bluuebunny/crossref_metadata_2025 huggingface dataset:
2210-PUB: Nonselective Mineralocorticoid Receptor Antagonist May Alter Morning Elevation of Plasma Glucose Levels after Waking
Authors: YAMAUCHI KEISHI
Published: June 2020

Previously, we reported that morning plasma glucose (PG) elevation before wake-up(W1) and after wake-up(W2), occur through different mechanisms in patients with type 2 diabetes. We measured three point PGs by Point-of-Care Testing (POCT) and flash glucose monitoring system (FreeStyle Libre Pro™); midnight (3 am), the time of awakening (about 6 am) and just before breakfast (8 am), hormones and their metabolites in 32 hospitalized patients with type 2 diabetes. Those with insulin therapy or overtly elevated fasting PG (>11 mmol/L) were excluded. W1 could be explained by relative insulin deficiency. Urinary normetanephrine, reflects a sum of production of norepinephrine was significantly correlated with W2 (R=0.422, p<0.01). Level of other antagonistic hormones including urinary metanephrine was not correlated with W2. Norepinephrine, a relatively selective agonist of alpha-adrenergic receptor, within the normal range, may be responsible for W2. It has been reported that spironolactone, a nonselective mineralocorticoid receptor antagonist, may have a deleterious effect on glycemia. Spironolactone (25mg) was administered 5 female diabetic patients with hypertension for seven days. Spironolactone significantly increased W2 (8 am PG minus 6 am PG) (0.1±0.4 mmol/L to 0.5±0.9 mmol/L, p<0.05) but not W1(6 am PG minus 3 am PG) (0.2±0.5 mmol/L to 0.2±0.3 mmol/L, p>0.05). The Urinary normetanephrine was increased by the treatment (0.19±0.19 mg/gCre to 0.26±0.11 mg/gCre, p<0.05). But the treatment did not change urinary metanephrine (0.16±0.10 mg/gCre to 0.17±0.08 mg/gCre, p>0.05). Further, eplerenone(50mg), a selective mineralocorticoid receptor antagonist affected neither W1 nor W2 in 2 male diabetes patients with hypertension. These results suggested that nonselective mineralocorticoid receptor antagonist may affect glucose metabolism via change of alpha-adrenergic tone.

Disclosure

K. Yamauchi: None.
2219-PUB: Comparison of Efficacy of Canagliflozin 100mg vs. Canagliflozin 300mg on hs-CRP in Patients with Type 2 Diabetes Mellitus
Authors: GUPTA VISHAL , TELI VAISHALI , PATEL ALTAF
Published: June 2020

Aim: To compare the efficiency of canagliflozin (C1) 100mg vs. canagliflozin (C3) 300mg on highly sensitive C reactive protein (hs-CRP) and other cardio-renal (CR) biomarkers.

Methodology: Between July and Sept 2018, a cohort of 190 T2DM patients aged 18-75 yrs, irrespective of baseline A1c, receiving SGLTi C1 or C3 were identified. A propensity score 1:1 matching was done for both the groups with variables that could affect treatment outcomes and to minimise confounding. Patients were evaluated every 2-3months for CR biomarkers (body mass index (BMI), A1c, systolic (S) BP, diastolic (D) BP, Lipid profile (TC, LDL, TG, HDL), Hs-CRP, creatinine, eGFR and urinary albumin/creatinine ratio {UACR}). NT-ProBNP was evaluated at 12 months. T2DM with history of IHD, revasularisation, major surgery, hyperkalemia >5.5Meq/L and eGFR<45 were excluded. Baseline characteristics were analyzed using descriptive statistics expressed as % or mean±SD. Comparison between the groups was performed using paired and unpaired t-test expressed as mean ± SE and p value <0.05 was considered significant(S). For interaction between drug class, ANOVA was used.

Results: 44 patients were identified in C1 gr and 44 in C3 gr. Baseline characters were well matched in both gr except, SBP (mean±SD) (C1 129.05±17.54 vs. C3 138.05±22.22, P-0.38).C1 gr (baseline to 12m): there was a S reduction in hs-CRP, A1c, BMI, SBP, DBP, TC, TG, LDL. C3 gr (baseline to 12m): there was a S reduction in hs-CRP, A1c, BMI, SBP, DBP, TC, LDL. Difference between C1 and C3 at 12m: There was no difference in hs-CRP mg/L {C1 1.88±0.43 vs. C3 1.31±0.46, p-0.371}, A1c% {C1 1.27±0.19 vs. C3 1.44±0.34, p-0.666}, BMI kg/m2 {C1 1.24±0.27 vs. C3 1.23± 0.25, p-0.988}, NT-ProBNP pg/ml {C1 63.95±65.52 vs. C3 61.53±61.71, p-0.864} eGFR {C1 6.39±3.37 vs. C3 0.99±3.20, p-0.952}, UACR mg/gm {C1 25.48±10.86 vs. C3 9.61±7.87, p-0.240}, Lipid profile, SBP and DBP between both gr.

Conclusion: Canagliflozin 100mg is as good as canagliflozin 300mg in reduction of hs-CRP and CR markers.

Disclosure

V. Gupta: None. V. Teli: None. A. Patel: None.
2222-PUB: Differences In Clinical Background between Patients with and without Increased Glucagon Secretion while on SGLT2 Inhibitors: A Comparison of Canagliflozin and Other SGLT2 Inhibitors
Authors: ISHIGURO MIZUKI , MORI YUTAKA , NISHIMURA RIMEI
Published: June 2020

Objective: This study was conducted to characterize differences in clinical background between patients with and without increased glucagon secretion while on SGLT2 inhibitors (S).

