O Diabetes Mellitus é uma das maiores causas de morte no mundo. O desenvolvimento do Diabetes Mellitus tipo 2 (DM2) está relacionado com uma série de fatores genéticos e ambientais, culminando com o desenvolvimento do DM2. Já a hiperglicemia, característica marcante da doença, está associada a uma série de complicações metabólicas e comorbidades. No entanto, nào se sabe a influência de um controle apropriado da doença, com menores níveis glicêmicos. No presente trabalho, foi utilizada a técnica de microarrays para comparar os perfis transcricionais (mRNA e microRNA) de células mononucleares de sangue periférico (PBMCs) em três grupos distintos: um grupo de pacientes DM2 descompensados (DM2-D, n=13); um grupo de pacientes DM2 compensados (DM2-C, n=14), e um grupo controle (n=10). Os dados foram analisados por meio de duas linguagens de programação: R e PERL. Após a extração dos dados utilizando-se o software Feature Extraction, versão 10.7 (Agilent Techonologies), foram realizadas correção do background, exclusão dos outliers, normalização dos dados pelo método quantile e, por fim, o ajuste de variações nãobiológicas. Os dados foram então submetidos a análise estatística rank products, sendo identificados 415 mRNAs diferencialmente expressos no grupo DM2-C relativamente aos controles, 285 no grupo DM2-D em comparação aos controles e 478 em pacientes DM2-D comparados aos DM2-C. Posteriormente, os genes diferencialmente expressos foram submetidos à analise de enriquecimento funcional (DAVID). Foram encontrados 22 e 56 termos biológicos enriquecidos (p-corrigido Benjamini-Hochberg < 0,05) para as comparações DM2-C versus controle e pacientes DM2-D versus DM2-C, respectivamente. Em ambas as comparações, um processo biológico foi considerado de interesse para o presente trabalho: resposta inflamatória. Na análise por GSEA e GSA, foram identificados 110 grupos gênicos diferencialmente expressos na comparação DM2-C versus controle. Já para a comparação DM2-D versus controles foram encontrados 297 grupos gênicos diferencialmente expressos, enquanto que na comparação DM2-D versus DM2-C, 161 grupos gênicos diferencialmente expressos. Dentre os grupos gênicos diferencialmente expressos, três merecem destaque: regulação do reparo do DNA (GO: 0006282), resposta ao superóxido (GO: 0000303) e resposta ao estresse do retículo endoplasmático (GO: 0034976). Ainda, 97 microRNAs foram diferencialmente expressos na comparação DM2-C versus controles, 54 na comparação DM2-D versus controles e 101 na comparação DM2-D versus DM2-C. Assim, diferentes grupos gênicos provavelmente foram modulados pela hiperglicemia, além de terem sido descobertos novos microRNAs relacionados a altos níveis de glicose. / Diabetes mellitus is a major cause of death worldwide. The development of type 2 Diabetes Mellitus (T2D) is associated with a number of genetic and environmental factors, culminating in the development of T2D. Hyperglycemia, a hallmark of the disease, is associated with a number of metabolic complications and comorbidities. However, the influence of a proper control of the disease, with lower glucose levels is unknown. In this study, we used the microarrays technique to compare the transcriptional profiles (mRNA and microRNA) of peripheral blood mononuclear cells (PBMCs) in three distinct groups: a group of patients with uncontrolled T2D patients (T2D-U, n = 13) a group of controlled T2D patients (T2D-C, n = 14) and control group (n = 10). Data were analyzed using two programming languages: R and PERL. After extracting the data using the Feature Extraction software, version 10.7 (Agilent Technologies), background correction, outliers exclusion, data normalization by quantile and adjustmesnt of non-biological variations were performed. The data were then statistically analyzed by the rank products test, which identified 415 differentially expressed mRNAs in T2D-C group compared to controls, 285 in group T2D-U in comparison with controls and 478 when T2D-U and T2D-C are compared. Thereafter, the differentially expressed genes were subjected to functional enrichment analysis (DAVID). 22 and 56 biologically enriched terms were found (Benjamini-Hochberg-corrected p value<0.05), when comparing T2D-C with controls and T2D-U with T2D-C, respectively. In both comparisons, inflammatory response was selected as a biological process of interest. The analysis by GSEA and GSA identified 110 differentially expressed gene sets in comparison T2D-C versus control. As for the comparison T2D-U versus control, 297 gene sets were found differentially expressed, whereas in comparison T2D-U versus T2D-C, 161 differentially expressed gene sets were found. Among the differentially expressed gene sets, three stand out: regulation of DNA repair (GO: 0006282), superoxide response (GO: 0000303) and response to endoplasmic reticulum stress (GO: 0034976). Still, 97 microRNAs were differentially expressed in the T2D-C versus controls comparison, 54 when comparing T2D-U versus controls and 101 in the comparison of T2D-U versus T2D-C. Thus, different gene sets were probably modulated by hyperglycemia, and new microRNAs related to high levels of glucose were discovered.

