Due to the technology development, the diet habit has completely changed. It accompanied by the metabolite diseases relevant to blood glucose and lipids, which are dependent with the atherosclerosis and cardiovascular disease. In this study, we using matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/MS) to characterize triglycerides in human plasma. In the other, the glycosylated hemoglobin in human whole blood was detected by liquid electrospray laser desorption ionization (Liquid ELDI/MS). Triglycerides are energy source (9 kcal/g) in human body, derived from glycerol and three fatty acids. It is a main constituent of vegetable oil and animal fats. In clinical diagnosis, human plasma was mixed with triglyceride Kit to react to the final 520 nm UV-absorbing substance, then the concentration was quantified consistent with the calibration line by UV/Visible spectrometry. By the way, it needed Kit chemicals for one trial. MALDI-TOF/MS is a simple and easy method to operate to detect complex compounds in human plasma, only need to optimize the parameters (solvent collection, sample dilution, matrix selection, sample pretreatment ) to form a homogeneous crystals. The developed ¡§seed layer¡¨ method can reduce the sweet spot effect and cause a lower with-in spot variation (RSD < 20%) compared to ¡§premix¡¨ method (RSD >30%). Combined with statistic software 2D peak distribution, a semi-quantification can be observe of 24 different triglyceride concentration human plasmas. The level of glycosylated hemoglobin (HbA1c) in whole blood is currently the most important measurement of long-term control of the glycemic state of diabetes. As a result of the interferences of high concentrations of metabolites, proteins and salts in whole blood, tedious sample cleanup procedures must be performed prior to subjecting the sample solutions to conventional LC/MS and MALDI analyses for the detection of HbA1c. Electrospray laser desorption ionization mass spectrometry (ELDI/MS), a two-step ambient ionization technique, has been developed to characterize analytes directly from the liquid sample surface. One drop of the diluted hole blood (1/10, v/v in water) was placed on the stainless steel plate. The sample droplet was irradiated with a pulse laser, the desorbed analytes were post-ionized in an electrospray (ESI) plume (ESI solution: 70% methanol in water, 0.1% acetic acid), and the analyte ions were detected by a ion trap mass analyzer. Through this study, the protocol for efficiently characterizing HbA1c present in a drop of diluted whole blood with ELDI/MS was established. We successfully detected the ion signal of HbA1c with ELDI/MS. Quantification of the level of HbA1c in the whole blood of diabetic patients was achieved by calculating the ratio of the ion peak area of the glycosylated and non-glycosylated hemoglobin ions. A linear relationship exists for the quantitative results of HbA1c in whole blood of 20 diabetic patients obtained between ELDI/MS and that through conventional spectroscopic measurement.

Diabetes mellitus is a significant problem in the United States with the burden being greater in the African American population. Because diabetes is complex and costly, the importance of self-care management changes the disease management paradigm from “provider-centered” to patient-centered”. Empowerment is a possible solution for barriers to better diabetes management. Patient empowerment is helping patients discover and develop the inherent capacity to be responsible for their own life. Although patient empowerment is a valuable philosophy, there are gaps between the philosophy and actual practice. There are limited studies addressing the effectiveness of patient empowerment at improving diabetes management. Therefore, this study examined the association of patient empowerment and diabetes management by gender, age, socioeconomic status and education level by using the data from the Patient Empowerment to Improve Diabetes Care intervention conducted in the Diabetes Clinic of the Grady Health System (GHS). In this study, diabetes management was measured by glycated hemoglobin (HbA1c) level which shows the average blood glucose level over the past two to three months. Patient empowerment was measured by two standardized tools which were the Diabetes Empowerment Scale-Short Form and Patient Activation Measure. In this study, patient empowerment scores measured by these tools were not associated with HbA1c level in African American diabetes patients of the Diabetes Clinic of the GHS. Further study is necessary to understand the association between patient empowerment and diabetes disease management by using different measures of patient empowerment, different levels of disease management, and measurement in different settings.