Methods: Of the 75 type 2 diabetic patients admitted for glycemic control who were not receiving incretin-related drugs nor S at admission, 22 patients received S but no incretin-related drugs after admission and were subjected to meal tolerance tests (MTTs) during early morning fasting hours at admission and after improving glycemic control. Blood samples were drawn from these patients preprandially and 30, 60, and 120 minutes postprandially to measure their glucose, C-peptide, and glucagon (Mercodia) values. First, based on changes in glucagon secretion observed in MTTs, they were divided into those with increased AUC glucagon (n = 13) and those without (n = 9) and compared for changes in MTT parameters. Then, they were also divided canagliflozin (Cana) group (n = 12) and other S (non-Cana) group (n = 10) and compared for changes in MTT parameters.

Results: Although those without increased AUC glucagon showed a significant increase in ΔCPR/Δglucose 0-30 min after improving glycemic control, those with increased AUC glucagon did not. Increased Δ CPR/Δ glucose 0-30 min values were noted in 5 of 13 of those with increased AUC glucagon but in 9/9 of those without, suggesting that those without increased AUC glucagon were more likely to be associated with increased Δ CPR/Δ glucose 0-30 min values. On the other hand, no significant difference was seen in changes in AUC glucagon or in the proportion of patients with increased AUC glucagon between the Cana and non-Cana groups.

Conclusions: Study results suggest that differences in the recovery of insulin secretion between patients may affect glucagon secretion to a greater extent than differences between S with or without SGLT1-inhibitory properties.

Disclosure

M. Ishiguro: None. Y. Mori: None. R. Nishimura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K.K., Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited.
2226-PUB: Direct Sanitary Cost of Diabetes Mellitus Ambulatory Treatment in the Institute of Prevision Social of Paraguay
Authors: ARZAMENDIA SADY P. , ROMERO FABIOLA , VALINOTTI ELIZABETH
Published: June 2020

The Institute of Prevision Social (IPS), social security of Paraguay is responsible for the complete provision of diseases treatment of the worker and his family. Diabetes mellitus (DM) is one of the most prevalent diseases in our country.

Aim: To determine the direct health cost of DM outpatient treatment (medications and medical visits) of IPS in 2018.

Methods: Observational, descriptive, transverse. Data were collected on the type and quantity of antidiabetic medication consumed and the number of visits per patient with type 1 and 2 DM, of the computer registry: “SIH” from January to December 2018, available at all IPS centers in the country.

Results: 67,664 patients who received antidiabetic medication were included. Female 50.5%, age 64.5 ± 21.53 years. 79.7% use oral medication (1 or more drugs.) 30.3% use insulins (alone or in combination). In order of frequency, the most commonly used drugs are: Metformin 73% Glimepiride 41%, Insulin NPH 20% Basal insulin analogues 16%, Regular Insulin 5.4% Sitagliptin. 2% and ultrarapid analogs 1.8% of the total population. One visit per patient was averaged every 3.7 months with the internist, family doctor or endocrinologist; cost of $ 7,14/visit (stipulated by the Paraguayan Society of Internal Medicine), which yields an annual cost of outpatient visits of $2,166,720. The estimated annual cost used in antidiabetic medications was $ 3,842,977: Basal insulin analogs $ 1,802,808, NPH insulin $ 811,260, Ultrarapid insulin analogs $ 568,788, , Metformin $ 330,249, Sitagliptin $ 167,754, Glimepiride $ 103,656, Human rapid insulin 58,433 $; averaging a cost per patient of $ 89 per year.

Conclusion: The high costs generated by the disease, even without the calculation of hospitalizations, complications, work disability, suggests the need to promote primary prevention policies for DM. On the other hand, the optimization of health resources, using cost/effective medication, could help reduce health expenditure in our institution.

Disclosure

S.P. Arzamendia: None. F. Romero: None. E. Valinotti: None.
2241-PUB: The Effectiveness of Individualized Exercise Programs in a Multidisciplinary Pediatric Clinic for Patients with Type 2 Diabetes
Authors: EUROPA LEAH VENICE B. , BUENNAGEL LYNN N.
Published: June 2020

Background/Purpose: The American Diabetes Association projects the incidence of type 2 diabetes (T2DM) among pediatric patients will increase to 49% by 2050. Physical activity and exercise modifications are primary recommendations in controlling diabetes. The purpose of this study is to describe the effects of a physical therapist (PT) prescribed personalized fitness plan to improve cardiovascular fitness in adolescents with T2DM.

Methods: Data was collected from patients treated at a multidisciplinary T2DM clinic at Children’s Hospital Los Angeles (CHLA). Physical therapy assessments were done when the patient visited the PT in clinic and included post-exercise heart rate, resting heart rate, rating of perceived exertion, and VO2 max. Multiple regression analysis was used to assess associations between change in fitness and covariates: age, sex, time since diagnosis, and time between first and last PT assessment.

Results: Fifty two patients who had at least 2 PT assessments at the T2DM clinic from April 2016 to October 2018 were included in the study. Patients with higher initial post-exercise heart rate experienced the greatest benefit from an individualized exercise program. Patients with lower initial VO2 max scores also experienced the greatest increase in VO2 max over time. There was no significant association with resting heart rate and rating of perceived exertion in regards to age, sex, time since diabetes diagnosis, and time between first and last PT assessment.

Conclusion: Prescribing a personalized fitness plan can improve fitness measures in patients with the lowest baseline fitness levels.

Implications: Maintaining a healthy and active lifestyle can be difficult for youth with T2DM especially if they lived a sedentary lifestyle prior to diagnosis. Health care providers and educators must consider the age and interests of the patient and family when creating a personalized fitness program.

Disclosure

L.B. Europa: None. L.N. Buennagel: None.

Funding

Good Hope Medical Foundation
2242-PUB: Gender-Specific Factors Associated with Metabolic Syndrome among Children and Adolescents in Korea
Authors: CHOI JIHEA , YOON TAE WOONG , YU MINHEUI , KANG DAE RYONG , CHOI SARAH E.
Published: June 2020

Purpose: Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and atherosclerotic cardiovascular diseases, and its pathological process starts from childhood and adolescence. Childhood and adolescence is an important developmental stage where gender-specific body image, self-identity, and health habits are formed. This study examined gender-specific factors associated with MetS among Korean children and adolescents.

