Oral Glucose Research Articles

MON-307 Prospective, Longitudinal Study of Glucose-Suppressed GH Levels in 87 Acromegaly Patients with IGF-1 Normalization After Surgical Therapy: Prognostic Value of Nadir GH Levels for Long-Term Remission or Recurrence

Surgical removal of the GH-secreting tumor is the initial treatment of choice for acromegaly. Outcome of surgery is assessed by measuring IGF-1 and glucose-suppressed GH levels. IGF-1 normalization is an essential biochemical criterion for remission. The cut-off for nadir GH after oral glucose that signifies remission, however, is debated. It also remains unclear whether GH levels provide additional prognostic or clinically relevant information when IGF-1 results are definitive. To address this question, we examined how initial postoperative glucose-suppressed GH levels change over time on serial testing in patients who achieve initial remission as defined by IGF-1 normalization. We studied 87 acromegaly patients (48M, 39F) who achieved a normal IGF-1 level after surgery alone longitudinally from 1996 to 2019. All had GH measured before and 60, 90 and 120 minutes after 75 or 100 mg oral glucose (OGTT) at ≥ 3 months after surgery and GH and IGF-1 repeated ≥ 1 year later. GH was by measured by sensitive, 22KDa GH specific assays, either a IRMA (DSL, International Reference Standard (IRS) 88/624) or a chemiluminescence immunoassay (IDS-iSYS, IRS 98/574). OGTT Nadir GH levels were also measured in healthy subjects; n=46 (26 M, 20 F, ages 19-71 yr.) by DSL and n=46 (29 M, 17 F; ages 20-66 yr.) by IDS-iSYS. Nadir GH levels in acromegaly patients were compared to the 95%CI of healthy subjects’ mean and categorized relative to healthy subjects’ 97.5 percentile, which was 0.14 µg/L for both assays. IGF-1 levels were compared to age and gender adjusted normal ranges. Subjects were grouped based on initial nadir GH ≤ or > 0.14 µg/L and the patterns of change in nadir GH and IGF-1 at last follow up or until IGF-1 became elevated (i.e. recurrence). Follow up durations are given as median(range). In follow up, 73 patients remained in remission (normal IGF-1) and 14 had a recurrence (elevated IGF-1). Of the 73 in remission, 55 had initial nadir GH ≤ 0.14 µg/L that persisted to 10 yr.(1-22yr.) of follow up, 5 had initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 9(3-21)yr., 10 had GH > 0.14 µg/L that persisted at 5.5(2-22)yr., and 3 had GH > 0.14 µg/L that fell to ≤ 0.14 µg/L at 5(4-7)yr. of follow up. Of the 14 that recurred, 11 had an initial and persistent GH > 0.14 µg/L and developed an elevated IGF-1 level after 6(1-23) yr.. The 3 other patients that recurred had an initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 1-6 years later and subsequently developed an elevated IGF-1 level by 14-16 years of follow up. In summary, we found that the pattern of normal IGF-1 along with nadir GH > 0.14 µg/L on initial testing or developing with time, was associated with recurrence in 14/32 patients. We also found that initial nadir GH ≤ 0.14 µg/L was highly predictive of long-term persistent remission: 60/63 such patients remained in remission. In conclusion, glucose-suppressed GH levels are of prognostic value in acromegaly patients with normal IGF-1 after surgery.

MON-679 What’s in a Bottle? the Importance of Careful Medication Review to Prevent Life Threatening Hypoglycemia

