It is currently accepted that the most appropriate diet in the treatment of non-insulin-dependent diabetes mellitus &quoteNIDDM&quote is high in carbohydrates, high in fibre and low in fat. Dietary fibre reduces the rate of carbohydrate absorption, which may have a beneficial effect on insulin action. Furthermore, high fibre diets also increase the amount of carbohydrates which are not absorbed from the small intestine. These malabsorbed carbohydrates are fermented by the bacterial population in the large intestine, producing short chain fatty acids &quoteSCFA&quote, including propionate, which has been shown to alter liver carbohydrate metabolism. This thesis investigated the actions of slowed carbohydrate absorption and carbohydrate malabsorption in streptozotocin-induced &quoteSTZ&quote diabetic rats. High carbohydrate diet supplemented with guar gum, a soluble dietary fibre, fed to STZ diabetic rats improved insulin sensitivity. investigation of the alterations in the stomach and small intestine demonstrated that guar increased the viscosity of the meal in the intestine. The action of increased fermentation, producing more propionate, was investigated by supplementing propionate into the diets of STZ diabetic rats or when perfused into isolated rat livers. No changes in insulin action or liver glucose metabolism were measured. in addition, it was shown that guar gum reduces food intake in STZ diabetic rats. Mild reductions in food intake in STZ diabetic rats were shown to increase insulin action. In summary, STZ diabetic rats fed high carbohydrate, high fibre diets reductions in food consumption and slowed carbohydrate absorption are important factors which may lower blood glucose concentrations and increase insulin action. increased SCFA production is unlikely to contribute significantly to the improvements in insulin action.

Thesis (Ph. D.)--University of Wisconsin--Madison, 2000. / Includes bibliographical references (leaves 125-131).

[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.

Thesis (M.S.)--University of Michigan, 1994.

Thesis (M.S.)--University of Michigan, 1994.

Thesis (Ph. D.)--University of Wisconsin--Madison, 2000. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 125-131).

