Academic literature on the topic 'Non-insulin-dependent diabetes – Complications'

1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects. 2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P < 0.001, non-insulin-dependent patients, 286.8, 54.7-2370 (105), P < 0.001, control subjects, 79.8, 25.3-892.9 (21); S-D-lactoylglutathione [mean ± SD (n) pmol/106 erythrocytes], combined diabetic patients, 3.37 ± 0.85 (24), control subjects 4.76 ± 1.95 (8) P < 0.05; D-lactate [mean ± SD or median, range (n) nmol/g], insulin dependent patients, median 18.3, 5.7-57.4 (42), P < 0.001, non-insulin-dependent patients, 20.0 ± 8.9, 2.6-48.4 (105), P < 0.001, control subjects 9.7 ± 4.3, 1.8-19.7 (21). The reduced glutathione concentrations in blood samples from the insulin-dependent and non-insulin-dependent diabetic patient groups were not different from the control group values (P>0.05). 3. The activities of glyoxalase enzymes in erythrocytes were increased: glyoxalase I activity [mean ± SD (n) m-units/106 erythrocytes] was increased in diabetic patients, relative to normal control subjects: insulin-dependent patients, 4.35 ± 1.54 (41), P < 0.001; non-insulin-dependent patients, 4.61 ± 1.79 (101), P < 0.001; control subjects, 3.21 ± 1.81 (21); glyoxalase II activity [mean ± SD (n) m-units/106 erythrocytes] was increased in the non-insulin-dependent diabetic patient group, relative to normal control subjects [non-insulin-dependent diabetic patients, 2.10 ± 0.46 (102); subject controls, 1.83 ± 0.27 (21); P < 0.05]. 4. In insulin-dependent diabetic patients, the concentration of methylglyoxal correlated positively with the duration of diabetes, and the concentration of D-lactate correlated positively with haemoglobin A1c and negatively with the reduced glutathione concentration. D-Lactate concentration correlated positively with blood glucose concentration in patients with non-insulin-dependent diabetes mellitus. 5. There was a positive logistic correlation of duration of disease with retinopathy, nephropathy, neuropathy, or any combination thereof. Retinopathy also gave a positive logistic correlation with haemoglobin A1c concentrations and a negative logistic correlation with D-lactate concentration. 6. When paired for duration of diabetes, patients with retinopathy, neuropathy or nephropathy, or any combination thereof, had significantly higher age, level of haemoglobin A1c and glyoxalase I activity than patients with uncomplicated diabetes (P < 0.05). 7. We conclude that the glyoxalase system is modified in erythrocytes in both insulin-dependent and non-insulin-dependent diabetic patients and that this modification is related to the development of diabetic complications.

Background: Diabetics with ankle fractures experience more complications than the general population, but it is unclear whether complications differ between type 1 and 2 diabetics and between insulin- and non–insulin-dependent diabetics. This study aims to determine if there is a difference in postoperative complication rates between these groups. Methods: An administrative health care database from a large commercial insurer was queried to identify operatively treated ankle fractures in patients with type 1 (T1D), type 2 (T2D), type 2 insulin-dependent (T2ID), and type 2 non–insulin-dependent (T2NID) diabetes. Postoperative complications were identified to include postoperative stiffness, posttraumatic arthritis, amputation, implant removal, and infection. Subgroup analysis was performed to control for comorbidities. Results: A total of 20 703 closed and 2873 open operatively treated ankle fractures were identified. Patients with T1D experienced higher rates of amputation, postoperative infection, and total complications than patients with T2D (P < .05). Patients with T2ID