RESUMEN
PURPOSE: Metformin is the most commonly prescribed anti-diabetic medication. However, it is often used despite the presence of contraindications and in unlicensed indications. The main aim of this study was to evaluate the frequency of metformin use before hospitalization in spite of contraindications in patients with type 2 diabetes mellitus (T2DM) and to evaluate the prevalence of metformin - associated side effects. MATERIAL/METHODS: 558 hospitalized patients (mean age = 66.65 ± 12.73 years) with poorly controlled T2DM were enrolled. Detailed medical history including the duration of T2DM, duration of hypoglycemic agents usage prior to hospitalization and possible metformin-associated side effects was recorded. Patients were subjected to a thorough physical examination and indispensable biochemical and diagnostic research panel was performed to establish the degree of heart failure, sufficiency of the respiratory system and kidney function. RESULTS: 335 out of 558 patients were treated before hospitalization with metformin alone or in combination with other hypoglycemic agents, mostly sulfonylureas. Contraindications to metformin were found in 275 patients and despite this 120 of them were using this medication in an average dose of 1793.91 ± 701.61 mg. However, none of them reported any serious adverse effects and no significant pH changes were observed. Only three patients reported moderate dyspepsia. CONCLUSIONS: The results of this study indicate a relatively good tolerability of metformin by patients with the traditional contraindications to this drug. These findings support other authors' suggestion that indications and contraindications to metformin should be re-evaluated.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Prescripción Inadecuada/efectos adversos , Metformina/administración & dosificación , Anciano , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Metformina/uso terapéutico , Persona de Mediana EdadRESUMEN
The results of clinical studies revealed that gliclazide may reduce the risk of cancer in type 2 diabetic patients (T2DM), although the mechanism of possible protective effect is not sufficiently explored. The increased level of DNA damage and impaired DNA repair system in diabetes mellitus may play a substantial role in neoplastic transformation. Recently, we have demonstrated that gliclazide protected DNA against damage introduced by the oxidative stress, but its action on the DNA repair mechanisms is unclear. Therefore, the aim of this study was to assess whether gliclazide has any effect on the DNA repair pathways, e.g. nucleotide excision repair (NER) and non-homologous end joining (NHEJ). NER activity was assessed in the extract of human lymphocytes and pancreatic cancer cells (PANC-1) treated or not with gliclazide by use of an UV-irradiated plasmid as a substrate and by quantitative PCR performed to evaluate the efficacy of the removal of UV-induced lesions from the p53 gene by intact cells. The efficacy of NHEJ pathway was examined by a simple and rapid in vitro assay based on fluorescent detection of repair products. We did not observe significant differences between the efficiency of NER and NHEJ for extracts of lymphocytes alone and lymphocytes treated with gliclazide. Contrary, gliclazide increased the efficacy of NER (46.0% vs. 84.0%, p<0.01) and NHEJ (58.0% vs. 66.0%, p<0.05) in PANC-1 cells. In conclusion, the present study showed that gliclazide did not affect NER and NHEJ in human normal cells, but it may stimulate DNA repair in cancer cells.
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Carcinoma Ductal Pancreático/genética , Reparación del ADN/efectos de los fármacos , Gliclazida/farmacología , Linfocitos/efectos de los fármacos , Adolescente , Adulto , Línea Celular Tumoral , ADN/biosíntesis , ADN/metabolismo , Daño del ADN/efectos de los fármacos , Daño del ADN/genética , Genes p53 , Humanos , Hipoglucemiantes/farmacología , Masculino , Rayos Ultravioleta , Adulto JovenRESUMEN
BACKGROUND: The prognosis of diabetic patients after non-cardiac surgery remains controversial. This study was designed to compare the long-term mortality between diabetic and non-diabetic control patients undergoing non-cardiac surgery and to evaluate the possible risk factors. METHODS: We investigated 274 consecutive diabetic patients and 282 non-diabetic control patients who underwent non-cardiac surgery within 1 year in a tertiary care hospital in Finland. The control group was matched for the same type of operations. Patients were followed for up to 7 years on average. The main outcome measure was mortality within 7 years. RESULTS: Mortality both in the short-term postoperatively (< or =21 days) and in the long-term (up to 87 (1/2) months) was significantly higher in the diabetic patients compared with the non-diabetic group: 3.5 vs. 0% (P<0.05) and 37.2 vs. 15% (P<0.00001), respectively. The major causes of death among diabetic subjects were diseases of the cardiovascular system (56.8%) compared with non-diabetic patients (18.6%), P<0.0001. We found that diabetes mellitus per se is not a risk factor for post-operative mortality but a combination of variables had a significant effect on both short- and long-term mortality. CONCLUSION: Diabetic patients undergoing non-cardiac surgery had a significantly higher incidence of short-term post-operative and long-term mortality compared with non-diabetic subjects. We propose a model of predictors of death among diabetic individuals undergoing non-cardiac surgery within a 7-year follow-up. The majority of deaths were associated with cardiovascular diseases.
