Treadmill training attenuate STZ-induced cognitive dysfunction in type 2 diabetic rats via modulating Grb10/IGF-R signaling.

Type 2 diabetes is a major factor contributing to cognitive decline and Alzheimer's disease (AD). Treadmill running is considered to be a critical approach for mice and rats to lower blood sugar and improve learning and memory capacity. The growth factor receptor-bound protein 10 (Grb10) has been proposed to inhibit insulin signaling and defective brain insulin signaling resulted in the cognitive deficits in patients with AD. However, the positive roles of treadmill training on diabetic- related impaired cognitive function and their molecular mechanisms remain unclear. Here, to investigate whether there was neuroprotective effects of treadmill training on impaired cognitive function caused by diabetes, the rats were injected intraperitoneally with streptozotocin at a dose of 30 mg/kg to establish diabetic model (DM). We found that higher Grb10, BACE1 and PHF10 protein levels in the hippocampus of DM rats, lower phosphorylation IGF-1Rß and IRS-1(ser307). However, 8 weeks treadmill training effectively reduced abnormal Grb10, enhanced postsynaptic density protein PSD-93, PSD-95, SYN expressions of hippocampus, restored PI3K/Akt/ERK and mTOR/AMPK signaling, thus alleviated spatial learning and memory deficit, compared with DM group. Additionally, treadmill training also increased GLUT4 transportation. Overall, our findings suggest that treadmill intervention improved cognitive impairments caused by diabetes disease partly through modulating Grb10/ PI3K/Akt/ERK as well as mTOR/AMPK signaling.

Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury.

To observe the changes in NLR family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of diabetes-induced lung injury, and investigate the effect of low-dose ethanol on the production of NLRP3 inflammasome. The type I diabetic mellitus (DM) rat model was established, and the rats were divided into four groups: normal control group (CON group), low-dose ethanol group (EtOH group), diabetes group (DM group) and DM+EtOH group. The rats were fed for 6 and 12 weeks, respectively. The ratio of lung wet weight/body weight (lung/body coefficient) was calculated, and the changes of pulmonary morphology and fibrosis were observed by HE and Masson staining. The changes in pulmonary ultra-structure were examined by electron microscopy. The expressions of mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) and NLRP3 inflammasome key factors, NLRP3, ASC and caspase-1 proteins were detected by western blot. Compared with the CON group, the lung/body coefficient was increased (P<0.05), lung fibrosis occurred, ALDH2 protein expression was decreased, and NLRP3, ASC and caspase-1 protein expressions were increased in the DM rats (P<0.05). Compared with the DM group, the lung/body coefficient and fibrosis degree were decreased, ALDH2 protein expression was increased (P<0.05), and NLRP3, ASC and caspase-1 protein expressions were decreased in the DM+EtOH group (P<0.05). Hence, low-dose ethanol increased ALDH2 protein expression and alleviated diabetes-induced lung injury by inhibiting the production of NLRP3 inflammasome.

Long-term treatment of polysaccharides-based hydrogel microparticles as oral insulin delivery in streptozotocin-induced type 2 diabetic mice.

To develop a more effective and safer drug for the treatment of type 2 diabetes mellitus (T2DM), polysaccharides-based hydrogel microparticles as oral insulin delivery was prepared and explored. This study was aimed to evaluate the antidiabetic effects and hypoglycemic mechanism with long-term administration(four weeks) of oral insulin hydrogel microparticles in type 2 diabetic mice on a model of diabetes using a high fat diet combined with streptozotocin. The results revealed that the long-term treatment of oral insulin polysaccharides-based hydrogel microparticles could significantly alleviate the symptoms of polyphagia, polydipsia, polyuria and weight loss in diabetic mice. Also, oral administration of insulin hydrogel microparticles could significantly reduce fasting blood glucose levels, ameliorate insulin resistance and increase insulin sensitivity in the mice with T2DM. The concentration of plasma TG, TC, LDL-C, FFA, BUN, CRE significantly decreased and the levels of HDL-C increased showed that insulin polysaccharides-based hydrogel microparticles were effective in regulating lipid metabolism and prevent diabetic nephropathy complication in diabetic mice. In addition, the supplementation of insulin hydrogel microparticles could significant improve the antioxidant capacity by increasing the level of SOD, CAT and decreasing the level of MDA, GPT, NO, TNF-α, and reverse histological deterioration of kidney and pancreas in diabetic mice. The above outcome concluded that insulin polysaccharides-based hydrogel microparticles may exhibit promising anti-diabetic activity and the potential to be a drug candidate for T2DM.