A nifedipina é uma dihidropiridina, antagonista de canal de cálcio utilizada no tratamento hipertensão arterial na gravidez. O presente estudo visa avaliar a influência do DM2 na farmacocinética da nifedipina em gestantes hipertensas. Foram avaliadas 12 gestantes hipertensas (grupo controle) e 10 gestantes hipertensas portadoras de DM 2 controlado (grupo DM), em uso de nifedipina retard (20 mg, 12/12 horas). A partir da 34ª semana de gestação foram coletadas amostras seriadas de sangue para a análise farmacocinética nos tempos zero, 10, 20, 30, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, 600, 660 e 720 minutos após a administração do medicamento. Na resolução da gravidez coletou-se sangue materno e fetal para determinar a taxa de transferência placentária da nifedipina. Foram coletadas também alíquotas de sangue do espaço interviloso e de líquido amniótico para a determinação da distribuição do fármaco nestes compartimentos. As concentrações de nifedipina em plasma e líquido amniótico foram analisadas por LC-MS/MS. Os parâmetros farmacocinéticos e de transferência placentária da nifedipina, reportados como mediana foram comparados usando o teste Mann-Whitney, com nível de significância fixado em p<0,05. Os parâmentros encontrados para o grupo controle foram Cmax 26,41 ng/mL; tmax 1,79h; AUC0-12 235,99 ng.h/mL; Kel 0,16 h-1; t1/2 4,34 h; Vd/F 560,96 L; ClT/F 84,77 L/h. Para o grupo DM, foram encontrados os seguintes parâmetros Cmax 23,52 ng/mL; tmax 1,48h; AUC0-12 202,23 ng.h/mL; Kel 0,14 h-1; t1/2 5,00 h; Vd/F 609,40 L; ClT/F 98,94 L/h. As razões da concentração plasmática da nifedipina na veia umbilical, artéria umbilical, espaço interviloso e líquido amniótico pela concentração plasmática na veia materna foram para o grupo controle e para o grupo DM 0,53 e 0,44; 0,46 e 0,33; 0,78 e 0,87, respectivamente, e 0,05 para ambos os grupos. A razão da concentração plasmática da artéria umbilical pela veia umbilical foi 0,82 para o grupo controle e 0,88 para o grupo DM. Não houve influência do DM2 na farmacocinética e transferência placentária da nifedipina em gestantes hipertensas portadoras de diabetes controlado. O estudo sugere que o regime de dose da nifedipina não precisa ser modificado. / Nifedipine is a dihydropyridine calcium channel blocker used in the treatment of hypertension in pregnant women. The present study aims to evaluate de effect of T2DM on the pharmacokinetics of nifedipine in hypertensive pregnant women.12 hypertensive pregnant women (control group) and 10 hypertensive pregnant women with controlled T2DM, using nifedipine retard (20 mg, 12/12h) were evaluated. From 34th week of gestation, serial blood samples were collected for pharmacokinetics analysis at times zero, 10, 20, 30, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, 600, 660 e 720 minutes after drug administration. At delivery, maternal blood, umbilical vein and umbilical artery were collected to determine the rate of placental transfer of nifedipine. Aliquots from placental intervillous space and amniotic fluid were also collected to determine the drug distribution in these compartments. The concentrations of nifedipine in plasma and amniotic fluid were analyzed by LC-MS/MS. Pharmacokinetics and transplacental transfer parameters of nifedipine, reported as median, were compared using Mann-Whitney test, with the level of significance set at p<0.05. The parameters presented for control group were Cmax 26.41 ng/mL; tmax 1.79h; AUC0-12 235.99 ng.h/mL; Kel 0.16 h-1; t1/2 4.34 h; Vd/F 560.96 L; ClT/F 84.77 L/h. For T2DM group the parameters presented were Cmax 23.52 ng/mL; tmax 1.48h; AUC0-12 202.23 ng.h/mL; Kel 0.14 h-1; t1/2 5.00 h; Vd/F 609.40 L; ClT/F 98.94 L/h. The ratios of plasma concentration of nifedipine in umbilical vein, umbilical artery, intervillous space and amniotic fluid for plasma concentration of maternal vein for control group and T2DM group were 0.53 and 0.44; 0.46 and 0.33; 0.78 and 0.87, respectively, and 0.05 for both groups. The ratios of plasma concentration of umbilical artery and umbilical vein were 0.82 for control group and 0.88 for T2DM group. T2DM does not influence the pharmacokinetics of nifedipine in hypertensive pregnant women with controlled diabetes. The study suggests that the nifedipine dose regimen doesnt need to be modified.

