Decrease In Blood Glucose Concentration Research Articles

The Acute Effects of Exercise Intensity on Blood Glucose Levels in Type 1 Diabetics

For individuals with Type 1 diabetes mellitus (T1DM), regular physical activity is a fundamental strategy in the management of glycemic control. Previous studies have shown that continuous, moderate-intensity exercise in individuals with T1DM decreases blood glucose concentrations, often resulting in hypoglycemia, whereas vigorous-intensity exercise can increase blood glucose, impacting the risk of hyperglycemia. Sprint interval training (SIT), characterized by brief, all-out bursts of supramaximal exercise, has been shown to improve indices of cardiometabolic health, despite a minimal time commitment. However, the effects of low volume SIT on individuals with T1DM is largely unknown. PURPOSE: to contrast the acute effects of exercise intensity on blood glucose levels in Type 1 diabetics. METHODS: Four recreationally active college- age students with T1DM, completed a treadmill test to determine maximal aerobic speed (MAS), and performed each of the following 20-min treadmill-based protocols: 1) Moderate-intensity continuous training (MICT): 5-min warm-up (WU), 10 minutes at 70% MAS, 5-min cool-down (CD); 2) high-intensity interval training (HIIT): 5-min WU, 1-min at 90% MAS, 1-min at 30% MAS repeated 5 times, 5-min CD; 3) SIT: 5-min WU, 30-sec at 120% MAS, 2-min, 50-sec at 30% MAS repeated 3 times, 5-min CD. Blood glucose was monitored via glucometer every 5-min during exercise and for 45-min after. RESULTS: A statistically significant decline in blood glucose was observed in both the MICT and HIIT conditions (p <0.001, respectively) but not in the SIT condition (p = 0.696). From baseline to the 45-min mark, blood glucose decreased by 27% in both the MICT (180 ± 27 to 132 ± 39) and HIIT (183 ± 29 to 132 ± 15) protocols, but only 11% in the SIT (193 ± 41 to 165 ± 70) protocol. CONCLUSIONS: The results of this study provide initial proof-of-concept that a low volume SIT protocol can maintain target blood glucose levels while exercising in individuals with T1DM.

HYPOGLYCEMIC AND LIPID LOWERING EFFECT OF AQUEOUS FRESH LEAF EXTRACT OF CHROMOLAENA ODORATA (LINN) IN ALBINO WISTAR RATS FED DIFFERENT CONCENTRATIONS OF CHOLESTEROL ENRICHED DIET

Objectives: High lipids and carbohydrate have been seriously implicated to cardiovascular problems, which has led to several uses of medicinal plants for traditional remedies. The present study investigated the lipid lowering activity of fresh leaf extract of Chromolaena odorata in Albino wistar rats. Methods: Twenty (20) rats used for the study were grouped into four groups of five (5) rats each. Group I served as normal control, group II, III and IV served as test groups, fed 75, 108 and 148 g of cholesterol enriched diet for one week and thereafter, administered with 50, 100 and 150 mg/kg body weight of fresh leaf extract of Chromolaena odorata respectively for four (4) days. Lipid profile and blood glucose were assayed at fed state and after administration. Results showed a significant (p<0.05) increase in total cholesterol, triacylglycerol, low density lipoprotein, blood glucose concentration and body weight compared with control group in fed state. Results: Administration with fresh leaf extract of Chromolaena odorata showed a significant (p<0.05) increase in high density lipoprotein, significant (p<0.05) decrease in blood glucose concentration, low density lipoproteins, triacylglycerol, total cholesterol and body weight of rats. The oral treatment with 50, 100 and 150 mg/kg body weight of the fresh leaf extract of this study demonstrated a general hypoglycemic and hypolipidemic activity not necessary a dose dependent pattern. Conclusion: It may therefore be concluded that the hypoglycemic and hypolipidemic activity of Chromolaena odorata taken freshly squeezed could be due to its phytochemical and antioxidants content. Peer Review History: Received 24 February 2018; Revised 3 March; Accepted 8 March, Available online 15 March 2018 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Adebayo Gege Grace Iyabo, University of Ibadan, Nigeria, funbimbola@gmail.com Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, alialkaf21@gmail.com Similar Articles: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC ACTIVITY OF DRACAENA CINNABARI BALF. RESIN ETHANOLIC EXTRACT OF SOQATRA ISLAND IN EXPERIMENTAL ANIMALS This article has been cited by: Ndife, Joel et al. “Development and comparative evaluation of green and black tisanes using scent leaves (Chromolaena odorata).” Journal of Food Science 3 (2019): 448-455. Pubmed

