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Master of Science / Department of Kinesiology / Katie Heinrich / Background: The American College of Sports Medicine physical activity guidelines call for 150 minutes of moderate or 75 minutes of vigorous aerobic exercise plus two days of resistance training (A-RT) per week for health benefits. Yet, most adults do not achieve the recommended amount of physical activity per week frequently citing lack of time as a barrier. High-intensity exercise protocols have improved glucose control, insulin sensitivity, fitness, and body composition, in less total time than lower intensity protocols, but have been studied as singular modes of exercise. CrossFit (CF) temporally combines A-RT together utilizing constantly varied multi-joint, full range-of-motion movements in substantially less training time than lower-intensity protocols. The aim of this study was to compare the effects of CF versus A-RT on glucose control in overweight/obese, physically inactive individuals. Methods: Eighteen overweight/obese (BMI 30.3 ± 2.8) adults (28.5 ± 5.9 years) were randomized to one of two groups: CF (3 days/week for 60 minute sessions) or A-RT (3 days/week of aerobic exercise for 50 minutes, plus ~20 minutes resistance exercise on 2 of those days) over 8-weeks. Fasting plasma glucose and 1-hour oral glucose tolerance tests were taken at baseline and post-training along with Eurofit fitness measures, VO2 peak, and body composition via dual energy X-ray absorptiometry. Results: Glucose control and body composition did not change significantly within or between groups. Both groups significantly improved muscular endurance (pushups completed on knees, CF+39.5%, p < 0.05; A-RT+24.4%, p = 0.01). The CF group improved on number of situps (CF+6.8%, p = 0.01) and VO2 peak (CF+9.1%, p < 0.05). Time spent exercising was significantly different between groups with the CF group averaging 38.7 ± 15.6 minutes per week and 13.1 ± 0.9 minutes per workout, and the A-RT group averaging 190.0 ± 10.7 minutes per week and 63.3 ± 3.6 minutes per workout. Conclusion: Eight weeks of A-RT or CF did not produce significant changes in glucose control or body composition in overweight/obese adults. However, despite exercising significantly less time per week CF training demonstrated greater improvements in fitness measures than A-RT.

This thesis is an investigation of the factors that impact psychological adjustment and metabolic control in children and adolescents with type 1 diabetes. Studies suggest that aspects of the family environment (stressful life events, family functioning and parent mental health) and child characteristics such as age, sex, executive functioning and hopeful thinking impact psychological adjustment and metabolic control. There is also evidence that coping processes mediate these associations. The purpose of this study was to 1) explore and identify developmental differences in coping processes in a sample of children with T1D, 2) identify the family system characteristics that are associated with child coping processes and psychological adjustment, and 3) identify the family and child characteristics that impact metabolic control. Survey data were collected through convenience sampling from an outpatient hospital clinic. Children aged 8 to 17 completed self-reports of hopeful thinking and illness-related coping style. Caregivers provided demographic information and completed questionnaires on their child’s physical health, stressful life events, mental health, family functioning, as well as the child’s initiative, emotional control, and psychological adjustment. Ratings of child metabolic control (HbA1C) were also retrieved from hospital patient records. A predictive model examining direct and indirect contributions of the family environment and coping variables toward child adjustment and metabolic control was tested. Age and sex differences in children’s coping style were identified. Family functioning and parent mental health were found to predict child psychological adjustment. Coping processes, including avoidant coping, coping efficacy and executive functioning mediated relations between family functioning and child adjustment. Results provided partial support for a mediational model of family system characteristics that influence psychological adjustment in the sample. Family functioning and parent mental health had a direct impact on children’s psychological adjustment, as well as indirect effects on adjustment through coping processes (i.e., coping style, coping efficacy, initiative and emotional control). Child age was found to moderate some paths in the proposed model. Clinical and research implications are discussed.

This work discusses the mean of blood glucose in human body. Determination of glucose and held it in the physiological range.

Insulin human inhalation powder, a rapid-acting inhaled insulin, was approved by the FDA in June 2014 for patients with type 1 or type 2 diabetes. For patients reluctant to start insulin therapy because of fear of injections, insulin human inhalation powder may be an alternative. This article discusses appropriate dosing, use, and monitoring.

