bluuebunny/crossref_metadata_2025_split huggingface dataset:
237-LB: Identification of Small Molecules That Increase Beta-Cell Mass in Hyperinsulinemic Zebrafish Alström Syndrome Model
Authors: DUNLEAVEY JESSICA , ANNIS DAVID A. , HOSTELLEY TIMOTHY L. , ZAGHLOUL NORANN A. 
Published: June 2019

Alström syndrome is an autosomal recessive obesity ciliopathy caused by loss-of-function mutations in the ALMS1 gene. In addition to multi-organ dysfunction, such as cardiomyopathy, retinal degeneration, and renal dysfunction, the disorder is characterized by high rates of obesity, insulin resistance and early onset type 2 diabetes mellitus (T2DM). We previously published data supporting the alms1 loss-of-function zebrafish mutant as a monogenic model for mechanistic interrogation of T2DM phenotypes. Both adult and larval alms1-/- animals exhibit reduced insulin+ areas alongside defective peripheral glucose uptake and concomitant hyperinsulinemia in larval alms1-/- animals. Gene expression changes in beta-cells isolated from alms1-/- mutants revealed changes consistent with insulin hyperproduction, insulin hypersecretion and glucose sensing failure. Therefore, we used this model, in which hyperinsulinemia is the primary and causative defect underlying generation of T2DM, in a high-throughput screen to examine small molecule compounds effecting pancreatic mass in vivo. The external development, simple growing conditions, and large number of progeny in the zebrafish allow for rapid screening with parallel elimination of lethal compounds. We examined the Microsource Spectrum Collection 2000, a library of 2,560 compounds, for those which increase beta-cell mass in wildtype, alms1-/- animals or both. These identified compounds are indicated in future studies for beta-cell proliferation pathways, T2DM diabetes-specific interactions, and potential targets for future therapeutic development.

Disclosure
J. Dunleavey: None. D.A. Annis: None. T.L. Hostelley: None. N.A. Zaghloul: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
2379-PUB: Team-Based Diabetes Care Demonstrates Sustained Effect on A1C
Authors: VIOLAGO JANELLE , BONONI PATRICIA 
Published: June 2019

Background: One of the goals of DM management is to achieve glycemic control to prevent or delay acute and chronic complications. ADA recommends planned visits through team-based approach to improve delivery of DM care. AHN Diabetes Academy (DA) is a 12-week team-based care program for patients w/A1C &gt;9%, T1DM, or worsening complications.
Objective: Determine if patients who participated in DA have sustained glucose control at 1 year.
Method: Compare A1C at the start, end of DA and at 1-year follow-up.
Results: A total of 221 patients were enrolled from 9/26/16 to 10/22/17. Seventy-seven % had T2DM, 21% had T1, 2% had T1.5. Thirty-nine were lost to follow-up or did not have A1C at 1 year, allowing data analysis for 182 patients at 1 year. Mean A1C decreased significantly from 9.4 to 7.7% for all patients from enrollment to discharge; A1C at 1-year follow-up was 7.8%, unchanged from discharge showing sustained glycemic control at 1 year (Figure). When DM subtypes were analyzed, mean A1C decreased significantly for T1 and T2 from enrollment to discharge, no statistical change in T1.5 (likely due to small sample size). No significant change in mean A1C from discharge to 1 year for all subtypes.
Conclusion: AHN DA achieved sustained glycemic control at 1 year after completion of 12-week team-based program. Teaching Points: Team based care attains sustained glycemic control at 1 year, is effective for T1 and T2DM, and benefits those at high risk for acute and chronic complications.

Disclosure
J. Violago: Stock/Shareholder; Spouse/Partner; Abbott, AbbVie Inc., Cardinal Health, Eli Lilly and Company, Johnson & Johnson, Merck & Co., Inc., Pfizer Inc. P. Bononi: Other Relationship; Self; Medtronic.
2393-PUB: First Metabolic Control Results in Insulin-Treated Diabetes Patients from Republic of Macedonia Derived from National eHealth System
Authors: SMOKOVSKI IVICA , MILENKOVIC TATJANA 
Published: June 2019