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Diabetes Mellitus/mortalidad , Procedimientos Quirúrgicos Operativos/mortalidad , Factores de Edad , Anciano , Índice de Masa Corporal , Causas de Muerte , Diabetes Mellitus Tipo 1/mortalidad , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Type 2 diabetes mellitus is associated with increased oxidative stress. Free radicals produced during this stress may damage various cellular components. Gliclazide, a second-generation sulfonylurea, is an oral hypoglycemic drug that possesses antioxidant properties. Therefore, gliclazide may diminish the harmful consequences of oxidative stress in diabetic patients. The aim of our study was to evaluate the action of gliclazide on DNA damage and repair in normal human peripheral blood lymphocytes and insulinoma mouse cells (beta-TC-6). DNA damage and repair were induced by hydrogen peroxide, gamma and ultraviolet radiation and MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) in the presence or absence of gliclazide and were analysed by the alkaline comet assay. DNA double-strand breaks were assayed by pulsed-field gel electrophoresis. Gliclazide protected DNA of both kinds of cells from DNA damage induced by chemicals and radiations. These results suggest that gliclazide may diminish the risk of free radical-related diseases associated with type 2 diabetes mellitus and possibly cancer.
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Daño del ADN/efectos de los fármacos , Gliclazida/farmacología , Hipoglucemiantes/farmacología , Insulinoma/patología , Linfocitos/sangre , Linfocitos/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo Cometa , ADN/metabolismo , Reparación del ADN/efectos de los fármacos , Electroforesis en Gel de Campo Pulsado , Humanos , Ratones , Factores de TiempoRESUMEN
The Trp64Arg amino-acid variant of the beta3 adrenoreceptor gene may be associated with a genetic predisposition to human obesity and related disorders, including type 2 diabetes mellitus. This relationship has been reported in various ethnic groups, however it was not extensively studied in Polish population. Therefore, the aim of the study was to investigate the association of Trp64Arg polymorphism of the beta3 adrenergic receptor gene with overweight and type 2 diabetes mellitus in polish subjects. The Trp64Arg polymorphism was determined by PCR-based MspI restriction fragment length polymorphism (PCR-RFLP). The study population consisted of 358 subjects, among whom 200 were diagnosed as overweight (BMI > 27 kg/m (2)). Among overweight subjects 111 presented with type 2 diabetes mellitus and 89 with normal glucose metabolism. All study participants were unrelated Caucasians and inhabited the city of Lodz, Poland. The frequency of the Arg allele did not differ significantly between overweight and normal weight patients (13 % vs. 11 %, OR 1.17, CI 0.74 - 1.85). The same applied to overweight diabetic patients vs. overweight patients without diabetes mellitus (13 % vs. 13 %, OR 0.97, CI 0.54 - 1.76). The obtained results suggest no association between Trp64Arg polymorphism of the beta3-AR gene and the incidence of overweight and type 2 diabetes mellitus in Polish population.