Diabetes: an Overview for Clinical Oncologists.

Diabetes and cancer are common conditions highly prevalent in the general population. The co-existence of diabetes and cancer in a patient is therefore not unexpected. Diabetes increases the risk of mortality from cancer and morbidity from the treatment of cancer. Furthermore, many cancer chemotherapeutic regimens increase glucose levels, especially those involving glucocorticoids. Many clinical oncologists will deal with patients with diabetes in their clinical work, and some working knowledge of diabetes diagnosis and management is helpful when managing such patients. This overview aims to summarise the clinical diagnosis and management of diabetes, review the potential links between diabetes and cancer, and provide some practical guidance on the management of hyperglycaemia in patients undergoing cancer therapy.

Study design choices for evaluating the comparative safety of diabetes medications: An evaluation of pioglitazone use and risk of bladder cancer in older US adults with type-2 diabetes.

AIM: The aim of the study was to empirically demonstrate the effect of varying study designs when evaluating the safety of pioglitazone in treating bladder cancer. METHODS: We identified Medicare beneficiaries above 65 years of age with diabetes between 2008 and 2015 and with classified exposure (at least two claims within 180 days) to glucose-lowering drugs (GLD), pioglitazone or another drug. The effects of varying the following study design parameters on bladder cancer risk were assessed: use of a new vs existing drug, choice of referent (all non-users and users of GLDs, non-insulin GLDs and DPP-4s) and whether or not censoring accounted for treatment change. We used the Cox proportional hazards model to obtain adjusted HRs and 95% CIs. RESULTS: We included 1,510,212 patients classified as pioglitazone users (N = 135,188) or non-users (N = 1,375,024). Users had more diabetic complications than non-users, but fewer than insulin users. The HR ranged from 1.10 (1.01-1.20) to 1.13 (0.99-1.29) when censoring ignored treatment change, suggesting a weak association or none between pioglitazone and bladder cancer, probably under-estimating risk. However, the HR was 1.20 (1.01-1.42) when cohorts were restricted to new users, censored upon treatment change, and when DPP-4 was used as the referent, suggesting an increased risk of bladder cancer associated with pioglitazone. CONCLUSIONS: The continued demand for new GLDs indicates the need for more robust observational methods to improve the value of generating real-world evidence in equipping clinicians to make informed prescribing decisions. Although there is no one-size-fits-all approach, we recommend active comparator new user study designs that compare therapeutically equivalent drugs and account for treatment changes during follow-up to present the least biased comparative safety estimates.

A long noncoding RNA LOC103690121 promotes hippocampus neuronal apoptosis in streptozotocin-induced type 1 diabetes.

Diabetes related cognitive impairment is a severe complication. The diabetes-induced cognitive impairment is associated with insulin resistance and glucose-induced neuron apoptosis in the brain. We intended to investigate the association of long non-coding RNAs with diabetes-induced cognitive impairment in rats. Here, Type 1diabetes (T1D) rat model was induced using streptozotocin (STZ). The diabetic rats showed significant cognitive dysfunction, with increased latency period to find the hidden platform during morris water maze test. The brain injury and reduced neuronsin STZ-induced diabetic rats was determined using hematoxylin and eosin staining and Nissl's staining. We performed the LncRNA microarray analysis and identified 101 differentially expressed lncRNAs in streptozotocin (STZ)-induced type 1 diabetes (T1D) comparing with control. Among these lncRNA, LOC103690121 was upregulated. in vitro glucose treatment in hippocampal neurons showed LOC103690121 and neuron apoptosis was increased by glucose treatment. Transfection experiments showed LOC103690121 overexpression promoted neuron apoptosis, and its inhibition suppressed glucose-induced apoptosis. Western blot analysis showed that the expression profiles of apoptosis related proteins (cleaved-caspase-3, -8, -9, and Bax) were in line with LOC103690121 expression, while the profiles of Bcl-2 and PI3K/Akt signaling pathway was contrast to LOC103690121 expression. In conclusion, the results of our study confirmed lncRNA LOC103690121 promoted STZ-induced cognitive impairment in diabetic rats by promoting neuron apoptosis through PI3K/Akt signaling pathway.