Republic of Macedonia (RoM) is estimated to have third highest diabetes prevalence in Europe. National eHealth System (NeHS) was introduced since 2015, enabling physicians to optionally record metabolic parameters. Our aim was to evaluate national metabolic control in insulin-treated pts, based on data derived from NeHS. NeHS was searched for all insulin-treated pts, as of 01-May-2017, with data in their Electronic Healthcare Records (EHR) for any of following parameters: HbA1c, BMI, Total Cholesterol (TC), LDL Cholesterol (LDL), Triglycerides (TG), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP). Mean values were calculated and number of pts identified to pre-specified thresholds: HbA1c - 7% and 8%; BMI - 25 kg/m2 and 30 kg/m2; TC - 5 mmol/l; LDL - 2.6 mmol/l; TG - 1.7 mmol/l; SBP - 140 mmHg and DBP - 90 mmHg. Total number of insulin-treated pts in RoM was 37,011 out of 84,568 diagnosed pts (43.8%). Of those, 6.204 (16.8%), mean age 63.8 ± 11.7 years, 54.7% women, were identified as having data in EHR for any metabolic parameter. Mean HbA1c was 7.8 ± 1.8% (n=6,204); 2,346 pts (37.8%) ≤ 7%, 1,607 (25.9%) &gt;7% and ≤ 8%; and 2,251 (36.3%) &gt;8%. Mean BMI was 30.4 ± 5.2 kg/m2 (n=1,920); 273 pts (14.2%) ≤ 25 kg/m2, 739 (38.5%) &gt;25 and ≤ 30 kg/m2, and 908 (47.3%) &gt;30 kg/m2. Mean TC was 5.3 ± 1.4 mmol/l (n=1,838); 988 pts (53.8%) &gt;5 mmol/l. Mean LDL was 3.2 ± 1.1 mmol/l (n=433); 290 pts (67.0%) &gt;2.6 mmol/l. Mean TG was 2.3 ± 1.6 mmol/l (n=1,588); 938 pts (59.1%) &gt;1.7 mmol/l. Mean SBP was 134.5 ± 17.3 mmHg (n=1,055); 232 pts (22.0%) &gt;140 mmHg. Mean DBP was 81.1 ± 8.5 mmHg (n=1,055); 65 pts (6.2%) &gt;90 mmHg. These are the first metabolic control results in insulin-treated pts from RoM, derived from NeHS. There is a need for improvement of glycemic control (36.3% of pts with HbA1c &gt;8%), weight and lipid management. Since 16.8% of pts have any metabolic data in EHR, change from optional to mandatory recording is necessary to improve individual and national metabolic control.

Disclosure
I. Smokovski: Advisory Panel; Self; Sanofi. T. Milenkovic: None.
2408-PUB: Benchmarking Care Outcomes for Youth with Diabetes after Transition to Adult Care in Australia
Authors: HOLMES-WALKER JANE , RUETER PHIDIAS , FARRELL KAYE 
Published: June 2019

In 2001 a model of care for transition of youth with diabetes (YWD) was implemented at Westmead Hospital and published in 2007. In 2017, Australian National Diabetes audit (ANDA) conducted a month survey of all people with diabetes attending participating centers. The Australian Diabetes Data Network (ADDN) is a newly established national database.
Aim: To determine if benefits are conferred by a youth specific transition care model as compared with other Australian adult health care settings for YWD age 16-25.
Methods: An audit of all T1D Westmead clinic attendees aged 16-25 in 2017 including age, duration diabetes, HbA1c, urine microalbumin/creatinine ratio in the last 12 months, BP, most recent retinal review and results compared with the ANDA outcomes for youth attending adult health care settings for management of diabetes. Subjects within 1 year diagnosis and pregnancy excluded.
Results: Key: HbA1c median (25th-75th centile), [n] missing * p&lt;0.05. HbA1c did not differ across all adult centers. In subgroup analysis only MDI treated were lower in the ANDA centers. A significantly greater proportion had urine microalbumin screening and BP screening, in the Westmead cohort.
Conclusion: Similar levels of diabetes control were achieved regardless of center indicating importance of follow-up in this age group although control was suboptimal. Complications screening was more effective with a dedicated transition.

Disclosure
J. Holmes-Walker: None. P. Rueter: None. K. Farrell: None.
2409-PUB: Assessment of Oral Microbiota in Adolescents with Type 1 Diabetes Mellitus and Periodontal Disease
Authors: CHAKRABORTY PAMPITA , GHOSH SUJOY 
Published: June 2019