Background: Over 1 in 9 emergency department (ED) visits are due to drug-related adverse events (1) and careful medication review is essential for patient safety. Clinical Case: A 73-year-old male presented to the ED after his family found him to be tremulous with a blood glucometer reading of 30 mg/dL. He was given glucagon and oral glucose however this did not help his blood glucose and he was brought in for further evaluation. He had a history of chronic kidney disease, hepatocellular carcinoma (HCC) and diabetes mellitus type 2 for which he was on no medication at the time of presentation. He reported being on Glipizide nine months ago. In the ED, he had a temperature of 98.3°F; pulse of 76 beats/min; respiratory rate of 18 breaths/min and blood pressure of 166/71. On physical examination, he was in no acute distress with normal neurologic, cardiac and respiratory exam. Laboratory workup was notable for glucose 40 mg/dL, HbA1c 5.0%, Cr 2.55 mg/dL, eGFR 24, ALT 7 IU/L and AST 23 U/L. CT abdomen and pelvis was consistent with known diagnosis of HCC. The patient was given 4 boluses of D50W and started on a continuous dextrose infusion along with octreotide infusion due to persistent hypoglycemia. Patient’s blood glucose improved one day later and he remained stable off the dextrose and octreotide infusions. Further laboratory evaluation revealed ACTH 9 pg/mL (ref 6-50), Random Cortisol 16.1 at 1:36pm, TSH 1.40uIU/ml, Free T4 1.09 ng/dL, Cosyntropin stimulation test at baseline 15.4 ug/dL; at 30 min 22 ug/dL; at 60 min 28.3 ug/dL and Beta-Hydroxybutyrate 0.11 mmol/L. With a blood sugar level of 32 mg/dL, he was found to have Insulin level 35.9 (ref 3.0-25.0mU/L), Pro-insulin 55.6 (ref < 18.8pmol/L) and C-peptide 9.21 (ref 0.8-3.85ng/mL). The patient’s family brought his medications for review with no clear discrepancies noted. Closer inspection of the tablets inside each pill bottle revealed that the pills inside the Docusate-Senna container did not match the description for the same but instead matched the description for Glipizide. The patient disclosed that he had emptied the Glipizide tablets into the bowel regimen container for “safe keeping” when it was discontinued. He was inadvertently taking two Glipizide tablets twice a day as the VNA had mistakenly used these pills to fill his pill box. This serious error in confirming the patient’s medications resulted in his severe hypoglycemia. His Sulfonylurea screen returned positive for Glipizide. Conclusion: Sulfonylureas, an essential component of diabetes management, have a dangerous side effect of hypoglycemia and errors in its administration can be fatal. Therefore, thorough medication reconciliation and review of the actual pills is essential to prevent such errors. Reference: Zed PJ, et al. Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study. Can Med Assoc J. 2008;178(12):1563-1569.

LO18: The state of the evidence for emergency medical services (EMS) care of prehospital hypoglycemia: an analysis of appraised research from the Prehospital Evidence-based Practice Program

Introduction: The Prehospital Evidence-based Practice (PEP) program is an online, freely accessible, continuously updated repository of appraised EMS research evidence. This report is an analysis of published evidence for EMS interventions used to assess and treat patients suffering from hypoglycemia. Methods: PubMed was systematically searched in June 2019. One author screened titles, abstracts and full-texts for relevance. Trained appraisers reviewed full text articles, scored each on a three-point Level of Evidence (LOE) scale (based on study design and quality) and three-point Direction of Evidence (DOE) scale (supportive, neutral, or opposing findings for each intervention's primary outcome), abstracted the primary outcome, setting and assigned an outcome category (patient or process). Second party appraisal was conducted for all included studies. The level and direction of each intervention was plotted in an evidence matrix, based on appraisals. Results: Twenty-nine studies were included and appraised for seven interventions: 5 drugs (Dextrose 50% (D50), Dextrose 10% (D10), glucagon, oral glucose and thiamine), one assessment tool (point-of-care (POC) glucose testing) and one call disposition (treat-and-release). The most frequently reported study primary outcomes were related to: clinical improvement (n = 15, 51.7%), feasibility/safety (n = 8, 27.6%), and diagnostics (n = 6, 20.7%). The majority of outcomes were patient focused (n = 18, 62.0%). Conclusion: EMS interventions for treating hypoglycemia are informed by high-quality supportive evidence. Both D50 and D10 are supported by high-quality evidence; suggesting D10 may be an effective alternative to the standard D50. “Treat-and-release” practices for hypoglycemia are supported by moderate-quality evidence for the patient related outcomes of relapse, patient preference and complications. This body of evidence is high-quality, patient-focused and conducted in the prehospital setting thus generalizable paramedic practice.

Newly Approved Novel Dosage Forms of Glucagon for Management of Severe Hypoglycemia.

The prevalence and clinical impact of diabetes mellitus (DM) continues to increase in the United States and throughout the world. Older adults are at increased risk for adverse outcomes associated with hypoglycemia, particularly in situations where a lack of awareness may arise because typical symptoms are not necessarily present, serve to prompt medical intervention with oral glucose. Glucagon emergency kits that have been available to date require multiple-step reconstitution that may compromise timely and appropriate administration of lifesaving glucagon treatment during episodes of severe hypoglycemia. In settings such as long-term care facilities, trained medical professionals may not be readily available, meaning that glucagon must be administered by laypersons. Novel dosage forms of glucagon that have recently been approved for marketing in the United States allow glucagon to be delivered more easily, which may positively impact effective treatment of severe hypoglycemia among older people. Nasal glucagon and glucagon autoinjection "pens" are as effective as glucagon kits and increase the likelihood glucagon will be appropriately used by patient caregivers. The safety, efficacy, and convenience of these new devices may improve outcomes and reduce health care costs of older people with diabetes.

