There is an ever growing demand for low cost biosensors in medical diagnostics. A well known commercially successful example is glucose biosensors which are used to diagonize and monitor diabetes. These biosensors use electrochemical analysis (electro analysis) as transduction mechanism. Electro analytical techniques involve application of electrical stimulus to the chemical/biochemical system under consideration and measurement of electrical response due to the oxidation and reduction reactions that occur because of the stimulus. They offer a lot of advantages in terms of sensitivity, selectivity, cost effectiveness and compatibility towards integration with electronics. Besides glucose, there are several biomolecules of significance for which electro analysis can potentially be used to develop low cost, rapid, easy to use biosensors. One such biomolecule is Glycated Hemoglobin (GHb). It is a post translational, non-enzymatic modification of hemoglobin with glucose and is a very good biomarker that indicates the average value of blood glucose over the past 120 days. It is always expresses as a percentage of total hemoglobin present in blood. Monitoring diabetes based on the value of percentage Glycated hemoglobin is advantageous as it gives an average value of glucose unlike plasma glucose values which vary a lot on a day to day basis depending on the dietary habits and the stress levels of the individual. This thesis is focused on the development of a low coat, easy to use, disposable sensor for measuring percentage Glycated hemoglobin. The first challenge in developing such a sensor is isolation of hemoglobin. Unlike glucose which is present in blood plasma (liquid content of blood), hemoglobin resides inside red blood cells also known as erythrocytes. O isolate hemoglobin, these cells have to be broken or lysed. All the existing approaches rely on mixing blood with lysing reagents to lyse erythrocytes. Ideal biosensors should be devoid of liquid reagents. Keeping this in perspective, in this thesis, this challenge is addressed by developing two entirely buffer/reagentless techniques to lyse erythrocytes and isolate hemoglobin. In the first technique, cellulose acetate membranes are embedded with lysing reagents and are used for lysing reagents and are used for lysing application. In the second techniques, commercially available nylon mesh nets are modified with lysing reagents to lyse and isolate hemoglobin. These membranes or mesh nets can be easily integrated on top of a disposable strip. After isolating hemoglobin, the next challenge is to selectively detect Glycated hemoglobin. Boronic acid conjugates are known to bind Glycated hemoglobin. Using this principle, a new composite is sysnthesized to specifically detect glc\ycated hemoglobin. The composite (GO-APBA) is a result of functionalization of Graphene Oxide (GO) with 3-aminophenylboronic acide (APBA). Detection of Glycated hemoglobin is achieved by modifying screen printed electrode strips with the synthesized compound, thus taking a step forwards achieving the objective. Since Glycated hemoglobin is always expressed as a percentage of hemoglobin, the next challenge is to detect total hemoglobin. In this thesis a low cost way of detecting hemoglobin is achieved by using GO modified or surfactant modified screen printed electrode strips. Furthermore, the potential interferences that blood plasma can cause in these measurements are eliminated with the help of permselective coatings. Thus using the technologies developed in this thesis, measurements of percentage Glycated hemoglobin can be potentially made on handheld electronic devices akin to glucose meters by using just a drop of blood.

