[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

Thesis (M.D.)--University of Adelaide, Dept. of General Practice, 2005. / Includes publications published as a result of ideas developed in this thesis, inserted at end. "April 2005" Includes bibliographical references (leaves 210-242).

Thesis (Ph.D. in Epidemiology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 100-117). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

[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.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

M.Cur. / The former Transkei is a predominantly rural region of the Eastern Cape Province. The poor infrastructure in this area results in inaccessibility of the available health services. The majority is ill equipped to deliver optimum diabetes care. There is an increase of lower limb amputations and lack of knowledge among patients with diabetes in the former Transkei. These complications can be prevented by patient education on self-management and appropriate footcare procedures. This qualitative study was conducted to explore and describe the experiences and footcare practices of diabetic patients who live in the rural areas of Transkei. A sample of 15 participants was drawn from Umtata Hospital Diabetic Clinic register through predetermined selection criteria. The sample consisted of five men aged 49 - 74 years, and ten women aged 30 - 64 years. Five patients (two men and three women) had foot ulcers or an amputation, while ten patients had no obvious foot problems. In-depth phenomenological interviews were conducted with all 15 patients. Interviews were tape recorded in Xhosa, transcribed, and translated into English for analysis. Direct observation of footcare was done with eight patients from the sample. Content analysis of the phenomenological interviews was facilitated by a protocol; and a checklist guided direct observation of footcare. A debate took place among the three coders to come to a consensus about the themes that emerged from their individual analyses. Guba's model of trustworthiness was utilised to ensure that the findings of this study reflect the truth. Ethical considerations were based on the guidelines cited by the Democratic Nursing Organisation of South Africa (1998: 2.3.1-2.3.4) and the South African Medical Research Council (1993: 32-44). Findings revealed predominantly negative experiences in the internal and external environments of the persons with diabetes; as well as poor footcare knowledge and practices. The recommendations relate to improving diabetes as well as footcare knowledge and skills through education; promoting adherence to diabetes treatment regimens; providing emotional support; improving the selfimage of persons with diabetes; changing health beliefs; improving the quality of diabetes care in public health facilities; and increasing diabetes awareness among employers of diabetic persons.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 4 uppsatser. Även tryckt utgåva.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010. / Härtill 4 uppsatser.