Background: Cancer and diabetes are the second and twelfth leading global causes of death, respectively. Cancer incidence is increased in diabetics compared to non-diabetics. Common pathobiological pathways are shared by the two diseases: hyperglycaemia, hyperinsulinaemia, chronic inflammation and altered concentrations of endogenous hormones. These pathways can all directly or indirectly be linked to chronic hyperglycaemia. Lifestyle factors also affect cancer, diabetes and hyperglycaemia. Hypothesis: Chronic hyperglycaemia is the common biological pathway linking cancer, diabetes and lifestyle factors. Chronic hyperglycaemia can be assessed by monitoring glycated haemoglobin (HbA1c) levels. Aim: The first aim is to investigate whether the link between diabetes and increased cancer risk can be explained by increasing HbA1c levels. Secondly, glycaemic and overall models of lifestyle factors should be developed and compared to determine the relative influence of lifestyle factors on blood glucose level and, subsequently, cancer risk. This could clarify whether improved glycaemic control via lifestyle factors is sufficient to significantly reduce cancer risk. Method: Dose-response meta-analyses on cancer risk and HbA1c levels were performed and the results communicated via a research article. Statistical glycaemic and overall models were developed from published studies on colorectal cancer (CRC), lifestyle factors and HbA1c, via meta-analysis. Log-linear and restricted cubic spline models were considered for studies relating CRC risk to lifestyle factors or HbA1c. Linear models were considered for studies relating HbA1c to lifestyle factors. Only statistically significant models were compared. Results: Increased cancer risk with increasing HbA1c levels was present for a number of cancers, with some cancer types also showing increased risk in the pre-diabetic and normal HbA1c ranges. Comparison of the glycaemic and overall models revealed that HbA1c significantly affected cancer risk and was significantly affected by lifestyle factors. However, the overall effects of lifestyle factors were much stronger than their glycaemic effects (between 9% and 25% difference in risk between overall effects and glycaemic effects at the exposure levels analysed). Glycaemic and overall models for cigarette smoking and chronic stress revealed increased cancer risk with increasing exposure, but decreased cancer risk for increased dietary fibre intake. The glycaemic model for alcohol consumption displayed decreased cancer risk, while the overall model revealed increased cancer risk, emphasising the strong effect of carcinogenic substances in alcohol. Conclusions: Risk for a number of cancers increased with HbA1c levels in diabetic and non-diabetic persons. Cancer prevention by improved blood glucose control seems plausible. The overall effects of lifestyle factors on cancer risk are much stronger than their glycaemic effects. Lifestyle factors alone do not provide enough reduction in blood glucose levels. Other therapeutic strategies for reducing blood glucose levels, such as pharmacotherapeutics or fasting, should be investigated. The possible harmful effects of reducing blood glucose levels, such as neuroglycopaenia, should be considered before implementation of therapeutic strategies. Although there seems to be a strong association between HbA1c and cancer risk, this does not imply causality. The possibility of residual confounding cannot be ignored, even though the most adjusted estimates were used to develop the models, where possible. / MIng (Electrical and Electronic Engineering), North-West University, Potchefstroom Campus, 2014

Background Due to population growth, aging, urbanisation, increasing prevalence of obesity and physical inactivity, diabetes mellitus (DM) has become one of the most important and prevalent chronic diseases. Glycated haemoglobin A1c (HbA1c) assessment is currently being used all over to monitor glycaemic control as a cornerstone of diabetes care. It might also be a useful screening tool for non–insulin dependent DM, also known as type 2 DM (T2DM). Elevated HbA1c can be linked with long–term risk of cardiovascular complications. Aim The aim of the study was to determine whether HbA1c can be used as reliable screening tool for early detection of T2DM in an African population. Methods This study was a cross–sectional study and was part of the South African, North–West Province (SANWP) leg of the 12–year Prospective Urban and Rural Epidemiological (PURE) study. Baseline data was collected from March to December 2005. A total of 2010 volunteers were recruited from randomly selected households. Data was collected on socio–demographic characteristics, physical activity, dietary intakes, blood pressure and anthropometry. HbA1c, fasting plasma glucose (FPG), liver enzymes and HIV status were determined. Ethical approval for the PURE study was obtained in July 2004. Oral glucose tolerance tests (OGTT) were also done for a sub–group of 465 subjects. The Statistical Consultation Services of the North–West University were consulted to analyse data with