nÃo hà / A diabetes à considerada um fator de risco significativo para a ocorrÃncia de doenÃas periodontais. Entretanto, à necessÃrio que estudos a respeito deste assunto seja realizado em diferentes populaÃÃes, com diferentes caracterÃsticas. O objetivo deste estudo transversal foi avaliar os parÃmetros clÃnicos periodontais de diabÃticos do tipo 2 com diferentes padrÃes de controle glicÃmico. Foram selecionados portadores desta doenÃa, de ambos os gÃneros, residentes na sede do municÃpio de Sobral - CearÃ. Estes deveriam ser nÃo-fumantes, com idade igual ou superior a 40 anos, possuir pelo menos 6 dentes na arcada dentÃria e fazer uso de medicaÃÃo hipoglicemiante. Os indivÃduos foram submetidos ao exame clÃnico periodontal: Ãndice de placa visÃvel (IP), sangramento gengival (IG), sangramento à sondagem (SS), profundidade de sondagem (PS) e recessÃo gengival (RG), realizado por um examinador previamente calibrado. Os indivÃduos foram divididos em trÃs grupos de acordo os nÃveis de hemoglobina glicada â Hb1Ac (Controlados - C: Hb1Ac ≤ 7%, n=103; Descontrolados - D: 7,1% ≤ Hb1Ac ≤ 9%, n= 60; Elevado Descontrole = E: Hb1Ac ≥ 9,1%, n=22). NÃo foram observadas diferenÃas significantes em relaÃÃo Ãs mÃdias de idade em anos, mÃdia de dentes presentes, IP, IG e SS. Verificou-se diferenÃa significante entre os grupos para as mÃdias de Hb1Ac e tempo de diagnÃstico da doenÃa. NÃo foi verificada associaÃÃo estatisticamente significante entre elevados nÃveis glicÃmicos e a maior presenÃa de dentes e de sÃtios periodontais com PS ≥ 6 mm. Entretanto quando foram analisados apenas os indivÃduos que apresentaram 20 ou mais dentes isso foi observado. Assim, pÃde-se concluir que o pobre controle glicÃmico dos diabÃticos do tipo 2, foi associado a maior presenÃa de periodontite apenas nos indivÃduos com elevado nÃmero de dentes. / Diabetes is a significant risk factor for the occurrence of periodontal diseases. Studying the relationship of both diseases in different populations with heterogeneous characteristics are still necessary to better understand them. The aim of this cross-sectional study was to evaluate the clinical periodontal parameters of type 2 diabetes patients with different levels of glycemic control. There were selected type 2 diabetics residing in the urban area of Sobral, Ceara. They must be non-smokers, aging 40 years or more and presenting at least and 6 teeth in their mouth. All had to be using any medication to control the glycemic level. Subjects were assigned to three groups based on their respective glycated hemoglobin levels - Hb1Ac (Control - C: Hb1Ac ≤ 7%, n=103; Moderate control - M: 7,1% ≤ Hb1Ac ≤ 9%, n= 60; Poor control = P: Hb1Ac ≥ 9,1%, n=22). The following clinical data were obtained from all patients: Plaque Index (PI), Gingival Index (GI), bleeding on probing (BOP), probing depth (PD) and gingival recession (GR). The mean age, number of teeth, PI, GI and BOP did not show any significance between groups. But this was observed for Hb1Ac mean levels and time of diabetes diagnosis. The presence of at least one periodontal site with PD ≥ 6 mm was considered for the diagnosis of periodontitis. There was no association between the increase of the glycemic level and the presence of periodontitis. However, data from patients presenting at least 20 teeth showed a significant association between periodontal diseases and higher glycemic levels. It can be concluded that the poor glycemic control was associated to the presence of periodontitis only in subjects with high number of teeth.

maria.cristina.rc2690@gmail.com / Article / Introduction: There is limited and controversial information regarding the potential impact of depression on glycemic control. This study aims to evaluate the association between depression and poor glycemic control. In addition, the prevalence of depression and rates of poor glycemic control were determined. Methods: Cross-sectional study performed in the endocrinology unit of two hospitals of ESSALUD in Peru. The outcome of interest was poor glycemic control, evaluated by glycated hemoglobin (HbA1c: < 7% versus ≥ 7%), whereas the exposure of interest was depression defined as 15 or more points in the Patient Health Questionnaire-9 tool. The association of interest was evaluated using Poisson regression models with robust standard errors reporting prevalence ratios (PR) and 95% confidence intervals (95% CI) adjusting for potential confounders. Results: A total of 277 participants, 184 (66.4%) males, mean age 59.0 (SD: 4.8), and 7.1 (SD: 6.8) years of disease were analyzed. Only 31 participants (11.2%; 95% CI: 7.5%–14.9%) had moderately severe or severe depression, whereas 70 (25.3%; 95% CI 20.3%–30.8%) had good glycemic control. Depression increased the probability of having poor glycemic control (PR = 1.32; 95% CI 1.15–1.51) after adjusting for several potential confounders. Conclusions: There is an association between depression and poor glycemic control among type 2 diabetes patients. Our results suggest that early detection of depression might be important to facilitate appropriate glycemic control and avoid further metabolic complications. / We would like to thank Dr Viviana Ulloa who helped us to access data and T2D patients, and Dr Percy Mayta- Tristan for revising initial versions of the manuscript. AB-O is supported by Wellcome Trust Research Training Fellowship in Public Health and Tropical Medicine (Grant number 103994/Z/14/Z). / Revisión por pares

