The prevalence of obesity and diabetes is increasing in the United States and abroad and strategies are needed to prevent the progression from an at-risk state to the clinically diagnosed diseases. Flavanols in cocoa powder have been shown to reduce blood glucose concentrations, improve insulin sensitivity, and decrease gut permeability in animals and humans, but it is unknown if this occurs in adults with prediabetes. Therefore, we first hypothesized that an acute dose of cocoa would reduce postprandial glucose and enhance insulin and incretin hormone responses to a mixed meal challenge compared to a placebo. Second, we hypothesized that 15 g cocoa/day for 4-weeks would reduce gut permeability, attenuate endotoxin response to a high fat meal, improve insulin sensitivity, and improve measures of skeletal muscle substrate flexibility in a randomized, double blinded, placebo controlled parallel group design. To test the first hypothesis, 30 overweight or obese volunteers who were at-risk for diabetes completed two meal challenges using a randomized crossover design. Blood samples were collected hourly for 4 hours and were analyzed for glucose, insulin, C-peptide, glucagon-like peptide 1 (GLP-1), and gastric inhibitory peptide (GIP). Cocoa did not influence these measures. However, participants with the lowest fasting blood glucose concentrations were more likely to respond to the cocoa as hypothesized. To test our second hypothesis, 15 overweight or obese adults at risk for developing diabetes consumed either the cocoa or placebo treatments along with a controlled diet for one month. Overall, cocoa did not seem to influence insulin sensitivity, gut permeability, or endotoxin levels, although cocoa may influence skeletal muscle substrate metabolism. In conclusion, the data for both studies suggests that cocoa did not exert substantial effects on the evaluated outcomes. However, the experiments did provide valuable information about incretin hormone levels in adults with impaired glucose tolerance. More research is needed to understand how cocoa can affect glucose homeostasis for overweight or obese adults. / Ph. D.

No description available.

Thesis (MSc (Biomedical Sciences))--Cape Peninsula University of Technology, 2018. / Background: Early detection of individuals who are at risk of developing Glucose Intolerance would decrease the morbidity and mortality associated with this disease. MicroRNA is one of the most widely studied biomolecules involved in epigenetic mechanisms, hence it offers unique opportunities in this regard. Circulating microRNAs are associated with disease pathogenesis during the asymptomatic stage of disease. This has therefore attracted a lot of attention as a potential biomarker for identifying individuals who have an increased risk of developing Glucose Intolerance. The identification of high risk biomarkers for Glucose Intolerance will go a long way to eliminate the possible complications that arise due to late diagnosis and treatment of Glucose Intolerance. This could ultimately lead to better ways to prevent, manage and control the Glucose Intolerance epidemic that is rampant worldwide. The aim of the study is to investigate expression of circulating microRNA’s in blood of mixed ancestry subjects with glucose intolerance. Methods: A quantitative cross-sectional study design involving 36 individuals [who were age, gender and BMI (Body Mass Index) matched] from a total population of 1989 participants of mixed ancestry descent, residing in Bellville South, South Africa was used. Participants were classified as controls (normoglycemic), pre-diabetic (preDM) and diabetic (DM) (screen detected diabetic) according to WHO criteria of 1998. MicroRNAs were extracted from serum using the Qiagen miRNeasy Serum/Plasma Kit (ThermoFisher). The purified micro RNAs were reverse-transcribed to cDNA (complementary deoxyribonucleic acid) using the Qiagen RT2 First Strand Kit. Then, using Qiagen miScript SYBR Green PCR kit and miScript miRNA PCR arrays (ThermoFisher), the real time polymerase chain reaction was done to determine the expression profile the circulating micro RNAs present in the serum of the participants. Results: The 36 participants were evenly divided into 3 groups of 12 participants each as mentioned earlier. There were significant differences between groups in the waist (cm) (p=0.0415) and waist/hip ratio (p=0.0011) with highest values in the DM group and lowest in the normal group. Clinical parameters varied significantly according to glycemic status. As expected, the FBG (mmol/L) (p<0.0001), 2 HRs Post Glucose (mmol/L) (p<0.0001), HbA1c (%) (p=0.0009), Fasting Insulin (mIU/L) (p=0.0039), were all highest in the DM and lowest in the control group. In contrast, the 2 HRs Post Insulin (mIU/L) (p = 0.0027) was highest in the preDM group and lowest in the normal group, while the Glucose/Insulin ratio (p=0.0477) was highest in the normal group and lowest in the preDM group. Triglycerides (mmol/L) (p=0.0043) and Total Chol (mmol/L) (p=0.0429) were significantly increased through the three groups, with highest values in the DM group and lowest in the normal group. Furthermore, 12 of the 84 miRNAs studied were expressed through all the 3 groups and they exhibited both inverse and positive correlations between the clinical parameters, especially the glucose parameters (Fasting blood glucose, 2 hours post glucose, Fasting blood insulin, 2 hours post insulin and Glycated Hemoglobin).

