En biologie clinique, disposer de mesures fiables et comparables, indépendamment du temps et du laboratoire, est primordial afin de permettre une prise en charge et un suivi adaptés des patients. Le moyen privilégié est d’établir la traçabilité métrologique des résultats de mesure aux unités du système international (SI), notamment par le biais de méthodes de référence et de matériaux de référence certifiés d’ordre supérieur. Ces travaux de thèse se sont attachés à caractériser deux méthodes de référence primaires candidates. Une méthode d’énumération absolue des lipoprotéines par ES-DMA pour l’évaluation du risque cardiovasculaire a été développée et caractérisée. Les résultats obtenus ont mis en évidence certaines limitations instrumentales rendant l’établissement de la traçabilité au SI difficile. Malgré les avantages certains de cette méthode pour l’analyse avancée de lipoprotéines, la fidélité et la robustesse des mesures ne sont pas suffisantes pour la considérer comme méthode de référence primaire. Une méthode de quantification de l’hémoglobine glyquée HbA1c, un biomarqueur du diabète sucré, par LC-MS/MS associée à la dilution isotopique a été mise en place et validée. La traçabilité au SI des résultats de dosage a été établie, toutefois, les incertitudes de mesures demeurent élevées et la comparabilité avec la méthode de référence IFCC reste à évaluer sur un nombre plus significatif d’échantillons et de laboratoires. Pour conclure, ces travaux ont mis en évidence les défis associés à la mise en place de nouvelles chaînes de traçabilité ainsi que les problématiques liées au développement de méthodes de référence primaires pour le dosage de biomarqueurs complexes. / Ensuring reliability and between-laboratory comparability of in-vitro diagnostic test results is essential for appropriate and internationally harmonized decision making and patient follow-up. To this end, a privileged way is to establish results metrological traceability to the international system of units (SI) through the development of primary reference methods and higher order reference materials. This thesis aimed at characterizing two candidate primary reference procedures.A method for lipoprotein absolute quantification by ES-DMA for cardiovascular diseases risk assessment was developed and characterized. Results evidenced some advantages of this method compared to other advanced lipoprotein testing assays, but some instrumental weaknesses make the establishment of results traceability to the SI difficult in the current state-of-the-art. Precision and robustness are additionally not sufficient for this method to be considered as a primary reference method.A method for the quantification of glycated hemoglobin HbA1c, a biomarker of diabetes mellitus, by LC/MS/MS associated to isotopic dilution was implemented and validated. Results traceability to the SI units could successfully be established. However, measurement uncertainties remain large and comparability with the IFCC reference method is still to be further assessed on a significant number of samples and laboratories.To conclude, this study highlighted the challenges associated with the implementation of new traceability chains and the difficulties related to the development and characterization of primary reference procedures for the quantification of complex biological markers.