experienced higher rates of amputation, infection, and total complications than those with T2NID (P < .0001). Subgroup analysis controlling for comorbidities showed a higher total complication rate for T1D compared with T2D in closed ankle fractures (P < .02) and for T2ID compared with T2NID in both open and closed ankle fractures (P < .0001). Conclusions: Patients with T1D and T2ID have higher complication rates than patients with T2D and T2NID, respectively. Foot and ankle surgeons should be cautioned not to classify diabetics as one cohort and should use these findings to stratify risk among this patient population. Levels of Evidence: Level III: Diagnostic

[Truncated abstract] Cardiovascular reflex control of the vasculature is important in maintaining adequate tissue oxygenation in the face of disturbances in physiological homeostasis. Alterations in blood oxygen levels and blood distribution evoke integrated neural, mechanical and humoral responses which modulate peripheral vasomotor tone to maintain systemic cardiovascular integrity. The balance between the local effects of hypoxia and changes in chemoreflex control of vascular tone during hypoxia determine whether net vasoconstriction or vasodilatation is evident in the peripheral vasculature. The mechanisms contributing to hypoxic vasodilatation per se have not previously been defined in healthy humans. Study 1 of this thesis (Chapter 3) investigated the mechanisms contributing to vasomotor responses to chemoreflex activation in the human forearm ... Study 2 (Chapter 4a) investigated the mechanisms controlling vasomotor responses to isocapnic hypoxia in subjects with type 2 diabetes ... Study 3 (Chapter 5) compared the vascular responses to decreased venous return in individuals with and without right atrial afferent innervation ... The results of this thesis indicate that in healthy humans isocapnic hypoxia induces sympathetic vasoconstriction, which masks underlying β-adrenoceptor mediated vasodilatation. The normal vasomotor response to isocapnic hypoxia is impaired in subjects with type 2 diabetes. Despite intact vasoconstrictor responses, subjects with type 2 diabetes exhibited attenuated adrenaline-mediated vasodilatation compared to healthy control subjects, suggesting that the chemoreflex in these subjects is ill-equipped to respond to hypoxic stress. In clinical terms, impaired reflex vasomotor

[Formulae and special characters can only be approximated here. Please see the pdf version of the Abtract for an accurate reproduction.] Type 2 diabetes at least doubles the risk of cardiovascular disease. This can partly be explained by the increased prevalence of risk factors such as hypertension, dyslipidaemia and obesity. However, the underlying abnormality of insulin resistance and the presence of more recently identified risk factors including endothelial dysfunction, increased inflammation, and increased oxidative stress might also contribute towards the heightened cardiovascular risk. Fish oil, which contains eicosapentaenoic acid (EPA, 20:5 n-3), has wide-ranging beneficial effects on these and other abnormalities, and has reduced cardiovascular mortality in secondary prevention studies. Animal and human studies have recently established that in addition to EPA, docosahexaenoic acid (DHA, 22:6 n-3) also has beneficial effects, and furthermore, may have less detrimental effects than EPA on glycaemic control which has worsened in some fish and fish oil studies involving Type 2 diabetic subjects. Study 1 : This intervention study aimed to determine the independent effects of EPA and DHA on cardiovascular risk factors and glycaemic control in individuals with Type 2 diabetes receiving treatment for hypertension. In a double-blind placebo-controlled trial of parallel design, 