Background and Aims: Periodontal disease (PD) is a complex chronic inflammatory disease in which inflammation in the periodontal tissues is stimulated by the long-term presence of the subgingival biofilm. Various studies have investigated the role of inflammatory mechanisms in the link between PD and diabetes (DM), relatively few have investigated relationships between the oral microbiota and DM. Thus, qualitative and quantitative analyses of biofilms in diabetic cases are important to find the exact association between them. Here our aim was to elucidate the role of the microbiome in PD and its association with type 1 diabetes (T1D).
Methods: Age matched individuals was selected. The cohort for plaque was stratified into 3 groups- those having T1D (n = 9), periodontal disease (PD) (n = 8) and both T1D and PD (DP) (n=11).
Results: Detailed analysis of the taxonomic differences revealed seven statistically significant genera and one phylum. The phylum of Firmicutes was significantly over expressed in PD group (p = 0.009). The genera of Abiotrophia, Actinomyces, Peptostreptococcusand Streptococcuswere over abundant in the PD group (p &lt; 0.05). Similarly, Aggregatibacter was significantly over abundant in only T1D and Campylobacter in only DP. Comparison between T1D and PD also revealed Proteobacteriato be significantly abundant in T1D (p = 0.042) but not in PD samples. Also, culture-based biofilm study showed significant growth in periodontal cases with poorly controlled glycemia as compared to the T1D with good glycemic control and healthy controls. Biofilm forming bacteria was commonly isolated and identified from the oral sample by the standard bacteria culture and metagenome sequencing.
Conclusion: Our study enriches the understanding of oral microbiota and sheds light on the identification of certain microorganism and glycaemic control in the pathogenesis of PD in T1D, which may have implication in treatment and management of PD in T1D.

Disclosure
P. Chakraborty: None. S. Ghosh: None.

Funding
Department of Science & Technology, Government of India, West Bengal; Research Society for the Study of Diabetes in India
2418-PUB: Incident Diabetes Complications among Women with T1D Based on Parity
Authors: POLSKY SARIT , FOSTER NICOLE C. , DUBOSE STEPHANIE , AGARWAL SHIVANI , LYONS SARAH , PETERS ANNE L. , UWAIFO GABRIEL I. , DIMEGLIO LINDA , SHERR JENNIFER , LEVY CAROL J. 
Published: June 2019

We aimed to assess the association between pregnancy and occurrence of diabetes-related complications in women with type 1 diabetes (T1D). Females 16-40 years old in the T1D Exchange clinic registry completing an initial questionnaire during 2011-13 and repeating it between 2016-18 (N=497; age 22±5 years, duration 12 [6,17] years, 87% non-Hispanic White) were categorized into 2 cohorts: first pregnancy during 2011-13 (preg; n=28) and never pregnant (never; n=469). No participants had complications reported at baseline. Funduscopic exam data were not uniformly available. There was a trend for lower HbA1c 5 years after study enrollment in the preg group (7.3%±1.3%) compared with the never group (7.9%±1.4%), P=0.14 adjusted for age, race/ethnicity, and body mass index. Both albuminuria and nephropathy within 5 years of study enrollment were found at higher frequency in the women who had never been pregnant (Table). Rates of neuropathy within 5 years of enrollment were similar between the groups. While rates of cardiovascular disease within 5 years of study enrollment were low for both groups (0 in preg group and 2 participants in never group), the pregnant cohort despite having lower A1c had higher frequency of some cardiovascular disease risk factors (e.g., obesity). In persons with T1D without reported complications at enrollment, pregnancy was not associated with new complication development 5 years after delivery.

Disclosure
S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US. N.C. Foster: None. S. DuBose: None. S. Agarwal: None. S. Lyons: None. A.L. Peters: Advisory Panel; Self; Abbott, Becton, Dickinson and Company, Bigfoot Biomedical, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Livongo Health, MannKind Corporation, Medscape, Merck & Co., Inc., Omada Health, Inc., OptumRx, Inc., Sanofi US, Zafgen, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Jaeb Center for Health Research, MannKind Corporation, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc. G.I. Uwaifo: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Eli Lilly and Company, Insulet Corporation. Consultant; Self; Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi. Research Support; Self; Dexcom, Inc., Insulet Corporation. C.J. Levy: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Allergan.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
2427-PUB: Role of Cardiac Autonomic Alterations and of Free Fatty Acids (FFA) on Hypertension in Overweight Patients
Authors: REZKI AMEL , FYSEKIDIS MARINOS , COSSON EMMANUEL , VALENSI PAUL 
Published: June 2019

