bluuebunny/crossref_metadata_2025 huggingface dataset:
34-LB: Clinically Meaningful Improvements of Gastroparesis Overall Symptoms Using Tradipitant
Authors: CARLIN JESSE L. , LIEBERMAN VERNA R. , DAHAL ARYA , KEEFE MADISON S. , XIAO CHANGFU , BIRZNIEKS GUNTHER , POLYMEROPOULOS MIHAEL H.
Published: June 2019

Background: Patients with diabetic and idiopathic gastroparesis with delayed gastric emptying and moderate to severe nausea were enrolled into a phase II multicenter, randomized, double-blind, placebo-controlled trial. Subjects were randomized to receive oral 85mg tradipitant bid or placebo (1:1) for 4 weeks. Of the 152 patients, 60% of patients had idiopathic and 40% had diabetic gastroparesis.

Methods: The primary outcome was change in average nausea from baseline, measured using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptoms were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM).

Results: A statistically significant and clinically meaningful improvement in nausea and overall gastroparesis symptoms was observed in patients on tradipitant. Subjects receiving tradipitant had a significant decrease in their average nausea score compared to placebo with LS mean difference (95% CI) of -0.53 (-0.92, -0.13, p=0.0099) as well as a significant increase in nausea free days (28.8% increase on tradipitant compared to 15.0% increase on placebo, p=0.0160). A clinically meaningful response of 1-point or more improvement on the GCSI total score was observed in 46.0% of patients on tradipitant compared to 24.2% of patients on placebo (p=0.0086).

Conclusions: Tradipitant treatment resulted in statistically and clinically meaningful improvements in nausea and overall gastroparesis symptoms. Tradipitant was well tolerated with comparable rates of adverse events between tradipitant and placebo groups. These robust efficacy results suggest tradipitant has the potential to become a first line treatment for idiopathic and diabetic gastroparesis.

Disclosure

J.L. Carlin: Employee; Self; Vanda Pharmaceuticals, Inc. V.R. Lieberman: Employee; Self; Vanda Pharmaceuticals, Inc. Stock/Shareholder; Self; Vanda Pharmaceuticals, Inc. A. Dahal: Employee; Self; Vanda Pharmaceuticals, Inc. Stock/Shareholder; Self; Vanda Pharmaceuticals, Inc. M.S. Keefe: Employee; Self; Vanda Pharmaceuticals. Stock/Shareholder; Self; Vanda Pharmaceuticals. C. Xiao: Employee; Self; Vanda pharmaceutical inc. G. Birznieks: Employee; Self; Vanda Pharmaceuticals. M.H. Polymeropoulos: Employee; Self; Vanda Pharmaceuticals Inc.
342-LB: Iron Regulatory Protein 2 Regulates Proinsulin Production in Pancreatic Beta Cells through Iron-Dependent Cdkal1-Catalyzed tRNA Modification
Authors: FERREIRA DOS SANTOS MARIA C. , RAJAN MALINI , LEIBOLD ELIZABETH
Published: June 2019

Iron regulatory protein 2 (Irp2) is a key regulator of cellular iron metabolism in vertebrates. Irp2 controls the post-transcriptional expression of the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-storage protein ferritin. Here we show that Irp2-/-mice develop diabetes characterized by glucose intolerance and impaired glucose-stimulated insulin secretion from pancreatic β-cells. Impaired glucose-stimulated insulin secretion in Irp2-/-β-cells is not due to insulin resistance but rather to a reduction in insulin stores caused by impaired proinsulin processing. Loss of Irp2 reduces TfR1 expression and iron content, and increases ferritin expression and iron sequestration causing cellular iron deficiency that impairs mitochondrial Fe-S cluster biosynthesis. This in turn reduces the function of Cdk5-regulated subunit-associated protein 1 like (Cdkal1), a 4Fe-4S cluster enzyme that catalyzes the 2-methythio (ms) modification of t6A37 of tRNALys(UUU)to ms2t6A37, which is critical for efficient translation of lysine codons in proinsulin. Irp2-deficient β cells show reduced ms2t6A37 levels and lysine incorporation into proinsulin. Increasing cellular iron content in Irp2-deficient β cells normalizes mitochondrial function, ms2t6A37 levels, proinsulin and insulin content, and insulin secretion. These study reveals a previously unidentified link between insulin processing and cellular iron homeostasis, and show that Irp2 is required for normal β cell function and whole body glucose homeostasis.