Hintergrund und Ziel: Der hausärztliche Bereich ist von zentraler Bedeutung für die Betreuung von Patienten mit Diabetes mellitus. Die Autoren untersuchten a) die Prävalenz von Diabetes mellitus Typ 1 und Typ 2, b) die Art und Häufigkeit von nichtmedikamentösen und medikamentösen Behandlungen und deren Zusammenhang mit dem Vorliegen von diabetestypischen Komplikationen sowie c) die Qualität der Stoffwechseleinstellung anhand des HbA1c. Methodik: Auf der Grundlage einer bundesweiten Zufallsstichprobe von 3 188 Arztpraxen („response rate“ [RR] 50,6%) wurden 55 518 Patienten (RR 93,5%) im September 2003 in einer prospektiven Querschnittsstudie standardisiert mit Fragebögen, Arztgespräch und Labormessungen untersucht. Neben Diabetes mellitus wurden 28 weitere Erkrankungen explizit erfasst, darunter auch die typischen makrovaskulären (koronare Herzkrankheit, zerebrovaskuläre Erkrankungen, periphere arterielle Verschlusskrankheit) und mikrovaskulären Komplikationen (Neuropathie, Nephropathie, Retinopathie, diabetischer Fuß). Ergebnisse: Es wurde eine Prävalenz des Diabetes mellitus von 0,5% (Typ 1) bzw. 14,7% (Typ 2) dokumentiert. 49,5% (Typ 1) bzw. 50,2% (Typ 2) der Patienten hatten bereits mikro- oder makrovaskuläre Folge- bzw. Begleiterkrankungen. 6,8% der Patienten erhielten keine Therapie, 13,5% wurden nur mit Diät/Bewegung behandelt, und 75,3% erhielten orale Antidiabetika und/oder Insulin, davon 26,6% eine Kombinationstherapie mit verschiedenen Antidiabetika. Die Behandlungsintensität war im Vergleich zu Diabetikern ohne Komplikationen bei Patienten mit mikrovaskulären Kom- plikationen deutlich höher (Odds-Ratio [OR] 3,02) als bei denen mit makrovaskulären Komplikationen (OR 0,98). Ein HbA1c-Wert ≥ 7,0% fand sich bei 39,6% der Patienten. Schlussfolgerung: Im Vergleich zu früheren Untersuchungen im hausärztlichen Bereich hat die Rate der medikamentös behandelten Diabetiker zugenommen. Eine Kombinationstherapie wird häufiger eingesetzt. Die Qualität der Einstellung scheint sich ebenfalls verbessert zu haben. / Background and Purpose: The primary care sector is of key importance for the management of patients with diabetes mellitus. The authors investigated (a) the prevalence of diabetes mellitus type 1 and type 2, (b) the type and frequency of non-drug and drug treatment and its association with the presence of diabetic complications, and (c) the quality of metabolic control by HbA1c. Method: Using a nationwide probability sample of 3,188 general practices (response rate [RR] 50.6%), a total of 55,518 (RR 93.5%) patients were assessed in a prospective cross-sectional study by their physicians in September 2003 in a standardized manner using questionnaires, physician interview, and laboratory assessments. In addition to diabetes mellitus, 28 diseases were explicitly screened for, among them typical macrovascular (coronary heart disease, cerebrovascular disease, peripheral arterial disease) and microvascular disease (neuropathy, nephropathy, retinopathy, diabetic foot) complications. Results: The prevalence of diabetes mellitus was 0.5% (type 1) and 14.7% (type 2), respectively. 49.5% (type 1) and 50.2% (type 2) of patients had micro- or macrovascular complications. 6.8% did not receive any treatment, 13.5% received non-drug treatment, and 75.3% received oral antidiabetic drugs and/or insulin (26.6% a combination of two or more). Compared to diabetics without any complications, treatment intensity was significantly higher in patients with microvascular complications (odds ratio [OR] 3.02), but not in those with macrovascular complications only (OR 0.98). An HbA1c value ≥ 7.0% was recorded in 39.6% of patients. Conclusion: Compared to previous studies in this setting, the proportion of diabetics with drug treatment has increased. More patients receive antidiabetic drug combinations. Quality of blood sugar control appears to have improved as well.

