bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Body Shape Index for Predicting Type 2 Diabetes in Korean Elderly Population—The Chungju Metabolic Disease Cohort (CMC) Study
Authors: LIM SUN-YOUNG , LEE JIN-HEE , YOON KUN-HO 
Published: June 2018

Obesity has known as the main cause of type 2 diabetes (T2DM). Many simple surrogate indices of obesity, such as body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR) has been used, however, there is controversy about which indicator is most useful. Recently a new index (a body shape index, ABSI) was developed as a more reliable surrogate index than BMI in determination of the association between cardiovascular events and body composition. We aim to assess whether or not ABIS is better than BMI and WC to predicting T2DM incidence in Korea elderly population. The CMC study is a prospective cohort study of metabolic disease. A total of 5,390 subjects (2,034 men, 3,356 women) age 40 and older, free of T2DM at baseline (2003-2006) were included in the present study, and we estimated the cumulative incidence of T2DM after 4 years follow-up. ABSI was calculated using waist circumference, weight, height (WC/(BMI2/3height1/2)). Adjusted relative risk(RR) for diabetes was estimated by Poisson regression model where index values were computed separately for each control, and receiver operating characteristic (ROC) curve analysis was applied. There were no associations between ABIS and T2DM incidence in both sexes. In men, BMI and WC did not show significant associations either, and in women, the RR of highest quartile relative to the lowest quintile was significant (1.95 (1.27-3.01)) only in WC. AUCs (area under the ROC curve) and 95% CIs of WC were 0.613(0.591-0.634) in men and 0.642 (0.626-0.659) in women, and showed significant differences compared with the AUCs of ABSI (0.567 (0.545-0.588) for men, 0.580(0.563-0.597) for women) and BMI (0.578 (0.556-0.599) for men, 0.601 (0.584-0.618) for women) in both sexes. In this study, ABSI was not better than a WC in predicting the ability for T2DM, and WC was a good surrogate index of obesity to T2DM incidence especially in Korea elderly women.

Disclosure
S. Lim: None. J. Lee: None. K. Yoon: None.
Anemia Is Inversely Associated with Serum C-Peptide Concentrations in Patients with Type 2 Diabetes
Authors: CHUNG JIN OOK , PARK SEON-YOUNG , CHO DONG HYEOK , CHUNG DONG JIN , CHUNG MIN YOUNG 
Published: June 2018

Results: The aim of the study was to investigate the relationship between anemia and serum C-peptide concentrations in Korean patients with type 2 diabetes. A total of 1,300 subjects with type 2 diabetes were investigated in this cross-sectional study. Fasting C-peptide concentration, 2-hour postprandial C-peptide concentration, and δC-peptide (postprandial C-peptide minus fasting C-peptide) concentration were measured in all patients. Anemia was defined according to the World Health Organization. Fasting C-peptide level, postprandial C-peptide level, and δC-peptide level was lesser in subjects with anemia. According to the grade of anemia, the average C-peptide levels were significantly different after adjusting for other covariates (fasting C-peptide level: no anemia, 0.73 mmol/l; grade I anemia, 0.66 mmol/l; grade II anemia, 0.62 mmol/l; P for trend = 0.002; postprandial C-peptide level: no anemia, 1.54 mmol/l; grade I anemia, 1.36 mmol/l; grade II anemia, 1.32 mmol/l; P for trend &lt; 0.001; δC-peptide level: no anemia, 0.75 mmol/l; grade I anemia, 0.64 mmol/l; grade II anemia, 0.60 mmol/l; P for trend = 0.001). In the multivariate model, the association between anemia and serum C-peptide concentrations remained significant, after adjustment for confounding factors including age, gender, familial diabetes, body mass index, duration of diabetes, glycated hemoglobin, free fatty acid, hypertension, and hyperlipidemia (fasting C-peptide level: β= -0.057, P =0.032; postprandial C-peptide level: β= -0.098, P &lt;0.001; δC-peptide level: β= -0.095, P &lt;0.001, respectively). Our results showed that anemia was inversely associated with serum C-peptide concentrations in subjects with type 2 diabetes.