Star-shaped polyester-based elastomers as an implantable delivery system for insulin: Development, pharmacokinetics, pharmacodynamics, and biocompatibility

Elastomers are largely developed for biomedical applications; however, little is reported on them although they are an effective and controllable delivery system for proteins. In the present study, we investigated the pharmacokinetics, biosecurity, and hypoglycemic effect of an insulin-loaded elastomer formulation in diabetic rats. Cylindrical insulin-loaded elastomers were fabricated using a UV cross-linking process based on methyl-acrylic-star-poly(ε-caprolactone-co-D,L-lactide) cyclic ester and methyl-bi-acrylic-poly(ε-caprolactone-b-polyethylene glycol-b-ε-caprolactone) (CLPEGCLMA). The encapsulated insulin was well protected during the formulation. An in vitro pharmacokinetic study revealed that the rate of insulin release from the elastomers was affected by the hydrophilicity/hydrophobicity of the system and controlled by the CLPEGCLMA (hydrophilic prepolymer) composition. It was observed that insulin release followed the Higuchi model. In addition, the more hydrophilic elastomers showed higher degradation rates in vivo. Furthermore, in the pharmacodynamic study, all the elastomers, except those that contained star-poly(ε-caprolactone-co-D,L-lactide) (number-average molecular weight, Mn), polyethylene glycol (PEG) (kMn), ε-caprolactone/PEG (mol/mol), and CLPEGCLMA (weight, %) at a ratio of 3432:10:20:30, respectively, decreased blood glucose concentration and maintained it at a stable level. It was observed that the hypoglycemic effect of the drug-loaded elastomers was directly proportional to the rate of in vitro insulin release; however, emaciation was not observed. Moreover, elastomers play a positive role in biosecurity. Therefore, the elastomers might be effective carriers for the delivery of peptide drugs in the form of implants.

USING A DIGESTAMIN AS A FEED ADDITIVE IN EGYPTIAN BUFFALO COWS (Bubalus bubalis) DIETS

لإhis current work was performed to estimate the milk production and composition, blood parameters and some reproductive properties of Egyptian buffalo cows (Bubalus bubalis) fed a digestamin as feed additive. A total of 27 Egyptian buffalo cows were used in this study. The experimental buffaloes aged 4-8 years between the 2nd and 5th parity at late pregnancy (one month pre partum). Three main experimental basal diets were formulated from corn silage, berseem hay, rice straw and concentrate feed mixture containing 14 % CP and digestsmin was added at 0, 0.1, and 0.5% of DM, respectively. The current study showed that, increasing digestamin supplementation in buffalo cows diets increased significantly (P<0.01) average milk yield, total solids, fat, lactose, protein. On the other hand, there was a significant decrease (P<0.01) in milk total solid not fat, ash and somatic cells count by increasing digestamin supplementation to 0.5% level. Increasing digestamin levels also, significant increased (P<0.01) blood total protein, albumin and total lipids. Oppositely, there was a significant decrease (P<0.01) blood plasma globulin, glucose, AST and ALT concentration with increasing digestamin levels. The experimental diets with digestaminrecorded the higher (P<0.01) calf birth, calf birth at weaning, daily weight gain compared to other experimental diets, while the higher body weight and placenta weight of buffalo cows were obtained by control buffalo cows. Generally, there was a significant improved (P<0.01) in reproduction parameters of the experimental buffalo cows by digestamin supplementation. It could be concluded that, digestamin as a feed additive can improve the growth, productive and reproductive performance of Egyptian buffalo cows (Bubalus bubalis). So, it could be used in diets of Egyptian buffalo (Bubalus bubalis) especially with 0.5% of DM.

