The aim of this thesis is to investigate different methods of improving the glycaemic control of diabetic out-patients, within the scope of the author's training both as a therapeutic dietitian and as a teacher. Evidence is presented from the literature, which indicates that high-carbohydrate, high-fibre diets are of benefit in diabetes, that supplements of viscous fibre improve glycaemic control, and that education of the diabetic patient may help to achieve good diabetic control, provided that the patient also complies with all parameters of therapy. Three main studies have been undertaken: - (1) An educational project, to investigate the effect of a mass-education programme on compliance and control in diabetic out-patients. (2) An investigation of the effect of long-term high-fibre diets in diabetic out-patients. (3) A study of the use of guar gum in the diabetic diet. In Study 1, a large random sample of patients attending a diabetes outpatient clinic were tested by means of a detailed questionnaire, in order to assess their existing knowledge of the disease. A suitable education programme was then devised and patients were exposed to this in the clinic situation. Another sample of patients was then re-tested with the same questionnaire and statistical analysis was used to assess the effect of this programme on knowledge, compliance and control. Results indicate that, while patients' knowledge scores improved, there was no improvement in dietary compliance and also no significant change in the standard of diabetic control in the clinic population. In Study 2 we investigated the practical aspects of administering a high-fibre diet to diabetic out-patients in Cape Town, in the light of the reported benefits of diets containing large amounts of dietary fibre (OF) in the control of diabetes. Readily-available, low-cost foodstuffs with a high OF content, were incorporated into suitable, individualised high-fibre meal plans for 10 selected diabetic out-patients. Patients were closely monitored over a period of 9 months, for 3 months of which the high-fibre diet was prescribed. Various parameters of glycaemic control were recorded and analysed, and the patients' compliance to the new regimen was assessed. Only 3 patients approached the projected fibre intake, but significant negative correlations were found between the dietary fibre increments and both mean plasma glucose and mean serum triglyceride changes. These findings suggest that, were it not for poor dietary compliance, a high-fibre diet might result in significant improvement in diabetic control, and that education and motivation are of prime importance when making major changes to patients' eating habits. Study 3 investigates the use of guar gum, when incorporated into the diabetic diet in both short- and medium-term studies. This viscous fibre has been shown by workers overseas to be effective in lowering postprandial glycaemia. In this study a palatable vehicle for the gum, a digestive-type biscuit, was tested for its effect on glycaemic control when incorporated into the usual meal plans of diabetic out-patients, and also against an oral glucose load as a reference standard. It was found to be effective in reducing the post-prandial rise in blood glucose, and in improving glycaemic control, as shown by reduced fasting blood glucose values and decreased 24-hour urinary glucose excretion. The biscuit proved to be palatable and acceptable to patients, and the guar gum was effective in much smaller quantities than have previously been tested. It may therefore prove a valuable adjunct to diabetes therapy. Results of these studies indicate that compliance to therapeutic recommendations is the crux of achieving good diabetic control. Increased diabetic knowledge alone does not lead to improved diabetic control, and compliance to altered eating habits is difficult to achieve unless prior education and motivation has taken place. The simplest means of achieving better glycaemic control of diabetes appears to be the use of a supplement of viscous fibre, which will improve the glycaemic response to the patients' usual meals.

Zhou, Yu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 89-107). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

by Li Chi Yeung. / Thesis submitted in: November 2004. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 151-176). / Abstracts in English and Chinese. / Thesis Committee --- p.i / Acknowledgement --- p.ii / Abstract (English Version) --- p.iii / Abstract (Chinese Version) --- p.v / Content Page --- p.vii / List of Tables --- p.xiii / List of Figures --- p.xv / Abbreviation --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Diabetes Mellitus --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.1 / Chapter 1.1.2 --- Economic Impact --- p.3 / Chapter 1.2 --- "Digestion, Absorption and Metabolism of Carbohydrates" --- p.4 / Chapter 1.2.1 --- Carbohydrate Digestion --- p.4 / Chapter 1.2.2 --- Carbohydrate Absorption --- p.6 / Chapter 1.2.3 --- Insulin Secretion --- p.6 / Chapter 1.3 --- Pathophysiology of Diabetes Mellitus --- p.7 / Chapter 1.3.1 --- Insulin-Dependent Diabetes Mellitus (lDDM) --- p.7 / Chapter 1.3.1.1 --- Genetics --- p.8 / Chapter 1.3.1.2 --- Autoimmunity --- p.9 / Chapter 1.3.2 --- Non-Insulin-Dependent Diabetes Mellitus (NlDDM) --- p.11 / Chapter 1.3.2.1 --- Insulin Resistance --- p.11 / Chapter 1.3.2.2 --- Impaired Insulin Secretion --- p.14 / Chapter 1.4 --- Management of Diabetes Mellitus --- p.15 / Chapter 1.4.1 --- Sulfonylureas --- p.15 / Chapter 1.4.2 --- Biguanides --- p.16 / Chapter 1.4.3 --- Problems Encountered in the Management of Diabetes --- p.16 / Chapter 1.4.4 --- Role of Dietary Fiber in the Management of Diabetes Mellitus --- p.18 / Chapter 1.4.4.1 --- Dietary Fiber and Gastric Emptying Time --- p.19 / Chapter 1.4.4.2 --- Dietary Fiber and Glucose Absorption in Small Intestine --- p.20 / Chapter 1.4.5 --- Other Natural Products used for Diabetes Treatment…… --- p.22 / Chapter 1.5 --- Mushrooms --- p.22 / Chapter 1.5.1 --- The Definition of Mushrooms --- p.23 / Chapter 1.5.2 --- Nutritional Values of Mushrooms --- p.24 / Chapter 1.5.3 --- Production of Mushrooms --- p.25 / Chapter 1.6 --- Medicinal (Antidiabetic) Properties of Mushrooms --- p.28 / Chapter 1.6.1 --- Ganoderma lucidum --- p.29 / Chapter 1.6.2 --- Tremella aurantia --- p.33 / Chapter 1.6.3 --- Auricularia auricula --- p.36 / Chapter 1.6.4 --- Grifola frondosa --- p.37 / Chapter 1.7 --- Medicinal Uses of Hericium erinaceus --- p.39 / Chapter 1.7.1 --- HeLa Cell Proliferation Inhibitors --- p.39 / Chapter 1.7.2 --- Induction of Growth of Nerve Cells --- p.42 / Chapter 1.7.3 --- Antitumour Activity --- p.42 / Chapter 1.7.4 --- Antidiabetic Effect --- p.43 / Chapter 1.8 --- Objectives --- p.45 / Chapter Chapter 2 --- Materials and Methods --- p.46 / Chapter 2.1 --- Extraction of Polysaccharides from the Fruiting Body of H. erinaceus --- p.46 / Chapter 2.1.1 --- Small-scale Extraction --- p.46 / Chapter 2.1.2 --- Large-scale Extraction --- p.47 / Chapter 2.2 --- Physico-Chemical Characterization of HE-polysaccharides --- p.52 / Chapter 2.2.1 --- Carbohydrate Content: Phenol-Sulfuric Acid Method --- p.52 / Chapter 2.2.2 --- Protein Content: Lowry Assay --- p.52 / Chapter 2.2.3 --- Uronic Acid Content --- p.53 / Chapter 2.2.4 --- Molecular Weight Determination by High Pressure Liquid Chromatography (HPLC) --- p.55 / Chapter 2.2.5 --- Determination of Monosaccharide Composition of Non-Starch Polysaccharides by Gas Chromatography (GC) --- p.56 / Chapter 2.2.5.1 --- Acid Depolymerisation --- p.56 / Chapter 2.2.5.2 --- Neutral Sugar Derivatisation --- p.56 / Chapter 2.2.5.3 --- Determination of Neutral Sugar Composition by Gas Chromatography (GC) --- p.57 / Chapter 2.2.6 --- Structural Study of Polysaccharides by Methylation --- p.59 / Chapter 2.2.6.1 --- Preparation of dry Dimethyl Sulfoxide (DMSO) --- p.59 / Chapter 2.2.6.2 --- Preparation of Methylsulfinyl Methyl Sodium (CH3SOCH2-Na+) from the dry DMSO and Sodium Hydride --- p.59 / Chapter 2.2.6.3 --- Methylation Procedure --- p.60 / Chapter 2.2.6.4 --- Preparation of Partially Methylated Alditol Acetates (PMAAs) --- p.61 / Chapter 2.2.6.5 --- Analysis of the PMAAs by GC --- p.62 / Chapter 2.2.7 --- The Measurement of Viscosity --- p.62 / Chapter 2.3 --- In vitro Hypoglycemic Tests of HE-Polysaccharides --- p.64 / Chapter 2.3.1 --- Glucose Dialysis Retardation Index (GDRl) --- p.64 / Chapter 2.3.1.1 --- Experimental Setup --- p.64 / Chapter 2.3.1.2 --- Measurement of Glucose in the Dialysate --- p.65 / Chapter 2.3.2 --- Inhibition of Amylolysis --- p.66 / Chapter 2.3.2.1 --- Experimental Setup --- p.66 / Chapter 2.3.2.2 --- Measurement of Maltose in the Dialysate --- p.66 / Chapter 2.4 --- In vivo Hypoglycemic Evaluation of HE-Polysaccharides --- p.67 / Chapter 2.4.1 --- Oral Glucose Tolerance Test (OGTT) --- p.67 / Chapter 2.4.2 --- Induction of Type l Diabetes in Normal BALB/c Mice --- p.69 / Chapter 2.4.2.1 --- lnduction Protocol --- p.69 / Chapter 2.4.2.2 --- Measurement of Plasma Glucose Level --- p.70 / Chapter 2.4.3 --- Hypoglycemic Test on Normal and Diabetic BALB/c Mice --- p.71 / Chapter 2.4.4 --- Measurement of Insulin Level by Enzyme-Linked Immunoadsorbent Assay (ELlSA) --- p.72 / Chapter 2.4.4.1 --- Plasma Samples used in ELlSA --- p.72 / Chapter 2.4.4.2 --- Assay Procedure --- p.73 / Chapter 2.5 --- Statistical Evaluation --- p.74 / Chapter Chapter 3 --- Results and Discussion --- p.75 / Chapter 3.1 --- Yield of Polysaccharides extracted from H. erinaceus --- p.75 / Chapter 3.2 --- Physico-chemical Properties of HE Polysaccharides --- p.79 / Chapter 3.2.1 --- "Carbohydrate, Protein and Uronic Acid Content" --- p.79 / Chapter 3.2.2 --- Monosaccharide Compositions --- p.83 / Chapter 3.2.3 --- Molecular Weight of the HE polysaccharides --- p.85 / Chapter 3.2.4 --- Structure of HE polysaccharides --- p.90 / Chapter 3.2.5 --- Conclusion for the Physico-chemical Properties of HE-Polysaccharides --- p.96 / Chapter 3.2.6 --- Viscosity of HE Polysaccharides --- p.99 / Chapter 3.3 --- In vitro Study of the Hypoglycemic Effect of HE-Polysaccharides --- p.101 / Chapter 3.3.1 --- Glucose Dialysis Retardation Index (GDRl) --- p.101 / Chapter 3.3.2 --- Inhibition of α-Amylase Activity --- p.105 / Chapter 3.4 --- In vivo Hypoglycemic Evaluation of HE-Polysaccharides --- p.109 / Chapter 3.4.1 --- In vivo Oral Glucose Tolerance Test (OGTT) in Normal Mice --- p.109 / Chapter 3.4.1.1 --- Oral Glucose Tolerance Test --- p.109 / Chapter 3.4.1.2 --- Effect of Change of Viscosity of HE Polysaccharide in the Gl Tract of Mice --- p.114 / Chapter 3.4.2 --- Establishment of a Diabetic Murine Model --- p.120 / Chapter 3.4.3 --- Hypoglycemic Activity of HE-polysaccharides in Normal Mice --- p.123 / Chapter 3.4.4 --- Hypoglycemic Activity of HE-polysaccharides in Diabetic Mice --- p.126 / Chapter 3.4.5 --- Change of Plasma Insulin Level in the Hypoglycemic Test --- p.132 / Chapter 3.4.6 --- Comparison of Hypoglycemic Activity of HE-Polysaccharides in Normal and Diabetic mice --- p.139 / Chapter 3.4.6.1 --- Severity of Diabetic Conditions lnduced --- p.139 / Chapter 3.4.6.2 --- Change in Insulin Secretion --- p.140 / Chapter 3.4.6.3 --- Glucose Transporter --- p.140 / Chapter 3.5 --- Other Factors that Affect in vivo Hypoglycemic Activity of the HE-polysaccharides --- p.141 / Chapter 3.5.1 --- Route of Administration: Oral Feeding and Intraperitoneal Injection --- p.141 / Chapter 3.5.2 --- Molecular Mechanisms of Hypoglycemic Activity --- p.142 / Chapter 3.5.3 --- Glucose Toxicity --- p.144 / Chapter 3.5.3.1 --- Insulin Resistance --- p.144 / Chapter 3.5.3.2 --- Impaired Insulin Secretion --- p.145 / Chapter Chapter 4 --- Conclusions and Future Works --- p.147 / References --- p.151

