodependiente / Present pharmacological agents in the treatment of non-insulin-dependent diabetes

Se plantea que debido a la heterogeneidad patogénica de la diabetes mellitus no insulino, se debe considerar que diferentes agentes farmacológicos serán necesarios para tratar con éxito la enfermedad, por lo cual se realiza una revisión bibliográfica de las líneas de tratamiento actuales y en perspectivas para esta compleja entidad. Las modalidades terpéuticas actuales incluyen 5 grupos de agentes esenciales: los inhibidores de las alfaglucosidasas intestinales, las sulfonilureas, las biguanidas, la insulina y el recién incorporado grupo de las tiazolidinedionas, que si se utilizan en los comienzos de la enfermedad o en pacientes con resistencia insulínica, pudieran retrasar o prevenir el desarrollo de ésta, y pueden interferir en la reducción progresiva de la función pancreática. Se expone un grupo importante de agentes farmacológicos, así como sus posibles mecanismos de acción, sobre los cuales se ha estado investigando, para ampliar e incrementar la terapéutica de la diabetes, entre los que se encuentran los análogos de la insulina, los agentes insulinomiméticos y los preparados orales de insulina, los agentes insulinotrópicos no sulfonilureas, los análogos de la amilina, los péptidos similares al glucagón, los antagonistas alfa-2 adrenérgicos, los moduladores del metabolismo de la glucosa y algunas sustancias de origen vegetal con posibles efectos hipoglucémicos

Tratamiento farmacológico de la diabetes mellitus no insulinodependiente / Pharmacological therapy of non insulin dependent diabetes mellitus

Se describe la terapéutica farmacológica en la diabetes mellitus no dependiente de insulina (sulfonilureas, biguanidas, acarbosa e insulina). Se comentan sus mecanismos de acción, efectos secundarios y la necesidad de individualizar el tratamiento de acuerdo con el factor patogénico predominante en la hiperglucemia

Glimepirida / Glimepiride

Recientemente se ha incorporado al arsenal terapéutico disponible para el tratamiento de la diabetes mellitus no insulinodependiente (DM-NID), un nuevo derivado sulfonilureico, la Glimepirida, llamada de tercera generación y que se utiliza en menores dosis que las ya existentes