Orientadores: Maria Cândida Ribeiro Parisi, Denise Engelbrecht Zantut-Wittmann / Texto em português e inglês / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T20:42:36Z (GMT). No. of bitstreams: 1 Coelho_CamilaRibeiro_D.pdf: 2296244 bytes, checksum: c5e2df235d7e14987d80dcffad142e95 (MD5) Previous issue date: 2014 / Resumo: A depressão vem sendo reconhecida como um fator de risco para ulceração em pacientes portadores de diabetes mellitus. Usando amostra de conveniência, este estudo transversal foi conduzido com o objetivo de comparar sintomas depressivos e comportamentos de autocuidado em população de portadores de pé diabético com úlcera e portadores de pé de risco. Foram estudados 100 portadores de diabetes mellitus tipo 2, classificados em 2 grupos: pacientes com pé de risco para ulceração e pacientes com úlcera. Avaliamos o comportamento de autocuidado com os pés (Questionário de Avaliação de Autocuidado com os pés), sintomas de depressão (Inventário Beck de Depressão), além das variáveis sócio-demográficas e clínicas. Pacientes com úlcera obtiveram resultados evidenciando escores maiores, indicativos de depressão (20.37), que os pacientes que não haviam desenvolvido úlceras em pés (15.70) (p=0.030). Em relação aos comportamentos de autocuidado, não encontramos diferença significativa entre os dois grupos (p=0.219). As seguintes variáveis mostraram-se significativas para o desenvolvimento de úlceras em pé diabético: sexo masculino (p<0.001, OR =14.87, IC 95% 3.83 ¿ 57.82) e depressão grave (p=0.049, OR= 6.56 95% IC 1.01-42.58). A despeito da presença de comportamentos adequados de autocuidado com os pés, pacientes com úlcera apresentaram mais sintomas de depressão em comparação aos pacientes com risco para o desenvolvimento de úlceras. São necessárias futuras pesquisas que estabeleçam a relação causal entre as variáveis e o potencial papel de intervenções para a depressão. Estes resultados, assim como os de outros estudos, apontam para a importância da avaliação da depressão em pacientes portadores de úlceras de pé diabético / Abstract: Depression has been recognized as a risk factor for foot ulceration in persons with diabetes mellitus. The purpose of this study was to evaluate symptoms of depression and self-care behaviors in patients with diabetic foot ulcer and with foot at risk and compare them. Using convenience sampling methods, a cross-sectional study was conducted among persons with type 2. One hundred patients with type 2 diabetes were studied and divided into two groups: patients with foot at risk for ulceration and patients with ulcer. Symptoms of depression (Beck Depression Inventory- BDI) and foot self-care behavior were assessed. Patients with ulcer obtained higher BDI score results indicative of depression (20.37) than the patients that had not developed foot ulcers (15.70) (p=0.030). Regarding self-care behaviors, we did not find a significant difference between the two groups (p=0.219). The following variables were significant for the development of diabetic foot ulcers: male gender (p<0.001, OR =14.87, IC 95% 3.83 ¿ 57.82) and severe depression (p=0.049, OR= 6.56 95% IC 1.01-42.58). Despite reported adequate self-care behaviors, patients with an ulcer had more symptoms of depression than patients who were at risk for developing a foot ulcer. Studies examining cause-and-effect relationships between these observations and the potential role of depression interventions are needed. The results of this and other studies suggest depression screening is important in patients with diabetes mellitus and foot ulcers / Doutorado / Clinica Medica / Doutora em Clínica Médica