nÃo hà / A pentoxifilina (PTX) à um inibidor nÃo-seletivo da fosfodiesterase, com aÃÃes antiinflamatÃrias vasculares e reolÃgicas que podem neutralizar algumas das mudanÃas no diabetes mellitus (DM) que contribuem para amenizar os seus efeitos secundÃrios como a neuropatia, a retinopatia e a nefropatia. Tendo em vista as propriedades antiinflamatÃrias da pentoxifilina e o envolvimento da inflamaÃÃo com o DM, buscou-se investigar seus possÃveis efeitos hipoglicemiante e hipolipemiante no modelo de DM induzido por aloxano em ratos. A pentoxifilina (PTX) em estudos pilotos apresentou efeito hipoglicemiante e reduziu os nÃveis de triglicerÃdeos em animais com diabetes induzidos por aloxano, nas doses 5, 25, 50 e 100 mg/Kg. A administraÃÃo oral da associaÃÃo de pentoxifilina (PTX) com glibenclamida (GLI), PTX5 + GLI2, causou reduÃÃes significativas nos nÃveis plasmÃticos de glicose e triglicerÃdeos em curto e longo prazo, evidenciando que o mecanismo de aÃÃo da PTX pode ser explicado via canais de K+ATP-dependentes. A administraÃÃo oral da associaÃÃo de Pentoxifilina (PTX) com Metformina (MET), PTX5 + MET5, ocasionou uma reduÃÃo da hiperglicemia apenas a longo prazo, sugerindo nÃo compartilharem o mesmo mecanismo. A PTX nÃo bloqueou a hiperglicemia induzida pelo Diazoxido (DZD), um antagonista da GLI, que inibe a secreÃÃo de insulina prolongando o tempo de abertura dos canais de K+ATP-dependentes, sugerindo que outros fatores, alÃm do bloqueio de canais de K+-ATP dependentes, podem estar envolvidos. A reduÃÃo nos valores de hemoglobina glicada (A1C) e de frutosamina mostraram que o tratamento com PTX50 e com a associaÃÃo PTX5+GLI2 melhorou o controle glicÃmico dos animais em estudo, indicando que esta droga pode inibir o desenvolvimento de lesÃes micro e macrovasculares advindas do DM. A PTX mostrou um marcante efeito antiinflamatÃrio, melhorando o estado geral dos ratos em experimentaÃÃo. Reduziu, de forma significativa, o edema de pata nas doses de 50 e 100 mg/Kg, todavia foi visto que o perfil inflamatÃrio no rato diabÃtico tem um padrÃo diferenciado do rato normal, evidenciando uma amplificaÃÃo do processo inflamatÃrio no rato diabÃtico quando comparado ao rato normal. Foi visto ainda que os nÃveis de TNF-&#8733; e IL-6 aumentaram de modo significante apÃs a induÃÃo do edema de pata nos ratos diabÃticos, entretanto nos ratos tratados com PTX os nÃveis teciduais destas citocinas mostraram-se significativamente mais baixos, o que fala a favor de uma evidente aÃÃo antiinflamatÃria da PTX. A PTX mostrou tambÃm um importante efeito antioxidante reduzindo, de forma significativa, as liberaÃÃes de nitrito tecidual e sÃrica, atuando favoravelmente na reduÃÃo de radicais livres. O tratamento prolongado com PTX foi eficaz em manter o padrÃo normal do pÃncreas, do fÃgado e dos rins nos grupos diabÃticos tratados com PTX50 e com PTX5+GLI2, indicando uma aÃÃo protetora da PTX contra a citotoxicidade induzida pelo aloxano. Os efeitos hipoglicemiante e hipotrigliceridÃmico da PTX, aqui demonstrados, podem està correlacionado com sua aÃÃo sobre o estresse oxidativo e sobre a low grade inflammation, o que torna a PTX um importante alvo terapÃutico para o manejo do diabetes mellitus na clÃnica / Pentoxifylline (PTX) is a non-selective inhibitor of phosphodiesterase with anti-inflammatory vascular and rheological properties. The drug can neutralize some of the changes seen in diabetes mellitus (DM), contributing to attenuate diabetes secondary complications as neuropathy, retinopathy and nephropathy. Considering PTX anti-inflammatory properties and the known involvement of inflammation with DM, we investigated its possible hypoglycemic and hypolipidemic effects in the model of alloxan-induced DM in rats. Pentoxifylline pilot studies in reduced plasma levels of glucose and triglycerides in animals with diabetes induced by alloxan at the doses of 5, 25, 50 and 100 mg/kg. Oral administration of the combination of PTX with glibenclamide (GLI), PTX5 + GLI2, caused significant reductions in plasma levels of glucose and triglycerides in the short and long term, indicating