Obesity, characterized by an excess of adipose tissue, is an established risk factor for cardiovascular disease and type II diabetes. Different mechanisms linking obesity with these comorbidities have been postulated but remain poorly understood. Adipose tissue secretes bioactive signaling molecules, termed adipokines, which regulate various biological functions including appetite, energy balance, glucose homeostasis, and inflammation. Chemerin is a novel adipokine that regulates adipocyte differentiation and metabolism by binding to and activating the G protein-coupled receptor chemokine like receptor-1 (CMKLR1). Herein, we have shown that serum levels of the novel adipokine chemerin are significantly elevated in mouse models of obesity/diabetes. Administration of exogenous chemerin exacerbates glucose intolerance, lowers serum insulin levels, and decreases tissue glucose uptake in obese/diabetic but not normoglycemic mice. In CMKLR1-deficient mice food consumption, total body mass, and percent body fat are lower compared to wildtype controls, regardless of diet (low or high fat). CMKLR1-/- mice also exhibited decreased hepatic and white adipose tissue TNF? and IL-6 mRNA levels coincident with decreased hepatic dendritic cell infiltration, decreased adipose CD3+ T cells and increased adipose natural killer cells. CMKLR1-/- mice were also glucose intolerant compared to wildtype mice, and this was associated with decreased glucose stimulated insulin secretion as well as decreased skeletal muscle and white adipose tissue glucose uptake. Collectively, these data provide compelling evidence that chemerin/CMKLR1 signaling influences adipose tissue development, inflammation, and glucose homeostasis and may contribute to the metabolic derangements characteristic of obesity and obesity-related diseases.

To determine the influence of muscle mass and absolute work on glucose tolerance and insulin sensitivity following exercise, glucose and insulin responses to an oral glucose tolerance test (OGTT) were analyzed in twelve subjects at baseline and 16 to 18 hrs following three different exercise trials performed on a cycle ergometer: 1) two-legged exercise at 60% of two-leg maximal oxygen uptake (VO2max), 2) one-legged exercise at 60% of the oneleg VO2max, and 3) a second one-leg trial at 60% of one-leg VO2max with work matched to the work obtained during the two-leg trial. Each trial was preceeded by two days of inactivity and a three day diet replication. Analysis of serum glucose concentrations during the post-exercise OGTTs demonstrated that glucose tolerance was unaffected by either the amount of active tissue incorporated in the exercise and/or the amount of work completed by the active tissue. On the other hand, serum insulin concentrations following the two-leg trial decreased 23.5% from 347.62 ±37.98 to 266.05 :L41.62 gU/ml in comparison to the one-leg trial (p < 0.05). The incorporation of a smaller muscle mass which completed an equal amount of absolute work as the larger muscle mass (i.e. one-leg work matched trial) resulted in a large (19%), but nonsignificant reduction in the total insulin compared to the one-leg relative work trial. In addition, total insulin following the two-leg and the one-leg work matched trials were reduced by 19% and 14%, respectively, in comparison to baseline. However, they did not reach statistical significance. The results of this study indicate that the incorporation of a larger muscle mass during an acute bout of aerobic exercise results in a reduction in serum insulin in response to a post-exercise oral glucose challenge. In addition, increasing the absolute work of a muscle mass results in similar reductions in serum insulin regardless of the amount of muscle mass involved in the exercise. While glucose tolerance was unaltered by either the amount of active tissue and/or the amount of work completed by the active tissue. / School of Physical Education