Disclosure
J. Chung: None. S. Park: None. D. Cho: None. D. Chung: None. M. Chung: None.
The Role of HbA1c on Mortality in Patients with Medical History of Ischemic Stroke and Paroxysmal Atrial Fibrillation
Authors: KANELLOPOULOU KONSTANTINA , MATSOUKIS IOANNIS L. , GANOTOPOULOU ASIMINA , ATHANASOPOULOU THEODORA , TRIANTAFILLOPOULOU CHRYSOULA , SIANNI ALEXANDRA 
Published: June 2018

Objective: The correlation of HbA1c level with mortality in patients with ischemic stroke and Paroxysmal Atrial Fibrillation (pAfib).
Method: 278 patients with medical history of ischemic stroke and pAfib confirmed with cerebral Computed Tomography and electrocardiogram or rhythm Holter respectively, were included in the study. All patients visited for routine health screening examination or with minor deseases the departments of internal medicine of three tertiary hospitals. The mean age was 78±12 years. The participants were divited into two groups: In group A, 167 patients (60%) that had diabetes mellitus type II (DMT2) were included. Among them, 92 were women (55%) and 75 were men (45%). The remaining 111 patients (58 women (52%) and 53 men (48%)) had no medical history of DMT2, and were included in group B. Among others, HbA1c was measured in all patients in months 6,12,18,24,36 and a survival/ events follow-up was recorded. The study duration was 36 months.
Results: In group A, 20 deaths of patients (12%) were reported, among them 8 were men (40%) and 12 were women (60%) with average HbA1c measurements during the follow-up period: 2 patients (10%) with 6,5&lt;HbA1c&lt;7, 6 patients (30%) with 7&lt;HbA1c&lt;8,5 and 12 patients (60%) with HbA1c&gt;8,5. In group B, 10 deaths (9%) were reported. Among them, 4 men (40%) and 5 women (60%) with measurement 6&lt;HbA1c&lt;6,5 and 1 woman (10%) with HbA1c&lt;6. The mortality for patients with ischemic stroke and pAfib is increased with the increase of HbA1c in patients with DMT2 in a statistically significant manner (p 0.0031). An non-statistically significant increase in mortality was also observed in group B. (p 0.22).
Conclusion: The increase in the level of HbA1c increases the mortality in patients with ischemic stroke and pAfib especially in those with DMT2.

Disclosure
K. Kanellopoulou: None. I.L. Matsoukis: None. A. Ganotopoulou: None. T. Athanasopoulou: None. C. Triantafillopoulou: None. A. Sianni: None.
Poor Glycaemic Control—Identifying Variables Associated with Therapeutic Inertia and Lack of Therapeutic Adherence
Authors: CEBRIAN ANA , GUISASOLA FERNANDO ALVAREZ , COS FRANCESC XAVIER , QUINTERO MANUEL RUIZ , MILLARUELO JOSE MANUEL , BELTRAN DOMINGO OROZCO ,   SEMFYC DIABETES THE SPANISH SOCIETY OF FAMILY MEDICINE DIABETES GROUP
Published: June 2018

