La mise sous schéma insulinique multi-injections des patients diabétiques âgés est risquée et complexe. L’éventuelle perte d’autonomie induite par le traitement et la variabilité des besoins insuliniques doivent être prises en compte. Dans les protocoles thérapeutiques, le démarrage de l’insulinothérapie se base sur la prescription d’une posologie faible ajustée en fonction de résultats glycémiques. Un temps d’adaptation est donc nécessaire afin de prescrire la dose optimale. Pour ces raisons, cette thèse propose une méthodologie originale pour modéliser l’insulinothérapie chez les sujets âgés diabétiques de type 2 à partir de certaines variables endogènes (cliniques et biologiques) avec deux objectifs : 1. aider les médecins dans la phase de détermination de la prescription insulinique, 2. individualiser le traitement en fonction du profil physiologique du patient. La méthodologie, basée sur la logique floue, a permis l’analyse d’un échantillon de 71 diabétiques âgés de plus de 65 ans. Trois profils types de besoins insuliniques ont été mis en évidence et les variables discriminantes à l’origine de cette typologie ont été identifiées. La méthodologie s’inspirant du raisonnement à base de cas permet d’individualiser le traitement en proposant la dose à prescrire à partir des plus proches cas sélectionnés dans l’échantillon. Ces travaux apportent deux contributions principales : - sur l’insulinothérapie des personnes âgées diabétiques de type 2, - sur la méthodologie originale du traitement numérique des données médicales lors de suivis thérapeutiques. / Starting insulin therapy with daily multi-injections in the elderly type 2 diabetic patients is a difficult challenge. The possible loss of autonomy induced by the treatment and the variability of the insulin needs must be taken into account. In the therapeutic protocols, starting insulin therapy is based on the prescription of low dosage adjusted according to blood glucose results. A time of adjustment is therefore necessary to prescribe the optimal dose.For these reasons, this thesis proposes an original methodology for modeling insulin therapy in elderly subjects with type 2 diabetes from certain biological and clinical endogenous variables with two objectives:1. assist physicians at the stage of determination of insulin prescription, 2. individualize insulin treatment depending on the physiological profile of the patient. The methodology based on fuzzy logic, allowed the analysis of a sample of 71 diabetic patients aged over 65 years. Three profiles types of insulin requirements and the discriminating variables underlying this typology have been identified. Methodology based on case based reasoning allows individualizing the treatment to prescribe insulin dosage from the closest (nearest) cases selected in the sample.Our works provide two main contributions:- on insulin therapy in elderly type 2 diabetic patients, - on the original methodology of the digital process of medical data at therapeutic follow-ups.

There is growing evidence that patients with type 2 diabetes mellitus have increased cancer risk. We examined the association between diabetes, cancer, and cancer-related mortality and hypothesized that insulin sensitizers lower cancer-related mortality. Participants in the Diabetes Cardiovascular Risk and Evaluation: Targets and Essential Data for Commitment of Treatment study, a nationwide cross-sectional and prospective epidemiological study, were recruited from German primary care practices. In the cross-sectional study, subjects with type 2 diabetes mellitus had a higher prevalence of malignancies (66/1308, 5.1%) compared to nondiabetic subjects (185/6211, 3.0%) (odds ratio, 1.64; 95% confidence interval, 1.12-2.41) before and after adjustment for age, sex, hemoglobin A1c, smoking status, and body mass index. Patients on metformin had a lower prevalence of malignancies, comparable with that among nondiabetic patients, whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders; inclusion of metformin in these regimens decreased the prevalence of malignancies. In the prospective analyses, diabetic patients in general and diabetic patients treated with insulin (either as monotherapy or in combination with other treatments) had a 2- and 4-fold, respectively, higher mortality rate than nondiabetic patients, even after adjustment for potential confounders (incidence of cancer deaths in patients with type 2 diabetes mellitus [2.6%] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [1.2%]). Our results suggest that diabetes and medications for diabetes, with the exception of the insulin sensitizer metformin, increase cancer risk and mortality.

Introduction: The diploma thesis deals with the issue of compensation of type 1 diabetes mellitus during pregnancy and its relation to the health of mother and child. It further summarizes and describes the variable factors that may have a direct effect on current glycemic variability and long- term compensation of diabetes. Aims: The theoretical part describes the characteristics of type 1 diabetes mellitus and the possibilities of therapy in pregnancy. Subsequently, factors influencing the compensation of diabetes in this period are summarized and described in more detail, especially food composition and possibilities of influencing postprandial glycemia, effects of type and intensity of physical activity and psychosocial aspects related mainly to stress from potential negative effects of glycaemia on the fetus. At the end of the theoretical part, the risks and complications for the mother and the fetus arising from long-term unsatisfactory compensation of diabetes are presented. The aim of the practical part of the thesis was to determine the extent of women's knowledge about the compensation of diabetes in pregnancy, followed by determining the effect of the extent of knowledge on long-term compensation, expressed by glycated hemoglobin. Methods: Data for the diploma thesis were obtained on the...