SPSS 17.0 and STATISTICA 9.0. Results The HbA1c values within the diabetic FPG groups were 7.46% for men and 8.08% for women. HbA1c values increased significantly progressively from the normal FPG groups to the groups with impaired FPG and the diabetic FPG groups for both men and women. No significant increases were found in HbA1c between the OGTT groups (normal 2 hour plasma glucose (PG), impaired 2–hour PG and diabetic 2–hour PG). Total cholesterol, triglycerides, body mass index and FPG increased significantly and high–density lipoprotein cholesterol decreased significantly with an increase in HbA1c values in men and women. In addition, systolic blood pressure increased significantly in women with increased HbA1c. Thus, with an increase in HbA1c, an increase in the number of risk factors was observed. When using HbA1c and FPG in combination, 43 subjects of the whole population were detected with having a risk of developing T2DM. However, when considering the commonality of subjects identified to be diabetic or at risk by the OGTT, FPG and HbA1c individually, only one subject was identified by all the methods as having diabetes or being at risk to develop diabetes. Discussion and conclusions An increase in HbA1c and FPG was associated with an increase in risk factors and therefore with metabolic syndrome (MS). MS is associated with an increased risk of developing T2DM and therefore it can be concluded that HbA1c was useful for detecting in this population individuals at increased risk of developing T2DM. The use of FPG and HbA1c in combination was considered a better screening tool when compared to HbA1c alone. Factors other than what were measured in this study might be the cause of the unexpected results obtained in the participants with impaired OGTT. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2011.

Background Due to population growth, aging, urbanisation, increasing prevalence of obesity and physical inactivity, diabetes mellitus (DM) has become one of the most important and prevalent chronic diseases. Glycated haemoglobin A1c (HbA1c) assessment is currently being used all over to monitor glycaemic control as a cornerstone of diabetes care. It might also be a useful screening tool for non–insulin dependent DM, also known as type 2 DM (T2DM). Elevated HbA1c can be linked with long–term risk of cardiovascular complications. Aim The aim of the study was to determine whether HbA1c can be used as reliable screening tool for early detection of T2DM in an African population. Methods This study was a cross–sectional study and was part of the South African, North–West Province (SANWP) leg of the 12–year Prospective Urban and Rural Epidemiological (PURE) study. Baseline data was collected from March to December 2005. A total of 2010 volunteers were recruited from randomly selected households. Data was collected on socio–demographic characteristics, physical activity, dietary intakes, blood pressure and anthropometry. HbA1c, fasting plasma glucose (FPG), liver enzymes and HIV status were determined. Ethical approval for the PURE study was obtained in July 2004. Oral glucose tolerance tests (OGTT) were also done for a sub–group of 465 subjects. The Statistical Consultation Services of the North–West University were consulted to analyse data with SPSS 17.0 and STATISTICA 9.0. Results The HbA1c values within the diabetic FPG groups were 7.46% for men and 8.08% for women. HbA1c values increased significantly progressively from the normal FPG groups to the groups with impaired FPG and the diabetic FPG groups for both men and women. No significant increases were found in HbA1c between the OGTT groups (normal 2 hour plasma glucose (PG), impaired 2–hour PG and diabetic 2–hour PG). Total cholesterol, triglycerides, body mass index and FPG increased significantly and high–density lipoprotein cholesterol decreased significantly with an increase in HbA1c values in men and women. In addition, systolic blood pressure increased significantly in women with increased HbA1c. Thus, with an increase in HbA1c, an increase in the number of risk factors was observed. When using HbA1c and FPG in combination, 43 subjects of the whole population were detected with having a risk of developing T2DM. However, when considering the commonality of subjects identified to be diabetic or at risk by the OGTT, FPG and HbA1c individually, only one subject was identified by all the methods as having diabetes or being at risk to develop diabetes. Discussion and conclusions An increase in HbA1c and FPG was associated with an increase in risk factors and therefore with metabolic syndrome (MS). MS is associated with an increased risk of developing T2DM and therefore it can be concluded that HbA1c was useful for detecting in this population individuals at increased risk of developing T2DM. The use of FPG and HbA1c in combination was considered a better screening tool when compared to HbA1c alone. Factors other than what were measured in this study might be the cause of the unexpected results obtained in the participants with impaired OGTT. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2011.