Two main causes of poor glycaemic control has been describe in diabetic patients: lack of patient adherence to antidiabetic drugs and lack of treatment intensification by the physician.
Aim: To analyse variables associated to therapeutic inertia(TI) or lack of adherence in diabetic patients with poor glycaemic control in Spanish primary care.
Methods: Observational cross sectional nationwide study. 48 primary care physicians (PCP) from the Spanish working group on diabetes mellitus from the Sociedad Española de Medicina de Familia. 4patients randomly selected from each surgery. Individualized glycemic targets were calculated according to the algorithm from Cahn A et al (Diabetes Care 2016). TI was defined as a patient with good adherence, according to PCP opinion, but with poor individualized glycaemic control (GC).
Results: 60.5% of patients had good GC (group A), and 39.5% had poor control, 22.1% due to TI (group B) and 17.4% due to poor therapeutic adherence (PTA) (Group C). All three group of patients differ according to the following variables, respectively: age (69.5 vs. 70.5 vs. 63.8 years; p=0.000); HbA1c (6.27 vs. 7.75 vs. 8.46%; p=0.000); number of antidiabetic drugs (1.3 vs. 2.0 vs. 2,1; p=0.000); prevalence of osteoarthritis (50.5 vs. 44.4 vs. 29,7%; p=0.013); risk of hypoglycaemia (66.7 vs. 64.3 vs. 37.5%; p=0.000); physicians time (years) in the practice (12.5 vs. 15.3 vs. 11.5 years; p=0.000). No differences were found in number of comorbidities, gender, cognitive impairment, micro or macro vascular complications, cancer, thyroid dysfunction, dyslipidemia, arterial hypertension, COPD, anxiety, or depression.
Conclusions: 39.5% of diabetic patients have poor glycaemic control according to individualized targets; 22.1% due to TI and 17.4% due to poor therapeutic adherence. Patients with TI compared to patients with PTA were older, with lower A1c, higher risk of hypos, higher prevalence of ostheoartritis and with a PCP with more years in the practice.

Disclosure
A. Cebrian: None. F. Alvarez Guisasola: None. F. Cos: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Sanofi Pasteur. Speaker's Bureau; Self; Sanofi Pasteur. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Eli Lilly and Company. M. Ruiz Quintero: None. J. Millaruelo: None. D. Orozco Beltran: None.
The MODY Masquerade
Authors: ENGLERT DANIEL , DENDY JARED 
Published: June 2018

Introduction: Maturity Onset Diabetes of the Young (MODY) is a relatively uncommon, but increasingly recognized cause of diabetes. Many MODY patients are misdiagnosed as type 1 or type 2 diabetes mellitus (DM) and may be treated suboptimally for many years before they are recognized. We present one such patient who went 49 years before accurate diagnosis.
Case: A 59 year-old female with a history of type 2 DM presented with complaints of difficulty controlling her blood sugar. She was being treated with metformin, and had been recently started on low dose glimepiride due to persistently elevated hemoglobin A1c (HbA1c). She was diagnosed as type 2 DM at 10 years of age. Her weight was normal at the time of diagnosis, and she did not require insulin. Family history included many family members diagnosed as type 2 DM, including her maternal grandmother, mother, brother, sister, son, and two nieces. All were diagnosed in their teens, and only her son currently requires insulin. On exam, she was not obese (BMI 26 kg/m2) with no signs of insulin resistance. Antibodies to glutamic acid decarboxylase (GAD Ab) were undetectable, and C-peptide was elevated to 4.04 ng/mL in response to mild hyperglycemia. Genetic testing revealed a defect in the Hepatocyte Nuclear Factor 4 Alpha (HNF4A) gene, consistent with MODY subtype 1. The dose of glimepiride was increased, and her HbA1c improved from 8.1% to 6.1% after two months.
Discussion: MODY is a form of diabetes caused by single gene mutations related to beta cell development, regulation, and function. These defects lead to impaired glucose sensing and insulin release. MODY should be suspected in patients with a strong family history of diabetes, lack of signs of insulin resistance, onset at young age, and absence of features of type 1 DM (i.e., negative GAD Ab and detectable C-peptide). MODY subtype 1 patients are typically sensitive to sulfonylurea therapy, and this is considered first-line treatment. However, some patients may develop progressive beta cell dysfunction as they age and will ultimately require insulin therapy.

Disclosure
D. Englert: None. J. Dendy: None.
Effects of Diabetes on Retinal Protein Lysine Malonylation
Authors: ABCOUWER STEVEN F. , SHANMUGAM SUMATHI , HAGER HEATHER M. , LIN CHENG-MAO , FORT PATRICE E. , GARDNER THOMAS W. , SAS KELLI , PENNATHUR SUBRAMANIAM 
Published: June 2018