Orientador: Dennys Esper Corrêa Cintra / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Aplicadas / Made available in DSpace on 2018-08-25T14:56:46Z (GMT). No. of bitstreams: 1 Lazari_VanessadeOliveira_M.pdf: 4172597 bytes, checksum: 62cbaf2cfa729f497e7b3cc4cdf3e7a1 (MD5) Previous issue date: 2013 / Resumo: A obesidade é uma doença metabólica absolutamente fora de controle. As condições primárias associadas são hipertensão arterial, dislipidemias, diversos tipos de câncer, resistência à insulina (RI) e principalmente o diabetes mellitus tipo 2 (DM2). Dentre as características secundárias, esteatose hepática e síndrome do ovário policístico figuram entre as principais. Tais doenças acometem número cada vez maior de indivíduos e sobrecarregam sistemas públicos mundiais de saúde. A inflamação crônica e de baixo grau, designada "meta-inflamação", por acometer todo o organismo, parece ser o pano de fundo principal do processo obesogênico, resultando no descontrole da ingestão alimentar e na predisposição ao surgimento da RI podendo progredir para o DM2. Diante da ineficiência de terapêuticas farmacológicas atuais para o controle da obesidade, o investimento em estratégias anti-inflamatórias tem sido incentivado. Nesse intuito, ácidos graxos insaturados (AGIs), especialmente os ômega-3 (?3) e ômega-9 (?9) têm-se mostrado eficientes em atenuar a inflamação por meio da ativação do receptor GPR120, e em recuperar a sensibilidade à insulina em diversos tecidos. O objetivo deste trabalho foi avaliar as ações e mecanismos anti-inflamatórios dos AGIs ?-linolênico (?3) e oléico (?9), presentes em elevadas concentrações no óleo de semente de linhaça e oliva respectivamente, em tecidos periféricos metabolicamente ativos de animais obesos e diabéticos induzidos por dieta rica em gordura (HF), e suas repercussões na regulação glicêmica do organismo. O tratamento via dieta HF com substituição em 10% da fração saturada pelos respectivos óleos, foi eficiente em restabelecer o controle da fome dos animais que consequentemente ganharam menos peso em relação aos seus controles obesos. Dados fisiológicos obtidos por meio de medições de glicemia de jejum e dos testes de tolerância à insulina (ITT) e à glicose (GTT) evidenciaram melhoras na homeostase glicêmica, confirmado em nível molecular pelo aumento da atividade das principais proteínas envolvidas na via da insulina como o IR, IRS-1 e Akt. Possivelmente esses resultados deram-se em virtude da redução da expressão de peptídeos pró-inflamatórios como TNF-?, IL-6 e IL-1?, seguidos pelo aumento da expressão da IL-10, de caráter anti-inflamatório. No fígado, a melhora na sensibilidade à insulina, resultou em inibição da enzima GSK-3 propiciando o restabelecimento do controle hepático sobre o metabolismo da glicose. Análises por hematoxilina/eosina (HE) e imunohistoquímica evidenciaram menor acumulação lipídica e redução da infiltração de macrófagos M1 no parênquima hepático, resultando em melhora do fenótipo de esteatose hepática macrovesicular e recuperação funcional deste tecido. Houve diminuição da hipertrofia dos adipócitos, fato que contribuiu com a remissão da inflamação. Foi verificada a presença do receptor GPR120 nestas células, permitindo, portanto a entrada dos AGIs. A técnica de espectrometria de massa atestou a incorporação dos AGIs de interesse no fígado, sustentando a hipótese de que os efeitos benéficos encontrados ocorreram em decorrência das ações destes nutrientes. Esses achados permitem concluir que fontes alimentares dos AGs ?3 e ?9 modulam de forma potente a resposta inflamatória no organismo. Tais ações são controladas pelo GPR120, receptor comum a esses AGs, e parecem ocorrer de maneira tecido-específica com repercussões sistêmicas, positivas para o controle glicêmico / Abstract: Obesity is characterized as a metabolic disease absolutely out of control which nowadays reaches epidemic levels. The diseases associated to thiscomorbid as hypertension, dyslipidemia, several kinds of cancer, insulin resistance (IR), type 2 diabetes (DM2) and secondary conditions as hepatic steatosis and polycystic ovary syndrome affect a large number of people,burdening the public health system. The low grade chronic inflammation seems to be the main cause of the obesogenic processes, resulting in an uncontrolled food intake and the predisposition for insulin resistance (IR), which can lead to type II diabetes. Once there is no effective pharmacological therapy to treat obesity so far, the investment in anti-inflammatory approaches has been encouraged. In this regard, unsaturated fatty acid, mostly 3-omega (?3) and 9-omega (?9) have been shown effective in decreasing the inflammatory process by activating its common receptor, the GPR120, by recuperating the insulin sensibility in several tissues resulting in improvements in the systemic glucose homeostasis. The purpose of this study was to evaluate the potential antiinflammatory effects of the fatty acids ?