Objective: In diabetic patients, autonomic alterations are associated with hypertension. In healthy individuals, FFAs were shown to enhance sympathetic activity. We aimed to examine the influence of autonomic function alterations and FFA on hypertension and artery stiffness (pulse wave velocity, PWV) in overweight patients with normal or impaired glucose intolerance (NGT orIGT) or orally-treated type 2 diabetes.
Patients and Methods: We included 122 normotensive or well-controlled hypertensive patients;38 NGTs, 28 IGTs, 15 well-controlled T2Ds, 41 poorly-controlled T2Ds; meanage 41.1/41.7/53.8/54.2 years BMI 38.4/36.6/28.7/29.3 kg/m²; HbA1c 5.2/5.5/6.7/9.1% respectively. At fasting, cardiac vagal (HFnu-HR) and sympathetic (LFnu-HR) activity and sympatho-vagal balance (LF/HF-HR) were measured by spectral analysis of heart rate variations, PWV by applanation tonometry;FFA measured in IGTs and poorly-controlled T2Ds.
Results: Spectral indexes were similar in NGT, IGT and well-controlled T2D patients (meanHF-HRnu 68% andLF-HRnu 32%), but different vs. poorly-controlled T2Ds (37% and63%, respectively). Comparedto patients with HF-HR&gt;median value, those with HF-HR&lt;median were older (p&lt;0.01), had lower BMI (p&lt;0.05); similar glycemic status, HbA1c, PWV; higher LF/HF-HR(p&lt;0.001) and more of them were hypertensive (40% vs. 20%, p&lt;0.04), these differences remaining significant after adjustment for age, BMI, glycemic status. FFA correlated positively with LF-HR and negatively with HF-HR (p&lt;0.04), also after multiple adjustment, in IGTs but not in poorly-controlled T2Ds (of whom49% were hypertensive).
Conclusion: In NGT, IGT orwell-controlled T2D overweight patients, lower vagal activity may contribute to hypertension independently from glycemic status, and FFA may reduce vagal activity and enhance sympathetic activity and thus promote hypertension while in poorly-controlled T2Ds this profile is more likely related to long-term hyperglycemia.

Disclosure
A. Rezki: None. M. Fysekidis: None. E. Cosson: Board Member; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., LifeScan, Inc., Lilly Diabetes, Medtronic, Merck Sharp & Dohme Corp., Novartis France, Novo Nordisk A/S, Roche Diagnostics France, Sanofi. Research Support; Self; Air Liquide, Lilly Diabetes, Novo Nordisk A/S, Roche Diagnostics France, Roche Foundation, Sanofi. P. Valensi: None.
2440-PUB: Characterization of Cardiometabolic Risk Profiles of Individuals Presenting to an Urban Medical Center in Cambodia with Prediabetes and T2DM
Authors: HAAS ANDREA , PENG SOVANN , MENH PHANAVARINE , CURRAN PETER G. , HUDSON MARGO 
Published: June 2019

Introduction: The prevalence of prediabetes and T2DM is increasing globally, and especially in developing countries like Cambodia. Comparisons between metabolic risk profiles of patients with prediabetes and T2DM in Cambodia have not previously been reported.
Aims: To compare the clinical characteristics of patients with newly diagnosed prediabetes and T2DM who presented to the Community Medical Center in Phnom Penh, Cambodia. A secondary aim was to determine if any sex differences exist among individuals with T2DM.
Methods: A retrospective study of 763 patients diagnosed with prediabetes or T2DM from July 2015 to July 2018 who had a complete biophysical profile. Comparisons were performed between groups using unpaired Student’s t-test.
Results: Results are summarized in Table 1. Individuals with prediabetes had lower TG levels but otherwise had similar cardiometabolic risk profiles to those with T2DM. Females compared to males with T2DM presented with lower HbA1c levels, but with higher corrected waist circumferences, higher LDL, and a greater number of cardiometabolic risk factors.
Conclusion: Cardiometabolic risk profiles were nearly indistinguishable in those with newly diagnosed prediabetes and T2DM. While females with T2DM presented with lower HbA1c values, they had a greater number of cardiometabolic risk factors compared to males.

Disclosure
A. Haas: None. S. Peng: None. P. Menh: None. P.G. Curran: None. M. Hudson: None.

Funding
National Institutes of Health
2441-PUB: Early-Onset Type 2 DM in Young and Middle-Aged Adults in a Diabetes Clinic
Authors: SUNTHARAMOORTHY KAJANA , DAVE SHRUTI , MUHAMMAD UMER , JAVAID EARAJ , GUPTA NIKHIL 
Published: June 2019