Motivation - Brain-derived neurotrophic factor (BDNF) is a protein complex, synthesised and secreted mainly by the central nervous system and is involved in neuronal maintenance. Research suggests that BDNF is implicated in various neurological and psychiatric diseases, while recent evidence suggests a role for the neurotrophin on the periphery as well. Indeed, the specific functional role of BDNF and its action mechanism in the cardiovascular system, especially in that of Africans, is yet to be determined. The cardiovascular health profile of black South Africans is a major concern as research has shown that this group suffers from an array of cardiovascular risk factors that may result in organ damage. Sub-clinical atherosclerosis or structural endothelial dysfunction contributes to ever-increasing morbidity and mortality in the world. However, no studies regarding the associations between BDNF and structural vascular disease have been undertaken relating to black African participants. Objectives - The objective of this study was to determine whether BDNF is associated with changes in ambulatory blood pressure (BP) and whether a relationship between BDNF and structural endothelial dysfunction exists in black African male and female participants, determined by cross sectional wall area (CSWA) and albumin:creatinine ratio (ACR). Methodology - The study included 172 black African teachers (82 males and 90 females) who were employed by the Kenneth Kaunda Education district of the North-West Province, South Africa. Ambulatory blood pressure recordings were obtained with the use of a Meditech CE120 CardioTens ® apparatus. Blood pressure readings were measured at 30 min intervals during the day and 60 min intervals during the night. Anthropometric measurements were performed in triplicate by registered level II anthropometrists according to standardised procedures. A high-resolution ultrasound scan with carotid intima-media thickness (CIMT) images from at least two optimal angles of the left and right common carotid artery were obtained using a SonoSite Micromaxx ultrasound system. The lumen diameter between the near and far wall of the lumen-intima interface and the averages of both the left and right common carotid arteries were calculated. Subsequently, the carotid cross-sectional wall area (CSWA) was calculated. Participants, who fasted overnight, provided eight-hour blood and urine samples to determine serum BDNF and metabolic markers, for example, hyperglycaemia (HbA1c) and gamma glutamyl transferase (GGT). Urinary albumin and creatinine levels were determined by means of a turbidimetric method with the use of a Unicel DXC 800 analyser from Beckman and Coulter (Germany) and expressed as a ratio between albumin and creatinine (ACR). BDNF median split x Gender interaction effects for structural ED justified stratification of BDNF into low and high (≤ / > 1.37 ng/ml) gender groups. Results and Conclusion - On average, male participants were overweight (BMI 25-30kg/m2) and abused more alcohol.21 African men revealed a vulnerable cardiometabolic profile with values exceeding cut–points (European Society of Hypertension). These men demonstrated increased acute and chronic glucose (HbA1c) levels indicating a pre-diabetic state; as well as a disturbed lipid profile with lower HdL and increased triglycerides. Overall BDNF levels were lower than reference ranges (6.97 – 42.6 ng/ml). The men revealed mean lower BDNF levels, ambulatory BP values exceeding guideline cut-points (ambulatory SBP > 130mmHg; DBP > 80mmHg) as well as a hypertensive state compared to their female counterparts. Pertaining to structural endothelial dysfunction, the mean ACR value in men exceeded normal laboratory values (< 3.5mg/mmol). The African women displayed an obese state with low grade inflammation (CRP, 12.27 ± 11.67mg/l). A single two-way ANCOVA interaction on main effects (BDNF median split x Gender) demonstrated significant interaction for CIMTf [F (1,164); 3.99, p=0.05] and cholesterol [F (1,164); 4.12, p=0.05]. Therefore, a median split approach was followed which stratified gender groups into lower (≤ 1.37 ng/ml) and higher BDNF levels (>1.37 ng/ml). The low BDNF men revealed higher cholesterol than the high BDNF group, independent of BMI and age. Only the low BDNF women indicated significantly higher values for structural vascular markers (p< 0.05) than the high BDNF female group. In conclusion, we accept our hypothesis, as hypertrophic remodelling of the carotid artery was associated with lower BDNF levels. This may imply attenuated or possibly down-regulated BDNF levels acting as a compensatory mechanism for the mean higher BP levels. In women, metabolic risk and hypertrophic remodelling were evident within higher circulating levels of BDNF, underpinning different underlying mechanisms for impaired neurotrophin health in men and women. Novel findings of BDNF revealed the impact of central neural regulation on the circulatory system, which may contribute to cardiometabolic risk in Africans. / MSc (Physiology), North-West University, Potchefstroom Campus, 2014