-linolenic(?3) and oleic (?9), found in high concentrations in flaxseed and olive oil respectively on active metabolic tissue as liver, skeletal muscle and white adipose tissue of obese and diabetic animals induced by high fat diet, as well as its effects on insulin signaling and glycemic regulation. The high fat treatment with 10% replacement of the saturated portion by ?3 or ?9 oil was effective in restoring the control of food intake in the animals, which consequently gained less weight compared to the obese group. Physiological data from fasting glycemic measure, insulin and glucose tolerance test (ITT and GTT) have showed improvements in the glycemic homeostasis, which was molecularly confirmed by the increase in the activity of the main proteins involved in the insulin signaling pathway as the IR, IRS-1 and AKT. We believe that these results are due to the decrease in proinflammatory peptides expression as TNF-?, IL-6 and IL-1? and increase in the IL-10 expression, known by its anti-inflammatory effects. Improvements in insulin sensitivity in liver resulted in GSK-3 inhibition culminating in the glucose hepatic metabolic reestablishing which contributes to restore the control of plasma glucose levels. Hematoxilin/Eosin (HE) and Immunohistochemistry analysis showed lower lipid accumulation and decreased macrophage infiltration in hepatic parenchyma corroborating the reducing in macrovesicular steatosis and functional recovering of this tissue. There was reduction in adipocyte size, which contributed to "meta-inflammation" remission. We could note the presence of GPR120 receptor in membrane of these cells probably allowing the ?3 and ?9 entry. Mass spectrometry technique attested high incorporation of these fatty acids in liver suggesting the beneficial effects found were due to these nutrients actions. These findings allow us to conclude that alimentary sources of ?3 and ?9 fattty acids modulate effectively the systemic inflammatory response, resulting in the insulin sensibility restoration and in the glucose tolerance improvement. Such nutrients have shown to be important therapeutic nutrigenomic tools against obesity and its associated comorbidities / Mestrado / Nutrição / Mestra em Ciências da Nutrição e do Esporte e Metabolismo

Background: The One Drop vertical bar Mobile app supports manual and passive (via HealthKit and One Drop's glucose meter) tracking of self-care and glycated hemoglobin A(1c) (HbA(1c)). Objective: We assessed the HbA(1c) change of a sample of people with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the One Drop vertical bar Mobile app on iPhone and Apple Watch, and tested relationships between self-care tracking with the app and HbA(1c) change. Methods: In June 2017, we identified people with diabetes using the One Drop vertical bar Mobile app on iPhone and Apple Watch who entered two HbA(1c) measurements in the app 60 to 365 days apart. We assessed the relationship between using the app and HbA(1c) change. Results: Users had T1D (n=65) or T2D (n=191), were 22.7% (58/219) female, with diabetes for a mean 8.34 (SD 8.79) years, and tracked a mean 2176.35 (SD 3430.23) self-care activities between HbA(1c) entries. There was a significant 1.36% or 14.9 mmol/mol HbA(1c) reduction (F=62.60, P<.001) from the first (8.72%, 71.8 mmol/mol) to second HbA(1c) (7.36%, 56.9 mmol/mol) measurement. Tracking carbohydrates was independently associated with greater HbA(1c) improvement (all P<.01). Conclusions: Using One Drop vertical bar Mobile on iPhone and Apple Watch may favorably impact glycemic control.

No description available.

