bluuebunny/crossref_metadata_2025 huggingface dataset:
2131-P: BET Bromodomain Inhibition Upregulates SIRT1 In Pancreatic ß-Cells
Authors: JONES LIPINSKI RACHEL A. , WYNIA-SMITH SARAH , NORD JOSHUA , SMITH BRIAN C.
Published: June 2020

Diabetes develops as a result of both genetic and environmental influences; however, low concordance rates of type 1 diabetes between monozygotic twins and increased penetrance of type 2 diabetes during aging suggests an, as yet, poorly understood epigenetic role in diabetes development and progression. The epigenetic code, of which lysine acetylation (Kac) is a major histone post-translational modification, regulates the structure and dynamics of chromatin leading to epigenetically-controlled changes in gene accessibility toward transcription factors. Histone acetylation is regulated by histone acetyltransferases and deacetylases which write and erase sites of histone acetylation, respectively. SIRT1 is a key protein deacetylase in the control of glucose homeostasis. Decreased SIRT1 can lead to impaired insulin signaling, therefore drugs that enhance either SIRT1 expression or enzymatic activity may treat insulin resistance. Bromodomains are epigenetic readers that interpret the complex pattern of histone acetylation by binding Kac residues on histones and other nuclear proteins. Of particular interest are the bromodomain and extraterminal domain (BET) family of bromodomain-containing proteins, which have recently emerged as a potential target to treat or prevent diabetes. Interestingly, we recently found that treatment of β-cells with BET bromodomain inhibitors leads to increased SIRT1 expression levels, although the underlying mechanism was unclear. Here, we use an insulinoma β-cell line (INS832/13) and primary rat islets to determine the mechanism through which BET proteins suppress SIRT1 expression. To modulate SIRT1 and BET protein levels and activity, we used a combination of small molecules that either inhibit or degrade BET proteins, in conjunction with CRISPR/Cas9 knockout β-cell lines of both SIRT1 and the individual BET proteins.

In summary, BET inhibitors may provide an indirect means to increase SIRT1 activity in β-cells and improve β-cell function in the context of diabetes.

Disclosure

R.A. Jones Lipinski: None. S. Wynia-Smith: None. J. Nord: None. B.C. Smith: None.

Funding

American Diabetes Association (1-18-IBS-068 to B.C.S.); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119359)
2133-PUB: D10 vs. D50 for Treatment of Inpatient Hypoglycemia
Authors: JONES-RYAN MADELINE L. , ADDASI NOOR , KNEZEVICH JON T. , SAMSON KAELI , DRINCIC ANDJELA T.
Published: June 2020

Hypoglycemia is a common, difficult to prevent adverse outcome of inpatient diabetes care, which is associated with increased morbidity, mortality and length of stay. ADA standards of care 2020 recommend institutional adoption of evidence-based hypoglycemia management protocols. However, little data is available assessing the efficacy of common hypoglycemia treatment modalities utilized.

The aim of this retrospective study was to evaluate efficacy and safety of 4 hypoglycemia treatment modalities based on initial blood glucose; 50 ml of D50 (T1), 250 ml of D10 (T2), 25 ml of D50 (T3) and 125 ml of D10(T4). Chart review was done on 4,626 admitted to a tertiary medical center between 6/1/16 - 2/28/17 and 6/1/17 - 2/28/18, with 1 or more episodes of hypoglycemia. Patients included in the analysis were non-pregnant adults treated with insulin or oral glucose lowering agents who needed treatment with IV Dextrose. 618 patients met the inclusion criteria. Comparisons were made between the 4 treatment modalities after adjusting for baseline blood glucose; standard protocols recommend T1 and T2 for ADA level 2 hypoglycemia, vs. T3 and T4 for level 1 hypoglycemia. Mean blood sugars were : 48+/13 (T1), 4 8+/-12 (T2), 60 +/-7 (T3), and 61 +/-6 (T4). A difference in resolution of hypoglycemia at time 1 (a median of 21 minutes after treatment) was noted; 96.8% in T1, 94.5% in T2, 97.3% in T3 and 98.6% in T4 (P<0.0001). At time 2 (a median of 2.3 hours after the treatment), recurrent hypoglycemia was 25.8% in T1, 17.6% in T2, 15% in T3 and 16.5% in T4 (p=0.005). Hyperglycemia (>180 mg/dL) at time 2 was higher in T1 and T2, 11.7% and 11% respectively, compared with 6.3% in T3 and only 2.9% in T4 (P=0.005). 50 ml of D50 was associated with the highest rate of recurrent hypoglycemia. Across all arms, recurrent hypoglycemia was common at 2 hours after initial treatment, with time widely varied (19 minutes to 12 hours). Protocols should include ongoing monitoring after initial hypoglycemia.

Disclosure

M.L. Jones-Ryan: None. N. Addasi: None. J.T. Knezevich: Speaker’s Bureau; Spouse/Partner; Valeritas, Inc. K. Samson: None. A.T. Drincic: None.
2135-PUB: Identifying the Anthropometric Measurement and Lipid and Glucose Indexes That Best Correlate with Metabolic Syndrome in a Chinese Population
Authors: XIN ZHONG
Published: June 2020