Protective effect of Berberis asiatica root on biochemical and histopathological changes in streptozotocin-induced diabetic Wistar rats

Background: This study was designed to evaluate the effect of Berberis asiatica root extract (BAE) against streptozotocin induced elevated blood glucose level and other liver and kidney functions changes in adult male Wistar rats.Methods: Thirty male Wistar rats were divided into five groups of six rats in each (Groups I-V). Group I and Group II served as normal control and disease control, respectively. Group III received standard anti-diabetic drug glibenclamide (5mg/kg), while Group IV and Group V received the low dose (250mg/kg) and high dose (500mg/kg) of BAE. Serum blood glucose, SGOT, SGPT, ALP, total bilirubin, BUN, serum creatinine, TC, TG, HDL-C, LDL-C, and VLDL-C were estimated using standard methods. After collection of samples for biochemical evaluation, the pancreas from each animal was isolated and examined for histological changes.Results: BAE and glibenclamide treated disease rats showed significant (p &lt;0.05) decrease in blood glucose concentration. Treatment with BAE at 250mg/kg and 500mg/kg in Group IV and V and standard drug glibenclamide in Group III showed significant (p &lt;0.05) reduction in the level of liver function substances such as SGOT, SGPT, ALP and total bilirubin as compared to disease group, as well as showed significant (p &lt;0.05) decrease in renal panel. Liver function parameters were significantly (p &lt;0.05) improved in groups treated with BAE. Histopathological analysis revealed the protective effect of BAE against streptozotocin induced damage to islets of Langerhans.Conclusions: This study showed the destruction of islets of Langerhans and elevation in blood glucose level as well as alteration in other biochemical parameters were ameliorated by the effect of Berberis asiatica extract.

Cardioprotective effects of pectin-insulin patch in streptozotocin-induced diabetic rats.

Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus. Despite the beneficial effects of subcutaneous insulin, reports suggest that the therapy itself precipitates cardiovascular risks due to the high insulin concentration administered. It is therefore necessary to seek alternative routes of insulin administration that may bypass the undesirable effects associated with high plasma insulin concentrations. Accordingly, the present study investigated the effects of a novel transdermal pectin-insulin patch on selected markers of cardiovascular function in diabetes. Pectin-insulin matrix patches (20.0, 40.8, and 82.9 μg/kg) were prepared as described previously. The three formulations were applied to streptozotocin-induced diabetic rats thrice daily. Blood glucose concentrations and mean arterial pressure (MAP) were monitored weekly for 5 weeks. Rats were then killed and blood collected for analysis of the lipid profile, cardiotropin-1, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP). The patches decreased blood glucose concentrations and diabetes-induced disturbances in lipid profile were attenuated by patch application (82.9 μg/kg). The diabetes-induced increase in MAP was also attenuated in patch (82.9 μg/kg)-treated rats. Patch treatment resulted in a decreased heart weight: body weight ratio, as well as reductions in cardiotropin-1, TNF-α, and hsCRP concentrations. Application of the pectin-insulin patch protects against the debilitating cardiovascular effects associated with conventional diabetes treatment. This suggests that the pectin-insulin patch may provide an effective alternative therapeutic approach to the commonly used subcutaneous insulin injections in the management of diabetes.