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Diabetes Mellitus Tipo 2/genética , Mutación Missense/genética , Sobrepeso/genética , Receptores Adrenérgicos beta 3/genética , Triptófano/genética , Anciano , Femenino , Genotipo , Glucosa/metabolismo , Humanos , Masculino , Polonia , Polimorfismo Genético/genética , Receptores Adrenérgicos beta 3/químicaRESUMEN
Insulinoma tumors are often difficult to detect, as the symptoms largely precede occurrence of a visualized tumor. We report the case of an insulinoma patient with long delayed diagnosis and marked adaptation to extreme hypoglycemia. The patient with a 7-yr history of seizures was found to have plasma glucose concentration during a starvation test as low as 16 mg/dl, with no clinically significant symptoms and concomitant normal plasma insulin levels: 10-30 microIU/ml. All attempts to localize a tumor with repeated abdominal ultrasound examinations or computed tomography scanning were unsuccessful. The patient did not tolerate the introduced oral treatment with diazoxide. Once it had become technically available, endoscopic ultrasonography of the pancreas was performed. It revealed a 10 mm tumor in the pancreatic head. The tumor was subsequently removed surgically. During the operation plasma insulin concentration rose almost 15-fold, which confirmed the insulin-secreting character of the growth. Microscopic examination revealed benign insulinoma, with partially trabecular structure. One month after the operation the patient had normal plasma glucose values of 60-120 mg/dl, but she constantly complained of excessive thirst, which occurred soon after the operation and slowly subsided in the following weeks. In conclusion, the present report demonstrates that insulinoma should be considered and searched for in every case of hypoglycemia associated with normal insulin levels. It also confirms the essential role of endoscopic ultrasonography in the diagnosis of insulin-secreting tumors.
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Endosonografía , Insulina/sangre , Insulinoma/sangre , Insulinoma/diagnóstico por imagen , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico por imagen , Adaptación Fisiológica , Adulto , Glucemia/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Hipoglucemia/etiología , Hipoglucemia/fisiopatología , Insulinoma/complicaciones , Insulinoma/cirugía , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/cirugía , Índice de Severidad de la EnfermedadRESUMEN
We analysed the distribution of genotypes and frequency of alleles of two polymorphisms in the urokinase-type plasminogen activator (uPA) gene: a C-->T substitution in exon 6 and a T-->C substitution in intron 7 in 89 children with type 1 diabetes mellitus and insulin resistance compared with 120 non-diabetic control subjects. All genotypes were determined by the allele-specific polymerase chain reaction. We found that the frequency of the T/T homozygote (15%) in the patient group was significantly (P<0.05) higher than in the controls (7%). There were no differences in the distribution of the T-->C polymorphism between patients and controls, which suggests that this genetic change is probably phenotypically silent. In conclusion, our results indicate that the higher percentage of T/T homozygotes in patients might be associated with T1DM coexisting with insulin resistance.
Asunto(s)
Diabetes Mellitus Tipo 1/genética , Resistencia a la Insulina/genética , Activador de Plasminógeno de Tipo Uroquinasa/genética , Niño , Preescolar , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Polimorfismo GenéticoRESUMEN
BACKGROUND: Progressive beta-cell failure is a characteristic feature of type 2 diabetes; consequently, beta-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice. DESIGN: Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30-120 mg daily or glimepiride 1-6 mg daily as monotherapy or in combination with their current treatment (metformin or an alpha-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition. RESULTS: HbA1c decreased similarly in both groups from 8.4% to 7.2% on gliclazide MR and from 8.2% to 7.2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6.5%. The mean difference between groups of the final HbA1c was -0.06% (noninferiority test P < 0.0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L(-1) occurred significantly less frequently (P = 0.003) with gliclazide MR (3.7% of patients) compared with glimepiride (8.9% of patients). The distribution of the sulphonylurea doses was similar in both groups. CONCLUSIONS: This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gliclazida/administración & dosificación , Hipoglucemiantes/administración & dosificación , Compuestos de Sulfonilurea/administración & dosificación , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Femenino , Gliclazida/efectos adversos , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Compuestos de Sulfonilurea/efectos adversos , Resultado del TratamientoRESUMEN
Streptozotocin (STZ) is an antibiotic which can be used to induce diabetes in experimental animals in order to have an insight into pathogenesis of this disease. To use STZ as a diabetogenic substance, its molecular mode of action should be elucidated. Using the alkaline comet assay, we showed that STZ at concentrations in the range 0.01-100 micromol/L induced DNA damage in normal human lymphocytes and HeLa cancer cells in a dose-dependent manner. Lymphocytes were able to remove damage to their DNA within a 30-min repair incubation, whereas HeLa cells completed the repair in 60 min. Vitamins C and E at 10 and 50 micromol/L diminished the extent of DNA damage induced by 50 micromol/L STZ. Pretreatment of the lymphocytes with the nitrone spin trap, alpha-(4-pyridil-1-oxide)-N-tert-butylnitrone (POBN) or ebselen, which mimics glutathione peroxidase, or pyrrolidine dithiocarbamate (PDTC) reduced the extent of DNA damage evoked by STZ. The cells exposed to STZ and treated with endonuclease III (Endo III), formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (AlkA), the enzymes recognizing oxidized and alkylated bases, displayed greater extent of DNA damage than those not treated with these enzymes. These results suggest that free radicals may be involved in the formation of DNA lesions induced by streptozotocin. The drug can also alkylate DNA bases. This broad range of DNA damage induced by STZ indicates that the drug may seriously affect genomic stability in normal and pathological cells.
