2 型糖尿病(T2D)的發展歷史悠久，但導致T2D 患者胰島素抵抗的確切病理還沒有完全理解。骨骼肌佔大多數(70-80%)的胰島素引導的葡萄糖的吸收，所以它一直是胰島素抵抗的研究焦點。許多 T2D 患者的骨骼組織顯示線粒體功能障礙，但線粒體功能障礙和胰島素抵抗之間的關係尚不清楚還在辯論中。在這個項目中，這種關係是通過研究游離脂肪酸(FFA)( 24 小時處理)對 C2C12 小鼠骨骼肌細胞的效果來闡明。 / 免疫印記法顯示FFA 誘導胰島素抵抗，結合二維電泳和質譜分析的蛋白質組學研究發現FFA 有抑制糖酵解，增加β-氧化作用，沒有改變檸檬酸循環和抑製氧化磷酸化的作用。FFA 抑制電子傳遞鏈的幾個組成部分，揭示線粒體功能障礙，背後的原因可推測為FFA 增加令β-氧化作用增加，但沒有協調改變率檸檬酸循環，導致積累不完全β-氧化的中轉體，導致線粒體過載，最終導致胰島素抵抗。 / There is a long history of Type 2 diabetes (T2D) research development, but the exact pathology leading to insulin resistance of T2D is still not fully understood. T2D is frequently characterized by tissue insulin resistance and it is often associated with an elevated concentration of palmitic acid (PA, a major kind of dietary fatty acid) in serum. Due to this correlation, much of the effort in the field had been concentrated on the effect of PA in insulin action and glucose metabolism, and how elevated PA could possibly cause insulin resistance in specific tissues. / Skeletal muscle accounts for the majority (70-80%) of insulin-mediated glucose uptake, so it has been the focus of insulin resistance studies. Many T2D patients having elevated serum free fatty acid (FFA, where PA is a kind of FFA) also show mitochondrial dysfunction in their skeletal tissue, but the relationship between mitochondrial dysfunction and insulin resistance in skeletal muscle remains unclear and under debate. In this project, the three-party relationship was elucidated by studying the effect of 24hrs of incubation of palmitic acid (PA) on skeletal muscle using C2C12 mouse skeletal cells as model. / PA-treated C2C12 cells show reduction in insulin-stimulated Akt phosphorylation when compared with untreated C2C12 cells. Comparative proteomic study for both total proteins and mitochondrial proteins with 2D gel electrophoresis and mass spectrometry unveil, when compared with untreated cells, PA-treated C2C12 cells show down-regulation in enzymes involved in glycolysis(e.g. glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, fructose-bisphosphate aldose A), up-regulation in enzymes involved in beta-oxidation(e.g. 3-ketoacyl-CoA thiolase, 3-hydroxyacyl-CoA dehydrogenase), and down-regulation in proteins involved in oxidative phosphorylation(e.g. ATP synthase subunits, NADH-ubiquinone oxidoreductase 75kDa subunit, cytochrome b-c complex subunit 1). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Lam, Chor Kwan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 69-78). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Thesis/Assessment Committee --- p.i / Declaration --- p.ii / Abstract (in English) --- p.iii / Abstract (in Chinese) --- p.v / Acknowledgments --- p.vi / Table of Contents --- p.vii / List of Abbreviations --- p.x / List of Figures --- p.xiii / List of Tables --- p.xiv / Chapter 1. --- Literature review --- p.1 / Chapter 1.1. --- Introduction to diabetes mellitus --- p.1 / Chapter 1.1.1. --- Definition and prevalence --- p.1 / Chapter 1.1.2. --- Diagnosis and classification --- p.2 / Chapter 1.1.3. --- Symptoms and complications --- p.4 / Chapter 1.1.4. --- Causes and risk factors --- p.5 / Chapter 1.1.5. --- Prevention and treatment --- p.6 / Chapter 1.2. --- The role of muscle tissue in pathophysiology of T2DM --- p.7 / Chapter 1.3. --- Insulin receptor substrate-1 and Fatty acids-induced insulin resistance --- p.15 / Chapter 1.4. --- Introduction of proteomics --- p.18 / Chapter 1.4.1. --- The application of proteomics in disease discovery --- p.18 / Chapter 1.4.2. --- Application of Proteomics --- p.19 / Chapter 1.4.3 --- Two-dimensional gel electrophoresis --- p.20 / Chapter 1.4.4 --- Organelles proteomics --- p.21 / Chapter 1.4.5. --- Mass spectrometry --- p.22 / Chapter 1.4.6 --- Application of proteomic technology in disease pathology --- p.24 / Chapter 1.4.7 --- Current challenges --- p.25 / Chapter 1.5 --- Objectives --- p.27 / Chapter 2 --- Materials and Methods --- p.28 / Chapter 2.1 --- Fatty acid preparation --- p.28 / Chapter 2.2 --- Cell culture --- p.28 / Chapter 2.2.1 --- Treatment of C2C12 myotubes with Palmitic acid --- p.28 / Chapter 2.2.2 --- MTT assay for viability measurement --- p.29 / Chapter 2.2.3 --- Determination of the IC₅₀ values --- p.31 / Chapter 2.3 --- Proteomic analysis of C2C12 cells with and without PA treatment --- p.32 / Chapter 2.3.1 --- Protein sample preparation from C2C12 skeletal muscle cells --- p.32 / Chapter 2.3.2 --- Protein quantitation --- p.33 / Chapter 2.3.3 --- 2D Gel electrophoresis --- p.34 / Chapter 2.3.4 --- Image analysis --- p.36 / Chapter 2.3.5 --- In gel digestion and MALDI-ToF MS --- p.37 / Chapter 2.4 --- Mitochondrial purification and protein extraction --- p.38 / Chapter 2.4.1 --- Ultracentrifugation method --- p.38 / Chapter 2.4.2 --- Mitochondrial Isolation Kit --- p.39 / Chapter 2.5 --- Western Immunoblotting --- p.40 / Chapter 2.5.1 --- Protein sample preparation --- p.40 / Chapter 2.5.2 --- SDS-PAGE --- p.40 / Chapter 2.5.3 --- Western blotting --- p.40 / Chapter 2.5.4 --- Membrane Blocking and Antibody Incubations --- p.41 / Chapter 2.5.5 --- Detection of Proteins --- p.42 / Chapter 3 --- Results --- p.43 / Chapter 3.1 --- Differentiation of C2C12 myoblast into myotubes --- p.43 / Chapter 3.2 --- The effect of Palmitic acid on C2C12 Proliferation --- p.44 / Chapter 3.3 --- Comparison of total protein profiles of palmitic acid-treated C2C12 myotubes with control myotubes --- p.45 / Chapter 3.4 --- Western blotting of Akt and Phospho-Akt in C2C12 cells treated with Palmitic acid after acute exposure to insulin --- p.50 / Chapter 3.5 --- Comparison of two mitochondria isolation methodsultracentrifugation and mitochondrial isolation kit --- p.51 / Chapter 3.5.1 --- Quantity of extracted mitochondrial protein --- p.51 / Chapter 3.5.2 --- Purity of extracted mitochondrial protein --- p.52 / Chapter 3.6 --- Comparison of mitochondrial protein profiles between palmitic acid-treated and control C2C12 myotubes --- p.53 / Chapter 3.7 --- Western blotting of insulin receptor substrate-1 and its serine phosphorylation --- p.58 / Chapter 4 --- Discussion --- p.59 / Chapter 4.1 --- Investigation of anti-proliferating effect of Palmitic acid on C2C12 using MTT assay --- p.59 / Chapter 4.2 --- Comparison of total protein profiles of palmitic C2C12 myotubes with control myotubes --- p.60 / Chapter 4.3 --- Western blotting of insulin receptor substrate-1and its serine phosphorylation --- p.62 / Chapter 4.4 --- Western blotting of Akt and Phospho-Akt in C2C12 cells treated with Palmitic acid after acute exposure to insulin --- p.63 / Chapter 4.5 --- Comparison of mitochondrial protein profiles between palmitic acid-treated and control C2C12 myotubes --- p.65 / Chapter 4.6 --- Problems faced and future prospect --- p.68 / Chapter 5 --- References --- p.69

As the prevalence of atherosclerosis has risen to an alarming level throughout the world, this thesis investigated: (1) the effects of type 2 diabetes mellitus on the risk factors for atherosclerosis and the intima-media thickness (IMT) of the common carotid arteries (a surrogate marker for atherosclerosis), (2) the contribution of various risk factors to the IMT of the common carotid arteries and (3) the interrelationship between the risk factors. / Atherosclerosis is the process by which the inner lining of a large or medium artery is deposited with lipids, cellular waste and other substances. It reduces the vessel's elasticity, lumen size and blood flow. Atherosclerosis is the primary underlying mechanism leading to cardiovascular and cerebrovascular diseases, the second and third leading causes of death in Hong Kong. / Both traditional and emerging risk factors for atherosclerosis were studied: traditional risk factors include age, blood pressure, indices of glycaemia control (fasting glucose, insulin and haemoglobin-Alc), and fasting lipids, while the emerging risk factors include, abdominal fat volume (subcutaneous and visceral), inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitivity c-reactive protein (hsCRP)), adiponectin, stress hormones (24 hr urinary noradrenaline and adrenaline, and plasma cortisol), and occupational stress (measured by a effort-reward imbalance questionnaire). / Starting with 204 subjects recruited from three different studies, data from 84 normoglycaemic subjects, 23 patients with impaired glucose tolerance (IGT) and 77 patients with diabetes mellitus (DM) were included in the analysis. When the IMT of the common carotid arteries and various risk factors were compared between normoglycaemic, IGT and DM subjects: (1) the IMT of the common carotid arteries showed an increasing trend with the worsening of glycaemia control (normal<IGT<DM), (2) increased prevalence of hypertension, dyslipidaemia, and obesity were observed among DM patients, and (3) increased levels of inflammatory markers, reduced concentration of adiponectin (a anti-inflammatory substance), and increased plasma cortisol concentration were also found among DM subjects. As the studies were limited by sample size, only a few risk factors were found significantly related to the carotid IMT. Age was the only common risk factor which was found to be correlated to the IMT of both the normoglycaemic and the DM/IGT subjects. (Abstract shortened by UMI.) / Fok Siu Pong. / "June 2005." / Adviser: Lester A. H. Critchley. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0173. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 200-228). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Apolipoprotein E (apoE) is a lipid transport protein which plays a key role in lipid metabolism. In addition to the well known polymorphic coding alleles epsilon2, epsilon3 and epsilon4, APOE promoter single nucleotide polymorphisms (SNPs) have also been reported to modify disease susceptibilities in humans. / In a case-control study involving 710 Chinese type 2 diabetes and 198 non-diabetic subjects, genotyping of three SNPs (-491A/T, -219G/T and +113G/C) within the APOE proximal promoter identified that -491A was associated with increased risk for type 2 diabetes in women (OR=2.44, 95%CI=1.15-5.19, p=0.017). However, the three tested SNPs were not associated with the risk of diabetic nephropathy (DN). Yeast one-hybrid screening of the human brain cDNA library using the polymorphic DNA sequences spanning the APOE promoter -491 site as the 'baits' identified one of the interacting transcription factors being the activating transcription factor 4 (ATF4). Electrophoretic-mobility-shift assay confirmed the physical interaction of the purified recombinant ATF4 protein and APOE promoter -491 A/T spanning region (-521 to -461). The binding of ATF4 to the -491T-containing sequence was stronger than that of the -491A-containing sequence. Chromatin immunoprecipitation (ChIP) assay further confirmed the interaction between ATF4 and APOE promoter -491-spanning region in vivo. The functional significance of APOE -491A/T polymorphism was supported by the dual-luciferase reporter assay showing that -491 A to T single nucleotide substitution significantly decreased the activity of the cloned APOE promoter (-1019 to +407) in human kidney (293), liver (WRL-68) and astrocyte (U-87) cell lines. Further analysis showed that ATF4 over-expression significantly down-regulated the activities of the cloned APOE promoter. The suppression of ATF4 on APOE promoter with -491A allelic form was significantly stronger than that with -491T allelic form in 293 cells (p<0.05). Interestingly, overexpression of recombinant ATF4 stimulated endogenous APOE transcription by about 10% in WRL-68 cells. / In conclusion, APOE promoter -491A/T polymorphism modifies the risk of type 2 diabetes in Hong Kong Chinese women. The -491A/T polymorphism controls APOE promoter activity and is interactive with transcription factor ATF4. / My thesis project aimed at testing two hypotheses: (1) APOE promoter SNPs associate with the risks of type 2 diabetes and diabetic nephropathy, (2) APOE promoter SNPs modify transcriptional control of the gene. / Geng, Hua. / "September 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4559. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 140-151). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

