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- All Subjects: Diabetes
- Creators: Herman, Richard
- Creators: Gaesser, Glenn A
- Member of: Theses and Dissertations
Description
Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
Description
Noninvasive neuromodulation could help treat many neurological disorders, but existing techniques have low resolution and weak penetration. Ultrasound (US) shows promise for stimulation of smaller areas and subcortical structures. However, the mechanism and parameter design are not understood. US can stimulate tail and hindlimb movements in rats, but not forelimb, for unknown reasons. Potentially, US could also stimulate peripheral or enteric neurons for control of blood glucose.
To better understand the inconsistent effects across rat motor cortex, US modulation of electrically-evoked movements was tested. A stimulation array was implanted on the cortical surface and US (200 kHz, 30-60 W/cm2 peak) was applied while measuring changes in the evoked forelimb and hindlimb movements. Direct US stimulation of the hindlimb was also studied. To test peripheral effects, rat blood glucose levels were measured while applying US near the liver.
No short-term motor modulation was visible (95% confidence interval: -3.5% to +5.1% forelimb, -3.8% to +5.5% hindlimb). There was significant long-term (minutes-order) suppression (95% confidence interval: -3.7% to -10.8% forelimb, -3.8% to -11.9% hindlimb). This suppression may be due to the considerable heating (+1.8°C between US
on-US conditions); effects of heat and US were not separable in this experiment. US directly evoked hindlimb and scrotum movements in some sessions. This required a long interval, at least 3 seconds between US bursts. Movement could be evoked with much shorter pulses than used in literature (3 ms). The EMG latency (10 ms) was compatible with activation of corticospinal neurons. The glucose modulation test showed a strong increase in a few trials, but across all trials found no significant effect.
The single motor response and the long refractory period together suggest that only the beginning of the US burst had a stimulatory effect. This would explain the lack of short-term modulation, and suggests future work with shorter pulses could better explore the missing forelimb response. During the refractory period there was no change in the electrically-evoked response, which suggests the US stimulation mechanism is independent of normal brain activity. These results challenge the literature-standard protocols and provide new insights on the unknown mechanism.
To better understand the inconsistent effects across rat motor cortex, US modulation of electrically-evoked movements was tested. A stimulation array was implanted on the cortical surface and US (200 kHz, 30-60 W/cm2 peak) was applied while measuring changes in the evoked forelimb and hindlimb movements. Direct US stimulation of the hindlimb was also studied. To test peripheral effects, rat blood glucose levels were measured while applying US near the liver.
No short-term motor modulation was visible (95% confidence interval: -3.5% to +5.1% forelimb, -3.8% to +5.5% hindlimb). There was significant long-term (minutes-order) suppression (95% confidence interval: -3.7% to -10.8% forelimb, -3.8% to -11.9% hindlimb). This suppression may be due to the considerable heating (+1.8°C between US
on-US conditions); effects of heat and US were not separable in this experiment. US directly evoked hindlimb and scrotum movements in some sessions. This required a long interval, at least 3 seconds between US bursts. Movement could be evoked with much shorter pulses than used in literature (3 ms). The EMG latency (10 ms) was compatible with activation of corticospinal neurons. The glucose modulation test showed a strong increase in a few trials, but across all trials found no significant effect.
The single motor response and the long refractory period together suggest that only the beginning of the US burst had a stimulatory effect. This would explain the lack of short-term modulation, and suggests future work with shorter pulses could better explore the missing forelimb response. During the refractory period there was no change in the electrically-evoked response, which suggests the US stimulation mechanism is independent of normal brain activity. These results challenge the literature-standard protocols and provide new insights on the unknown mechanism.