BakgrundDiabetes typ 2 är en av de vanligaste kroniska sjukdomarna i Sverige. Det innebär att cellernas respons till insulin har blivit nedsatt. Genom att kontrollera blodsockret minskas risken att drabbas av komplikationer. Målsättningen med insulinbehandling är patientens välmående och ett stabilt blodsocker. När patienterna är inne i en förändring känner de sig sårbara, då de behöver lära sig nya mönster. SyfteAtt beskriva upplevelsen hos personer med diabetes typ 2 vid övergång från tablett till insulinbehandling i Sverige. MetodKvalitativ litteraturöversikt genomfördes utifrån 11 vetenskapliga artiklar. Insamlingen av resultat artiklarna gjordes utifrån databaserna CINAHL, PubMed och MEDLINE. Artiklarna analyserades enligt Fribergs analysmetod. ResultatResultatet presenteras i fem huvudteman: Svårt att förstå vad som hänt, olika rädslor, förändring i vardagen, behov av stöd och bättre kontroll av blodsockret. KonklusionNär patienterna skulle börja med insulinbehandling hade de svårt att förstå vad som hänt. De blev rädda när de fick råd från vårdpersonalen att söka om komplikationer på nätet. Patienterna hade för höga krav som gjorde att de mådde dåligt. Deras självförtroende förbättrades när de visste mer om diabetesen. När de fick träffa vårdpersonalen skapade det ett lugn hos patienterna. Genom att träffa andra som har samma sjukdom förbättrades patienternas egenvård. / BackgroundType 2 diabetes is one of the most common chronic diseases in Sweden. This means that the cells' response to insulin has been impaired. By controlling blood sugar, the risk of complications is reduced. The goal of insulin therapy is the patient's well-being and stable blood sugar. When patients are in the midst of a change, they feel vulnerable, as they need to learn new patterns. AimTo describe the experience in people with type 2 diabetes when switching from tablet to insulin treatment in Sweden. MethodA qualitative literature review was conducted based on 11 scientific articles. The collection of the results was done based on the databases CINAHL, PubMed and MEDLINE. The articles were analyzed according to Friberg's method of analysis. Findings:The results are presented in five main themes: Difficult to understand what has happened, different fears, change in everyday life, need for support and better control of blood sugar. ConclusionWhen the patients were about to start insulin treatment, they had difficulty understanding what had happened. They were frightened when they were advised by the healthcare professional to search for complications online. The patients' demands were too high, which made them feel bad. Their self-confidence improved when they knew more about the diabetes. When they got to meet the healthcare staff, it created a sense of calm among the patients. By meeting others who have the same disease, the patients' self-care improved.

Gestationdiabetes (GDM) ist eine der häufigsten Schwangerschaftserkrankungen mit einer Inzidenz von 3-10% je nach untersuchter Population. GDM ist definiert als eine erstmals in der Schwangerschaft diagnostizierte Glukosetoleranzstörung. Die kindlichen Komplikationen resultieren aus der maternalen Hyperglykämie , die zu erhöhten fetalen Blutglukosespiegeln und reaktivem fetalen Hyperinsulinismus führt. Der fetale Hyperinsulinsmus gilt als Ursache für die typische Diabetes assoziierte fetale und neonatale Morbidität, wie Makrosomie, verzögerte Lungenreife, Totgeburten, neonataler Hypoglykämie und nicht zu vergessen, einem lebenslang erhöhten Risiko für Diabetes. Die Behandlung des GDM konzentriert sich auf eine strenge Stoffwechselkontrolle zur Vermeidung von maternaler Hyperglykämie. Dies erfordert Diät und intensive Blutzuckerselbstkontrolle bei allen und zusätzliche Insulintherapie bei 30% der Schwangeren. Trotz dieser Intervention ist die Rate an neonatalen Komplikationen weiterhin erhöht. Das primäre Ziel der in der vorgelegten Habilitationsschrift zusammengefassten Studien war, zu bestimmen, in welchem Ausmaß die maternalen Glukosewerte in Schwangerschaften , die nach dem Standardmanagement behandelt