近年來，腸促胰島素類藥物胰高血糖素樣肽－1受體（GLP-1R）激動劑（如liraglutide，exenatide）和二肽基肽酶-4（DPP-4）抑制劑（如sitagliptin，vildagliptin）在2型糖尿病治療中得到廣泛應用。然而，2型糖尿病患者中腸促胰島素效應嚴重受損。研究表明，2型糖尿病患者的腸促胰島素激素（GLP-1和GIP）分泌並不顯著降低，因此腸促胰島素效應受損主要是由於2型糖尿病患者中β細胞對腸促胰島素激素反應性降低。GIP在2型糖尿病患者中刺激胰島素分泌的功能幾乎完全消失。相比較，GLP-1刺激胰島素分泌功能在2型糖尿病患者中部分保留。2型糖尿病中腸促胰島素效應受損的具體機制目前仍不清楚。本論文主要從2型糖尿病患者的腸促胰島素效應受損的機理及對腸促胰島素類藥物療效的影響上進行相關研究。 / 我們較早的研究發現高血糖能降低胰島β細胞GLP-1R受體的表達，從而損傷胰島β細胞GLP-1R信號通路是2型糖尿中腸促胰島素受損的部分原因。由於高血脂和高血糖都是糖尿病的主要特徵，我進一步研究了高血脂對β細胞的腸促胰島素信號通路的影響。體外實驗表明，棕櫚酸能降低胰島β細胞中GLP-1R的表達，並且抑制了GLP-1刺激的cAMP產生及CREB的磷酸化；在β細胞中外源性表達GLP-1R能部分恢復棕櫚酸損傷的GLP-1刺激cAMP產生及CREB的磷酸化。此外，在db/db小鼠和HFD誘導的肥胖及糖尿病小鼠模型中，降脂藥bezafibrate和niacin 能顯著提高腸促胰島素類藥物sitagliptin 和exendin-4的降糖效果，並且伴隨著對胰島形態結構的改善以及增加胰島β細胞質量。 / 另一方面，2型糖尿病患者胰島β細胞的功能和品質持續性的減少。其中慢性的高血糖和高血脂是兩個主要因素。臨床研究發現sitagliptin的降糖效果隨著糖尿病持續的時間增加而降低，而具體機理並不清楚。我們以前研究發現高血糖損傷胰島β細胞GLP-1R的表達及其信號通路是2型糖尿病腸促胰島素效應受損的重要原因。我進一步探討了exendin-4在STZ-HFD 誘導的較輕程度糖尿病（MH）小鼠（相對較輕的高血糖以及β細胞質量減少）和重度糖尿病(SH)小鼠（嚴重高血糖以及β細胞質量減少）的治療效果。研究發現， exendin-4只在MH小鼠中顯著降低血糖，改善糖耐量，恢復正常胰島結構及增加β細胞質量。而在兩組小鼠中exendin-4 都能降低體重，增加胰腺重量，但對食都沒影響。儘管exendin-4能顯著降低MH小鼠中胰島素耐量實驗葡萄糖水平，但HORM-IR無顯著差異。此外，exendin-4處理對胰島素刺激的肝臟及肌肉組織中磷酸化AKT和GSK水準在兩組小鼠中都無明顯改變。 / 總之，我的研究強調了血糖血脂的控制在2型糖尿病患者中的重要作用。我也發現高血糖、高血脂導致2型糖尿病患者β細胞功能持續受損的同時也損傷了GLP-1R信號通路，以至腸促胰島素類藥物療效的降低。我們的研究對腸促胰島素類藥物在2型糖尿病患者中的合理使用提供了重要資訊。 / Incretin-based drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. liraglutide and exenatide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. sitagliptin and vildagliptin), which inhibit degrading intact GLP-1, have been a novel therapeutics for the treatment of type 2 diabetes. Type 2 diabetes mellitus (T2DM) is associated with reduced incretin effects. The underlying mechanism, however, is not well understood. / Our previous studies showed that hyperglycemia downregulates glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) which potentially contributes to the impaired incretin responses in cells. Whereas the effects of hyperlipidemia, another common clinical feature of T2DM, on GLP-1 response is largely unknown. In this study, I investigated the effects of free fatty acids (FFA) on incretin receptor signalings, and examined the glucose-lowering efficacy of incretin-based drugs in combination with lipid-lowering agents. I found that palmitate treatment decreased GLP-1R expression in rodent insulinoma cell lines, which was associated with impaired GLP-1 stimulated cAMP production and phosphorylation of CREB. Over-expression of GLP-1R restored the cAMP production and the phosphorylation of CREB. Treatment with bezafibrate or niacin in combination with des-fluoro-sitagliptin or exendin-4 produced more robust glycemic control associated with improved pancreatic islet morphology and islet cell function in db/db mice and HFD-fed mice. / On the other hand, chronic hyperglycemia and hyperlipidemia can cause a progressive deterioration in pancreatic beta-cell function and mass in patients with type 2 diabetes mellitus. It has been reported that the efficacy of incretin-based therapeutics is attenuated with the duration of diabetes. In our previous study, we have shown that hyperglycemia downregulates GLP-1 receptor which in turn may contribute to the impaired incretin effect in type 2 diabetes. In this study, I further investigated the efficacy of GLP-1 based drug exendin-4 in a rodent model of type 2 diabetes with different degrees of hyperglycemia and reduction of beta cell mass. I found that in moderate hyperglycemia (MH) group but not in severe hyperglycemia (SH) group, exendin-4 treatment significantly reduced fed glucose levels and plasma lipid profiles, improved glucose tolerance and glucose stimulated insulin secretion, and was associated with restored islets morphology and increased beta cell mass. Exendin-4 significantly decreased body weight gain and increased pancreatic mass both in MH and SH group. Although glucose levels were significantly reduced in MH group with exentin-4 treatment during insulin tolerance test, exendin-4 had no effects on HORM-IR, food intake, and insulin stimulated p-AKT/p-GSK in liver and muscle in both MH and SH group. / In summary, my findings highlight the importance of comprehensive lipid and glycemic control in type 2 diabetes mellitus. I found that factors including hyperglycemia and hyperlipidemia that cause progressive decline in beta cell failure impaired beta cell GLP-1R signaling as well as the efficacy of incretin-based therapies. These results add to our knowledge regarding the mechanism of incretin-based therapy in improving glycemic control in type 2 diabetic patients and provide new insights in designing treatment strategies including incretin-based therapy for type 2 diabetic patients. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Kang, Zhanfang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 103-123). / Abstract also in Chinese. / 論文摘要 --- p.viii / Impaired Incretin Effects in Type 2 Diabetes: Mechanism and Therapeutic Implication --- p.1 / DECLARATION --- p.i / ACKNOWLEGEMENTS --- p.ii / ABBREVIATIONS --- p.iii / PUBLICATIONS AND AWARDS --- p.v / Chapter 1 --- Abstract --- p.vi / Chapter 2 --- Chapter : Introduction --- p.1 / Chapter 2.1 --- The history of incretin discovery --- p.1 / Chapter 2.2 --- The incretin hormones:GLP-1 and GIP --- p.1 / Chapter 2.3 --- Gene structure and regulation of incretin hormone gene expression --- p.2 / Chapter 2.3.1 --- Gene structure and regulation of GLP-1 gene expression --- p.2 / Chapter 2.3.2 --- Gene structure and regulation of GIP gene expression --- p.5 / Chapter 2.4 --- Secretion and metabolism of GLP-1 and GIP --- p.5 / Chapter 2.4.1 --- Regulation of GLP-1 and GIP secretion --- p.5 / Chapter 2.4.2 --- Degradation of GLP-1 and GIP by DPP-4 enzyme --- p.8 / Chapter 2.5 --- GLP-1 and GIP receptor --- p.10 / Chapter 2.6 --- biological actions of GLP-1 and GIP --- p.11 / Chapter 2.6.1 --- Actions of GLP-1 in peripheral tissues --- p.12 / Chapter 2.6.2 --- Actions of GIP in peripheral tissues --- p.17 / Chapter 2.7 --- Impaired incretin effect in type 2 diabetes patients --- p.17 / Chapter 2.7.1 --- Secretion of incretin hormones in patients with type 2 diabetes --- p.18 / Chapter 2.7.2 --- Impaired the responsiveness to GLP-1 and GIP in pancreatic beta cells --- p.19 / Chapter 2.8 --- Incretin-based drugs --- p.19 / Chapter 2.9 --- Type 2 diabetes and beta cell failure --- p.21 / Chapter 2.9.1 --- Natural history of type 2 diabetes --- p.21 / Chapter 2.9.2 --- Decline of beta cell function and mass in type 2 diabetes --- p.22 / Chapter 2.9.3 --- Factors for progressive loss of beta cell function and mass --- p.24 / Chapter 3 --- Chapter: Pharmacological reduction of free fatty acids restores the efficacy of incretin-based therapies in diabetic mouse models through beta cell GLP-1 receptor signalings --- p.30 / Chapter 3.1 --- Summary --- p.30 / Chapter 3.2 --- Introduction --- p.32 / Chapter 3.3 --- Materials and Methods --- p.35 / Chapter 3.3.1 --- Chemicals and Reagents --- p.35 / Chapter 3.3.2 --- Preparation of 8 mM sodium palmitate solution with 10.5% BSA --- p.35 / Chapter 3.3.3 --- Construct of an adenoviral vector for expressing mouse GLP-1R --- p.36 / Chapter 3.3.4 --- Cell culture and treatment --- p.37 / Chapter 3.3.5 --- RNA extraction and quantitative RT-PCR --- p.37 / Chapter 3.3.6 --- Analysis of phosphorylation of CREB --- p.38 / Chapter 3.3.7 --- Measurement of insulin secretion --- p.39 / Chapter 3.3.8 --- RT-PCR analysis of mouse GLP-1R expression --- p.39 / Chapter 3.3.9 --- Measurement of cAMP production --- p.40 / Chapter 3.3.10 --- Animals and experimental protocols --- p.40 / Chapter 3.3.11 --- Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) --- p.41 / Chapter 3.3.12 --- Acute glucose-lowering actions of Ex-4 and D-GIP in db/db Mice --- p.41 / Chapter 3.3.13 --- Lipid levels measurement --- p.42 / Chapter 3.3.14 --- Histological analysis --- p.42 / Chapter 3.3.15 --- Statistical analysis --- p.42 / Chapter 3.4 --- Results --- p.43 / Chapter 3.4.1 --- Reduced expression of GLP-1R in palmitate-treated b cells and islets of hyperlipedemic db/db mice. --- p.43 / Chapter 3.4.2 --- Palmitate impairs GLP-1 stimulated cAMP production and p-CREB in rodent insulinoma cell lines --- p.45 / Chapter 3.4.3 --- Palmitate reduced GLP-1 and GIP stimulated insulin secretion in rat INS-1E cells --- p.46 / Chapter 3.4.4 --- Mouse GLP-1R mRNA is expressed in rat INS-1E cells after infected with Ad-GLP-1R --- p.47 / Chapter 3.4.5 --- Expression of exogenous GLP-1R restores GLP-1 stimulated cAMP production and p-CREB in palmitate-treated rodent insulinoma cell lines --- p.48 / Chapter 3.4.6 --- Lipid lowering enhances the efficacy of DPP-4 inhibitor des-fluoro-sitagliptin in db/db mice --- p.50 / Chapter 3.4.7 --- Lipid-lowering enhances the efficacy of DPP-4 inhibitor des-flouro-sitagliptin in HFD-fed mice --- p.56 / Chapter 3.4.8 --- Lipid lowering enhances the efficacy of an agonist to GLP-1R (Ex-4) but not to GIPR (D-GIP) in db/db mice --- p.59 / Chapter 3.5 --- Discussion --- p.67 / Chapter 4 --- Chapter : Further study on the impairment of incretin effect by hyperglycemia in a rodent model of type 2 diabetes --- p.71 / Chapter 4.1 --- Summary --- p.71 / Chapter 4.2 --- Introduction --- p.73 / Chapter 4.3 --- Materials and Methods --- p.76 / Chapter 4.3.1 --- Animals and treatment --- p.76 / Chapter 4.3.2 --- Oral glucose tolerance test and insulin tolerance test --- p.76 / Chapter 4.3.3 --- Plasma parameters --- p.77 / Chapter 4.3.4 --- Histological staining and quantification of beta cell mass --- p.77 / Chapter 4.3.5 --- Insulin signaling analysis --- p.78 / Chapter 4.3.6 --- Western blot analysis --- p.78 / Chapter 4.3.7 --- Statistical analysis --- p.79 / Chapter 4.4 --- Results --- p.80 / Chapter 4.4.1 --- Exendin-4 reduced fed glucose levels in MH mice but not in SH mice --- p.80 / Chapter 4.4.2 --- Exendin-4 reduced body weight gain and did not affect food intake in both MH mice and SH mice --- p.81 / Chapter 4.4.3 --- Exendin-4 improved glucose tolerance and glucose stimulated insulin secretion in MH mice but not in SH mice --- p.83 / Chapter 4.4.4 --- Effects of exendin-4 on insulin sensitivity in MH and SH mice --- p.84 / Chapter 4.4.5 --- Effects of exendin-4 on lipid profiles in MH and SH mice --- p.86 / Chapter 4.4.6 --- Effects of exendin-4 on tissues weight in MH and SH mice --- p.87 / Chapter 4.4.7 --- Pancreatic islet morphology and analysis of beta cell mass --- p.88 / Chapter 4.4.8 --- Exendin-4 had no significant effects on insulin signaling pathway in liver and muscle --- p.91 / Chapter 4.5 --- Discussion --- p.94 / Chapter 5 --- Chapter : Summary --- p.100 / Chapter 6 --- References --- p.103