59 subjects in good to moderate glycaemic control (HbA1c < 9%) were recruited from media advertising and randomised to 4 g/day of EPA, DHA or olive oil (placebo) for 6 weeks. Thirty-nine men and 12 post-menopausal women aged 61.2±1.2 yrs completed the study. Relative to placebo, and with Bonferroni adjustments for multiple comparisons, serum triglycerides fell by 19% (p=0.022) and 15% (p=0.022) in the EPA and DHA groups respectively. There were no changes in serum total cholesterol, or LDL- and HDL-cholesterol, although HDL2-cholesterol increased 16% with EPA (p=0.026) and 12% with DHA (p=0.05). HDL3-cholesterol fell by 11% (p=0.026) with EPA supplementation and LDL particle size increased by 0.26±0.10 nm (p=0.02) with DHA. Urinary F2-isoprostanes, an in-vivo marker of oxidative stress was reduced by 19% following EPA (p=0.034) and by 20% following DHA. DHA but not EPA supplementation reduced collagen-stimulated platelet aggregation (16.9%, p=0.05) and thromboxane release (18.8%, p=0.03), but there were no significant changes in PAF-stimulated platelet aggregation. Fasting glucose rose by 1.40±0.29 mmol/l (p=0.002) following EPA and 0.98±0.29 mmol/l (p=0.002) following DHA. Neither EPA nor DHA had any significant effect on HbA1c, fasting serum insulin or C-peptide, insulin sensitivity, stimulated insulin secretion, 24-hr ambulatory blood pressure and heart rate, markers of inflammation, and fibrinolytic or vascular function. Study 2 : This study aimed to examine the influence and causes of increased inflammation on vascular function in subjects recruited for Study 1. Compared with healthy controls (n=17), the diabetic subjects (n=29) had impaired flow-mediated dilatation (FMD) (3.9±3.0% vs 5.5±2.4%, p=0.07) and glyceryl-trinitrate mediated dilatation (GTNMD) (11.4±4.8% vs 15.4±7.1%, p=0.04) of the brachial artery. They also had higher levels of the inflammatory markers C-reactive protein (2.7±2.6 mg/l vs 1.4±1.1 mg/l, p=0.03), fibrinogen (3.4±0.7 g/l vs 2.7±0.3 g/l, p<0.001) and tumor necrosis factor-alpha (20.9±13.4 pg/l vs 2.5±1.7 pg/l, p<0.001). In diabetic subjects, after adjustment for age and gender, leukocyte count was an independent predictor of FMD (p=0.02), accounting for 17% of total variance. Similarly, leukocyte count accounted for 23% (p<0.001) and IL-6 for 12% (p=0.03) of variance in GTNMD. Von Willebrand factor, a marker of endothelial cell activation was correlated with leukocyte count (r=0.38, p=0.04), FMD (r=-0.35, p=0.06) and GTNMD (r=-0.47, p=0.009), whilst P-selectin, a marker of platelet activation was correlated with fibrinogen (r=0.58, p=0.001). Conclusion : EPA and DHA have similar beneficial effects on triglycerides, HDL2 cholesterol and oxidative stress in individuals with Type 2 diabetes and hypertension. However, DHA also increases LDL particle size and reduces collagen-stimulated platelet aggregation and thromboxane release, thus offering more potential than EPA as an anti-thrombotic agent. The beneficial effects of both oils were potentially offset by deterioration in glycaemic control. Neither oil affected blood pressure or vascular function. Longer-term studies with major morbidity and mortality as the primary outcome measures are required to assess the overall benefits and risks of EPA and DHA. The cross-sectional observations from Study 2 are consistent with the hypothesis that impaired vascular function in individuals with Type 2 diabetes and hypertension is at least in part secondary to increased inflammation, with associated endothelial and platelet activation.

Fok, Tsz Nam = 香港二型糖尿病併發症風險評估模型 / 霍梓楠.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (p. 71-72).
Abstracts in English and Chinese.
Fok, Tsz Nam = Xianggang er xing tang niao bing bing fa zheng feng xian ping gu mo xing / Huo Zinan.