Considerable research has been performed on the effects of exercise and glucose tolerance, however, most of this work has examined aerobic exercise designs. This study examines the immediate post-exercise glucose turnover in eight male subjects exposed to a single bout of running and PRE. Both exercise protocols were designed to be of similar duration and at an intensity representing a typical exercise session. This study was conducted in an effort to offer individuals with NIDDM an alternative to the established aerobic forms of exercise for improved glucose control. Each subject completed two preliminary procedures, which consisted of a maximal graded exercise test and a session where a 1 RM was established on six different Cybex variable resistance machines. Subjects then completed a baseline oral glucose tolerance test (OGTT) in which eight blood samples were analyzed for glucose, insulin, hemoglobin, and hematocrit. Two exercise protocols, separated by 3 to 10 days, consisting of a 40 minute treadmill run at 75% VO2max and a 40 minute, 3 set x 10 repetition based on 75% of the1 RM, were performed and followed 45 minutes later by another OGTT. The results demonstrated that there were no apparent differences in blood glucose or insulin levels post-exercise between the exercise modes. However, the form of exercise did seem to have a varied effect on insulin production. The results of the OGTT demonstrated an explicit difference in the insulin response between the lifting and running trials, with the lifting trial being significantly higher than the resting or running trials. The increased insulin levels observed in the lifting trial may be indicative of increased secretion from the pancreas or that the secreted insulin is simply not being used. The insulin resistance observed in the lifting trial may be due to the muscles inability to respond to insulin or some other metabolic factor(s) released during exercise. Additional studies should be performed on different populations to examine the effects of PRE and running in a effort to better understand the mechanisms responsible for glucose uptake. / School of Physical Education

ABSTRACT Introduction: Renal transplant recipients (RTR) with abnormal glucose tolerance (AGT) are at an increased risk of graft failure and cardiovascular disease (CVD). CVD is the major cause of death in RTR. Whilst there are numerous known risk factors for AGT in RTR, it is unknown whether lifestyle factors are found in the presence or play a role in the development of AGT in RTR. The nutritional status of RTR in an Australian population has also not been extensively investigated. Investigation into these areas could help identify modifiable areas for change in the RTR population. Multidisciplinary lifestyle modification, including diet and physical activity (PA) advice from a dietitian, may help reduce modifiable risk factors for CVD in RTR with AGT. Aims: The principle aims of this thesis are to; 1) assess the incidence of obesity and central obesity in RTR and compare to rates in the general Australian population, 2) investigate and compare modifiable lifestyle factors and adipokine levels in RTR with AGT and normal glucose tolerance (NGT) and 3) investigate the effect of a multidisciplinary lifestyle intervention (including dietetic advice) on modifiable CVD risk factors in RTR with AGT. Methods: Chapter 1 presents a review of the literature describing the main nutritional challenges in RTR, cardiovascular risk factors in RTR including adipokine profiles and the role of body composition, diet and PA in RTR. Chapter 2 details the clinical, biochemical, nutritional, body composition, PA and statistical methodologies used in this thesis. In Chapter 3 a descriptive analysis of the anthropometry and cardiovascular risk profile of RTR in an Australian setting is investigated. Chapter 4 investigates the nutritional status of RTR with NGT and AGT in more detail, assessing diet, PA, adipokines and body composition. In Chapter 5, the current literature on lifestyle intervention management (including nutritional management) for obesity and type 2 diabetes mellitus in the general population is discussed. Building on previous chapters, Chapter 6 investigates the effect of a multi-disciplinary lifestyle intervention (with dietetic input) on modifiable cardiovascular risk factors in RTR with AGT. Results: In Chapter 3 it was found that RTR are significantly more centrally obese than those in the general population, and this was particularly the case in younger RTR. Central obesity was associated with CVD risk factors in RTR. Chapter 4 found that a lower level of PA, obesity and central obesity are associated with AGT in RTR, whereas no difference in adipokines or dietary intake was found. In Chapter 6, multidisciplinary lifestyle intervention with dietetic input was found to improve certain risk factors for CVD in RTR with AGT, such as dietary factors (total fat and saturated fat intake) and lipid levels. Conclusions: Central obesity is a common problem in RTR, particularly in those with AGT. Higher levels of PA are associated with lower risk of AGT in RTR, and may help reduce the incidence of central obesity in RTR. Multidisciplinary lifestyle intervention, with dietetic input, can improve some modifiable CVD risk factors in RTR with AGT, however more intensive intervention is required to significantly reduce the incidence of obesity. Key Words: Renal Transplant; Abnormal Glucose Tolerance, Obesity; Cardiovascular Disease; Physical Activity Australian and New Zealand Standard Research Classifications (ANZSRC) 1111 Nutrition and Dietetics, 1102 Cardiovascular medicine and Haematology, 1199 Other Medicine and Health Sciences