Purpose: The addition of short chain acyl groups to lysines is emerging as key post-translational modifications (PTM) linking metabolite levels to metabolic enzyme activities. Malonyl-lysine (Kmal) targets and inhibits glycolysis and beta-oxidation enzymes. Recently, formation of Kmal was suggested to act as a sink for mitochondrial malate, preventing its inhibition of succinate dehydrogenase in the electron transport chain (ETC). Using the db/db T2DM mouse model, we recently found that diabetes increases retinal glycolysis and beta-oxidation metabolite levels, whereas malate was the only TCA cycle metabolite significantly increased. Metabolic flux measurement with 13C-labeled glucose also demonstrated increased enrichment of labeled malate. We therefore compared the relative levels of Kmal-modified proteins in retinas from diabetic mice as well as in postmortem retinas from diabetic patients to determine if this PTM is altered by diabetes.
Methods: Immunofluorescence (IF) with antibodies specific to acetyl-lysine, to succinyl-lysine and to Kmal was used to probe retinal sections from BKS-db/db mice and BKS-db/+ controls (n=9/group) at 24 weeks of age. Kmal modifications were also examined in mouse retinas from mice made diabetic with streptozotocin (STZ) and controls (n=6/group) and a limited number of retinal sections from postmortem eyes of diabetic (n=4) and control (n=2) patients. Antibodies to markers of retinal ganglion and glial cells were used to co-localize Kmal-modified proteins.
Results: Only Kmal IF intensity was significantly reduced by approximately 30% in both db/db and STZ diabetic mouse retinas. Kmal IF exhibited a 25% reduction in human diabetic retinas. Kmal-modified proteins were concentrated in the ganglion cell layer and largely coincided with Müller glia endfeet and/or astrocytes.
Conclusions: The results suggest that protein malonylation in glial cells is diminished in the diabetic retina, which may increase glycolysis and beta-oxidation while inhibiting the ETC.

Disclosure
S.F. Abcouwer: None. S. Shanmugam: None. H.M. Hager: None. C. Lin: None. P.E. Fort: None. T.W. Gardner: Research Support; Self; Novo Nordisk A/S. K. Sas: None. S. Pennathur: None.
Association of IL-6 and CRP Levels with Gestational Diabetes Mellitus
Authors: SIDDIQUI SAMREEN , WAGHDHARE SWATI , PANDA MANJU , DUBEY SHWETA , JHA SUJEET 
Published: June 2018

Aim: Gestational diabetes mellitus (GDM) is a common clinical condition characterized by glucose intolerance of varying severity in the second or third trimester of pregnancy. Inflammatory mediators like interleukin-6 (IL-6) and acute phase protein like C-reactive protein (CRP) are supposed to contribute to development of GDM, however clinical data supporting this hypothesis is limited. This study was designed to analyze the association of inflammatory mediators like IL-6 and CRP with development of GDM in Indian females.
Methods: A case control study design included pregnant women diagnosed as GDM (n=53) and pregnant women having normal glucose tolerance (n=50), screened according to the criteria of American Diabetes Association. Serum levels of interleukin -6 (IL-6) and C-reactive protein (CRP) were analysed in study subjects by enzyme linked immunoassay and correlated with various clinical parameters.
Results: Serum IL-6 levels were significantly high (p&lt;0.05) in GDM females as compared to non-GDM females. The IL-6 levels correlated with pre-pregnancy body mass index (BMI), fasting blood sugar (FBS) levels and postprandial sugar (PPBS) levels. Unlike IL-6, CRP levels did not show significant differences between the GDM and non-GDM females. However, we did observe a positive correlation of CRP levels with BMI, FBS and PPBS. GDM group also showed association with age, BMI and family history of diabetes. The occurrence of GDM was observed more in the females &gt; 30 years of age in our population subset.
Conclusion: High IL-6 levels in gestational diabetes may indicate a possible role for inflammation in pathophysiology of GDM.

