Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene – KCNJ11:c1001G>7 (p.Gly334Val) – and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

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...

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Chronic Hepatitis C and Insulin Resistance / 대한소화기학회지

Insulin resistance is frequently associated with chronic liver disease, and the interaction between hepatitis C virus (HCV) infection and insulin resistance is a major public health issue, bound to increase in the near term. Because of their potential synergism on liver disease severity, a better understanding of the clinical consequences of the relationship between HCV infection and insulin resistance is needed. This translates into accelerated liver disease progression, reduced response to anti-viral agents and, in susceptible individuals, increased risk of developing type 2 diabetes. HCV may also cause hepatic steatosis, especially in patients infected with genotype 3, although the clinical impact of viral steatosis is debated. Little is known regarding the effect of anti-diabetic agents on HCV infection, and a possible association between use of exogenous insulin or a sulfonylurea agents and the development of hepatocellular carcinoma has recently been reported. Thus, modified lifestyle and pharmacological modalities are urgently warranted in chronic hepatitis C with metabolic alterations.

Diabetes Mellitus Tipo 2 no mundo: atualização do tratamento medicamentoso / Type 2 Diabetes Mellitus in the world: an update of drug treatment

O diabetes mellitus tipo 2 (DM2) está alcançando proporções epidêmicas, e embora as mudanças no estilo de vida possam manter o controle glicêmico, o curso da doença, em longo prazo, requer algum tipo de intervenção farmacológica. É bem conhecido que os indivíduos que se mantêm mal controlados apresentam mais complicações macro e microvasculares e a redução da hemoglobina glicada (HbA1c) diminui significativamente o risco de desenvolvimento de complicações microvasculares em pacientes com DM2. Atualmente há seis classes de antidiabéticos orais: sulfonilureias, meglitinidas, biguanidas, tiazolidinedionas (TZDs), inibidores da alfa-glicosidase e os incretinomiméticos. As sulfonilureias e as meglitinidas estimulam a secreção de insulina; a metformina age principalmente suprimindo a produção hepática de glicose; as tiazolidinedionas melhoram a resistência periférica à insulina e os inibidores da alfa-glicosidase retardam a degredação e a digestão dos carboidratos complexos no intestino. Uma nova opção terapêutica para o DM2 são as drogas incretinomiméticas. Dentre elas temos os análogos de GLP-1 (exenatida e liraglutida) e os inibidores da DPP-IV. Ambos estimulam a secreção de insulina, suprimem a secreção de glucagon e desaceleram o esvaziamento gástrico; a redução de peso é característica dos análogos. O bom controle glicêmico em longo prazo e a prevenção do DM2 requerem uma abordagem agressiva e abrangente. No entanto, uma vez instalada a doença, além das modificações do estilo de vida, o tratamento farmacológico deve ser iniciado e cuidadosamente monitorado, com o uso de drogas que agem nos diversos mecanismos fisiopatológicos conhecidos. Novos estudos serão sempre necessários para se obter mais informações a respeito do diabetes e, assim, aprimorar o desenvolvimento de novas drogas.

The type 2 diabetes has reached epidemic proportions in the worldwide and lifestyle modification provide insufficient glucose control over the long-term course of the disease, the vast majority of patients require some type of pharmacological intervention. Several studies have shown that individuals who remain poorly controlled have more macro and microvascular complications and the decrease in glycated hemoglobin (HbA1c) significantly reduces the risk of developing microvascular complications in type 2 diabetes. At the moment, there are six classes of oral antidiabetics drugs: sulfonylureas, meglitinides, biguanides (metformin), thiazolidinediones (pioglitazone), alpha-glucosidase inhibitors (acarbose) and incretin-mimetics drugs. The sulfonylureas and meglitinide acting insulin secretion; metformin acts primarily by suppressing hepatic glucose production; thiazolidinediones improve insulin resistance; and alpha-glucosidade inhibitors retard the degradation and digestion of complex carbohydrates in the intestine and incretin-mimetics drugs that stimulate insulin secretion, suppress glucagon secretion, slows gastric emptying and weight loss (it is characteristic of the GLP-1 analogues). The good longterm glycemic control and prevention of type 2 diabetes requires an aggressive and comprehensive approach. However, once installed the disease, in addition to lifestyle modifications, pharmacotherapy should be initiated and carefully monitored using drugs that act on different pathophysiologicals mechanisms. New studies are always necessary to obtain more information about diabetes and thus improve the development of new drugs.