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2016-11-29T11:27:04Z No. of bitstreams: 1 Maurício Aguiar de Paula.pdf: 1738364 bytes, checksum: 310f918b6425fcb252dd0eefbda88d2c (MD5) / Made available in DSpace on 2016-11-29T11:27:04Z (GMT). No. of bitstreams: 1 Maurício Aguiar de Paula.pdf: 1738364 bytes, checksum: 310f918b6425fcb252dd0eefbda88d2c (MD5) Previous issue date: 2016-09-30 / Introduction: Diabetic retinopathy (DR), a frequent complication and one of the main preventable causes of blindness in Brazil and worldwide, it is asymptomatic in the early stages. The inappropriate metabolic and pressoric control is related to its onset and progression. Typically, diabetic patients seen in primary care of the Unified Health System (SUS) in Sorocaba and region are referred to the specialized service of ophthalmology (Ophthalmologic Hospital of Sorocaba - HOS) only when symptoms are already at an advanced stage of DR, which it requires ophthalmic intervention as laser or even surgery. For the accomplishment of these procedures is needed clinical setting that currently occurs in the primary care by generating counter-delay, low resolution and resulting social, economic and individual losses (even blindness). Objectives Create and offer multidisciplinary program of intensive clinical setting and diabetes education (DE) to patients with diabetic retinopathy (DR) treated at HOS; assess possible changes in the level of understanding and metabolic control of this population after attending the program; assess development in ophthalmologic table after the intervention referred to completion of the proposed procedures compared to similar people who did not undergo intervention; analyze the costs of treatment of DR forward the alternative of timely and intensive clinical setting, inserted in the specialized eye care process. Materials and Methods The program consisted of four individual medical care in consecutive weeks with support of groups of DE, with the aid of "Conversation Maps"™, in the first and third weeks. Therapeutic adjustments were based on clinical evaluation and structured blood glucose monitoring map analysis of seven measures of the three interleaved days preceding the next attendance. One group underwent clinical-educational intervention (n = 24) and another, control (n = 24) only assesseded the data obtained from medical records. Both had the same clinical characteristics. The intervention group was assessed before and after in terms of knowledge about DM, treatment adherence and attitudes in fighting the disease with appropriate questionnaires. It was compared the evolution of the ophthalmic conditions under the two groups on the achievement of specified procedures and costs involved in the activities of each clinical setting process: current (primary care) and proposed by the study. For economic analysis the activities of each clinical setting process were focused, defined its unit costs and compared alternatives through the cost-effective method. Results There were significant differences in the intervention group with improved of glycemic control, higher rate of accomplishment of scheduled procedures (96% vs. 48%; p = 0.00), lower performance time (1.2 month vs. 5 months) and better cost-effectiveness ratio. It proved to be a significant increase in knowledge about the disease, treatment adherence and improved attitude to the disease. Discussion Intensive clinical setting program with DE in support for patients with DR at an advanced stage offered in a specialized service as an alternative to currently practiced in primary care is more cost-effective, takes place in less time and can minimize personal losses, social and institutional arising from the development of DR related to inadequate clinical control / Introdução: A retinopatia diabética (RD), complicação frequente e uma das principais causas evitáveis de cegueira no Brasil e no mundo, é assintomática em estágios iniciais. O controle metabólico e pressórico inadequado está relacionado com sua instalação e progressão. Habitualmente, pacientes diabéticos atendidos na atenção primária em Sorocaba e região são encaminhados para o serviço especializado de oftalmologia (Hospital Oftalmológico de Sorocaba - HOS) apenas quando apresentam sintomas, já em estágio avançado da RD, o que exige intervenção oftalmológica, como o laser ou mesmo, cirurgia. Para a realização destes procedimentos há necessidade de ajuste clínico que, atualmente, ocorre na rede básica através de contrarreferência, gerando demora, baixa resolutividade e consequentes perdas sociais, econômicas e individuais (até cegueira). Objetivos Criar e oferecer programa multiprofissional de ajuste clínico intensivo e de educação em diabetes (ED) a pacientes com RD atendidos no HOS; avaliar possíveis mudanças no nível de entendimento e no controle metabólico desta população após a participação no programa; avaliar a evolução do quadro oftalmológico após a intervenção com relação a realização dos procedimentos propostos em comparação com população semelhante que não sofreu a intervenção; analisar os custos do tratamento da RD frente a alternativa de ajuste clínico oportuno e intensivo, inserido no processo de atendimento oftalmológico especializado. Material e Métodos O programa consistiu de quatro atendimentos médicos individuais em semanas consecutivas com suporte de ED, com auxílio de “Mapas de Conversação”™, na primeira e terceira semanas. Os ajustes terapêuticos basearam-se na avaliação clínica e análise da automonitorização glicêmica estruturada com sete medidas de três dias intercalados que antecediam o próximo atendimento. Um grupo sofreu intervenção clínico-educativa (n=24) e do outro, controle, (n=24) apenas avaliou-se os dados de prontuário. Ambos apresentavam as mesmas características clínicas. O grupo intervenção foi avaliado antes e após quanto ao conhecimento sobre DM, adesão ao tratamento e atitudes no enfrentamento da doença com questionários apropriados. Comparou-se a evolução do quadro oftalmológico nos dois grupos quanto à realização dos procedimentos indicados e custos envolvidos nas atividades de cada processo de ajuste clínico: o usual (da rede básica) e o proposto pelo estudo. Para a análise econômica foram mapeadas as atividades de cada processo de ajuste clínico, definidos seus custos unitários e comparadas as alternativas através do método de custoefetividade. Resultados Constatou-se diferença significante no grupo intervenção com melhora do controle glicêmico, maior taxa de realização de procedimentos agendados (96% vs 48%; p=0,00), menor tempo de realização (1,2 mês vs 5 meses) e melhor índice custo-efetividade. Comprovou-se incremento significante no conhecimento sobre a doença, adesão ao tratamento e na melhora da atitude frente à doença. Discussão Programa de ajuste clínico intensivo com suporte em ED para pacientes com RD em estágio avançado oferecido em serviço especializado como alternativa ao atualmente praticado na atenção primária tem melhor relação custo-efetividade, transcorre em menor tempo e pode minimizar as perdas pessoais, sociais e institucionais decorrentes da evolução da RD relacionada ao controle clínico inadequado