To accurately predict the outcome of a late phase study, pharmacometric models can help in drug development. Making informed decision on which models to use will also facilitate drug development. This can depend on the mechanism of action for the drug as well as stability and runtime factors. This is an investigation of four published semi-mechanistic pharmacometric models to predict glycosylated red blood cells (HbA1c) in a late phase study of an anti-diabetic drug together with an assessment of their stability and power to detect drug effects. Mean plasma glucose (MPG), fasting plasma glucose (FPG) or FPG and fasting serum insulin (FSI) are used together with HbA1c as drivers for change in the models. We find that less complex models, with fewer differential equations, are quicker to run and more stable, and that MPG alone is superior to FPG or FPG and FSI to detect a drug effect. The findings are useful for drug development in the anti-diabetic area, and show that a less mechanistic model performs well under these conditions.

Sweden holds third place of diabetes incidence in young people after Finland and Sardinia. One fifth of the population is nowadays of foreign descent. We have a substantial number of immigrants from countries where the risk for T1D is considerably lower. Migration as a natural experiment is a concept to assess the risk for diabetes in offspring of immigrant parents and assess the interaction between genetics (genotype) and the impact of environment (phenotype). Aims: To study the risk of incurring diabetes for children of immigrant parents living in Sweden (I) and further study the risk if the child is born in Sweden or not (II); to specifically study and evaluate if children from East Africa have increased risk to develop T1D (III). To investigate if clinical and sociodemographic status at T1D onset differs between immigrant children compared to their Swedish indigenous peers (IV). Finally to study the clinical outcome and the impact of socio-demographic factors at diabetes onset after three years of treatment (V). Methods: All five studies are observational, nationwide and population based, on prospectively collected data. Statistics mainly by logistic and linear regressions. Results: Parental country of origin is a strong determinant for diabetes in the offspring. Children born to immigrant parents seem to keep their low risk compared to their Swedish peers (I). When adding the factor of being born in Sweden, the pattern changed; there was a significantly (p &lt; 0.001) increased risk for T1D if the child was born in Sweden (II). East Africans have a substantial risk for T1D and especially if the children are born in Sweden (III). Immigrant children and adolescents have worse metabolic start at T1D onset compared to their indigenous Swedish peers (IV). After 3 years of treatment, the immigrant children had a sustained higher median HbA1c, compared to their Swedish peers (V). Conclusions: Genotype and influences during fetal life or early infancy have an important impact for the risk of T1D pointing towards epigenetics playing a substantial role. Children with an origin in East Africa have a high risk of incurring T1D. Immigrant children have worse metabolic start at T1D onset, which sustains after three years of treatment

O diabetes mellitus (DM) é uma doença que está associada com aumento da morbidade, mortalidade e custos econômicos. O DM tipo 2 é a forma de diabetes mais comum, acometendo 85%-90% de todos os casos. O mau controle glicêmico é um fator determinante do desenvolvimento e progressão das complicações do DM. A hemoglobina glicada (A1C) se tornou a medida de referência para o controle de DM por mais de duas décadas. Existe um grande incentivo, tanto da perspectiva de saúde pública quanto da clínica, em detectar pessoas com risco futuro de desenvolver DM2, pois este é um forte fator de risco para doença cardiovascular. Também existem evidências que é possível prevenir ou retardar o DM nas pessoas com tolerância a glicose diminuída, desde que estes casos sejam identificados e tratados adequadamente. Os testes disponíveis hoje para o diagnóstico do DM, glicemia de jejum (GJ) e teste oral de tolerância à glicose (TOTG), carecem de sensibilidade