Abstract --- p.i
概要 --- p.iii
Acknowledgements --- p.iv
Chapter 1 --- Introduction --- p.1
Chapter 2 --- Dataset Information --- p.3
Chapter 3 --- Background and Literature Review --- p.9
Chapter 3.1 --- The Idea of Risk Model --- p.9
Chapter 3.2 --- Discrimination Problem --- p.10
Chapter 3.3 --- Receiver Operating Characteristic (ROC) Curve --- p.11
Chapter 3.4 --- Summary Indices of the ROC Curve --- p.13
Chapter 3.4.1 --- Area Under ROC Curve (AROC) --- p.14
Chapter 3.4.2 --- Maximum Vertical Distance --- p.16
Chapter 3.5 --- Discrimination Performance in Prognostic Model --- p.18
Chapter 3.5.1 --- Survival Data --- p.18
Chapter 3.5.2 --- Survival Function --- p.20
Chapter 3.5.3 --- Time-dependent ROC Curve for Censored Data --- p.21
Chapter 3.6 --- Earlier Work on Diabetic Complications Risk Models --- p.22
Chapter 3.6.1 --- Maximization of the AROC --- p.28
Chapter 4 --- Model Development --- p.29
Chapter 4.1 --- Overview --- p.29
Chapter 4.2 --- Estimating the ROC curve and the AROC --- p.29
Chapter 4.3 --- Choosing Suitable Risk Factors --- p.30
Chapter 4.4 --- Mixing Risk Factors and Optimizing Coefficients --- p.31
Chapter 4.5 --- Validation of Risk Equations Using Test Set --- p.33
Chapter 5 --- Results and Validation --- p.34
Chapter 5.1 --- Performance of the Risk Factor Candidates --- p.34
Chapter 5.2 --- Estimation of the Coefficients --- p.37
Chapter 5.3 --- Checking the Uniqueness of the Solution --- p.41
Chapter 5.4 --- Validation Using Test Set --- p.46
Chapter 5.5 --- Comparison of AROC-optimized and MVD-optimized Risk Equations --- p.56
Chapter 6 --- Comparison of our Results with Earlier Work --- p.58
Chapter 7 --- "Discussion, Outstanding Issues and Future Works" --- p.66
Chapter 7.1 --- Comparison Between the AROC and the MVD --- p.66
Chapter 7.2 --- Applications of Risk Models --- p.68
Chapter 7.3 --- Limitations of the study --- p.69
Chapter 7.4 --- Outstanding Issues and Future Works --- p.69
Chapter 7.4.1 --- The Estimation of Error Due to Sampling Variance --- p.69
Chapter 7.4.2 --- Time-dependent Coefficients --- p.69
Chapter 7.4.3 --- Extending the Idea to other Datasets --- p.70
Chapter 7.5 --- Conclusion --- p.70
Bibliography --- p.71

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

碩士
台北醫學院
醫學研究所
86
The association between fat intake and the blood biochemical levels was foun d in the complications of non-insulin-dependent diabetes mellitus(NIDDM) pati ents.Total 298 subjects(131 males and 167 females) were taken structure-questi onnaire aboutindividual ,family medical history, and diet intake habits . Meanwh ile , we wrotethe clinical biochemical levels and complications of 298 subject s down .The result shows the average age and with NIDDM age of women older th an those of men. But the systolic blood pressure and height of men are larger than those of women.There are 158 patients with hypertension, 51 persons with retinopathy, 48 subjects withcardio-vascular disease and 23 subjects with canc ers.The different treatments showthe much different risk among hypertension, retinopathy, cardio-vascular disease and cancer.The fat intake is association with the complications. The amount of red and white meat is larger ,then the odds ratio of cardio-vascular diseases is higher. The frequence of vitamin A and vitamin C intake is higher and the odds ratio of cancer also seems higher. There are 5 subjects dead and 5 persons with foot amputation during 1996 to 1998.

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.

Background. Diabetes mellitus is a complex metabolic disorder characterized by clustering of multiple cardiovascular risk factors. Diabetic albuminuria is associated with increased prevalence of both micro-vascular and macro-vascular complications. This thesis examined vascular function (Flow-mediated dilatation, FMD) in type 2 diabetic patients with particular emphasis on its relationships with nephropathy. Independent predictors for FMD in Chinese population using data from both diabetic and non-diabetic subjects as well as the predictive value of FMD on clinical endpoints and death in type 2 diabetic patients with nephropathy were examined.
Conclusions. In Chinese subjects with or without type 2 diabetes, hyperglycaemia, hypertriglyceridemia, smoking and albuminuria were independent predictors for FMD. Type 2 diabetic subjects with overt nephropathy had impaired endothelium-dependent and endothelium-independent dilatation, suggesting vascular dysfunction beyond the endothelium. In agreement with studies from Caucasians, smoking was the most important determinant for vascular dysfunction in Chinese type 2 diabetic patients with overt nephropathy. Furthermore, FMD was predictive of new onset of cardiovascular events and related death in Chinese type 2 diabetic patients with overt nephropathy.