Chan, Yuet Wa. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 217-232). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

A polineuropatia é uma complicação freqüente do diabetes melito, sendo causa de alta morbidade entre pacientes diabéticos. Atualmente o tratamento da polineuropatia diabética consiste na prevenção, através do controle glicêmico, e no tratamento sintomático. O estresse oxidativo assume importante papel na patogenia da polineuropatia diabética, justificando-se o uso de anti-oxidantes no seu tratamento. O ácido tiótico é um co-fator essencial no metabolismo dos carboidratos com propriedades anti-oxidantes. O objetivo deste estudo foi avaliar a eficácia do uso de ácido tiótico para o tratamento da polineuropatia diabética em pacientes com diabetes melito tipo II, através de exame neurológico e estudo eletroneurográfico comparativo antes e após o uso da medicação. Foi realizado um estudo duplo-cego, cruzado, comparado com placebo, com duração de 24 meses, configurando-se a formação de quatro grupos de pacientes, os quais receberam: 1) placebo durante todo o estudo; 2) ácido tiótico durante todo o estudo; 3) ácido tiótico por um ano, e depois placebo; e 4) placebo por um ano, e ácido tiótico a seguir, por mais um ano. Foram incluídos doentes com glicemia entre 140 e 260 mg/dl, hemoglobina glicosilada menor ou igual a 10% e polineuropatia periférica diabética em graus leve e moderado. O protocolo constou da avaliação de sintomas neuropáticos, como dor, hipoestesia e parestesias; força muscular em segmentos distais dos membros inferiores; reflexos bicipital, patelar e aquileu bilateralmente, teste de sensibilidade dolorosa, tátil, e vibratória, e condução nervosa. As velocidades e amplitudes dos potenciais evocados foram obtidas através de estimulação bilateral dos seguintes nervos: condução motora dos nervos mediano e tibial posterior; condução sensitiva dos nervos mediano, ulnar e sural. Estas variáveis foram quantificadas segundo uma escala pré-estabelecida, diretamente proporcional à gravidade da neuropatia. O acompanhamento clínico foi realizado trimestralmente, com registro dos níveis glicêmicos e hemoglobina glicosilada. Os pacientes foram submetidos a avaliação neurofisiológica após 12 e 24 meses do início do estudo. De 43 doentes diabéticos incluídos aleatoriamente, 25 apresentavam polineuropatia periférica ao exame eletroneuromiográfico. Destes, 18 adequavam-se aos critérios de inclusão e exclusão. Cinco pacientes foram excluídos ao longo do estudo, sendo 4 por abandono do protocolo, e 1 por efeitos colaterais. O tratamento foi administrado por via oral a 13 pacientes, na dose de 600 mg/dia. A idade dos doentes variou entre 48 e 65 anos, sendo 5 do sexo feminino, e 8 do masculino. Não houve diferença significativa entre a média do controle glicêmico do grupo placebo e do grupo droga. Somente as variáveis exame neurológico e eletroneurográfico adequaram-se à distribuição normal. A análise univariada realizada com sintomas, exame neurológico e eletroneurográfico não demonstrou diferença estatisticamente significante entre os grupos, assumindo-se p>0,05. A análise de co-variância realizada com as variáveis exame neurológico e eletroneurografia demonstrou que o ácido tiótico foi capaz de influenciar favoravelmente a evolução da neuropatia nestes doentes. Não foram observados efeitos colaterais no grupo que fez uso de ácido tiótico / Polyneuropathy is a frequent complication of diabetes mellitus, being a major cause of morbidity among diabetic patients. Besides prevention through glicemic control, treatment of diabetic polyneuropathy is nowadays just symptomatic. Oxidative stress plays an important role in diabetic polyneuropathy pathogeny, justifying the use of antioxidant drugs in its treatment. Thioctic acid is an essential cofactor in carbohydrate metabolism with anti-oxidant properties. The aim of this study was to evaluate thioctic acid efficacy in the treatment of diabetic neuropathy in type II diabetes, through comparative neurological examination and electroneurographic studies before and after drug use. It was a double-blind, crossed, placebo-controlled study, lasting 24-months. Four groups were studied:1) placebo and placebo; 2) thioctic acid and thioctic acid; 3) thioctic acid and placebo, and 4) placebo and thioctic acid. Only patients with glicaemia between 140 and 260 mg/dl, glicosilated hemoglobin under 10% and mild or moderate diabetic peripheral polyneuropathy were included. The protocol consisted of evaluation of neuropathic symptoms, like pain, hipoesthesia and paresthesias; distal lower limbs muscle strength, bicipital, patelar and aquilean reflexes, examination of pain, tactile and vibratory sensibility, and nerve conduction studies. Nerve conduction velocities and amplitudes were obtained though bilateral stimulation of the following nerves: motor conduction of median and posterior tibial; sensitive conduction of median, ulnar and sural nerves. These variables were quantified according to a pre-established scale, directly proportional to neuropathy severity. Clinical follow-up was trimestral, with register of glicemic levels and glicosilated haemoglobin. Patients were submitted to neurophysiologic evaluation after 12 and 24 months. Of 43 diabetic patients randomly assigned, 25 presented peripheral polyneuropathy on electroneurography. 18 fit inclusion and exclusion criteria. Five patients were excluded throughout the study, 4 lost follow-up, and one for side effects. The treatment was administered orally to 13 patients, 600 mg daily. The age of these patients ranged from 48 to 65 years, being 5 female, and 8 male. There was no significant difference in glicaemic control between groups. Only neurological examination and electroneurography had normal distribution. Univariated analysis with symptoms, neurological examination, and electroneurography demonstrated there was no statistically significant difference between placebo and drug groups, assuming p>0,05. Co-variance analysis was done with neurological examination and electroneurography variables, showing that thioctic acid favourably influenced the neuropathy outcome of these patients. No adverse effects were observed in the thioctic acid group