Newly Approved Novel Dosage Forms of Glucagon for Management of Severe Hypoglycemia

The prevalence and clinical impact of diabetes mellitus (DM) continues to increase in the United States and throughout the world. Older adults are at increased risk for adverse outcomes associated with hypoglycemia, particularly in situations where a lack of awareness may arise because typical symptoms are not necessarily present, serve to prompt medical intervention with oral glucose. Glucagon emergency kits that have been available to date require multiple-step reconstitution that may compromise timely and appropriate administration of lifesaving glucagon treatment during episodes of severe hypoglycemia. In settings such as long-term care facilities, trained medical professionals may not be readily available, meaning that glucagon must be administered by laypersons. Novel dosage forms of glucagon that have recently been approved for marketing in the United States allow glucagon to be delivered more easily, which may positively impact effective treatment of severe hypoglycemia among older people. Nasal glucagon and glucagon autoinjection "pens" are as effective as glucagon kits and increase the likelihood glucagon will be appropriately used by patient caregivers. The safety, efficacy, and convenience of these new devices may improve outcomes and reduce health care costs of older people with diabetes.

Abstract MP44: Nitrite Generating Capacity Assessed Through the Oral Microbial Metagenome is Associated With Cardiometabolic Risk

Introduction: Nitric oxide (NO) is important for cardiometabolic health. The enterosalivary nitrate-nitrite-NO pathway generates NO following oral microbiota-mediated production of salivary nitrite. We investigated the association between the abundance of genes in this pathway and cardiometabolic biomarkers. Hypothesis: Microbial genes favoring increased oral nitrite generation are associated with better cardiometabolic profile. Methods: We enrolled 784 diabetes-free adults in the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS). Subgingival plaques were collected from 6-8 teeth/participant. 16S rRNA microbial genes (Illumina, MiSeq) were sequenced; PICRUSt2 estimated abundance of microbial genes in the nitrate-nitrite pathway associated with either nitrite generation or depletion. Gene abundance was summed within each group, and a ratio between nitrite generation to depletion (GDR) was calculated; higher levels suggest increased nitrite generating capacity. Systolic and diastolic blood pressure were measured and HbA1C, insulin, and glucose levels were determined in fasting blood. Z-scores were calculated for cardiometabolic biomarkers and averaged to form a cardiometabolic z-score (CMZ-score). Adjusted multivariable linear models were used to regress the CMZ-score and individual Z-scores on GDR. Results: Participants were 69% female and aged 19-58 years (mean=32±9). Mean CMZ-score was 0.00±0.7. Mean (range) GDR was 1.88 (0.22-7.84). Mean CMZ-scores (SE) across GDR quartiles were 0.17 (0.06), 0.01 (0.05), -0.04 (0.05), and -0.14 (0.05), p-value for trend=0.02. Linear regression coefficients summarizing associations between GDR and individual Z-scores (Table) show lower Z-score for systolic and diastolic blood pressure, HbA1C, and insulin levels in those with higher GDR. Conclusions: Increased capacity for nitrite production by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

Emerging Role of Lymphatics in the Regulation of Intestinal Lipid Mobilization.

Intestinal handling of dietary triglycerides has important implications for health and disease. Following digestion in the intestinal lumen, absorption, and re-esterification of fatty acids and monoacylglycerols in intestinal enterocytes, triglycerides are packaged into lipoprotein particles (chylomicrons) for secretion or into cytoplasmic lipid droplets for transient or more prolonged storage. Despite the recognition of prolonged retention of triglycerides in the post-absorptive phase and subsequent release from the intestine in chylomicron particles, the underlying regulatory mechanisms remain poorly understood. Chylomicron secretion involves multiple steps, including intracellular assembly and post-assembly transport through cellular organelles, the lamina propria, and the mesenteric lymphatics before being released into the circulation. Contrary to the long-held view that the intestinal lymphatic vasculature acts mainly as a passive conduit, it is increasingly recognized to play an active and regulatory role in the rate of chylomicron release into the circulation. Here, we review the latest advances in understanding the role of lymphatics in intestinal lipid handling and chylomicron secretion. We highlight emerging evidence that oral glucose and the gut hormone glucagon-like peptide-2 mobilize retained enteral lipid by differing mechanisms to promote the secretion of chylomicrons via glucose possibly by mobilizing cytoplasmic lipid droplets and via glucagon-like peptide-2 possibly by targeting post-enterocyte secretory mechanisms. We discuss other potential regulatory factors that are the focus of ongoing and future research. Regulation of lymphatic pumping and function is emerging as an area of great interest in our understanding of the integrated absorption of dietary fat and chylomicron secretion and potential implications for whole-body metabolic health.

TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones.

We studied if macronutrients of the diet have different effects on leukocyte activation, and if these effects are influenced by sex hormones or obesity. We analyzed leukocyte cell surface and gene expression of toll-like receptors 2 and 4 (TLR2 and TLR4) during fasting and after macronutrient loads in women with polycystic ovary syndrome and female and male controls. Fasting TLR2 surface expression in neutrophils was higher in men than in women. Obese subjects presented higher TLR2 gene expression than nonobese individuals, particularly in men. In contrast, surface TLR4 expression was lower in men and in obese individuals. Postprandial cell-surface expression decreased similarly after all macronutrient loads. Neutrophil TLR2 decreased only in obese subjects whereas TLR4 showed a greater decrease in nonobese individuals. However, TLR2 gene expression increased after glucose ingestion and decreased during the lipid load, while TLR4 was induced in response to lipids and mostly to glucose. Postprandial TLR gene expression was not influenced by group of subjects or obesity. Both cell-surface and gene postprandial expression inversely correlated with their fasting levels. These responses suggest a transient compensatory response aiming to prevent postprandial inflammation. However, obesity and sex hormones showed opposite influences on surface expression of TLR2 and TLR4, but not on their gene expression, pointing to regulatory posttranscriptional mechanisms.

Plasma glucagon levels measured by sandwich ELISA are correlated with impaired glucose tolerance in type 2 diabetes.

Glucagon dysfunction as well as insulin dysfunction is associated with the pathogenesis of type 2 diabetes (T2DM). However, it is still unclear whether the measurement of plasma glucagon levels is useful in understanding the pathophysiology of T2DM. We recently reported that sandwich ELISA provides more accurate plasma glucagon values than conventional RIA in healthy subjects. Here we used sandwich ELISA as well as RIA to assess plasma glucagon levels, comparing them in T2DM patients and healthy subjects during oral glucose (OGTT) or meal tolerance tests (MTT). We confirmed that sandwich ELISA was able to detect more significant difference between healthy subjects and T2DM patients in the fasting levels and the response dynamics of plasma glucagon than RIA. We also found significant differences in the following glucagon parameters: (1) fasting glucagon, (2) the area under the curve (AUC) of glucagon in OGTT, and (3) the change in glucagon between 0 and 30 min (ΔGlucagon0-0.5h) in OGTT or MTT. Among these, the most apparent difference was ΔGlucagon0-0.5h in MTT. When we divided T2DM patients into two groups whose ΔGlucagon0-0.5h in MTT was either below or above the maximum value in healthy subjects, the group with higher ΔGlucagon0-0.5h showed more significant impairment of glucose tolerance. These results suggest that the assessment of plasma glucagon levels by sandwich ELISA might enhance our understanding of the pathophysiology of T2DM.

Infrequent small bowel intestinal bacterial overgrowth in malnourished Zambian children

There is evidence that children with malnutrition have an increased frequency of small intestinal bacterial overgrowth (SIBO) due to impaired gastric acidity, impaired intestinal motility, and dysbiosis. Children with malnutrition respond to antibiotic therapy but it is not clear if this effect is mediated by treatment of SIBO. We set out to determine the frequency of SIBO in children of varying nutritional status in a poor community in Lusaka, Zambia. Hydrogen breath testing, following a dose of 1g/kg oral glucose, was used to determine the presence of SIBO amongst the study participants. Forty nine children, 45 of whom had varying degrees of malnutrition, completed a full series of observations at 15, 30 and 60 minutes. Four children (8%) had a rise of 10ppm from baseline, consistent with SIBO. No correlation with nutritional status was observed. In this small study of Zambian children, SIBO was infrequent and unrelated to nutritional status.

