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The present studies were conducted to determine the effects of obesity on insulin resistance, inflammatory state and risk for laminitis, and the effectiveness of exercise training to reduce obesity and insulin resistance in equids. Practical methods of assessing adiposity were developed and verified, including a condition scoring system for neck crest adiposity and morphometric measurements for generalized (girth:height) and localized (neck circumference:height) adiposity. Evaluation of 74 and 57 pony mares in March of two consecutive years resulted in the identification of predictive tests for incipient pasture-associated laminitis, including hyperinsulinemia (> 32 mU/L), hyperleptinemia (> 7.3 ng/mL), and generalized (body condition score ≥ 7) and localized (cresty neck score ≥ 4) obesity. Induction of obesity in 13 Arabian geldings by 4 months of overfeeding resulted in compensated insulin resistance (minimal model analysis) with hyperinsulinemia and hyperleptinemia. Although lipid concentrations (nonesterified fatty acids and triglyceride) decreased on a high concentrate diet, they did not differ before and after weight gain. The resulting obesity-induced insulin resistance was accompanied by an increase in chemokine (monocyte chemoattractant protein [MCP]-1, MCP-2, interleukin [IL]-8) but not inflammatory cytokine (tumor necrosis factor [TNF]α, IL-1β, IL-6) mRNA expression in subcutaneous adipose tissue. Additionally, there was a decrease in plasma TNFα protein concentration with weight gain. By using 12 of the obese, insulin resistant Arabian geldings (8 exercised, 4 control) it was demonstrated that 8 weeks of moderate intensity exercise training reduced adiposity (4% reduction in body weight, 35% reduction in fat mass) without affecting glucose and insulin dynamics or plasma hormone and lipid concentrations. Collectively, these studies demonstrate the impact obesity has on metabolism and risk for laminitis in equids, and that exercise training may provide an effective countermeasure for the reduction of obesity. / Ph. D.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 5, 2010). Thesis advisor: Paul J. Fadel. "December 2009" Includes bibliographical references.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Insulin resistance is common among obese adolescents; however, the extent of this problem is not clear. We conducted a systematic review of PubMed-Medline, CINAHL, The Web of Science, EMBASE and Scopus for observational studies evaluating components defining insulin resistance (insulin, C-peptide and homeostatic model assessment-insulin resistance [HOMA-IR]) in obese adolescents (12–18 years) versus non-obese adolescents. Our systematic review and meta-analysis followed the PRISMA guidelines. Data were combined using a random-effects model and summary statistics were calculated using the mean differences (MDs). 31 studies were included (n = 8655). In 26 studies, fasting insulin levels were higher in obese adolescents when compared to non-obese adolescents (MD = 64.11 pmol/L, 95%CI 49.48–78.75, p < 0.00001). In three studies, fasting C-peptide levels were higher in obese adolescents when compared to non-obese adolescents (MD = 0.29 nmol/L, 95%CI 0.22–0.36, p < 0.00001). In 24 studies, HOMA-IR values were higher in obese adolescents when compared to non-obese adolescents (MD = 2.22, 95%CI 1.78–2.67, p < 0.00001). Heterogeneity of effects among studies was moderate to high. Subgroup analyses showed similar results to the main analyses. Circulating insulin and C-peptide levels and HOMA-IR values were significantly higher in obese adolescents compared to those non-obese. / Revisión por pares

Thesis (M. Sc.(Biochemistry)) -- University of Limpopo, 2020 / Diabetes mellitus has become a global epidemic, particularly type 2 diabetes. Obesity is one of the causes of type 2 diabetes mellitus due to its link with induced insulin resistance. There is no cure for diabetes mellitus and, as such, it is managed by using standard drugs which have side effects, and can be toxic, expensive and unavailable. People have resorted to the use of medicinal plants to treat diabetes and its complications. The aim of this study was to test the anti-obesity and anti diabetic properties of Bidens pilosa crude extract and its sub-fractions using C2C12 myoblasts and 3T3-L1 adipocytes. The crude extract and the most active sub fractions were selected for further analysis because of their ability to stimulate glucose uptake and induction of adipogenesis. Bidens pilosa leaves were selected for this current study. They were firstly extracted using absolute methanol and further subjected to solvent-solvent fractionation to obtain the n-butanol, ethyl acetate, water, hexane, chloroform and 35% water in methanol sub-fractions. Qualitative phytochemical analysis was performed using thin layer chromatography (TLC) and standard chemical tests. Total phenolic and flavonoid content were determined quantitatively using a calorimetric method with Folin-Ciocalteu’s reagent. For their antidiabetic potential, the extracts were evaluated chromogenically and calorimetrically for antiglycation and α-amylase inhibitory activity. The