Bakgrund: Typ 2-diabetes är en folksjukdom som är utspridd över hela världen och förutses bli allt mer förkommande. Sjukdomen och dess komplikationer innebär en livsstilsförändring för de som drabbas men även en stor kostnad för samhället. Egenvård är en stor del i behandlingen av typ 2-diabetes och sjukvården har en viktig roll i att genom patientutbildning, råd och stöd motivera patienter till att genomföra egenvården.                                                                       Syfte: Syftet var att beskriva typ 2-diabetespatienters upplevelser av egenvård.                         Metod: Litteraturstudie som baserades på 12 artiklar med kvalitativ metod. Artikelsökning gjordes i databaserna PubMed, CINAHL, SveMed+ och PsycINFO.                                                   Resultat: Resultatet visade att god kontakt med kunnig vårdpersonal och tillgång till patientutbildningar som bidrar till kunskap hos patienterna främjar egenvården vid typ 2-diabetes. Även stöd och motivation från familj och andra personer i sin närhet ökar patienternas motivation till att utföra egenvård. Faktorer som hindrar eller gör det svårare för patienter att utföra egenvård är bland annat brist på stöd från vårdpersonal, familj och vänner. Egenvårdsbrist är också en konsekvens av vilken kultur patienten tillhör samt vilken socioekonomisk status patienten har.                                                                            Slutsats: Grundläggande för god egenvård är en individanpassad vård där både vårdpersonalens och patientens kunskap om typ 2-diabetes och dess behandling ska vara hög. / Background: Type 2 diabetes is a widespread disease and is expected to become increasingly prevalent. The disease and its complications mean a lifestyle change for the people that are afflicted but it also implies to a great cost on society. Self care is a major part in diabetes treatment and healthcare plays an important role in motivating patients to carry out self-care through patient education, counseling and support.                                                                     Aim: The aim of this study was to describe the experiences of self-care by type 2 diabetes patients.                                                                                                                                  Method: Literature study based on 12 articles with qualitative method. Article search was made in the databases PubMed, CINAHL, SveMed + and PsycINFO.                                             Results: The result showed that good contact with skilled healthcare professionals and access to patient education that contributes to knowledge promotes self-care in type 2 diabetes. Also support and motivation from family and other people in their vicinity increases the patient's motivation to perform self-care. Factors that prevent or make it more difficult for patients to perform self-care are lack of support from healthcare professionals, family and friends. Self-deficiency is also a consequence of the culture and the socio-economic status of the patient.                                                                        Conclusion: The foundation for good self-care is individualized care where both the healthcare professional's and the patient's knowledge about type 2 diabetes and its treatments is high.

Le diabètes mellites de type 2 (T2DM) est caractérisé par une hyperglycémie provenant d’une dérégulation de la sécrétion d’insuline combinée avec une altération de l’action de l’insuline. CaMK1D est un nouveau gène identifié, dont le rôle reste à explorer. Dans l’étude exposée ici, j’ai montré que CaMK1D a un effet majeur sur la régulation du glucose. J’ai observé une réduction exceptionnelle des taux de glucose sanguins à jeun, ce qui entraine une amélioration globale de la tolérance au glucose. Les souris mutantes montrent une augmentation conséquente dans les niveaux sanguins d’insuline. Les souris invalidées pour CaMK1D présentent des ilots pancréatiques de taille plus importante due à une hypertrophie des cellules béta. De plus, les souris mutantes sont protégées contre la stéatose hépatique. Dans l’ensemble, mon travail met en évidence le nouveau rôle clé de CaMK1D chez les cellules béta et apporte plus de compréhension quant à son rôle lors du développement du T2DM. / Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia resulting from defects in insulin secretion in combination with impaired insulin action. CaMK1D represents one potential candidate gene, the in vivo function remained elusive. In this work, I have found that CaMK1D plays a central role in blood glucose regulation. Pancreas-specific CaMK1D knockout mice display dramatically reduced fasting blood glucose levels leading to an overall improved glucose tolerance. CaMK1D knockout mice show markedly higher ad libitum and fasting insulin levels. Interestingly, pancreas-specific CaMK1D knockout mice display islet hyperplasia caused by beta-cell hypertrophy. Furthermore, conditional knockout mice are protected against high-fat feeding-induced hepatic steatosis. Overall, my work establishes an essential role of CaMK1D in pancreatic beta-cells and provides further understanding about its role in the development of T2DM.