Impact of drugs on hypoglycemia in hospitalized patients

Hypoglycemia is a life-threatening condition that can be encountered during hospitalization. Several risk factors have been identified such as critical illness or general anesthesia. Drug-induced hypoglycemia is classically related to several antidiabetic drugs. However, a growing number of reports associating hypoglycemia to non-antidiabetic drugs have been published recently, suggesting that this side effect can be underreported. The aim of this study was to investigate the potential risk between prescribed drugs and hypoglycemia episode during hospitalization. Patients from a regional hospital admitted between 2013 and 2015 were analyzed. Point of care blood glucose values and prescribed drugs were extracted from electronic records. Hypoglycemia cases were defined as having at least one hypoglycemic event (random glucose value < 3.8 mmol/L) and normoglycemic cases as having all fasting glucose concentrations during hospitalization ranging between 4.5 and 5.8 mmol/L. Patients who did not meet these criteria were excluded for analysis. Cox proportional hazard models were used to assess the first event of hypoglycemia after admission. Multivariate logistic regressions were carried out to identify drugs associated with hypoglycemia. Three hundred and forty-nine patients (53% males; median age = 74 years) were included in the analysis, among them 47 (13%) had at least one hypoglycemia event and 302 (87%) were normoglycemic. No differences in age and gender were found between the two groups. Patients with a hypoglycemic event had a longer duration of hospitalization (median = 11 vs. 7 days, P < 0.01) and were more prone to polymedication than normoglycemic patients (median = 11 vs. 8 drugs, P < 0.01). One hundred and fifty-four patients (44%) had at least one antidiabetic agent, among them 58 patients (38%) had at least one drug-drug interaction (DDI) with a non-antidiabetic drug resulting to a possible decrease of blood glucose concentration. No influence of DDI on hypoglycemia rate was observed. The number of prescribed antidiabetic agents was associated with an increased risk of hypoglycemia during hospitalization (hazard ratio = 2.5, IC95 = 1.7–3.7, P < 0.01). After adjusting by gender, age and insulin use, morphine was found associated with hypoglycemia (odds-ratio = 3.0, IC95 = 1.1–8.1, P = 0.03). Trends (P = [0.05–0.1]) were observed for torasemide, vancomycin, escitalopram and paracetamol. Patients with antidiabetic drugs are at risk for hypoglycemia event and should thus be closely monitored during hospitalization. Several drugs were found to be marginally associated with hypoglycemia events and should be replicated in further studies.

A Primary Study of the Antioxidant, Hypoglycemic, Hypolipidemic, and Antitumor Activities of Ethanol Extract of Brown Slimecap Mushroom, Chroogomphus rutilus (Agaricomycetes).

In vivo and in vitro treatments were carried out to investigate the effects of a 95% ethanol extract of Chroogomphus rutilus (CRE) on antioxidant, hypoglycemic, hypolipidemic, and antitumor properties. CRE showed potent radical scavenging activity against DPPH in vitro. It could increase antioxidant enzymatic activities (superoxide dismutase and glutathione peroxidase) and could reduce malondialdehyde content in vivo in mice in which aging was induced by D-galactose. CRE had hypoglycemic activity and could significantly inhibit α-glucosidase activity in vitro and decrease blood glucose concentration in vivo. CRE could decrease the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and increase the high-density lipoprotein cholesterol level in diabetic mice. The MTT assay showed that CRE also had a certain inhibitory effect on the tumor cells. These results suggest that CRE may be beneficial for human health and could be useful for applications in medicine, the food industry, and agriculture.

Effect of Dapagliflozin Treatment on Fluid and Electrolyte Balance in Diabetic Rats

AimThis study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on fluid or electrolyte balance and its effect on urea transporter-A1 (UT-A1), aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in diabetic rats. MethodsDiabetes mellitus (DM) was induced by injection of streptozotocin into the tail vein. Serum Na+, K+, Cl− concentration, urine Na+, K+, Cl− excretion, blood glucose, urine glucose excretion, urine volume, urine osmolality and urine urea excretion were analyzed after the administration of dapagliflozin. UT-A1, AQP2 and NKCC2 proteins were detected by western blot. ResultsDapagliflozin treatment decreased blood glucose concentration by 38% at day 7 and by 47% at day 14 and increased the urinary glucose excretion rate compared with the untreated diabetic animals. Increased 24-hour urine volume, decreased urine osmolality and hyponatremia, hypokalemia and hypochloremia observed in diabetic rats were attenuated by dapagliflozin treatment. Western blot analysis showed that UT-A1, AQP2 and NKCC2 proteins are upregulated in DM rats over control rats; dapagliflozin treatment results in a further increase in inner medulla tip UT-A1 protein abundance by 42% at day 7 and by 46% at day 14, but it did not affect the DM-induced upregulation of AQP2 and NKCC2 proteins. ConclusionDapagliflozin treatment augmented the compensatory changes in medullary transport proteins in DM. These changes would tend to conserve solute and water even with persistent glycosuria. Therefore, diabetic rats treated with dapagliflozin have a mild osmotic diuresis compared to nondiabetic animals, but this does not result in an electrolyte disorder or significant volume depletion.