Inhibitory effect of valproate sodium on pain behavior in diabetic mice involves suppression of spinal histone deacetylase 1 and inflammatory mediators.

Anti-epileptic medications are included in the international guidelines for managing neuropathic pain. Valproate sodium (VPS) was recently described as "the forgotten analgesic" and has been reported to relief pain in various models of neuropathic pain. Some studies reported anti-inflammatory and histone deacetylase 1 (HDA1) inhibitory properties for sodium valproate. The aim of the current study was to investigate the modulatory effect of VPS on pain behavior and inflammatory reactions in alloxan-induced diabetic neuropathy focusing on HDA1 inhibition and glia reactivity. 28 Male Swiss albino mice were allocated into four groups, (1) vehicle group, (2) alloxan-diabetic group, (3 & 4) alloxan+VPS (25 or 50 mg/kg) groups. VPS was given daily for 5 weeks by oral gavage. Pain behavior demonstrated increased allodynia (von-Frey filaments) and hyperalgesia (hot-plate test) in alloxan-diabetic mice that was reduced significantly by at least one of VPS doses. Sciatic nerves in diabetic mice showed increased histopathology score, increased silver staining for the nerves-indicating myelopathy- and a decrease in immunostaining for nerve growth factor. Spinal cord of diabetic mice showed greater histopathologic score, increased CD11b and glia fibrillary acidic protein (GFAP) immunostaining than vehicle treated mice. Molecular investigations highlighted greater content of spinal histone deacetylases, tumor necrosis factor-α (TNF-α) and interlukin-1ß (IL1ß) that were favorably modified by VPS. Overall, the current data confirmed that the pain killing and anti-inflammatory activity of VPS is at least partly mediated through inhibition of spinal HDA1 and glia reactivity. These findings support the view of inviting antiepileptics for treating neuropathies.

"Dangerous duo": Chronic nicotine exposure intensifies diabetes mellitus-related deterioration in bone microstructure - An experimental study in rats.

AIMS: Bony complications of diabetes mellitus (DM) are still insufficiently understood. Our aims were to analyze the individual and combined effects of chronic hyperglycemia and nicotine exposure on the femoral trabecular and cortical microarchitecture on a rat experimental model. MAIN METHODS: The micro-computed tomography based bone microstructural evaluation was performed on male Wistar rats divided into four groups: control (n = 7), experimentally-induced DM (n = 8), chronically exposed to nicotine (n = 9) and the DM group exposed chronically to nicotine (n = 9). KEY FINDINGS: Chronic hyperglycemia caused mild trabecular deterioration; yet, the combination of hyperglycemia and nicotine exposure showed more deleterious effects on the trabecular bone. Namely, the DM + nicotine group had significantly lower bone volume fraction, fewer and more rod-like shaped trabeculae, along with higher trabecular separation and lower connectivity than the control group (p < 0.05). Nicotine alone did not show any significant deterioration compared to the control group. DM and DM + nicotine groups had lower cortical porosity than control and nicotine groups (p < 0.05). Cortical thickness did not show any significant intergroup differences, whereas bone perimeter and the mean polar moment of inertia were reduced in DM + nicotine group. SIGNIFICANCE: Mild effects of chronic hyperglycemia on bone structure were accentuated by the chronic nicotine exposure, although nicotine alone did not cause any significant bone changes. That suggests a synergistic effect of hyperglycemia and nicotine on bone deterioration and increased propensity to fracture. Indeed, better understanding of risk factors driving bone structural deterioration is a precondition to limit the complications associated with DM.

Pathological lesions and global DNA methylation in rat prostate under streptozotocin-induced diabetes and melatonin supplementation.