In this investigation, we compared the performance of various parameters including Waist-to-Height Ratio (WHtR), Waist-Hip Ratio (WHR), Waist Circumference (WC), Body Mass Index (BMI), and triglycerides glucose related Index including TyG index, TyG-BMI, TyG-WC in detecting Metabolic Syndrome (MS). (TyG index: TG× FPG, TyG-BMI: TyG index × BMI, TyG-WC: TyG index × WC) In 2013, 2972 registered permanent residents in a rural satellite town of Beijing, aged ≥ 20 years, were invited to participate in the study. MS patients were identified with the criteria of Chinese Diabetes Society (CDS). The receiver-operating characteristics (ROC) curve analyses and the respective area under the ROC curves (AUC) were used to compare the association of the different index with MS.In men, the AUC was 0.81 (0.78-0.84) for BMI, 0.77 (0.74-0.81) for WHtR, 0.68 (0.63-0.72) for WHR, 0.77 (0.74-0.80) for WC in detecting MS, respectively. In women, the AUC was 0.78 (0.76-0.81), 0.76 (0.73-0.78), 0.66 (0.64-0.68), 0.76(0.74-0.78), respectively. The correlation between BMI and MS was higher than other indicators by comparing AUCs (P<0.05). In men, the AUC was 0.88 (0.86-0.90) for TyG index, 0.89 (0.87-0.92) for TyG-BMI, 0.88 (0.86-0.90) for TyG-WC, respectively. In women, the AUC was 0.88 (0.86-0.90), 0.88 (0.86-0.92), 0.87 (0.85-0.89), respectively. There were no significant differences for these three indexes. However, the correlation between TyG index and MS was higher than BMI (P<0.05).The cut-off points for BMI evaluating MS were 25.0 Kg/m2 in men and 25.3 Kg/m2 in women, and for TyG index were 8.87 in men and 8.80 in women. BMI is an efficient surrogate marker in the evaluation of MS in Chinese people. It can be used to screen MS patients and self-assess the risk in common people easily. TyG index is better than BMI in the evaluation of MS. This will help general practitioners to assess the risks of their patients quickly.

Disclosure

Z. Xin: None.

Funding

Expert Promotion Program of Beijing Health Systems (2015-3-017)
2140-PUB: Effect of Metformin on Incretin Secretion in Patients with Diabetes and Chronic Heart Failure
Authors: KOPECKY JAN , HOŠKOVÁ EVA , VELEBA JIRI , MELENOVSKY VOJTECH , PELIKANOVA TEREZIE
Published: June 2020

Aim: Metformin (MET) is a mainstay for treatment of type 2. diabetes (DM). Its use in patients with chronic heart failure (HF) patients is recent, associated with lower frequency of cardiovascular events and with better survival, but mechanisms of action are unclear. GLP-1 incretin is reported to have cardioprotective effects. Our aim was to assess the effects of MET on glucose metabolism, incretin secretion and cardiac function in patients with DM and HF.

Methods: A randomized, double-blind, placebo-controlled, crossover study testing the effect of 3 - month usage of metformin vs. placebo. Treatment naive patients with DM and HF were randomized to metformin (2 g/day) or to placebo group. At the beginning and the end of each intervention period (baseline, after MET and after placebo) panel of various metabolic tests including meal test and cardiac function tests (echocardiography, cardiopulmonary exercise test) was done.

Results: Metformin significantly reduced HbA1c. During meal test, metformin significantly reduced AUC of glucose, insulin and amylin; and increased GLP-1 and peptide YY. Details in Table. There was no change in cardiac function as assessed by echocardiography and spiroergometry.

Conclusions: Metformin therapy in patients with HF improves diabetes compensation and has no significant effect on cardiac function. Improvement might be partly mediated by alteration of gut endocrine function.

Disclosure

J. Kopecky: None. E. Hošková: None. J. Veleba: None. V. Melenovsky: None. T. Pelikanova: None.

Funding

VZ 00023001 IKEM
215-LB: Ablation of Nos-1 Neurons in the PVH Reveals an Essential Role in Sustaining Metabolic Homeostasis, Independent of Melanocortin Function
Authors: FAULKNER LATRICE D. , GONZALEZ IAN E. , OLSON DAVID , MEEK THOMAS H.
Published: June 2020

The paraventricular hypothalamus (PVH) is vital for energy balance regulation, as developmental or mechanical lesions targeting the PVH lead to massive obesity. We have shown that activation of PVH neurons expressing nitric oxide synthase-1 (Nos1PVH) suppresses food intake and increases energy expenditure. This differentiates these neurons from the well-studied melanocortin 4 receptor-expressing population (Mc4RPVH), as activation of Mc4RPVH neurons suppresses feeding but does not alter energy expenditure. In situ hybridization studies in our laboratory show that Mc4R and Nos1 mRNAs do not overlap in the PVH, suggesting that these cell populations may regulate energy balance independently. We hypothesize that the contributions of Nos1PVH neurons to maintaining metabolic homeostasis are independent of Mc4RPVH neurons. To test this hypothesis, we used established Nos1 and Mc4R Cre-expressing lines to create a Nos1Cre+Mc4RCre dual recombinase model. Then, we inactivated Nos1PVH and Mc4RPVH neurons alone or in combination. Several metabolic parameters were monitored for 8 weeks post-injection. These experiments allowed us to examine the interdependency of Nos1 and Mc4R PVH populations in energy balance control. Silencing the Nos1PVH population alone resulted in the acute onset of obesity without affecting feeding behavior. This phenotype was exacerbated when we simultaneously silenced both Nos1 and Mc4R PVH neurons. This suggests an additive interaction between the two groups; although a synergistic effect cannot be excluded. Future studies will focus on the effects of Nos1PVH inactivation on energy expenditure and defining the Nos1 neurocircuitry that facilitates PVH-mediated metabolic regulation. Our overall goal is to unravel the cellular and neurobiological mechanisms engaged by Nos1PVH neurons and open new avenues for treating obesity.

