Дисертації з теми "Postprandial blood glucose"

Dissertação para obtenção do grau de Mestre em Nutrição Clínica
Background: Cinnamon has been shown to reduce postprandial glycaemia and enhance insulin sensitivity in healthy adults.
Aims: To study the effect of C. burmannii on the postprandial blood glucose response of healthy subjects and its antioxidant capacity in a semi-solid food.
Design: Twenty four apparently healthy subjects participated in this study. They were randomly assigned in group A (reference meal) or group B (test meal). The blood glucose concentrations were measured before the ingestion of the meals and 30, 60, 90 and 120 minutes after the start of the meal. The test meal used consisted of 100 g of mousse mixed with 3 g of cinnamon.
Results: The addition of 3 g of cinnamon to the mousse had no significant effect in blood glucose response in terms of the areas under the curve (AUC) and in the different postprandial times (p>0,05). The mean Cmax was significantly lower after the ingestion of the reference meal than after the ingestion of the mousse with 3 g of C.burmannii (96 mg/dl VS 104,42 mg/dl; p=0,011). The chemical analysis showed that the mousse with 3 g of cinnamon has a much higher phenolic content and antioxidant capacity than the mousse without cinnamon.
Conclusions: The inclusion of cinnamon in the mousse increased the antioxidant capacity of this semi-solid food, however it did not reduce the postprandial glucose response in healthy subjects.

PURPOSE: The purpose of this study is to examine the effects of different types of carbohydrates on blood glucose response in collegiate soccer athletes at rest. This will help to determine the effectiveness of a carbohydrate supplement in providing sustained energy and maintained performance if ingested prior to a soccer match. METHODS: In a cross-over design, 10 female collegiate soccer players (n= 10, age 20.10 ± .99 years, height 65.55 ± 2.77 inches, weight 64.12 ± 8.36 kilograms) from the University of South Florida reported to the laboratory on five separate occasions after an overnight fast. Once a baseline blood glucose measurement was obtained, subjects ingested one of four different carbohydrate beverages (dextrose, maltodextrin, Vitargo®, and waxy maize) and a control (water). Each subject consumed 1 gram of carbohydrate per kilogram body weight in a 7% solution. Order of carbohydrate and control supplements was randomly assigned for each participant. After the subject ingested one of the test beverages blood glucose measurements were taken at the 30, 45, 60, 90, 120, and 180 minute time points (a total of three hours). The same procedures took place during each subject's visit. A series of one-way analysis of variance (ANOVA) were performed using SPSS 19 to determine differences in the blood glucose response at each time point between the carbohydrate supplements. RESULTS: No significant difference existed between treatments for blood glucose levels at baseline. At 30, 45, and 60 minutes, blood glucose concentrations following dextrose, maltodextrin, and Vitargo® ingestion were significantly higher as compared to the placebo ingestion. No significant difference was observed between waxy maize and placebo at these time points. At ninety minutes the blood glucose concentrations for dextrose and Vitargo® were significantly higher than placebo, and at 120 minutes only Vitargo® was significantly higher than the placebo. Finally, at 180 minutes, the blood glucose concentration for waxy maize was significantly higher than all other treatments. CONCLUSION: The main finding of this study was that waxy maize does not observe a sharp increase in blood glucose response following ingestion but maintains an elevated blood glucose concentration over an extended period of time. All other treatments (maltodextrin, dextrose, and Vitargo®) resulted in a significant rise in blood glucose within the first thirty minutes following ingestion.

Approximately 25.8 million people, 8.3% of the population in the United States have diabetes mellitus (DM), which makes this disease one of the biggest public health problems facing this country. Type 2 diabetes (T2DM) is a heterogeneous disease characterized by variable degrees of insulin resistance, impaired insulin secretion, and increased glucose production. Currently, the insulin secretagogues known as sulfonylureas represent the major mainline drug class for long-term treatment. However, serious side effects, such as hypoglycemia and loss of potency with long-term use necessitate the development of novel insulin secretagogues. Transient receptor potential (TRP) channels have been reported to be involved in pancreatic insulin secretion. TRPA1 is a Ca2+-permeable nonselective cation channel. TRPA1 can be activated by molecules produced during oxidative glycolysis. TRPA1 may be an attractive candidate for drug development because of its involvement in the mechanism of insulin secretion. Previous studies have shown TRPA1 is expressed in rat pancreatic islets and that its activation promotes insulin release. This study was designed to determine if TRPA1 is expressed in mouse and human pancreatic β cells and whether it can promote insulin secretion. I demonstrated that TRPA1 is expressed in mouse and human pancreatic islets. I measured TRPA1-induced membrane currents using patch-clamp and used Ca2+ imaging to demonstrate that TRPA1 agonists induce Ca2+ influx in rat β cell-derived RINm5F cells. I confirmed that TRPA1 KO mice have no TRPA1 mRNA or protein in pancreatic β cells. I used isolated islet cells to demonstrate TRPA1-induced Ca2+ influx using Ca2+ imaging. By using pancreatic islets obtained from wild-type and TRPA1 KO mice, I determined that TRPA1 is important for insulin secretion. Finally, I determined that intraperitoneal administration of a TRPA1 agonist and antagonist affected blood glucose levels and plasma insulin levels in a manner consistent with the TRPA1 acting to increase insulin secretion. Furthermore, glucose tolerance was impaired in TRPA1 KO mice upon intraperitoneal glucose tolerance test (IPGTT) challenge compared to wild-type mice. In summary, I have shown TRPA1 is expressed not only in rat pancreatic islets but also in mouse and human pancreatic islets. I confirmed the localization of TRPA1 in pancreatic β cells. All of the experimental results are consistent with the concept that TRPA1 acts as to increase the insulin-secreting capacity of pancreatic β cells. According to my data, TRPA1 may play a role in promoting insulin secretion in patients with T2DM. Therefore, pharmacological activation of TRPA1 may be a novel therapeutic method for the treatment of diabetes.