Method: Using data from the Korea National Health and Nutrition Examination Survey 5th and 6th waves (2010-2015), a total of 4,149 respondents (representing 4.6 million children and adolescents aged 10 to 18) were evaluated. MetS was defined based on the guidelines of the modified NCEP ATP III. Data were analyzed with descriptive statistics, independent t-test, χ2 -test and univariate logistic regression analysis (p < .05).

Results: The prevalence rate of MetS in Korean children and adolescents was 4.17% (4.88% in boys and 3.42% in girls). The prevalence of abdominal obesity was significantly higher in girls (8.96% vs. 11.17%), and the prevalence of low HDL-C and elevated BP were significantly higher in boys (14.13% vs. 9.65%; 29.15% vs. 25.65%). For boys, increasing age, BMI, Waist-to-Height ratio (WHtR), one meal per day, weight loss effort, and perceived body shape as “fat” were significantly associated with MetS. For girls, BMI, WHtR, familial medical history of low HDL-C, weight loss effort, and perceived body shape as “average” and “fat” were significantly associated with MetS. Risk factors unique to boys were age and frequency of meal per day, whereas familial medical history of low HDL-C and perceived body shape as “average” were specific to girls.

Conclusion: We found gender differences in the prevalence of MetS and its associated risk factors in Korean children and adolescents. Gender-difference should be considered in an effort to address MetS and risk factors in this population.

Disclosure

J. Choi: None. T. Yoon: None. M. Yu: None. D. Kang: None. S.E. Choi: None.

Funding

National Research Foundation of Korea (2017R1C1B5076837)
2249-PUB: Clustering Analysis as a Tool to Define Endotypes in Type 1 Diabetes (T1D)
Authors: SILLER ALEJANDRO F. , GU XIANGJUN , TOSUR MUSTAFA , ASTUDILLO MARCELA , BALASUBRAMANYAM ASHOK , BONDY MELISSA , REDONDO MARIA J.
Published: June 2020

Due to heterogeneity in pediatric T1D, uniform treatment strategies are unlikely to benefit all patients equally. T1D endotypes, or subgroups with distinct characteristics amenable to particular interventions, are a potential solution, but defining endotypes remains a challenge. We used electronic medical records (EMR) to define clusters of distinct presentations of pediatric T1D in a diverse population with a high prevalence of obesity. We analyzed data collected through an EMR Population Health Diabetes Registry of 604 children newly diagnosed with T1D at a large academic hospital in southwestern USA. Using PROC Cluster (SAS 9.4), we applied the Centroid Clustering method to find the optimal number of clusters that minimized the sum of squared distance, then used SAS PROC Tree to identify subjects in each cluster. Variables used were age, DKA at diagnosis, weight, sex, race/ethnicity, c-peptide, hemoglobin A1c (A1c), thyroglobulin antibody (TgAb), and thyroid peroxidase antibody (TPO). Due to multiple testing, p-values <0.01 were statistically significant. This yielded 6 clusters: Cluster 1 (n=424), was characterized by low C-peptide, normal weight, negative TgAb and TPO, intermediate or high A1C; Cluster 2 (n=73) by obesity, low or intermediate C-peptide, and negative TgAb and TPO; Cluster 3 (n=42) by positive TgAb; Cluster 4 (n=33), by positive TPO and negative TgAb; Cluster 5 (n=19) by high or intermediate C-peptide without obesity or intermediate C-Peptide with obesity and negative TgAb and TPO; Cluster 6 (n=13) by obesity, high C-peptide and negative TgAb and TPO. After adjusting for age, BMI Z-score and race/ethnicity, clusters were statistically different for A1c, C-peptide and TPO and TgAb status (all p<0.01), but not for glucose or DKA. This strategy identifies distinct groups in T1D based on objective criteria. Endotypes from clustering analysis of more EMR data could be used for targeting therapeutic strategies to groups with similar characteristics and help personalize T1D treatment and care.

Disclosure

A.F. Siller: None. X. Gu: None. M. Tosur: None. M. Astudillo: None. A. Balasubramanyam: None. M. Bondy: None. M.J. Redondo: None.

Funding

Baylor College of Medicine
2251-PUB: Assessment of Fear of Hypoglycemia in a Large, Clinical Sample of Fathers of Children with Type 1 Diabetes
Authors: AMBURGEY DEBORAH J. , ODONNELL HOLLY , GOMER TARA , REZNICK-LIPINA TYLER , MAJIDI SHIDEH , DRISCOLL KIMBERLY A.
Published: June 2020

The Hypoglycemia Fear Survey-Parent (HFS-P) is the most commonly used questionnaire to assess parental worries and behaviors about low blood glucoses occurring in their children with T1D. The purpose of this study was to provide descriptive statistics on the HFS-P’s three subscales using a large clinical sample of fathers, data that are notably absent from the extant literature. As part of their child’s routine T1D clinic visits, 302 fathers completed the HFS-P, which comprises three subscales: Maintaining High Blood Glucose (BG), Worry/Helplessness About Low BG, and Worry About Negative Social Consequences. Higher scores indicate greater fear/worry about hypoglycemia. Child demographic and medical variables were extracted from medical records. Child characteristics were: 43% female; mean age = 15.1±3.3 yrs (range 10-22); mean A1C = 8.7±1.9%. Fathers’ were more likely to engage in maintaining high BG behaviors with younger children (r=-0.17, p<0.01). Fathers’ mean Maintaining High BG scores were significantly higher in 10-12 year olds (4.1±2.5) then in 13-17 year olds (3.4±2.6) and 18-22 years olds (3.2±2.6; F=3.01; p<0.05). There were no differences in mean Worry/Helplessness About Low BG or Worry About Negative Social Consequences scores by age group (ps=0.14 and 0.68, respectively). None of the three subscales was significantly correlated with glycemic control (ps>0.15). This is the first study to provide normative data for the three subscales comprising the HFS-P derived from a large clinical sample as all other studies have used research samples. Clinicians using the HFS-P to monitor worries and behaviors associated with hypoglycemia can use these data to assess fathers’ progress. These data also support other studies showing that glycemic control and fear of hypoglycemia are not related; although findings are generally mixed. This study adds to a growing body of literature on the importance of assessing fear of hypoglycemia in parents of children with T1D.