Effectiveness of adding vildagliptin to the treatment of diabetic patients nonresponsive to the combination of metformin and a sulphonylurea / Eficácia da adição de vildagliptina ao tratamento de pacientes diabéticos não responsivos à combinação de metformina e uma sulfonilureia

OBJECTIVE: To evaluate the effectiveness of adding vildagliptin to the treatment of patients with inadequately controlled type 2 diabetes mellitus (T2DM) treated with a combination of metformin and a sulphonylurea. SUBJECTS AND METHODS: 37 T2DM patients with HbA1c ranging from 7.7 percent to 12.4 percent (mean of 9.30 ± 1.38), despite the use of metformin in combination with a sulphonylurea, were additionally treated with vildagliptin (100 mg/day) for at least 6 months. RESULTS: During triple oral therapy (TOT) HbA1c levels < 7 percent were achieved in 11 patients (29.7 percent), whereas levels of fasting plasma glucose (FPG) < 120 mg/dL were observed in 12 patients (32.4 percent). Both findings were observed in 10 patients (27.0 percent). Compared to nonresponsive subjects, lower mean baseline HbA1c and FPG levels were seen in responsive patients, but the difference was only statistically significant for fasting plasma glucose (FPG). Moreover, there was considerable overlap between the two groups. CONLUSION: Our preliminary results suggest that TOT with metformin, a sulphonylurea and vildagliptin may be useful for some T2DM patients nonresponsive to combination therapy with metformin and sulphonylurea.

OBJETIVO: Avaliar a eficácia da adição de vildagliptina ao tratamento de pacientes com diabetes melito tipo 2 (DM2) inadequadamente controlados com a terapia de combinação com metformina e sulfonilureia. SUJEITOS E MÉTODOS: 37 pacientes com DM2 e HbA1c variando entre 7,7 por cento e 12,4 por cento (média, 9,30 ± 1,38), apesar do uso de metformina associada a uma sulfonilureia, foram adicionalmente tratados com vildagliptina (100 mg/dia) durante, pelo menos, 6 meses. RESULTADOS: Durante a terapia oral tripla TOT), níveis de HbA1c < 7 por cento foram alcançados em 11 pacientes (27,9 por cento), enquanto a glicemia de jejum (GJ) < 120 mg/dL foi observada em 12 pacientes (32,4.1 por cento). Ambos os resultados foram descritos em 10 pacientes (27,0 por cento). Em comparação com indivíduos não responsivos, os pacientes responsivos tinham níveis basais mais baixos de HbA1c e GJ, mas a diferença foi estatisticamente significativa somente para glicemia de jejum. Além disso, houve grande sobre-posição entre os dois grupos. CONSLUSÃO: Nossos resultados preliminares sugerem que a TOT com metformina, uma sulfonilureia e vildagliptina pode ser útil para alguns pacientes com DM2 não responsivos à combinação com metformina e uma sulfonilureia.

Diabetes Mellitus tipo 2 no mundo: novas abordagens terapêuticas / Type 2 diabetes in the world: new therapeutic approaches

A Federação Internacional de Diabetes (/DF) publicou novos dados indicando a enormidade da epidemia mundial da doença. Esses dados demonstram que o diabetes afeta atualmente 246 milhões de pessoas em todo o mundo, sendo que 46% destes com idades entre 40 e 59 anos. Dados atuais predizem que, se nada for feito, o número total de portadores de diabetes ultrapassará 380 milhões de pessoas em 20 anos. O estilo de vida moderno trouxe inúmeras mudanças de hábito e comportamento, como menor tempo dedicado à prática de atividades físicas regulares, um cotidiano mais estressante, além da maior oferta de alimentos industrializados, ricos em carboidratos simples e gorduras, pobres em fibras, minerais e vitaminas. Atualmente dedica-se mais tempo a atividades em frente às telas de computadores e a jogos de videogame e programas de televisão. Como consequência, tem-se observado maior incidência de doenças metabólicas, tais como obesidade, diabetes mellitus tipo 2 (DM 2), hipertensão arterial sistêmica (HAS), dislipidemia e, portanto, doenças cardiovasculares (DCVs), gerando a necessidade crescente de pesquisas em busca de novas opções terapêuticas para estas doenças. O presente trabalho visa fazer uma breve revisão sobre os avanços terapêuticos do diabetes mellitus tipo 2.