Introduction: Incidence of type 2 diabetes (T2DM) among young adults has been increasing rapidly. We have noticed a significant increase in consultations received for patients with T2DM diagnosed at age &lt;40 and much younger ages. Patients diagnosed at younger age are at higher risk of microvascular and macrovascular complications over their lifetime. We aim to characterize the clinical characteristics of this patient population.
Methods: All patients (new and follow-up) with T2DM and age≤ 50 years, at our Diabetes and Endocrinology Centre were included. 95 patients (21% of all patients in our diabetes registry) met the eligibility criteria. Demographic variables. comorbidities, diabetes complications, vitals, lab parameters and medications were reviewed.
Results: n=38 (40%) were females. Sixty-eight (71%) were South Asians. Mean age at diagnosis was 34 years(± 7.2). Normal, overweight and obese BMI was seen in 25%, 42% and 33% of South Asians and 12%, 25% and 62% of Caucasians, respectively. South Asians were diagnosed at a younger age with 9%, 16% and 57% diagnosed at age &lt;20, 21-30 and 31-40, respectively, compared to Caucasians 0%, 12.5% and 50% for the same age distribution above. Prevalence of dyslipidemia (86%), Hypertension (62%), retinopathy (4%), neuropathy (21%), nephropathy (29%), CAD (4%), stroke 2% and PVD was 0%, reflecting the younger population in this study.
Conclusion: A large proportion of patients in our diabetes registry are young or middle aged. South Asian ethnicity increases risk of diabetes at a younger age and lower BMI. The epidemic of diabetes at a young age is likely related to increased sedentary lifestyle, inadequate sleep, stress and increasing use of technology and screens.

Disclosure
K. Suntharamoorthy: None. S. Dave: None. U. Muhammad: None. E. Javaid: None. N. Gupta: Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc., Sanofi.
245-LB: Association between the Risk of T2D Incidence and the Genetic Variants of GCK and HDAC4 Genes Interacting with Alcohol Consumption in Korea
Authors: YUN JI HO , JANG HAN BYUL , YOO MIN-GYU , LEE HYE-JA , PARK SANG IK 
Published: June 2019

Chronic alcohol consumption is well-known as an independent risk factor for type 2 diabetes (T2D), which is related with impaired glucose homeostasis and insulin resistance. The identification of genetic variants and the association with diseases may help to explain the genetic etiology of type 2 diabetes. In this study, we aimed to search for the single nucleotide polymorphisms (SNPs) associated with T2D risk, which also interact with alcohol consumption. We conducted genome-wide interaction study using the Korea Association Resource (KARE) data. We found that two SNPs, HDAC4 (rs3791370) and GCK (rs758989) are associated with T2D and also interact with alcohol consumption (odds ratio [OR] 1.74, and OR 1.37, respectively). We further investigated the association between these SNPs and response to alcohol consumption in risk of T2D incidence. In alcohol consumption group, these SNPs significantly increased the risk of T2D incidence compared with nonalcohol consumption group (HDAC4; hazard ratio [HR] 1.29, GCK; HR 1.34). Moreover, genotype association analysis showed that the presence of the risky allele (hetero risky allele [CR] + minor homo risky allele [RR]) in GCK SNP significantly increased the risk of T2D incidence (1.47, p = 0.032) compared with major homo C allele [CC] in alcohol consumption group after adjustment with age, BMI, smoking, physical activity, and history of diabetes. However, presence of the risky allele in HDAC4 SNP marginally increased the risk of T2D incidence (1.47, p = 0.0652). Based on our data, we suggest that HDAC4 and GCK SNPs could be a potential factor for increase of T2D incidence risk, which may be helpful to better understand the genetic basis of T2D in association with alcohol consumption.

Disclosure
J. Yun: None. H. Jang: None. M. Yoo: None. H. Lee: None. S. Park: None.

Funding
Korea National Institute of Health (2019-NI088-00)
2451-PUB: Diabetes Kills Productive Years of Life
Authors: PANCHAL DHARMENDRA , SABOO BANSHI D. , GOKLANI RUTUL 
Published: June 2019

Aim: To study the trend of prevalence of diabetes in different age groups.
Method: We have retrospectively analyzed diabetes patient coming to OPD in term of their age of onset and year of onset of diabetes in type 2 diabetes patients from 1st January 2018 to 31st December 2018. There were total 976 patients with type 2 diabetes who visited OPD.
Result: Age distribution of patients with type 2 diabetes attending OPD from 1st January 2018 to 31st December 2018 was as below:
Table: age distribution of patients with type 2 diabetes attending OPD from January 2018 to December 2018.
Conclusion: Average age of onset of type 2 diabetes is still mostly between 35 to 45 years. As the time advances the graph continue to affect more and more younger people in their productive age group which is 35 to 45 years. It not only affects individual’s productivity but also has power to affect any strong economy. There is a strong need to improve our lifestyle and behavior to food and physical activity to fight with this tsunami.
Figure 1. Age Distribution Over the Years for Onset of Type 2 Diabetes.
Figure 2. Average Age of Onset of Type 2 Diabetes.

Disclosure
D. Panchal: None. B.D. Saboo: None. R. Goklani: None.