Incidence and disease course of new-onset diabetes mellitus in breast and colorectal cancer patients undergoing chemotherapy: A prospective multicenter cohort study.

AIMS: To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM. METHODS: This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy. RESULTS: Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007). CONCLUSIONS: DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03062072).

A botanical drug composed of three herbal materials attenuates the sensorimotor gating deficit and cognitive impairment induced by MK-801 in mice.

OBJECTIVES: A botanical drug derived from the ethanolic extract composed of Clematis chinensis Osbeck (Ranunculaceae), Trichosanthes kirilowii Maximowicz (Cucurbitaceae) and Prunella vulgaris Linné (Lamiaceae) has been used to ameliorate rheumatoid arthritis as an ethical drug in Korea. In our study, we investigated the effect of this herbal complex extract (HCE) on schizophrenia-like behaviours induced by MK-801. METHODS: HCE (30, 100 or 300 mg/kg, p.o) was orally administered to male ICR mice to a schizophrenia-like animal model induced by MK-801. We conducted an acoustic startle response task, an open-field task, a novel object recognition task and a social novelty preference task. KEY FINDINGS: We found that a single administration of HCE (100 or 300 mg/kg) ameliorated MK-801-induced abnormal behaviours including sensorimotor gating deficits and social or object recognition memory deficits. In addition, MK-801-induced increases in phosphorylated Akt and GSK-3ß expression levels in the prefrontal cortex were reversed by HCE (30, 100 or 300 mg/kg). CONCLUSIONS: These results imply that HCE ameliorates MK-801-induced dysfunctions in prepulse inhibition, social interactions and cognitive function, partly by regulating the Akt and GSK-3ß signalling pathways.

Aster glehni Extract Ameliorates Scopolamine-Induced Cognitive Impairment in Mice.

The leaves of Aster glehni Fr. Schm. (Asteraceae) have been used to treat insomnia in Korea. Insomnia is a common adverse effect of therapeutic agents for Alzheimer's disease (AD), and the control of sleep disturbance may prevent dementia. We hypothesized that the leaves of A. glehni can attenuate cognitive dysfunctions observed in AD. We observed the ameliorating effects of the ethanolic extract of leaves of A. glehni (AG-D) on memory dysfunction through the Morris water maze test, the passive avoidance test, and the Y-maze test. We performed acetylcholinesterase (AChE) activity assay and Western blotting to determine the mechanism of action of AG-D. AG-D significantly attenuated memory dysfunction observed in the above behavior studies and inhibited the activity of AChE. AG-D also increased the levels of phosphorylation extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase 3ß (GSK-3ß) and the expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampi. These results suggest that AG-D ameliorates memory impairments by AChE inhibition and activation of ERK-CREB-BDNF and PI3K-Akt-GSK-3ß signaling pathways. Taken together, this study suggests that AG-D could be used as a potential treatment for cognitive dysfunction.

The Ameliorating Effects of Bee Pollen on Scopolamine-Induced Cognitive Impairment in Mice.

Bee pollen consists of floral pollen mixed with bee secretions and nectar. It has been considered as a functional food and has different kinds of biologically active ingredients, such as flavonoids, polyphenols, phytosterols and minerals. However, its function in cognition has yet been investigated. In the present study, we investigated the ameliorating effect of bee pollen against scopolamine-caused cognitive impairment through the passive avoidance test, the Y-maze test and the Morris water maze test. In addition, Western blotting was employed to verify the effects of bee pollen on memory-related signaling molecules in the hippocampus. Bee pollen extract (100 or 300 mg/kg, per os (p.o.)) obviously reversed scopolamine-caused cognitive impairment in the passive avoidance test, ameliorated spontaneous alternation versus the scopolamine-treated group in the Y-maze test and prolonged swimming time in the target zone in the Morris water maze test. In addition, the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), protein kinase B (Akt) and glycogen synthase kinase-3ß (GSK-3ß), and the expression levels of brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) in the hippocampi, were increased in response to the treatment with bee pollen extract (100 or 300 mg/kg, p.o.). These results indicated that bee pollen ameliorates cognitive impairment induced by cholinergic blockade through the enhancing conversion of proBDNF to mature BDNF by tPA, probably, through the ERK-CREB pathway or Akt-GSK-3ß signaling pathway and would be a useful agent for the treatment of cognitive dysfunction.

Ethanolic Extract of Opuntia ficus-indica var. saboten Ameliorates Cognitive Dysfunction Induced by Cholinergic Blockade in Mice.