cytotoxicity of the extracts on 3T3-L1 preadipocytes and C2C12 myotubes were determined using the MTT assay. The adipogenesis inducing effect of the extract was tested using the adipogenesis kit. More compounds were found on chromatograms eluted in EMW mobile phase (Ethyl acetate: methanol: water). The extracts were shown to contain a variety of secondary metabolites, and high phenolic and flavonoids contents. Crude, chloroform, n butanol and water sub-fractions had high antioxidant activity. Alpha amylase activity was highly inhibited in the crude extract and all sub-fractions, with the highest inhibitory activity observed in the crude extract and the chloroform, n-butanol and water Sub-fractions (IC50 1.25 ± 2.5 mg/ml). The cytotoxic profiles indicated that all extracts are non-cytotoxic at concentrations of 15.63 µg/ml. Extracts at a concentration of 31.25 µg/ml were shown to stimulate the accumulation of triglycerides using 3T3-L1 adipocytes. The extracts also exhibited significant (P < 0.05) glucose uptake activity. In conclusion, Bidens pilosa contains constituents that inhibit α-amylase, antiglycation formation and modulates uptake of glucose in 3T3-L1 adipocytes. The use of B. pilosa in combination with insulin revealed the synergistic effects in facilitating glucose uptake in both C2C12 myotubes and 3T3- L1 adipocytes. This suggests that there might be some binding compounds found in the plant extracts that are responsible for the stimulation of expression of several genes that encode for proteins involved in the metabolism of glucose. However, the use of B. pilosa, in combination with metformin, results in a decreased glucose uptake. Bidens pilosa have the fast-acting insulin mimetic properties. Furthermore, the plant was shown to stimulate the accumulation of triglycerides in 3T3-L1 adipocytes, signifying the plant can induce adipogenesis at 30µg/ml / South African Medical Research Council (SAMRC)

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Introduction. Pima Indians living in the United States (U.S.) have the highest prevalence of type 2 diabetes mellitus in the world. Their Mexican counterparts, living a traditional lifestyle in the mountain of Sonora, Mexico, have at least five times less diabetes than the U.S. Pima Indians. The effects of a traditional lifestyle in reducing type 2 diabetes risk factors and the association of factors to type 2 diabetes were evaluated in a sample of 1211 genetically related Pima Indians living different lifestyles (224 from Mexico and 887 from U.S.). Subsets of these populations were used to address specific questions. First, differences in insulin resistance between subjects with normal glucose tolerance (194 Mexican versus 449 U.S. Pima) were evaluated. Second, the effect of physical activity and obesity explaining differences in metabolic syndrome prevalence were evaluated in 224 and 447 Mexican and U.S. Pima Indians. Third, factors associated with type 2 diabetes were evaluated in each Pima Indian population (224 from Mexico and 887 from U.S.).Methods. Demographic, physical, biochemical, and lifestyle factors were measured in 1996 in a cross-sectional study of Pima Indians 20 years of age or older living in Maycoba, Sonora Mexico and contrasted to results from a sample of U.S. Pima Indians participating in an ongoing epidemiological study that used similar methods and selection criteria. Insulin resistance was estimated by both fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR). Metabolic syndrome was defined using the Third Report of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP III) criteria. Body mass index (BMI) was calculated by dividing weigh in kilograms by the square of height in meters (Kg/m2). Physical activity was measured using a questionnaire developed for the U.S. Pima Indians and adapted to the Mexican Pima Indian population. Type 2 diabetes was defined according to the 1999 WHO criteria after an oral glucose tolerance test. Multiple linear regression analysis was used to answer the first question (related to differences in insulin resistance) and multiple logistic regressions analysis to answer the second (related with differences in metabolic syndrome) and third questions (related to factors associated with type 2 diabetes).Results. Insulin resistance was much lower in the Mexican Pima Indians than in genetically related U.S. counterparts, even after controlling for differences in obesity, age and sex. In addition, the unadjusted prevalence of metabolic syndrome was 24.1% and 56.6 % in the Mexican and U.S. Pima Indians, respectively. However, most of the difference in metabolic syndrome prevalence was explained by differences in obesity and physical activity. Furthermore, in Mexican Pima Indians, type 2 diabetes was independently associated with age, fasting insulin, and waist circumference. In the U.S. Pima Indians, type 2 diabetes was associated with with age, sex, fasting insulin, total cholesterol, blood pressure and physical activity.Conclusion. The findings underscore the importance of lifestyle in the prevention of type 2 diabetes risk factors, such as insulin resistance and metabolic syndrome, even in individuals with high propensity to develop diabetes.