In diabetic patients with overt nephropathy, smoking (current and ex-smokers), waist hip ratio (WHR) and serum creatinine were independent predictors for impaired FMD. The latter was predictive of advancement of IMT and was an independent predictor for new onset of combined cardiovascular diseases and related death after a follow up period of 42 months (log rank test=6.04, p=0.014 using Cox regression analysis) after controlling for all confounding factors. In addition, fasting total cholesterol and plasma glucose were predictive for all-cause mortality while serum creatinine predicted new onset of renal endpoint. In a subgroup analysis in diabetic patients with overt nephropathy, smokers who developed CVD or ESRD had greater diminution of FMD than those who did not develop clinical endpoints.
Methods and results. FMD was assessed using high-resolution ultrasound scan. In the cross-sectional study, the sample population was divided into four groups according to the presence or absence of type 2 diabetes and level of albuminuria. They included the non-diabetic group (N=52), diabetic group with normoalbuminuria (N=18), diabetic group with microalbuminuria (N=18) and diabetic group with overt nephropathy defined as macroalbuminuria and renal insufficiency (N=22). Compared to non-diabetic subjects, type 2 diabetic subjects with nephropathy had impaired FMD (4.54% +/- 2.25 vs. 2.50% +/- 2.31, p<0.05) and impaired GTN-dependent dilatation (GTND) (14.30% +/- 3.77 vs. 12.70% +/- 4.70, p<0.05). They also had reduced endothelium-dependent dilatation to endothelium-independent dilatation ratio when compared to non-diabetic subjects (0.19 +/- 0.17 vs. 0.32 +/- 0.15, p<0.05). These findings suggest that the impaired vascular dilatation was due to dysfunction of both endothelium and vascular smooth muscle cells. In the entire cohort, fasting plasma glucose, fasting triglyceride, smoking and albuminuria were independent predictors for FMD.
Lai Wai Keung Christopher.
"February 2006."
Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6298.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2006.
Includes bibliographical references (p. 202-252).
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.

Conclusion. The equations developed in this study provide a more accurate estimate of GFR, ranging from normal to renal impairment, in both Chinese diabetic and non-diabetic patients, compared to currently available GFR formulae.
Hypothesis/objectives. Type 2 diabetes mellitus is a major health burden associated with increased morbidity and mortality as well as socio-economic impact. A rapid increase in disease prevalence has been reported and predicted in China and other Asian countries. Patients with low and declining GFR and microalbuminuria are at high CVD risk. A simple and precise predictive equation of GFR for Chinese diabetic patients is essential in the light of the growing epidemic of diabetes and CKD in Chinese population both for monitoring and treatment purposes. In this pilot study, a set of accurate, simple and clinically practical equations to predict GFR in Chinese type 2 diabetic patients was established. Their performance was validated using separate samples of diabetic and non-diabetic subjects and compared with other widely used GFR formulae.
Methods. 202 type 2 diabetic patient and 46 non-diabetic patients were enrolled in the study. Of these 135 were randomly selected as the training sample; the remaining 67 diabetic patients and 46 non-diabetic patients constituted 2 validation groups. The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equation including MDRD and CG equations in the validation samples.