by Lynn Wah Wong Tsang. / Consent form in Chinese. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 127-145). / Declaration --- p.i / Acknowledgments --- p.ii / Table of Contents --- p.iii / List of Tables --- p.vii / List of Figures --- p.x / List of Appendix --- p.xi / Chapter CHAPTER1 --- INTRODUCTION / Chapter 1.1 --- General Introduction --- p.2 / Chapter 1.2 --- Literature Review --- p.6 / Chapter 1.2.1 --- Classifications of Diabetes Mellitus --- p.6 / Chapter 1.2.2 --- Diagnostic Criteria of Diabetes Mellitus --- p.6 / Chapter 1.2.3 --- Characteristics of NIDDM --- p.9 / Chapter 1.2.4 --- Epidemiology of NIDDM --- p.13 / Chapter 1.2.5 --- Pathophysiology of NIDDM --- p.16 / Chapter 1.2.6 --- Determinants and Causes of NIDDM --- p.16 / Chapter 1.2.7 --- Etiology and Risk Factors ofNIDDM --- p.20 / Chapter 1.2.7.1 --- Genetic Factors --- p.20 / Chapter 1.2.7.2 --- Environmental Factors --- p.20 / Chapter 1.2.7.2.1 --- Physical Inactivity --- p.20 / Chapter 1.2.7.3 --- Body Weight and Fat Distribution --- p.21 / Chapter 1.2.7.4 --- Gestational Diabetes Mellitus --- p.22 / Chapter 1.2.7.5 --- Impaired Glucose Tolerance --- p.23 / Chapter 1.2.8 --- Complications --- p.23 / Chapter 1.2.9 --- Oral hypoglycaemic agents --- p.25 / Chapter 1.2.9.1 --- Insulin Secretagogues --- p.25 / Chapter 1.2.9.2 --- Metformin --- p.26 / Chapter 1.2.9.3 --- Apha-Glucosidase Inhibitors --- p.26 / Chapter 1.2.9.4 --- Insulin Sensitizers --- p.27 / Chapter 1.2.10 --- Oral Hypoglycaemic Agent Failure --- p.27 / Chapter 1.2.11 --- Use of Insulin in NIDDM --- p.28 / Chapter 1.2.12 --- Combination Therapy --- p.30 / Chapter CHAPTER2 --- RESEARCH DESIGN AND METHODS / Chapter 2.1 --- Study Protocol --- p.37 / Chapter 2.2 --- Objectives --- p.37 / Chapter 2.3 --- Overall Design --- p.38 / Chapter 2.3.1 --- Selection of Patients --- p.38 / Chapter 2.3.1.1 --- Inclusion Criteria --- p.38 / Chapter 2.3.1.2 --- Exclusion Criteria --- p.40 / Chapter 2.3.2 --- Recruitment Period --- p.40 / Chapter 2.3.2.1 --- Screening Period --- p.40 / Chapter 2.3.2.2 --- Pre-Run-In Period --- p.41 / Chapter 2.3.3 --- Run-in Period --- p.42 / Chapter 2.3.3.1 --- Stabilization --- p.43 / Chapter 2.3.3.2 --- Randomization --- p.44 / Chapter 2.3.3.2.1 --- Combination Group --- p.45 / Chapter 2.3.3.2.2 --- Insulin Group --- p.47 / Chapter 2.3.4 --- Evaluation Periods --- p.48 / Chapter 2.3.5 --- Study Medications --- p.49 / Chapter 2.3.6 --- Clinical Assessments --- p.50 / Chapter 2.4 --- Withdrawals --- p.50 / Chapter 2.5 --- Investigations --- p.51 / Chapter 2.6 --- Analytical Methods --- p.52 / Chapter 2.7 --- Statistical Analysis --- p.53 / Chapter CHAPTER3 --- RESULTS / Chapter 3.1 --- Study Population --- p.56 / Chapter 3.2 --- Randomization --- p.58 / Chapter 3.3 --- Study Results --- p.63 / Chapter 3.3.1 --- Indices of Glycaemic Control and Lipids --- p.63 / Chapter 3.3.1.1 --- Glucose Values --- p.63 / Chapter 3.3.1.2 --- Glucosylated Haemoglobin and Glycated Plasma Protein Concentration --- p.64 / Chapter 3.3.1.2.1 --- Glucosylated Haemoglobin --- p.64 / Chapter 3.3.1.2.2 --- Glycated Plasma Protein Concentration --- p.68 / Chapter 3.3.1.3 --- Plasma Lipid Concentrations --- p.69 / Chapter 3.3.2 --- Clinical Determinants --- p.70 / Chapter 3.3.2.1 --- Blood Pressure Measurements --- p.70 / Chapter 3.3.2.2 --- Body Weight Evaluations --- p.71 / Chapter 3.3.3 --- Insulin Types Used --- p.76 / Chapter 3.3.4 --- Insulin Dosage Requirements --- p.76 / Chapter 3.3.5 --- Subjective Well Being and Acceptability of Insulin Injection --- p.78 / Chapter 3.3.6 --- Hypoglycaemic Events --- p.85 / Chapter 3.3.7 --- Subsequent Study Discontinuation --- p.85 / Chapter 3.3.8 --- Responders versus no Responders --- p.86 / Chapter CHAPTER4 --- GENERAL DISCUSSION / Chapter 4.1 --- Summary of Results --- p.92 / Chapter 4.2 --- Acute and Long Term Effects of --- p.101 / Combination Therapy / APPENDIX --- p.111 / REFERENCES --- p.127 / Chapter 2 --- Abstracts summarized recent data not incorporated in this thesis --- p.147

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-05-11T20:22:22Z No. of bitstreams: 1 ClarissaSilva.pdf: 1338092 bytes, checksum: 88748a1261e4efc9259f90f82be7a663 (MD5) / Made available in DSpace on 2017-05-11T20:22:22Z (GMT). No. of bitstreams: 1 ClarissaSilva.pdf: 1338092 bytes, checksum: 88748a1261e4efc9259f90f82be7a663 (MD5) Previous issue date: 2016-03-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / The Diabetes mellitus (DM) is a heterogeneous group of metabolic disorders has in common hyperglycemia, result from defects in insulin action or insulin secretion or both. This is one of the health problems of greater magnitude in Brazil. So the selfcare activities are essential in carriers of diabetes mellitus type two to maintain and improve their health. However represent challenge for carries and health professionals. The research aimed to analyze the factors associated to knowledge about diabetes and to self-care activities of carries of Diabetes mellitus type two. For that was conducted a cross-sectional analytical study with a quantitative approach with 360 carries of diabetes mellitus type two attended at Ambulatory Endocrinology of Federal University of Maranhão. The data collect was conducted in the period from february to july 2015. For data collection was used three instruments, one containing identification data with open and closed questions concerning sociodemographic and clinical variables, self-care activities questionnaire with Diabetes (QAD) and questionnaire of scale knowledge of