Disclosure

L.D. Faulkner: None. I.E. Gonzalez: None. D. Olson: Research Support; Self; MedImmune, Inc, Novo Nordisk A/S. T.H. Meek: Employee; Self; Novo Nordisk Inc.
215-OR: Silencing CCKBR Containing Neurons in the VMN Restrains Hepatic Glucose Production to Ameliorate Diabetes in Mice
Authors: AFFINATI ALISON , FLAK JONATHAN , BOZADJIEVA NADEJDA , KODUR NANDAN , CRAS-MÉNEUR CORENTIN M. , SANDOVAL DARLEEN A. , MYERS MARTIN G.
Published: June 2020

Optimal glucose control remains elusive for many patients with diabetes despite current therapies, necessitating the development of novel therapeutic modalities. While the central nervous system (CNS) plays a crucial role in glucose homeostasis, specific CNS targets for therapeutic intervention in diabetes have remained elusive. We recently demonstrated that the cholecystokinin b receptor (CCKbR)-expressing subpopulation of ventromedial hypothalamic nucleus (VMN; VMNCCKBR) neurons not only mediate the counter-regulatory response, but also elevate blood glucose by insulin-independently modulating hepatic glucose production under normal physiologic conditions. To test the potential therapeutic utility of these neurons for the treatment of diabetes, we cre-dependently expressed tetanus toxin in the VMN of Cckbrcre mice to silence VMNCCKBR neurons in streptozotocin (STZ)-induced (insulinopenic; Type 1 model) and leptin-deficient (ob/ob; obese Type 2 model) mice. While STZ-treated control mice became hyperglycemic and lost approximately 20% of their body weight over two weeks, VMNCCKBR-silenced mice were protected from these effects of STZ, despite similar hormone levels in STZ-treated control and CCKBRTTmice. Similarly, silencing of VMNCCKBR neurons in ob/ob mice normalized fasting and ad libitum-fed blood glucose despite identical food intake, body weight and body composition in control and VMNCCKBR-silenced mice. While VMNCCKBR-silenced ob/ob mice exhibited no alterations in glucose or insulin tolerance compared to controls, glucose clamps demonstrated decreased hepatic glucose output in the VMNCCKBR-silenced animals. These data suggest that VMNCCKBR neurons represent potential targets to reduce hepatic glucose production and ameliorate hyperglycemia in diabetes.

Disclosure

A. Affinati: Research Support; Self; Novo Nordisk Inc. J. Flak: None. N. Bozadjieva: None. N. Kodur: None. C.M. Cras-Méneur: None. D.A. Sandoval: Research Support; Self; MedImmune, Novo Nordisk A/S. M.G. Myers: Research Support; Self; AstraZeneca, Novo Nordisk Inc.

Funding

National Institutes of Health (5T32DK7245-42, 1F32DK122660-01)
2151-PUB: Association of Homocysteine with Early Nephropathy in Patients with Type 2 Diabetes
Authors: LI JIANBO , LV QING , LU HUAN , ZHANG HONGMAN , ZHOU JUN
Published: June 2020

Early predication and intervention of diabetic nephropathy is increasingly imperative. Hyperhomocysteinemia is common and chronically induces arteriolar thickening, and tubulointerstitial and podocyte injury, therefore, could play a causative role in early renal injury in the kidney in type 2 diabetes. In this study, we for the first time investigated the relation of plasma total homocysteine concentration to early nephropathy in type 2 diabetes. We enrolled 183 type 2 diabetic patients in a cross-sectional study. Early diabetic nephropathy status was diagnosed by presence of microalbuminuria. Plasma total homocysteine levels were measured using fluorescence polarization immunoassay. Variables for diabetic nephropathy were obtained from fasting blood samples and interviewer- questionnaire. We found that plasma total homocysteine concentrations were elevated in subjects with early diabetic nephropathy than without (13.3±2.9)µmol/l vs. (8.5 ± 1.4)μmol/l, p < 0.01). The association of homocysteine with the diabetic nephropathy was independent of major traditional risk factors for diabetic nephropathy (duration of diabetes, HbA1c, and blood pressure) and determinants of higher homocysteine concentration (age, sex, serum folate and vitamin B12, Biguanide use, and serum cystatin or creatinine levels,) (OR: 1.36 (1.08-1.74), p < 0.05). Furthermore, per increase of 5.0 μmol/l plasma homocysteine was related to early nephropathy (OR: 1.15 (1.04-1.29), p < 0.05), after controlling for per unit increase of other factors: per 5 year increase of duration of diabetes, per 1% increase of HbA1c, per 10 nmol/l increase of serum folate, per 100 pmol/l increase of serum B12, per 0.1 mg/L increase of serum cystatin or per 10 μmol/l increase of creatinine, and per 10 or 5 mmHg increase of systolic or diastolic blood pressure. We concluded that plasma total homocysteine concentration was independently associated with occurrence of early diabetic nephropathy. Future prospective studies are warranted.

Disclosure

J. Li: None. Q. Lv: None. H. Lu: None. H. Zhang: None. J. Zhou: None.

Funding

National Natural Science Foundation of China (81070655); Jiangsu Provincial Natural Science Foundation of China (BK2009441)
2156-PUB: Diabetic Foot Ulcers: Correlation of Nutritional Status of Type 2 Diabetic Patients of Hyderabad Sindh, Pakistan
Authors: SHAIKH IMRAN ALI
Published: June 2020

Objectives: To know the correlation of foot ulcers to the nutritional status of type 2 Diabetic patients of Hyderabad.

Study Design: Cross sectional study.

Place of Study: Private clinics of consultants of Hyderabad, Sindh, Pakistan.

Duration of Study: February 2015 to June 2016.

Methodology: 387 diabetic type 2 patients were selected from different clinics of physicians, orthopedics and diabetic consultants of sadder Hyderabad Sindh Pakistan. The mean age was 40±11.5 years. All patients were enrolled on prescribed proforma. Thorough clinical examination was done. Wagner’s classification was used to categorize diabetic foot ulcers. Nutritional status was classified on Mini Nutritional Assessment score and patients were divided into three groups according to Mini nutritional score. Blood samples were obtained for Hemoglobin%, blood sugar, serum calcium and serum albumin estimation. All patients were assessed radiologically by x-rays of involved foot. ANOVA test was used and p value <0.05 was considered statically significant.

Results: There was linear correlation in between Mini nutritional assessment and severity of diabetic foot ulcer (p <0.03). Biochemical parameter were also significantly associated with the severity of ulcers. Serum albumin was decreased in grade 4 ulcer significantly (p value <0.04), while hemoglobin was also decreased in grade 4 ulcer, p value (<0.05). There was no association of serum calcium to severity of foot ulcer, (p value >0.07).