e/ou especificidade. Recentes estudos têm evidenciado que a A1C pode ser uma nova ferramenta para diagnóstico do DM, sendo que diversos pontos de corte tem sido estudados. Maiores investigações para a validação do desempenho diagnóstico deste teste na predição do DM são necessárias para podermos utilizar esta ferramenta com segurança na triagem e diagnóstico do DM. / Diabetes mellitus (DM) is a disease associated with greater mortality and economical costs. Type 2 DM is the commonest form of DM, accounting for 85-90 % of its cases. Glycemic levels are a determinant factor for the development and progression of DM complications. Glycated hemoglobin (A1C) became the reference measure of glycemic control for more than two decades. There is a great incentive in detecting persons with future risk of developing DM, because this is a strong risk factor for cardiovascular disease. Also there are evidences that it is possible to prevent or to delay DM in persons with prediabetes, since identified and treated appropriately. Available tests for DM diagnosis, fasting glycemia (FG) and oral glucose tolerance test (OGTT), lack sensibility and/or specificity. Recent studies have shown that A1C can be a new tool for DM diagnosis and several cutoff points have been analyzed. However, the validation of this test as diagnostic modality to detect DM might be necessary in order to provide a useful tool for DM diagnosis.

A prevalência de diabetes mellitus (DM) está aumentando constantemente em todo o mundo a uma taxa alarmante. Devido às suas complicações que causam uma maior morbidade, invalidez e mortalidade, o DM representa um enorme problema para a saúde pública. Com isso, ações, tanto em diagnóstico como em tratamento, são necessárias para desacelerar a tendência atual e prevenir o desenvolvimento das complicações do DM. Recentemente, a hemoglobina glicada (HbA1c) foi introduzida nos critérios diagnósticos de DM. Os resultados de HbA1c são igualmente apropriados para o diagnóstico, apesar de não necessariamente detectarem DM nos mesmos indivíduos detectados pelos critérios de glicemia. No entanto, os níveis de HbA1c podem ser influenciados por qualquer condição que altere a vida útil dos eritrócitos e metabolismo da hemoglobina, independentemente da glicemia, resultando em erro diagnóstico neste grupo da população com estas condições. Além disso, estudos epidemiológicos revelaram que a glicemia pós-prandial tem um maior risco de causar complicações cardiovasculares em relação à hiperglicemia persistente e pode ser acessada com precisão usando a albumina glicada (AG) e não a HbA1c. Nesse contexto, estudos recentes têm evidenciado que a AG pode ser um marcador para diagnóstico do DM e também ser utilizado como um marcador alternativo à HbA1c para o controle glicêmico. No entanto, esses estudos, foram realizados apenas na população asiática e podem não ser aplicáveis a outros grupos étnicos. Por isso, mais investigações para a validação do desempenho diagnóstico da AG na predição do DM em diferentes grupos etnicos são necessárias. Neste estudo avaliamos o desempenho da AG no diagnóstico do DM em 242 indivíduos brasileiros com idade média de 54,4 anos (+ 13,0). Baseando-se nos valores de glicose plasmática durante o teste oral de tolerância à glicose (TOTG), o DM foi detectado em 31,8%. AG ≥16,8% apresentou acurácia similar para a detecção de DM conforme definido por HbA1c >6,5%. O uso da razão glicemia de 2h pós-sobrecarga de 75g de glicose (2hPG) e AG (2hPG/AG) melhora a sensibilidade, reduz o número de diagnósticos incorretos por AG ou HbA1c >6,5% e possui um acurácia comparável ao TOTG, indicando que o uso de uma estratégia aplicando a razão da glicemia pós-prandial (GPP) real e AG (GPP/AG) pode ser mais conveniente para pacientes e aumentar o desempenho diagnóstico do teste. Estudos para validar esta estratégia são necessários. / The prevalence of diabetes mellitus (DM) is constantly increasing worldwide at an alarming rate. Due to its complications that cause greater morbidity, disability and mortality, DM represents a heavy burden on public health. Therefore, actions in both, diagnosis and treatment, are necessary to slow down the current tendency and avoid the development of DM complications. Recently, the