Thesis (MNutr)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Introduction: Intensive lifestyle intervention in people with Type 2 Diabetes Mellitus (T2DM) is associated with weight loss, significant reductions in HbA1c% and a reduction in cardiovascular disease risk factors. Small towns unfortunately experience a deficit of dieticians, thus limiting access to lifestyle intervention. Furthermore, a limited number of South African studies have evaluated the effect of dietary habits, anthropometric status, activity level (AL) and dietician-led medical nutrition therapy (MNT) on glycaemic control in patients with T2DM. This study thus aimed to identify the association between glycaemic control and lifestyle habits in adults with T2DM living in Thabazimbi. The role of the dietician with regard to optimal glycaemic control was also investigated with great interest. Methods: Individuals (>18 years) with T2DM who had a recent HbA1c test result and no acute infection/illness were included in the study over a 7 month recruitment period. Weight, height and waist circumference were measured, AL and dietetic contact evaluated, and dietary habits assessed by means of a structured questionnaire. Six home-measured post-prandial glucose (PPG) measurements and HbA1c% were used to evaluate glycaemic control. Results: A total of 62 (59.7% males) patients were included. The mean age was 60.13 ±10.85 years and mean T2DM disease duration was 121 ±96.56 months. Only 6.45% of participants had a normal Body Mass Index classification. Most (90.32%) participants had a substantially increased waist circumference (WC). Half of the participants had a sedentary/low AL, whilst 48.39% had an active/moderately active AL. Almost all (95%) participants indicated it was necessary for persons with DM to consult a dietician for MNT, however only 63% of participants actually consulted one. Mean dietary compliance was 74.53 ±10.93%. The average HbA1c% and PPG of participants were respectively 7.50 ±1.62% and 8.90 ±3.21mmol/l. A significant negative association (r=-0.31; p=0.02) was found between HbA1c% and percentage dietary compliance. The number of dietetic sessions completed and average PPG were also significantly [(r=0.40; p=0.001), (r=-0.34; p=0.01)] associated with percentage dietary compliance. In turn PPG had a significant positive (r=0.30; p=0.02) association with DM disease duration. Both the good HbA1c and good PPG control groups had significantly (p=0.01, p=0.04) better dietary habits than the poor HbA1c and PPG control groups. When compared to the poor PPG group, the good PPG group made significantly (p=0.04) better dietary decisions with regard to the main meal’s carbohydrate quality and quantity. Body Mass Index, WC, AL and extent of dietetic contact didn’t play a significant role in the glycaemic classification (good vs. poor) of participants. Conclusion: The longer T2DM is present, the worse PPG control becomes. Optimal dietary habits play a significant positive role in both the long- and short term glycaemic control of people with T2DM in Thabazimbi. The choice and portion size of the main meal’s carbohydrates has been identified to be the most important dietary role-player in the glycaemic control of this study population. This study also shows that if individuals with DM spend enough time with a dietician, it could potentially contribute to better dietary compliance and subsequent better glycaemic control. / AFRIKAANSE OPSOMMING: Inleiding: Intensiewe leefstyl intervensie onder diegene met Tipe 2 Diabetes Mellitus (T2DM) word geassosieer met gewigsverlies, beduidende verlaging in HbA1c% asook ’n vermindering in verskeie kardiovaskulêre-siekte risiko faktore. Plattelandse dorpies beleef egter ’n tekort aan dieetkundiges, wat gevolglik toegang tot leefstyl intervensie beperk. Daar is ook ’n beperkte hoeveelheid Suid-Afrikaanse studies wat die impak van eetgewoontes, antropometriese status, aktiwiteitsvlak en dieetkundige-begeleide dieetterapie op glisemiese beheer in T2DM pasiënte evalueer. Die doel van die studie was dus om die verband tussen glisemiese beheer en leefstyl gewoontes in volwassenes met T2DM in Thabazimbi te bepaal. Die rol van die dieetkundige met betrekking tot optimale glisemiese beheer was ook met groot belangstelling nagevors. Metodes: Diegene (>18 jaar) met T2DM wat oor ’n onlangse HbA1c toets uitslag beskik het en nie enige akute siektes/infeksie gehad het nie, is oor ’n 7 maande werwingsperiode ingesluit. Gewig, lengte en middel-omtrek was gemeet, aktiwiteitsvlak en dieetkundig-kontak bepaal, en eetgewoontes geassesseer m.b.v. ’n gestruktueerde vraelys. Ses tuis-bepaalde na-ete bloedsuiker lesings en HbA1c% was gebruik om glisemiese beheer te evalueer. Resultate: Twee-en-sestig (59.7% mans) pasiënte het aan die studie deelgeneem. Die gemiddelde ouderdom was 60.13 ±10.85 jaar en die gemiddelde T2DM duurte 121 ±96.56 maande. Slegs 6.45% van die deelnemers het ’n gesonde Liggaam-Massa-Indeks gehad. Meeste (90.32%) deelnemers se middel-omtrek was ook ruimskoots verhoog. Die helfte van die deelnemers het ’n passiewe/lae aktiwiteitsvlak gehad, terwyl 48.39% ’n aktief/matig-aktiewe aktiwiteitsvlak gerapporteer het. Amper al (95%) die deelnemers het aangedui dat mense met T2DM ’n dieetkundige moet raadpleeg vir dieetterapie. Slegs 63% van die deelnemers het egter werklik ’n dieetkundige vir diabetes dieetterapie geraadpleeg. Gemiddelde dieet-gehoorsaamheid was 74.53 ±10.93% en die gemiddelde HbA1c % en na-ete bloedsuiker vlakke van deelnemers was onderskeidelik 7.50 ±1.62% en 8.90 ±3.21mmol/l. Daar was ’n beduidende negatiewe verband (r=-0.31; p=0.02) tussen HbA1c % en persentasie dieet-gehoorsaamheid. ’n Beduidende verband was ook tussen persentasie dieet-gehoorsaamheid en die hoeveelheid voltooide dieetterapie sessies (r=0.40; p=0.001) asook die gemiddelde na-ete bloedglukose vlak (r=-0.34; p=0.01) geïdentifiseer. Na-ete bloedglukose het ook ’n beduidende positiewe (r=0.30; p=0.02) verband met die duurte van diabetes getoon. Beide die goeie HbA1c en goeie na-ete glukose groepe het beduidend (p=0.01, p=0.04) beter eetgewoontes as die swak HbA1c en swak na-ete glukose groepe gehad. Die goeie na-ete glukose groep het veral beduidend (p=0.04) beter dieet keuses m.b.t die hoofmaal se koolhidraat kwaliteit en kwantiteit gemaak. Lengte-Massa-Indeks, middel-omtrek, aktiwiteitsvlak en die mate van dieetkundige kontak het nie ’n beduidende rol in die glisemiese klassifikasie (goed teenoor swak) van deelnemers gespeel nie. Gevolgtrekking: Na-ete bloedsuiker beheer word al hoe slegter hoe langer T2DM teenwoordig is. Optimale eetgewoontes speel ’n beduidende positiewe rol in beide die lang- en kort-termyn glisemiese beheer van mense met T2DM in Thabazimbi. Die keuse en porsie grootte van die hoofmaal se koolhidrate blyk die belangrikste dieet rolspeler in die glisemiese beheer van die studie populasie te wees. Die studie dui ook aan dat as mense met T2DM genoeg tyd saam met ’n dieetkundige deurbring, dit moontlik kan bydra tot beter dieet-gehoorsaamheid en gevolglik beter glisemiese beheer.