ContributorsGulick, Daniel Withers (Author) / Kleim, Jeffrey (Thesis advisor) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Herman, Richard (Committee member) / Helms Tillery, Steven (Committee member) / Arizona State University (Publisher)
Created2015
Description
Cardiovascular disease and diabetes are major health burdens. Diabetes is a primary risk factor of cardiovascular disease, and there is a strong link between obesity and risk of developing diabetes. With the prevalence of prediabetes highest among overweight/obese individuals, investigation into preventative strategies are needed. Aerobic exercise is a potent stimulus for both insulin and non-insulin dependent glucose uptake into the skeletal muscle. A single exercise session can improve insulin sensitivity within hours after exercise. The effects of intensity, type, and volume of exercise on glucose homeostasis have been studied extensively; however, controlling for muscle contraction frequency with a constant exercise intensity and workload has not been examined. The purpose of this study was to compare muscle contraction frequency during aerobic exercise by altering cycling cadence on insulin sensitivity and vascular health. Eleven obese males (age=28yr, BMI=35kg/m2) completed three conditions in random order: 1) control-no exercise; 2) 45-min cycling at 45 revolutions per minute (45RPM) at 65-75%VO2max; 3) 45-min cycling at 90RPM at 65-75%VO2max. Glucose control and insulin sensitivity were assessed with oral glucose tolerance tests (OGTT) 4 hours post-exercise. Vascular health was assessed via flow-mediated dilation (FMD) pre-exercise, 1-hr and 2-hr post exercise and ambulatory blood pressure was assessed pre-exercise, and continually every 15 min post-exercise. Linear mixed models were used to compare the mean differences in outcome variables. There were no significant differences found between control and both exercise conditions for all OGTT outcomes and no differences were found between control and exercise in FMD (all, p>0.05). Significant effects for exercise were found for both brachial and central blood pressure measures. Brachial systolic blood pressures were lower at 2- and 4-hr post-exercise by approximately -10 and -8mmHg, respectively (p<0.001 and p=0.004) versus control. Central systolic blood pressures were lower at 2-, 3-, and 4-hr post-exercise by approximately -8, -9 and -6mmHg, respectively (p<0.001, p=0.021 and p=0.004) versus control. In conclusion, aerobic exercise, regardless of muscle contraction frequency, were unable to effect glucose control and insulin sensitivity. Similarly, there was no effect on vascular function. However, there was a significant effect of aerobic exercise on reducing post-exercise blood pressure.
ContributorsJarrett, Catherine Lee (Author) / Gaesser, Glenn A (Thesis advisor) / Angadi, Siddhartha S (Committee member) / Dickinson, Jared M (Committee member) / Whisner, Corrie M (Committee member) / Todd, Michael W (Committee member) / Arizona State University (Publisher)
Created2017
Description
Brown adipose tissue (BAT) is thought to be important in combating obesity as it can expend energy in the form of heat, e.g. thermogenesis. The goal of this study was to study the effect of injected norepinephrine (NE) on the activation of BAT in rats that were fed a high fat diet (HFD). A dose of 0.25 mg/kg NE was used to elicit a temperature response that was measured using transponders inserted subcutaneously over the BAT and lower back and intraperitoneally to measure the core temperature. The results found that the thermic effect of the BAT increased after the transition from low fat diet to a high fat diet (LFD) yet, after prolonged exposure to the HFD, the effects resembled levels found with the LFD. This suggests that while a HFD may stimulate the effect of BAT, long term exposure may have adverse effects on BAT activity. This may be due to internal factors that will need to be examined further.
ContributorsSion, Paul William (Author) / Herman, Richard (Thesis director) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
There has been an alarming rise in the prevalence of obesity which has been attributed to the paralleled rise in consumption of high-fat foods. It’s commonly accepted that high-fat diets can lead to increased weight gain, however not all fats have the same physiological action. This study primarily focuses on the effect of canola oil, a monounsaturated fat, on energy homeostasis and body composition when it’s given as a supplement to a high-fat diet composed of saturated fatty acid. Rodent models were divided into three dietary groups: 1) low-fat diet (LFD), 2) high-fat diet (HFD) and 3) canola oils supplemented HFD (HF+CAN). After 4 weeks of dietary intervention, samples of epididymal fat, perinephric fat, and liver were analyzed across the three groups to see if the changes in energy homeostasis could be explained by the cellular behavior and composition of these tissues. Interestingly, the supplement of canola oil appeared to reverse the deleterious effects of a saturated fat diet, reverting energy intake, body weight gain and adipose tissue sizes to that (if not lower than that) of the LFD group. The only exception to this effect was the liver: the livers remained larger and fattier than those of the HFD. This occurrence is possibly due to a decrease in free fatty acid uptake in the adipose tissues—resulting in smaller adipose tissue sizes—and increased fatty acid uptake in the liver. The mechanism by which this occurs has yet to be elucidated and will be the primary focus of upcoming studies on the effect of monounsaturated fat on other diets.