wurden, prädiktiv sind für kindliche Morbidität sowohl in der frühen als auch im späteren Verlauf der Schwangerschaft. In einem zweiten Schritt wollten wir untersuchten, ob die Einbeziehung des fetalen Wachstums das Outcome verbessert und als Mittel zu antenatalen Risikoabschätzung hilfreich ist. Wir fanden eine ausgezeichnete Korrelation zwischen dem Grad der maternalen Hyperglykämie und der Morbidität in der Frühschwangerschaft. Die Höhe der Nüchternglukosewerte zum Zeitpunkt der Diagnose war der stärkste Prädiktor für kongenitale Fehlbildungen in einer großen Kohorte von 3700 Frauen. Dahingegen waren weder die diagnostischen Kriterien für GDM noch die Werte der mütterlichen Blutzuckertagesprofile prädiktiv für Morbidität in späteren Verlauf der Schwangerschaft. Entgegen der Übereinkunft, dass die Diagnose GDM mindestens zwei pathologische Werte in einem oralen Glukosetoleranztest erfordert, fanden wir bereits bei einem pathologischen Wert eine erhöhte Rate an fetalem Hyperinsulinismus, Makrosomie und neonataler Hyperglykämie. Im Gegensatz dazu war das Vorliegen einer maternalen Adipositas eng mit der Entstehung einer fetalen Makrosomie assoziiert. Wir wählten den fetalen Abdominalumfang (AU) als Mass für Makrosomie, da sich dieser als hervorragender Prädiktor für die Entstehung einer Diabetes assoziierten Maskrosomie erwiess. Zudem sahen wir eine gute Korrelation der fetalen Insulinspiegel, indirekt bestimmt über das Insulin im Fruchtwasser , und dem fetalen AU. Nach unseren Daten, schließt ein AU < 75. Perzentile das Vorliegen eines gravierenden Hyperinsulinismus aus. Basierend auf dieser Erkenntnis führten wir drei Interventionsstudien durch, bei denen die Indikation für Insulintherapie bei Schwangeren mit GDM primär nach dem fetalen AU gestellt wurde. Wir konnten zeigen, dass dieser Therapieansatz, der Insulintherapie auf Frauen mit Risiko für neonatale Morbidität , definiert als AU > 75. Perzentile , konzentriert, in einer niedrigeren Makrosomie- und Sektiorate resultiert, wenn bei Schwangerschaften mit AU > 75. Perzentile trotz maternaler Normoglykämie Insulin gegeben wird. Anderseits konnte 40% der Frauen mit Hyperglykämie eine Insulintherapie erspart werden ohne Verschlechterung des Outcomes , da der Fet während der gesamten Schwangerschaft ein normales Wachstum zeigte. Im Gegenteil, bei diesen Frauen war die Rate an Wachstumsretardierung deutlich geringer als in der Standardgruppe, in der hyperglykämische Frauen mit Insulin behandelten wurden trotz normalem oder bereits grenzwertigem fetalen Wachstum. Zusammenfassend lässt sich feststellen , das bei Schwangerschaften mit GDM die maternalen Blutzuckerwerte ein guter Prädiktor sind für Morbidität in der Frühschwangerschaft , jedoch nur begrenzt hilfreich sind, einen fetalen Hyperinsulinismus und seine Folgen hervorzusagen. Die Einbeziehung der fetalen Makrosomie als klinisches Zeichen eines möglichen Hyperinsulinismus, ermöglicht, die intensive Intervention durch Insulintherapie auf Schwangere zu konzentrieren mit erhöhten Risiko für neonatale Morbidität. / Gestational diabetes (GDM) is one of the most frequent disorders in pregnancy. The incidence ranges between 3-10% dependent on the background diabetes risk of the investigated population. GDM is defined as any glucose intolerance diagnosed first in pregnancy. The implications for the offspring result from the maternal hyperglycemia which leads to increased fetal blood glucose concentration and reactive fetal hyperinsulinism. Fetal hyperinsulinism is the cause for the diabetes associated fetal and neonatal morbidity, like macrosomia, delayed maturity of lungs and liver, stillbirth , neonatal hypoglycemia and an increased risk for diabetes in later life. Treatment of GDM focuses on tight glucose control to avoid maternal hyperglycemia. This requires diet and intensive self glucose monitoring for all women and additionally insulin therapy in 30% of the patients. Despite good glucose control the rate of neonatal morbidity is still elevated compared to pregnancies without glucose intolerance. The primary goal of the presented work was to