Conclusion: Diabetic foot ulcers are common in type 2 diabetic patients and nutritional status is strongly associated with grade of severity. It is important to assess nutritional status of all diabetic patients.

Disclosure

I. Shaikh: None.
2159-PUB: Factors Associated with Health-Related Quality of Life among Diabetic Foot Ulcer Patients: A Cross-Sectional Survey from Saudi Arabia
Authors: ALDAWISH MOHAMMED , AL-AYED MOUSAB
Published: June 2020

Objective: To estimate the Health-Related Quality of Life (HRQOL) related risk factors in Diabetic Foot Ulcer (DFU) patients.

Methods: This cross-sectional study was performed using 81 type 2 diabetes patients with DFU, from January 2019 to May 2019, at one of the chief tertiary hospitals in Riyadh, Saudi Arabia. The study population was chosen with purpose and convenience, based on patient availability during their regular and customary outpatient clinic visits. Using the Arabic version of the Short-Form 36-Item Survey (SF-36) these patients were interviewed and the HRQOL was assessed.

Results: From the univariate analysis preformed, it was evident that the independent factors mentioned induced vital variations in the patients’ physical functions viz., age, gender, education, occupation, smoking, duration of diabetes, hypertension, dyslipidemia, body mass index (BMI) and the number of diabetes-associated complications, hypertension and dyslipidemia. The physical health of the patient was strongly influenced by gender, education, occupation, income, BMI and number of complications. The emotional health of the patient was affected by dyslipidemia, deformity and prior amputations, as well as BMI and glycosylated hemoglobin (HbA1c). The social standing of the patient was impacted by age, income, education, and occupation. The degree of pain experienced by the patient varied with age and number of complications, as well as with the notable differences in their general health. The factors of age, education, occupation, income and number of complications induced several health changes to differing degrees.

Conclusion: The DFU patients generally revealed low HRQOL. However, prospective and large-scale studies are required, in the future, to support these findings.

Disclosure

M. Aldawish: None. M. Al-Ayed: None.
216-OR: O-GlcNAc Transferase in the Ventromedial Hypothalamus Regulates Lipid Metabolism through Fat Depot–Specific Sympathetic Innervation
Authors: WANG QI , ZHANG BICHEN , YANG YUNFAN , MI JIA , TIAN GENG , ONG QUNXIANG , YANG XIAOYONG
Published: June 2020

The ventromedial hypothalamus (VMH) is a primary site that initiates counter-regulatory response and regulates food intake, maintaining glucose and lipid homeostasis. Known as a nutrient sensor and metabolic regulator, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of intracellular proteins is catalyzed by O-GlcNAc transferase (OGT). How O-GlcNAc signaling in the VMH regulates whole-body metabolism remains unknown. Here, using the mouse model with VMH neuron-specific OGT deletion (VOK), we report that OGT is a nutrient sensor in VMH neurons that primarily regulates lipid metabolism. VOK mice show increased body weight and adiposity as well as reduced energy expenditure. OGT deletion in VMH neurons has no significant effects on food intake, physical activity, substrate utilization, glucose tolerance or insulin sensitivity. Lipolysis in subcutaneous and visceral white adipose tissues (WATs) is reduced in VOK mice, indicated by reduced activation of hormone-sensitive lipase (HSL) via cAMP-dependent protein kinase (PKA). In addition, VOK mice have lower serum glucagon and norepinephrine levels and show impaired depot-specific sympathetic innervation to WATs. These data reveal that O-GlcNAc signaling in VMH neurons specifically controls lipid metabolism through depot-specific sympathetic innervation.

Disclosure

Q. Wang: None. B. Zhang: None. Y. Yang: None. J. Mi: None. G. Tian: None. Q. Ong: None. X. Yang: None.

Funding

American Diabetes Association (1-19-IBS-119 to X.Y.); National Institutes of Health (R01DK089098, R01DK102648)
2163-PUB: Prevalence of Multiple Stress Factors in Young Adults with Type 2 Diabetes
Authors: DAVE SHRUTI , SUNTHARAMOORTHY KAJANA , MOHYIDDIN SYED SIKANDER , MUHAMMAD UMER , MALIK SANA , GUPTA NIKHIL
Published: June 2020

Introduction: Incidence of type 2 diabetes (T2DM) among young adults (age <= 40) has been increasing rapidly. We hypothesize that this could be due to increasing levels of stress seen in this age group due to demographic, economic and environmental shifts that have occurred in the past 30 years.

Method: Modifiable vs. non-modifiable risk factors were evaluated at a specialist diabetes and endocrinology clinic. Consecutive patients meeting the inclusions criteria (T2DM between the ages of 18 to 40), were provided with study questionnaire at their appointment over a 3 month period. The questionnaire assessed socio-economic factors, self-reported levels of stress, dietary habits, sleep duration and physical activity.

Results: 52 patients (Males = 38 (73%)) completed the study questionnaire. Mean age (± SD) at diagnosis of T2DM was 31 (± 5.8). Thirty five (79%) were immigrants to Canada, of which 47% had immigrated to Canada within the last 10 years (2010-2019). Of the study participants, mean stress level (on a scale of 1-10) was 5.9 (± 2.7). Work stress was reported by 79.1%, financial stress by 43.7%, family related stress by 39.5%, and unemployment related stress by 10.4% of the patients. Other stressors reported were weight management and medication coverage. Twenty (38%) participants reported sleeping an avg of ≤ 6 hrs/day. Moderate intensity physical activity (≥ 150 mins per week) prior to diagnosis was reported by 36% patients.

Discussion: High prevalence of modifiable risk factors such as stress, decreased physical activity, inadequate sleep was found in young adults with T2DM. Immigrants are at high risk of T2DM at a young age likely due to stressors as well as diet and lifestyle changes involved in relocating to a new country. Education regarding higher risk of T2DM at an early age, and interventions to reduce modifiable risk factors is paramount at an individual and societal level, in order to stem the epidemic of young onset T2DM.