Disclosure

D.J. Amburgey: None. H. ODonnell: None. T. Gomer: None. T. Reznick-Lipina: None. S. Majidi: Advisory Panel; Self; Companion Medical. K.A. Driscoll: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (7K23DK091558-05)
2253-PUB: A Rare Case of Fulminant Type 1 Diabetes Postpartum
Authors: LANE KYRSTIN , OXMAN RACHAEL
Published: June 2020

Amongst women with gestational diabetes (GDM), the incidence of type 1 diabetes (T1DM) was 3.4% at 9 months post-partum and 6.6% at 2 years post-partum in one prospective study. Higher number of autoantibodies (Abs) during pregnancy is associated with a higher risk of T1DM. In rare cases, women with GDM can develop antibody-negative T1DM post-partum. The presentation of fulminant T1DM defined as rapid onset ketoacidosis, undetectable C-peptide, A1C<8.5%, elevated pancreatic enzymes and often negative antibodies has only rarely been reported in the post-partum period and predominantly in individuals of Japanese descent. In our case, a 34-year-old woman of Indian descent presented for GDM which required low dose Detemir 6 units nightly. She had an uncomplicated delivery and stopped insulin. On post-partum day 8 she was hospitalized for 1 day of non-specific malaise symptoms and was incidentally found to have elevated lipase 398 U/L, serum glucose 93 mg/dL and mildly bulky pancreas by ultrasound imaging. Initially she clinically improved, but on post-partum day 15 she developed symptoms of fatigue, polyuria, polydipsia, and weight loss which progressed to vomiting, tachycardia and tachypnea. She was readmitted on post-partum day 19 with glucose 482 mg/dL, arterial pH 6.95, anion gap 34, and moderate ketones consistent with severe Diabetic Ketoacidosis. Hemoglobin A1C was 6% and lipase was normal. New onset T1DM was diagnosed based on undetectable C-peptide, though GAD and ICA Abs were negative. She was treated with an insulin infusion and later transitioned to a basal-bolus subcutaneous insulin regimen. Repeat labs at 12 months post-partum confirmed persistent undetectable C-peptide and negative Abs. We present a unique case of a woman of Indian descent with GDM found to have fulminant T1DM in the early post-partum period. To our knowledge, this is the first case of fulminant diabetes post-partum reported in a patient of Indian ethnicity. Our case highlights the importance of consideration of this rare diagnosis in diverse populations.

Disclosure

K. Lane: None. R. Oxman: None.
2261-PUB: Type 2 Diabetes Mellitus Debut in Peru: The DDPeru Study
Authors: ROCCA JESUS , CALDERON MARIA , WHITTEMBURY ALVARO , ULLOA VIVIANA
Published: June 2020

Objective: To describe the clinical and metabolic characteristics of debut type 2 diabetes mellitus (T2D) Peruvian patients and to evaluate if there are any differences between the different geographical regions. To describe the initial pharmacological treatment of these patients.

Methods: Case series study that took place in different regions of Peru, from July 2016 to November 2017. The inclusion criteria were: patient older than 20 years old, ambulatory setting, first time diagnosis of T2D through: fasting glycemia ≥ 126 mg/dl or random glycemia ≥ 200 mg/dl with symptoms, or oral glucose tolerance test (OGTT) ≥ 200 mg/dl on the 2 hour sample. Also, a description of their initial treatment was registered.

Results: Five hundred eighty-one patients were identified, from which two hundred eighty-four (48.9%) were women. The average age of diagnosis was 53.2 ± 12.8 years old. Average weight was 77.3 +/- 16.6 kg, from which 228 patients (39.2%) were over weighted and 178 (30.6%) had type I obesity. Average glycemia was 249.4 mg/dl and average HbA1c was 8.9 %. In those who had abdominal ultrasonography (US), 56.7% had fatty liver. Most of the patients that were from Lima or the northern region of the country, had higher levels of glycemia and HbA1c. The T2D patients that were from high altitude presented more often fatty liver in the US, and lower levels of total cholesterol and LDL-c than those patients from the coast. The younger the patient, more cardiometabolic risk factors were present. Sixty percent of the patients received monotherapy, being metformin the preferred drug.

Conclusions: Patients with T2D debut from Lima and the northern region of Peru, and also the younger patients, have more cardiometabolic risk factors than their counterparts from the rest of the country and the older ones. We didn’t find any clinical difference between patients from the coast or from high altitude. Metformin was the most prescribed drug to treat these patients.

Disclosure

J. Rocca: Consultant; Self; Merck KGaA. Other Relationship; Self; Novo Nordisk A/S. M. Calderon: None. A. Whittembury: None. V. Ulloa: Employee; Self; Novo Nordisk A/S.

Funding

Novo Nordisk Peru S.A.C.
2269-PUB: Correlation between Serum Uric Acid Level in Adult Males and Their Fasting Blood Glucose Level in the Time of 1.5 Years
Authors: WANG YAN
Published: June 2020

Objective: Investigating the correlation between serum uric acid (SUA) level in adult males and their fasting blood glucose (FBG) level in the time of 1.5 years.

