>Magister Scientiae - MSc / The plant Hypoxis hemerocallidea, also known as the African potato, is commonly used as a traditional medicine to treat diabetes in South Africa. The mechanism by which it lowers blood glucose levels is not known. The main aim of this research was to study the possible hypoglycemic effect of HH using RIN-5 F pancreatic tumor cells. To accomplish this, the study was divided into three parts: (1) to test whether exposure of RIN-5F cells to glucose and HH extract affect the cell proliferation and cell viability, (2) to test whether the HH extract have an effect on insulin secretion, and (3) to test whether the HH extract has an effect on alpha amylase and alpha glucosiadase enzyme activity. The RIN-5F cells were exposed to different concentrations of glucose (5, 10, 20, 37.5, 50, 55, 74, and 92.3 mM) for different times (1, 3, 6 and 24 hours). The RIN-5F cells were also exposed to different concentrations of HH (50, 100, 150, 200 and 500 μ/ml) for different times (1, 3, 6 and 24 hours). Cell proliferation was evaluated using crystal violet staining and cell viability was evaluated using the XTT assay. To evaluate the effect of glucose and HH on RIN-5 F cell insulin secretion the cells were exposed to HH (100 μg/ml or 500 μg/ml) and / or glucose (2 mM or 50 mM) for 30 or 90 minutes. Insulin, α-amylase activity and α-glucosidase activity were evaluated by using commercially available colorimetric assays. Enzymatic activity in the presence of HH was compared with positive controls for α-amylase activity or α-glucosidase activity. Results are expressed as means ± SEM or median. Statistical differences among groups were analyzed by analyses of variance. P < 0.05 was considered as significant. An increase in the cell viability and cell proliferation was found when RIN-5 F cells were exposed to high glucose concentrations and a high dose of HH extract for a short time period (1, 3 and 6 hours). When the cells were exposed to the HH extract over 24 hours, HH did not affect cell viability significantly. Insulin secretion from RIN-5 F cells was increased when exposed to low glucose (2 mM) or high glucose (50 mM) for 30 minutes. Insulin secretion was increased from RIN5F cells after exposure to low HH (100 μg/ml) or high HH (500 μg/ml) for 30 minutes. Exposure of RIN5-F cells to HH for 90 minutes caused a further increase in insulin secretion from (4.3±0.17 mIU/mg protein; P ≤ 0.01) in 100 μg/ml, to (7.87±0.17 mIU/mg protein; P ≤ 0.001) in 500 μg/ml. At both 30 minutes and 90 minutes, insulin secretion was significantly higher when cells where exposed to 500 μg/ml HH compared to 100 μg/ml HH. Insulin secretion by cells exposed to 2 mM glucose + 100 μg/ml HH (4.69±0.16 mIU/mg protein; P ≤ 0.001) was significantly higher than when exposed to 2 mM glucose only (2.27±0.17 mIU/mg protein), while the insulin secretion in 2 mM glucose + 500 μg/ml HH (2.56±0.17 mIU/mg protein; P > 0.05) was not significantly different from that in 2 mM glucose treated cells (2.27±0.17 mIU/mg protein). Similar results are obtained after 90 minutes. In the presence of high-glucose (50 mM), at both 30 minutes and 90 minutes, insulin secretion was significantly decreased when cells where exposed to low concentration of HH (100 μg/ml) and high concentration of HH (500 μg/ml). The HH extract produced α-amylase enzyme inhibition. The maximum inhibition was at a concentration of 10μg/ml (922±117U/ml; P ≤ 0.01). The 5 μg/ml concentrations failed to produce significant inhibition. The HH extract had significant α- glucosidase inhibitory activity at a concentration of 5μg/ml (0.12±0.3U/ml; P ≤ 0.001) or 10μg/ml (0.13±0.3U/ml; P ≤ 0.001). In conclusion, based on its ability to inhibit α-amylase and α- glucosidase activity HH has the potential to be used in control of blood glucose levels. The HH aqueous extract increased insulin secretion under our basic experimental conditions and in the presence of low glucose levels, but not at high (50 mM) glucose concentrations. Insulin secretion in the presence of different glucose concentrations, in the presence of HH, needs further investigation. It is recommended that the ability of HH to stimulate insulin secretion be evaluated at 15-20 mM glucose.