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Antibióticos Antineoplásicos/toxicidad , Daño del ADN/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Linfocitos/efectos de los fármacos , Mutágenos/toxicidad , Estreptozocina/toxicidad , Antibióticos Antineoplásicos/antagonistas & inhibidores , Ácido Ascórbico/farmacología , Ensayo Cometa , Reparación del ADN/efectos de los fármacos , Enzimas Reparadoras del ADN/farmacología , Relación Dosis-Respuesta a Droga , Antagonismo de Drogas , Células HeLa , Humanos , Óxidos de Nitrógeno/farmacología , Piridinas , Estreptozocina/antagonistas & inhibidores , Vitamina E/farmacologíaRESUMEN
A single guanine insertion (1G/2G polymorphism) in the promoter of the matrix metalloproteinase (MMP-1) gene creates a binding site for the transcription factor and may affect the level of transcription of MMP-1. An elevated level of MMP-1 in cancer cells may facilitate their invasion and contribute to metastasis. To evaluate the contribution of 1G/2G polymorphism in the development and/or progression of breast cancer we genotyped 135 subjects with breast cancer. The 1G/2G polymorphism was determined by the method based on restriction endonuclease digestion. We found that the frequency of the 2G allele was higher in lymphnode-metastasis patients than in the group without metastasis (p < 0.001). We did not find differences between distribution of the genotypes and frequencies of alleles in cancer patients and in healthy subjects served as control. Our results suggest that allele 2G may be associated with lymphnode metastasis in patients with breast cancer and therefore it can be considered as a prognostic marker in this disease.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Metaloproteinasa 1 de la Matriz/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Alelos , Biomarcadores de Tumor , Progresión de la Enfermedad , Genotipo , Humanos , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. GH treatment improves the profile of many cardiovascular risk markers in individuals with GH deficiency (GHD). The aim of the present was to assess whether GH replacement may decrease plasma total homocysteine, an independent cardiovascular risk factor, thus potentially contributing to benefits of GH replacement in adult subjects with GHD. Twenty-five patients (17 female, 8 male), mean age 39-years, with GHD were studied. GH status had been determined by an insulin tolerance test and/or arginine stimulation test. After an overnight fast, plasma insulin, IGF-1, total homocysteine (Hcy), free thyroxine (FT4), creatinine, vitamin B12, and folate were measured at baseline (V1), 3 months (V2) and then at 6 months (V3) on GH treatment. The data were analysed by hierarchical statistical models, univariate and multivariate correlation. GH treatment resulted in an increase in IGF-1 (p<0.001, p<0.001), and insulin (p=0.068, p<0.001), at each visit, respectively. Hcy levels increased from V1 to V2 (7.7+/-0.53 to 9.15+/-0.45 micromol/L; p=0.051), but this was followed by a decline at V3 (to 8.8+/-0.59), so that the overall change of Hcy levels from V1 to V3, once individuals had achieved 'adequate' GH replacement, was no longer significantly different (p=0.090). When separated by gender, at 6 months (V3) there was a small, but significant increase in Hcy in men (p=0.028), but not in women (p=0.58). There was no significant change in B12, folate, free T4 or creatinine levels. Univariate analysis revealed that only B12 and folate showed significant negative relationships with Hcy (B12: parameter= -0.013, p<0.001; folate: parameter=-1.31, p<0.001), but not between Hcy and IGF-1 (p=0.18). In a multiple variable model, both B12 and folate remained significantly negatively associated with plasma total homocysteine (p=0.018; p<0.001, respectively). In this observational study normalisation of IGF-1 levels in adult subjects with growth hormone deficiency was not associated with a fall in total homocysteine. Before firm conclusions can be drawn about the contribution of changes in plasma homocysteine concentrations to cardiovascular prognosis in adult GHD patients receiving GH replacement, further controlled studies are required.