Results. Independent factors associated with GFR included age, serum creatinine concentration, serum urea nitrogen level and serum albumin levels (P < 0.005 for all factors). Two predictive formulae, sRFCD and RFCD, were established. Simplified Renal formula in Chinese Diabetes (sRFCD) Study (ml/min/1.73 m2) is: GFR (for men) = 90400 x (Age)-0.495 (yr) x [ SCr]-1.097 (mumol/l) GFR (for women) = 58983 x (Age)-0.542 (yr) x [SCr]-1.012 (mumol/l) and Renal formula in Chinese Diabetes (RFCD) Study (ml/min/1.73 m2) is: GFR (for men) = 11825 x (Age)-0.494 x [SCr]-1.059 (mumol/l) x [Alb]+0.485 (g/l) GFR (for women) = 34166 x ( Age)-0.489 x [SCr] -0.877 (mumol/l) x [SUN] -0.150 (mmol/l) The multiple regression model explained 89.9% and 89.4% respectively of the variance in the logarithm of GFR. Compared to other GFR formulae, the sRFCD and RFCD formulae showed less bias and were more precise and accurate in estimating GFR in diabetic patients whereas the sRFCD and MDRD formulae showed better performance in non-diabetic patients.
Leung Tak Kei.
"July 2006."
Adviser: Juliana C. N. Chan.
Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5117.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2006.
Includes bibliographical references (p. 161-180).
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.

Poon, Chui Wa Christina.
"August 2011."
Thesis (M.Phil.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 123-131).
Abstracts in English and Chinese.
ABSTRACT --- p.i
論文摘要 --- p.vi
ACKNOWLEDGEMENTS --- p.ix
PUBLICATIONS --- p.x
Abstracts --- p.x
ABBREVIATIONS --- p.xii
Chapter 1. --- GENERAL INTRODUCTION --- p.1
Chapter 1.1. --- Diabetes --- p.1
Chapter 1.1.1. --- Overview --- p.1
Chapter 1.1.2. --- Diagnostic Criteria of Type-2 Diabetes --- p.2
Chapter 1.1.3. --- Type-2 Diabetes (T2DM) --- p.3
Chapter 1.1.3.1. --- Impaired Insulin Synthesis and Insulin Secretory Defects in Type-2 Diabetes --- p.3
Chapter 1.1.3.2. --- β-Cell Dysfunction --- p.5
Chapter 1.1.3.3. --- Insulin Resistance --- p.5
Chapter 1.1.4. --- Glucose Toxicity --- p.6
Chapter 1.1.4.1. --- Fasting Hyperglycemia --- p.8
Chapter 1.1.4.2. --- Postprandial Hyperglycemia --- p.8
Chapter 1.2. --- Oxidative Stress --- p.8
Chapter 1.2.1. --- ROS and Mitochondria --- p.8
Chapter 1.2.2. --- ROS Production by Mitochondria --- p.9
Chapter 1.2.3. --- The Relationship of Glucose Recognition by β-cells and Oxidative Stress --- p.11
Chapter 1.2.4. --- Important Roles of Glutathione in Pancreatic β-cells and Glutathione Synthesis --- p.14
Chapter 1.2.5. --- N-acetyl-L-cysteine - A Potential Drug Treatment for Type-2 Diabetes? --- p.17
Chapter 1.3. --- Role of F-actin Cytoskeleton on Glucose-induced Insulin Secretion --- p.18
Chapter 1.4. --- Current Clinical Treatments for Type-2 Diabetes Mellitus --- p.21
Chapter 1.4.1. --- Metformin --- p.22
Chapter 1.4.2. --- Sulfonylureas --- p.22
Chapter 1.4.3. --- Thiazolidinediones --- p.23
Chapter 1.4.4. --- Glinides (Meglitinide Analogues) --- p.23
Chapter 1.4.5. --- α-Glucosidase (AG) Inhibitors --- p.24
Chapter 1.4.6. --- Dipeptidyl Peptidase-4 (DPP-4) Inhibitors --- p.24
Chapter 1.4.7. --- (Clinical) Antioxidant Treatment --- p.24
Chapter 1.5. --- Animal Models Used in Type-2 Diabetes Research --- p.25
Chapter 1.6. --- Aims of Study --- p.27
Chapter 2. --- RESEARCH DESIGN & METHODS --- p.28
Chapter 2.1. --- Materials --- p.28
Table 1. Sources and concentrations of drugs tested in this study: --- p.28
Culture Medium - --- p.29
General Reagents --- p.29
Chapter 2.2. --- Isolation of Islets of Langerhans and Single Pancreatic β-Cells --- p.31
Chapter 2.3. --- Measurement of Mitochondrial ROS Levels --- p.32