Aerobic exercise interventions involving individuals with type 1 diabetes have had little positive effect on blood glucose control as reflected by hemoglobin A1c. The few existing interventions involving resistance exercise, either alone or combined with aerobic exercise, while small in sample size, have had better outcomes. The purpose of this research program was to examine the changes in blood glucose levels during activity and for 24 hours post-exercise (as measured by continuous glucose monitoring) when resistance exercise is performed, either on its own or combined with aerobic exercise, as compared to aerobic exercise alone or no exercise. Twelve physically active individuals with type 1 diabetes performed 5 separate exercise sessions in random order separated by at least five days: 1) no exercise/control; 2) aerobic exercise (45 minutes of treadmill running at 60% VO2peak); 3) resistance exercise (45 minutes of weight lifting – 3 sets of 8 repetitions of 7 different exercises); 4) aerobic then resistance exercise (2 and 3 combined with the aerobic exercise first); 5) resistance then aerobic exercise (2 and 3 combined with the resistance exercise first). We found that resistance exercise was associated with a lower risk of hypoglycemia during exercise, less carbohydrate intake during exercise, less post-exercise hyperglycemia and more frequent (but less severe) nocturnal hypoglycemia than aerobic exercise. When aerobic and resistance exercise were combined, performing resistance exercise prior to aerobic exercise (rather than the reverse) resulted in attenuated declines in blood glucose during aerobic exercise, accompanied by a lower need for carbohydrate supplementation during exercise and a trend towards milder post-exercise nocturnal hypoglycemia.

BACKGROUND: The prevalence of Alzheimer’s disease (AD) and other types of dementia is expected to drastically increase between now and midcentury because of the aging baby boomer population. It is projected that by 2030, 74 million people aged 65 and older will comprise nearly 20% of the population (United States Census Bureau, 2017). By 2060, it is estimated that about 13.8 million people will have AD. In 2020, the estimated total health care costs for treating individuals with AD in 2020 is $305 billion (Wong, 2020). As the population ages, the cost is expected to increase to more than $1 trillion. This significant economic and health care burden could be greatly alleviated by the development of a treatment that would delay the onset of the disease or prevent the disease altogether. Increasing evidence supports cardiovascular health being linked to the health of the brain. Diabetes is a particular risk factor that increases the likelihood of cardiovascular disease and is consequently associated with a higher risk of developing AD and other dementias. AIM: The aim of this study was to determine the association between persistent high blood glucose during midlife to late life and the risk of incident dementia and AD. METHODS: This study included 1287 Framingham Offspring participants (669 women, mean age 68.6 ± 5.7 years) who were free of dementia and attended 5 consecutive examinations at 4-year intervals starting at midlife (Exam 3: 1983–1987, mean age 54.6 ± 5.8 years) until late life (Exam 7: 1998–2001, mean age 68.6 ± 5.7 years). These participants were subsequently followed up for incident dementia after a period of time (mean 14 ± 4.5 years). Based on the resulting data, this study examined the effect of midlife diabetes (fasting blood glucose level ≥ 126 mg/dL), late-life diabetes, 10-mg/dL incremental increases in fasting blood glucose (FBG), persistence of diabetes during midlife to late life, and a steep increase in FBG from midlife to late life over an 18-year exposure period. Further stratified analysis was completed on a subgroup of participants with a steep incline in FBG to determine if there was an interaction effect with apolipoprotein E4 (APOE4) carrier status. RESULTS: During the follow-up period, 172 participants developed dementia, and of these cases, 135 participants had AD. Multivariable Cox proportional hazards models showed that persistent high FBG was associated with greater than 2-fold increase in risk of both incident dementia (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.37-3.33) and AD ([HR] 2.18, 95% [CI] 1.33-3.57) after adjusting for age, sex, education, APOE4, prevalent cardiovascular disease (CVD), and midlife diabetes treatment. In addition, individuals who experienced a steep increase in their FBG from Exam 3 to Exam 7 were associated with an increased risk of developing AD (p value = 0.022). Further stratification by APOE4 carrier status with a steep increase in FBG revealed that APOE4 non-carriers were associated with an approximate 2-fold increased risk for developing incident dementia ([HR] 1.90, 95% [CI] 1.12-3.16; p value < 0.05) and AD ([HR] 2.30, 95% [CI] 1.28-4.06; p value < 0.05). CONCLUSIONS: Persistent high blood glucose was associated with an increased risk for developing incident dementia and AD in a community-based cohort. A steep increase in FBG during midlife to late life also increased the risk for developing dementia and AD in this cohort. These data support the potential of sustained cognitive benefits from lower blood glucose levels in midlife but also suggest that sharp increases in blood glucose levels in older adults may be a risk marker for dementia and AD.

Diabetes mellitus, whether type 1 or type 2, offers special challenges to home health care providers. Treatment of diabetes can become increasing complex. While insulin remains the cornerstone of treatment in patients with type 1 diabetes (T1DM), the utilization of insulin to safely control blood glucose is also necessary for many patients with type 2 diabetes (T2DM). Many different insulin products are available, with each product possessing different characteristics and adverse effect potential. Balancing glycemic control with patient safety is paramount. The individualization of insulin therapy can be challenging for both patients and health care professionals. Regular evaluation of blood glucose monitoring is vital for patient assessment. This article provides a review of insulin for providers caring for patients in the home health care setting.