that the mechanism of action of PTX can be explained via K+ATP-dependent channels. The oral administration of the combination of pentoxifylline (PTX) with metformin (MET), PTX5+MET5, caused a reduction of only the long term hyperglycemia, suggesting that these two drugs do not share the same mechanism. PTX did not block the hyperglycemia induced by diazoxide (DZD), an antagonist of GLI, which inhibits insulin secretion by prolonging the opening time of the K+ATP-dependent-channel. This result suggests that other factors, in addition to the blockade of the K+ATP dependent channels, may be involved. The reduction in glycosylated hemoglobin (A1C), and fructosamine showed that treatment with the combination PTX5+GLI2 and PTX50, improved glycemia in the study, indicating that this drug can inhibit the development of macrovascular and microvascular injury resulting from DM. The PTX showed a marked anti-inflammatory effect, improving the general condition of rats subjected to acute inflammation models. PTX reduced significantly, the paw edema at doses of 50 and 100 mg / kg, However, the inflammatory profile in diabetic rats have a different pattern of that seen in non-diabetic rat, showing an amplification of the inflammatory process. We showed that the levels of TNF-&#945; and IL-6 were significantly increased after the induction of paw edema in diabetic rats, but in the rats treated with PTX tissue levels of these cytokines were significantly lower, which indicating a clear anti-inflammatory action of PTX. PTX also showed a significant antioxidant effect reducing significantly the release of tissue and serum nitrite, acting favorably in the reduction of free radicals. The prolonged treatment with PTX was effective in maintaining the normal histological pattern of the pancreas, liver and kidneys in diabetic groups treated with PTX50 PTX5 + and GLI2, indicating a protective effect of PTX against alloxan-induced cytotoxicity. The hypoglycemic and hypotriglyceridemic effects of PTX, shown here, may correlate with its effect on oxidative stress and on low grade inflammation, making PTX an important candidate for the management of diabetes mellitus in the clinic

Introdução: O exercício físico como parte do tratamento do diabetes mellitus gestacional (DMG) pode ajudar na manutenção das concentrações da glicemia de jejum. Objetivos: Conduzir uma revisão sistemática, com metanálise de ensaios clínicos randomizados, para avaliar o efeito do exercício supervisionado e estruturado ou o efeito do aconselhamento de atividade física, em mulheres com DMG, e comparar ao pré-natal usual para o controle da glicemia. Métodos: Os estudos elegíveis foram identificados a partir das bases de dados MEDLINE, EMBASE, Web of Science, Scopus e SportDiscus até 4 de Junho de 2015. Os dados foram extraídos de ensaios clínicos randomizados que compararam o pré-natal usual ao pré-natal usual somado ao exercício supervisionado e estruturado (pelo menos uma vez na semana) ou ao aconselhamento de atividade física, pelas quais os valores de glicemia de jejum pré e pós-intervenção estavam disponíveis. A metanálise de efeitos randômicos foi conduzida para a diferença entre as médias pós-intervenção da glicemia de jejum. Resultados: Foram encontradas 664 publicações, nas quais 82 foram avaliadas pela elegibilidade e oito foram incluídas na análise final. O efeito total do exercício nas concentrações absolutas da glicemia de jejum não foi significativamente diferente (P = 0,11) comparado ao pré-natal usual. Entretanto, o aconselhamento de atividade física comparado ao pré-natal usual demonstrou uma redução significativa nas concentrações da glicemia de jejum (diferença da média ponderada -3,88 mg/dL, 95% CI-7,33 a -0,42; I2, 48%; P para heterogeneidade < 0,15). Conclusão: O exercício supervisionado ou o aconselhamento de atividade física em mulheres com DMG não foi significativamente diferente comparado ao pré-natal usual nas concentrações de glicemia de jejum. Visto que o pré-natal usual inclui algum tipo de recomendação de atividade física, estes resultados não são surpreendentes. O aconselhamento de atividade física com o pré-natal usual inclui modificações da dieta que podem motivar as mulheres com DMG a serem mais ativas e aderentes ao aconselhamento nutricional, enquanto que o exercício estruturado pode ser mais difícil de atingir. / Background: Exercise as part of the treatment for gestational diabetes mellitus (GDM) may help maintain fasting glucose concentrations. Objective: A systematic review with meta-analysis was performed to evaluate the effect of weekly-supervised exercise or physical activity (PA) counseling in GDM women compared to standard care (SC) on glycemic control. Methods: Eligible trials were identified from MEDLINE, EMBASE, Web of Science, Scopus