INTRODUCTION Rheumatoid arthritis (RA) is a disease of chronic inflammation in the joints and organs. RA patients exhibit 4-fold increased incidence of CVD, increased prevalence of insulin resistance (IR) and increased mortality. Aerobic and resistance training (RT) programs have been suggested for the management of RA symptoms and reduction of comorbidities, including insulin resistance. Exercise has been shown by recent evidence to be safe and beneficial in RA patients. RT has been documented to improve inflammation and insulin sensitivity. The present study was undertaken to examine the impact of a sixteen week intensive training regimen on disease status, body composition, markers of inflammation and indicators of insulin resistance in RA patients undergoing infliximab therapy, a potent RA treatment.METHODS30 RA patients were randomized into exercise (EX) or control (C) groups. EX patients underwent a 16-week supervised, intensive, progressive and individualized resistance training regimen. Participants were monitored by professional fitness trainers during all exercise sessions. Subjects were assessed prior to and after intervention. Assessments included disease status, strength and functional testing, anthropometrical and body composition analysis, analysis of markers of inflammation and assessment of insulin sensitivity.RESULTS EX subjects significantly increased in strength and functional ability without worsening of disease state, and increased lean mass from baseline. Fat mass was significantly reduced in EX. Glucose and resistin levels increased significantly following EX intervention. Mean IR was unchanged, but EX subjects with elevated IR did show improvement following training. Regression analysis indicates duration of infliximab therapy to be correlated with improved insulin sensitivity.CONCLUSIONS RA patients taking infliximab tolerated an intensive resistance training program. Participants increased strength and lean mass while decreasing fat mass and displayed improved functional capacity. Disease status was not worsened by the regimen. Though the mean measure of IR did not improve, those patients with the most adverse scores did show improvement following the intervention. Furthermore, regression analysis indicates that infliximab treatment duration was linked to reduced IR. In conclusion, resistance training improved strength and functional ability in RA patients taking infliximab without disease degradation, and may help reduce IR in those patients with elevated resistance.