Motivation - Brain-derived neurotrophic factor (BDNF) is a protein complex, synthesised and secreted mainly by the central nervous system and is involved in neuronal maintenance. Research suggests that BDNF is implicated in various neurological and psychiatric diseases, while recent evidence suggests a role for the neurotrophin on the periphery as well. Indeed, the specific functional role of BDNF and its action mechanism in the cardiovascular system, especially in that of Africans, is yet to be determined. The cardiovascular health profile of black South Africans is a major concern as research has shown that this group suffers from an array of cardiovascular risk factors that may result in organ damage. Sub-clinical atherosclerosis or structural endothelial dysfunction contributes to ever-increasing morbidity and mortality in the world. However, no studies regarding the associations between BDNF and structural vascular disease have been undertaken relating to black African participants. Objectives - The objective of this study was to determine whether BDNF is associated with changes in ambulatory blood pressure (BP) and whether a relationship between BDNF and structural endothelial dysfunction exists in black African male and female participants, determined by cross sectional wall area (CSWA) and albumin:creatinine ratio (ACR). Methodology - The study included 172 black African teachers (82 males and 90 females) who were employed by the Kenneth Kaunda Education district of the North-West Province, South Africa. Ambulatory blood pressure recordings were obtained with the use of a Meditech CE120 CardioTens ® apparatus. Blood pressure readings were measured at 30 min intervals during the day and 60 min intervals during the night. Anthropometric measurements were performed in triplicate by registered level II anthropometrists according to standardised procedures. A high-resolution ultrasound scan with carotid intima-media thickness (CIMT) images from at least two optimal angles of the left and right common carotid artery were obtained using a SonoSite Micromaxx ultrasound system. The lumen diameter between the near and far wall of the lumen-intima interface and the averages of both the left and right common carotid arteries were calculated. Subsequently, the carotid cross-sectional wall area (CSWA) was calculated. Participants, who fasted overnight, provided eight-hour blood and urine samples to determine serum BDNF and metabolic markers, for example, hyperglycaemia (HbA1c) and gamma glutamyl transferase (GGT). Urinary albumin and creatinine levels were determined by means of a turbidimetric method with the use of a Unicel DXC 800 analyser from Beckman and Coulter (Germany) and expressed as a ratio between albumin and creatinine (ACR). BDNF median split x Gender interaction effects for structural ED justified stratification of BDNF into low and high (≤ / > 1.37 ng/ml) gender groups. Results and Conclusion - On average, male participants were overweight (BMI 25-30kg/m2) and abused more alcohol.21 African men revealed a vulnerable cardiometabolic profile with values exceeding cut–points (European Society of Hypertension). These men demonstrated increased acute and chronic glucose (HbA1c) levels indicating a pre-diabetic state; as well as a disturbed lipid profile with lower HdL and increased triglycerides. Overall BDNF levels were lower than reference ranges (6.97 – 42.6 ng/ml). The men revealed mean lower BDNF levels, ambulatory BP values exceeding guideline cut-points (ambulatory SBP > 130mmHg; DBP > 80mmHg) as well as a hypertensive state compared to their female counterparts. Pertaining to structural endothelial dysfunction, the mean ACR value in men exceeded normal laboratory values (< 3.5mg/mmol). The African women displayed an obese state with low grade inflammation (CRP, 12.27 ± 11.67mg/l). A single two-way ANCOVA interaction on main effects (BDNF median split x Gender) demonstrated significant interaction for CIMTf [F (1,164); 3.99, p=0.05] and cholesterol [F (1,164); 4.12, p=0.05]. Therefore, a median split approach was followed which stratified gender groups into lower (≤ 1.37 ng/ml) and higher BDNF levels (>1.37 ng/ml). The low BDNF men revealed higher cholesterol than the high BDNF group, independent of BMI and age. Only the low BDNF women indicated significantly higher values for structural vascular markers (p< 0.05) than the high BDNF female group. In conclusion, we accept our hypothesis, as hypertrophic remodelling of the carotid artery was associated with lower BDNF levels. This may imply attenuated or possibly down-regulated BDNF levels acting as a compensatory mechanism for the mean higher BP levels. In women, metabolic risk and hypertrophic remodelling were evident within higher circulating levels of BDNF, underpinning different underlying mechanisms for impaired neurotrophin health in men and women. Novel findings of BDNF revealed the impact of central neural regulation on the circulatory system, which may contribute to cardiometabolic risk in Africans. / MSc (Physiology), North-West University, Potchefstroom Campus, 2014

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

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.