Impairments in insulin sensitivity can occur in patients with chronic kidney disease (CKD). Correction of metabolic acidosis has been associated with improved insulin sensitivity in CKD, suggesting that metabolic acidosis may directly promote insulin resistance. Despite this, the effect of acid or alkali loading on insulin sensitivity in a rodent model of CKD (remnant kidney) has not been directly investigated. Such studies could better define the relationship between blood pH and insulin sensitivity. We hypothesized that in remnant kidney rats, acid or alkali loading would promote loss of pH homeostasis and consequently decrease insulin sensitivity. To test this hypothesis, we determined the impact of alkali (2 wk) or acid (5-7 days) loading on plasma electrolytes, acid-base balance, and insulin sensitivity in either sham control rats, 2/3 nephrectomized rats, or 5/6 nephrectomized rats. Rats with 5/6 nephrectomy had the greatest response to insulin followed by rats with 2/3 nephrectomy and sham control rats. We found that treatment with 0.1 M sodium bicarbonate solution in drinking water had no effect on insulin sensitivity. Acid loading with 0.1 M ammonium chloride resulted in significant reductions in pH and plasma bicarbonate. However, acidosis did not significantly impair insulin sensitivity. Similar effects were observed in Zucker obese rats with 5/6 nephrectomy. The effect of renal mass reduction on insulin sensitivity could not be explained by reduced insulin clearance or increased plasma insulin levels. We found that renal mass reduction alone increases sensitivity to exogenous insulin in rats and that this is not acutely reversed by the development of acidosis.

A crossover design study was conducted to determine if reducing pain, by using alternative sites off the finger tip, would increase testing frequency and improve clinical outcome as measured by glycosylated hemoglobin. Subjects with type I and type 2 diabetes tested with the FreeStyle alternative-site meter (group I) or tested with their original meter (group 2). After 3 months the subjects used the alternate meter. Testing frequency and blood glucose concentrations were recorded for the month before the study began and monthly thereafter. Glycosylated hemoglobin was tested initially, at the crossover point, and at study conclusion. Insulin users increased testing frequency from 2.4 to 3.0 tests per day. Testing frequency for non-insulin users remained the same at 1.5 tests per day. Testing frequency was essentially the same with the FreeStyle and the original meters. The average hemoglobin A1c was 7.4% (standard deviation 1.5%) initially, 7.3% (standard deviation 1.5%) at the crossover point, and 6.9% (standard deviation 1.1%) after 6 months. There was no significant difference in hemoglobin A1c measurements between meter types after 6 months. Thirteen months later a final hemoglobin A1c, testing frequency, and a questionnaire regarding meter preference and pain rating were obtained. Seventy-four percent of participants preferred the alternative-site meter, which was rated as significantly (p < .05) less painful. Testing frequency significantly improved (p = .001) while free strips were being provided. Testing frequency 13 months later was not significantly different from the baseline (p = .101). Hemoglobin A 1 c was significantly lower 6 months after the study began (p = .000) and 13 months later (p = .008) at baseline.

Doctor Educationis / Diabetes has since been a global epidemic; an estimated 5.0 million deaths of diabetes in the world have been recorded; one in 11 adults have diabetes (415 million); and by 2040, one adult in 10 (642 million) will have diabetes. In Africa, more than two thirds of people with diabetes are undiagnosed, and 42 million have diabetes in the Sub-Saharan region with 324 877 adult deaths in South Africa (IDF, 2015). The global prevalence (age-standardized) of diabetes has nearly doubled since 1980, rising from 4.7% to 8.5% in the adult population. This reflects an increase associated with risk factors such as overweight or obese (WHO, 2016). Medicinal plants on the other hand, have played a significant role in the treatment and prevention of diabetes for centuries. In South Africa, indigenous medicinal plants have increasingly been used in the treatment of diabetes. In this study, a new anti-diabetes herbal compound named Jiang Tang 2016 (JT2016), made of three well researched South African indigenous medicinal plants is investigated for its hypoglycemic effects in HFD/STZ induced diabetic SD rats. These plants have been used for centuries in the indigenous system of medicine against various ailments, they are easily accessible, they grow in abundance, and are economically sustainable

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第18467号 / 人健博第21号 / 新制||人健||2(附属図書館) / 31345 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 任 和子, 教授 横出 正之, 教授 田村 恵子 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19996号 / 工博第4240号 / 新制||工||1656(附属図書館) / 33092 / 京都大学大学院工学研究科電気工学専攻 / (主査)教授 土居 伸二, 教授 小林 哲生, 准教授 蛯原 義雄 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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