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Homocisteína/sangre , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Adulto , Creatinina/sangre , Femenino , Ácido Fólico/sangre , Humanos , Ensayo Inmunorradiométrico , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Modelos Lineales , Estudios Longitudinales , Masculino , Tiroxina/sangre , Vitamina B 12/sangreRESUMEN
Nickel is a toxic and carcinogenic environmental and occupational pollutant and quercetin is a dietary flavonoid that is reported to modulate effects of many mutagens and carcinogens. We investigated the ability of nickel chloride to induce DNA damage in human colonic mucosa cells in the presence of quercetin, using the alkaline comet assay. Nickel chloride (5-250 micromol/L) evoked dose-dependent DNA damage and quercetin at 50 micromol/L decreased the extent of this damage. The cells exposed to nickel chloride progressively removed their DNA damage and the presence of 50 micromol/L quercetin in the repair-incubation medium did not affect the repair kinetics. Cells exposed to nickel and treated with endonuclease III, an enzyme recognizing oxidized bases, displayed a greater extent of DNA damage than those not treated with the enzyme. Quercetin did not exert a significant effect on the production of oxidized bases by nickel. Pretreatment of the cells with a nitrone spin trap, N-tert-butyl-alpha-phenylnitrone, decreased the extent of DNA damage evoked by nickel. Quercetin caused a further decrease in the extent of the damage in the presence of the trap. The results obtained suggest that reactive oxygen species, including free radicals, might be involved in the formation of DNA lesions induced by nickel chloride in colonic mucosa cells and that quercetin may exert protective effects in these cells.
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Colon/efectos de los fármacos , Daño del ADN , Depuradores de Radicales Libres/farmacología , Radicales Libres , Mucosa Intestinal/efectos de los fármacos , Níquel/toxicidad , Quercetina/farmacología , Línea Celular , Supervivencia Celular , Ensayo Cometa , Óxidos N-Cíclicos , Reparación del ADN , Relación Dosis-Respuesta a Droga , Humanos , Cinética , Modelos Químicos , Níquel/farmacología , Óxidos de Nitrógeno/farmacología , Oxígeno/metabolismo , Factores de TiempoRESUMEN
The effects of natural compounds, vitamin C and quercetin, present in fruits and vegetables, on the DNA damaging activity of a food carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined using the comet assay. Vitamin C, at a concentration of 50 microM, inhibited MNNG-induced DNA damage in human lymphocytes. Quercetin, up to a concentration of 10 microM, increased the extent of DNA damage, but at concentrations above 10 microM decreased damage below control values. Furthermore, quercetin had a strong antioxidant activity against oxidative damage evoked by H2O2 at 10 microM. The results obtained suggest that vitamin C and quercetin may have anti- or pro-oxidative properties depending on the state of the cell.
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Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Daño del ADN/efectos de los fármacos , Metilnitronitrosoguanidina/farmacología , Quercetina/farmacología , Adulto , Cobre/farmacología , Frutas/química , Humanos , Peróxido de Hidrógeno/farmacología , Linfocitos/química , Verduras/químicaRESUMEN
INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is a well-established method in diagnosis and management of biliary and pancreatic diseases. The procedure carries the risk of serious complications; the most common is pancreatitis. The severity of ERCP-related pancreatitis largely depends on the inflammatory response to the procedure. AIMS: The aim of our study was to evaluate the inflammatory response after diagnostic and therapeutic ERCP based on monitoring of plasma concentration of the following substances: amylase, lipase, white blood cells, interleukin 6 (IL-6), C-reactive protein (CRP), hydrogen peroxide, malonylodialdehyde (MDA), and conjugated dienes (CD). METHODOLOGY: The study was performed on 40 patients who were divided into two groups according to the procedure performed: Group1-28 patients after ERCP with endoscopic sphincterotomy (ES) and Group 2-12 patients after diagnostic ERCP. The parameters were measured before ERCP and 2, 24, and 48 hours after the procedure. RESULTS: After diagnostic and therapeutic ERCP, the increase in plasma concentration of amylase, lipase, IL-6, and CRP were observed. Acute pancreatitis developed in three of the patients from group 1. The increase in lipase and CRP concentration was significantly higher after therapeutic ERCP with ES than after the diagnostic procedure. Asymptomatic hyperamylasemia and hyperlipasemia occurred more often after therapeutic than diagnostic ERCP. A positive correlation between the increase of IL-6 and CRP concentration was found. After uncomplicated diagnostic or therapeutic ERCP, no increase of reactive oxygen species and lipid peroxidation products was observed. CONCLUSION: Diagnostic ERCP stimulates a systemic inflammatory response, the intensity of which is magnified after ES. After uncomplicated ERCP, the balance between oxidative and anti-oxidative mechanisms is retained.