Disclosure

M.C. Ferreira dos Santos: None. M. Rajan: None. E. Leibold: None.

Funding

American Diabetes Association (1-18-PMF-020 to M.C.F.D.S.); National Institute of Diabetes and Digestive and Kidney Diseases
345-LB: Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF): A New Therapeutic Target for Wolfram Syndrome
Authors: MORIKAWA SHUNTARO , MAHADEVAN JANA , YAGI TAKUYA , ABREU DAMIEN , KANEKURA KOHSUKE , BROWN CRIS M. , URANO FUMIHIKO
Published: June 2019

Endoplasmic reticulum (ER) stress is an emerging target for human chronic disorders, including β cell death in type 1 and type 2 diabetes, as well as neurodegenerative diseases. However, there is currently no treatment for preventing ER stress-mediated cell death due to its complex nature. Our strategy for overcoming this challenge is to focus on a rare monogenic disease, Wolfram syndrome. Wolfram syndrome is a rare genetic disease characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, impaired hearing and neurodegeneration. As this syndrome is caused by the loss-of-function of the WFS1 gene which is involved in ER calcium homeostasis and ER stress-mediated cell death, it is ideal for testing potential new treatments targeting the ER. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a trophic factor whose expression and secretion is enhanced by ER stress and ER calcium depletion. It has been demonstrated that MANF plays a critical role in the survival of ER stressed β cells and neurons, raising the possibility that MANF can be beneficial for patients suffering from ER stress-related disorders. In this study, we show that treatment with recombinant MANF peptide in cell models of Wolfram syndrome suppresses the caspase 3/7 activation and terminal ER stress markers, including C/EBP homologous protein (Chop) and Tribbles 3 (Trb3), and activates the mTOR/S6K signaling pathway. Furthermore, the proliferation of β cells in a WS mouse model is activated by recombinant MANF peptide treatment and adeno-associated virus induced MANF overexpression. Our results indicate that molecular pathways regulated by MANF are promising drug targets for ER stress-related disorders, including β cell death in diabetes and Wolfram syndrome.

Disclosure

S. Morikawa: None. J. Mahadevan: None. T. Yagi: None. D. Abreu: None. K. Kanekura: None. C.M. Brown: None. F. Urano: Board Member; Self; Healthbeat. Research Support; Self; Aetas, Amylyx, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Stock/Shareholder; Self; CytRx. Other Relationship; Self; Novus Biologicals.

Funding

National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (DK112921, DK020579); National Institutes of Health/National Center for Advancing Translational Science (TR002065); Unravel Wolfram Syndrome Fund; Lois and Samuel Silberman Fund; Stowe Education Fund; Ellie White Foundation for Rare Genetic Disorders; Eye Hope Foundation; Snow Foundation (to F.U.); National Institutes of Health (F30DK111070 to D.A.)
359-OR: 12/15-Lipoxygenase in Islets and Macrophages Independently Promotes Autoimmune Diabetes in NOD Mice
Authors: PINEROS ALVAREZ ANNIE ROCIO , KULKARNI ABHISHEK , ORR KARA , GLENN LINDSEY , REISSAUS CHRISTOPHER A. , HERNANDEZ-PEREZ MARIMAR , GANNON MAUREEN , MCDUFFIE MARCIA J. , NADLER JERRY , MIRMIRA RAGHAVENDRA , MORRIS MARGARET A. , TERSEY SARAH A.
Published: June 2019