Motivation: Metabolic syndrome is a constellation of risk factors predisposing to coronary heart disease (CHD) and is classified as a "disease of modern civilization". Characteristics of the metabolic syndrome include abdominal obesity, increased triacylglycerol (TG) concentrations, increased small dense low-density lipoprotein(LDL) particles, decreased high-density lipoprotein cholesterol (HDL-C), hypertension, insulin resistance, inflammation, glucose intolerance and/or type 2 diabetes mellitus. Subjects with metabolic syndrome may be susceptible to oxidative stress due to their prolonged exposure to elevated glucose levels. A variety of natural antioxidants exists (e.g. glutathione, l3-carotene, vitamin C, polyphenols) that may prevent oxidative damage to biological structures. Nuts are rich sources of unsaturated fatty acids, protein, fibre, .micronutrients, phytochemicals and antioxidants. Duet o their high antioxidant content, it can, therefore, be speculated that nuts may play a role in the prevention of oxidative stress in subjects with the metabolic syndrome. Objective: - To investigate the effect of a high walnut and a high unsalted cashew nut diet on the antioxidant status of subjects with metabolic syndrome. Methods: Sixty eight subjects with diagnosed metabolic syndrome (according to the ATP III criteria) were recruited to take part in this parallel, randomized, controlled feeding trial. Subjects were mainly recruited from the North-West University, Potchefstroom Campus and surrounding areas. After a run-in period of three weeks during which the participants followed a prudent diet, subjects were randomly divided into three groups receiving either walnuts or cashew nuts (63- 108g/day)as part of a prudent diet, or continued with the prudent control diet. The intervention was followed for eight weeks. Fasting blood samples were taken at the beginning(after the three week run-in period) and at the end of the intervention. Antioxidant variables including oxygen radical absorbance capacity (ORAC), reduced glutathione (GSH)/oxidized glutathione (GSSG), diacron reactive oxygen metabolites (dRom) were measured at the beginning and the end of the intervention. C-reactive protein (CRP), fibrinogen and plasminogen activator-inhibitor activity (PAI-1a) were also measured as markers of inflammation. The antioxidant capacity and the polyphenol content of the diets and the walnuts and cashew nuts were determined at the end of the intervention. Results: A significant decrease in dRom and significant increases in GSSG, the redox status of glutathione (GSH/GSSG) and ORAC were observed in all three groups from baseline to end. GSH remained unchanged from baseline to end in all three groups. No significant differences in changes in dRom (p = 0.92), GSSG (p = 0.99), GSH/GSSG (p = 0.86), antioxidant capacity (p = 0.10) and GSH (p = 0.34) were observed from baseline to end between groups. The total polyphenol content of the walnut and control diets were similar and significantly higher than the cashew nut diet. The antioxidant capacity of the walnut and cashew nut diets showed a tendency to be higher than the control diet (p = 0.07 and p = 0.06 respectively). CRP, fibrinogen and PAI-1a concentrations did not differ significantly between groups. Conclusion No significant differences between the groups receiving walnuts, cashew nuts or no nuts were observed in GSH, GSSG, GSH/GSSG, dRom or ORAC. Therefore, there seems to be no beneficial effect of the inclusion of walnuts and cashew nuts in the diet on the antioxidant status of the participants. / Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2006.

An estimated 86 million Americans in the United States age 20 and older are classified as prediabetic. Prediabetes is defined as an individual having a higher blood sugar than normal increasing the risk for developing type 2 diabetes (T2DM). T2DM is among the top ten leading causes of death in the United States and costs an estimated 245 billion dollars annually. Interventions need to take place among patients with prediabetes in order to prevent the T2DM epidemic from compounding. This study examined the effects of a six-week low carbohydrate diet on A1C values, weight and BMI, and cardiovascular markers among patients with prediabetes. A retrospective chart review examined 1,169 patients with prediabetes that met inclusion criteria from July 2013 to April 2016. Patients had completed a six-week low carbohydrate diet program with weekly clinic visits with a nurse practitioner and followed the prescribed low carbohydrate diet. A significant difference in means was found when comparing pre A1C values (M= 5.93, SD= 0.20) and post A1C values (M= 5.57, SD= 0.25); (t (1142) = 49.3, p = 0.00), pre intervention weight (M= 227.0, SD= 52.0) and post intervention weight (M = 209.5, SD = 48.0); (t (1168) = 79.3, p = 0.00), and pre BMI (M = 36.8, SD = 7.0) and post BMI (M = 34.0, SD = 6.6); (t (1168) = 77.8, p = 0.00). Additionally, statistical significance was found for cardiovascular markers including systolic and diastolic blood pressures, total cholesterol, LDL, HDL and triglycerides. These findings suggest that a low carbohydrate diet is effective at improving metabolic risk factors for prediabetes and preventing the progression to T2DM. Low carbohydrate diets should be further examined for long term effectiveness and could be recommended to patients with prediabetes in order to reverse the epidemic of T2DM.