A polineuropatia é uma complicação freqüente do diabetes melito, sendo causa de alta morbidade entre pacientes diabéticos. Atualmente o tratamento da polineuropatia diabética consiste na prevenção, através do controle glicêmico, e no tratamento sintomático. O estresse oxidativo assume importante papel na patogenia da polineuropatia diabética, justificando-se o uso de anti-oxidantes no seu tratamento. O ácido tiótico é um co-fator essencial no metabolismo dos carboidratos com propriedades anti-oxidantes. O objetivo deste estudo foi avaliar a eficácia do uso de ácido tiótico para o tratamento da polineuropatia diabética em pacientes com diabetes melito tipo II, através de exame neurológico e estudo eletroneurográfico comparativo antes e após o uso da medicação. Foi realizado um estudo duplo-cego, cruzado, comparado com placebo, com duração de 24 meses, configurando-se a formação de quatro grupos de pacientes, os quais receberam: 1) placebo durante todo o estudo; 2) ácido tiótico durante todo o estudo; 3) ácido tiótico por um ano, e depois placebo; e 4) placebo por um ano, e ácido tiótico a seguir, por mais um ano. Foram incluídos doentes com glicemia entre 140 e 260 mg/dl, hemoglobina glicosilada menor ou igual a 10% e polineuropatia periférica diabética em graus leve e moderado. O protocolo constou da avaliação de sintomas neuropáticos, como dor, hipoestesia e parestesias; força muscular em segmentos distais dos membros inferiores; reflexos bicipital, patelar e aquileu bilateralmente, teste de sensibilidade dolorosa, tátil, e vibratória, e condução nervosa. As velocidades e amplitudes dos potenciais evocados foram obtidas através de estimulação bilateral dos seguintes nervos: condução motora dos nervos mediano e tibial posterior; condução sensitiva dos nervos mediano, ulnar e sural. Estas variáveis foram quantificadas segundo uma escala pré-estabelecida, diretamente proporcional à gravidade da neuropatia. O acompanhamento clínico foi realizado trimestralmente, com registro dos níveis glicêmicos e hemoglobina glicosilada. Os pacientes foram submetidos a avaliação neurofisiológica após 12 e 24 meses do início do estudo. De 43 doentes diabéticos incluídos aleatoriamente, 25 apresentavam polineuropatia periférica ao exame eletroneuromiográfico. Destes, 18 adequavam-se aos critérios de inclusão e exclusão. Cinco pacientes foram excluídos ao longo do estudo, sendo 4 por abandono do protocolo, e 1 por efeitos colaterais. O tratamento foi administrado por via oral a 13 pacientes, na dose de 600 mg/dia. A idade dos doentes variou entre 48 e 65 anos, sendo 5 do sexo feminino, e 8 do masculino. Não houve diferença significativa entre a média do controle glicêmico do grupo placebo e do grupo droga. Somente as variáveis exame neurológico e eletroneurográfico adequaram-se à distribuição normal. A análise univariada realizada com sintomas, exame neurológico e eletroneurográfico não demonstrou diferença estatisticamente significante entre os grupos, assumindo-se p>0,05. A análise de co-variância realizada com as variáveis exame neurológico e eletroneurografia demonstrou que o ácido tiótico foi capaz de influenciar favoravelmente a evolução da neuropatia nestes doentes. Não foram observados efeitos colaterais no grupo que fez uso de ácido tiótico / Polyneuropathy is a frequent complication of diabetes mellitus, being a major cause of morbidity among diabetic patients. Besides prevention through glicemic control, treatment of diabetic polyneuropathy is nowadays just symptomatic. Oxidative stress plays an important role in diabetic polyneuropathy pathogeny, justifying the use of antioxidant drugs in its treatment. Thioctic acid is an essential cofactor in carbohydrate metabolism with anti-oxidant properties. The aim of this study was to evaluate thioctic acid efficacy in the treatment of diabetic neuropathy in type II diabetes, through comparative neurological examination and electroneurographic studies before and after drug use. It was a double-blind, crossed, placebo-controlled study, lasting 24-months. Four groups were studied:1) placebo and placebo; 2) thioctic acid and thioctic acid; 3) thioctic acid and placebo, and 4) placebo and thioctic acid. Only patients with glicaemia between 140 and 260 mg/dl, glicosilated hemoglobin under 10% and mild or moderate diabetic peripheral polyneuropathy were included. The protocol consisted of evaluation of neuropathic symptoms, like pain, hipoesthesia and paresthesias; distal lower limbs muscle strength, bicipital, patelar and aquilean reflexes, examination of pain, tactile and vibratory sensibility, and nerve conduction studies. Nerve conduction velocities and amplitudes were obtained though bilateral stimulation of the following nerves: motor conduction of median and posterior tibial; sensitive conduction of median, ulnar and sural nerves. These variables were quantified according to a pre-established scale, directly proportional to neuropathy severity. Clinical follow-up was trimestral, with register of glicemic levels and glicosilated haemoglobin. Patients were submitted to neurophysiologic evaluation after 12 and 24 months. Of 43 diabetic patients randomly assigned, 25 presented peripheral polyneuropathy on electroneurography. 18 fit inclusion and exclusion criteria. Five patients were excluded throughout the study, 4 lost follow-up, and one for side effects. The treatment was administered orally to 13 patients, 600 mg daily. The age of these patients ranged from 48 to 65 years, being 5 female, and 8 male. There was no significant difference in glicaemic control between groups. Only neurological examination and electroneurography had normal distribution. Univariated analysis with symptoms, neurological examination, and electroneurography demonstrated there was no statistically significant difference between placebo and drug groups, assuming p>0,05. Co-variance analysis was done with neurological examination and electroneurography variables, showing that thioctic acid favourably influenced the neuropathy outcome of these patients. No adverse effects were observed in the thioctic acid group