Type 1 diabetes is a serious disease that must be monitored and controlled artificially by supplying exogenous insulin to the body. The artificial pancreas (AP) is a closed-loop system that resulted from integrating an insulin pump with a CGM and uses a control algorithm to automate insulin infusion. In this work, a novel tuning system and a multivariable control approach are presented for an AP system aimed to be robust against patient variability, meals and exercise. To enhance safety, fault detection 2/2 strategies are also developed as an integral part of the system. The approaches have been extensively validated in simulation and in an inpatient clinical trial
La T1D és una greu que requereix de monitorització i que ha de ser controlada de forma artificial subministrant insulina exògena. El pàncrees artificial (AP) és un sistema de llaç tancat resultant d'integrar una bomba d'insulina amb un CGM, i utilitza un sistema de control per automatitzar la infusió d'insulina. En aquest treball es presenten un nou sistema d’ajust i un sistema de control de vàries variables per a sistemes AP, dissenyat per ser robust davant la variabilitat del pacient, a menjars i exercici. Per augmentar la seguretat del pacient, també es dissenyen estratègies de detecció de fallades com una part integral dels sistema. Les estratègies proposades en aquest treball han estat validades extensivament en simulació i durant un assaig clínic, amb resultats prometedors

In this thesis I propose a novel method to estimate the dose and injection-to-meal time for low-risk intensive insulin therapy. This dosage-aid system uses an optimization algorithm to determine the insulin dose and injection-to-meal time that minimizes the risk of postprandial hyper- and hypoglycaemia in type 1 diabetic patients. To this end, the algorithm applies a methodology that quantifies the risk of experiencing different grades of hypo- or hyperglycaemia in the postprandial state induced by insulin therapy according to an individual patient’s parameters. This methodology is based on modal interval analysis (MIA). Applying MIA, the postprandial glucose level is predicted with consideration of intra-patient variability and other sources of uncertainty. A worst-case approach is then used to calculate the risk index. In this way, a safer prediction of possible hyper- and hypoglycaemic episodes induced by the insulin therapy tested can be calculated in terms of these uncertainties.
En esta tesis se propone un nuevo método para estimar la dosis y el instante de inyección que genere el menor riesgo para una terapia intensiva de insulina. El sistema de dosificación utiliza un algoritmo de optimización para determinar la dosis de insulina y el instante de inyección que reduzcan al máximo el riesgo de hiperglucemia e hipoglucemia posprandial en pacientes diabéticos tipo 1. Para ello, el algoritmo aplica una metodología que cuantifica el riesgo de sufrir diferentes grados de hipoglucemia e hiperglucemia en estado postprandial inducida por la terapia de insulina de acuerdo a los parámetros de cada paciente. Aplicando análisis intervalar modal se predice el nivel de glucosa postprandial considerando la variabilidad intrapaciente y otras fuentes de incertidumbre. Con un planteamiento del peor caso se calcula una predicción más segura de posibles episodios de hiperglucemia e hipoglucemia inducida por la terapia de insulina en términos de dichas incertidumbres.

Insulin therapy for Type 1 Diabetes (T1D) has several ramifications with different degrees of automation. The advances in sensors and monitoring devices have led to an increasing availability of data. Additionally, machine learning algorithms usage has sprung, allowing the development of models for Blood Glucose (BG) forecasting with relative ease. Nevertheless, BG forecasting is still a challenging task for prediction horizons beyond 30 min and, even more so, with missing or erroneous data, which is a common burden in the field. This thesis is devoted to generate machine learning models that forecast either BG levels using regression algorithms or postprandial hypoglycemia using classification algorithms. The application of these models range from Multiple Daily Injections (MDI) therapy up to Sensor Augmented Pump (SAP) therapy.
La teràpia amb insulina per a pacients amb T1D tenen vàries ramificacions amb diferents graus d’automatització. Els avenços en sensors i dispositius de monitorització comporten un increment en la disponibilitat de dades. A més a més, l’ús d’algoritmes d’aprenentatge automàtic s’han popularitzat, facilitant així el desenvolupament de models per pronosticar Glucosa en Sang (GS) amb major facilitat. No obstant això, preveure els nivells de GS és una tasca complexa per a finestres de predicció més enllà de 30 minuts, i més encara, amb dades errònies o absents, la qual cosa és una limitació molt freqüent en aquest camp. Aquesta tesis està dedicada a la generació de models basats en aprenentatge automàtic per predir ja siguin nivells de GS utilitzant algoritmes de regressió o hipoglucèmia postprandial utilitzant algoritmes de classificació. L’aplicació d’aquests models van des de la teràpia de múltiples injeccions diàries (MID), fins a la teràpia SAP