The association between functional oral health literacy and periodontal disease among adults with type 2 diabetes mellitus in the northeast region of Thailand

Aim: To analyze the association between functional oral health literacy (FOHL) and oral health behaviors with periodontal disease among adults with type 2 diabetes mellitus (T2DM). Materials and Methods: A cross-sectional analysis study was conducted among 1110 adults with T2DM who were selected by multistage random sampling from 10 hospitals of five provinces in the northeast region of Thailand. A structured questionnaire was developed, and face to face interview and also clinical oral examination and blood glucose investigation were carried out. Data distribution was performed by descriptive statistic and chi-square test. The multiple logistic regression was used to determine the association between variables after adjustment for confounders. Results: In this study, a total of 1110 adults with T2DM divided into two groups according to the severity of periodontal disease showed 51.89% of moderate–severe periodontal disease. The study examined the association of periodontal disease with the independent variables after adjusted odd ratios, it was found to be statistically significant with the FOHL level (adjusted odds ratio [AOR] = 1.80, 95% confidence interval [CI] = 1.30–2.40), toothbrushing frequency (AOR = 1.73, 95% CI = 1.24–2.40), smoking (AOR = 2.25, 95% CI = 1.45–3.40), and betel nut crewing (AOR = 2.13, 95% CI = 1.28–3.45). Moreover, the demographic characteristics of patients with T2DM associated with the severity of periodontal disease in variables of gender, age, education level, duration with diabetes, and health insurance were also statistically significant at P < 0.05. Conclusion: The FOHL level and oral behaviors among adults with T2DM were statistically significant with periodontal disease. However, the patients of T2DM with low FOHL and poor oral health behaviors need extra support from dental health personnel to reduce the risk of oral disease.

The Incretin Effect in Female Mice With Double Deletion of GLP-1 and GIP Receptors.

To establish the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) for the incretin effect after oral glucose, studies were undertaken in female mice with genetic deletion of receptors for GIP and GLP-1 (double incretin receptor knockout [DIRKO] mice) and their wild-type (WT) counterparts. Insulin secretion was explored after oral glucose (doses ranging from 0 to 100 mg), after intravenous glucose (doses ranging from 0 to 0.75 g/kg), and after oral and intravenous glucose at matching circulating glucose. DIRKO mice had glucose intolerance after oral glucose challenges in association with impaired beta-cell function. Suprabasal area under the curve for C-peptide (AUCC-peptide) correlated linearly with suprabasal AUCglucose both in WT (r = 0.942, P = .017) and DIRKO mice (r = 0.972, P = .006). The slope of this regression was lower in DIRKO than in WT mice (0.012 ± 0.006 vs 0.031 ± 0.006 nmol C-peptide/mmol glucose, P = .042). In contrast, there was no difference in the insulin response to intravenous glucose between WT and DIRKO mice. Furthermore, oral and intravenous glucose administration at matching glucose levels showed that the augmentation of insulin secretion after oral glucose (the incretin effect) in WT mice (11.8 ± 2.3 nmol/L min) was entirely absent in DIRKO mice (3.3 ± 1.2 nmol/L min). We conclude that GIP and GLP-1 are required for normal glucose tolerance and beta-cell function after oral glucose in mice, that they are the sole incretin hormones after oral glucose at higher dose levels, and that they contribute by 65% to insulin secretion after oral glucose.

Dual glucagon-like peptide-1 receptor/glucagon receptor agonist SAR425899 improves beta-cell function in type 2 diabetes.

To evaluate the change in insulin sensitivity, β-cell function and glucose absorption after 28 days of treatment with high and low doses of SAR425899, a novel dual glucagon-like peptide-1 receptor/glucagon receptor agonist, versus placebo. Thirty-six overweight to obese subjects with type 2 diabetes were randomized to receive daily subcutaneous administrations of low-dose SAR425899 (0.03, 0.06 and 0.09 mg) and high-dose SAR425899 (0.06, 0.12 and 0.18 mg) or placebo for 28 days; dose escalation occurred after days 7 and 14. Mixed meal tolerance tests were conducted before treatment (day -1) and on days 1 and 28. Oral glucose and C-peptide minimal models were used to quantify metabolic indices of insulin sensitivity, β-cell responsiveness and glucose absorption. With low-dose SAR425899, high-dose SAR425899 and placebo, β-cell function from day -1 to day 28 increased by 163%, 95% and 23%, respectively. The change in area under the curve for the rate of meal glucose appearance between 0 and 120 minutes was -32%, -20% and 8%, respectively. After 28 days of treatment, SAR425899 improved postprandial glucose control by significantly enhancing β-cell function and slowing glucose absorption rate.

Goat Milk Consumption Ameliorates Abnormalities in Glucose Metabolism and Enhances Hepatic and Skeletal Muscle AMP-Activated Protein Kinase Activation in Rats Fed with High-Fat Diets.