glycated hemoglobin test (HbA1c) was introduced in the diagnostic criteria for DM. The HbA1c results are equally appropriate for diagnostic testing, though not necessarily detect DM in the same subjects detected by plasma glucose criteria. However, blood HbA1c levels may be influenced by any condition that changes the lifespan of erythrocytes and hemoglobin metabolism regardless of glycemia, resulting in the misdiagnosis of this population group. In addition, epidemiological studies have shown that postprandial glycemia has a higher risk of causing cardiovascular complications than chronic hyperglycemia and can be accurately assessed using the glycated albumin (GA) test rather than HbA1c. In this context, recent studies have shown that GA may be a marker for the diagnosis of DM and also be used as an alternative marker to HbA1c on many occasions. However, these studies have been conducted only in the Asian population and may not be applicable to other ethnic groups. Therefore, further investigations to validate the diagnostic performance of GA in the prediction of DM in different ethnic groups are necessary. In this study, we evaluated the GA performance in the diagnosis of DM in 242 Brazilian individuals with a mean age of 54.4 years (+ 13.0). Based on plasma glucose values during oral glucose tolerance test (OGTT), DM was detected in 31.8%. AG ≥16.8% presented similar accuracy for detecting DM as defined by a HbA1c >6.5%. The use of the 2-h plasma glucose after a 75-g OGTT and GA (2hPG/GA) ratio improves sensitivity, reduces the number of incorrect diagnoses by GA or HbA1c >6.5% and has an accuracy comparable to OGTT, indicating that the use of approach applying the postprandial glucose (PPG) and GA (PPG/GA) may be more convenient for patients and increase the diagnostic performance of the test. Studies to validate this approach are needed.

O diabetes mellitus (DM) é uma doença que está associada com aumento da morbidade, mortalidade e custos econômicos. O DM tipo 2 é a forma de diabetes mais comum, acometendo 85%-90% de todos os casos. O mau controle glicêmico é um fator determinante do desenvolvimento e progressão das complicações do DM. A hemoglobina glicada (A1C) se tornou a medida de referência para o controle de DM por mais de duas décadas. Existe um grande incentivo, tanto da perspectiva de saúde pública quanto da clínica, em detectar pessoas com risco futuro de desenvolver DM2, pois este é um forte fator de risco para doença cardiovascular. Também existem evidências que é possível prevenir ou retardar o DM nas pessoas com tolerância a glicose diminuída, desde que estes casos sejam identificados e tratados adequadamente. Os testes disponíveis hoje para o diagnóstico do DM, glicemia de jejum (GJ) e teste oral de tolerância à glicose (TOTG), carecem de sensibilidade e/ou especificidade. Recentes estudos têm evidenciado que a A1C pode ser uma nova ferramenta para diagnóstico do DM, sendo que diversos pontos de corte tem sido estudados. Maiores investigações para a validação do desempenho diagnóstico deste teste na predição do DM são necessárias para podermos utilizar esta ferramenta com segurança na triagem e diagnóstico do DM. / Diabetes mellitus (DM) is a disease associated with greater mortality and economical costs. Type 2 DM is the commonest form of DM, accounting for 85-90 % of its cases. Glycemic levels are a determinant factor for the development and progression of DM complications. Glycated hemoglobin (A1C) became the reference measure of glycemic control for more than two decades. There is a great incentive in detecting persons with future risk of developing DM, because this is a strong risk factor for cardiovascular disease. Also there are evidences that it is possible to prevent or to delay DM in persons with prediabetes, since identified and treated appropriately. Available tests for DM diagnosis, fasting glycemia (FG) and oral glucose tolerance test (OGTT), lack sensibility and/or specificity. Recent studies have shown that A1C can be a new tool for DM diagnosis and several cutoff points have been analyzed. However, the validation of this test as diagnostic modality to detect DM might be necessary in order to provide a useful tool for DM diagnosis.