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2011. / Studies have shown that oxidative stress (OS) is a major pathological risk factor in various diseases, including type 2 diabetes mellitus (T2DM). Hyperglycemia independently is a generator of free radicals, hence increases the level of OS in T2DM subjects. The oxidation of LDL is suggested to play a significant role in the pathogenesis of macrovascular complications observed in diabetic patients. In subjects with hyperglycemia or normoglycemia we investigated the relationship between MDA-protein adducts, HNE-protein adducts and auto-antibodies against oxLDL, and cardiovascular profile as measured by hs- CRP. From an epidemiological study that screened a high risk urban population for diabetes using oral glucose tolerance test, 98 hyperglycaemie and 79 normoglycaemic individuals were selected for this study. Enzyme linked immuno-sorbent-assay methods were used to determine the levels of serum MDA-protein adducts, HNE-protein adducts or auto-antibodies against oxLDL. High sensitive CRP was measured by nephelometry.

Studies on rat islet preparations have shown melatonin inhibits MAO activity and thereby reduces glucose mediated insulin release. The objective of this work is to investigate the effects of melatonin on insulin release, and on glucose mediated insulin release in the intact and in the pinealectomized rat.

The objective of these studies was to design an optimal nutritional supplement suitable for grazing horses using fat and fiber to replace the grain and molasses in the traditional sweet feed. Thoroughbred mares and foals grazing bluegrass/clover pastures were used in these studies, twenty mares and their foals in 1994 to 1995, and twenty mares and foals in 1995 to 1996. Seasonal variation in pasture was examined, and the need for supplementation of nutrients and fibers was assessed. The nutritional status of grazing mares, foals, weanlings and yearlings, fed either a starch and sugar supplement (SS) or a fat and fiber supplement (FF), was examined using growth measurements, radiographic bone evaluations, milk composition and glucose tolerance tests. These studies suggest that fiber may be an important component of an ideal supplement for improved grass/legume pastures. Seasonal variation in pasture indicated an increase in hydrolyzable and rapidly fermed carbohydrates during periods of rapid growth. The FF supplement may have buffered seasonal changes and the increased hydrolyzable carbohydrate content in rapidly growing pasture, as evidenced by smoother growth curves in the yearlings. Young horses, after weaning until the following May, had lower estimated bone mineral content when fed the FF supplement. The lower bone mineral content in the FF supplemented horses may have been due to decreased absorption of calcium or metabolic and hormonal changes associated with adaptation to the different energy sources in the supplements. Milk composition of FF supplemented mares was influenced in ways likely to improve foal health. The FF supplemented mares had enhanced linoleic acid content, which may reduce the risk of gastric ulcers in foals, and increased immunoglobulin G concentration, which may enhance passive immunity. The carbohydrate status of mares, as assessed by glucose tolerance tests, indicated a slower glucose clearance that could be a metabolic adaptation of the mares to the SS and FF supplements. / Ph. D.