Disclosure
S. Siddiqui: None. S. Waghdhare: None. M. Panda: None. S. Dubey: None. S. Jha: None.
Self-Reactivity and T-Cell Receptor Repertoire of Effector and Regulatory T Cells in Autoimmune Diabetes
Authors: KONG YUELIN , SPROUSE MARAN L. , JING YI , BETTINI MATTHEW , BETTINI MARIA 
Published: June 2018

T cell infiltration and accumulation in pancreatic islets during autoimmune diabetes is to a large degree driven by TCR reactivity to beta cell antigens. However, it is not fully clear whether the strength of TCR reactivity to beta cell antigens is an important determinant of effector or regulatory T cell function. We observed that CD5 expression is proportional to the level of self-reactivity based on Nur77-GFP reporter of TCR signaling and insulin tetramer staining of islet infiltrating T cells. Using RNAseq profiling, TCR sequencing, and cell transfer we show that CD5 segregates functionally and transcriptionally distinct effector and regulatory T cells, demonstrating that reactivity to beta cell antigens is an important determinant of effector and regulatory T cell function in autoimmune diabetes.

Disclosure
Y. Kong: None. M.L. Sprouse: None. Y. Jing: None. M. Bettini: None. M. Bettini: None.
Deficiency in Absent in Melanoma (AIM) 2, an Innate Immunity Protein, Is Associated with Hepatic Steatosis
Authors: GONG ZHENWEI , JIANG RUIHUA , SU KAI , GOETZMAN ERIC , DONG HENRY , MUZUMDAR RADHIKA 
Published: June 2018

Absent in Melanoma (AIM) 2, an HIN-200 domain family interferon inducible gene, is a cytosolic sensor for double-stranded DNA, forms the AIM2 inflammasome, and is a tumor suppressor gene. Lack of AIM2 increases the risk for cancers including liver cancer. We had earlier shown that mice with whole body deletion of AIM2 (AIM2-/-) exhibit increased body weight and total fat mass (without change in lean mass), visceral and subcutaneous adiposity, elevated fasting glucose and impaired glucose tolerant test without significant change in food intake. To assess the effects of AIM2-/- on liver, we analyzed liver weight, gene expression and protein levels of key players of hepatic lipid metabolism in female wild type (WT) and AIM2-/- mice (14-month-old, n=7/group) on chow diet. Fatty acid oxidation in liver was determined by incubating 14C-palmitate with liver lysate, and trapping and quantifying the 14CO2 generated from the 14C-palmitate. We found that liver was enlarged in AIM2-/- mice compared to WT controls (liver weight 1.25±0.03 vs. 1.62±0.09 g, p&lt;0.01 and liver/body weight 0.037±0.001 vs. 0.042±0.002 in WT and AIM2-/- respectively, p=0.02). Histological examination demonstrated significantly increased lipid deposition in the liver of AIM2-/- mice. Expression levels of lipogenic genes, such as ACC1 (4 fold), ACC2 (3.2 fold), PPARγ (2.8 fold), C/EBPα (2.4 fold), CD36 (2.4 fold), Fasn (4.3 fold) and SREBP-1c (3.8 fold) were significantly increased in AIM2-/- mice; increases in lipogenic gene expression in the liver are likely due to the phosphorylation and nuclear localization of STAT3. Fatty acid oxidation was not affected in liver of AIM2-/- mice (22.8±2.4 vs. 25±3.9 pmoles/ug/hr, p=0.52). Taken together, our data provides strong evidence that AIM2 is a regulator of hepatic fat, thereby providing a novel target for treatment of NALFD. AIM2 is a novel link between innate immunity, cancer and obesity.

Disclosure
Z. Gong: None. R. Jiang: None. K. Su: None. E. Goetzman: None. H. Dong: None. R. Muzumdar: None.
A Novel Role of Growth Differentiation Factor 3 for the Regulation of Muscle Metabolism
Authors: HAYS TRISTAN T. , PATSALOS ANDREAS , HAMMERS DAVID , HUANG CHUNTENG , RESTREPO ISABELLA , HAJIAN MATINE , AYALA JULIO , NAGY LASZLO 
Published: June 2018