Diabetes mellitus is a major public health concern. Although the accessible novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance (IR) and loss of &beta;-cell mass and function. Therefore, the search for naturally occurring, low-cost, and safe compounds that could enhance insulin sensitivity and protect functional &beta;-cell mass can be an effective strategy to prevent this disease. Kaempferol, a flavonol present in various medicinal herbs and edible plants, has been shown to elicit various pharmacological activities in preclinical studies. However, studies investigating the effect of kaempferol on diabetes are limited. In this dissertation, I explored the anti-diabetic potential of dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice. First, kaempferol was supplemented in the diet to determine whether it can prevent IR and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. To evaluate its efficacy for treating diabetes, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice. The results demonstrated that long-term oral administration of kaempferol prevents HFD-induced metabolic disorders in middle-aged obese mice. Oral administration of kaempferol improved glucose intolerance and insulin sensitivity, and this effect was associated with increased Glut4 and AMPKa expression in muscle and adipose tissues. Consistent with our findings from the in iii vitro study in C2C12 muscle cell line, these findings suggest that kaempferol may reduce IR at the molecular level by improving glucose metabolism in peripheral tissues. In the second study, dietary kaempferol supplementation prevented hyperglycemia and glucose intolerance by protecting &beta;-cell against the induced damage in obese STZ-induced diabetic mice. In the third study, the administration of kaempferol by oral gavage significantly ameliorated hyperglycemia and glucose intolerance and reduced the incidence of diabetes from 100 % to 77.8% in lean STZinduced diabetic mice. This kaempferol effect was associated with reduced hepatic glucose production, the primary contributor to hyperglycemia, and increased glucose oxidation in the muscle of diabetic mice. Kaempferol treatment restored hexokinase activity in the liver and skeletal muscle and reduced pyruvate carboxylase (PC) activity and glycogenolysis in the liver. Unlike its effect on T2D mice, kaempferol effect in lean STZ-induced diabetic mice was not associated with changes in plasma insulin levels. In the last study, we found that administration of kaempferol by oral gavage significantly improved blood glucose control by suppressing hepatic glucose production and improving glucose intolerance in obese insulin-resistant mice. Similar to its effect in old obese mice, kaempferol enhanced whole-body insulin sensitivity. Kaempferol increased Akt and hexokinase activity and decreased PC activity in the liver. However, kaempferol did not exert any changes in glucose metabolism or insulin sensitivity when administered to healthy lean mice. Overall, findings from these studies provide new insight into the role of kaempferol in the regulation of glucose homeostasis and suggest that kaempferol may be a naturally occurring anti-diabetic compound by improving insulin sensitivity, improving glucose regulation and metabolism, and preserving functional &beta;-cell mass. / Ph. D.

Diabetes mellitus is a growing public health concern, presently affecting 25.8 million or 8.3% of the American population. While the availability of novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance and loss of -cell mass and function, and it is is always associated with the impairment in energy metabolism, causing increased intracellular fat content in skeletal muscle (SkM), liver, fat, as well as pancreatic islets. As such, the search for novel agents that simultaneously promotes insulin sensitivity and 𝜷-cell survival may provide a more effective strategy to prevent the onset and progression of this disease. Kaempferol is a flavonol that has been identified in many plants and used in traditional medicine. It has been shown to elicit various pharmacological activities in epidemiological and preclinical studies. However, to date, the studies regarding its effect on the pathogenesis of diabetes are very limited. In this dissertation, I explored the anti-diabetic potential of the dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice. For the first animal study, kaempferol was supplemented in the diet to determine whether it can prevent insulin resistance and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. For the second animal study, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice to evaluate its efficacy for treating diabetes and further determining the underlying mechanism. The results demonstrated that dietary intake