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Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Pancreatitis/etiología , Adulto , Amilasas/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Peróxido de Hidrógeno/sangre , Interleucina-6/sangre , Recuento de Leucocitos , Lipasa/sangre , Peroxidación de Lípido , Masculino , Malondialdehído/sangre , Especies Reactivas de Oxígeno/metabolismoRESUMEN
A reversed-phase high-performance liquid chromatographic method for the determination of free and total cysteine in urine is described. The method involves reductive conversion of cysteine dimer and cysteine mixed disulphides to their reduced counterpart with the use of tri-n-butylphosphine, ultraviolet-labeling with 2-chloro-1-methylquinolinium tetrafluoroborate, and liquid chromatographic separation with isocratic conditions. In developing this method the following parameters were investigated and optimized: the time, pH and reagent excess in the derivatization step, and mobile phase buffer concentration, pH, organic modifier and column temperature in the separation step. The method provides quantitative information on free and total cysteine based on assays with derivatization before and after reduction with tri-n-butylphosphine. The calibration graph, obtained with the use of normal urine spiked with growing amounts of cystine, was linear over the concentration range covering most experimental and clinical cases. The assay has a low pmol detection and quantitation limits, low imprecision and high recovery. The method was validated for urine samples received from several donors. Cystine was chosen as a primary calibrator for these assays.
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Cisteína/orina , Quinolinas/química , Tampones (Química) , Calibración , Cromatografía Líquida de Alta Presión , Cisteína/química , Humanos , Concentración de Iones de Hidrógeno , Estándares de Referencia , Sensibilidad y Especificidad , Espectrofotometría UltravioletaRESUMEN
A large proportion, from 30% to 50%, of diabetic patients frequently manifests loss of the normal diurnal variation of blood pressure, i.e. their blood pressure does not show at least 10% fall at night (non-dippers). It has been demonstrated that non-dippers are at increased risk of end-organ damage, in particular, renal and cardiovascular complications. As no reliable means of reversing impaired blood pressure variation has been established so far, we aimed at assessing the effect of a long-acting angiotensin-converting enzyme (ACE) inhibitor trandolapril on the disturbed circadian blood pressure rhythm in diabetics without hypertension or nephropathy. A total of 18 type 1 diabetes patients (8 male, 10 female), aged 33.5+/-4.8, with duration of diabetes 5.8+/-2.8 years and HbA(1c) 6.6+/-0.4% (range 5.8--7.1%) were enrolled into the study. Ten well-matched type 1 diabetes patients served as an untreated control group. Twenty-four-hour ambulatory blood pressure measurements (ABPM) were performed thrice in each subject: before trandolapril, 2 mg once daily in the morning, was started; after the first dose of the drug; and after 2 weeks of the treatment. Mean (+/-S.D.) values of systolic, diastolic blood pressure, night fall in systolic, and diastolic blood pressure in the treatment group were (1) at baseline: 124.0+/-5.8 mm Hg, 89.3+/-4.2 mm Hg, 3.0+/-2.2%, 5.1+/-3.8%; (2) after the first dose: 116.1+/-7.6 mm Hg (P<.01 vs. baseline), 82.6+/-6.7 mm Hg (P<.01 vs. baseline), 4.2+/-2.6%, 4.7+/-2.5%; and (3) after 14-day treatment: 116.6+/-8.1 mm Hg (P<.01 vs. baseline), 76.9+/-9.6 mm Hg (P<.01 vs. baseline), 17.6+/-6.9% (P<.01 vs. baseline and after 24-h values), 19.4+/-8.0% (P<.01 vs. baseline and after 24-h values), respectively. ABPM results for the untreated controls were similar in all three measurements. In conclusion, within 14 days of trandolapril treatment, circadian blood pressure variation was successfully restored in normoalbuminuric normotensive insulin-dependent diabetic patients.