Chronic hyperglycemia increases production of reactive oxygen species, which favors carcinogenesis. The association between diabetes and prostate cancer is controversial. Melatonin has antioxidant, anti-inflammatory, and antiproliferative properties. We investigated whether low doses of melatonin prevent the tissue alterations caused by diabetes and alter prostate histology of healthy rats. We also investigated whether experimental diabetes promoted the development of pathological lesions in the ventral prostate of rats. Melatonin was provided in drinking water (10 µg/kg/day) from age 5 weeks until the end of experiment. Diabetes was induced at 13 weeks by administration of streptozotocin (40 mg/kg, ip). Rats were euthanized at 14 or 21 weeks. Histological and stereological analyses were carried out and the incidence and density of malignant and pre-malignant lesions were assessed. Immunohistochemical assays of α-actin, cell proliferation (PCNA), Bcl-2, glutathione S-transferase (GSTPI), and DNA methylation (5-methylcytidine) were performed. Melatonin did not elicit conspicuous changes in the prostate of healthy animals; in diabetic animals there was a higher incidence of atrophy (93%), microinvasive carcinoma (10%), proliferative inflammatory atrophy, PIA (13%), prostatitis (26%), and prostate intraepithelial neoplasia, PIN (20%) associated with an increase of 40% in global DNA methylation. Melatonin attenuated epithelial and smooth muscle cell (smc) atrophy, especially at short-term diabetes-and normalized incidence of PIN (11%), inflammatory cells infiltrates, prostatitis (0%) and PIA (0%) at long-term diabetes. MLT was effective in preventing inflammatory disorders and PIN under diabetic condition. Although MLT has antioxidant action, it did not influence DNA methylation and not avoid carcinogenesis at low doses.

Effect of intra-operative single dose of dexamethasone for control of post-operative nausea and vomiting on the control of glucose levels in diabetic patients.

BACKGROUND: Dexamethasone adds a unique challenge to glycemic control, and it may complicate patient care if there is an association between intra-operative dexamethasone and blood glucose levels. METHODS: We analyzed 396 diabetic patients who underwent general anesthesia for various surgical procedures and were hospitalized post-operatively for at least 24 h between January 2015 and June 2016. Patients were classified into two groups-those who received dexamethasone intra-operatively and those who did not. The groups were analyzed for blood glucose changes during and following their procedure. RESULTS: A total of 396 diabetic patients (152 (38.8%) dexamethasone group; 244 (62.2%) control) were included. The dexamethasone group had significantly lower preoperative blood glucose (135.5 mmol/L) compared to the control group (144.4 mmol/L) (p = 0.04) and significantly lower proportion of patients who had received insulin during surgery (14.9%) compared to the control group (23.4%) (p = 0.04). Overall, glucose levels declined from pre-op to post-op day 1 by 9.6 (62.9) (p = 0.007). CONCLUSION: Diabetic patients receiving dexamethasone for control of post-operative nausea during surgery are at greater risk for increasing blood glucose levels and difficult glycemic control during and after surgery compared to patients receiving other medications to control post-operative nausea.

Adverse glycaemic effects of cancer therapy: indications for a rational approach to cancer patients with diabetes.

Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies have reported an increased risk of cancer in patients with diabetes. Furthermore, many patients with cancer already have diabetes, or develop hyperglycaemia as a consequence of the tumor or of cancer therapies, and coexisting diabetes confers a greater risk of mortality for many malignancies. Managing oncologic patients with diabetes is often complicated, since the co-existence of diabetes and cancer poses several complex clinical questions: what level of glycaemic control to achieve, which therapy to use, how to deal with glucocorticoid therapies and artificial nutrition, how diabetes complications can affect cancer management, which drug-drug interactions should be taken into account, or even how to manage diabetes at the end of life. In the clinical setting, both at hospital and at home, there are little agreed, evidence-based guidelines on the best management and criteria upon which clinical decisions should be based. A practical solution lies in the implementation of care networks based on communication and ongoing collaboration between Oncologists, Endocrinologists, and the nursing staff, with the patient at the centre of the care process. This manuscript aims to review the current evidence on the effect of cancer therapies on glucose metabolism and to address some of the more common challenges of diabetes treatment in patients with cancer.

Resveratrol inhibits hyperglycemia-driven ROS-induced invasion and migration of pancreatic cancer cells via suppression of the ERK and p38 MAPK signaling pathways.