of kaempferol for 5 months (mo) improved insulin sensitivity and glucose tolerances, which were associated with increased Glut4 and AMPKα expression in muscle and adipose tissues in middle-aged mice fed a high-fat (HF) diet. In vitro, kaempferol increased lipolysis and restored chronic high fatty acid-impaired glucose uptake and glycogen synthesis in SkM cells, which were associated with improved AMPKα activity and Glut4 expression. In addition, dietary kaempferol treatment preserved functional pancreatic 𝜷-cell mass and prevented hyperglycemia and glucose intolerance in STZ-induced diabetic mice. Data from the second study show that oral administration of kaempferol significantly improved blood glucose control in obese mice, which was associated with reduced hepatic glucose production and improved whole body insulin sensitivity without altering body weight gain, food consumption, or the adiposity. In addition, kaempferol treatment increased Akt and hexokinase activity, but decreased pyruvate carboxylase and glucose-6 phosphatase activity in the liver homogenate without altering their protein expression. Consistently, kaempferol decreased pyruvate carboxylase activity and suppressed gluconeogenesis in HepG2 cells as well as primary hepatocytes isolated from the livers of obese mice. Kaempferol directly blunted the activity of purified pyruvate carboxylase. In the last study, we found that kaempferol stimulates basal glucose uptake in primary human SkM. In C2C12 mouse myotubes, kaempferol also increased insulin stimulated glycogen synthesis and preserved insulin dependent glycogen synthesis and glucose uptake in the presence of fatty acids. Kaempferol stimulated Akt phosphorylation in a similar time-dependent manner as insulin in human SkM cells. Consistent with this, kaempferol increased Akt and AMPK phosphorylation in isolated murine red SkM tissue. The effect of kaempferol on glucose uptake was blunted in the presence of chemical inhibitors of glucose transporter 4 (Glut4), phosphoinositide 3-kinase (PI3K), glucose transporter 1 (Glut1), and AMPK. The AMPK inhibitor also prevented kaempferol-stimulated Akt phosphorylation. Further, kaempferol improved the stability of insulin receptor substrate-1. Taken together, these studies suggest that the kaempferol is a naturally occurring compound that may be of use in the regulation of glucose homeostasis and diabetes by improving insulin sensitivity and glucose metabolism, as well as by preserving functional 𝜷-cell mass. / Ph. D. / Diabetes mellitus, more commonly referred to as diabetes, is a cause for concern in the context of public health. Currently, 25.8 million or 8.3% of the American population is affected by some type of diabetes. While the development of new drugs, techniques, and surgeries have improved the survival rate of individuals with diabetes, the number of diabetes cases continues to rise. Type 2 diabetes (T2D) is a result of the inability of tissues to respond to insulin and a loss of insulin producing β-cell mass and function. T2D is always associated with an impairment in the storage and release of energy, causing increased fat content in skeletal muscle (SkM), liver, and fat cells, as well as pancreatic islets. As such, the search for new agents that simultaneously promotesthe ability of body tissues to respond to insulin and β-cell survival may provide a more effective strategy to prevent the onset and progression of this disease. Kaempferol is a flavonol that has been identified in many plants and used in traditional medicine. It has been shown to elicit various drug-like activities in incidence and distribution studies as well as in preclinical studies. However, to date, the studies regarding its effect on the onset and progression of diabetes are very limited. In this dissertation, I explored the anti-diabetic potential of the dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice. For the first animal study, kaempferol was added to the diet to determine whether it can prevent insulin resistance and high blood glucose in high fat (HF) diet-induced obese mice or chemically-induced obese diabetic mice. For the second animal study, kaempferol was given once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean chemically-induced diabetic mice to evaluate its efficacy for treating diabetes and further determining its mechanism. The results demonstrated that dietary intake of kaempferol for 5 months (mo) improved insulin sensitivity and the ability of body tissues to respond to glucose, which were associated with increased expression of the insulin sensitive glucose transporter (Glut4) and a central regulator of metabolism (AMPKα) in muscle and adipose tissues in middle-aged mice fed a high-fat (HF) diet. In cell culture, kaempferol increased triglyceride