Disclosure

S. Dave: None. K. Suntharamoorthy: None. S. Mohyiddin: None. U. Muhammad: None. S. Malik: None. N. Gupta: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi.
2165-PUB: Jabuticaba Juice Improve Glucagon-Like Peptide-1 in Healthy Participants: Results from a Pilot, Single-Blinded, Randomized Controlled Trial
Authors: GERALDI MARINA V. , CAZARIN CINTHIA B.B. , VASQUES ANA CAROLINA J. , NETO BRUNO G. , MAROSTICA JUNIOR MARIO R.
Published: June 2020

Introduction: The effects of jabuticaba on health, particularly on glucose metabolism and GLP-1 deserve further clinical investigation.

Objective: The objective was to evaluate whether consumption of a jabuticaba juice preload containing 503 mg gallic acid equivalent and 2g of fibers would exert any effect on postprandial glycaemia, insulin, C-peptide, GLP-1, and appetite sensations.

Methods: Sixteen healthy subjects (11 women; 5 men; 28.4 ± 3.8 years; BMI 21.7 ± 2.3 kg m−2) completed a randomized, crossover intervention study. Jabuticaba or control beverage was consumed before a white wheat bread (WWB) challenge meal. Blood samples were taken frequently over the following 2 h. Blood glucose, serum insulin, C-peptide, and antioxidant capacity, plasma GLP-1, and appetite sensations were evaluated.

Results: Postprandial GLP-1 response as AUC, was higher after consumption of jabuticaba juice compared with control (95.6±41.4 vs. 82.7±24.6 ng/mL; p = 0.03). The GLP-1 significantly increased after jabuticaba juice, peaking at 60 min (1.21±0.5 vs. 0.71±0.2 ng/mL; p = 0,019). The AUC of antioxidant capacity was higher for jabuticaba juice vs. control (37.9±19.4 mmol TE/mL vs. 32.4±8.4; p = 0.005). Postprandial glucose, insulin, C-peptide levels, and appetite sensations were not significantly different between groups.

Conclusion: Inclusion of jabuticaba juice before a WWB challenge meal might be beneficial for antioxidant status and GLP-1 concentrations, but we did not find supporting evidence in glycaemia, C-peptide, insulin, insulin sensitivity and appetite sensations in healthy subjects.

Disclosure

M.V. Geraldi: None. C.B.B. Cazarin: None. A.J. Vasques: None. B.G. Neto: None. M.R. Marostica Junior: None.

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) (001); CNPq (403328/2016-0; 301108/2016-1); FAPESP (2015/50333-1)
2169-PUB: Premeal Consumption of a Small, Ready-to-Drink Whey Protein Shot Suppresses Postprandial Hyperglycemia in Adults with Type 2 Diabetes
Authors: SMITH KIERAN , TAYLOR GUY S. , BOWDEN DAVIES KELLY A. , BRUNSGAARD LISE H. , JENSEN ERIK , WALKER MARK , STEVENSON EMMA J. , WEST DANIEL J.
Published: June 2020

Background: The consumption of large (∼50g) doses of whey protein [WP] before meals (i.e., preload) has been shown to improve postprandial glycemic [PPG] excursions in people with type 2 diabetes [T2D]. Yet, studies to date have not accounted for treatment palatability, the energy associated with large WP doses, or the burden allied with preload preparation, limiting its ecological translation. Herein, we examined the PPG responses to a mixed-meal tolerance test [MMTT] following prior consumption of a low dose of WP from a novel, pre-made shot in people with T2D.

Methods: Nine adults with T2D (8M/1F; HbA1c 57.6±10.1 mmol∙mol) attended the laboratory on two occasions, ∼14d apart. After an overnight fast, subjects randomly consumed a bespoke, ready-to-drink WP (15g) or placebo [PLA] shot (100ml) 10min prior to a 4hr MMTT (387kcal; 58% CHO). At 4hr, a further shot was consumed 10min before an ad libitum lunch. Subjective appetite and preload palatability were assessed by visual analog scales. Interstitial glucose was measured throughout. Data (mean±SD) were analyzed by a two-way repeated measures ANOVA.

Results: Compared to PLA, WP attenuated early [0-60min] (-48.9±35.9%; p=0.01) and total [0-240min] PPG area under the curve (-22.7±17.5%; p<0.001). During both trials, peak PPG occurred ∼80min post-MMTT and was reduced following WP (-13.8±7.8% [range: -23.0 to +2.1%]; p<0.01). The peak incremental change in PPG was 1.36±1.08 mmol∙L less following WP vs. PLA (p<0.01). Subjective appetite (p>0.05) and ad libitum energy intake were similar between trials (p=0.48). Both preloads were rated highly palatable.

Conclusion: Consuming a small, bespoke WP shot lowers post-meal hyperglycemia in people with T2D without affecting satiety and satiation. We highlight the potential for small, contemporary WP beverages that encompass both glycemic benefit but also patient taste and convenience, which may have lasting clinical value beyond formal research studies.

Disclosure

K. Smith: None. G.S. Taylor: None. K.A. Bowden Davies: None. L.H. Brunsgaard: None. E. Jensen: Employee; Self; Arla Foods Ingredients. M. Walker: None. E.J. Stevenson: None. D.J. West: None.

Funding

Arla Foods Ingredients Group P/S
2189-PUB: Insulin Pen Injection Techniques in Patients with Type 2 Diabetes in China
Authors: LI FAN , FISH ANNE , TOKAC UMIT
Published: June 2020

Background and Objective: In the midst of a type 2 diabetes epidemic in China where hemoglobin A1C needs to be better controlled, clinicians strive to examine and work to correct patients’ poor insulin pen injection practices. We explored insulin injection techniques, injection site problems, and A1C.

Methods: In a large cross-sectional study of adult patients with type 2 diabetes (n=455) from 10 medical centers, patients answered an in-depth questionnaire and had their insulin injection technique observed. Researchers assessed for lipohypertrophy (LH) by observing and palpating injection sites. Logistic regression and linear regression were used to examine factors related to presence of LH and A1C.