The pathogenesis of type 1 diabetes (T1D) involves the interaction of the immune system with β cells. 12/15-lipoxygenase (12/15-LOX), an enzyme involved in arachidonic acid metabolism, is expressed in both β cells and macrophages. Global deletion of the gene encoding 12/15-LOX (Alox15) prevents diabetes in the NOD mouse model of T1D via reduction in production of proinflammatory mediators in islets and macrophages. However, the importance of 12/15-LOX in islets vs. macrophages remains unclear. To address this issue, we generated both inducible islet-cell-specific (NOD-Alox15∆islet) and myeloid-lineage-specific (Alox15∆myel) Alox15 knockout mice on the NOD background. Control female mice (Alox15loxp/loxp, Pdx1PB-CreERTM+, and LysM-Cre+) exhibited diabetes incidence greater than 75%, whereas both Alox15∆islet and Alox15∆myel showed a dramatic decrease in the incidence of diabetes (<10%, P<0.05). During the pre-diabetic phase (8 weeks of age), both control and Alox15∆islet mice exhibited similar β-cell mass (0.70±0.08 g vs. 0.72±0.06 g, P=NS) and insulitis severity (score 1.89±0.17 vs. 1.74±0.19, P=NS), whereas Alox15∆myel mice had increased β-cell mass (1.56±0.02c g, P<0.05) and insulitis (score 1.18±0.08, P<0.05). We next examined the nature of immune cells present in the spleen and pancreatic lymph node (pLN). Alox15∆islet mice showed increased Tregs (CD4+FoxP3; P<0.05) with no changes in Th1 (CD4+IFNγ+) and Th17 (CD4+IL17+) cells in both the spleen and pLN compared to control mice (P=NS). Additionally, Alox15∆islet female mice exhibited decreased IL-1β production by dendritic cells. By contrast, Alox15∆myel mice showed only decreased pLN proinflammatory macrophages (F480+IL1β+) and dendritic cells (CD11c+IL1β+) compared to controls (P<0.05). Together, these data suggest that 12/15-LOX functions independently in both the islet and macrophage through different mechanisms, promoting the destruction of β cells during the pathogenesis of autoimmune T1D.

Disclosure

A. Pineros Alvarez: None. A. Kulkarni: None. K. Orr: None. L. Glenn: None. C.A. Reissaus: None. M. Hernandez-Perez: None. M. Gannon: None. M.J. McDuffie: Stock/Shareholder; Self; Adenosine Therapeutics, LLC. J. Nadler: None. R. Mirmira: None. M.A. Morris: Stock/Shareholder; Spouse/Partner; Sanofi US. S.A. Tersey: None.

Funding

National Institutes of Health (R01DK105588 to R.M., J.N.)
368-P: Effects of Mild Hypoglycaemia on Cognitive Function in Type 2 Diabetes
Authors: NILSSON MALIN , JENSEN NICOLE J. , GEJL MICHAEL , BRANDSLUND IVAN , STORGAARD HEIDI , ZANDER METTE , MISKOWIAK KAMILLA , RUNGBY JØRGEN
Published: June 2019

Background: Previous studies have demonstrated cognitive impairment during severe hypoglycaemia. This study provides quantitative results on cognitive function during an acute mild hypoglycaemic episode in patients with type 2 diabetes.

Methods: In this double-blinded randomized cross-over study, 25 patients with type 2 diabetes attended two experimental visits with hyperinsulinaemic glucose clamping; one hypoglycaemic clamp (PG 3.0 ± 0.2 mmol/l) and one euglycaemic clamp (PG 6.0 ± 0.2 mmol/l). Cognitive function was assessed during each condition with a neurocognitive test battery measuring verbal memory, executive function, sustained attention and psychomotor speed.

Results: The participant’s cognitive performances were impaired during hypoglycaemia with mean score in the primary outcome test, SDMT, of 48.7 (hypoglycaemia) and 56.6 (euglycaemia); the estimated treatment difference was -7.9 (95% CI -10.9, -4.9; p=<0.0001). The composite score of overall speed of complex cognitive processing showed a highly significant deterioration during the hypoglycaemic condition of -0.7 (95% CI -0.9, -0.6; p=<0.0001) (Figure). Age, sex, fasting C-peptide and hypoglycaemic symptom severity did not influence the effect of hypoglycaemia on cognitive function.

Conclusion: Acute mild hypoglycaemia (3 mmol/l [54 mg/dl]) negatively affects cognitive function in patients with type 2 diabetes.

Disclosure

M. Nilsson: None. N.J. Jensen: None. M. Gejl: Other Relationship; Self; Novo Nordisk A/S. I. Brandslund: None. H. Storgaard: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Zander: None. K. Miskowiak: None. J. Rungby: None.