The Effects of Supplementary Mulberry Leaf (Morus alba) Extracts on the Trace Element Status (Fe, Zn and Cu) in Relation to Diabetes Management and Antioxidant Indices in Diabetic Rats.

Mulberry leaves (Morus alba) have been used in folk medicine to mitigate symptoms of diabetes. The mulberry plant contains phenolic compounds that are able to decrease blood glucose concentration. Since various phenolics have antioxidant and metal binding properties, they can be used to alleviate oxidative stress and chelate trace elements involved in redox reactions. The aim of this study was to evaluate the effects of dietary supplementation with mulberry leaf extracts (acetone–water (AE) and ethanol–water (EE)) on the trace element status (Fe, Zn and Cu) in relation to diabetes management and antioxidant indices in high-fat diet-fed/STZ diabetic rats. The experiment was performed on 38 male Wistar rats with diabetes (induced by high-fat diet (HF) and streptozotocin injection) or the control fed with AIN-93M or high-fat diet. As a result, five experimental groups were used: (1) a healthy control group fed with AIN-93M; (2) an HF control group; (3) a diabetic HF group; (4) a diabetic HF + AE group (6 g/kg diet); (5) a diabetic HF + EE group (6 g/kg diet). The rats were fed with appropriate diets for 4 weeks. The content of trace elements (Fe, Zn and Cu) in the serum and tissues was measured by means of atomic absorption spectrometry (AAS). Biochemical analyses (glucose, TBARS, FRAP) were performed on the blood serum. It was shown that the AE decreased hepatic and renal Fe stores, while the EE increased hepatic Cu levels in diabetic rats and confirmed their ability to regulate the Fe and Cu status in diabetes. The results confirmed a significant hypoglycaemic and antioxidant potential of both mulberry leaf extracts in diabetic rats.

Low digestion property of amylosucrase-modified waxy adlay starch.

Structural and digestion properties of amylosucrase-modified waxy adlay starch were investigated. The unique reaction of amylosucrase caused a decrease and an increase in the proportion of short chains and long chains, respectively, via attachment of glucosyl units to the non-reducing ends of branch chains. The in vitro digestion profile of amylosucrase-modified starch revealed that elongated branch chains were the main reason for high contents of slowly digestible and resistant starches due to formation of a more perfect crystalline structure via easy association between elongated branch chains. The glucose response in mice after consumption of amylosucrase-modified starch was similar to the response for commercial resistant starch with a gradual increase followed by a gradual decrease in blood glucose concentrations over a prolonged time. Both in vitro and in vivo tests were used to verify increased resistance to digestive enzymes caused by amylosucrase modification.

Antihyperglycemic and antidiabetic effects of Ethyl (S)-2-(1-cyclohexylsulfamide carbamoyloxy) propanoate in streptozotocin-induced diabetic Wistar rats

In this study, we examined the antihyperglycemic and antidiabetic effects of a novel synthesized molecule, the Ethyl (S)-2-(1-cyclohexylsulfamide carbamoyloxy) propanoate (ESP1b), in streptozotocin (STZ)-induced diabetic Wistar rats. Experimental diabetes mellitus was produced by a single intraperitoneal injection of STZ (55mg/kg b.w.). Seven day post-injection, animals have received ESP1b orally at the doses of 5, 10 and 20mg/kg b.w. daily for 28 days. This resulted in a clear decline, in a dose dependent manner, of blood glucose levels during the oral glucose tolerance test (OGTT) and the four weeks of treatment period. ESP1b at 20mg/kg b.w. has alleviated body weight loss, improved plasma insulin concentration and at the same time markedly decreased the values of glycosylated hemoglobin, lipoproteins and atherogenic ratios. Additionally, ESP1b notably restored renal as well as hepatic functions tests. Histopathological examinations of pancreatic tissue also confirmed the previous biochemical findings. Considering the obtained results, it may be concluded that ESP1b possess a potent antihyperglycemic activity in STZ-diabetic rats possibly related to an insulin-secretagogue effect, which may be responsible for the moderate decrease in blood glucose concentration observed in normal rats administrated with this tested compound.