Results: Mean years taking insulin was 5.20, and 83.30% injected insulin ≥2 times/day. Mean needle reuse was 8.95 times (range 1-59), but was not correlated with LH or A1C. Percent with incorrect site rotation was 22.80% and presence of LH was 11.14%. A1C was 9.03±2.13%. Presence of LH was significantly associated with longer duration of insulin injection (OR=1.10, p=0.01, 95% CI [1.02, 1.17]) and total number of insulin injections/day (OR=2.27, p<0.001, 95% CI [1.49, 3.44]), but not with incorrect site rotation (OR=0.45, p=0.07, 95% CI [0.19, 1.06]). Odds of presence of LH in participants using 5 mm needles were 3.95 times (p=0.01, 95% CI [1.48, 10.54]) that of 4 mm needles. Higher A1C was significantly associated with the presence of LH (ß=0.54, p<0.01, 95% CI [0.20, 0.88]).

Conclusion: Needle reuse is a major problem in Chinese patients with type 2 diabetes, and A1C is poorly controlled. Patients with LH are more likely to have higher A1C. Given the diabetes epidemic in China, immediate measures must be implemented to improve insulin injection techniques and prevent LH for better glycemic control. This study indicated that 4 mm needles may have an advantage over 5 mm needles in regard to the presence of LH, yet further studies are needed to examine this relationship.

Disclosure

F. Li: None. A. Fish: None. U. Tokac: None.
219-OR: Comparison of the Impact of Autologous Cell Therapy and Conservative Treatment on Chronic Limb-Threatening Ischemia in Patients with Diabetic Foot: A Randomized Controlled Trial
Authors: DUBSKY MICHAL , BEM ROBERT , NEMCOVA ANDREA , HUSÁKOVÁ JITKA , FEJFAROVA VLADIMIRA , JIRKOVSKA ALEXANDRA , SUTORIS KAROL
Published: June 2020

Background: Autologous cell-therapy (ACT) is a new treatment method for patients with diabetes and no-option chronic limb-threatening ischemia (NO-CLTI). We aimed to assess the impact of ACT on CLTI in comparison with standard treatment (ST) in a randomized controlled trial.

Methods: Forty diabetic patients with NO-CLTI were randomized to receive either cell therapy (n=20) or standard conservative therapy (n=16); 4 patients dropped out of the study. After 3 months, those in the ST group were switched to ACT (cell therapy crossover). The effect on ischemia and diabetic foot was assessed by changes in transcutaneous oxygen pressure (TcPO2) and the number of healed patients at 3 months. Amputation rates and amputation-free survival (AFS) were assessed at 3 months and then during 12-month follow-up.

Results: TcPO2 increased significantly in the ACT group after 1 and 3 months (both p<0.001) whereas TcPO2 in the control group remained unchanged (NS). After the crossover to cell therapy in patients of the ST group, we observed a significant increase in TcPO2 at 1 and 3 months after the injection of ACT (p=0.036 and p<0.001, respectively). We also observed significantly more healed patients at 3 months in the ACT group compared to the ST group (p=0.01). The rates of major amputation and AFS at 3 months were not significantly different between the ACT and ST groups (both NS). In Kaplan-Meier estimate, patients treated initially by ACT showed a trend towards higher AFS rates compared to those treated initially by ST who received ACT after the 3-month delay, but without a significant difference (65 vs. 43.8%).

Conclusions: Our study showed that ACT in patients with no-option CLTI and diabetic foot significantly improved limb ischemia and wound healing when compared to standard conservative therapy, without influencing amputation rates and with a trend to higher 1-year AFS in comparison with delayed ACT treatment in ST group.

Disclosure

M. Dubsky: None. R. Bem: None. A. Nemcova: None. J. Husáková: None. V. Fejfarova: None. A. Jirkovska: None. K. Sutoris: None.

Funding

Ministry of Health of the Czech Republic (16-27262A, 00023001)
2191-PUB: Challenging the 50%/50% Basal/Bolus Insulin Ratio Rule: Have We Been Wrong? A Cross-Sectional Study
Authors: HODISH ISRAEL , WILLIS MARK , SRITHARAN SAJITHA , BASHAN ERAN
Published: June 2020

There is a generally-held belief that the ratio between basal and bolus insulin requirements in patients using insulin therapy should be 50%/50%. Yet, it appears this belief was based on a small study with healthy individuals, which may not be applicable to patients with insulin deficiency. To assess the validity of the rule we followed patients with type 2 diabetes treated with basal-bolus insulin therapy that has been frequently adjusted by a technology-based titration service. To keep glycemia stable, the service adjusts insulin dosage at least weekly and thus treatment closely tracks insulin requirements. We performed a cross-sectional study, accumulating data on N=306 patients over an average±SD period of 3.4±1.7 years. Insulin titrations occurred every 6.8±1.5 days to enable HbA1c maintenance at 7.2±0.7%. In 74.8% of the patients the average basal insulin fraction was less than 50% of total daily dose of insulin, and in about a third it was less than 38% (Figure). Additionally, the basal fraction did not remain stable in each patient over time (Figure). In 79.7% of the patients, it changed more than 20% and in 50% more than 29.8% (e.g., basal fraction changes in a single patient would range between 20% and 50% over time). In patients with type 2 diabetes treated with insulin, basal-bolus ratio is not 50%/50% and it changes over time. Thus, this ratio should not be used as a treatment guide.

Disclosure

I. Hodish: Stock/Shareholder; Self; Hygieia. M. Willis: Employee; Self; Hygieia. S. Sritharan: None. E. Bashan: Employee; Self; Hygieia. Stock/Shareholder; Self; Hygieia.
2196-PUB: The Influence of Insulin Degludec on Type 2 Diabetes Mellitus Regulation and Patient Quality of Life Compared with Insulin Glargine in Low-Income Patients
Authors: KOUTSOVASILIS ANASTASIOS , SOTIROPOULOS ALEXIOS , PAPPA MARIA , BOUSBOULAS STAVROS , PEPPAS THEODOROS
Published: June 2020

Background: Insulin glargine is a well known long-acting insulin analog in the contemporary treatment of type 2 diabetes mellitus (T2DM). A new long-acting, but more expensive insulin, degludec, shows greater duration compared to already existing long-acting insulins.