Bakgrund: Typ 2-diabetes är ett växande folkhälsoproblem. Trots detta finns det få studier som undersöker hur personer upplever det att få denna diagnos, hur de hanterar nödvändiga livsstilsförändringar samt hur stödet från diabetessjuksköterskan upplevs. Syfte: Att beskriva individers upplevelser och erfarenheter av att diagnostiseras med typ 2-diabetes samt hur de upplever stödet från diabetessjuksköterskan på vårdcentralen den första tiden efter diagnos. Metod: Kvalitativ intervjustudie med semistrukturerade frågor. Nio deltagare inkluderades med bekvämlighetsurval. Intervjuerna analyserades med både manifest och latent innehållsanalys enligt Graneheim och Lundmans metod. Resultat: Analysen från intervjuerna resulterade i två teman och sju subteman. Det första temat var Upplevelser och känslor den första tiden efter en diabetesdiagnos med följande subteman: Upplevelser vid diagnostillfället, Upplevelser och känslor av att leva med diabetes samt Hantering av vardagslivet. Det andra temat var Upplevelser och erfarenheter av diabetesvården med tillhörande subteman: Upplevelser av stöd från diabetessjuksköterskan, Multiprofessionellt team, Förbättringsområden och Hälsolitteracitet. Slutsats: Upplevelsen av att få diagnosen typ 2-diabetes kunde komma chockartat eller som en lättnad att det inte var värre. Trots att kunskapen fanns om nödvändiga livsstilsförändringar så var det svårt att få till hållbara strategier och lösningar i vardagen. Stödet från diabetessjuksköterskan var viktigt och kunde påverka hur motiverade deltagarna var att införa hälsosamma rutiner i sitt liv. / Background: Type 2 diabetes is a growing public health problem. Despite this, there are few studies exploring how people react to this diagnosis, how they deal with the necessary lifestyle changes and what they think about the support offered by the diabetes nurse. Aim: To describe individuals’ perceptions and experiences of being diagnosed with type 2 diabetes as well as their impressions of the support offered by the diabetes nurse at the primary health center during the initial period after the diagnosis. Methods: Qualitative interview study with semi structured questions. Nine participants were selected through convenience sampling. The interviews were analysed through both manifest and latent content analysis in accordance with the Graneheim and Lundman method. Results: The analysis of the interviews resulted in two themes and seven subthemes. The first theme concerns Perceptions and emotions during the initial period of a diabetes diagnosis with the following subthemes: Perceptions at the time of diagnosis, Views and emotions regarding life with diabetes and Handling of everyday life. The second theme concerns Views on and experiences of diabetes care with the following subthemes: Views on the support received from the diabetes nurse, Multi-professional team, Areas of improvement and Health literacy. Conclusion: The announcement of a type 2 diabetes diagnosis sometimes came as a chock and sometimes as a relief. Despite being aware of the necessary lifestyle changes, the interviewees had difficulties applying sustainable strategies and solutions in their daily lives. Support from the diabetes nurse was important and could influence the participants’ commitment to introducing healthy habits into their lives.

Introduction: Type 2 diabetes mellitus (T2DM) is a worldwide spread disease of affluence which prevalence has been growing. Although, the probability of its manifestation is being linked above all with environmental factors, genetic susceptibility plays an important role too. The aim of this thesis was to find out the association of four polymorphisms with the risk of T2DM manifestation in Czech population. Polymorphisms rs10203174 THADA, rs6819243 MAEA, rs849135 JAZF1 and rs1552224 ARAP1 (CENTD2) were chosen based on their risk in British population. Methodology: We studied groups of 712 Czech patients with T2DM and 752 healthy controls selected as a random sample of Czech population in the post-MONICA study. For a genotypisation rs10203174 and rs6819243 we used the PCR-RFLP method. For an analysis of genotypes rs849135 and rs1552224 was used the real-time PCR method. The results were analysed via odds ratio (OR) a chi-square test. Results: In case of the rs1552224 variant, the risk was proved with statistical significance (P = 0,01). The value of OR for the risk allele T is 1,37 (95% CI 1,07-1,75). In case of the polymorphisms rs10203174, rs6819243 and rs849135 no significant association with the disease was proved. For rs10203174 the value of OR of the allele C is 1,20 (95% CI 0,91-1,56, P = 0,20), OR of...