abstract: ABSTRACT Many natural interventions have been effective at lowering postprandial glucose concentrations (PPG) in research trials and, theoretically, should have favorable effects on the prevention and management of T2DM. Natural interventions include vinegar, nuts and exercise. Green tea has been demonstrated to also possessing antiglycemic effects. Thus, green tea, and its most abundant catechin EGCG, are being consumed for its potential health benefits in cancer prevention and in its inhibitory effects on α-amylase. Many studies have found EGCG to inhibit α-amylase an enzyme needed in the breakdown of carbohydrates (CHO). Other studies have looked at EGCG and its potential for lowering PPG concentrations due to its inhibitory effects on α-amylase in both mice and humans. Yet there is no research on Matcha tea specifically. Matcha tea is green tea in powder form; hence, it is consumed in its entirety unlike traditional teas which are steeped in bags. The purpose of this study was to determine whether Macha tea impacts PPG concentrations in healthy adults. Twelve subjects completed this randomized controlled, single blinded, crossover study. On three separate occasions the twelve subjects consumed a bagel and jam with either water, Lipton green tea, or Macha tea. Fasting blood glucose was taken upon their arrival. Once the tea or water and bagel with jam were consumed PPG concentrations were measured every 30 minutes until 120 minutes were reached. Results showed no statistically significant effects on PPG concentrations in either test groups (p=.960). However, this study did not measure EGCG levels in the tea provided. Therefore, further research should be done with known EGCG amounts to see its effects on PPG concentrations to fully rule out its potential.
Dissertation/Thesis
Masters Thesis Nutrition 2018

abstract: Background: Acetic acid in vinegar has demonstrated antiglycemic effects in previous studies; however, the mechanism is unknown. Objective: To determine whether acetic acid dissociates in the addition of sodium chloride and describe a flavorful vinaigrette that maintains the functional properties of acetic acid. Design: Phase I - Ten healthy subjects (23-40 years) taste tested five homemade vinaigrette and five commercial dressings. Perceived saltiness, sweetness, tartness, and overall tasted were scored using a modified labeled affective magnitude scale. Each dressing was tested three times for pH with a calibrated meter. Phase II – Randomized crossover trial testing six dressings against a control dressing two groups of nine healthy adult subjects (18-52 years). Height, weight and calculated body mass index (BMI) were performed at baseline. Subjects participated in four test sessions each, at least seven days apart. After a 10-hour fast, participants consumed 38g of the test drink, followed by a bagel meal. Capillary blood glucose was obtained at fasting, and every 30 minutes over a 2-hour period the test meal. Results: Dressing pH reduced as sodium content increased. In the intervention trials, no significant differences were observed between groups (p >0.05). The greatest reduction in postprandial glycemia (~21%) was observed in the dressing containing 200 mg of sodium. Effect size was large in both group 1 (η2=0.161) and group 2 (η2=0.577). Conclusion: The inclusion of sodium into acetic acid may impair its ability to attenuate blood glucose after a meal.
Dissertation/Thesis
Masters Thesis Nutrition 2017

abstract: Curcumin is an active ingredient of Curcuma longa (Turmeric) and is studied extensively for its antioxidant, anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer properties. The purpose of this study was to examine the effects of turmeric on blood glucose and plasma insulin levels. The study utilized a placebo-controlled, randomized cross-over design with participants serving as their own control. Eight glucose tolerant healthy participants completed the full study. Three-weeks washout period was kept in between six-weeks. Prior to the test meal day, participants were asked to eat a bagel with their evening dinner. During the day of the test meal, participants reported to the test site in a rested and fasted state. Participants completed mashed potato meal tests with 500 mg of turmeric powder or placebo mixed in water, followed by 3 weeks of 500 mg turmeric or placebo supplement ingestion at home. During this visit blood glucose finger picks were obtained at fasting, 30, 60, 90, and 120 min post-meal. Blood plasma insulin at fasting and at 30 min after the test meal were also obtained. During week 4, participants reported to the test site in a rested and fasted state where fasting blood glucose finger pricks and blood plasma insulin were measured. During week 5 to 7, participants were given a washout time-period. During week 8, entire process from week 1 to 4 was repeated by interchanging the groups. Compared to placebo, reduction in postprandial blood glucose and insulin response were non-significant after ingestion of turmeric powder. Taking turmeric for 3 weeks had no change in blood glucose and insulin levels. However, taking turmeric powder supplements for 3 weeks, showed a 4.4% reduction in blood glucose. Change in insulin at 30 min were compared with baseline insulin level showing no significant change between placebo and turmeric group. Fasting insulin after 3-weeks consumption of turmeric did not show any significant change, but showed a larger effect size (0.08). Future research is essential to examine the turmeric powder supplement benefits over a long period of time in healthy adults and whether it is beneficial in preventing the occurrence of type 2 diabetes.
Dissertation/Thesis
Masters Thesis Nutrition 2017

The purpose of this project was to determine the effects of 6 g of ground cinnamon added to farina (Cream of Wheat) cereal on blood glucose levels between obese and normal weight individuals. Thirty students, aged 19-30 years, were recruited to participate in this study. During study visits, participants were given one of two test meals (74 g of farina with and without 6 g of cinnamon) followed by seven blood glucose measurements over a two-hour period. A significant difference was seen in glycemic response between the two dietary conditions, but not between the two BMI groups (normal and obese). The two BMI groups were combined for analysis of dietary conditions. Ingestion of the cinnamon cereal resulted in significantly lower blood glucose responses at minutes 15, 30, 45 and 60 compared to the plain cereal. The results of this study confirm the positive glucose-lowering effects of cinnamon.
Department of Family and Consumer Sciences