Chapter 2.4. --- Measurement of Islets Insulin Release and Insulin Content --- p.34
Chapter 2.4.1. --- Preparation of Samples --- p.34
Chapter 2.4.2. --- Enzyme-Link Immunosorbent Assay (ELISA) --- p.35
Chapter 2.5. --- Immunocytochemistry --- p.35
Chapter 2.6. --- Data and Statistical Analysis --- p.37
Chapter 3. --- RESULTS --- p.38
Chapter 3.1. --- "Effects of L-NAC, Various Oxidative Stress Inducers/Reducers and Actin Polymerisation/Depolymerisation Inducers on Releasable Insulin Levels and Insulin Contents in Response to Low Glucose (5 mM) and High Glucose (15 mM) of Isolated Pancreatic Islets of (db+/m+) and (db+/db+) Mice" --- p.38
Chapter 3.1.1. --- Effect of L-NAC on Insulin Secretion and Insulin Contents --- p.38
Chapter 3.1.2. --- Effect of Cytochalasin B on Insulin Secretion and Insulin Contents --- p.39
Chapter 3.1.3. --- Effect of 4-Phenyl Butyric Acid on Insulin Secretion and Insulin Contents --- p.43
Chapter 3.1.4. --- Effect of Ursodeoxycholic Acid on Insulin Secretion and Insulin Contents --- p.46
Chapter 3.1.5. --- Effect of Hydrogen Peroxide on Insulin Secretion and Insulin Contents --- p.49
Chapter 3.1.6. --- Effect of Jasplakinolide on Insulin Secretion and Insulin Contents --- p.53
Chapter 3.1.7. --- Effect of Thapsigargin on Insulin Secretion and Insulin Contents --- p.57
Chapter 3.1.8. --- Effect of BSO on Insulin Secretion and Insulin Contents --- p.61
Chapter 3.2. --- "Effects of L-NAC, Various Oxidative Stress Inducers/Reducers and Actin Polymerisation/Depolymerisation Inducers on Mitochondrial ROS Levels in Response to High Glucose (15 mM) Challenge in Isolated Single Pancreatic β-Cells of (db +/m+) and (db +/db +) Mice" --- p.65
Chapter 3.2.1. --- "Effects of L-NAC (20 mM), 4-Phenyl Butyric Acid (4-PBA) (1 mM), Ursodeoxycholic Acid (UA) (500 μg/ml), H202 (200 μM), Thapsigargin (0.5 μM) and DL-Buthionine-[S,R]-Sulfoximine (BSO) (0.1 μM) Pre-treatments on Mitochondrial ROS Level in Response to High Glucose (15 mM) Challenge" --- p.65
Chapter 3.2.2. --- "Effects of L-NAC (20 mM), Cytochalasin B (10 μM) and Jasplakinolide (5 μM) Pre-treatments on Mitochondrial ROS Level in Response to High Glucose (15 mM) Challenge_" --- p.76
Chapter 3.3. --- "Effects of L-NAC, Various Oxidative Stress Inducers/Reducers and Actin Polymerisation/Depolymerisation Inducers on F-actin Cytoskeleton Levels Incubated in Low Glucose (5 mM) and High Glucose (15 mM) Medium in Single Pancreatic β-Cells of Non-Diabetic (db +/m+) and Diabetic (db +/db +) Mice" --- p.81
Chapter 4. --- DISCUSSION --- p.100
Chapter 4.1. --- General Discussion --- p.100
Chapter 5. --- SUMMARY --- p.120
Chapter 6. --- FUTURE PERSPECTIVES --- p.121
Chapter 7. --- REFERENCES --- p.123

The aim of this chapter is to provide nurses with the knowledge to be able to assess, manage, and care for people with type 1 and type 2 diabetes mellitus in an evidence-based and person-centred way. Diabetes mellitus is a long-term condition that can affect people of all ages; consequently, people with diabetes mellitus can be found in every healthcare environment, from hospitals to care homes. The chapter will provide a comprehensive overview of the classifications, causes, and risk factors of diabetes. The key principles of patient assessment are established, before exploring best practice to deliver care, prevent acute complications, and minimize long-term complications. Nursing assessments and priorities are highlighted throughout, and the nursing management of the symptoms and common health problems associated with diabetes can be found in Chapters 19, 22, 24, 25, 26, and 28, respectively. Diabetes mellitus is a group of metabolic conditions with hyperglycaemia occurring