Diabetes endangers health and causes serious economic impediment. The aim of this study is to identify the effects of goat milk consumption on glucose metabolism of rats with high-fat (HF) diet. Sixty male Sprague Dawley rats are divided into five groups and fed with different diets for 24 weeks: goat-milk-based HF diet (GHF group; goat milk powder+HF diet), cow-milk-based HF diet (CHF group; cow milk powder+HF diet), HF diet, HF diet plus acarbose (HF+A group; acarbose+HF diet), and chow diet (CD group). Fasting glucose in GHF-fed rats are lower than HF-fed rats on weeks 16 and 20. GHF-fed rats display improved insulin sensitivity in oral glucose and insulin tolerance tests. Compared with HF-fed rats, glycated hemoglobin and triglycerides in GHF-fed rats are lower and high-density lipoprotein level is higher. AMP-activated protein kinase activation (AMPK) in the liver and skeletal muscle is higher in GHF rats than HF rats. Phosphoenolpyruvate carboxykinase and glucose 6-phosphatase protein levels in the liver are lower and hexokinase 2 protein level in the skeletal muscle is higher in GHF rats compared with HF rats. Goat milk consumption can ameliorate abnormalities in glucose metabolism, and AMPK pathway in the liver and skeletal muscle plays an important role in the process.

Comparison of the Effect of Yakson Touch and Oral Glucose on the Severity of Phlebotomy Pain in Preterm Infants

Background: Infants are exposed to different painful procedures during hospitalization in the neonatal intensive care unit (NICU). Due to the harmful effects of pain on infants, NICUs require methods by the aid of which the pain in infants can be controlled. Yakson touch and oral glucose are among non-pharmacological methods for pain relief in infants. In this regard, the present study was conducted to compare the effect of Yakson touch and oral glucose on the severity of phlebotomy pain in preterm infants.Methods: In this randomized clinical trial, 99 preterm infants hospitalized in NICU were randomly allocated to three groups, including Yakson touch (n=33), oral glucose (n=33), and control (n=33). In the oral glucose group, 1 cc of 50% glucose was orally given to the infants 1 min before phlebotomy. In the Yakson touch group, touching was performed for 5 min, and then the phlebotomy was performed. The infants in the control group did not receive a specific treatment. Infant pain level was determined before and after the phlebotomy using video recording based on Neonatal Infant Pain Scale. The data were analyzed using the analytical statistical tests, including the analysis of variance, Chi-square, Wilcoxon, and Kruskal-Wallis, in SPSS software (version 20).Results: The mean scores of pain in the two experimental groups were significantly lower than that of the control group (P=0.001), but there was no significant difference between the two experimental groups (P>0.05).Conclusion: According to our findings, both two methods (i.e., Yakson touch and oral glucose) can reduce phlebotomy pain in preterm infants hospitalized in intensive care unit. It is recommended to use Yakson touch in case of lack of access to glucose.

Moderate preventative effect with intraperitoneal liraglutide injection in high-fat diet induced C57BL/6J obese mouse model

BackgroundAlthough glucagon-like peptide-1 (GLP-1) based drugs including liraglutide have been among type 2 diabetes drugs for more than a decade, further studies with them in animal models may help to expand their future implications. ObjectiveHere we mainly assessed the potential preventative effect of liraglutide and the C-terminal fragment of GLP-1 (GLP-128-36) on obesity development in a high-fat-diet (HFD) induced obese mouse model. MethodsMale C57BL/6J mice were fed with HFD for 10 days (instead of 8 weeks or longer by other studies), followed by liraglutide, or GLP-128-36 administration 6 days per week for 5 weeks. In addition to daily body weight monitoring, oral glucose and intraperitoneal insulin tolerance tests were conducted. Plasma as well as hepatic triglyceride contents were also measured. ResultsIn comparison to PBS control, liraglutide but not GLP-128-36 administration, moderately attenuated HFD-induced body weight gain, accompanied by moderately improved glucose disposal and attenuated fasting blood glucose level. Liraglutide administration attenuated HFD induced hepatic and plasma triglyceride (TG) elevation, while GLP-128-36 administration reduced plasma but not hepatic TG level. In HFD fed mice, liraglutide treatment also improved insulin stimulated Akt (Ser473) phosphorylation in the liver. Notably, the daily body weight lowering effect of liraglutide was consistently decreased after the mice were rested for one day. ConclusionsWe conclude that preventative effect of liraglutide on obesity development is moderate in our experimental settings and such an effect was absent for GLP-128-36. Further investigations are needed for evaluating the weight management effect of both GLP-1-based and incretin-based drugs.