碩士
國立屏東科技大學
資訊管理系所
106
Abstract Student ID：N10556004 Title of thesis：Applying Data Mining Technology to Explore the Effectiveness of Postprandial Blood Glucose Control in Diabetic Patients Total page：74 Name of Institute：Department of Management Information System, National Pingtung University of Science and Technology Date of Graduate：June, 2018 Degree Conferred：Master Name of Student：Chun-Chuan Chung Advisor：Deng-Neng Chen The Contents of Abstract in This Thesis： The population of diabetes is in an increasing trend nowadays. The Ministry of Health and Welfare has announced that the diabetes is ranked fifth of ten leading causes of death from 2017. Diabetes is a chronic metabolic syndrome disease, and it can get more easily to cause severe disease. Diabetes will damage health and waste more medical resources by long term.With the development of information technology and data science, data mining techniques have been extensively applied in all kinds of fields. This study has analyzed the medical examination database of a Regional Hospital in Southern Taiwan and applied C4.5 decision tree classifier in WEKA 3.8.1 to identify 6 key factors and extract 9 rules for the effectiveness of postprandial blood glucose control in diabetic patients. This research has revealed that the diabetic patients not receiving health education with different treatments will affect the postprandial blood glucose control. In order to enhance the credibility of the analysis results, we collected relevant medical literature and conducting an in-depth interview with a clinical medical expert for evaluation of the analysis results. The conclusions show that every result is similar to clinical experience. The contribution of this study is to apply data mining techniques to explore information that provide references and application for healthcare personnel. With the developed model of this study, doctors can provide better healthcare and treatment to diabetic patients by rules, and lower the huge medical burden. Keywords: data mining, Diabetes, Decision Tree algorithm

This thesis focuses on gastric motor function in patients with longstanding diabetes, and the role of gastric emptying and gastrointestinal hormones in the regulation of glycaemia in health and patients with type 2 diabetes mellitus. Diabetes is a common chronic disorder worldwide, with the prevalence of type 2 diabetes escalating due to an increasingly sedentary lifestyle and rising rates of obesity. Diabetes is associated with micro- and macrovascular complications, particularly in the context of poor glycaemic control (1993, 1998). Another complication of type 1 and 2 diabetes is gastroparesis (Horowitz et al., 2001, Horowitz M, 1986, Horowitz et al., 1989, Horowitz et al., 1991) (delayed gastric emptying in diabetes) and there is limited information about the natural history and prognosis of this condition. While the prognosis of diabetic gastroparesis has been assumed to be poor, limited data in a small cohort followed for a mean period of 12 years suggest otherwise, with neither deterioration in the rate of gastric emptying (Jones et al., 2002) nor increased mortality due to the condition itself (Kong et al., 1999). The study reported in Chapter 3 evaluated the longitudinal progression of gastric emptying in patients with longstanding diabetes over a 25 year period to determine if there is a progressive slowing of gastric emptying or whether gastric emptying is relatively stable with a good prognosis from the outset, and to ascertain the potential impact of glycaemic control and/or autonomic function. The study concludes that gastric emptying and upper gastrointestinal symptoms are relatively stable over 25 years, while there was a deterioration in autonomic function and an improvement in glycaemic control. The study reported in Chapter 4 examined the prognosis of diabetic gastroparesis and its findings highlight that this condition is neither associated with a poor prognosis nor a higher rate of mortality. There is increasing recognition that glycated haemoglobin (HbA1c), which is a measure of overall glycaemic control, is influenced more by postprandial, rather than fasting, blood glucose levels in the majority of patients with type 2 diabetes. This makes intuitive sense, because the majority of one’s time is spent in a postprandial state, digesting the caloric load of the ingested meal, which in healthy subjects empties from the stomach in a tightly regulated process at a rate of 1-4kcal/minute (Khoo et al., 2009). Accordingly, good control of postprandial glucose excursions should be a priority for the treatment of diabetes. The rate of gastric emptying itself influences the magnitude of the initial rise in postprandial glycaemia in health as well as type 1 and 2 diabetes (Jones et al., 1996, Horowitz et al., 1993, Horowitz et al., 1986), whereby slower emptying is associated with diminished postprandial glucose excursions. The overall rate of gastric emptying is dependent on the integration of motor activity in each region of the stomach and slower gastric emptying is associated with suppression of antral and duodenal contractions, and stimulation of phasic and tonic pyloric pressures, with the latter acting as a brake to gastric outflow (Horowitz et al., 1994). When glucose is given by the oral/enteral route, the stimulation of insulin is markedly greater than with an isoglycaemic intravenous glucose infusion. This phenomenon is known as the ‘incretin effect’ and is mediated by the gastrointestinal hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are secreted from the small intestine in response to nutrients (Ma et al., 2009a). GLP-1 and GIP both stimulate insulin secretion from the pancreas in the setting of elevated blood glucose levels, and are responsible for ~70% of the postprandial insulin response in healthy humans (Horowitz and Nauck, 2006). GLP-1 analogues, such as exenatide, are now widely used in the management of type 2 diabetes, in whom the response to exogenous GIP is attenuated markedly (Holst and Gromada, 2004) but the insulin response to GLP-1 remains intact (Elahi et al., 1994). It appears that an important action of GLP-1 analogues in reducing postprandial glycaemia is by retardation of small intestinal motility modulating carbohydrate absorption (Linnebjerg et al., 2008, Little et al., 2006). An alternative to the use of exogenous GLP-1 analogues in the management of type 2 diabetes is to develop dietary strategies which stimulate endogenous GLP-1 release. Glutamine, which is widely used as a nutritional supplement, appears to be the most potent amino acid in inducing GLP-1 release (Reimann et al., 2004). It has been reported that 30g glutamine, given in 300mL water, stimulates GLP-1 release in both healthy subjects and patients with type 2 diabetes (Greenfield et al., 2009) and Samocha-Bonet et al (Samocha-Bonet et al., 2011) reported that 15g and 30g glutamine when given as a drink, before an oral glucose load in patients with type 2 diabetes, dose-dependently stimulate GLP-1 and diminish subsequent glycaemic excursion. However, the effect of glutamine on the rate of gastric emptying of glucose could potentially influence the observed effect on glycaemia as it is now appreciated that the rate of gastric emptying itself has a major influence on postprandial glucose levels in healthy subjects and patients with type 1 and 2 diabetes (Chang et al., 2010). The study reported in Chapter 5 examined the effects of intraduodenal glutamine on GLP-1, GIP and insulin release and the subsequent glycaemic response to an intraduodenal glucose load, in health and type 2 diabetes, of which the intraduodenal route of delivery of glutamine will bypass the stomach, thus, eliminating any influence of glutamine on the rate of gastric emptying of glucose. This study showed that intraduodenal glutamine has minimal effect on the glycaemic response to intraduodenal glucose, despite its ability to stimulate GLP-1, GIP and insulin release, and stimulate phasic pyloric contractions, suggesting that slowing of gastric emptying may play a major role for the glucose lowering effect seen with oral glutamine.
Thesis (M.Phil.) -- University of Adelaide, School of Medicine, 2012