and SportDiscus up to 4 June 2015. Data were retrieved from randomized controlled trials comparing SC with SC plus weekly-supervised (at least once a week) prenatal exercise or PA counseling for which fasting blood glucose (FBG) values pre and post intervention were available. Random-effects meta-analysis was conducted for mean difference in FBG post exercise intervention. Results: Our search yielded 664 publications of which 82 were assessed for eligibility. Eight were analyzed and all were included in the meta-analysis. The overall effect of exercise on absolute FBG concentrations was not different (P=0.11) compared to SC. However, PA counseling versus SC showed a significant reduction in the absolute FBG concentrations (weighted mean difference -3.88 mg/dL, 95% CI-7.33 to -0.42; I2, 48%; P for heterogeneity<0.15). Conclusions: Supervised exercise or PA counseling in GDM women was not significantly different compared to SC on FBG concentrations. Since SC includes some type of PA recommendation, these results are not surprising. PA counseling with SC including dietary modifications may help motivate GDM women to be more active and adherent to nutrition advice, while structured exercise may be more difficult to achieve.

A Síndrome Metabólica (SM) é uma condição de prevalência crescente no mundo e existe pouca informação sobre o efeito do tratamento periodontal nos parâmetros metabólicos em pacientes com SM. O objetivo desta tese é comparar o efeito do tratamento periodontal nos níveis de hemoglobina glicada, glicose em jejum, triglicerídeos, colesterol HDL, colesterol total, insulina, resistência à insulina, função de células beta, proteína C reativa (PCR) e pressão arterial (PA) em pacientes com periodontite e SM em um período de 6 meses. Metodologia/ Desenho: Esta tese compreende uma análise parcial de um ensaio clínico randomizado com indivíduos com diagnóstico concomitante de periodontite _ ≥ 2 sítios interproximais com perda de inserção (PI) ≥4 mm ou ≥2 sítios interproximal com profundidade de sondagem (PS) ≥ 5mm em dentes não-adjacentes e não no mesmo dente e SM (Federação Internacional do Diabetes-2009). Setenta e dois indivíduos foram randomizados para grupo teste (tratamento periodontal imediato) ou controle (tratamento periodontal tardio-após 6 meses). Os pacientes receberam avaliação odontológica e realizaram exames sanguíneos nos tempos inicial, 3 e 6 meses, além de tratamento médico para hiperglicemia, dislipidemia e hipertensão quando necessário. O desfecho primário foi alteração na hemoglobina glicada e os desfechos secundários foram alterações na glicose, triglicerídeos, colesterol total e HDL, insulina, resistência à insulina, função de células beta, PCR e PA. A análise estatística foi realizada utilizando o modelo de Equações de Estimações Generalizadas (GEE: Generalized Estimating Equations). Resultados: Não houveram diferenças significativas nos parâmetros periodontais e metabólicos em ambos os grupos no exame inicial. Houve redução significativa de placa, sangramento marginal, fatores retentivos de placa, sangramento subgengival, média de PS e de PI no grupo teste. Não houve diferença significativa nos parâmetros metabólicos e na pressão arterial aos 3 e 6 meses comparando-se indivíduos que receberam tratamento periodontal ou não. Na análise intra-grupo, indivíduos do grupo controle reduziram os níveis de insulina e resistência à insulina e aumentaram colesterol HDL aos 3 e 6 meses. Na análise do percentil 75º de hemoglobina glicada e de sangramento subgengival, a comparação intra-grupo mostrou redução significativa de hemoglobina glicada no grupo teste dos 3 para os 6 meses, além de melhora no grupo controle de insulina, resistência à insulina e HDL. Conclusão: A despeito da melhora nos parâmetros periodontais no grupo teste, não houve efeito do tratamento periodontal nos parâmetros metabólicos e na PA. / Metabolic syndrome (MS) is a condition of increasing prevalence in the world and there is a little information on the effect of periodontal treatment on levels of metabolic parameters in patients with MS. The objective of this thesis is to compare the effect of periodontal treatment on levels of glycated hemoglobin, fasting glucose, triglycerides, HDL cholesterol, total cholesterol, insulin, insulin resistance, beta cell function, C-reactive protein (CRP) and blood pressure (BP) in patients with periodontitis and MS in a period of 6 months. Methods / Design: This thesis comprises a partial analysis of a randomized clinical trial with patients with concomitant diagnosis of periodontitis _ ≥ 2 interproximal sites with clinical attachment loss (CAL) ≥4 mm or ≥2 interproximal sites with probing depth (PD) ≥ 5mm in non-adjacent teeth and SM (International Diabetes Federation, 2009). Seventy-two