The International Diabetes Federation (/DF) has published new data indicating the enormity of the diabetes epidemic in the globe. That data show that the disease now affects a staggering 246 million people worldwide, with 46% of a11 those affected in the 40-59 age group. The new data predict that the total number of people living with diabetes will skyrocket to 380 million within twenty years if nothing is done. The modern life style has brought many changes such as more variety of food rich in sugar, fat and poor in fiber, vitamins and minerals, less time to practice a regular physical activity and a more stressful lifestyle. Nowadays, people spend more time in front of their computers, playing video games and watching programs of TV. As a consequence, many metabolic diseases have been increasing such as obesity, type I1 diabetes mellitus, high blood pressure, hyperlipidemia and cardiovascular diseases, leading the growing necessity of researches for new therapeutic options to these diseases. This article is a short review of type II diabetes mellitus's new treatment.

Long-term response to sulfonylurea in a patient with diabetes due to mutation in the KCNJ11 gene / Resposta a longo prazo com sulfonilureia em um paciente com diabetes associado à mutação no gene KCNJ11

OBJECTIVE: To report the long-term (30-month) effect of the switch from insulin to sulfonylurea in a patient carrying the p.G53D (c.158G>A) mutation in KCNJ11 gene. SUBJECT AND METHOD: A 29-year-old male patient was diagnosed with diabetes in the third month of life and after identification of a heterozygous p.G53D mutation in the KCNJ11 gene, the therapy was switched from insulin to sulfonylurea. RESULTS: Long-term follow-up (30 months) showed that good metabolic control was maintained (HbA1c: 6.6 percent) and the glibenclamide dose could be reduced. CONCLUSION: Long-term therapy with sulfonylureas in patients with neonatal diabetes due to mutation in the KCNJ11 gene is safe and promotes sustained improvement of glycemic control.

OBJETIVO: Reportar o efeito a longo prazo (30 meses) da substituição de insulina por sulfonilureia em um paciente com a mutação p.G53D (c.158G>A) no gene KCNJ11. SUJEITO E MÉTODO: Paciente do sexo masculino, atualmente com 29 anos de idade, foi diagnosticado com diabetes melito no terceiro mês de vida e, após identificação da mutação p.G53D (c.158G>A) em heterozigose no gene KCNJ11, a terapia foi substituída de insulina para sulfonilureia. RESULTADOS: Seguimento a longo prazo (30 meses) mostrou que o bom controle metabólico foi mantido (HbA1c: 6,6 por cento) e a dose de glibenclamida pode ser reduzida. CONCLUSÃO: A terapia com sulfonilureia a longo prazo em pacientes com diabetes neonatal decorrente de mutações no gene KCNJ11 é segura e promove uma melhora persistente no controle metabólico.

Transient neonatal diabetes due to activating mutation in the ABCC8 gene encoding SUR1.

We report a 2 month male child presenting with diabetic ketoacidosis (DKA) and seizures treated with intravenous fluids and intravenous insulin infusion till the ketoacidosis was reversed, thereafter responding well to sulphonylureas and at age of 13 months going into complete remission. At age of 11 mo developmental delay in the form of negative neck holding and inability to sit without support was seen. The child is 3 yr of age now ,euglycemic without any insulin or oral hypoglycemic agents but has severe developmental delay. Genetic analysis was negative for mutations of KCNJ11, 6q24, Glucokinase and IPF-1 genes. A mutation R1183W was found in the ABCC8 gene encoding SUR1, which was the cause of neonatal diabetes in this case.