determine to what extend maternal glycemia in GDM pregnancies treated according to the standard management predicts morbidity as well in early as well as in late pregnancy. In a second step, we investigated whether inclusion of fetal growth pattern improves the neonatal outcome and provides an additional tool for antenatal risk assessment. We found an excellent correlation between the level of maternal hyperglycemia and morbidity in early pregnancies. The fasting glucose at diagnosis of GDM was the strongest predictor for congenital anomalies in a large cohort of 3700 women with GDM. In later pregnancy, we were faced with a different situation. The data of our studies indicated that neither the current diagnostic criteria nor the maternal glucose values during therapy reliably predict neonatal morbidity. The diagnosis of GDM requires two elevated values in an oral glucose tolerance test but we found elevated amniotic fluid insulin, neonatal macrosomia and hypoglycemia even in women with only one elevated value. The values of the daily glucose profiles had not been predictive for the development of fetal macrosomia defined as an abdominal circumference (AC) > 90the percentile. In contrast, maternal obesity was tightly related to excessive fetal growth. We choose the fetal AC to diagnose intrauterine macrosomia since the fetal AC revealed to be an excellent predictor for neonatal macrosomia. Additionally, the fetal AC showed a good correlation to the fetal insulin levels determined by measurements of amniotic fluid insulin. A fetal AC > 75th percentile reliable excluded severe hyperinsulinism in our population. Based on this knowledge we performed three intervention studies where the decision for insulin therapy in women with GDM was predominately based on the fetal AC measurement. We could show that insulin therapy concentrated on pregnancies at risk for morbidity, defined as AC > 75th percentile, is a safe approach which results in a lower rate of neonatal macrosomia when insulin is given in pregnancies with AC > 75th percentile despite of normal maternal glucose level. On the other side, insulin could be avoided in 40% of the women with hypergylcemia since the fetal AC stayed < 75th percentile. In these women, the outcome even could be improved since insulin therapy in pregnancies with normal growth resulted in a high rate of growth retardation in the study group treated according the standard management. In summary, in pregnancies with GDM maternal blood glucose predicts morbidity in early pregnancy but it is of limited value to predict fetal hyperinsulinsm and it’s sequelae. The inclusion of fetal growth pattern in the considerations of therapy offers the opportunity to concentrate intensive intervention on pregnancies at high risk for morbidity.

Glycaemic control in critically ill patients has been a topic of considerable attention for the past 20 years. In literature and at scientific meetings, there have been ongoing debates regarding the efficacy of glycaemic control in these patients with frequently entirely opposite opinions. These range from a strict invasive approach with target glycaemia 4-6 mmol/l to a liberal approach tolerating even values higher than 12 mmol/l. In the preview of this PhD thesis we have analysed so far published literature and describe the reasons for this inconsistency. According to the results of recent studies, the most significant efficacy of tight glycaemic control has been observed in cardiac surgical patients. If we consider the concept of tight glycaemic control as efficient strategy, there are three important questions remaining unanswered as follow. Does the specific algorithm-protocol play a key part in the concept of tight glycaemic control alongside the knowledge and skills of nursing staff in safe and efficient blood glucose control? What is the ideal timing of starting the strategy of tight glycaemic control (TGC) in cardiac surgical patient? And is there any benefit in outcome respect to mortality or morbidity? Do we have any more safe and efficient option or add-on to standard perioperative...