Funding

Investigator Initiated Studies Program of Merck Sharp & Dohme Corp.
369-P: Effects of Nocturnal Hypoglycemia on Quality of Life and Mood During Daily Life in Type 1 Diabetes—A CGM-Based Analysis
Authors: HENRIKSEN MARIE M. , ANDERSEN HENRIK U. , THORSTEINSSON BIRGER , PEDERSEN-BJERGAARD ULRIK
Published: June 2019

Objective: To assess the effect of spontaneous nocturnal hypoglycemia on quality of life and mood the subsequent days in type 1 diabetes.

Research Design and Methods: A total of 153 persons with type 1 diabetes participated in 6 days of blinded continuous glucose monitoring (CGM) while daily documenting hypoglycemic symptoms, quality of life and mood. Hypoglycemia was defined by interstitial glucose ≤ 70 mg/dl (IG70) and ≤ 54 mg/dl (IG54) for > 15 minutes and was classified as asymptomatic if no hypoglycemic symptoms were reported in the diary.

Results: Self-estimated quality of life assessed by the EQ-5D VAS (but not by the WHO Well-Being Index) was higher the day after an asymptomatic (but not after a symptomatic) hypoglycemic night as compared with non-hypoglycemic nights (IG70: p = 0.021 and IG54: p = 0.048). The effect increased with longer duration and lower glucose nadir of nocturnal hypoglycemia (IG70: p = 0.04). The finding was confined to participants with reduced hypoglycemia awareness. There was no effect on mood of nocturnal hypoglycemia.

Conclusions: Individuals with type 1 diabetes and impaired awareness report higher quality of life following nights with asymptomatic - but not symptomatic - hypoglycemia. The effect was amplified by lower glucose nadir and longer duration of the episodes and may contribute to explain resistance to implementation of interventions against hypoglycemia in many people with impaired hypoglycemia awareness.

Disclosure

M.M. Henriksen: None. H.U. Andersen: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; Nordic Infucare. Stock/Shareholder; Self; Novo Nordisk Inc. B. Thorsteinsson: None. U. Pedersen-Bjergaard: Advisory Panel; Self; AstraZeneca, Sanofi-Aventis, Zealand Pharma A/S. Speaker's Bureau; Self; Novo Nordisk A/S.

Funding

Nordsjællands Hospital; Jascha Foundation; Danish Medical Research Grant; The Toyota Foundation, Denmark
37-LB: Diabetic Retinopathy (DR) Screening Performance of an Artificial Intelligence (AI) System: Analysis from a Pivotal Multicenter Prospective Clinical Trial
Authors: BODE BRUCE W. , IPP ELI , SHAH VIRAL N. , SADDA SRINIVAS R.
Published: June 2019

A prospective study (NCT03112005) evaluated DR screening using the EyeArt AI eye screening system against the ETDRS clinical reference standard (CRS). A total of 893 subjects with diabetes were enrolled at 15 U.S. clinical centers and completed 2-field fundus photography for analysis by the EyeArt system and dilated 4-wide field stereo fundus photography for adjudicated expert grading to establish CRS.

The EyeArt system provided eye-level results for referable DR (rDR) [moderate non-proliferative DR (NPDR) or higher on the International Clinical DR (ICDR) severity scale or clinically significant diabetic macular edema (CSDME)] and for vision-threatening DR (vtDR) [severe NPDR or higher on the ICDR scale or CSDME]. Out of 1718 eyes with gradable CRS for rDR, 1392 eyes were negative and 326 were positive. Out of 1702 eyes with gradable CRS for vtDR, 1588 were negative and 114 were positive.

The EyeArt system was evaluated against CRS for identifying rDR and vtDR under an undilated protocol and a dilate-if-needed protocol (where dilated images were used for subjects with ungradable EyeArt results on undilated images). Results (Table) indicate that the EyeArt AI system compares favorably with the clinical reference standard and meets the predetermined study endpoints for the detection of referable and vision-threatening DR in people with diabetes.