Diagnosing lactose malabsorption in children: difficulties in interpreting hydrogen breath test results

Lactose malabsorption (LM) is caused by insufficient enzymatic degradation of the disaccharide by intestinal lactase. Although hydrogen (H2) breath tests (HBTs) are routinely applied to diagnose LM, false-negative results are not uncommon.Thirty-two pediatric patients (19 females, 13 males) were included in this prospective study. After oral lactose administration (1 g kg−1 bodyweight to a maximum of 25 g), breath H2 was measured by electrochemical detection. HBT was considered positive if H2 concentration exceeded an increase of ⩾20 ppm from baseline. In addition to H2, exhaled methane (CH4), blood glucose concentrations and clinical symptoms (flatulence, abdominal pain, diarrhea) were monitored.A positive HBT indicating LM was found in 12/32 (37.5%) patients. Only five (41.7%, 5/12) of these had clinical symptoms during HBT indicating lactose intolerance (LI). Decreased blood glucose concentration increments (⩽20 mg dL−1 (⩽1.1 mmol L−1)) were found in 3/5 of these patients. CH4 concentrations ⩾10 ppm at any time during the test were observed in 5/32 (15.6%) patients and in 9/32 (28.1%) between 1 ppm and 9 ppm above baseline after lactose ingestion. In patients with positive HBT 10/12 (83.3%) showed elevated CH4 (>1 ppm) above baseline in breath gas, whereas in patients with negative HBT this figure was only 4/17 (23.5%).In addition to determining H2 in exhaled air, documentation of clinical symptoms, measurement of blood glucose and breath CH4 concentrations may be helpful in deciding whether in a given case an HBT correctly identifies patients with clinically relevant LM.

Supplementation of Glucomannan Derived from Konjac Flour Improve Glucose Homeostasis and Reduce Insulin Resistance in Diabetes Rat Models

Dietary fiber from glucomannan has been studied to decrease blood glucose concentration, but its mechanism in diabetes is still unclear. The aim of our research is to study the effect of glucomannan, derived from konjac flour, in rat models of diabetes including gastrointestinal function, inhibition of DPP-IV enzyme and reducing in insulin resistance. A total of 25 male wistar rats were divided into 5 groups; normal group (Normal), diabetes group (DM), diabetes group administered with 100 mg/kg BW konjac flour (DM+KF1), 200 mg/kg BW konjac flour (DM+KF2) and 400 mg/kg BW konjac flour (DM+KF3). Diabetes was induced by a combination of 60% high fructose diet and twice intraperitoneal injection of streptozotocin (25 and 30 mg/kg BW) at one week interval. Konjac flour was given according to each dose for 4 weeks. At the end of the study, blood and tissue sample were collected for subsequent analysis, while isolated intestine used to measure jejunal serous glucose concentration using everted sac technique. The results indicate that glucomannan reduced fasting blood glucose levels, improved glucose tolerance, increased jejunal serous glucose concentration at in vitro technique and decreased insulin resistance as evidenced by a decreased in HOMA-IR index and increased in PI3K levels. However, glucomannan not decreased DPP-4 levels in any dose. This results indicate that glucomannan derived from Konjac flour had antidiabetic effects through improving in glucose homeostasis and reducing in insulin resistance in rat models of diabetes.