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Le diabète de type 1 (DT1) est une maladie complexe qui requiert une implication importante des patients pour contrôler leur glycémie et ainsi prévenir les complications et comorbidités. L’activité physique (AP) régulière et une attention constante pour les glucides ingérés sont des adjuvants essentiels au traitement insulinique. Nous avons démontré que le questionnaire BAPAD-1, spécifiquement développé pour des adultes atteints de DT1, est un outil valide (validité prédictive, fiabilité interne et reproductibilité) pour définir des barrières associées à l’AP. Bien que le niveau de barrières envers l’AP soit faible, la crainte de l’hypoglycémie est la barrière la plus importante chez cette population. L’adoption d’un mode de vie actif est associée à un profil corporel favorable. Les adultes, avec un DT1 et non diabétique, qui maintiennent un bon niveau d’AP, soit un ratio entre la dépense énergétique totale et celle au repos ≥ 1.7, ont une masse grasse, un indice de masse corporelle et un tour de taille significativement inférieurs à ceux d’adultes moins actifs. Le niveau d’AP peut être estimé au moyen d’un moniteur d’AP comme le SenseWear Armband™. Afin de compléter les études de validation de cet outil, nous avons évalué et démontré la reproductibilité des mesures. Toutefois, la dépense énergétique est sous-estimée durant les 10 premières minutes d’une AP d’intensité modérée sur ergocycle. L’utilisation de cet appareil est donc justifiée pour une évaluation de la dépense énergétique sur de longues périodes. Le calcul des glucides est une méthode largement utilisée pour évaluer la quantité d’insuline à injecter lors des repas. Nous avons évalué dans un contexte de vie courante, sans révision de la technique, la précision des patients pour ce calcul. L’erreur moyenne est de 15,4 ± 7,8 g par repas, soit 20,9 ± 9,7 % du contenu glucidique. L’erreur moyenne est positivement associée à de plus grandes fluctuations glycémiques mesurées via un lecteur de glucose en continu. Une révision régulière du calcul des glucides est probablement nécessaire pour permettre un meilleur contrôle glycémique. Nous avons développé et testé lors d’un essai clinique randomisé contrôlé un programme de promotion de l’AP (PEP-1). Ce programme de 12 semaines inclut une séance hebdomadaire en groupe ayant pour but d’initier l’AP, d’établir des objectifs et d’outiller les adultes atteints de DT1 quant à la gestion de la glycémie à l’AP. Bien que n’ayant pas permis d’augmenter la dépense énergétique, le programme a permis un maintien du niveau d’AP et une amélioration de la condition cardio-respiratoire et de la pression artérielle. À la fin du programme, une plus grande proportion de patients connaissait la pharmacocinétique de l’insuline et une plus grande variété de méthodes pour contrer l’hypoglycémie associée à l’AP était utilisée. En conclusion, le diabète de type 1 engendre des défis quotidiens particuliers. D’une part, le calcul des glucides est une tâche complexe et son imprécision est associée aux fluctuations glycémiques quotidiennes. D’autre part, l’adoption d’un mode de vie actif, qui est associée à un meilleur profil de composition corporelle, est limitée par la crainte des hypoglycémies. Le programme PEP-1 offre un support pour intégrer l’AP dans les habitudes de vie des adultes avec un DT1 et ainsi améliorer certains facteurs de risque cardio-vasculaire. / Type 1 diabetes (T1D) is a complex disease requiring continuous self-management. Physical activity (PA) and carbohydrate counting are essential counterparts to insulin therapy for blood glucose control in order to prevent complications and comorbidities. We have demonstrated the validity (predictive validity, internal validity and reproducibility) of the BAPAD-1 scale to assess perceived barriers associated with PA practice. Fear of hypoglycemia is the strongest perceived barrier among adults with T1D. An active lifestyle, as described by a physical activity level (ratio of total over resting energy expenditure) ≥ 1.7, is associated with a better body composition compared to less active adults. Adults who are more active show significantly less fat mass, smaller body mass index and smaller waist circumference. Motion sensors, like the SenseWear Armband™, are useful to estimate PA level. To complement prior validation studies, we evaluated and confirmed the reproducibility of the SenseWear Armband™ measurements. However, we also observed that energy expenditure is underestimated at the onset of moderate intensity ergocycling. Thus, this motion sensor should be used to evaluate energy expenditure over long periods of time rather than short length exercise. Carbohydrate counting is a widely used method to evaluate prandial insulin doses. We evaluated, in a real-life setting without prior method revision, the accuracy of adults with T1D for carbohydrate estimation. The mean meal error was 15.4 ± 7.8 g or 20.9 ± 9.7 % of total carbohydrate content. The mean meal error was positively associated with larger daily glucose fluctuations measured by a continuous glucose monitoring system. Regular educational tips regarding carbohydrate counting may be necessary to improve glycemic control. In order to improve PA practice, we developed and tested in a randomized controlled trial a PA promotion program (PAP-1). This 12-week program includes a weekly group session designed for PA initiation, goal setting and improving knowledge about glycemic control during PA. Even if the program failed to improve total energy expenditure, participants improved their cardiorespiratory fitness and blood pressure. At the end of the program, a larger proportion of the participants were knowledgeable of insulin pharmacokinetics and they used more various methods to prevent hypoglycemia related to PA. In conclusion, type 1 diabetes obtrudes many daily challenges. On one hand, carbohydrate counting is a complex job and its inaccuracy is associated with glycemic fluctuations. On the other hand, even if having an active lifestyle is associated with a better body composition, fear of hypoglycaemia may impede PA practice. The PAP-1 program offers support to adults with T1D to adopt an active lifestyle and thus improve some cardivascular risk factors.

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