Disclosure

B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. E. Ipp: Research Support; Self; Eyenuk Inc., Novartis Pharmaceuticals Corporation. V.N. Shah: Advisory Panel; Self; Sanofi US. Consultant; Self; Dexcom, Inc. S.R. Sadda: Consultant; Self; Carl Zeiss Meditec, Centervue, Heidelberg Engineering, Optos. Other Relationship; Self; Nidek. Other Relationship; Spouse/Partner; Topcon.

Funding

National Institutes of Health (EY027241, EY026864)
37-OR: Distinct Functional Beta-Cell Subpopulations in Intact Islets of Langerhans
Authors: KRAVETS VIRA , PISCOPIO ROBERT A. , SCHLEICHER WOLFGANG , BENNINGER RICHARD K.
Published: June 2019

Glucose-stimulated insulin secretion is driven by the coordinated Ca2+ response in pancreatic islets following glucose elevation. In mouse islets, spatial and temporal Ca2+ dynamics are disproportionally controlled by subpopulations of β-cells, as identified by optogenetics. It is unknown which factors underlie this functional heterogeneity of β-cells in intact islets. Here, we tested if distinct β-cell subpopulations may be identified based on Ca2+ response to glucose elevation, and if their Ca2+ uptake efficiency, metabolic activity and electrical coupling are significantly different. We used MIP-CreER GCaMP6s mouse model which expresses Ca2+-sensitive GFP specifically in β-cells. We performed simultaneous Ca2+ dynamics and metabolic activity (NADH) response to [2-11] mM glucose elevation, along with gap junction permeability measurements in individual islets. We observed three functional subpopulations of β-cells distinct from an islet average: cells with 1) the fastest response to glucose elevation (1st responders); 2) the fastest 2nd phase oscillatory Ca2+ response (wave-initiators); and 3) the non-coordinated Ca2+ oscillations (un-coordinated). While 1st responders and wave-initiators were in different sub-regions of the islet, both subpopulations accumulated more Ca2+ during initial Ca2+ elevation (p=0.0403, p=0.0101) compared to the islet-average. Wave-initiators were more metabolically active (p=0.0223). The un-coordinated cells accumulated less Ca2+ (p<0.001) and were less metabolically active (p=0.0296). Gap junction permeability was not significantly different between subpopulations.

In conclusion, the 1st phase Ca2+ uptake and 2nd phase Ca2+ oscillations emerge in spatially- and metabolically-distinct subregions of the islet. This is likely due to increased metabolic activity of the β-cells in these regions which leads to greater membrane depolarization and thus, disproportionately enhances the islet Ca2+response. (NIH R01 DK102950 R01 DK106412)

Disclosure

V. Kravets: None. R.A. Piscopio: None. W. Schleicher: None. R.K. Benninger: None.

Funding

National Institutes of Health
385-P: Blocking the Nicotinic Receptors of the Parasympathetic Nervous System Prevents Severe Hypoglycemia-Induced Fatal Cardiac Arrhythmias in Rats
Authors: RENO CANDACE M. , BAYLES JUSTIN , HUANG YIQING , OXSPRING MILAN B. , FISHER SIMON
Published: June 2019

In response to hypoglycemia, excessive stimulation of the parasympathetic nervous system (PNS) may induce bradycardia and fatal heart block. Since signaling via nicotinic receptors mediates the PNS response, it was hypothesized that these receptors may mediate hypoglycemia-induced cardiac arrhythmias. To test this hypothesis, mecamylamine (a nicotinic receptor antagonist; 7.5 mg/kg, n = 17) or saline (control; n = 20) was infused intravenously in Sprague Dawley rats during insulin-induced (0.2mU/kg/min) severe hypoglycemic (10-15 mg/dl) clamps for 3 hours with electrocardiogram recordings. Compared to controls, mecamylamine-treated rats required a 3-fold higher glucose infusion rate during severe hypoglycemia, consistent with lower peak epinephrine levels (5698±557 vs. 2418±396 pg/ml; p < 0.001). In control rats, hypoglycemia led to 2nd degree heart block (1.8±1.7/min), 3rd degree heart block (32%), and mortality (25%). However, mecamylamine treatment completely prevented 2nd and 3rd degree heart block resulting in 100% survival (*p < 0.05).