Efecto de los polimorfismos Gly972Arg del gen IRS1, SNP43 del gen CAPN10 y Pro12Ala del gen PPARG2 sobre la falla secundaria a sulfonilureas y metformina en pacientes con diabetes tipo 2 de Yucatán México / Effect of the Gly972Arg, SNP43 and Pro12Ala polymorphisms of the genes IRS1, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in Yucatán México

La diabetes tipo 2 (DT2) es elevada en Yucatán; 52% de los afectados presentan falla al tratamiento con sulfonilureas y metformina. Una posible explicación es por polimorfismos en los genes IRS1, CAPN10, PPARG2, involucrados en la disfunción de la célula b pancreática y respuesta baja a la acción de insulina. Se determinó la asociación de los polimorfismos Gly972Arg, SNP43 y Pro12Ala con el riesgo a la falla al tratamiento con sulfonilurea y metformina, en pacientes con DT2 de Yucatán, México. Se estudiaron ciento treinta y dos pacientes, clasificados con base al control de la hiperglucemia con sulfonilureas y metformina, en grupos de respondedores (HbA1c<8%) y no respondedores (HbA1c > 8%) al tratamiento. De cada sujeto, se obtuvieron datos demográficos, antropométricos, clínicos y metabólicos. Los polimorfismos se identificaron mediante el análisis del ADN por PCR/RFLP y PCR/OAL. Se calcularon las frecuencias genotípicas y alélicas y el equilibrio de Hardy-Weinberg. Se analizó estadísticamente con X² y regresión logística múltiple (Epi-Info 2000 y SPSS versión 12). Se observó diferencia significativa (p = 0,027) en el riesgo a la falla al tratamiento 4,69 veces mayor en sujetos obesos con genotipo AA SNP43, comparado con sujetos con genotipo GA: X² (OR= 4,69, IC: 1,15-20,59) y regresión logística múltiple, p= 0,048, (OR= 3,72, IC: 1,009-13,718). Se identificó interacción entre el genotipo AA y el IMC>27 (p=0,009). Los hallazgos sugieren que el polimorfismo SNP43 podría influir en la respuesta al tratamiento con sulfonilureas y metformina, con expresión dependiente de obesidad.

In Yucatán, 52% of patients with type 2 diabetes (DT2) present secondary failure to treatment associated with sulphonylurea and metformin. A possible explanation may be due to polymorphisms in the genes IRS1, CAPN10, PPARG2, which are involved in pancreatic b cell dysfunction and a poor response to the action of insulin. The association of the polymorphisms Gly972Arg, SNP43, and Pro12Ala, of the genes IRS1, CAPN10, PPARG2, with the risk of failure to sulphonylurea and metformin therapies was determinated in patients with DT2 in Yucatán, México. One hundred and thirty and two subjects with DT2 were classified in groups of responders (HbA1c< 8%) and non-responders (HbA1c> 8%) to the treatment, according to the control of hyperglucemia with sulphonylurea and metformin. Demographic, anthropometric and metabolic data were obtained from each subject. The polymorphisms were identified by means of DNA analysis by PCR/RFLP and PCR/OAL. Genotypic and allelic frequencies and the Hardy-Weinberg equilibrium were determined. Statistical analyses consisted of X² and multiple logistic regression tests (Epi-Info 2000 and SPSS version 12). Obese subjects carrying the genotype AA SNP43 showed 4.69 times more risk of failure to respond to treatment (p=0.027), when compared with subjects sharing GA genotype: X² (OR= 4.69, IC: 1.15-20.59) and multiple logistic regression, p= 0.048, (OR= 3.72, IC: 1.009-13.718). The interaction between genotype AA and the BMI> 27 showed also a significant difference (p=0.009). The findings suggest the fact that polymorphism SNP43 may influence the response to treatment with sulphonylurea and metformin, the expression being dependent on obesity.

Relationship between plasma leptin and plasma insulin levels in type-2 diabetic patients before and after treatment with glibenclamide and glimepiride.

Type 2 diabetes affects 100 million people throughout the world. Among the various factors implicated in the causation of this disease, the role of leptin, an obesity gene product, is increasingly being investigated. This especially assumes importance in the light of knowledge that obesity confers a minimum of 3-10 fold higher risk of diabetes. This study was planned to investigate the relationship between leptin and insulin levels in type 2 diabetic patients before and after treatment with glibenclamide or glimepiride. 60 type 2 diabetic patients were recruited for the study and were divided into 2 groups-one receiving glimepiride and the other group receiving glibenclamide for duration of 10 weeks. This study demonstrated a highly positive correlation of plasma leptin levels with BMI, plasma insulin and insulin resistance. No gender specific differences were observed in leptin concentrations. The study, however, failed to demonstrate any possible relationship between glycemic control as assessed by blood sugars/ glycosylated hemoglobin (HbAlc) and plasma leptin. The administration of glibenclamide or glimepiride significantly lowered blood glucose levels coupled with a decrease in (HbAlc). Both the drugs increased insulin concentrations. Glibenclamide increased leptin levels but they remained unaltered with glimepiride. Glibenclamide and glimepiride were found to be equally effective in their glucose lowering action. However, the patients receiving glibenclamide experienced higher episode of hypoglycaemic spells than those receiving glimepiride.