abstract: Type 1 diabetes (T1D) is a chronic disease that affects 1.25 million people in the United States. There is no known cure and patients must self-manage the disease to avoid complications resulting from blood glucose (BG) excursions. Patients are more likely to adhere to treatments when they incorporate lifestyle preferences. Current technologies that assist patients fail to consider two factors that are known to affect BG: exercise and alcohol. The hypothesis is postprandial blood glucose levels of adult patients with T1D can be improved by providing insulin bolus or carbohydrate recommendations that account for meal and alcohol carbohydrates, glycemic excursion, and planned exercise. I propose an evidence-based decision support tool, iDECIDE, to make recommendations to improve glucose control by taking into account meal and alcohol carbohydrates, glycemic excursion and planned exercise. iDECIDE is deployed as a low-cost and easy to disseminate smartphone application. A literature review was conducted on T1D and the state-of-the-art in diabetes technology. To better understand self-management behaviors and guide the development of iDECIDE, several data sources were collected and analyzed: surveys, insulin pump paired with glucose monitoring, and self-tracking of exercise and alcohol. The analysis showed variability in compensation techniques for exercise and alcohol and that patients made unaided decisions, suggesting a need for better decision support. The iDECIDE algorithm can make insulin and carbohydrate recommendations. Since there were no existing in-silico methods for assessing bolus calculators, like iDECIDE, I proposed a novel methodology to retrospectively compare insulin pump bolus calculators. Application of the methodology shows that iDECIDE outperformed the Medtronic insulin pump bolus calculator and could have improved glucose control. This work makes contributions to diabetes technology researchers, clinicians and patients. The iDECIDE app provides patients easy access to a decision support tool that can improve glucose control. The study of behaviors from diabetes technology and self-report patient data can inform clinicians and the design of future technologies and bedside tools that integrate patient’s behaviors and perceptions. The comparison methodology provides a means for clinical informatics researchers to identify and retrospectively test promising insulin blousing algorithms using real-life data.
Dissertation/Thesis
Doctoral Dissertation Biomedical Informatics 2017

博士
國立屏東科技大學
食品科學系所
105
Rice, the foremost food crop, is a staple food for people around the world. Moreover, rice varieties, processing, cookeries and physicochemical properties presents various GI (Glycemic Index) values. Most rice varieties are classified as high-GI foods. According to researches, people who have high-GI diets may increase risk of obesity, type 2 diabetes, diabetic complications, cardiovascular disease and some cancers. Low-GI diets, however improve insulin sensitivity and blood lipid and blood glucose level. Therefore, it is important to pay close attention to postprandial blood glucose and GI value of food. In order to study GI value of food, we investigated different methods of measuring GI values and physicochemical properties of foods in this study: (1) evaluating accuracy of GI by three different blood sampling methods; (2) measuring glycemic response and GI with gluten protein, dextrin fiber or canola oil added in cooked rice; (3) comparing effects of different cookeries, storage temperatures and storage durations on GI of cooked rice. First, we compared three different blood sampling methods (based on capillary whole blood, capillary plasma and venous plasma, respectively) of glycemic response, IAUC (incremental area under the blood glucose response curve) and GI for steamed rice, rice porridge and rice that stored overnight. The results showed that rice porridge produced the highest mean GI and mean IAUC (99.3 ± 0.6 and 4008.6 ± 390, respectively), followed by steamed rice (92.1 ± 0.4 and 3710 ± 363, respectively), and then that stored overnight rice (90.7 ± 0.4 and 3677 ± 366, respectively). In terms of blood sampling method, venous plasma show higher precision and lower coefficient of variation (CV) of GI, IAUC and glycemic response than other sampling method. Secondly, rice mixed with gluten protein, dextrin fiber or canola oil was tested for GI values. Venous plasma blood sample was taken to observe glycemic effect of rice according to first investigation. In this study, we determined the dose-response and mixture interaction effects of gluten protein, canola oil, and dextrin fiber combined with a portion of white rice on glycemic response and GI. The results showed that white rice has a GI value of 93.8±2.8. Supplementation with various amounts of canola oil and dextrin fiber reduced the GI slightly, whereas gluten protein significantly (p < 0.05) reduced the GI from 93.8 to 84.9 and 83.1, respectively. Analysis of the interaction of gluten, lipids, and dextrin on GI by using three-way ANOVA revealed that significant effects on GI value were found with gluten (p < 0.01) and dextrin (p < 0.05). Moreover, adding a gluten protein and dextrin fiber mixture yielded a larger glycemic control effect than adding a lipid and dextrin fiber mixture did. In conclusion, Food processing supplements gluten protein with rice products may associated with a reduction in overall postprandial glycemic response and induced a lower GI in healthy people. Finally studying, we examined the glycemic response of white rice to determine the effects of storage temperature (-20°C, 0°C, and 4°C) and storage duration (1, 3, and 5 days). Results were compared with cooked white rice (control, 25°C). Measurements were performed on Days 1, 3, and 5 to test the glycemic index (GI), incremental area under curve (IAUC), and blood glucose response. The results showed that the mean GI was highest for the control (93.5 ± 3.6), followed by those for the -20°C (87.4 ± 3.1), 4°C (84.1 ± 2.8), and 0°C (84.1 ± 2.7) test foods (Day 1). The GI values differed significantly with the storage duration (p < 0.05). In conclusion, white rice stored at 0°C for 5 days has the lowest glycemic response. Moreover, control group (25°C) exhibited the highest GI. In recent years, food choice and eating habits have changed dramatically. Our findings may serve as a reference for developing fast-food or low-GI emerge and conform to nutrition and health concepts applied to production of rice products.