Dados prévios ja demostram que o controle intensivo da glicemia diminui o risco de eventos microvasculares em pacientes com diabetes mellitus. No entanto, seu efeito cardiovascular é incerto. Nós sumarizamos os dados de estudos das principais bases de dados. 2 revisores extraíram dados de estudos randomizados de pacientes com diabetes tipo 2, que visavam 2 níveis de intensidade da glicemia. Investigou-se as retinopatia, neuropatias, nefropatias, mortalidade cardiocascular e total, infarto do miocárdio (IAM), acidente vascular cerebral, amputação de membros e episódios de hipoglicemia. Realizamos a meta-análise para obter o risco relativo (RR). Foram incluídos 7 estudos com 27.814 pacientes. O controle intensivo reduziu o RR de IAM e amputação, além progressão da retinopatia, incidência de neuropatia periférica, incidência e progressão de nefropatia e microalbuminúria. Entretanto, dobrou o risco de episódios de hipoglicemia. Não houve diferenças quanto à mortalidade e outros resultados. Conclui-se que controle intensivo reduziu o risco de alguns eventos, sem reduzir a mortalidade, porém as custas do dobro da incidência de de hipoglicemia. / Previous data already show that intensive glucose control reduces the risk of microvascular events in patients with diabetes mellitus. However, its cardiovascular effect is uncertain. We summarize data from studies of the major databases. 2 reviewers extracted data from randomized studies of patients with type 2 diabetes, aimed at two intensity levels of blood glucose. We investigated the retinopathy, neuropathy, nephropathy, and total mortality cardiocascular, myocardial infarction (IAM), stroke, limb amputation and episodes of hypoglycemia. We conducted a meta-analysis to obtain the relative risk (RR). We included seven studies with 27.814 patients. The intensive control reduced the RR of IAM, and amputation, and progression of retinopathy, incidence of peripheral neuropathy, incidence and progression of nephropathy and microalbuminuria. However, it doubled the risk of hypoglycemia. There were no differences in mortality and other outcomes. We conclude that intensive control reduced the risk of some events without reducing mortality, but the expense of twice the incidence of hypoglycemia.