breakdown and restored the ability of SkM cells to take up glucose and synthesize glycogen following long-term exposure to elevated fatty acids. These results were also associated with an improved AMPKα activity and Glut4 expression. In addition, kaempferol in the diet preserved functional pancreatic β-cell mass and prevented the development of high blood glucose and the inability of body tissues to respond to glucose in chemically-induced diabetic mice. Data from the second study show that oral administration of kaempferol significantly improved blood glucose control in obese mice, which was associated with reduced glucose production in the liver and an improved ability of the whole body to respond to insulin without altering body weight gain, food consumption, or fat storage. In addition, kaempferol treatment increased the activity of the final enzyme in glucose transport (Akt) and first enzyme (hexokinase) in glucose oxidation, but decreased the activity of the first and final regulatory enzymes in glucose production (pyruvate carboxylase and glucose-6 phosphatase respectively) without altering their protein expression. Consistently, kaempferol decreased pyruvate carboxylase activity and suppressed glucose production in HepG2 liver cells as well as primary liver isolated from obese mice. Kaempferol also directly blunted the activity of purified pyruvate carboxylase. In the last study, we found that kaempferol stimulates non-stimulated glucose uptake in primary human SkM. In C2C12 mouse muscle cells, kaempferol also increased insulin stimulated glycogen synthesis and prevented fatty acid impaired glycogen synthesis and glucose uptake stimulated by insulin. Kaempferol stimulated Akt phosphorylation (the active form of the enzyme) in a similar time-dependent manner as insulin in human SkM cells. Consistent with this, kaempferol increased Akt and AMPK phosphorylation in red SkM tissue from mice. The effect of kaempferol on glucose uptake was inhibited in the presence of chemical inhibitors of Glut4, phosphoinositide 3-kinase (an enzyme in the insulin signaling pathway), glucose transporter 1 (a basal glucose transporter), and AMPK. The AMPK inhibitor also prevented kaempferol-stimulated Akt phosphorylation. Further, kaempferol improved the stability of insulin receptor substrate-1. Taken together, these studies suggest that the kaempferol is a naturally occurring compound that may be of use in the regulation of glucose homeostasis and diabetes by improving insulin responsiveness and glucose storage and breakdown, as well as by preserving functional β-cell mass.

Purpose: The primary aim of this study was to determine the impact of various fast-interrupting shakes on markers of glycemic control including glucose, β-hydroxybutyrate (BHB), insulin, glucagon, GLP-1, and GIP. Methods: Twenty-seven adults (12 female, 15 male) completed all three conditions of this study. One condition consisted of a 38-hour water-only fast, and the other two conditions were similar but the fasts were interrupted at 24 hours by either a high carbohydrate/low fat (HC/LF) or a low carbohydrate/high fat (LC/HF) shake. Results: The water only fast resulted in 135.3% more BHB compared to the HC/LF condition (t = 7.77, p < 0.0001) and 69.6% more compared to the LC/HF condition (t = 5.12, p < 0.0001). Conversely, the LC/HF condition exhibited a 38.8% higher BHB level than the HC/LF condition (t = 2.70, p = 0.0086). Additionally, the area under the curve (AUC) for glucose was 14.2% higher in the HC/LF condition than in the water condition (t = 6.23, p < 0.0001) and 6.9% higher compared to the LC/HF condition (t = 3.14, p = 0.0024), with the LC/HF condition yielding 7.8% more glucose than the water condition (t = 3.21, p = 0.0020). At the 25-hour mark, insulin and glucose-dependent insulinotropic polypeptide (GIP) were significantly elevated in the HC/LF condition compared to the LC/HF condition (F = 3.84, p = 0.0002 and F = 2.27, p = 0.0244, respectively) and compared to the water condition (F = 7.00, p < 0.0001 and F = 9.96, p < 0.0001, respectively). Furthermore, insulin, glucagon-like peptide-1 (GLP-1), and GIP were increased in the LC/HF condition compared to the water condition at 25 hours (F = 3.19, p = 0.0016, F = 2.43, p = 0.0158, and F = 12.13, p < 0.0001, respectively). Notably, glucagon concentrations at the 25-hour mark decreased in the HC/LF group compared to the LC/HF condition (F = 3.37, p = 0.0009). However, by the 38-hour time point, no statistically significant differences were observed among the conditions for any of the analyzed hormones. Conclusions: While a LC/HF shake does not mimic a fast completely, it does preserve some of the metabolic changes including elevated BHB and glucagon, and decreased glucose and insulin compared to a HC/LF shake.