In summary, blocking nicotinic receptors prevents cardiac arrhythmias and mortality during severe hypoglycemia. Clinically, targeting the parasympathetic nervous system could be a logical approach to prevent sudden death in people with insulin-treated diabetes at risk for hypoglycemia.

Disclosure

C.M. Reno: None. J. Bayles: None. Y. Huang: None. M.B. Oxspring: None. S. Fisher: None.

Funding

National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; JDRF
390-P: Changes in Glycaemic Variability after RYGB: A One-Year Prospective Study with Comparison to Patients with Post-bariatric Hypoglycaemia
Authors: THARAKAN GEORGE , ILESANMI IBIYEMI I. , BEHARY PREESHILA , ALEXIADOU KLEOPATRA , DOYLE CHEDIE S. , CHAHAL HARVINDER , PURKAYASTHA SANJAY , MIRAS ALEXANDER , OLIVER NICK , AHMED AHMED , BLOOM STEPHEN , TAN TRICIA M.
Published: June 2019

Some patients suffer disabling hypoglycaemia after RYGB, typically post prandially: Post Bariatric Hypoglycaemia (PBH). We hypothesised that these patients have increased glycaemic variability (GV), as assessed by continuous glucose monitoring (CGM).

Method: Prospective study of 6 patients undergoing RYGB with mixed meal tests (MMT) and CGM at baseline (BL), at 1 month and at 12 months. This cohort was compared to 15 patients with hypoglycaemia.

Results: RYGB leads to improvement in postprandial glucose tolerance at 120 minutes, preceded by an early peak of glucose and insulin at 30 minutes (Figure 1). Compared to pre-surgery, hypoglycaemic patients have significantly elevated peak glucose and insulin levels at 30 minutes followed by hypoglycaemia at 120 minutes. GV increases post RYGB: mean amplitude of glycaemic excursions (MAGE) median (95% CI) at BL 3.1 (2.3-6.8); 1 m 2.8 (2.2-4.2); 12 m 4.5 (3.4-5.5). PBH patients exhibit similar GV: MAGE 4.4 (3.7-6.5). The %time in range (TIR) glucose <3.9 increases post-surgery (BL 0 (0-3.8); 1 m 1.8 (0.5-4.1); 12 m 8.0 (0-25.8) but patients with PBH exhibit similar %TIR<3.9: 6.8 (3.5-11.9).

Conclusion: PBH patients exhibit exaggerated early glucose and insulin secretion to MMT. ‘Real-world’ CGM demonstrates that GV and time in hypoglycaemia is not significantly different between RYGB without PBH and patients with PBH. All patients post RYGB are at risk of hypos.

Disclosure

G. Tharakan: None. I.I. Ilesanmi: None. P. Behary: None. K. Alexiadou: None. C.S. Doyle: None. H. Chahal: None. S. Purkayastha: None. A. Miras: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi. A. Ahmed: None. S. Bloom: None. T.M. Tan: Other Relationship; Self; Novo Nordisk A/S.

Funding

Medical Research Council UK
392-P: Impact of Late Glucose Checks on Hypoglycemia Incidence
Authors: DUNLAP LAURA J. , WEBER ALANA D. , SCAPINELLO JESSIE , SCHRADER ANDERSON , BURGESS WILLIAM P.
Published: June 2019

Objective: Hypoglycemia (hypo) is frequently associated with blood glucose (BG) readings that are late. However, there are few reports describing the quantitative effect of untimely BG readings. This work focused on the quantitative evaluation of BG timing and hypo events related to insulin infusion therapy.

Methods: This study is a retrospective, quantitative analysis of incidence of hypo, defined as < 70 mg/dL, relative to the lateness of the BG determination. The dataset includes 3.55 million de-identified BG readings and recorded times from 5 unaffiliated systems using the same eGMS for intravenous insulin infusion therapy between 2007-2017. The timing of all BGs scheduled for every 1 and 2 hour were calculated from the dataset without any restrictions or exclusions. Incidence of hypo events occurring from BG readings 5 minutes (min) late or less was used as a baseline to measure the relative risk of later, low BGs in 10 min increments. The relative risk of late BGs was further stratified by hospital, year, and goal range.