<p>Objectives: To evaluate the long term total imprecision of HbA1c testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) <3% for HbA1c and to study the cost of an external quality assurance program for point-of-care HbA1c The county uses Bayer DCA 2000™ for point-of care HbA1c testing currently having 23 of these instruments.</p><p>Methods: Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA1c testing. The samples were first analysed on a Bayer DCA 2000™ and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II™, Biorad). The testing was performed approximately 8 times per year with each instrument.</p><p>Results: The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%.</p><p>Conclusion: The DCA 2000™ systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.</p>

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: Type 1 diabetes is a chronic disease for which there is currently no cure, and high quality care is essential if acute and long-term complications are to be avoided. Many children and adolescents have inadequate metabolic control with increased risk for complications later in life, and adolescent girls have reported low quality of life. Differences in metabolic control between treatment centres have been found but the reasons for this are unclear. Diabetes is a largely self-managed disease. Patient education is central to successful self-management but little is known about how to make best use of diabetes communities on the Internet and integrate them into a practitioner-driven service. Aim: The main objective of this thesis was to gain better understanding of how to improve the quality of diabetes care for children and adolescents, aiming to have near-normal blood glucose, to prevent both acute and late complications and to have good quality of life. Methods: The geographic populations of two paediatric centres (n=400) received validated questionnaires on perceived quality of care and Health-Related Quality of Life (HRQOL). An intervention with a web portal containing diabetes-related information and social networking functions was carried out within the same population. Clinical variables from 18 651 outpatient visits registered in the Swedish paediatric diabetes quality registry, SWEDIABKIDS were analysed. Using data from SWEDIABKIDS, five centres with the lowest mean HbA1c, five with the highest, and five with the largest decrease in centre mean HbA1c between 2003 and 2007 were identified. Team members (n=128) were asked about structure, process, policy, and the messages given to patients about important diabetes issues. Results: Specific areas that were identified as needing improvement included information about self-care, waiting time at outpatient clinics and for treatment, and access to care. Diabetes seemed to reduce HRQOL. Subjects with better metabolic control and with higher frequency of injections reported slightly higher HRQOL, as did those living with both parents compared to those with separated parents. Only 35% of children and adolescents with diabetes in Sweden had an HbA1c level below the treatment target value. Mean HbA1c showed a correlation with mean insulin dose, diabetes duration, and age. A difference between centres was found, but this could not be explained by differences in insulin dose, diabetes duration, or age. Adolescent girls reported lower HRQOL, as did parents of girls aged &lt; 8 years. Girls also had poorer metabolic control, especially during adolescence. In teams with the lowest and the most decreased mean HbA1c, members gave a clear message to patients and parents and had a lower HbA1c target value. Members of these teams appeared more engaged, with a more positive attitude and a greater sense of working as a team. Members of teams with the highest mean HbA1c gave a vaguer message, felt they needed clearer guidelines, and had a perception of poor collaboration within the team. High insulin dose, large centre population, and larger teams also seemed to characterize diabetes centres with low mean HbA1c. The most frequently visited pages on the web portal were the social networking pages, such as blogs, stories and discussions, followed by the diabetes team pages. Those who used the portal most actively were younger, had shorter diabetes duration, and lower HbA1c, and were more often girls. The web portal was not found to have any significant beneficial or adverse effects on HRQOL, empowerment or metabolic control. Conclusions: The quality of diabetes care for children and adolescents in Sweden is not sufficiently good and needs to improve further if complications in later life are to be avoided. Psychosocial support for children and adolescents with diabetes should be appropriate for age and gender. The attitudes of the members in the diabetes care team and the message they give to patients and their parents seem to influence metabolic control in children and adolescents. A clear and consistent message from a unified team appears to have beneficial effects on metabolic control. A web portal that includes comprehensive information about diabetes, and the opportunity to communicate with other people with diabetes and with healthcare professionals may be a useful complement to traditional patient education tools. Members of the diabetes team should encourage its use.

Objectives: To evaluate the long term total imprecision of HbA1c testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) &lt;3% for HbA1c and to study the cost of an external quality assurance program for point-of-care HbA1c The county uses Bayer DCA 2000™ for point-of care HbA1c testing currently having 23 of these instruments. Methods: Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA1c testing. The samples were first analysed on a Bayer DCA 2000™ and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II™, Biorad). The testing was performed approximately 8 times per year with each instrument. Results: The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%. Conclusion: The DCA 2000™ systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.