Effect of Marantodes pumilum Blume (Kuntze) var.alata on β-cell function and insulin signaling in ovariectomised diabetic rats

BackgroundOestrogen deficiency leads to metabolic disturbances such as insulin resistance and impairment of adipose tissue or lipid metabolism. Marantodes pumilum (Blume) Kuntze (Primulaceae) is believed to have phytoestrogenic properties and is claimed to have beneficial effects in the treatment of diabetes mellitus (DM), but the mechanism behind its phytoestrogenic effects on estrogen-deficient diabetic condition have not been fully examined. PurposeThe present study investigated the effects of oral treatment with M. pumilum var. alata (MPA) extracts on the estrogen receptor, metabolic characteristics and insulin signaling pathway in pancreas and liver of ovariectomised nicotidamide streptozotocin-induced diabetes in female rats. Materials and methodsOvariectomised diabetic (OVXS) Sprague-Dawley rats were orally administered with either aqueous leaf extract and ethanol (50%) stem-root extract of MPA (50 or 100 mg/kg) respectively for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin, oral glucose and insulin tolerance test. Distribution and expression level of insulin, oxidative stress and inflammatory marker in the pancreatic islets and liver were evaluated by immunohistochemistry and western blot, respectively. ResultsOral treatment with aqueous leaf and ethanol (50%) stem-root extracts of MPA (100 mg/kg) significantly reversed the elevated fasting blood glucose, impaired glucose and insulin tolerance. The protein expression of insulin, glucose transporter (GLUT-2 and GLUT-4) increased in the pancreatic islets and liver. Furthermore, marked improvement in the tissue morphology following treatment with MPA was observed. Similarly, the western blots analysis denotes improved insulin signaling in the liver and decreased reactive oxygen species producing enzymes, inflammatory and pro-apoptotic molecules with MPA treatment. ConclusionsTaken together, this work demonstrate that 100 mg/kg of aqueous leaf extract and ethanol (50%) stem-root extract of MPA improves β-cell function and insulin signaling in postmenopausal diabetes through attenuation of oxidative stress and partially mediated by oestrogen receptor stimulation.

Abstract P142: Progression of Diabetic Kidney Disease in the Type 2 Diabetic Nephropathy Rat Model

Diabetic kidney disease (DKD) is a condition of hyperglycemia-induced renal injury that is one of the chief causes of end-stage renal disease (ESRD). Hypertension often affects people with type 2 diabetes and the combination of diabetes and hypertension is associated with high morbidity and mortality. Here we assessed the progression of DKD in the T2DN rat and tested if this model develops age dependent DKD similar to human patients. Sex difference in the development of DKD was further defined. For the assessment of disease progression, we used 12 weeks old (early stage) and &gt;40 weeks old (late stage) male Wistar (non-diabetic control), Goto-Kakizaki (GK) and Type 2 Diabetic Nephropathy (T2DN) rats. At 12 weeks, male rats of type 2 diabetes background showed significant increases in blood glucose (374 ± 96 and 329 ± 45 vs. 280 ± 24 mg/dL, respectively for T2DN, GK vs. Wistar) and kidney to body weight ratio (10.05 ± 1.19 and 9.39 ± 0.78 vs. 7.31 ± 1.13, respectively). Aged male T2DN rats had significant increases in progressive albuminuria from 8 to 12 to &gt;40 weeks of age (0.44 ± 0.16 vs 0.34 ± 0.17 vs 11.80 ± 5.67, respectively). T2DN rats also show significant reductions in the blood of the components of the renin-angiotensin-aldosterone system. There were significant changes in renal damage such as increases in percent of medullary protein casts and glomerulosclerosis (probability based; 1.2% vs 27.5%, respectively compared to age matched GK males). To explore the sexual dimorphisms in the development of DKD, we compared T2DN male and female rats when animals had the late stage of the disease (&gt; 48 weeks old). Aged males had a significant impairment in their body’s response to sugar load compared to the females as assessed by both IP and oral gavage glucose tolerance tests. Aged male T2DN rats had increases in nephrin shedding in their urine (10,357 ± 4,866 vs 3,227 ± 2,918, respectively), which correlates with the dramatic differences in albuminuria (11.8 ± 5.7 vs. 0.98 ± 0.64 Alb/Cre ratio, respectively). In contrast, serum albumin levels were elevated in female T2DN rats. Therefore, we report here that T2DN rat develops renal and physiological lesions similar to those seen in patients with type 2 diabetes, and there is a dramatic sex difference in the progression of renal damage.