碩士
國立屏東科技大學
食品科學系所
98
Diabetes is one of leading causes of death, according to the statistics by Department of Health , Executive Yuan of Taiwan. In modern medicine, diabetes could be controlled by various medication. However, drugs always have undesirable side effects. Therefore, it becomes the goal to find the plant content which can decrease glucose concentration of the blood, reduce the incidence of complication, and prevent the side effects. Alpha-Glucosidase inhibitors (AGIs) are the effective glucose-lowering medicines, and is a key enzyme of carbohydrates digestion. Inhibition of α-glucosidase leads to a delayed and reduced rise in post-prandial blood glucose levels. The purpose of this study is to evaluate inhibitory effect of mixture extracts of P. guajava L. and M. alba L. leaves on α-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. The inhibition of α-glucosidase activity was assayed in vitro. The IC50 values of Psidium guajava L. and Morus alba L. were 2.25 mg/mL and 0.1 mg/mL, espectively. The IC50 value of commercial anti-hyperglycemic agent (Glucobay) was 6.41 mg/mL. The IC50 value of mixture extracts of P. guajava L. and M. alba L. was 0.07 mg/mL. In cytotoxicity test, murine embryonic liver cell line (BNL CL.2) which were treated with various concentration and various time of mixture extracts, the survival percentages and the shape were no significant effect. In vivo, after feeding 8 weeks with mixture extracts, the results of oral sucrose challenge test showed that the extracts can reduce sucrose hydrolysis to monosaccharide, and delay the absorption of glucose, leading to the suppression of meal-induced increase of glucose. The mixture of plants can decrease in triglyceride, glutamic-oxalocetic transaminase(GOT), glutamic- pyruvic transaminase(GPT) concentration in plasma, and increase HDL concentration. In histopathology assay, the DCL, DCM, DCH, DCG of diabetic-induced groups were observed slight pathology less than diabetic control(DC) group.

碩士
國立中興大學
生物科技學研究所
107
Pu-erh tea, famous for its special aroma produced by particular processes. Pu-erh tea has been shown to ameliorate hyperglycemia by inhibit -glucosidase pathway, thus considered a healthy drink. In addition, hyperglycemia is major symptom in diabetes mellitus, and stabilized postprandial blood glucose (PBG) is one of strategies to cure and prevent diabetes. Clinical drug, acarbose, has the gastrointestinal adverse effects, such as flatulence, diarrhea, abdominal discomfort, impair patient compliance and limit clinical utility. Thus, finding a less side effects drug is highly anticipated. In experiment, Pu-erh tea infusions were determined to inhibit -glucosidase activity, and raw Pu-erh tea inhibited about 90% activity in 25 g/mL. Though the HPLC analysis, raw Pu-erh tea is rich in strictinin, ((-)-epigallocatechin gallate, EGCG). In vitro, the IC50 values of strictinin and EGCG against -glucosidase were 2.4 g/mL and 4.3 g/mL. In addition, we discover that the inhibition type of strictinin on -glucosidase is mixed type. In vivo, strictinin improve oral sucrose tolerance in C57BL/6J mice at dose 100 mg/kg, but didn’t improve oral glucose tolerance. The results indicated that strictinin decreased the PBG level by though inhibit -glucosidase path-way. Therefore, strictinin may have the potential to prevent diabetes.