ContributorsZuo, Connie Wanda (Author) / Washo-Krupps, Delon (Thesis director) / Deviche, Pierre (Committee member) / Herman, Richard (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Type II diabetes is a serious, chronic metabolic disease that has serious impacts on both the health and quality of life in patients diagnosed with the disease. Type II diabetes is also a very prevalent disease both in the United States and around the world. There is still a lot that is unknown about Type II diabetes, and this study will aim to answer some of these questions. The question posed in this study is whether insulin resistance changes as a function of time after the start of a high fat diet. We hypothesized that peripheral insulin resistance would be observed in animals placed on a high fat diet; and peripheral insulin resistance would have a positive correlation with time. In order to test the hypotheses, four Sprague-Dawley male rats were placed on a high fat diet for 8 weeks, during which time they were subjected to three intraperitonal insulin tolerance tests ((NovoLogTM 1 U/kg). These three tests were conducted at baseline (week 1), week 4, and week 8 of the high fat diet. The test consisted of serially determining plasma glucose levels via a pin prick methodology, and exposing a droplet of blood to the test strip of a glucometer (ACCUCHEKTM, Roche Diagnostics). Two plasma glucose baselines were taken, and then every 15 minutes following insulin injection for one hour. Glucose disposal rates were then calculated by simply dividing the glucose levels at each time point by the baseline value, and multiplying by 100. Area under the curve data was calculated via definite integral. The area under the curve data was then subjected to a single analysis of variance (ANOVA), with a statistical significance threshold of p<0.05. The results of the study did not indicate the development of peripheral insulin resistance in the animals placed on a high fat diet. Insulin-mediated glucose disposal was about 50% at 30 minutes in all four animals, during all three testing periods. Furthermore, the ANOVA resulted in p=0.92, meaning that the data was not statistically significant. In conclusion, peripheral insulin resistance was not observed in the animals, meaning no determination could be made on the relation between time and insulin resistance.
ContributorsBrown, Kellen Andrew (Author) / Caplan, Michael (Thesis director) / Herman, Richard (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
For the past couple decades, there has been a continuous rise in obesity and Type II Diabetes which has been attributed to the rise in calorically dense diets, especially those heavy in fats. Because of its rising prevalence, accompanied health concerns, and high healthcare costs, detection and therapies for these metabolic diseases are in high demand. Insulin resistance is a typical hallmark of Type II Diabetes and the metabolic deficiencies in obesity and is the main focus of this project. The primary purpose of this study is (1) detect the presence of two types of insulin resistance (peripheral and hepatic) as a function of age, (2) distinguish if diet impacted the presence of insulin resistance, and (3) determine both the short-term and long-term effects of caloric restriction on metabolic health. The following study longitudinally observed the changes in insulin resistance in high-fat fed and low-fat fed rodents under ad libitum and caloric restriction conditions over the course of 23 weeks. Fasting blood glucose, fasting insulin, body weight, and sensitivity of insulin on tissue were monitored in order to determine peripheral and hepatic insulin resistance. A high fat diet resulted in higher body weights and higher hepatic insulin resistance with no notable effect on peripheral insulin resistance. Caloric restriction was found to alleviate insulin resistance both during caloric restriction and four weeks after caloric restriction ended. Due to sample size, the generalizability of the findings in this study are limited. However, the current study did provide considerable results and can be viewed as a pilot study for a larger-scale study.
ContributorsZuo, Dana (Author) / Trumble, Benjamin (Thesis director) / Herman, Richard (Committee member) / Department of Psychology (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.
ContributorsMishra, Shambhavi (Co-author) / Numani, Asfia (Co-author) / Sweazea, Karen (Thesis director) / Plasencia, Jonathan (Committee member) / Economics Program in CLAS (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers, but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.
ContributorsNumani, Asfia (Co-author) / Mishra, Shambhavi (Co-author) / Sweazea, Karen (Thesis director) / Plasencia, Jon (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Background: Postprandial hyperglycemia can increase levels of oxidative stress and is an independent risk factor for complications associated with type 2 diabetes.
Purpose: To evaluate the acute effects of a 15-min postmeal walk on glucose control and markers of oxidative stress following a high-carbohydrate meal.