Aim: The aim of the study is to examine the effect of insulin degludec on T2DM glycaemic control and patient quality of life in low-income patients compared with insulin glargine. Material and Methods: 116 T2DM patients were enrolled in the study. 41 were insulin naïve treated with degludec (Group A), 40 were insulin naïve treated with insulin glargine (Group B) and 36 patients who were on glargine without satisfactory glycemic control were treated with degludec instead of glargine (Group C). Three and six months later, their glycemic control, insulin units, quality of life (SF-36), as well as flexibility in insulin use were assessed. All patients answered the PHQ-9 questionnaire

Results: The mean HbA1c for all patients was 8.42±1.23 (p=0.251). The reduction in HbA1c was similar between the three groups (p=0.182). Hypoglycemias became less frequent after the transition from insulin glargine to degludec (p=0.059). Patients in Group A showed less hypoglycemias in 3 months (p=0.036) and six months (p=0.033). Hypoglycemias were significantly reduced for Group B after the first 3 months (p=0.087). All three groups showed a significant improvement in quality of life but patients in Group A achieved the better score in physical (56.2±10.6 vs. 50.8±9.7 vs. 52.7±10.4, p=0.059) and mental (46.2±8.4 vs. 42.5±7.7 vs. 44.5±8.5, p=0.064) health summary compared to Group B and C respectively. Patients in Group A used fewer units compared to Group B and Group C (p=0.067)).

Conclusion: The use of degludec is associated with a lower rate of hypoglycemias and a good quality of life while many patients availed themselves of the possibility of degludec insulin’s flexible use.

Disclosure

A. Koutsovasilis: None. A. Sotiropoulos: None. M. Pappa: None. S. Bousboulas: None. T. Peppas: None.
2204-PUB: The Efficacy of Da Chaihu Decoction with Metformin Tablets for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
Authors: WANG JIABIN , WANG MENG , HUANG PEIYAO , WANG YANXIA , QIU JIE
Published: June 2020

Ethnopharmacological Relevance: Da Chaihu decoction (DCHD) is a traditional Chinese herbal formula commonly used for the treatment of type 2 diabetes mellitus.

Objective: To assess the efficacy of DCHD combined with Metformin Tablets for type 2 diabetes mellitus (T2DM).

Methods: A review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction: Excerpt Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Papers published until December 2019 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.3.

Results: Seven randomized controlled trials comprising 579 participants were included in the systematic review and meta-analysis. The results of meta-analysis showed that there was statistical difference of 7 RCTs between Da Chaihu decoction with Metformin Tablets group and was superior to Metformin Tablets group in fasting plasma glucose(FBG)(−0.71 mmol/L; 95% CI [−1.27,−0.15]) , plasma glucose 2 Hours after Meal (PBG) (−1.21 mmol/L; 95% CI [−1.88, −0.53]) and there was 3 RCTs in Triglyceride(TG) (−0.63 mmol/L; 95% CI [−1.08, −0.17]). There was no statistical difference of 3 RCTs in Total Cholesterol (TC) (−0.63 mmol/L; 95% CI [−1.08, −0.17]).

Conclusions: Current evidence shows that Da Chaihu decoction combined with Metformin Tablets exert certain efficacy and safety for the treatment of T2DM. However, due to the low quality of the included studies, the conclusion still needs more high-quality, multi-center randomized double-blind controlled trials to verify.

Disclosure

J. Wang: None. M. Wang: None. P. Huang: None. Y. Wang: None. J. Qiu: None.
2208-PUB: Effect of Pioglitazone on HOMA-IR, C-Peptide, HbA1c, and Weight
Authors: SHETH SHRUTI V. , PAREKH MALAY N. , PANCHAL DHARMENDRA
Published: June 2020

Aim: To observe the effect of Pioglitazone on improving HOMA-IR, c-peptide status, HbA1c and Weight.

Materials and Methods: Inclusion Criteria: Persons with type 2 diabetes since >5 years duration of age 18-50 years, on dual OAD therapy

Exclusion Criteria: Other forms of diabetes, pregnant patients or planning for pregnancy.

For the study, 116 patients were identified and screened. Baseline investigations and anthropometry was recorded.

Pioglitazone was added to the ongoing regimen of single or dual combination therapy for a period of 24 weeks. All patients were called for a total of 6 visits during the study period wherein their glycemic control, hypoglycemia events and medications were reviewed.

At the end of 24 weeks, anthropometry, investigations and glycemic control was reviewed.

Results: The average c-peptide, HOMA-IR and HbA1c levels had reduced significantly after the addition of Pioglitazone. Those patients who were on dual therapy of metformin with an SGLT2 inhibitor showed no significant weight changes at the end of the study. Other patients who were on monotherapy with metformin, dual therapy with metformin plus other OADs showed weight gain.

Conclusion: Pioglitazone is a very effective tool in diabetes management. It shows significant reduction in glycemia. Appropriate combination therapy with SGLT2 inhibitors may curb its issue of weight gain.