Introdução: O gene TCF7L2 (Transcription Factor 7-Like 2) codifica o fator de transcrição de mesmo nome que, tem importante papel na via Wnt de sinalização intra celular. A via Wnt é constituída por proteínas de integração e ligação dos processos de diferenciação e multiplicação celulares, interagindo com os fatores TCF, e ativando a expressão de genes relacionados ao TCF7L2, sendo este amplamente expresso em vários tecidos. Dados epidemiológicos atuais não deixam dúvidas quanto à forte associação de polimorfismos do gene TCF7L2 com o diabetes tipo 2 (DM2) em diferentes etnias. Apesar de serem pouco conhecidos os mecanismos que envolvem o gene TCF7L2 no DM2, tem sido bem demonstrada a associação do alelo T no rs7903146 com redução da secreção de insulina, redução do efeito das incretinas, principalmente do GLP-1, aumento na secreção de glucagon e a longo prazo, redução da meia vida da célula beta. Em vista destas evidências, aventamos a hipótese de que pacientes com DM2 portadores da variante rs7903146 do gene TCF7L2, ao ser tratados com GLP-1 mimético, poderiam responder de forma peculiar. Objetivos: Avaliar a resposta hormonal pancreática antes e após tratamento com GLP-1 mimético em indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2. Pacientes e Métodos: Foram genotipados162 indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2: idade (57,0 &#177; 7,6) anos, IMC (30,5 &#177; 5,1) kg/m2. Dessa amostra, 56 pacientes foram divididos em dois grupos conforme o genótipo, sendo 26 CC x 30 CT/TT, e a seguir tratados com Exenatide durante oito semanas. Os testes de refeição foram realizados antes e após o tratamento, para avaliação das concentrações plasmáticas de: Glicose (mg/dl), Insulina (&#956;U/dl), Pró-insulina (pmol/L), Peptideo-c (ng/ml); Glucagon (pg/ml) e GLP-1(pmol/L). Foram comparadas as áreas sob as curvas e os pontos das curvas durante o teste. Análise estatística por ANOVA com dois fatores e medidas repetidas, nível de significância maior que 5%. Resultados: A distribuição genotípica CC x CT x TT foi 41,4% x 47,5% x 11,1% respectivamente. A influência do alelo T na resposta pancreática durante o teste da refeição mostrou que as concentrações plasmáticas de insulina, pró-insulina e peptídeo-c foram maiores no grupo CT/TT do que no CC (p<0,05) mas, não houve diferença na secreção do glucagon, GLP-1 e na glicemia entre os grupos (NS).Com relação à influência do alelo T na resposta ao tratamento verificou-se que o grupo CT/TT apresentou maior redução da secreção de insulina (p<0,005), peptídeo-c (p<0,05) e pró-insulina (p<0,001) do que o grupo CC durante o teste da refeição após o tratamento. Observou-se diminuição da glicemia, do glucagon e do GLP-1 de forma semelhante em ambos os grupos. Além disso, houve diminuição semelhante do peso e da hemoglobina glicosilada em ambos os grupos. Discussão: Os resultados do presente estudo mostraram que a presença do alelo T em indivíduos com DM2 esteve associada à maior secreção de insulina, pró-insulina e peptídeo-c em relação aos não portadores, com semelhantes concentrações séricas de glucagon e glicose em resposta ao teste da refeição. Este dado demonstra que a função da célula &#946; dos portadores da variante rs7903146 apresenta características diferentes dos não portadores. Após o tratamento com Exenatide, os indivíduos com DM2 e genótipo CT/TT, apresentaram valores estatisticamente menores de insulina, pró-insulina e peptídeo-c do que o grupo CC. Os efeitos do GLP-1 na glicemia pós-prandial são atribuídos a mecanismos de supressão do glucagon, lentificação do esvaziamento gástrico e também a efeitos insulinotrópicos e decorrentes de aumento na sensibilidade periférica à insulina. Além disso, já foi demonstrado que o Exenatide aumenta a captação de glicose de forma insulino-independente em músculo esquelético, pelo estímulo dos transportadores de glicose. Portanto, acredita-se que as características da resposta observada após o tratamento nos portadores do alelo T correspondem ao efeito do Exenatide na célula &#946; melhorando o processamento da pró-insulina, peptídeo-c e insulina e ao aumento da captação periférica da glicose. Sugere-se que esse processo seja resultante da melhor interação com os receptores de GLP-1, tanto em fígado, músculo esquelético e pâncreas. Conclusões: Os dados sugerem que indivíduos com DM2 portadores do alelo T no rs7903146 do gene TCF7L2 apresentam mais benefícios do tratamento com Exenatide, pois a secreção de insulina, pró-insulina e peptídeo-c foram condizentes com maior qualidade na função de célula &#946; nesse grupo após o tratamento. Além disso, o presente estudo proporcionou adicionais evidências clínicas de que os problemas que associam o TCF7L2 ao DM2 estão relacionados à tolerância periférica a glicose. / Introduction:The TCF7L2 gene (Transcription Factor 7-Like 2) encodes the transcription factor of the same name that has an important role in the intracellular Wnt signaling. The Wnt pathway is composed of connecting and integrating proteins of cell proliferation and differentiation process by interacting with TCF factors, and activating the expression of genes related to TCF7L2, which is widely expressed in several tissues. Current epidemiological data leave no doubt as to the strong association of polymorphisms of the TCF7L2 gene with type 2 diabetes (T2DM) in different ethnic groups. Although they are poorly known mechanisms involving TCF7L2 gene in DM2 the association of the T allele of rs7903146 with reduced insulin secretion, reducing effect of incretins, mainly GLP-1, increase in glucagon secretion and long-term reduction in the half-life of the beta cell, have been well demonstrated. In view of this evidences, we hypothesized that patients with DM2 carriers of the variant rs7903146 of the TCF7L2 gene, being treated with GLP-1 mimetic, could respond in a peculiar way. Objectives: Evaluating the pancreatic hormone response before and after treatment with GLP-1 mimetic in individuals with T2DM carriers of rs7903146 variant of TCF7L2 gene. Patients and Methods: We genotyped 162 individuals with T2DM patients with the variant rs7903146 gene TCF7L2: age ( 57.0 &#177; 7.6 ) years old, BMI ( 30.5 &#177; 5.1 ) kg/m2. From this sample, 56 patients were divided into two groups according to the genotype, 26 x 30 CC CT / TT, and then treated with