Results: For all hospitals, goal ranges, and for each hospital database stratified by year, the relative risk of hypo appeared to have the same relationship as a function of minutes late. The results reveal that between 15-25 min late the risk of a hypo event was almost 2-fold and between 55-65 min late was 4-fold higher when compared to the baseline.

Discussion: The timing of the next BG has a profound effect on the incidence of hypo. The relationship of increased risk of hypo with lateness of BG readings remains irrespective of the goal range, year, hospital, or overall incidence of hypo in that hospital. All data within this study is from an eGMS with accurate time data. Future research efforts can compare different insulin dosing applications for the purpose of analyzing late BG checks and hypo.

Conclusion: Late BG readings contribute significantly to hypo. These observations should be an important mainstay of bedside care education. The findings also strongly endorse the use of alerts to maintain proper timing of BG readings

Disclosure

L.J. Dunlap: Employee; Self; Monarch Medical Technologies. A.D. Weber: Employee; Self; Monarch Medical Technologies. J. Scapinello: None. A. Schrader: Employee; Self; Monarch Medical Technologies. W.P. Burgess: Consultant; Self; Monarch Medical Technologies.
397-P: Relationship between HbA1c and Declines in Racial Differences of Serious Hypoglycemia in the Veteran Health Administration (VHA) 2004-2015
Authors: TSENG CHIN-LIN , SOROKA ORYSYA , MYERS CATHERINE E. , ARON DAVID C. , POGACH LEONARD M.
Published: June 2019

Annual rates of emergency department visits or hospitalizations for hypoglycemia (HYPO) were evaluated using a serial cross-sectional study design (2004-2015) of VHA/Medicare enrolled patients. Subjects were ≥65 years receiving secretagogues only (Secr), or insulin with or without Secr (Ins), and who had HbA1c value(s). Separately for Secr/Ins groups and by race/ethnicity, we assessed age/sex adjusted HYPO rates (per 1000 patients) and A1c values (from prior to an event or end of year for those without an event). In 2015, subjects were 99% men, 10% [B]lack, 6% [H]ispanic, and 75% [W]hite; 75% had major comorbidity categories; 24% had cardiovascular conditions only, and 9% advanced diabetes only. Ins use increased by 88%, similar among B/H/W. HYPO rates markedly declined for Ins and Secr in all races but remained higher for B. The percent of patients with A1c <7% decreased: 44.2%/32.9%[B], 51.0%/32.6%[W], and 41.3%/28.4%[H]; the percentage for A1c 7.0-7.9% increased: 28.6%/31.6%[B], 30.6%/35.8%[W], and 30.8%/32.4%[H]; the percentage for >9% also increased: 11.9%/15.8%% [B], 6.4/12.2%[W], and 12.0/17.6%[H]. Mean A1c values also increased in B/H/W, and were similar (difference ≤0.2%) between patients with and without HYPO. Guideline recommendations (post 2008) for individualized A1c goals may have mediated reductions in racial disparities for HYPO rates.

Disclosure

C. Tseng: None. O. Soroka: None. C.E. Myers: None. D.C. Aron: None. L.M. Pogach: None.

Funding

U.S. Department of Veterans Affairs (IIR14-082)
405-P: Transcription Factor Tcf21 Regulates Fibrosis in Ischemic or Hyperglycemic State
Authors: BABA YUSUKE , MAEZAWA YOSHIRO , KONDOU NAOMICHI , KOBAYASHI YOSHIO , YOKOTE KOUTARO
Published: June 2019