Disclosure

S.V. Sheth: None. M.N. Parekh: None. D. Panchal: None.
2238-PUB: A Diabetes Prevention Evaluation Model for Health Care Organizations: Pilot Results for Target Population
Authors: KHAN TAMKEEN , HUGHES ALEJANDRO , SACHDEV NEHA , BALAN ANITA , PERE DANIELLE
Published: June 2020

Health care organizations play a critical role in diabetes prevention by identifying and managing individuals with prediabetes. This project piloted a systematic diabetes prevention evaluation ’M.A.P. model’. The framework’s key components includes the ’M’ related to ’measuring accurately’ by identifying adults with prediabetes; the ’A’ related to ’acting rapidly’ by initiating treatment specifically, referral to a National Diabetes Prevention Program (DPP) lifestyle change program (LCP); and the ’P’ related to ’partnering with patients’ to support treatment participation in a LCP. The model was implemented at 3 grantee sites focused on building capacity to address diabetes prevention in a target disparate population of women who identify as Black and/or Hispanic. Aggregate data for a 12-month baseline period for the ’M’ metric found that the total number of adults at risk for abnormal glucose with laboratory tests ordered averaged only 57% (39-69%) of those eligible and 61% (39-69%) for those sites participating in the intervention. Documentation of a prediabetes diagnosis with an ICD-10 code was 51% (42-65%) for the total and 58% (42-65%) among the participating sites. The ’A’ metric submitted by 2 sites to date found only 8% (7-9%) of all patients and 10% (9-42%) of target population patients eligible for the LCP had a clinical referral order. Data for the ’P’ metric submitted by 1 site to date reported a 25% enrollment rate, of which 86% consisted of the target population, and 91% were referred from a primary care provider rather than a self-referral. The findings highlight that tracking metrics related to diabetes prevention in health care organizations is feasible. The initial results suggest that a structured evaluation model can help organizations and clinical care teams identify opportunities for improvement and guide targeted activities to increase prediabetes patient identification, National DPP LCP referrals, and program enrollment and completion rates.

Disclosure

T. Khan: None. A. Hughes: None. N. Sachdev: None. A. Balan: None. D. Pere: None.

Funding

Centers for Disease Control and Prevention (6NU38OT000289-01-01)
224-LB: Role of the Mitochondrial Calcium Uniporter in the Regulation of Hepatic Mitochondrial Metabolism and Gluconeogenesis
Authors: LAMOIA TRACI E. , LEE JI EUN , GUERRA MATEUS , GOODMAN RUSSELL , SHULMAN GERALD I.
Published: June 2020

The mitochondrial calcium uniporter (MCU) is a key regulator of mitochondrial calcium, however, the role of MCU in mediating hepatic mitochondrial metabolism and gluconeogenesis has received limited attention. In order to address these questions, we examined rates of mitochondrial oxidation in both liver slices and in awake liver-specific MCU knockout (MCU KO) mice. We found that deletion of MCU significantly increases glucagon-induced intrahepatic lipolysis (p<0.04) and glucose production (p<0.04) in ex vivo liver slices. We also observed significantly reduced liver triglyceride accumulation (p<0.05) and increased hepatic long chain acyl-CoA (p<0.02) and acetyl-CoA (p=0.05) content in MCU KO mice, consistent with increased intrahepatic lipolysis and fat oxidation. This effect was not due to changes in white adipose tissue lipolysis. Deletion of MCU also impaired glucose tolerance in chow-fed mice, indicating dysregulated hepatic glucose production in these mice. These metabolic alterations could be attributed to reduced mitochondrial buffering of cytoplasmic calcium, leading to a 77% increase in cytoplasmic calcium (p<0.0001). This led to activation of CAMKII (p<0.04) and subsequent increase in ATGL phosphorylation (p<0.04) in hepatocytes lacking MCU.

In conclusion, these results demonstrate a critical role for MCU in mediating hepatic mitochondrial oxidation and hepatic gluconeogenesis.

Disclosure

T.E. LaMoia: None. J. Lee: None. M. Guerra: None. R. Goodman: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, LLC, Merck & Co., Inc. Advisory Panel; Spouse/Partner; Merck & Co., Inc. Consultant; Self; Novo Nordisk A/S. Consultant; Spouse/Partner; Novo Nordisk A/S. Other Relationship; Self; Gilead Sciences, Inc., iMetabolic Biopharma Corporation. Other Relationship; Spouse/Partner; iMetabolic Biopharma Corporation. Other Relationship; Self; Maze Therapeutics.

Funding

National Institutes of Health (T32GM0007324)
224-OR: Effect of Macronutrient Intake on Glycemic Outcomes over 1 Year in Youth with T1D
Authors: LA BANCA REBECCA O. , VOLKENING LISA K. , DASSAU EYAL , MEHTA SANJEEV N. , LAFFEL LORI M.
Published: June 2020

Aim: Insulin bolus doses are mainly based on ambient glucose level and planned carbohydrate (CHO) intake, although fat and protein content of food also impact glycemic excursions. We examined the impact of macronutrient intake on glycemic outcomes in youth with T1D.

Methods: Youth (N=136, ages 8-17) with T1D provided diet (3-day food records) and glucose (3-day masked CGM [iPro™]) data every 3 months for 1 year (5 time points). Diet data were analyzed using Nutrition Data System for Research (NDSR). Macronutrient % intake was derived as the mean for each 3-day period. Glycemic outcomes were A1c and CGM metrics: glucose % time in range (TIR) 70-180 mg/dL, % time (T) <70, %T>180, and glucose CV. Longitudinal mixed models assessed the effect of macronutrient intake on glycemic outcomes.

Results: Youth (48% male) had a mean age of 12.8±2.5 years and T1D duration of 5.9±3.1 years; youth checked BGs 5.6±2.4 X/day and 73% used insulin pumps. At baseline, A1c=8.1±1.0%, %TIR=49±17% (11.8 hrs), %T<70=6±8% (1.4 hrs), %T>180=44±20% (10.6 hrs), and CV=41±8%; macronutrient % intake was 48±5% CHO, 36±5% fat, and 16±2% protein. Over 1 year, differences in macronutrient intake affected glycemic outcomes (Table).

Conclusions: Our data confirm the significant impact of fat and protein intake on glycemic outcomes. These findings offer an opportunity to tailor algorithms to assist with meal-time bolus dosing and automated insulin delivery systems.

Disclosure

R.O. La Banca: None. L.K. Volkening: None. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. S.N. Mehta: None. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US.

Funding

National Institutes of Health (P30DK036836, K12DK094721)