The stem of Opuntia ficus-indica var. saboten is edible and has been used as a medicinal herb on Jeju Island in Korea. We previously reported that the butanolic extract of O. ficus-indica var. saboten exerts the enhancement of long-term memory in mice. However, the antiamnesic effects of O. ficus-indica var. saboten and its mode of action has not been clearly elucidated. In the present study, we explored the effects of the ethanolic extract of stems of O. ficus-indica var. saboten (EOFS) on cognitive performance in mouse and attempted to delineate its mechanism of action. We used the passive avoidance, Y-maze, and novel object recognition tests to assess its effects on cognitive functions in scopolamine-induced memory-impaired mice. We observed that EOFS (100, 200, and 400 mg/kg) ameliorated scopolamine-induced cognitive dysfunction. We also explored its mechanism of action by conducting an acetylcholinesterase (AChE) activity assay using the mouse whole brain and Western blot using the mouse hippocampal tissue. Western blot analysis and the ex vivo study revealed that EOFS increased the levels of phosphorylated extracellular signal-regulated kinase and cAMP response element-binding protein (CREB) and the levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. It also inhibited AChE activity in the brain. Our findings suggest that EOFS would be useful for the treatment of cholinergic blockade-induced cognitive dysfunction.

Small Rice Bowl-Based Meal Plan versus Food Exchange-Based Meal Plan for Weight, Glucose and Lipid Control in Obese Type 2 Diabetic Patients.

BACKGROUND: The Korean National Health and Nutrition Examination Surveys reported 65% of daily energy intake (EI) as carbohydrate (CHO) in the Korean population and main source of CHO was cooked rice. We used a standardized-small sized rice bowl for diet education and investigated its effectiveness on body weight, glucose and lipid, compared to the conventional food exchange system in type 2 diabetes obese women. METHODS: Type 2 diabetic women with body mass index >/= 23 kg/m(2) were randomly assigned to small rice bowl-based meal plan (BM) and food exchange-based meal plan (ExM) group. Both groups were asked to reduce their EI by 500 kcal/day for 12 weeks. The macronutrient composition was instructed: 55 to 60% of EI as CHO, 15 to 20% as protein, and 20 to 25% as fat. BM group received only a simple instruction for application of the rice bowl. Nutrient intake was estimated with the 3-day dietary records. RESULTS: Finally, 44 subjects finished the study. The percent reduction of body weight was significant both BM group (-5.1 +/- 2.6%) and ExM group (-4.8 +/- 2.8%) after 12 weeks (P < 0.001) but there was no difference between the groups. There was no difference in the proportional change of CHO, protein and fat in EI between the groups. Additionally, the change of HbA1c and low density lipoprotein-cholesterol were not significantly different between the two groups. CONCLUSION: The BM group was as effective as ExM for body weight and glucose control in type 2 diabetes obese women.

The effects of resistance training on muscle and body fat mass and muscle strength in type 2 diabetic women.

BACKGROUND: Our goal was to investigate the effects of low intensity resistance training on body fat, muscle mass and strength, cardiovascular fitness, and insulin sensitivity in type 2 diabetes. METHODS: Twenty-eight overweight women with type 2 diabetes were randomly assigned to a resistance training group (RG, n = 13) or a control group (CG, n = 15). RG performed resistance training using elastic bands, of which strength was equal to 40 to 50% of one repetition maximum (1RM), for three days per week. Each exercise consisted of three sets for 60 minutes. We assessed abdominal fat using computed tomography, muscle mass using dual-energy X-ray absorptiometry, and muscle strength using Keiser's chest and leg press. Insulin sensitivity was measured using the insulin tolerance test, and aerobic capacity was expressed as oxygen uptake at the anaerobic threshold (AT-VO(2)) before and after the 12-week exercise program. RESULTS: The age of participants was 56.4 +/- 7.1 years, duration of diabetes was 5.9 +/- 5.5 years, and BMI was 27.4 +/- 2.5 kg/m(2), without significant differences between two groups. During intervention, a greater increase in muscle mass and greater decreases in both total fat mass and abdominal fat were observed in RG compared to those of CG (P = 0.015, P = 0.011, P = 0.010, respectively). Increase in 1RM of upper and lower extremities was observed in the RG (P = 0.004, P = 0.040, respectively), without changes in AT-VO(2) and insulin resistance in either group. CONCLUSION: In conclusion, the low intensity resistance training was effective in increasing muscle mass and strength and reducing total fat mass without change of insulin sensitivity in type 2 diabetic patients.