Retrospective evaluation of xylitol ingestion in dogs: 192 cases (2007–2012)

To summarize the signalment, clinical signs, prevalence of decreased blood glucose concentration (BG), prevalence of increased liver values, treatment, and outcome in dogs known to have ingested xylitol. Retrospective study from December 2007 to February 2012 SETTING: Three university teaching hospitals. One hundred ninety-two client-owned dogs with known or suspected xylitol ingestion. None. The median ingested xylitol dose was 0.32 g/kg (range 0.03-3.64 g/kg). Clinical signs were present in 39 (20%) dogs on presentation to the veterinary teaching hospitals. The most common clinical sign was vomiting (n = 25), followed by lethargy (12). The median duration of clinical signs prior to presentation was 93 minutes (range 0-5,040 minutes). Dogs that developed clinical signs ingested a significantly higher dose of xylitol than those that were asymptomatic. Thirty dogs became hypoglycemic (BG ≤ 3.3 mmol/L [60 mg/dL]) at some time point during their hospitalization. When evaluating all dogs, there was a significant difference between the initial and lowest BGs. Thirty dogs had increased alanine aminotransferase activity or total serum bilirubin concentration. Dogs with increases in alanine aminotransferase activity or total serum bilirubin concentration had a significantly lower nadir BG. All dogs survived to discharge and 158 were known to be alive at 28 days. The rest were lost to follow up. The prognosis for dogs evaluated by a veterinarian that ingest lower doses of xylitol and do not develop liver failure is excellent. Dogs ingesting xylitol should be hospitalized and monitored for variations in BG, because BG drops in most dogs following presentation. Additional studies are needed in dogs ingesting higher doses of xylitol before correlations between dose and the development of clinical signs or liver failure can be established. Treatment and prognosis for these dogs warrants further investigation.

Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

IntroductionNeuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer’s oxidative phosphorylation system.MethodsXenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2)]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content).ResultsKetogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention.ConclusionsOur data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting standard therapy regimens. Therefore, we propose that a ketogenic diet and/or calorie restriction should be further evaluated as a possible adjuvant therapy for patients undergoing treatment for neuroblastoma.

Rate-of-Change Dependence of the Performance of Two CGM Systems During Induced Glucose Swings

The accuracy of continuous glucose monitoring (CGM) systems is often assessed with respect to blood glucose (BG) readings. CGM readings are affected by a physiological and a technical time delay when compared to BG readings. In this analysis, the dependence of CGM performance parameters on the BG rate of change was investigated for 2 CGM systems. Data from a previously published study were retrospectively analyzed. An established CGM system (Dexcom G4, Dexcom, San Diego, CA; system A) and a prototype system (Roche Diagnostics GmbH, Mannheim, Germany; system B) with 2 sensors each were worn by 10 subjects in parallel. Glucose swings were induced to achieve rapidly changing BG concentrations. Mean absolute relative differences (MARD) were calculated in different BG rate-of-change categories. In addition, sensor-to-sensor precision was assessed. At BG rates of change of -1 mg/dl/min to 0 mg/dl/min and 0 mg/dl/min to +1 mg/dl/min, MARD results were 12.6% and 11.3% for system A and 8.2% and 10.0% for system B. At rapidly changing BG concentrations (<-3 mg/dl/min and ≥+3 mg/dl/min), higher MARD results were found for both systems, but system B was less affected (system A: 24.9% and 29.6%, system B: 10.6% and 16.3%). The impact of rate of change on sensor-to-sensor precision was less pronounced. Both systems were affected by rapidly changing BG concentrations to some degree, although system B was mostly unaffected by decreasing BG concentrations. It would seem that technological advancements in CGM systems might allow for a more precise tracking of BG concentrations even at rapidly changing BG concentrations.

Hypoglycemic effects of glycosaminoglycan from Urechis unicinctus in diabetic mice.