Diabetes (DKN). We used Spearman coefficient in the correlation between self-care activities with age and time of disease, the MannWhitney test for association of self-care of scores with the sociodemographic and clinical variables and the Chi Square test to association between knowledge and sociodemographic and clinical variables. For interpretation of statistic has adapted results the significance level of 5% (p < 0.05). The research has shown that carries of diabetes mellitus type 2 have generally low self-care for items general food, physical activity and monitory glycemia and the best self-care activities are related the specific food, medication and care of the feet. Observed that most participants had higher scores to 8, indicates a high degree of knowledge about disease. If found associations between the scores of knowledge and self-care activities with the socioeconomic and clinical variables. It was concluded that there are factors related to socioeconomic and clinical features that interfere with the self-care activities and the knowledge of carries with diabetes mellitus type 2 against disease. / O Diabetes Mellitus (DM) é um grupo heterogêneo de distúrbios metabólicos que apresenta em comum a hiperglicemia, resultado de defeitos na ação da insulina, na secreção de insulina ou em ambas. Esta constitui um dos problemas de saúde de maior magnitude no Brasil. Assim, as atividades de autocuidado são essenciais nas pessoas que têm diabetes mellitus tipo 2 para manter e melhorar a sua saúde, porém, representam desafio tanto para o indivíduo que a sofre quanto ao profissional da saúde. A pesquisa teve como objetivo analisar os fatores associados ao conhecimento sobre o diabetes e às atividades de autocuidado dos portadores de diabetes mellitus tipo 2. Para tanto, foi realizado um estudo analítico de corte transversal com abordagem quantitativa com 360 portadores de DM tipo 2 atendidos no Ambulatório de Endocrinologia do Hospital Universitário da Universidade Federal do Maranhão. A coleta dos dados foi realizada no período de fevereiro a julho de 2015. Para a coleta de dados, utilizaram-se três instrumentos, um contendo dados de identificação com questões abertas e fechadas referente às variáveis sociodemográficas e clínicas, o Questionário de Atividades de Autocuidado com o diabetes (QAD) e o Questionário da Escala de Conhecimento de Diabetes (DKN). Utilizou-se o coeficiente de Spearman na correlação entre as atividades de autocuidado com a idade e o tempo de doença, o teste Mann-Whitney para associação dos escores do autocuidado com as variáveis sociodemográficas e clínicas e o teste Qui Quadrado para associação entre o conhecimento e as variáveis sociodemográficas e clínicas. Para a interpretação estatística dos resultados foi adotado nível de significância de 5% (p<0,05). A pesquisa mostrou que os portadores de diabetes mellitus tipo 2 têm autocuidado geral baixo para os itens alimentação geral, atividade física e monitoramento da glicemia; e as melhores atividades de autocuidado estão relacionadas à alimentação específica, à medicação e ao cuidado com os pés. Observa-se que a maioria dos participantes obtiveram escores superiores a 8, indicando um grau elevado de conhecimento sobre a doença. Verificaram-se associações entre os escores de conhecimento e das atividades de autocuidado com as variáveis socioeconômicas e clínicas. Concluiu-se que existem fatores relacionados às características socioeconômicas e clínicas que interferem nas atividades de autocuidado e no conhecimento do portador de diabetes mellitus tipo 2 frente à doença.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-06-12T17:33:35Z No. of bitstreams: 1 KellySilva.pdf: 1053190 bytes, checksum: 14ae6885897006b813bbfa8df8168e7c (MD5) / Made available in DSpace on 2017-06-12T17:33:35Z (GMT). No. of bitstreams: 1 KellySilva.pdf: 1053190 bytes, checksum: 14ae6885897006b813bbfa8df8168e7c (MD5) Previous issue date: 2016-07-25 / Diabetes Mellitus (DM) is a heterogeneous group of metabolic disorders that have in common hyperglycemia. Diabetics under treatment with insulin therapy must embrace responsibility of the control and management of their condition on a daily basis; in this context the congnitive theory of self efficacy (SE) proposed by Bandura can be considered a decisive factor in achieving behavioral goals of diabtes, resulting in improvements to self-care and glycemic control. The research here presented aimed to analyse the self efficacy to the treatment of patients with diabetes mellitus type 1 and 2 in insulin therapy and its correlaton with sociodemographic and clinical variables. To that end, we conducted and analytical study of cross-sectional, with quantitative approach and sample consisting on 134 patients with DM type 1 and 2 in insulin therapy at University Hospital's Endocrinology Clinic - Unit President Dutra (HUUPD) of São Luís-MA. For data collection, we used two instruments: identification data with open and closed questions related to sociodemographic and clinical variables and the Insulin Management Diabetes Self Efficacy (IMDSES), Brazilian version. The search resulted 3.07 global media, on the scale of self efficacy, the areas that stood out with the highest and lowest average respectively were the general management domain (3.38) and the diet field (2.90). We have found the following significant correlations: marital status (widowed had more SE in the diet), education (the higher the education, the better the SE in the management, control and correction of glycemia), treatment with diet and insulin (higher SE in the diet), absence of dyslipidemia (increased SE to the overall management of diabtes) and age (higher SE for older in the diet). It was concluded that there are factors relates to socioeconomic and clinical features that interfare in self efficacy of patients with Diabetes mellitus type 1 e 2 in insulin therapy, against the desease. / O Diabetes Mellitus (DM) é um grupo heterogêneo de distúrbios metabólicos que apresentam em comum a hiperglicemia, resultado de defeitos na ação da insulina, na secreção de insulina ou em ambas. Os diabéticos que fazem tratamento com insulinoterapia devem assumir a responsabilidade do controle e gestão de sua condição no dia a dia. Nesse contexto, a teoria cognitiva da autoeficácia (AE) proposta por Bandura pode ser considerada um fator decisivo para atingir as metas comportamentais do diabetes, resultando em melhorias para o autocuidado e controle glicêmico. A pesquisa que se apresenta, teve como objetivo analisar a autoeficácia do tratamento dos portadores de diabetes mellitus tipo 1 e 2 em insulinoterapia e a sua correlação com as variáveis sociodemográficas e clínicas. Para tanto, foi realizado um estudo analítico de corte transversal, com abordagem quantitativa e amostra de 134 portadores de DM tipo 1 e 2 em insulinoterapia, atendidos no Ambulatório de Endocrinologia do Hospital Universitário - Unidade Presidente Dutra (HUUPD) de São Luís-MA. Para a coleta de dados, utilizaram-se dois instrumentos: dados de identificação com questões abertas e fechadas referente às variáveis sociodemográficas e clínicas e o Insulin Management Diabetes Self Efficacy (IMDSES), versão brasileira. A pesquisa resultou média global de 3,07 na escala de autoeficácia, os domínios que se destacaram com maior e menor média respectivamente foram o domínio administração geral (3,38) e o domínio dieta (2,90). Encontraram-se as seguintes correlações significativas: estado civil (viúvos tinham maior AE na dieta), escolaridade (quanto maior a escolaridade, melhor a AE na administração, controle e correção da glicemia), tratamento com dieta e insulina (maior AE na dieta), ausência de dislipidemia (maior AE para o manejo geral do diabetes) e idade (maior AE para os mais velhos na dieta). Concluiu-se que existem fatores relacionados às características socioeconômicas e clínicas que interferem na autoeficácia do portador de Diabetes mellitus tipo 1 e 2 em Insulinoterapia, frente à doença.

Orientador: Maria Aparecida Neves Jardini / Coorientador: Antônio Martins Figueiredo / Banca: José Benedito Oliveira Amorim / Banca: Milton Santamaria Júnior / Resumo: A Doença Periodontal (DP) e o Diabetes Mellitus tipo 2 (DM2) apresentam a mesma etiopatogênese inflamatória e demonstram uma relação bidirecional, pois DM2 afeta a severidade da DP, e esta pode contribuir para a carga inflamatória total do indivíduo, influenciando a evolução do DM2. O objetivo do presente estudo foi avaliar os fatores de risco para o desenvolvimento de aterosclerose em pacientes portadores de DM2, com e sem periodontite crônica. Foram analisados 48 pacientes, os quais foram divididos em 2 grupos: Teste (pacientes diabéticos com periodontite crônica) e Controle (pacientes diabéticos sem periodontite crônica). O grupo teste foi tratado com debridamento periodontal e o grupo controle recebeu profilaxia supragengival. Ambos os grupos receberam controle de placa a cada 3 meses. No baseline e 6 meses após o tratamento, foi realizada tomada dos parâmetros clínicos periodontais (IP, IG, PS, RG e NIC) e coleta de sangue para avaliação dos marcadores séricos inflamatórios (oxLDL, CT, TG, LDL, HDL, glicose, HbA1c, PCRus, leucócitos e neutrófilos). Os parâmetros periodontais mostraram melhora significativa (p<0,05) no grupo teste, exceto RG. IP e IG também diminuíram significativamente no grupo controle após 6 meses. CT e HbA1c apresentaram taxas significativamente maiores no grupo teste, em comparação com o grupo controle. As taxas de PCR-us e HbA1c diminuíram significativamente no grupo teste após a terapia periodontal. A contagem de leucócitos mostrou uma diminuição r... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Periodontal Disease (DP) and Type 2 Diabetes Mellitus (DM2) present the same inflammatory etiopathogenesis and demonstrate a bidirectional relationship, since DM2 affects the severity of PD, and this may contribute to the individual's total inflammatory load, influencing the evolution of DM2. The objective of the present study was to evaluate the risk factors for the development of atherosclerosis in patients with T2DM, with and without chronic periodontitis. We analyzed 48 patients, who were divided into 2 groups: Test (diabetic patients with chronic periodontitis) and Control (diabetic patients without chronic periodontitis). The test group was treated with periodontal debridement and the control group received supragingival prophylaxis. Both groups received plaque control every 3 months. Periodontal clinical parameters (IP, IG, PS, RG and NIC) and collection of blood for evaluation of serum inflammatory markers (oxLDL, CT, TG, LDL, HDL, glucose, HbA1c, hs-CRP, leukocytes and neutrophils). The periodontal parameters showed significant improvement (p <0.05) in the test group, except for RG. IP and IG also decreased significantly in the control group after 6 months. CT and HbA1c presented significantly higher rates in the test group compared to the control group. Rates of Hs-1c and HbA1c decreased significantly in the test group after periodontal therapy. The leukocyte count showed a significant decrease in the control group during the study time. Periodontal therapy promotes... (Complete abstract click electronic access below) / Mestre