Methods: Retrospective analysis based on two physical examinations including laboratory tests held at the Beijing Hospital during the period from 2014 to 2018, on 2337 adult males who work on non-physical jobs. Mean age was 61.6±13.3 at the first exam and 63.1±13.3 at the second exam. The two exams were held in the same season with an interval of 1-2 years (average 1.5). Results were collected from questionnaire, physical exams, and laboratory tests including levels of SUA, FBG, Hemoglobin Subunit Alpha 1, total cholesterol, triglycerides, LDL-c, HDL-c, creatinine, etc. During the first exam, no diabetes mellitus, gout, hepatic and renal insufficiency or malignant tumor was found, and all participants showed FBG < 7.0 mmol/L. Data were divided into 4 groups based on SUA levels obtained from the two exams. Group 1 (296 participants, 12.7%): SUA ≥ 420umol/L in both exams. Group 2 (458 participants, 19.6%): SUA ≥ 420umol/L in one exam while 240 ≤ SUA < 420umol/L in the other one. Group 3 (1479 participants, 63.3%): 240 ≤ SUA < 420umol/L in both exams. Group 4 (104 participants, 4.4%): SUA<240umol/L.

Results:1. A total of 136 participants (5.8%) showed FBG ≥ 7.0 mmol/L at the second exam, among which 29 (9.8%) belong to group 1, 40 (8.7%) belong to group 2, 65 (4.4%) belong to group 3, and 2 (1.9%) belong to group 4 (X2 24.000,P 0.000). 2. Risk analysis: Compared to group 4, the risk of individuals having FBG≥7.0mmol/L was 5.539 (95%CI 1.298-23.637) for group 1, 4.880 (95%CI 1.160-20.527) for group 2, and 2.344 (95%CI 0.566-9.712) for group 3.

Conclusions: The Hyperuricemia in adult males, especially those with Chronic Hyperuricemia, is correlated to the increase of FBG in the time of 1.5 years. Hyperuricemia is potentially a predictor of FBG increase in adult males, and clinical diagnosis of diabetes is required for those having FBG≥7.0mmol/L.

Disclosure

Y. Wang: None.
2273-PUB: Long-Term Incidence Rates of Complications in Patients with Type 2 Diabetes in Sweden
Authors: SVENSSON ANN-MARIE , FRANZÉN STEFAN , KLOK ROGIER M. , WEISS TRACEY , RAJPATHAK SWAPNIL , ELIASSON BJORN
Published: June 2020

While it is known that patients with type 2 diabetes mellitus (T2DM) are at an elevated risk of developing several complications, there are limited data on incidence of these diabetic complications based on extended follow-up time following diagnosis of T2DM. We conducted an observational database study among newly diagnosed T2DM patients using the National Diabetes and other registries in Sweden. We calculated the incidence rates (IR) for several diabetic complications as number of events per person years with 95% exact Poisson confidence intervals. A total of 100,878 persons with new diagnosis of T2DM were included; average age (SD) was 62.6 (12.5) years, and 42.7% was female. The mean follow-up time was 5.5 years with the maximum follow up of 17 years. The Figure below shows the cumulative incidence of different complications from time of diagnosis as well as the IR of these complications. The cumulative incidence for the different diabetic complications shows a steady increase over time.

Disclosure

A. Svensson: None. S. Franzén: None. R.M. Klok: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. T. Weiss: Employee; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Menarini Group. B. Eliasson: Consultant; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi.
2275-PUB: Demographic Profile and Severity of Premature Ejaculation among Person with Type 2 Diabetes Mellitus Attending a Tertiary Care Hospital of Bangladesh
Authors: AHMED MOHAMMAD A.U.
Published: June 2020

Background: As of 2014 worldwide about 9% (87 million) of the adult population have DM. Premature ejaculation (PE) is three times more common among them and diabetic patient experience the problem 10 to 15 years earlier than nondiabetic person.

Objective: It was aimed to find out premature ejaculation among patients with type 2 DM attending in a tertiary care hospital of Bangladesh.

Methods: This descriptive cross sectional study was conducted in the outpatient department of BIRDEM general hospital from July 2017 to June 2018. Total 225 adult respondents were recruited from diagnosed type 2 DM patients as per ADA 2016 criteria. A face to face interview was conducted with the help of premature ejaculation diagnostic tool (PEDT).

Result: Mean age of respondents 39.13 yrs±12.52 and age range was (21-65) years. Most of the respondents were married (73.3%). Among the study population, the prevalence of PE was 55.6%. Mean age of patients having PE was 38.36±8.89 year and age group of 21-30 years had higher incidence rate. Mean age of severe PE (within 15 sec) was found 41.17+_ 9.17 year and age group of 31-40 years had higher incidence rate. Among PE patients, 72% were married. Almost equal PE patients were from rural and urban habitat. Almost half PE patients (48%) had severe PE (within 15 seconds). Almost half of PE patients (48%) were suffering from type 2 DM for more than 10 years. PE was significantly higher (p<.001) among patients with poor glycaemic control (HbA1c>7).

Conclusion: PE is highly prevalent sexual dysfunction among type 2 DM patients, most of the times which remain under diagnosed and untreated. Large scale multi centered study would help to generalize as well as address the issue in a country like Bangladesh.