Increasing evidence suggests that there is a strong relationship between diabetes mellitus (DM) and pancreatic cancer. Our previous study revealed that hyperglycemia could enhance the invasive and migratory activities of pancreatic cancer cells. Resveratrol, a natural polyphenolic phytoalexin, has many biological and pharmaceutical properties, including antioxidant and anti-tumorigenic capabilities. The aim of the present study was to evaluate whether resveratrol affects hyperglycemia-induced reactive oxygen species (ROS) production as well as the invasion and migration of pancreatic cancer and its underlying mechanisms. Human pancreatic cancer Panc-1 cells were exposed to high glucose condition with or without resveratrol, N-acetylcysteine (NAC, a scavenger of free radicals), PD 98059 (an ERK inhibitor) or SB 203580 (a p38 MAPK inhibitor). The intracellular ROS and hydrogen peroxide (H2O2) were determined using 2,7-dichlorodihydrofluorecein diacetate and H2O2 assay. MTT, wound healing assay and transwell matrigel invasion assay were used to detect the proliferation, migration and invasion potential of cancer cells. The expressions of uPA, E-cadherin and Glut-1 were examined using QT-PCR and western blot analysis at mRNA and protein levels. The activation of p-ERK, p-p38 and p-NF-κB were measured by western blot analysis. The results of the present study showed that resveratrol could significantly decrease high glucose-induced production of ROS and H2O2 in Panc-1 cells. Resveratrol was also able to inhibit high glucose-induced proliferation, migration and invasion of pancreatic cancer cells. High glucose-modulated expression of uPA, E-cadherin and Glut-1 were inhibited by resveratrol. In addition, high glucose-induced activation of ERK and p38 MAPK signaling pathways as well as the transcription factor NF-κB could also be suppressed by resveratrol. Furthermore, resveratrol was able to suppress H2O2-induced migration and invasion abilities of pancreatic cancer cells. Taken together, these data indicate that resveratrol plays an important role in suppressing hyperglycemia-driven ROS-induced pancreatic cancer progression by inhibiting the ERK and p38 MAPK signaling pathways, providing evidence that resveratrol might be a potential candidate for chemoprevention of pancreatic cancer.

Androgen deprivation therapy is associated with diabetes: Evidence from meta-analysis.

AIMS/INTRODUCTION: There is still no obvious evidence proving that androgen deprivation therapy (ADT) would increase the risk of diabetes. To determine if ADT is associated with diabetes in men with prostate cancer, we carried out the present study. MATERIALS AND METHODS: We systematically searched Medline, Embase and the Cochrane Library Central Register through 2014. Studies comparing ADT vs control aimed at treating prostate cancer reporting diabetes as outcome were included. Data were extracted independently by two reviewers. This meta-analysis was reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses checklist. Observational studies were evaluated through the Meta-analysis Of Observational Studies in Epidemiology checklist. RESULTS: Eight studies were identified with 65,695 ADT users and 91,893 non-ADT users. The pooled incidence of diabetes was 39% higher in ADT groups. A significant association was observed in the overall analysis (risk ratio [RR] 1.39, 95% confidence interval [CI] 1.27-1.53; P < 0.001). In subgroup analyses, diabetes was found to be significantly associated with gonadotropin-releasing hormone (GnRH) alone (RR 1.45, 95% CI 1.36-1.54; P < 0.001), GnRH plus oral antiandrogen (RR 1.40, 95% CI 1.01-1.93; P = 0.04) and orchiectomy (RR 1.34, 95% CI 1.20-1.50; P < 0.001), but not with antiandrogen alone (RR 1.33, 95% CI 0.75-2.36; P = 0.33). Diabetes was strongly related to long duration of ADT (RR 1.43, 95% CI 1.22-1.68; P < 0.001), and was slightly associated with short duration of ADT (RR 1.29, 95% CI 1.12-1.49; P = 0.0004). CONCLUSIONS: ADT, especially long duration (>6 months) of this treatment, GnRH alone, GnRH plus antiandrogen and orchiectomy can increase the incidence of diabetes.

Comparative Study of the Antioxidant Effects of Metformin, Glibenclamide, and Repaglinide in Alloxan-Induced Diabetic Rats.

Diabetes mellitus is one of the serious global health problems affecting a significant proportion of both developed and developing countries. Overproduction of free radicals and oxidative stress has been associated with the development of diabetic complications. In the present study, the antioxidant effects of metformin (MET), glibenclamide (GLI), and repaglinide (REP) were evaluated in alloxan-induced diabetic rats. The findings from this study may possibly help in understanding the efficacy of these standard drugs in managing the complications arising from diabetes mellitus (DM). Alloxan (130 mg/kg BW) was administered as a single dose to induce diabetes. Four (4) groups of rats (n = 6) were used; group 1 served as diabetic control while groups 2, 3, and 4 were the diabetic test groups that received MET (25 mg/kg), GLI (2.5 mg/kg), and REP (0.5 mg/kg), respectively. The result of the study showed significant (p < 0.05) improvement in the altered antioxidant enzymes (SOD, CAT) and GSH concentration in diabetic treated rats compared with the diabetic control group. MET and REP produced significant effect on the MDA concentration while GLI showed insignificant reduction in the MDA concentration compared with the diabetic control. Findings from this study suggest that the administration of MET, GLI, and REP exerts significant antioxidant effects in alloxan-induced diabetic rats, thus contributing to the protective effect against oxidative stress-induced damage during diabetic complications.