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Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Ritmo Circadiano , Diabetes Mellitus Tipo 1/fisiopatología , Indoles/uso terapéutico , Adulto , Albuminuria , Monitoreo Ambulatorio de la Presión Arterial , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diástole/efectos de los fármacos , Femenino , Humanos , Masculino , Sístole/efectos de los fármacosRESUMEN
AIMS: To compare the new fasting with the 2-h post glucose challenge diagnostic criteria for diabetes mellitus in a high-risk Central European population. METHODS: The results of the 75-g oral glucose tolerance tests (OGTT) performed between 1st January 1990 and 31st December 1998 in patients at high risk of glucose metabolism disturbance were analysed. RESULTS: From 1554 patients with OGTT results available for the study, 1360 (759 women and 601 men, aged 65.5+/-6.9 years, body mass index 28.2 +/- 4.5 kg/m2) were included into the study. With the use of the post-challenge criteria, 41.3% of the analysed population had diabetes or impaired diabetes tolerance (IGT), whereas with the new fasting system only 16.6% would have been diagnosed with any type of glucose intolerance. Diabetes was significantly more often diagnosed with the post-challenge criteria than with the fasting ones: 16.2 vs. 5.3% (P < 0.0001). The subjects with diabetes diagnosed upon fasting glucose value were significantly younger than the subjects with diabetes diagnosed according to the 2-h glucose challenge: 65.7 +/- 6.2 vs. 68.8 +/- 7.0 years, respectively (P < 0.01). The sensitivity of the new criteria for the diagnosis of diabetes was 18.2%, and specificity 97.2%. A total of 77.8% of IGT cases would have been diagnosed as having normal glucose metabolism according to the fasting glucose. The sensitivity of the new criteria for the diagnosis of impaired glucose tolerance (IGT or impaired fasting glucose) was 14.6%, and specificity 89.8%. The overall kappa statistic (k) was low; 0.211 (95% confidence interval 0.149-0.27). CONCLUSIONS: The new lower fasting criteria might be too insensitive to identify a large proportion of individuals with diabetes or impaired glucose intolerance, particularly in a high-risk population.
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Glucemia/análisis , Diabetes Mellitus/diagnóstico , Intolerancia a la Glucosa/diagnóstico , Prueba de Tolerancia a la Glucosa , Factores de Edad , Anciano , Glucemia/metabolismo , Intervalos de Confianza , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Ayuno , Femenino , Intolerancia a la Glucosa/sangre , Humanos , Masculino , Polonia , Prevalencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Abnormalities of glucose metabolism are a common feature of acromegaly. Overt diabetes mellitus develops in about 10-15% of patients. We present an unusual complication of acromegaly: a 37-year old man with a 2-year history of acromegaly developed diabetic ketoacidosis 3 weeks after transsphenoidal adenomectomy. No specific cause for this sudden metabolic derangement could be demonstrated. Insulin need was very high in the first days after the onset of ketoacidosis, but was considerably reduced after initiation of treatment with octreotide and after successful re-operation.