Disclosure

M.A.U. Ahmed: None.
2278-PUB: Longitudinal Progression of Diabetes Mellitus in Wolfram Syndrome
Authors: RAY MARY KATHERINE , HERSHEY TAMARA , CHEN LING , WHITE NEIL H. , MARSHALL BESS A.
Published: June 2020

Wolfram Syndrome (WFS) is a rare, genetic, neurodegenerative disorder with associated features of diabetes mellitus (DM), diabetes insipidus, deafness, and optic atrophy. In order to design intervention studies, concrete markers of disease progression are required. DM in WFS is believed to be due to endoplasmic reticulum stress-induced failure of insulin secretion. Therefore, progressive loss of insulin production may be a viable marker of disease progression. The purpose of this study was to examine progression of DM, measured by beta-cell function, in WFS patients over time. N=44 (25F/19M) participants with genetically confirmed WFS attended the Washington University Wolfram Research Clinic from 2010-2019. A mixed meal tolerance test was administered to assess beta cell function (i.e., C-peptide). A hierarchical random coefficients model was used to relate C-peptide as a function of DM duration. Most patients (91%) had DM at time of study enrollment (N=39) or developed DM during the study (N=1). There was a significant association between C-peptide and DM duration, such that C-peptide decreased over time (F= 39.44, p=<0.0001). Given the high prevalence and easily dated onset of DM in WFS, deterioration in C-peptide could potentially be used as a biomarker to assess disease progression in intervention trials for WFS, particularly in those with duration of DM < 10 years as they may be less likely to experience a C-peptide floor effect.

Disclosure

M. Ray: None. T. Hershey: None. L. Chen: None. N.H. White: None. B.A. Marshall: None.

Funding

Washington University (HD070855, U54HD087011); Clinical and Translational Science Award (UL1RR024992); National Institute on Drug Abuse (5T32DA007261-27); Diabetes Research Center (DK020579); Snow Foundation, George Decker and Julio V. Santiago Pediatric Diabetes Research Fund; Mallinckrodt Institute of Radiology; McDonnell Center for Systems Neuroscience
2280-PUB: Cluster of Metabolic Disorders Increases Risk of Cancer in Chinese Patients with Type 2 Diabetes
Authors: ZHANG LEI , YANG YUXIU , MENG WEI , WANG JUN , CHEN SHUFANG , DONG YANHU
Published: June 2020

Aims: The study aimed to investigate the relationship between metabolic syndrome (MS) and risk of cancer in patients with type 2 diabetes (T2DM).

Methods: We enrolled 6587 patients with T2DM who were hospitalized in Qingdao Endocrine and Diabetes Hospital from Feb 2005 to Jan 2016. According to the number of MS component each patient had, they were divided into isolated T2DM, T2DM plus 1 component,2 components, 3 components and 4 components, respectively. The IDF Worldwide Definition of the Metabolic Syndrome was applied. Information on the diagnosis of cancer was obtained by matching ICD-10 codes recorded in local Healthcare medical records database. Prevalence of cancer was compared using Chi-square test. Logistic regression model was used to evaluate risk of cancer associated with MS.

Results: The prevalence of cancer was 4.2% among 6587 patients with T2DM. Female patients had higher prevalence than did male in total or in the MS subgroup. The prevalence of cancer were 3.8%, 3.9%, 3.8%, 5.1% and 5.0% in isolated DM, T2DM plus 1 component of MS, T2DM plus 2, T2DM plus 3 and T2DM plus 4 components, respectively (P for trend <0.05). Compared with those with less than 3 components, T2DM plus 3 or 4 components had increased risk of having cancer (OR=1.32, 95% CI: 1.04-1.69). Among T2DM patients who had more than 3 components of MS, a specific cluster of increased waist, elevated triglycerides (TG) and decreased High-Density Lipoprotein Cholesterol (HDL-C) was associated with the highest prevalence of cancer (10.7%), followed by 8.3% in T2DM patients plus hypertension, elevated TG and decreased HDL-C and 3.2% in T2DM patients plus hypertension, increased waist and elevated TG (χ2=26.6, P<0.05).

Conclusions: A cluster of metabolic disorders consisting of increased waist, elevated TG and decreased HDL-C seems to be oncogenic among Chinese patients with T2DM. For patients in combination with 3 or 4 MS components, it is important to conduct early cancer screening and prevention.

Disclosure

L. Zhang: None. Y. Yang: None. W. Meng: None. J. Wang: None. S. Chen: None. Y. Dong: None.
2285-PUB: Hippocampal Transcriptomic Changes Due to High-Fat Diet in Prediabetic Mice
Authors: ELZINGA SARAH , HENN ROSIE , O’BRIEN PHILLIPE D. , GUO KAI , EID STEPHANIE , RUMORA AMY E. , HINDER LUCY M. , HAYES JOHN M. , MENDELSON FAYE , FELDMAN EVA L. , HUR JUNGUK
Published: June 2020

The metabolic syndrome, prediabetes, and type 2 diabetes are increasingly common conditions worldwide, which predispose patients to the development of significant complications in both the central and peripheral nervous systems. Recently, our integrated lipidomics and transcriptomics study revealed an important role for lipid signaling pathways in peripheral nerves of mouse models of prediabetes and type 2 diabetes. While these data point to possible mechanisms of nerve damage peripherally, less is known about damage due to prediabetes and diabetes in the brain. This is of particular interest as growing evidence indicates that these conditions negatively affect cognition. Therefore, we performed RNA-Seq on hippocampi, a major site of learning and memory in the brain. Samples were isolated from a model of prediabetes and cognitive decline, wherein mice are fed a 60% high-fat diet (HFD). We identified various differentially expressed genes (DEGs) due to HFD, particularly after 11 wks (n=886), with fewer after 19 wks (n=111). Pathway analysis showed enrichment of pathways previously identified in the peripheral nervous system in response to HFD, including inflammatory and MAPK signaling pathways. Of interest, ∼31% of DEGs due to 11 wks of HFD overlapped with DEGs due to age (control animals only, comparing 19 to 11 wks of diet). These overlapping DEGs included genes such as fatty acid elongase 6 and hyccin (leukodystrophy protein FAM126A), which have roles in lipid metabolism and myelination, respectively. Enrichment analysis revealed multiple metabolic and protein processing pathways, such as oxidative phosphorylation and the proteasome. These data suggest that, like the peripheral nervous system, HFD effects similar pathways in the brain and may accelerate age-related gene expression changes in the hippocampus. However, more robust studies are needed to fully understand the influence of HFD on possible premature brain aging and how gene expression changes may contribute to cognitive decline.