This thesis focuses on the impact of dietary protein and fibre preloads on postprandial blood glucose and gastric emptying in type 2 diabetes mellitus. Key themes relate to: 1) The longitudinal evaluation of gastric emptying in type 2 diabetes 2) The evaluation of gastric emptying as measured by means of a ¹³C-octanoic acid breath test in older adults with type 2 diabetes 3) The evaluation of the acute effects of low dose ‘preloads’ of whey and guar, given alone or in combination before a meal, on postprandial glycaemia, GLP-1, insulin, and gastric emptying 4) The evaluation of the effects of 12 weeks’ treatment with a whey/guar preload on gastric emptying, postprandial glycaemia, and glycated haemoglobin (HbA1c), in type 2 diabetes. It is well established that the rate of gastric emptying plays a major role in determining the early postprandial glycaemic response, and that interventions that slow gastric emptying can reduce postprandial glycaemic excursions in type 2 diabetes. Gastric emptying is regulated by inhibitory feedback arising from the interaction of nutrients with the small intestine, mediated in part by the secretion of gut hormones. Gastric emptying is often disordered in people with type 2 diabetes; the emptying of solids and/or nutrient liquids is abnormally delayed in up to 30-50% with patients with longstanding type 2 diabetes, while gastric emptying may be accelerated in ‘early’ type 2 diabetes, although this has not been a consistent observation. Dietary strategies that slow gastric emptying, such as the use of ‘preloads’ (small quantities of macronutrient given in advance of the main meal), represent an appealing approach to reducing postprandial glycaemia. However, if modulating the rate of gastric emptying is to be developed further as a therapeutic strategy for postprandial glycaemic control, additional information is required about the natural history of gastric emptying in these patients. In the study reported in Chapter 2, I explored how the rate of gastric emptying changed over an interval of some 14 years in a group of patients with type 2 diabetes. The intra-individual variation of gastric emptying in health is modest, so that emptying is highly reproducible, although there is substantial inter-individual variation. Studies from tertiary referral centres involving patients with longstanding (typically 8-12 years) type 2 diabetes, relatively poor glycaemic control (HbA1c >8.5%), and a high prevalence of microvascular complications, indicate that 30-50% have abnormally delayed emptying of solids and/or nutrient liquids, whether studied by scintigraphy or stable isotope breath test, while a few have rapid emptying. Conversely, patients with ‘early’ type 2 diabetes (< 2 years) and/or an absence of autonomic neuropathy have been reported to have abnormally rapid emptying for solids and/or liquids, although this has not been observed in all series. Gastric emptying has a profound impact on control of glycaemia in type 2 diabetes, such that more rapid emptying of a glucose drink is associated with a higher blood glucose response. Scintigraphy is the gold standard technique used to quantify gastric emptying, but requires exposure of patients to ionising radiation and access to specialised equipment and personnel to undertake the assessment. An alternative method of measuring gastric emptying is by means of a stable isotope breath test, which can be used in an office-based setting, and has been validated against scintigraphy in both health and type 2 diabetes. There is also conflicting information regarding the effect of ageing on gastric emptying, with reports that emptying is either slowed, accelerated, or unchanged when compared to the young. When assessing the effects of type 2 diabetes on gastric emptying, it is important to select an age-matched healthy control group, particularly since type 2 diabetes cohorts tend to be older than the general population. In the study reported in Chapter 3, I evaluated the rate of gastric emptying using a ¹³C-octanoic acid breath test in community-based patients with type 2 diabetes, and compared this with age-matched healthy controls. Nutritional strategies to reduce postprandial glycaemia are attractive, and represent the greatest opportunity for optimising glycaemic control at an affordable cost as the healthcare demands of society escalate. Both the rate of gastric emptying, and the actions of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are major determinants of postprandial glycaemic excursions. In type 2 diabetes, the insulinotropic effect of GIP is diminished, whereas GLP-1 retains its capacity to stimulate insulin secretion, and also slows gastric emptying and suppresses glucagon secretion and energy intake. Stimulation of GLP-1 secretion is appealing in the management of type 2 diabetes. Whey protein, a by-product of the cheese-making process, can reduce postprandial glycaemia when taken with, or before, a meal, through interrelated mechanisms including enhancement of insulin and gut hormone secretion, slowing of gastric emptying, and reductions in appetite and energy consumption. Guar gum is a viscous soluble fibre, and when given with a meal, can decrease postprandial glycaemic excursions by slowing gastric emptying and inhibiting small intestinal absorption of glucose, associated with reduced, rather than increased plasma insulin levels, as well as attenuation of plasma GLP-1. Accordingly, combining both guar gum and whey protein in a dietary supplement may be advantageous. However, the relative contribution of whey and guar to glucose-lowering and slowing of gastric emptying when used alone, and whether their actions are additive or synergistic when given together, are uncertain. In the study reported in Chapter 4, I evaluated the comparative acute effects of whey protein and guar gum preloads, either alone or in combination, on postprandial glycaemia, GLP-1, insulin, and gastric emptying in type 2 diabetes. For the majority of people with type 2 diabetes who have relatively good overall glycaemic control (HbA1c ≤ 7.9%), postprandial glycaemia predominates over fasting blood glucose in contributing to HbA1c. Indeed, a ‘target’ HbA1c of ≤ 7% is difficult to achieve without minimizing postprandial glycaemic excursions. We have previously established that acute administration of high doses of whey protein preloads (50g) slows gastric emptying of the subsequent meal. An acute study in subjects with type 2 or pre-diabetes reported a preload incorporating low-dose whey (17g) together with guar (5g) slows gastric emptying and reduces postprandial glycaemia. However, it remains to be determined if a ‘pre-load’ strategy to reduce glycaemia are sustained with long-term use. Similarly, while a pre-load slows gastric emptying acutely, it is unknown whether this effect is sustained with daily pre-load administration. Moreover, whey supplements incur a substantial energy burden, so it is also important to determine if patients compensate by adjusting their overall intake with long-term use. In the study reported in Chapter 5, I evaluated the effects of a twice daily low dose whey/guar preload taken 15 minutes before breakfast and dinner over 12 weeks, in 79 patients with type 2 diabetes and relatively good glycaemic control treated with diet or metformin only, on HbA1c, gastric emptying, postprandial glycaemia and body weight and composition, in a single-blind, randomized, placebo-controlled trial.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 2018