Polymorphonuclear leukocyte function in type-2 diabetes mellitus patients and its correlation with glycaemic control.

Infection is an important cause of morbidity and mortality in diabetic patients. Chronic hyperglycaemia impairs host defense mechanism such as cell mediated immunity, polymorphonuclear leukocyte (PMNL) function, antibody formation etc. PMNL serves as bodies first line of defense against various infections. The present study was undertaken to establish a correlation between impaired PMNL function, blood glucose levels and its improvement with good glycaemic control with glibenclamide and glimepiride, with special reference to parameters such as respiratory burst and O2(-) and H2O2 production by diabetic neutrophils.

Diabetes tipo 2: nuevo algoritmo terapéutico basado en viejas drogas / Type 2 diabetes: new therapeutic algorithm based on old drugs

Este artículo resume la evidencia disponible sobre la eficacia de las sulfonilureas, la metformina, las ôglitazonasõ y la insulina para el tratamiento de los pacientes con diabetes tipo 2 y destaca el nuevo algoritmo consensuado por la Asociación Americana de Diabetes y la Asociación Europea para el Estudio de la Diabetes. Se sugiere que los profesionales que trabajan en el ámbito de la Atención Primaria se familiaricen con el uso de las glitazonas y la insulina.

Sulfonylurea Therapy in Two Korean Patients with Insulin-treated Neonatal Diabetes due to Heterozygous Mutations of the KCNJ11 Gene Encoding Kir6.2

Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life. In most cases, the causes are not known. Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K(+) channel have been described in patients with PND. We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively. After several years of insulin therapy, these patients were managed by oral glibenclamide therapy at a daily dose of 0.8-0.9 mg/kg. Their basal c-peptide levels increased after one week of glibenclamide therapy, and one month later, the insulin and c-peptide levels were in the normal ranges without any episodes of hyper- or hypoglycemia. These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.

Thailand diabetes registry project: glycemic control in Thai type 2 diabetes and its relation to hypoglycemic agent usage.

OBJECTIVE: To determine the pattern of hyperglycemic agent usage in Thai type 2 diabetics (T2 DM) who attended the diabetes clinic in university and tertiary-care hospitals. The achievement oftarget glycemic control by various modalities of treatment was also analyzed. MATERIAL AND METHOD: A cross-sectional, hospital-based diabetes registry of 8913 type 2 diabetic patients in 11 tertiary care hospitals and medical schools was carried out from April to December 2003. Demographic data, usage of hypoglycemic agents and level of glycemic control were collected to determine the pattern ofuse, associated factors, and achievement of glycemic control. RESULTS: Overall, 2342 (26.3%) of T2 DM achieved HbA1C less than 7%. The percentage of patients treated with metformin was 70.8%, sulfonylureas (SU) was 68.7% and insulin was 25.3%. Only 7.0% of patients received alpha-Glucosidase Inhibitor (AGI), 5.7% received ThaiZoliDinediones (TZD), 1.1% received repaglinide, and 3.2% was on diet control alone. Target glycemic control was achieved in 57.6%, 37.1%, 52%, 16.7%, 62.5%, 52% and 16.9% of patients who were on diet control only, monotherapy with SQU, metformin, TZD, AGI, repaglinide and insulin,respectively. Sulfonylureas were the most commonly used drug for monotherapy. Metformin with sulfonylurea was the most common combination therapy and was used in 39.5% of patients. More than 60% of the patients treated with metformin monotherapy had body mass index (BMI) of more than 25 kg/m2, as compare to less than half of patient treated with other monotherapy agent. Mean +/- SD duration of diabetes in thepatients treated with metformin alone was 5.9 +/- 5.5 years, less than that in the SU-treated patients (8.3 +/- 7.1 years) and also in the insulin-treated patients (14.8 +/- 9.0 years). TDZ were commonly prescribed in combination with sulfonylureas and metformin in subjects with relatively longer duration of diabetes. CONCLUSION: Better treatment strategies for glucose control ofdiabetic patients on medical treatments should be encouraged to improve glycemic control and reduce long term complications.