subjects were randomly assigned to the test group (immediate periodontal treatment) or control (periodontal treatment after 6 months). Patients received dental evaluation and performed blood tests in baseline, 3 and 6 months, and medical treatment for hyperglycemia, dyslipidemia and hypertension when needed. The primary outcome was change in glycated hemoglobin and secondary outcomes were changes in glucose, triglycerides, total and HDL cholesterol, insulin, insulin resistance, beta cell function, CRP and BP. Statistical analysis was performed using Generalized Estimated Equations (GEE). Results: There is no significant differences in periodontal and metabolic parameters in both groups at baseline. There was a significant reduction of plaque, marginal bleeding, plaque retentive factors, subgingival bleeding, mean PS and PI in the test group. There is no significant difference in metabolic parameters and blood pressure at 3 and 6 months compared to subjects who received periodontal treatment or not. In the intra-group analysis, control subjects improved insulin levels, insulin resistance and HDL cholesterol at 3 and 6 months. In the analysis of 75 percentile of glycated hemoglobin and subgingival bleeding, intra-group comparison showed significant reduction of glycated hemoglobin in the test group of 3 to 6 months, and reduction in control group of insulin, insulin resistance and improvement of HDL. Conclusion: Despite the improvement in periodontal parameters in the test group, there was no effect of periodontal treatment on metabolic parameters and BP.

O diabetes mellitus (DM) é uma doença crônica com alto índice de morbidade e mortalidade, sendo considerado um dos maiores problemas de saúde pública do século 21, afetando aproximadamente 415 milhões de pessoas. As complicações em longo prazo do DM incluem a doença renal, a qual pode levar à falência renal, a retinopatia com perda potencial da visão e neuropatia, bem como o risco de amputações. A hemoglobina glicada (A1c) é considerada o parâmetro de referência na avaliação do controle glicêmico de pacientes com DM. No entanto, a mensuração da A1c pode não ser adequada para avaliar as variações em curto prazo do controle glicêmico, devido ao longo tempo de vida dos eritrócitos (120 dias). Existem ainda algumas limitações do uso deste teste, como em pacientes com hemoglobinas variantes, persistência hereditária à hemoglobina fetal, anemia hemolítica, anemia renal, entre outros. A avaliação da glicação da albumina é considerada, por alguns autores, como um melhor marcador para o controle glicêmico do que a A1c, em situações onde a A1c é de difícil interpretação devido à presença de interferentes, uma vez que a glicação da albumina não é afetada pela alteração no tempo de sobrevida das hemácias, como ocorre com a A1c. Atualmente, não há nenhum teste de albumina glicada (AG) disponível na rotina prática no Brasil, sendo um método limitado à pesquisa. No entanto, vários estudos mostram dados promissores em relação à AG e o controle do DM em situações específicas. Assim, a AG tem sido considerada um marcador alternativo no controle glicêmico e há necessidade de maior investigação sobre a utilização deste teste na prática clínica. / Diabetes mellitus (DM) is a chronic disease with high morbidity and mortality, being considered one of the biggest public health problems of the 21st century, affecting approximately 415 million people. Long-term complications of DM include renal disease, which can lead to kidney failure, retinopathy with potential loss of vision and neuropathy, as well as the risk of amputations. Glycated hemoglobin (A1c) is considered the reference in the assessment of glycemic control in patients with diabetes mellitus (DM). However, A1c measurement may not be adequate to evaluate the short-term variations of glycemic control due to the long lifespan of erythrocytes (120 days). There are also some limitations of using this test, such as in patients with variant hemoglobins, hereditary persistence to fetal hemoglobin, hemolytic anemia, renal anemia, among others. The evaluation of albumin glycation is considered by some authors to be a better marker for glycemic control than A1c in situations where A1c is difficult to interpret due to the presence of interferents, since albumin glycation is not affected by alteration in the survival time of red blood cells, as occurs with A1c. Currently, there is no glycated albumin (GA) test available in routine practice in Brazil, being a method limited to the research. However, several studies show promising data about GA in DM control in specific situations. Therefore, GA has been considered an alternative marker in glycemic control and there is a need of further investigation into the use of this test in clinical practice.