Methods: Ten obese subjects (55.0 ± 10.0 yrs) with impaired fasting glucose (107.1 ± 9.0 mg/dL) participated in this repeated measures trial. Subjects arrived at the laboratory following an overnight fast and underwent one of three conditions: 1) Test meal with no walking or fiber (CON), 2) Test meal with 10g fiber and no walking (FIB), 3) Test meal with no fiber followed by a 15-min treadmill walk at preferred walking speed (WALK). Blood samples were taken over four hours and assayed for glucose, insulin, thiobarbituric reactive substances (TBARS), catalase, uric acid, and total antioxidant capacity (TAC). A repeated measures ANOVA was used to compare mean differences for all outcome variables.
Results: The 2hr and 4hr incremental area under the curve (iAUC) for glucose was lower in both FIB (2hr: -93.59 mmol∙120 min∙L-1, p = 0.006; 4hr: -92.59 mmol∙240 min∙L-1; p = 0.041) and WALK (2hr: -77.21 mmol∙120 min∙L-1, p = 0.002; 4hr: -102.94 mmol∙240 min∙L-1; p = 0.005) conditions respectively, compared with CON. There were no differences in 2hr or 4hr iAUC for glucose between FIB and WALK (2hr: p = 0.493; 4hr: p = 0.783). The 2hr iAUC for insulin was significantly lower in both FIB (-37.15 μU ∙h/mL; p = 0.021) and WALK (-66.35 μU ∙h/mL; p < 0.001) conditions, compared with CON, and was significantly lower in the WALK (-29.2 μU ∙h/mL; p = 0.049) condition, compared with FIB. The 4hr iAUC for insulin in the WALK condition was significantly lower than both CON (-104.51 μU ∙h/mL; p = 0.001) and FIB (-77.12 μU ∙h/mL; p = 0.006) conditions. Markers of oxidative stress were not significantly different between conditions.
Conclusion: A moderate 15-minute postmeal walk is an effective strategy to reduce postprandial hyperglycemia. However, it is unclear if this attenuation could lead to improvements in postprandial oxidative stress.
Purpose: To evaluate the acute effects of a 15-min postmeal walk on glucose control and markers of oxidative stress following a high-carbohydrate meal.
Methods: Ten obese subjects (55.0 ± 10.0 yrs) with impaired fasting glucose (107.1 ± 9.0 mg/dL) participated in this repeated measures trial. Subjects arrived at the laboratory following an overnight fast and underwent one of three conditions: 1) Test meal with no walking or fiber (CON), 2) Test meal with 10g fiber and no walking (FIB), 3) Test meal with no fiber followed by a 15-min treadmill walk at preferred walking speed (WALK). Blood samples were taken over four hours and assayed for glucose, insulin, thiobarbituric reactive substances (TBARS), catalase, uric acid, and total antioxidant capacity (TAC). A repeated measures ANOVA was used to compare mean differences for all outcome variables.
Results: The 2hr and 4hr incremental area under the curve (iAUC) for glucose was lower in both FIB (2hr: -93.59 mmol∙120 min∙L-1, p = 0.006; 4hr: -92.59 mmol∙240 min∙L-1; p = 0.041) and WALK (2hr: -77.21 mmol∙120 min∙L-1, p = 0.002; 4hr: -102.94 mmol∙240 min∙L-1; p = 0.005) conditions respectively, compared with CON. There were no differences in 2hr or 4hr iAUC for glucose between FIB and WALK (2hr: p = 0.493; 4hr: p = 0.783). The 2hr iAUC for insulin was significantly lower in both FIB (-37.15 μU ∙h/mL; p = 0.021) and WALK (-66.35 μU ∙h/mL; p < 0.001) conditions, compared with CON, and was significantly lower in the WALK (-29.2 μU ∙h/mL; p = 0.049) condition, compared with FIB. The 4hr iAUC for insulin in the WALK condition was significantly lower than both CON (-104.51 μU ∙h/mL; p = 0.001) and FIB (-77.12 μU ∙h/mL; p = 0.006) conditions. Markers of oxidative stress were not significantly different between conditions.
Conclusion: A moderate 15-minute postmeal walk is an effective strategy to reduce postprandial hyperglycemia. However, it is unclear if this attenuation could lead to improvements in postprandial oxidative stress.
ContributorsKnurick, Jessica (Author) / Johnston, Carol S (Thesis advisor) / Sweazea, Karen L (Committee member) / Gaesser, Glenn A (Committee member) / Shaibi, Gabriel Q (Committee member) / Lee, Chong D (Committee member) / Arizona State University (Publisher)
Created2015