Insulin resistance has become a major global health problem, and current insulin sensitization treatments have the unfortunate effect of also increasing adiposity. One solution to mitigate these side effects would be to selectively stimulate skeletal muscle metabolism to reduce fasting glucose levels and improve insulin sensitivity. Previous studies have described growth differentiation factor 3 (GDF3) as an adipokine, however our recent studies have identified GDF3 as a macrophage derived factor that stimulates myoblast fusion and promotes muscle regeneration. Thus, we hypothesize that GDF3 might also stimulate myocyte metabolism and skeletal muscle insulin sensitivity. We first assessed whether recombinant GDF3 treatment can stimulate glucose uptake in vitro. Differentiated C2C12 myotubes were treated with rGDF3 and [H3] 2-deoxy-D-glucose uptake was found to be increased upon GDF3 treatment. Next, we tested whether GDF3 could stimulate insulin sensitivity in vivo. GDF3 was adenovirally overexpressed in mice fed a high fat diet for 8 weeks and insulin sensitivity was assessed by insulin tolerance tests. GDF3 overexpression reduced fasting glucose levels and also demonstrated a tendency for improved insulin tolerance. Collectively, these data suggest that GDF3 could act as a potential insulin sensitizing agent and provide mechanistic insights into skeletal muscle glucose regulation.

Disclosure
T.T. Hays: None. A. Patsalos: None. D. Hammers: None. C. Huang: None. I. Restrepo: None. M. Hajian: None. J. Ayala: None. L. Nagy: None.
Identification of Warm-Sensitive Neurons in the Hypothalamic Preoptic Area as Powerful Regulators of Glucose Homeostasis
Authors: DEEM JENNIFER D. , OGIMOTO KAYOKO , VELASCO KEVIN R. , DAMIAN VINCENT , KNIGHT ZACHARY , SCHWARTZ MICHAEL W. , MORTON GREGORY J. 
Published: June 2018

Inhibition of warm sensitive neurons (WSN) in the hypothalamic preoptic area (POA) has been suggested to play a key role in the thermogenic response to cold exposure. As this response is enabled by a marked increase of insulin sensitivity in thermogenic tissues, we hypothesized that WSN inhibition mediates the metabolic as well as the thermogenic response, and therefore that WSN activation would have the opposite effects. To test this hypothesis, we utilized pharmacogenetic technology to activate or inhibit a recently identified subpopulation of POA WSN defined by their expression of the neuropeptide, Pacap, using the drug clozapine-N-oxide (CNO). We report that, as predicted, pharmacogenetic activation of this POA WSN population reduces energy expenditure (EE) (Sal vs. CNO: 0.32±0.10 vs. 0.21±0.02 kcal/hour; p&lt;0.05) and core temperature (Tc) (Sal vs. CNO: 35.4±0.1 vs. 30.4±0.1°C; p=0.0001), while inhibition had the opposite effect (EE: Sal vs. CNO: 0.25±0.03 vs. 0.26±0.03 kcal/hour; Tc: Sal vs. CNO: 35.8±0.1 vs. 36.4±0.2°C; p&lt;0.05). The response to pharmacogenetic activation of POA Pacap+ neurons was quite long-lived (∼2-3 days) and was accompanied by severe glucose intolerance both 1 hour and 24 hour following CNO relative to vehicle treatment (glucose AUC: 3610±1216 for saline vs. 23985±2742 for 1 hour CNO vs. 28459±2411 vs. 24 hour CNO au; p&lt;0.05 vs. saline). Moreover, this marked impairment of glucose tolerance occurred even after a compensatory increase of glucose-induced insulin secretion at the 24 hour time point (Plasma insulin (t=30): 0.42±0.10 for saline vs. 0.45±0.10 ng/mL for 1 hour CNO vs. 1.05±0.20 ng/mL for 24 hour CNO; p=ns). However, despite significant increases in Tc, acute inhibition of POA Pacap+ neurons did not improve glucose tolerance, possibly due to compensation by other WSN populations activated by the thermogenic response. We conclude that POA Pacap+ neurons constitute a subset of WSN that exert profound, previously unrecognized effects on glucose homeostasis.

Disclosure
J.D. Deem: None. K. Ogimoto: None. K.R. Velasco: None. V. Damian: None. Z. Knight: None. M.W. Schwartz: Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. G.J. Morton: None.