Several studies have been conducted that link poor control of hemoglobin A1c (HbA1c) to an increased risk of heart disease. However, there are limited published studies that link HbA1c and heart disease based on ethnicity and gender. To address this gap in literature, the purpose of this study was to assess the association between HbA1c and heart disease in African American males (aged 30-64 years old) while controlling for education, income, and access to care. The research questions were focused on establishing an association between HbA1c values and heart disease in African American men through the lens of the health belief model. Secondary data (N=243) were used from the Nutritional Health and Examination Survey (2011-2016) and analyzed. Chi-square analysis and multiple logistic regression were conducted to test for an association between HbA1c and heart disease in men aged 30-64 years old. The variables of Hba1c values, various forms of heart disease, and stroke were tested while controlling for age, education, income, and access to care. Key results indicated no association between HbA1c and heart disease; yet, it is recommended that future research on the topic should include a larger sample of those with heart disease, from other sources, to better assess the outcome. The positive social change implications include the addition of research related to gender-specific outcomes and ethnicity-related risk between HbA1c and heart disease, which can be used to achieve better disease management and provide educational opportunities for diabetic African-American men.

Nature has always served as a model for mimicking and inspiration to humans in their efforts to improve their life. Researchers have been inspired by nature to produce biomimetic materials with molecular recognition properties by design rather than evolution. Molecular imprinting is one way to prepare such materials. Such smart materials with new functionalities are at the forefront of the development of a relevant number of ongoing and perspective applications ranging from consumer to space industry. Molecularly imprinted polymers were developed by mimicking the natural enzymes or antibodies that serve as host for binding target molecules. These imprints were used as a recognition element to substitute natural biomolecules in biosensors. The concept behind molecular imprinting is to mold a material (with the desired chemical properties) around individual molecules. Upon removal of the molecular templates, one is left with regions in the molded material that fit the shape of the template molecules. Thus, molecular imprinting results in materials that can selectively bind to molecules of interest. Imprinted materials resulted in applications ranging from chemical separation to bioanalytics. In this work attempts were made particularly in the development of molecularly imprinted polymer based thermometric sensors. The main effort was focused towards the development of an covalently imprinted polymer that would be able to selectively bind fructosyl valine (Fru-Val), the N-terminal constituent of hemoglobin A1c ß-chains. Taking into account the known advantages of imprinted polymers, e.g. robustness, thermal and chemical stability, imprinted materials were successfully used as a recognition element in the sensor. One of the serious problems associated with the development of MIP sensors and which lies in the absence of a generic procedure for the transformation of the polymer-template binding event into a detectable signal has been addressed by developing the "thermometric" approach. In general the developed approach gives a new insight on MIP/Analyte interactions. / In dem Bestreben, ihr eigenes Leben zu verbessern, haben die Menschen stets die Natur nachgeahmt und sich von ihr inspirieren lassen. Die Natur hat Forscher zur Erzeugung smarter biomimetischer Stoffe mit molekularen Erkennungseigenschaften nach dem Vorbild der Evolution inspiriert. Eine der Methoden zur Herstellung solcher Substanzen ist das molekulare Prägen. Smarte Materialien mit neuen Eigenschaften stehen an der Spitze der Entwicklung potentieller Anwendungen vom Verbraucher bis hin zur Raumfahrtindustrie. Durch Nachahmung von natürlichen Enzymen oder Antikörpern wurden molekular geprägte Polymere (MIPs) entwickelt, die der Bindung von Zielmolekülen dienen. Diese geprägten Polymere (imprints) wurden anstelle von Biomolekülen als Erkennungselemente in Biosensoren eingesetzt. Das Konzept, das dem molekularen Prägen zugrunde liegt, besteht in der Formung eines