Indiana University-Purdue University Indianapolis (IUPUI) / Type 2 diabetes, a chronic condition affecting millions, continues to rise in epidemic proportions. Type 2 diabetes, managed through lifestyle changes, affects the entire family. Family caregivers provide vital support to these individuals; however, little research has been conducted surrounding the perceived difficulty or ease of caregiver activity and supportive behaviors. The purpose of this dissertation was to develop and psychometrically test a scale that measures this difficulty or ease of activities and behaviors. This was accomplished through the compilation of three distinct manuscripts. First, an integrative review was conducted to identify what is known regarding needs and concerns of family caregivers of persons with type 2 diabetes; findings revealed a need for more research. Then, based on these recommendations, a qualitative study was conducted that explored the needs and concerns identified by 33 American Indian, African American, and White family caregivers. All these caregivers had similar concerns related to needing general diabetes information, providing support to the family member, and taking care of their own health. Study themes were used to develop items for a new instrument, the Diabetes Caregiver Activity and Support Scale (D-CASS) that was psychometrically tested with 101 American Indian, African American, and White family caregivers of persons with type 2 diabetes. This study used a cross-sectional, descriptive-correlational design and provided evidence of internal consistency reliability (α = .82) and two-week test-retest reliability (intraclass correlation coefficient = .70) for the D-CASS. Criterion-related validity was established using a single-item criterion measuring overall how easy or difficult it was for caregivers to provide care for their loved ones (r = .65, p < .01). Unidimensionality was supported by factor analysis, with loadings ranging from .45 to .70, with 32% of the variance explained by the first factor (eigenvalue = 4.02). Model testing through a series of three hierarchical multiple regressions guided by a conceptual model provided further evidence of construct validity for the D-CASS. This dissertation provided better understanding of needs and concerns of family caregivers of persons with type 2 diabetes and led to the development of a psychometrically sound diabetes-specific instrument for future research.

Indiana University-Purdue University Indianapolis (IUPUI) / Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of incretin based therapeutics which aid in blood glucose management in Type II diabetes mellitus (T2DM). Recent studies have demonstrated direct cardiovascular benefits conferred by these agents including protection in ischemia and heart failure. Despite these observations, human clinical trials fail to support improvements in cardiovascular outcomes independent of glucose lowering effects in the T2DM populations. Prior data from our lab demonstrate that obesity impairs GLP-1 associated increases in myocardial glucose uptake. However, the reasons for this impairment/resistance to cardiac effects of GLP-1 in the setting of obesity remain ill defined. This investigation tested the hypothesis that underlying differences in the cardiac proteome and microRNA (miR) transcriptome could contribute to distinct cardiac responses to ischemia and activation of GLP-1 signaling in the setting of obesity. To identify whether obesity modulated cardiac functional responses to GLP 1 related drugs, we first examined the effects of obesity on cardiac function, miR transcriptome, and proteome in response to short duration ischemia-reperfusion (I/R). We observed divergent physiologic responses (e.g. increased diastolic volume and systolic pressure in lean, decreased diastolic volumes in obese) to regional I/R in obese vs lean hearts that were associated with significant molecular changes as detected by protein mass spectrometry and miR microarray. Molecular changes were related to myocardial calcium handling (SERCA2a, histidine-rich Ca2+ binding protein), myocardial structure and function (titin), and miRs relating to cardiac metabolism, hypertrophy, and cell death, including miR-15, miR-30, miR-199a, miR-214. Importantly, these effects were modified differently by GLP-1 agonism in lean vs obese swine. Additional studies investigated the functional effects of 30 days of treatment with the GLP-1 analogue liraglutide on a model of slowly-developing, unrelieved coronary ischemia. Liraglutide failed to reduce infarct size or collagen deposition. However, analysis of left ventricular pressure-volume relationships support that liraglutide improved diastolic relaxation/filling, load-dependent indices of cardiac function, and cardiac efficiency in response to sympathetic stimulation in obese swine. Taken together, these findings support that miR and proteomic differences underlie distinct changes in functional cardiac responses to I/R and pharmacologic activation of GLP-1 signaling in the setting of obesity.