Research Doctorate - Doctor of Philosophy (PhD)
Type 2 diabetes (T2D) is the most common chronic metabolic disorder resulting from either deficit of insulin secretion and/or action. The transition of normal glucose tolerance to T2D is usually accompanied by a cluster of metabolic risk factors such as low-grade inflammation, oxidative stress, insulin resistance (IR) and dyslipidaemia. IR is one of the marked independent predictors among these cluster of metabolic abnormalities that mediates the transition in high risk states such as obesity, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) to overt T2D. IR also is often associated with decreased clearance of lipids and lipoprotein abnormalities, together representing a greater risk of cardiovascular disease (CVD) in both high risk and individuals with T2D. Several studies have employed lipid ratios, homeostatic models, and anthropometric measures as surrogate markers for predicting IR. However, none of these accounted for both insulin and lipid availability in a single model to predict IR or metabolic syndrome (MetS). Therefore, the first aim of my PhD project, presented in the chapter 3, was to develop a novel marker for IR and MetS that accounts for both insulin and lipid availability in a single model. We proposed and evaluated a novel physiologically relevant marker, InsuTAG (product of fasting insulin and fasting triglycerides) as a predictor of IR and MetS. Cross-sectional analysis of data from the Retirement Health and Life-style Study (RHLS, n=618) showed that InsuTAG is a strong predictor of IR over existing lipid based surrogate markers and anthropometric measures. Receiver operating curve analysis indicated InsuTAG (93%) as the favourable marker for IR over other lipid based surrogate markers and anthropometry measures. Prevalence of MetS was significantly higher in individuals with InsuTAG values above the optimal cut-off value of 11.2. InsuTAG exhibited a greater area under than curve than HOMA-IR for identifying MetS. Together these observations indicate the potential of InsuTAG for predicting IR and MetS. Despite effective lifestyle and pharmacological interventions, the prevalence of T2D is growing at an alarming rate in Australia, in line with global prevalence. Failure of long term compliance to these interventions is a major barrier for their effectiveness in halting the transition to T2D in high risk state individuals, indicating a necessity for alternative effective approach. Given the fact that pathogenesis of T2D is chronic, complex and often involving multiple pathological pathways, use of well tolerated dietary bio-active compounds appears to be a potential strategy for delaying the onset of T2D. Several pre-clinical and in-vitro studies have reported the ability of dietary bio-actives to down regulate multiple pathological mechanisms (chronic low-grade inflammation, IR, oxidative stress and β-cell dysfunction) that are involved in the pathogenesis of T2D. We hypothesised that a combination of two lipid-lowering and anti-inflammatory dietary bio-active compounds, curcumin and long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), could potentially act in multiple pathways to improve the glycaemic control in individuals at high risk of developing T2D. My second aim, presented in chapter 4, was to evaluate the acute effects of curcumin and/or LCn-3PUFA on glycaemic responses. Therefore, in a randomised, cross over trial we investigated the postprandial glucose and insulin response to a single dose of curcumin and/or LCn-3PUFA in healthy individuals. The glucose levels were reduced by curcumin at as early as 30 min, and the maximum effect was observed at 60 min post meal consumption. Curcumin was found to be effective for lowering the insulin demand to control postprandial glucose levels. Similar results were observed following dietary supplementation with curcumin plus LCn-3PUFA. It was apparent that the postprandial effects on glycaemic control were primarily due to curcumin even in the combined treatment group. Thus, providing basis for long-term supplementation study with curcumin for glycaemic control. In chapter 5, a detailed study protocol for 2x2 factorial placebo controlled, double blinded randomised trial with long term (12 weeks) curcumin and LCn-3PUFA supplementation (COP-D trial) was presented. In chapter 6, we examined the effects of curcumin with or without LCn-3PUFA on glycaemic control and blood lipid levels in people at high risk of T2D. 12 weeks of supplementation with curcumin has effectively reduced the fasting insulin levels and IR in individuals with high risk of T2D. Parallel to these results, both curcumin and LCn-3PUFA were able to reduce the fasting triglycerides and atherogenic index of plasma, however the magnitude of reduction was greater with LCn-3PUFA supplementation. InsuTAG levels were also reduced with curcumin and LCn-3PUFA supplementation. However, this study failed to show any complimentary effects with concurrent administration of curcumin and LCn-3PUFA. Though IR and fasting triglycerides, were effectively reduced by these two bio-actives, we did not find any beneficial effects of curcumin and LCn-3PUFA supplementation on fasting glucose and glycosylated haemoglobin levels. In chapter 7, we designed a study to target commonly prevalent dyslipidaemia with curcumin and/or LCn-3PUFA in individuals with T2D (CALFOR-CVD trial). Participants were randomised to either placebo or curcumin or LCn-3PUFA, or curcumin plus LCn-3PUFA for six weeks. This pilot study has demonstrated that supplementation of curcumin can effectively reduce the TG. Contrasting to the results from chapter 6, magnitude of reduction in triglycerides in this study was higher with curcumin than LCn-3PUFA. Preliminary observations also presented a non-significant, but a noteworthy reduction of 0.5 mmol/L in total cholesterol and LDL-Cholesterol with curcumin supplementation. In line with observations from the COP-D trial, curcumin and LCn-3PUFA did not have any complimentary and/or added benefits. In conclusion, the results presented in this thesis demonstrate that InsuTAG has the potential to predict IR and MetS. This provides a basis for further research to validate InsuTAG with gold standard technique for IR and a longitudinal data analysis to determine the ability of InsuTAG to predict T2D in general population. With regards to the intervention trials, our hypothesis of targeting multiple pathways (IR and dyslipidaemia) in high risk and T2D patients with curcumin and LCn-3PUFA supplementation was successful. However, this thesis failed to provide any evidence on beneficial effects of combining curcumin and LCn-3PUFA for better glycaemic control to delay the onset of T2D. This could partly be due to presence of any unknown interactions between the two bio-actives or may be due to uncertainties in co-administration of curcumin and LCn-3PUFA. Thus, paving a way for further research to investigate beneficial effects with single formulation (curcumin and LCn-3PUFA) for achieving glycaemic control. This thesis constitutes a noted contribution to the research area of bio-markers and novel intervention strategies for T2D, and also presents a set of riddles that provides an extensive scope for future research.