To further utilize glycosaminoglycan from Urechis unicinctus, the hypoglycemic effect and possible mechanism of glycosaminoglycan on diabetic mice were evaluated. Diabetes was induced in mice by intraperitoneal injections of streptozotocin for 3 consecutive days and fed with high-sugar and high-lipid fodder. After diabetes was confirmed, the hypoglycemic effect of glycosaminoglycan from U. unicinctus was investigated in the diabetic mice. Results demonstrated that glycosaminoglycan could significantly decrease blood glucose concentrations, HOMA-IR, AUG, and liver MDA content in diabetic mice. In addition, it significantly enhanced liver SOD and GSH-Px activity, as well as liver GCK activity and hepatic glycogen levels. Glycosaminoglycan from U. unicinctus exhibited efficacy against diabetes, suggesting its potential use as a natural intervention against diabetes.

The vasodilating effect of a Hintonia latiflora extract with antidiabetic action

In the present study, it is shown for the first time that an extract of Hintonia latiflora (HLE) which is used as an antidiabetic herbal medicine, is not only able to decrease blood glucose concentration but additionally exerts a vasodilating effect. Accordingly, this extract might have a positive influence on diabetes-associated dysfunction of blood vessels.The vasodilating effect was demonstrated in vitro in aortic rings of guinea pigs as well as in vivo in rabbits. Aortic rings pre-contracted with noradrenaline (NA) could completely be relaxed by HLE (EC50: 51.98mg/l). In contrast, potassium-induced contractions were not diminished by HLE. Therefore, it can be suggested that the vasodilating effect of HLE is primarily the result of an inhibition of G protein-induced increase in intracellular calcium and not of a blockade of voltage-operated L-type calcium channels.The neoflavonoid coutareagenin (COU), a constituent of HLE which in part is responsible for the blood glucose-lowering effect of HLE, also relaxed NA-induced contractions of aortic rings (EC50: 32.55mg/l) and only weakly inhibited potassium-induced contractions.Experiments in aortic rat cells revealed that calcium transients evoked by vasopressin were suppressed by 60mg/l COU supporting the idea of an inhibition of G protein-induced intracellular calcium release by a constituent of HLE.To study the effect of HLE on vascular tone under in vivo conditions, ultrasound measurements were carried out in conscious rabbits which received a single oral dose of HLE. Under the influence of HLE, a vasodilation combined with a lowering of blood flow velocity could be observed in the abdominal aorta and the common carotid artery. Additionally, a decrease in blood glucose concentration in the HLE group occurred.The combination of a blood glucose-lowering with a vasodilating effect may be helpful for reducing angiopathies, typical long-term complications in patients with diabetes mellitus.

The strong relation between post-hemodialysis blood methylglyoxal levels and post-hemodialysis blood glucose concentration rise.

Hemodialysis is known to decrease blood glucose concentration (BGC), insulin, and methylglyoxal levels. However, the effects of decreases in these factors on the increase in post-hemodialysis BGC remain unknown. This study identifies the effects of hemodialysis-induced changes in concentrations of these elements on post-hemodialysis BGC. Study subjects included seventeen insulin-treated diabetes patients receiving hemodialysis. The fluctuations in BGC on hemodialysis-treatment days and non-hemodialysis-treatment days were evaluated using a continuous glucose monitoring system. BGC was evaluated before breakfast, before starting hemodialysis, at the end of hemodialysis, 1 h post-hemodialysis (lunch), and 6 h post-hemodialysis (dinner). BGC, insulin, and methylglyoxal levels were measured at the start and end of hemodialysis. This study also evaluated the changes in the concentrations of glucose and insulin in the arterial line and the venous line during hemodialysis. Hemodialysis decreases BGC, insulin, and methylglyoxal levels. Concentrations of glucose and insulin in the arterial line gradually decreased during dialysis, while concentrations in the venous line approached their original concentrations in the dialysis solution. BGC rose sharply after eating lunch 1 h post-hemodialysis. The blood glucose, insulin, and methylglyoxal concentrations at the end of hemodialysis were associated with the M values and the mean amplitude of glycemic excursion values between before lunch and dinner. In particular, methylglyoxal concentration at the end of hemodialysis was strongly related to the post-hemodialysis increase in BGC. Hemodialysis-induced decreases in methylglyoxal concentrations and methylglyoxal concentration at the end of hemodialysis influence post-hemodialysis fluctuations in BGC.