L'hyperglycémie est très souvent présente chez le patient de réanimation, liée à une insulinorésistance et une production accrue de glucose par le foie. La relation entre hyperglycémie en réanimation et pronostic défavorable était déjà établie lorsque Van den Berghe et al montra une réduction de mortalité associée à une insulinothérapie intensive visant à normaliser la glycémie. Du fait de l'impossibilité à reproduire cet effet bénéfique et de la mise en évidence d'une surmortalité associée à un contrôle glycémique strict par rapport à un contrôle visant une glycémie < 10mmol/L (étude NICE-SUGAR), le premier objectif de cette thèse fut de rechercher à l'aide d'une étude multicentrique (étude CGAO-REA) une association entre utilisation d'un logiciel facilitant le contrôle glycémique strict et réduction de mortalité. Malgré le résultat négatif de l'étude CGAO-REA, l'intérêt d'un système informatisé demeure en raison de la complexité du contrôle glycémique. Sont ainsi discutés les sujets suivants appliqués à la réanimation : aléas du contrôle glycémique, méthodes de mesure de la glycémie, contrôleurs glycémiques, insulinorésistance, variabilité glycémique, impact du statut diabétique et systèmes informatisés. Le deuxième objectif de cette thèse est de détailler les nouveaux objectifs du contrôle glycémique en réanimation et d'en présenter l'évolution et les perspectives. En s'inspirant des diabétologues engagés dans le développement d'un pancréas artificiel et en généralisant les évaluations in silico, des équipes pluridisciplinaires pourraient construire une station de contrôle informatisée afin d'obtenir un contrôle glycémique optimisé et individualisé en réanimation. / Stress-induced hyperglycemia is common in critically ill patients due to insulin resistance and increased hepatic output of glucose. The relationship between stress hyperglycemia and poor outcome for patients hospitalized in the intensive care unit (ICU) was already established when Van den Berghe et al demonstrated that tight glucose control (TGC) by intensive insulin therapy was associated with decreased mortality and rate of complications in surgical ICU patients. Because further randomized controlled studies have failed to replicate any mortality benefit and have even shown an increased mortality (the NICE -SUGAR study), the primary objective of this thesis was to test the hypothesis that TGC with a computerized decision-support system (CDSS) reduces the mortality in adult critically ill patients as compared to conventional glucose control targeting BG levels to <10 mmol/L (the CGAO-REA study). We discussed several aspects of glucose control in the ICU (integration in the clinical workflow, confounding issues in BG measurements, insulin resistance, glucose variability, impact of diabetic status) and reviewed existing computerized tools. Despite the negative result of the CGAO-REA study, the interest for CDSSs remains because meanwhile new therapeutic goals for glucose control in the ICU have emerged. The second objective of this thesis is to present ongoing developments. Based on research programs targeting an artificial pancreas for diabetic patients, in silico trials, multidisciplinary approaches integrating human factors, a computerized glucose control station could be developed to allow clinicians to achieve an optimized, individualized glucose control in the ICU.

Prescribed self-management behaviors have been found to be important factors affecting the rates of morbidity and mortality in multiple medical conditions including chronic diseases such as diabetes, a condition that disproportionately affects high health risk populations such as African Americans. This study focused on understanding health behaviors, beliefs, and associated factors such as support systems and access to care that played a role in diabetes self-management and glucose control. The study also explored diabetes self-management education and its role in diabetes self-management. The research conducted in Pinellas and Hillsborough counties in Florida, included twenty-five African American women between the ages of forty-six and eighty-seven, with self-identified diabetes mellitus (type 2 diabetes). The study also included seven diabetes self-management educators consisting of nutritionists, a nurse educator, physicians, and an exercise physiologist--key members of the diabetes self-management team. Additionally, five diabetes education programs were observed. Methods included semi-structured qualitative interviews, with direct and participant observation of the Diabetes Intervention Prevention Program (DIPP), the St. Petersburg Free Clinic Diabetes Program, and the Morton Plant Meese/Joslin Diabetes Program in Pinellas County. Hillsborough County sites included the USF Diabetes Program, and University Community Hospital's Diabetes Care Program. Site selection included a cross-section of program types: non-clinic/community-based, community-based clinic, hospital-based, and university clinic-based. The study also utilized a thirty-nine question survey designed to elicit information about self-management beliefs and behaviors. Results revealed several self-management behavioral variables affecting glucose control: (1) nutritional/dietary changes, (2) exercise, (3) medication use, (4) blood glucose monitoring, (5) physician-patient interaction, (6) support systems, and (7) patient education/knowledge. Results also identified access to care as a contributor to self-management. Two models of diabetes self-management emerged from the findings: a model of balanced self-management held by the diabetes educators and self-management programs, and a model of Interruption practiced by the women. Recommendations highlighted the need for the awareness of socio-cultural factors affecting self-management, the elimination of barriers affecting access to care, improvement in physician-patient interaction, provision of culturally aware patient education, and stronger community and family support systems.