Disclosure

S. Elzinga: None. R. Henn: None. P.D. O’Brien: None. K. Guo: None. S. Eid: None. A.E. Rumora: None. L.M. Hinder: None. J.M. Hayes: None. F. Mendelson: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation. J. Hur: None.

Funding

Program for Neurology Research and Discovery (T32DK007245, T32DK101357); National Institutes of Health (R24DK082841)
2286-PUB: Profiling MicroRNA (miRNA) and Metabolic Disease Association by Using Diffusion Model
Authors: HU PENGWEI , KUANG ZEMIN , HE TIANTIAN , HUANG YUAN , TANG ZEFANG , LI SHAOCHUN , MEI JING
Published: June 2020

Background: MiRNAs play an important role in complex human diseases, and the identification of disease and miRNA associations can accelerate drug development, individualized diagnosis, and treatment of diseases. From a miRNA perspective, the molecular mechanisms of many complex diseases, such as metabolic disease, are not fully understood. However, experimentally exploring the relationship between miRNA and disease is expensive and time-consuming. The purpose of this study was to examine whether the computational model could infer related miRNAs for metabolic disease.

Methods: miRNA and disease can construct a bipartite graph according to their associations. Here, we propose a novel graph-based two-way diffusion model to reconstruct the bipartite graph and then transform the prediction task into a matrix to complete the problem. The underlying assumption made by our model is that miRNA or diseases that are highly similar to each other tend to have similar correlations and vice versa. We calculate the miRNA similarities for all the miRNAs by use MiRNA functional similarity and miRNA Gaussian similarity. We also calculate the semantic similarity and Gaussian similarity for all the diseases. Access to a miRNA expression, our model can infer its correlation with each metabolic disease.

Results: To assess the predictive model, we used the HMDD V3.2 database, which included 35,547 miRNA-disease association entries consisting of 1,206 miRNA and 893 diseases identified from the literature. The results show that the prediction model can achieve AUCs of 0.916 based on 5-fold cross-validation. We took type 2 diabetes mellitus as a target for miRNA prediction, 9 out of the top 10 predicted potential miRNA were confirmed by literature (e.g., hsa-mir-205).

Conclusions: We can use the model to select the most likely miRNA targets that specific metabolic diseases would associate with. It is anticipated that our model would become a practical tool for the clinical metabolic diagnosis and lab experiments.

Disclosure

P. Hu: None. Z. Kuang: None. T. He: None. Y. Huang: None. Z. Tang: None. S. Li: None. J. Mei: None.

Funding

National Natural Science Foundation of China (61702424)
2288-PUB: Ameliorating Type 1 Diabetes in Mice via Implantation of APA Microencapsulated Human Stem Cell–Derived Islets
Authors: GUO LIXIN , PAN QI , SONG YIZHE , CAO YIZHAO , OU ZHENSHENG , CHEN XIAOFENG , LI WENJIA , TANG XINFA
Published: June 2020

Objective: Human pluripotent stem cells derived islets (SC-islets) provide a promising alternative source for beta cell replacement therapies for type 1 diabetes, while facing immune-rejection risks. Recent studies show that alginate-poly-L-lysine-alginate (APA) microcapsules have potentials to overcome the need for immunosuppression in allogeneic transplantation. In this study, APA encapsulated SC-islets were implanted into type 1 diabetes immune-competent mice models, to explore their ability to treat diabetes.

Method: First, we optimized differentiation method, SC-islets’ ratio of mature β cells and in vitro glucose response were measured; SC-islets encapsulated with APA were implanted into the intraperitoneal space of C57BL/6 STZ-induced diabetic mice (n=8), and blood glucose levels were further monitored.

Result: After optimization, SC-islets mature β cells (NKX6.1+/C-peptide+) reach 43.72 ± 1.62% (previous data was 21.01± 4.07%), and C-peptide positive cells increased from 34.93 ± 10.05% to 60.86 ± 1.15%. The SC-islets also included α or Δ cells, and responded to multiple sequential high-glucose challenges (insulin secreted ranged 2.10-3.27 μIU/103 cells). Then APA encapsulated SC-islets were implanted into the intraperitoneal space of diabetes mice. The fasting blood glucose decreased to normal level (3.70 ± 0.93 mM) on day 1 post-transplant, and the blood glucose maintained normal for 11 days. Similarly, random blood glucose returned to normal levels (11.01 ± 4.63 mM) on day 7 post-transplant.

Conclusion: Optimized SC-islets had a higher proportion of mature β cells and improved glucose response functions. The in vivo results showed that SC-islets in APA microcapsules can rapidly ameliorate hyperglycemia in diabetic mouse, while the duration time need further improvement through inhibiting fibrosis in alginate microspheres. Our results indicate that microencapsulated allogeneic SC-islets have potentials to treat diabetes.

Disclosure

L. Guo: None. Q. Pan: None. Y. Song: None. Y. Cao: None. Z. Ou: None. X. Chen: None. W. Li: None. X. Tang: None.
2289-PUB: Comparison of GalT-KO Porcine Islet Xenograft Survival between Microcapsule against Hypoxia and Microcapsule against Fibrosis in Diabetic Mice Model
Authors: LEE EUN YOUNG , YANG YEOREE , CHO YUNJUNG , LEE SEUNG-HWAN , CHO JAE-HYOUNG , YOON KUN-HO
Published: June 2020