<p>УВОД: Diabetes mellitus (DM) је водећа глобална епидемија 21. века, сложена болест коју карактерише поремећај метаболизма и хронична хипергликемија, која доводи до развоја микроваскуларних и макроваскуларних компликација. Повишене вредности гликемије у ДМT2 доводе до поремећаја ћелија крви и њихових параметара. Истраживања су показала да хема-толошки параметри имају допринос у настанку оштећења васкуларног ендотела и учествују у развоју дегенеративних промена и путем других механизама код пацијената са дијабетесом. Циљ истраживања је да се утврде могуће промене параметара комплетне крвне слике (ККС) у зависности од гликорегулације, дужине трајања болести и њихова повезаност са микро и макро ангиопатским комликацијама код пацијената са шећерном болести тип 2 (ДМT2). МЕТОДЕ: Студија је била проспективна у трајању од једне године, од 2016. до 2017. године. Истраживањем је обухваћено укупно 137 испитаника, од којих 90 болује од ДМТ2, а 47 је здравих, оба пола, старијих од 40 година, спроведена у Дому здравља &ldquo;Др Милорад Мика Павловић&rdquo;, Инђија, Србија. Да би се утврдила могућа корелација између параметара ККС, гликорегулације у ДМT2 и дегенеративних компликација, испитаници су подељени на више начина: на групу оболелих од ДМT2 и групу здравих; групе оболелих са вредностима HbA1c&le;7% и оне са вредностима HbA1c &gt;7%, као и на групе са и без дегенеративних компликација. Коришћењем стандардних биохемијских поступака анализирани су параметри ККС, параметри гликорегулације, липидни статус, а вршена су и антропометријска мерења. Подаци од пацијената прикупљени су путем упитника и електронског картона пацијента. РЕЗУЛТАТИ: Утврђена је статистички значајна разлика између група са и без шећерне болести за WBC, еозинофилне гранулоците, хемоглобин, MCH, MCHC, SE у 2016. год, неутрофилне гранулоците, моноците, RDW, PDW, SE у 2017. год. У групи чија је дужина трајања ДМT2 већа од 6 година утврђене су повишене вредности MCHC и PDW. У односу на гликорегулацију уочене су значајне разлике у PMDW, великим тромбоцитима и RDW у групи са HbA1c&gt;7%. У односу на дегенеративне микроваскуларне компликације постоје значајне разлике у броју лимфоцита и неутрофилних гранулоцита, а за макроваскуларне компликације у вредностима PDW-а. ЗАКЉУЧАК: На основу добијених резултата нашег истраживања може се закључити да постоји повезаност између појединих хематолошких параметара и гликорегулације, обољевања од шећерне болести као и повезаност са компликацијама код пацијената са ДМТ2.</p> / <p>UVOD: Diabetes mellitus (DM) je vodeća globalna epidemija 21. veka, složena bolest koju karakteriše poremećaj metabolizma i hronična hiperglikemija, koja dovodi do razvoja mikrovaskularnih i makrovaskularnih komplikacija. Povišene vrednosti glikemije u DMT2 dovode do poremećaja ćelija krvi i njihovih parametara. Istraživanja su pokazala da hema-tološki parametri imaju doprinos u nastanku oštećenja vaskularnog endotela i učestvuju u razvoju degenerativnih promena i putem drugih mehanizama kod pacijenata sa dijabetesom. Cilj istraživanja je da se utvrde moguće promene parametara kompletne krvne slike (KKS) u zavisnosti od glikoregulacije, dužine trajanja bolesti i njihova povezanost sa mikro i makro angiopatskim komlikacijama kod pacijenata sa šećernom bolesti tip 2 (DMT2). METODE: Studija je bila prospektivna u trajanju od jedne godine, od 2016. do 2017. godine. Istraživanjem je obuhvaćeno ukupno 137 ispitanika, od kojih 90 boluje od DMT2, a 47 je zdravih, oba pola, starijih od 40 godina, sprovedena u Domu zdravlja &ldquo;Dr Milorad Mika Pavlović&rdquo;, Inđija, Srbija. Da bi se utvrdila moguća korelacija između parametara KKS, glikoregulacije u DMT2 i degenerativnih komplikacija, ispitanici su podeljeni na više načina: na grupu obolelih od DMT2 i grupu zdravih; grupe obolelih sa vrednostima HbA1c&le;7% i one sa vrednostima HbA1c &gt;7%, kao i na grupe sa i bez degenerativnih komplikacija. Korišćenjem standardnih biohemijskih postupaka analizirani su parametri KKS, parametri glikoregulacije, lipidni status, a vršena su i antropometrijska merenja. Podaci od pacijenata prikupljeni su putem upitnika i elektronskog kartona pacijenta. REZULTATI: Utvrđena je statistički značajna razlika između grupa sa i bez šećerne bolesti za WBC, eozinofilne granulocite, hemoglobin, MCH, MCHC, SE u 2016. god, neutrofilne granulocite, monocite, RDW, PDW, SE u 2017. god. U grupi čija je dužina trajanja DMT2 veća od 6 godina utvrđene su povišene vrednosti MCHC i PDW. U odnosu na glikoregulaciju uočene su značajne razlike u PMDW, velikim trombocitima i RDW u grupi sa HbA1c&gt;7%. U odnosu na degenerativne mikrovaskularne komplikacije postoje značajne razlike u broju limfocita i neutrofilnih granulocita, a za makrovaskularne komplikacije u vrednostima PDW-a. ZAKLJUČAK: Na osnovu dobijenih rezultata našeg istraživanja može se zaključiti da postoji povezanost između pojedinih hematoloških parametara i glikoregulacije, oboljevanja od šećerne bolesti kao i povezanost sa komplikacijama kod pacijenata sa DMT2.</p> / <p>BACKGROUND: Diabetes mellitus (DM) is the leading global epidemic of the 21st century,a complex disease characterized by metabolism disorders and chronic hyperglycaemia, that leads to the development of microvascular and macrovascular complications. Elevated blood glucose level in T2DM lead to disturbance of blood cells and its parameters. Previous studies have reported that haematological parameters have contributed to the development of vascular endothelial damage and are involved in the development of degenerative changes through other mechanisms in patients with diabetes. The aim of the research is to determine possible changes in the complete blood count (CBC) parameters depending on glycemic control, the duration of the disease and their association with micro and macroangiopathic complications in patients with Type 2 diabetes mellitus (T2DM). METHODS: The study was prospective from 2016. to 2017. year. The study included a total of 137 subjects, 90 with T2DM and 47 healthy, of both gender over the age of 40 years, from the Health Care Center &quot;Dr Milorad Mika Pavlović&quot; Indjija, Serbia. The subjects were divided into several ways, in order to notice the possible correlation between the CBC parameters and glucose control in T2DM, with and without T2DM, two groups with HbA1c&le;7% and with HbA1c&gt;7%, and with and without complications. We analysed CBC parameters, parameters of glycoregulation, lipid status using standard biochemical methods, performed anthropometric measurements and collected patients data by questionnaire and electronic patient card. RESULTS: There were statistical difference between group with T2DM and healthy subjects for WBC, eos, Hgb, MCH, MCHC, ESR in 2016. and neutro, mono, RDW, PDW, ESR in 2017. In the group of T2DM patients with duration of disease longer than 6 years we found elevated value of MCHC, PDW. In relationship to glycoregulation, significant differences in PMDW, large platelets and RDW were found in the group HbA1c&gt;7%. According to degenerative complications significant differences were revealed in lympho, neutro in the group with microvascular complication, and PDW in the group with macrovascular complications. CONCLUSION: Based on the resuluts of our research, it can be concluded that there is an association between particular haematological parameters and glycoregulation, diabetes mellitus, as well as relationship with degenerative complications in patients with T2DM.</p>

Includes publications published as a result of ideas developed in this thesis, inserted at end. / "April 2005" / Includes bibliographical references (leaves 210-242) / 242 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines goal setting in people with diabetes as part of chronic disease management in a rural setting. The studies were performed in Eyre Peninsula with a significant (10-20%) Aboriginal population. / Thesis (M.D.)--University of Adelaide, Dept. of General Practice, 2005