Expression of SIRT1 and oxidative stress in diabetic dry eye.

OBJECTIVE: To explore the expression of SIRT1 with oxidative stress and observe physiological and pathological changes in the corneas as well as the association between SIRT1 and oxidative stress of diabetic dry eyes in mice. METHOD: Forty-eight C57BL/6Jdb/db mice at eight weeks of age were divided randomly into two groups: the diabetic dry eye group and the diabetic group. An additional forty-eight C57BL/6J mice at eight weeks of age were divided randomly into two groups: the dry eye group and the control group. Every mouse in the dry eye groups (diabetic and normal) was injected with scopolamine hydrobromide three times daily, combined with low humidity to establish a dry eye model. After the intervention, phenol red cotton string tests and corneal fluorescein staining were performed. In addition, HE staining and immunofluorescence were done. Expression of SIRT1 in the cornea was examined by real-time PCR and Western Blot and expression of FOXO3 and MnSOD proteins was detected by Western Blot. RESULTS: At one, four, and eight weeks post intervention, all of the groups except the controls showed significant decreases in tear production and increases in the corneal fluorescein stain (P<0.05 vs control). Between the experimental groups, the diabetic dry eye group had the least tear production and the highest corneal fluorescein stain score (P<0.05). As the disease progressed, all of the experimental groups showed obviously pathological changes in HE staining, particularly the diabetic dry eye group. In the 1(st) and 4(th) week, the expression of SIRT1, FOXO3, and MnSOD were significantly higher in the diabetic DE and DM groups but lower in the DE group compared to the controls (P<0.05). In the 8(th) week, the expression of SIRT1, FOXO3, and MnSOD was significantly down-regulated in the diabetic DE group and the DM group (P<0.05). Immunofluorescence showed similar results. CONCLUSION: In the condition of diabetic dry eye, tear production declined markedly coupled with seriously wounded corneal epithelium. Oxidative stress in the cornea was enhanced significantly and the expression of SIRT1 was decreased.

Association between comorbidities and dementia in diabetes mellitus patients: population-based retrospective cohort study.

AIMS: Most diabetes mellitus (DM) patients have several comorbidities; the correlation of these comorbidities with dementia in DM requires clarification. METHODS: Using claims data from Taiwan National Health Insurance, we identified 33,709 DM adults before the year 2000 and randomly selected 67,066 non-DM patients matched by sex and age. Subjects were followed until diagnosis with dementia, excluded due to death/withdrawal from the insurance program, or followed until 2011. We compared the incidence and hazard ratio (HR) for dementia in both cohorts. RESULTS: Comorbidities were more prevalent in DM patients, including hypertension, hyperlipidemia, stroke, coronary artery and/or kidney disease. The HR was higher for the DM cohort with comorbidities than those without: 1.88 vs. 1.46 with hypertension; 1.56 vs. 1.39 with hyperlipidemia; 1.73 vs. 1.37 with coronary artery disease; 2.36 vs. 2.29 with stroke and 1.88 vs. 1.50 with kidney disease. The HR for dementia in diabetics rose from 1.41 in those without comorbidities to 2.49 in those with ≥4 comorbidities. In the DM cohort, HR was 1.22 for non-insulin-users and 1.41 for insulin-users, and 1.49 for type 1 DM and 1.23 for type 2 DM. CONCLUSION: Diabetic patients have an elevated risk of dementia, and comorbidity increases this risk.

[Effect of moxibustion with ignited Zhuang-medicine medicated-thread on interstitial cells of Cajal in gastric antrum in diabetic gastroparesis rats].