Effect of enteral nutrition and probiotics on inflammatory factors and immune function in aplastic anemia rats

Objective To investigate the effect of enteral nutrition and probiotics on inflammatory factors and immune function in aplastic anemia (AA) rats. Methods AA rats model were established by intraperitoneal injection of fluorouracil and lavage Maryland, and the successful AA rats model were randomly divided into model group, enteral nutrition group, probiotics group and combination group, 10 rats in each group. Another 10 Wistar rats were selected as blank group. Rats in the blank group and model group were given saline lavage (same volume 0.9% NaCl), rats in the enteral nutrition group were given Peptisorb nutrient solution [10 g/(kg·d)] by lavage, rats in the probiotics group were given live Clostridium butyricum [2 g/(kg·d)] by lavage, and rats in the combination group were given Peptisorb nutrient solution [10 g/(kg·d)] and live Clostridium butyricum [2 g/(kg·d)] by lavage for 4 weeks. The pathological structure of the bone marrow were observed by HE staining, the contents of white blood cells (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (Hb) in blood cell were detected by analyzer, the levels of serum tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interleukin-11 (IL-11) were detected by ELISA method, and the contents of CD4+, CD8+ and NKT cells were detected by flow cytometry instrument. Results The contents of WBC, RBC, PLT and Hb in the model group were significantly lower than that in the blank group, the contents of WBC, RBC, PLT and Hb in enteral nutrition group, probiotics group and combination group were significantly higher than that in the model group, and the combination group was better than the enteral nutrition group and probiotics group (P 0.05). The level of TNF-α and IL-2 were significantly higher and the IL-11 level was significantly lower in the model group than in the blank group, the level of TNF-α and IL-2 were significantly lower and IL-11 level were significantly higher in the enteral nutrition group, probiotics group and combination group than in the model group, and the combination group was better than the enteral nutrition group and probiotics group (P 0.05). The contents of CD4+ and NKT cells were significantly lower and the CD8+ cells was significantly higher in the model group than in the blank group, the level of CD4+ and NKT cells were significantly higher and CD8+ cells were significantly lower in enteral nutrition group, probiotics group and combination group than in the model group, and the combination group was better than the enteral nutrition group and probiotics group (P 0.05). Conclusion Compared with normal consumption or oral glucose, the enteral nutrition combined with probiotics can reduce inflammatory response and improve bone marrow hematopoietic function and immune function in AA rats. Key words: Aplastic anemia; Enteral nutrition; Probiotics; Inflammation factors; Immune function

285-OR: Conversations and Reactions around Severe Hypoglycemia (CRASH): U.S. Results from a Global Survey of People with T1DM or Insulin-Treated T2DM and Caregivers

The CRASH study examines the experience and treatment of a severe hypoglycemia event (SHE) among people with T1DM (ppl w/T1DM) or insulin-treated ppl w/T2DM and caregivers. The online survey was conducted in 8 countries. To be eligible in the global study, ppl had experienced or cared for a person who had ≥1 SHE in the last 3 years. SHE was defined as low blood glucose requiring assistance for recovery. Here, we report U.S. data for 220 ppl with diabetes (n=110 T1DM; n=110 T2DM). Sixty-five (59.1%) ppl w/T2DM used insulin for &amp;gt;5 years, while mean (SD) duration of diabetes was 30.6 (16.6) years for ppl w/T1DM and 16.0 (8.7) years for ppl w/T2DM. Forty (36.4%) ppl w/T1DM and 22 (20.0%) ppl w/T2DM reported impaired awareness (Gold score ≥4). During the last SHE, glucagon use was low (T1DM [8.2%]; T2DM [3.6%]); reasons for not using glucagon were not having a prescription (T1DM [40.0%]; T2DM [59%]) or it was unavailable (T1DM [20.0%]; T2DM [17.1%]). Also, ppl w/T1DM (75.5%) and ppl w/T2DM (83.6%) reported using oral glucose only for treatment; use of healthcare provider assistance was low. The main causes reported for a SHE were eating less than planned (T1DM [27.3%]; T2DM [47.3%]) or exercising more than planned (T1DM [21.8%]; T2DM [20.0%]). Results indicate that treatment of a SHE mainly occurred outside the healthcare system with fewer ppl having glucagon as an option for recovery. Disclosure F.J. Snoek: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Research Support; Self; Sanofi. Speaker's Bureau; Self; Lilly Diabetes. A. Jiletcovici: Employee; Self; Eli Lilly and Company. D.M. Bushnell: None. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. S.K. Bajpai: Employee; Self; Eli Lilly and Company. E. Spaepen: Consultant; Self; Eli Lilly and Company. J. Thomas: Employee; Self; Eli Lilly and Company. Z. Balantac: Other Relationship; Self; Eli Lilly and Company. M. Peyrot: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Calibra Medical. Research Support; Spouse/Partner; Eli Lilly and Company. B. Mitchell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.