as the main feature. It is characterized by chronic increased blood glucose (hyperglycaemia), with disturbance of carbohydrate, protein, and fat metabolism, which results from defects in insulin secretion, insulin action, or both (World Health Organization (WHO), 1999). The hormone insulin, produced by the beta cells in the pancreas, controls blood glucose levels, keeping them within a narrow range in normal health (4–6 mmol/l before food). When blood glucose levels rise (for example, after a meal containing carbohydrates has been consumed), glucose enters the beta cells, eventually resulting in the release of insulin into the portal circulation. The classifications of diabetes mellitus (World Health Organization, 2006) are as follows….● Type 1 diabetes mellitus, previously known as insulin-dependent diabetes mellitus (IDDM) ● Type 2 diabetes mellitus, previously known as non-insulin-dependent diabetes mellitus (NIDDM) ● Gestational diabetes mellitus ● Others, such as disorders affecting the pancreas, and endocrine conditions…The features of type 1 and type 2 diabetes mellitus are outlined in Table 9.1. Gestational diabetes is carbohydrate intolerance, resulting in hyperglycaemia with onset or recognition during pregnancy (World Health Organization, 2006). However, the condition may have been present prior to pregnancy, but not been diagnosed. Diabetes mellitus may occur for other reasons, including genetic defects and diseases affecting the pancreas.

The UK Prospective Diabetes Study (UKPDS) Hypertension in Diabetes Study was a randomized intervention trial in patients with type 2 (non-insulin-dependent) diabetes mellitus to determine whether improved blood glucose control prevented complications and reduced the associated morbidity and mortality. The Hypertension in Diabetes Study, reported in this chapter, was included in a factorial design to assess whether improved control of blood pressure would reduce the incidence of diabetic retinopathy and loss of vision. The results clearly demonstrated the importance of lowering blood pressure to reduce the progression of retinopathy, incidence of macular edema, and loss of vision in persons with relatively short duration of type 2 diabetes and moderate to severe hypertension. Treatment begun early in the course of type 2 diabetes is likely to have a long-term effect of reducing visual loss secondary to diabetic macular edema in persons with type 2 diabetes.

Peripheral neuropathies are most frequently a complication of a variety of acute and chronic diseases and injuries, including diseases of the roots, plexuses, and peripheral nerves in various combinations, and are categorized as symmetric polyneuropathies, mononeuropathies, multifocal neuropathies, and radiculopathies. This chapter illustrates data about peripheral neuropathies in the general population and in selected cohorts at risk: diabetic neuropathy (present in 66% of insulin-dependent and 59% of non-insulin-dependent diabetic individuals), acute and chronic inflammatory (2–16% of all polyneuropathies in hospital-based studies), paraneoplastic, infectious (Mycobacterium leprae, HIV, predominant in resource-poor countries), toxic and iatrogenic (antibacterial, antiparasitic, cardiovascular and chemotherapeutic agents), due to entrapment (carpal tunnel syndrome), and inherited (Charcot-Marie-Tooth, familial amyloidotic polyneuropathy, hereditary motor/sensory neuropathies). The actual burden of peripheral neuropathies is unknown because incidence and prevalence are preferably calculated in patients with the underlying cause and for the variability and low validity and reliability of the diagnostic criteria.