Hypoxia and fibrosis are one of the most important obstacles for encapsulated islet transplantation. Previously, we have developed alginate-based microcapsules improving fibrosis (alginate-chitosan) or hypoxia (alginate-perfluorodecalin) and proved their effects. In this study, we compared long-term graft survival of encapsulated islet with microcapsule against fibrosis or hypoxia in diabetic mice model, using 1,3-galactosyltransferase gene-knockout (GalT-KO) pigs. Islets were isolated form GalT-KO pigs and then encapsulated with alginate-chitosan or alginate-perfluorodecalin microcapsule. To magnify graft survival gap between different microcapsules, marginal dose of islets were transplanted into streoptozotocin-induced diabetic mice intraperitoneally. Blood glucose level were measured for a year. Intraperitoneal glucose tolerance test (IPGTT) was performed at 6 and 12 months after transplantation. In the alginate-chitosan group, the blood glucose level of diabetic mice decreased after encapsulated islet transplantation. However, blood glucose level increased again within two months in 3 out of 4 mice. In the alginate-perfluorodecalin group, the blood glucose level of diabetic mice decreased after transplantation and maintained normoglycemia more than 6 months. Although blood glucose level tended to increase 6 months after transplantation, it remained below 300 mg/dL by one year. The area under curve (AUC) of IPGTT was similar between two groups at baseline. At 6 months after transplantation, AUC of IPGTT in alginate-perflourodecalin group lower than AUC of alginate-chitosan group. At one year after transplantation, microcapsules were retrieved. Dithizone stain was positive in most retrieved islet and fibrosis was minimal in both groups.

In conclusion, microcapsule against hypoxia showed a longer xenograft survival than microcapsule against fibrosis in diabetic mice.

Disclosure

E. Lee: None. Y. Yang: None. Y. Cho: None. S. Lee: None. J. Cho: None. K. Yoon: None.

Funding

Cooperative Research Program for Agriculture Science and Technology Development (PJ01345301); Rural Development Administration, Republic of Korea
229-LB: Plasma Lactate and Muscle Aerobic Substrate Oxidation: Does Elevated Lactate Precede Obesity?
Authors: BROSKEY NICHOLAS T. , JONES TERRY E. , YANG ZHEN , KHANG NKAUJYI , ZHENG DONGHAI , TANNER CHUCK J. , CORTRIGHT RONALD N. , HOUMARD JOSEPH A. , DOHM LYNIS
Published: June 2020

Background: The incidence of metabolic diseases is rising and there is a dire need for early detection of risk in order to implement prevention. Fasting plasma lactate concentrations have been shown to be elevated in individuals with obesity and predictive of the development of T2D. An elevated lactate concentration is the product of a shift to glycolysis and a possible reduction in oxidative capacity. However, it is unknown if there are associations between lactate and oxidative capacity in healthy individuals that may predispose them to metabolic disease.

Aim: The aim of this study was to determine if fasting lactate concentrations were linked with a reduction in skeletal muscle oxidative capacity in a young healthy population.

Methods: Young (age 22 ± 0.5; N=30) lean (BMI (22.4 ± 0.4 kg/m2) women were screened for fasting plasma lactate. Subjects underwent assessments of body composition, aerobic capacity (VO2 peak), skeletal muscle oxidative capacity via near infrared spectroscopy (NIRS) and fasting glucose and insulin were measured for calculating HOMA-IR. Fatty acid oxidation rate was also determined in a subset of samples from skeletal muscle biopsies (vastus lateralis).

Results: The women were insulin sensitive (HOMA-IR 1.1 ± 0.1) and had a mean fasting lactate of 0.9 ± 0.1 mmol/L. Time till exhaustion on the VO2 peak test was inversely associated with lactate (R2 = 0.20, p=0.05). Likewise, the rate of deoxygenated hemoglobin (NIRS) (R2 = 0.23, p=0.03) and skeletal muscle fatty acid oxidation (R2 = 0.72, p=0.004) were also inversely associated with fasting lactate. Lactate was inversely correlated with HDL:LDL (R2 = 0.57, p=0.02) and positively correlated with waist:hip (R2 = 0.52, p=0.02).

Conclusion: Plasma lactate was inversely related to skeletal muscle oxidative capacity and with metabolic parameters that are risk factors for obesity and T2D. Fasting plasma lactate may thus be a biomarker for identifying healthy individuals at risk for metabolic diseases.

Disclosure

N.T. Broskey: None. T.E. Jones: None. Z. Yang: None. N. Khang: None. D. Zheng: None. C.J. Tanner: None. R.N. Cortright: None. J.A. Houmard: None. L. Dohm: None.

Funding

National Institutes of Health (DK56112, DK120296)
2299-PUB: PNPLA3 I148M Involved in Mechanism of Variability in Antilipogenesis Response to Exenatide
Authors: CHEN YUNZHI , LIANG HUA , XU FEN
Published: June 2020

Background: GLP-1 receptor agonist, such as exenatide, has been proven to attenuate nonalcoholic fatty liver disease (NAFLD) in vivo and in vitro. Its potential mechanism remains elusive. PNPLA3 is a major susceptibility gene for NAFLD and its I148M polymorphism increases the risk of all disorders of NAFLD spectrum. However, whether genetic variation contributes to variability in exenatide response is still unclear.

Methods: Wild type (I148I) PNPLA3 knockin cells were constructed using HepG2 as a template which are homozygous for the PNPLA3I148M mutation by CRISPR/Cas 9 gene editing technique. Oil Red O staining combined with TG quantification were used to evaluate lipid accumulation. Western blot and RT-qPCR were conducted respectively to measure the protein and mRNA expression of lipid synthesis and inflammatory markers.

Results: Lipid deposition was increased in both wild type (I148I) and mutant (I148M) HepG2 cells treated with palmitoleic acid (PA), while mutant cells had a higher TG content than wild type cells. Exenatide treatment was showed to be more efficacious in mutant cells than in wild type cells on reducing the accumulation of TG. Exenatide-mediated inhibition of SREBP-1 and endoplasmic reticulum stress pathway, and activation of AMPK pathway, were more significant in mutatnt cells than in wild type cells.

Conclusion: PNPLA3 I148M might modify the treatment response to exenatide in NAFLD. This research would provide a novel insight for individualized exenatide treatment.

Disclosure

Y. Chen: None.