Polymers (mit den entsprechenden chemischen Eigenschaften) um einzelne Zielmoleküle herum. Nach Entfernen dieser molekularen Template bleiben Abdrücke im Polymer übrig, die der Form der Templatmoleküle entsprechen. Mit Hilfe des molekularen Prägens kann man also Stoffe herstellen, die sich selektiv an bestimmte Moleküle binden können. Geprägte Polymere finden breite Anwendung, etwa in chemischen Aufreinigungsprozessen und der Bioanalytik. Hauptanliegen der vorliegenden Arbeit war es, thermometrische Sensoren auf der Basis molekular geprägter Polymere zu entwickeln. Die Anstrengungen richteten sich vor allem auf die Entwicklung eines kovalent geprägten Polymers, das in der Lage ist, selektiv Fruktosyl-Valin (Fru-Val), den N-terminalen Bereich von Hämoglobin A1c, zu binden. Aufgrund der bekannten Vorzüge geprägter Polymere – z. B. Robustheit und thermische und chemische Stabilität – wurden geprägte Polymere erfolgreich als Erkennungselement im Sensor angewendet. Eine der größten Herausforderungen bei der Entwicklung von MIP-Sensoren, das Fehlen eines generischen Verfahrens zur Umwandlung der Bindungsreaktion in ein nachweisbares Signal, wurde mit der Entwicklung der thermometrischen Methode in Angriff genommen. Diese Methode führt allgemein zu neuen Einsichten in die Interaktionen zwischen MIP und Analyt.

Background: Glycated hemoglobin is the indicator of long-term diabetes control and a value below 7 percent is recommended by the American Diabetes Association (ADA) to reduce cardiovascular complications. Diabetic patients have a two- to four-fold risk of cardiovascular disease and approximately two-thirds of diabetic patients die as a result of cardiovascular complications. Three large prospective randomized controlled long-term trials within the last decade reported no significant reduction in cardiovascular complications in type 2 diabetic patients by intensive glycemic control. To the author's knowledge, no known retrospective studies have examined the association between mean serial glycated hemoglobin and coronary atherosclerosis (CA) or acute coronary syndromes (ACS). Objective: This study was designed to determine the association between mean serial glycated hemoglobin with incident CA or ACS in type 2 diabetic patients after controlling for age, gender, hypertension, low density lipoprotein cholesterol (LDL-C), microalbuminuria, aspirin use, statin use, insulin use, tobacco use, and body mass index (BMI). Methods: The study was a retrospective cohort database analysis using the Austin Travis County CommUnityCare[trademark] clinics' electronic medical record for the time period between October 1, 2004 and September 30, 2009. The primary outcome of the study was the incidence of CA or ACS and the primary independent variable was glycated hemoglobin (<7% vs. [greater than or equal to]7%). The study subjects included type 2 diabetic patients aged 30 to 80 years with at least one glycated hemoglobin value per year for a minimum of two consecutive years. Study subjects were excluded if CA or ACS occurred within six months of the index date (i.e., first glycated hemoglobin). Logistic regression analysis was used to address the study objective. Results: Overall, 3069 subjects met the study inclusion criteria with a mean follow-up period of approximately two years. Two percent (N=62) of the subjects had incident CA or ACS. After controlling for age, gender, hypertension diagnosis, LDL-C, microalbuminuria, aspirin use, statin use, insulin use, tobacco use and BMI, there was no significant association (OR=1.026, 95% CI=0.589-1.785, p=0.9289) between mean serial glycated hemoglobin and the incident diagnosis of CA or ACS. Increasing age (OR=1.051, 95% CI=1.025-1.077, p<0.0001), male gender (OR=1.855, 95% CI=1.105-3.115, p=0.0195) and normal weight (normal or underweight compared to obese: OR=0.122, 95% CI=0.017-0.895, p=0.0438) were significantly associated with incident CA or ACS. Conclusions: Mean serial glycated hemoglobin (comparing [greater than or equal to]7% to <7%) was not significantly associated with CA or ACS over a mean follow-up period of approximately two years. Until more evidence becomes available, clinicians and diabetic patients should target glycated hemoglobin level below or close to 7 percent as recommended by the ADA soon after diagnosis while concomitantly controlling nonglycemic risk factors of cardiovascular disease (statin use, aspirin use, blood pressure control, smoking cessation and life style modification), to reduce their long-term risk of incident CA or ACS. / text