exenatide for eight weeks. Meal tests were conducted before and after treatment to evaluate plasma concentrations of: Glucose ( mg / dl) Insulin ( U / dL ) Proinsulin (pmol / L), C-peptide (ng / ml) , Glucagon (pg / ml) and GLP-1 (pmol / L). The areas under the curves and the points of the curves were compared during the test. Statistical analysis by ANOVA with two factors and repeated measures, significance level greater than 5%. Results: The genotype distribution CC x CT x TT was 41.4% vs. 47.5% vs. 11.1 % respectively. The influence of the T allele in the pancreatic response during the test meal showed that plasma insulin concentrations, pro-insulin and c-peptide were higher in the CT / TT than in CC (p <0.05) but no difference in the glucagon secretion, GLP-1 and glucose in both groups (NS). Regarding to the influence of the T allele in response to treatment has been found that the group CT / TT presented greater reduction in insulin secretion (p <0.005) c-peptide (p <0.05) and proinsulin (p <0.001) than in CC group during the test meal after treatment. There was a decrease in blood glucose, glucagon and GLP-1 similarly in both groups. In addition, there was a similar decrease in weight and glycosylated hemoglobin in both groups. Discussion: The results of this study showed that the presence of the T allele in individuals with T2DM was associated with higher insulin secretion, proinsulin and c-peptide compared to non-carriers, with similar serum concentrations of glucagon and glucose in response to the test meal. This data demonstrates that the function of &#946; cells of carriers of the variant rs7903146 shows different features from non-carriers. After treatment with Exenatide, individuals with T2DM and genotype CT / TT, showed statistically lower values of insulin, proinsulin and c-peptide than the CC group. The effects of GLP-1 on postprandial glycemia mechanisms are attributed to suppression of glucagon, retardation of gastric emptying and also the insulinotropic effects and resulting increase in peripheral sensitivity to insulina. In addition, it was demonstrated that the Exenatide increases glucose uptake independent of insulin in skeletal muscle, the stimulation of glucose transporters way. Therefore, it is believed that the characteristics of the response observed after treatment in patients with the T allele corresponds to the effect of Exenatide in &#946; cell improving the processing of proinsulin, insulin and c-peptide and increasing peripheral glucose uptake. It is suggested that this process is best resulting from the interaction with the GLP-1 receptor in both liver, skeletal muscle and pancreas. Conclusions: These data suggest that individuals with T2DM patients with T allele in rs7903146 of TCF7L2 presents more benefits of treatment with Exenatide, because the secretion of insulin, proinsulin and c-peptide were consistent with higher quality in &#946; cell function in that group after treatment. Moreover, this study provided further evidence that the clinical problems associated with T2DM and TCF7L2 are related to peripheral glucose tolerance.

Introdução: O gene TCF7L2 (Transcription Factor 7-Like 2) codifica o fator de transcrição de mesmo nome que, tem importante papel na via Wnt de sinalização intra celular. A via Wnt é constituída por proteínas de integração e ligação dos processos de diferenciação e multiplicação celulares, interagindo com os fatores TCF, e ativando a expressão de genes relacionados ao TCF7L2, sendo este amplamente expresso em vários tecidos. Dados epidemiológicos atuais não deixam dúvidas quanto à forte associação de polimorfismos do gene TCF7L2 com o diabetes tipo 2 (DM2) em diferentes etnias. Apesar de serem pouco conhecidos os mecanismos que envolvem o gene TCF7L2 no DM2, tem sido bem demonstrada a associação do alelo T no rs7903146 com redução da secreção de insulina, redução do efeito das incretinas, principalmente do GLP-1, aumento na secreção de glucagon e a longo prazo, redução da meia vida da célula beta. Em vista destas evidências, aventamos a hipótese de que pacientes com DM2 portadores da variante rs7903146 do gene TCF7L2, ao ser tratados com GLP-1 mimético, poderiam responder de forma peculiar. Objetivos: Avaliar a resposta hormonal pancreática antes e após tratamento com GLP-1 mimético em indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2. Pacientes e Métodos: Foram genotipados162 indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2: idade (57,0 &#177; 7,6) anos, IMC (30,5 &#177; 5,1) kg/m2. Dessa amostra, 56 pacientes foram divididos em dois grupos conforme o genótipo, sendo 26 CC x 30 CT/TT, e a seguir tratados com Exenatide durante oito semanas. Os testes de refeição foram realizados antes e após o tratamento, para avaliação das concentrações plasmáticas de: Glicose (mg/dl), Insulina (&#956;U/dl), Pró-insulina (pmol/L), Peptideo-c (ng/ml); Glucagon (pg/ml) e GLP-1(pmol/L). Foram comparadas as áreas sob as curvas e os pontos das curvas durante o teste. Análise estatística por ANOVA com dois fatores e medidas repetidas, nível de significância maior que 5%. Resultados: A distribuição genotípica CC x CT x TT foi 41,4% x 47,5% x 11,1% respectivamente. A influência do alelo T na resposta pancreática durante o teste da refeição mostrou que as concentrações plasmáticas de insulina, pró-insulina e peptídeo-c foram maiores no grupo CT/TT do que no CC (p<0,05) mas, não houve diferença na secreção do glucagon, GLP-1 e na glicemia entre os grupos (NS).Com relação à influência do alelo T na resposta ao tratamento verificou-se que o grupo CT/TT apresentou maior redução da secreção de insulina (p<0,005), peptídeo-c (p<0,05) e pró-insulina (p<0,001) do que o grupo CC durante o teste da refeição após o tratamento. Observou-se diminuição da glicemia, do glucagon e do GLP-1 de forma semelhante em ambos os grupos. Além disso, houve diminuição semelhante do peso e da hemoglobina glicosilada em ambos os grupos. Discussão: Os resultados do presente estudo mostraram que a presença do alelo T em indivíduos com DM2 esteve associada à maior secreção de insulina, pró-insulina e peptídeo-c em relação aos não portadores, com semelhantes concentrações séricas de glucagon e glicose em resposta ao teste da refeição. Este dado demonstra que a