Sulphonylureas in the management of type 2 diabetes during the fasting month of Ramadan.

Although a majority of Muslim patients with type 2 diabetes fast during the month of Ramadan, there are no accepted guidelines for its management during this period. The few studies on this subject suggest that there are important alterations in energy intake and physical activity, and that most patients change their pattern of drug intake. This is associated with a greater risk of hypoglycaemia and ketoacidosis. The usual pattern of eating during Ramadan, and its influence on the normal diurnal variation of blood sugar with a regular non-fasting diabetic diet, suggests that anti-diabetic agents for use during this period need to be selected according to their pharmacokinetic and tablet formulation characteristics. The sulphonylureas are first line drugs in type 2 diabetes and used by a majority of patients. A comparison of the pharmacokinetics, efficacy, and safety characteristics of these agents suggests that a long-acting once daily formulation of gliclazide such as gliclazide modified release, taken in the evening, may be the sulphonylurea of choice during Ramadan.

Diabetes "Mellitus" do tipo II nos dias atuais / Diabetes mellitus type II in nowadays

A modernidade trouxe inúmeras mudanças de hábito e comportamento como menor tempo para prática de atividade física regular, um estilo de vida mais estressado, além de maior oferta de alimentos industrializados, ricos em carboidratos simples e gorduras, pobres em fibras, minerais e vitaminas. Atualmente passa-se mais tempo em frente aos computadores e às televisões. Como conseqüência tem-se observado maior incidência de doenças metabólicas, tais como obesidade, diabetes mellitus tipo II (DM II), hipertensão arterial sistêmica (HAS), dislipidemia e, portanto, doenças cardiovasculares (DCVs). O presente trabalho visa fazer uma breve revisão sobre diabetes mellitus tipo II e suas conseqüências para a saúde.

The modern life style has brought many changes such as more variety of food rich in sugar, fat and poor in fiber, vitamins and minerals, less time to practice a regular physical activity and a more stressful lifestyle. Nowadays, people spend more time in front of their computers and TV. As a consequence, many metabolic diseases have been increasing such as obesity, type II diabetes mellitus, high blood pressure, hyperlipidemia and cardiovascular diseases. This article is a short review of type II diabetes mellitus and its consequences.

Use of glimepiride and insulin sensitizers in the treatment of type 2 diabetes--a study in Indians.

AIM: Short-term efficacy of glimepiride, metformin and pioglitazone in newly diagnosed type 2 diabetes was compared with a group treated with diet and exercise. Effects on insulin secretion and sensitivity were also assessed. METHODS: New type 2 diabetic subjects, aged 30-60 years with BMI < 30 kg/m2 were selected. Subjects having glycosylated haemoglobin (HbA1c) of < 8.5% were advised diet and exercise (control group). Others having HbA1c > or = 8.5 to 11.0% were randomized to receive glimepiride (group 2), metformin (group 3) and pioglitazone (group 4). At the final review between 12-14 weeks, changes in plasma glucose, HbA1c, lipid profile, HOMA insulin resistance (HOMA-IR), beta cell function (HOMA-BF) and insulinogenic index (delta I/G) were measured. Comparisons were made using appropriate statistical analyses. RESULTS: Seventy-seven of the 97 subjects randomized equally into four groups, were available for review. Glycaemic parameters improved in all groups. Mean cholesterol decreased significantly in groups treated with metformin and pioglitazone. HDL-cholesterol increased with pioglitazone. Insulin resistance decreased significantly with metformin and pioglitazone, beta cell fuhction also showed improvement CONCLUSIONS: Glycaemic control was seen in all study groups, the improvement was better in drug treated groups than in the control group. Glimepiride improved insulin secretion including the early phase secretion and reduced plasma triglycerides. Metformin and pioglitazone had beneficial effects on lipid levels, improved insulin sensitivity and improved insulin secretion also.