OBJECTIVE: To observe the effect of Zhuang-medicine medicated-thread moxibustion therapy on interstitial cells of Cajal (ICC) in the gastric antrum of diabetic gastroparesis (DGP) rats, so as to investigate its mechanism underlying improving DGP. METHODS: Sprague-Dawley (SD) male rats were randomly divided into 3 groups: control (n = 30) , model (n = 30) and moxibustion (n = 30). The DGP model was established by intraperitoneal injection of streptozotocin (STZ) and by feeding the rats with high fat-sugar forage. Zhuang-medicine medicated-thread moxibustion was applied to "Zhongwan" (CV 12), bilateral "Pishu" (BL 20), "Weishu" (BL 21), "Neiguan" (PC 6) and "Zusanli" (ST 36) once per day, for 3 weeks except weekends. The gastrointestinal propulsion rate and weight of stool in 24 h were determined, and c-kit (a marker for ICC) expression of the gastric antrum tissue was measured by immunohistochemistry. RESULTS: The stool weight was significantly higher in the model group than in the control group (P < 0.01), but the rate of gastrointestinal propulsion and the rate of c-kit immunoreaction (IR) positive cells in the gastric antrum tissue were significantly lower in the model group than in the control group (P < 0.01). After moxibustion, the increased stool weight and the decreased gastrointestinal propulsion rate and decreased c-kit IR-positive cell rate were reversed (P < 0.01). CONCLUSION: Zhuang-medicine medicated-thread moxibustion therapy can improve gastrointestinal function in DGP rats, which may be associated with its effect in up-regulating the expression of c-kit IR-positive ICC.

Retrospective review of the incidence of monitoring blood glucose levels in patients receiving corticosteroids with systemic anticancer therapy.

BACKGROUND: Corticosteroids are used adjuvant to certain chemotherapy regimens, either as an antiemetic, to reduce other side effects, or to enhance cancer treatment. Additionally, they are frequently used for symptom control in cancer patients with end stage disease. Corticosteroid use may induce hyperglycemia in approximately 20-50% of patients, which may negatively affect patient outcomes. OBJECTIVE: To determine the frequency of blood glucose monitoring in patients with and without diabetes receiving continuous corticosteroids with chemotherapy, and to determine the incidence of treatment-emergent abnormal blood glucose levels and steroid-induced diabetes mellitus (DM). METHODS: A retrospective review was conducted for 30 genitourinary (GU) cancer patients who were treated with continuous oral corticosteroids as part of their chemotherapy regimen. The Canadian Diabetes Association (CDA) criterion for diagnosis of diabetes was applied to categorize patients into two distinct groups, patients with diabetes and patients without diabetes. This categorization was made based on glucose measurements completed prior to commencement of corticosteroid therapy. Glucose monitoring was defined as receiving a laboratory blood glucose test before first chemotherapy administration along with a test within a week of each subsequent treatment cycle. The CDA criteria for diagnosis of pre-diabetes and diabetes was used to classify glucose levels as hyperglycemic. RESULTS: The mean incidence of blood glucose monitoring was 19% and 76% in patients with diabetes and patients without diabetes, respectively. Approximately, 40% of patients with diabetes required an adjustment to their diabetes management and a further 20% required hospitalization. Fifteen patients without diabetes received a fasting blood glucose test, of which 40% had abnormal blood glucose results; half of these fell into the pre-diabetic range and half in the diabetic range. Ten patients without diabetes were tested for diabetes using the CDA criteria for diabetes diagnosis during or after their chemotherapy, of which 30% developed diabetes. CONCLUSIONS: In order to optimize patient care, blood glucose levels should be monitored in all patients receiving continuous oral corticosteroids as part of their chemotherapy. Future studies should be conducted prospectively to determine the most effective manner of monitoring in order to implement screening guidelines and avoid unnecessary morbidity.

Insulin priming effect on estradiol-induced breast cancer metabolism and growth.

Diabetes is a risk factor for breast cancer development and is associated with poor prognosis for breast cancer patients. However, the molecular and biochemical mechanisms underlying the association between diabetes and breast cancer have not been fully elucidated. Here, we investigated estradiol response in MCF-7 breast cancer cells with or without chronic exposure to insulin. We found that insulin priming is necessary and specific for estradiol-induced cancer cell growth, and induces anaplerotic shunting of glucose into macromolecule biosynthesis in the estradiol treated cells. Treatment with ERK or Akt specific inhibitors, U0126 or LY294002, respectively, suppressed estradiol-induced growth. Interestingly, molecular analysis revealed that estradiol treatment markedly increases expression of cyclin A and B, and decreases p21 and p27 in the insulin-primed cells. In addition, estradiol treatment activated metabolic genes in pentose phosphate (PPP) and serine biosynthesis pathways in the insulin-primed cells while insulin priming decreased metabolic gene expression associated with glucose catabolism in the breast cancer cells. Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells. These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.