Orientador: James Venturini / Resumo: Dermatofitoses são infecções fúngicas causadas por fungos dermatofíticos que geralmente afetam a camada córnea da pele, cabelos e unhas, mas sob certas condições podem apresentar envolvimento invasivo. A espécie Trichophyton rubrum é o dermatófito mais frequentemente isolado em espécimes clínicos. Além disso, pacientes com diabetes mellitus tipo II (DM-II) são mais suscetíveis a esta infecção fúngica e a relação dermatófito-hospedeiro é pouco compreendida. Contudo, o perfil pró-inflamatório observado em pacientes com hiperglicemia é uma condição complicadora nessa relação. Os receptores de reconhecimento padrão (PRRs) presentes nos fagócitos, como os receptores de manose (MR), dectina-1, toll-like (TLR) -2 e -4, reconhecem estruturas fúngicas e são responsáveis por desencadear mecanismos de ativação e regulação celular durante o processo inflamatório. Assim, o presente estudo tem como objetivo determinar o papel desses receptores na ativação de monócitos de pacientes com DM-II e dermatofitoses por T. rubrum. Exoantígenos de T. rubrum foram obtidos de pacientes com diabetes e indivíduos normoglicêmicos. Os PRRs foram bloqueados em monócitos e monócitos THP-1 de pacientes com DM-II e indivíduos normoglicêmicos desafiados com Exo_Tr_NG e Exo_Tr_DM. Posteriormente, o TNF e MIP-1α e IL-1β foram dosados. A expressão desses receptores foi avaliada por citometria de fluxo. Nenhuma diferença estatística foi observada no ensaio de inibição de monócitos de pacientes diabéticos e indivíd... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Dermatophytoses are fungal infections caused by dermatophytic fungi that usually affect the cornea layer of the skin, hair and nails, but under certain conditions may present invasive involvement. The species Trichophyton rubrum is the dermatophyte most often isolated in clinical specimens. In addition patients with type II diabetes mellitus (DM-II) are more susceptible to this fungal infection. The dermatophyte-host relationship is poorly understood; However, the pro-inflammatory profile observed in patients with hyperglycemia is a complicating condition in this relationship. The pattern recognition receptors (PRRs) present in phagocytes, such as the mannose (MR), dectin-1, toll-like (TLR) -2 and -4 receptor, recognize fungal structures and are responsible for triggering mechanisms of cellular activation and regulation during the inflammatory process, as well as influence on the polarization of the adaptive immune response. Thus, any interference in this process may impair the host to effectively and pathogenically eliminate pathogens. Thus, the present study aims to determine the role of these receptors in the activation of monocytes of patients with DM-II. Exoantigens of T. rubrum were obtained from patients with diabetes and normoglycemic individuals. PRRs were blocked in THP-1 monocytes and monocytes from DM-II patients and normoglycemic individuals challenged with Exo_Tr_NG and Exo_Tr_DM. Subsequently, TNF and MIP-1α and IL-1β were dosed. The expression of these recepto... (Complete abstract click electronic access below) / Mestre

Diabetesmellitus typ 2 ökar kraftigt både i Sverige och i övriga världen. Detta kanrelateras till sämre matvanor och övervikt. Förvirringen kring vad människorska äta för att hålla sig friska och sunda har aldrig varit större. Det finnsskilda uppfattningar och media sänder olika budskap. Sjuksköterskan ska arbetaefter vetenskap och beprövad erfarenhet, och ska därmed kunna ge rättinformation till patienter avseende kost. Syftet med litteraturstudien var attkartlägga effekterna av lågkolhydratkost till patienter med diabetes typ 2genom att sammanställa aktuell forskning. Resultatet visade bland annatbetydande viktreduktion samt minskning av HbA1c och antidiabetika.Inga negativa effekter på kardiovaskulära riskfaktorer sågs. Sjuksköterskan kandärför ge information om lågkolhydratkost och dess effekter för att underlättaför diabetes patienter att ta beslut i sin egenvård. Det ställer dock krav påuppföljning från sjukvården för att undvika hypoglykemi hos patienterna. Dåartikelsökningen endast genererade i kvantitativa studier behövs det iframtiden kvalitativa studier för att få fram effekterna av lågkolhydratkost påpatientens upplevelse av hälsa och livskvalitet. Det behövs ocksåuppföljningsstudier för att få fram långtidseffekterna av att ätalågkolhydratkost för diabetiker. / Diabetes mellitus type 2 is increasing rapidly in Sweden and all over the world. This can be related to bad eating habits and overweight. The confusion about what people should eat to stay healthy and slim has never been bigger. There are different ideas and media sends different messages. The nurse shall work for science and proven experience, and will therefore be able to provide the right information to patients regarding diet. The purpose of this study was to identify the effects of low carbohydrate diet in patients with type 2 diabetes by compiling the current research. The result showed among other things, significant weight reduction and decrease of HbA1c and antidiabetic medications. No negative effects were observed on the cardiovascular risk factors. The nurse can therefore provide information about low carbohydrate diet and its effects to make it easier for diabetics to make decisions in their self-care. It does however require follow-up from health care to avoid hypoglycaemia in patients. Since the article search only generated in quantitative studies, qualitative studies are needed in the future to obtain the long term effects of low carbohydrate diet in patients experience of health and quality of life. It also needs follow-up studies to obtain the long term effects of eating low carbohydrate diet for diabetics.