função da célula &#946; dos portadores da variante rs7903146 apresenta características diferentes dos não portadores. Após o tratamento com Exenatide, os indivíduos com DM2 e genótipo CT/TT, apresentaram valores estatisticamente menores de insulina, pró-insulina e peptídeo-c do que o grupo CC. Os efeitos do GLP-1 na glicemia pós-prandial são atribuídos a mecanismos de supressão do glucagon, lentificação do esvaziamento gástrico e também a efeitos insulinotrópicos e decorrentes de aumento na sensibilidade periférica à insulina. Além disso, já foi demonstrado que o Exenatide aumenta a captação de glicose de forma insulino-independente em músculo esquelético, pelo estímulo dos transportadores de glicose. Portanto, acredita-se que as características da resposta observada após o tratamento nos portadores do alelo T correspondem ao efeito do Exenatide na célula &#946; melhorando o processamento da pró-insulina, peptídeo-c e insulina e ao aumento da captação periférica da glicose. Sugere-se que esse processo seja resultante da melhor interação com os receptores de GLP-1, tanto em fígado, músculo esquelético e pâncreas. Conclusões: Os dados sugerem que indivíduos com DM2 portadores do alelo T no rs7903146 do gene TCF7L2 apresentam mais benefícios do tratamento com Exenatide, pois a secreção de insulina, pró-insulina e peptídeo-c foram condizentes com maior qualidade na função de célula &#946; nesse grupo após o tratamento. Além disso, o presente estudo proporcionou adicionais evidências clínicas de que os problemas que associam o TCF7L2 ao DM2 estão relacionados à tolerância periférica a glicose. / Introduction:The TCF7L2 gene (Transcription Factor 7-Like 2) encodes the transcription factor of the same name that has an important role in the intracellular Wnt signaling. The Wnt pathway is composed of connecting and integrating proteins of cell proliferation and differentiation process by interacting with TCF factors, and activating the expression of genes related to TCF7L2, which is widely expressed in several tissues. Current epidemiological data leave no doubt as to the strong association of polymorphisms of the TCF7L2 gene with type 2 diabetes (T2DM) in different ethnic groups. Although they are poorly known mechanisms involving TCF7L2 gene in DM2 the association of the T allele of rs7903146 with reduced insulin secretion, reducing effect of incretins, mainly GLP-1, increase in glucagon secretion and long-term reduction in the half-life of the beta cell, have been well demonstrated. In view of this evidences, we hypothesized that patients with DM2 carriers of the variant rs7903146 of the TCF7L2 gene, being treated with GLP-1 mimetic, could respond in a peculiar way. Objectives: Evaluating the pancreatic hormone response before and after treatment with GLP-1 mimetic in individuals with T2DM carriers of rs7903146 variant of TCF7L2 gene. Patients and Methods: We genotyped 162 individuals with T2DM patients with the variant rs7903146 gene TCF7L2: age ( 57.0 &#177; 7.6 ) years old, BMI ( 30.5 &#177; 5.1 ) kg/m2. From this sample, 56 patients were divided into two groups according to the genotype, 26 x 30 CC CT / TT, and then treated with exenatide for eight weeks. Meal tests were conducted before and after treatment to evaluate plasma concentrations of: Glucose ( mg / dl) Insulin ( U / dL ) Proinsulin (pmol / L), C-peptide (ng / ml) , Glucagon (pg / ml) and GLP-1 (pmol / L). The areas under the curves and the points of the curves were compared during the test. Statistical analysis by ANOVA with two factors and repeated measures, significance level greater than 5%. Results: The genotype distribution CC x CT x TT was 41.4% vs. 47.5% vs. 11.1 % respectively. The influence of the T allele in the pancreatic response during the test meal showed that plasma insulin concentrations, pro-insulin and c-peptide were higher in the CT / TT than in CC (p <0.05) but no difference in the glucagon secretion, GLP-1 and glucose in both groups (NS). Regarding to the influence of the T allele in response to treatment has been found that the group CT / TT presented greater reduction in insulin secretion (p <0.005) c-peptide (p <0.05) and proinsulin (p <0.001) than in CC group during the test meal after treatment. There was a decrease in blood glucose, glucagon and GLP-1 similarly in both groups. In addition, there was a similar decrease in weight and glycosylated hemoglobin in both groups. Discussion: The results of this study showed that the presence of the T allele in individuals with T2DM was associated with higher insulin secretion, proinsulin and c-peptide compared to non-carriers, with similar serum concentrations of glucagon and glucose in response to the test meal. This data demonstrates that the function of &#946; cells of carriers of the variant rs7903146 shows different features from non-carriers. After treatment with Exenatide, individuals with T2DM and genotype CT / TT, showed statistically lower values of insulin, proinsulin and c-peptide than the CC group. The effects of GLP-1 on postprandial glycemia mechanisms are attributed to suppression of glucagon, retardation of gastric emptying and also the insulinotropic effects and resulting increase in peripheral sensitivity to insulina. In addition, it was demonstrated that the Exenatide increases glucose uptake independent of insulin in skeletal muscle, the stimulation of glucose transporters way. Therefore, it is believed that the characteristics of the response observed after treatment in patients with the T allele corresponds to the effect of Exenatide in &#946; cell improving the processing of proinsulin, insulin and c-peptide and increasing peripheral glucose uptake. It is suggested that this process is best resulting from the interaction with the GLP-1 receptor in both liver, skeletal muscle and pancreas. Conclusions: These data suggest that individuals with T2DM patients with T allele in rs7903146 of TCF7L2 presents more benefits of treatment with Exenatide, because the secretion of insulin, proinsulin and c-peptide were consistent with higher quality in &#946; cell function in that group after treatment. Moreover, this study provided further evidence that the clinical problems associated with T2DM and TCF7L2 are related to peripheral glucose tolerance.