Asunto(s)
Acromegalia/complicaciones , Cetoacidosis Diabética/diagnóstico , Adulto , Glucemia/metabolismo , Cetoacidosis Diabética/tratamiento farmacológico , Cetoacidosis Diabética/etiología , Prueba de Tolerancia a la Glucosa , Hormona de Crecimiento Humana/sangre , Humanos , Insulina/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/análisis , Imagen por Resonancia Magnética , Masculino , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/cirugía , Factores de TiempoRESUMEN
Diabetes develops in more than half of the patients with chronic alcoholic pancreatitis (CAP), mostly due to increasing insulin deficiency. In this regard CAP-related diabetes (CAP-DM) is similar to the type 1 diabetes. Data on microvascular complications in CAP-DM are scarce. The aim of the study was the analysis of microvascular complications frequency in relation to metabolic control in comparison with type 1 diabetes mellitus. The study subjects were 50 patients divided into two groups: group 1-25 patients with CAP-DM (15 men, 10 women, mean age 44.6 +/- 8.4 yrs, duration of diabetes 3.7 +/- 2.1 yrs, body mass index (BMI) 22.4 +/- 2.9 kg/m2, duration of CAP 7.0 +/- 3.5 years), and group 2-25 well-matched type 1 diabetes patients (14 men, 11 women, mean age 42.3 +/- 7.6 yrs, duration of diabetes 4.1 +/- 2.8 yrs, BMI 24.0 +/- +/- 2.5 kg/m2). CAP was diagnosed on the basis of clinical examination, ultrasound and computed tomography scans, and in some cases upon the results of endoscopic retrograde pancreatography. Fasting plasma glucose, glycated hemoglobin (HbA1c), total serum cholesterol, triglycerides, urea and creatinine concentrations were measured. Fundoscopy was performed in all the subjects, in addition fluorescein examination was conducted in 15 and 18 patients from groups 1 as 2 respectively. Fasting plasma glucose, HbA1c level and insulin requirement were significantly lower in CAP-DM patients than in type 1 diabetes subjects (133 +/- 48 vs 174 +/- 59 mg/dl, p < 0.01; 8.3 +/- 2.0 vs 9.8 +/- 1.1%, p < 0.01; 36 +/- 15 vs 57 +/- 11 IU/day, p < 0.001 respectively). However, the prevalence of background retinopathy (group 1-13/25, group 2-11/25), and microalbuminuria (group 1-14/25, group 2-13/25) was similar in both groups. No statistically significant differences were found between CAP-DM and type 1 diabetic patients in regard to blood lipids, triglycerides, urea and creatinine concentrations. We conclude that microvascular complications may be encountered in pancreatic diabetes as often as in type 1 diabetes. Therefore this particular type of secondary diabetes should be regarded by no means as a "milder" type of the disease.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/etiología , Angiopatías Diabéticas/sangre , Neuropatías Diabéticas/sangre , Retinopatía Diabética/sangre , Insulina/deficiencia , Pancreatitis Alcohólica/sangre , Pancreatitis Alcohólica/complicaciones , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Recent epidemiologic studies show increasing "epidemic" of diabetes mellitus throughout the world. Reliable data on diabetes prevalence in Poland are scarce. Therefore Polish Ministry of Health initiated a programme aiming at gathering substantial amount of epidemiologic data on the prevalence of diabetes and other metabolic disorders. The aim of the present study was to evaluate the prevalence of diabetes, obesity and lipid disorders in a well-defined urban population aged 35 and over. The study subjects were 6000 randomly chosen inhabitants of the Central District of Lodz. All were invitated to participate in the study by mail. Every participant underwent full medical examination, with body mass index (BMI) calculation, and blood pressure as well as waist-to-hip ratio measurements. Serum total, LDL and HDL cholesterol and triglycerides were assessed. In non-diabetes subjects oral glucose tolerance test (75 g) (OGTT) according to WHO protocol was performed unless their fasting capillary blood glucose exceeded 8 mmol/l. In selected subjects serum samples were stored for future insulin and C-peptide assays. 2018 persons took part in the study (response rate 33.6%), including 1217 (60.3%) women and 801 men (39.7%), mean age 58.2 years. 179 (8.9%) persons claimed to have been diagnosed with diabetes previously (8.9%). OGTT was performed in 1574 subjects. Impaired glucose tolerance (IGT) was found in 342 (17.0%), and diabetes in 138 (6.8%) subjects. Total diabetes prevalence reached therefore 15.7%. Excessive body weight (BMI > or = 25 kg/m2) was noted in 806 (39.9%), and obesity (BMI > or = 30 kg/m2) in 626 (31.0%) persons. Total cholesterol > 5.2 mmol/l was observed in 1170 (58.0%), LDL-cholesterol > 3.5 mmol/l in 734 (36.4%), cholesterol HDL < 0.9 mmol/l in 953 (47.2%), and triglycerides > 1.7 mmol/l in 1392 osób (69.0%) subjects. In conclusion, high prevalence of known and unknown diabetes together with other metabolic disorders is strikingly high in adult urban population, which in all may require effective implementation of specific nationwide prevention programmes.