Cardiac fibrosis after ischemic heart diseases or in diabetic cardiomyopathy is critical for maintaining cardiac functions. Tcf21 is a bHLH transcription factor expressed in epicardium and cardiac fibroblasts. Tcf21 knockout mice die immediately after birth because of cardiac malformation. On the other hand, little is known about its function in the adult heart. Therefore, we aimed to elucidate the role of Tcf21 after cardiac injury. Tcf21 was deleted after birth using inducible Cre-LoxP system to circumvent the lethality (iTcf21 KO). Isoproterenol (ISO) was injected (200 mg/kg) at eight weeks of age. Mice were sacrificed seven days and four weeks after ISO injection, and histological analysis was performed. Besides, cardiac fibroblasts were isolated from Tcf21 knockout embryos and subjected to RNA-seq analysis. Fibroblasts proliferation capacity was also assessed by BrdU uptake. Finally, Tcf21 expression in hyperglycemic state induced by streptozocin (STZ) was evaluated. At day 7, 1.98 ± 0.40% of the total cardiac area showed fibrosis in control, however, the fibrosis area was smaller in iTcf21 KO mice (0.67 ± 0.14%, P < 0.001). Cardiac ultrasound revealed fractional shortening was maintained in iTcf21 KO mice compared to control. Immunostaining demonstrated Ki67-positive cells decreased in iTcf21 KO (57.1% compared to controls, P = 0.032). Isolated cardiac fibroblasts from Tcf21 KO showed lower BrdU uptake (76.0 ± 3.3% for controls and 47.8 ± 7.4% for Tcf21 KO, P = 0.002) and decreased phosphorylation of Erk. RNA-seq analysis revealed potential downstream targets for Tcf21 including Il33 and Col1a1. Gene Ontology analysis demonstrated involvements of Tcf21 in the extracellular matrix and angiogenesis. STZ-induced hyperglycemic state did not evoke significant fibrosis but upregulate Tcf21 expression compared with control. These findings suggest lack of Tcf21 suppresses fibrosis after cardiac injury. Tcf21 and its targets would be a potential novel therapeutic target for cardiac diseases.

Disclosure

Y. Baba: None. Y. Maezawa: None. N. Kondou: None. Y. Kobayashi: Speaker's Bureau; Self; Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited. K. Yokote: None.
418-P: The Branched-Chain Amino Acids Valine and Leucine Predict All-Cause Mortality in Cardiovascular Disease Patients Independently from the Presence of Type 2 Diabetes Mellitus
Authors: MUENDLEIN AXEL , LEIHERER ANDREAS , SAELY CHRISTOPH H. , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , FRAUNBERGER PETER , DREXEL HEINZ
Published: June 2019

Circulating branched-chain amino acids (BCAAs) are linked with mortality in population-based studies. Whether they also predict mortality in patients with established cardiovascular disease (CVD) is unclear. We therefore determined serum BCAAs by NMR spectroscopy in 327 patients with established CVD. Prospectively, deaths were recorded over a mean follow-up period of 8.1±3.5 years. At baseline, serum valine, leucine and isoleucine were significantly associated with T2DM (all p-values <0.001). Prospectively, death occurred in 49.5% of patients with T2DM and in 37.2% nondiabetic patients (p=0.036). Table 1 shows the associations of BCAAs with mortality univariately and after multivariate adjustment including presence of T2DM in the total study cohort as well as separately for patients with T2DM and for nondiabetic patients. Low valine as well as low leucine predicted mortality independently from the presence of T2DM in the total cohort and, in subgroup analysis, specifically in patients with T2DM. We conclude that low valine and leucine serum levels predict mortality in patients with established CVD independently from the presence of T2DM.

Disclosure

A. Muendlein: None. A. Leiherer: None. C.H. Saely: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. H. Drexel: None.
423-P: Racial and Ethnic Disparities in Mortality and Cardiovascular Disease in Patients with Type 2 Diabetes in a U.S. Integrated Health-Care System
Authors: AN JAEJIN , NICHOLS GREGORY A. , QIAN LEI , WEI RONG , HARRISON TERESA , MUNIS MERCEDES A. , LI ZHUOXIN , WEISS TRACEY , IGLAY KRISTY , RAJPATHAK SWAPNIL , REYNOLDS KRISTI
Published: June 2019

Previous research has documented higher mortality rates and risk of diabetes complications in ethnic minorities in the U.S. While genetic predisposition and lifestyle are potential important factors associated with this disparity, the role of access to care has not been well studied. We examined all-cause mortality and incidence of cardiovascular disease (CVD) by race/ethnicity in a type 2 diabetes (T2DM) population within in a large U.S. integrated healthcare system. We identified adult patients with incident T2DM between 1/1/2003-12/31/2014 using electronic health record (EHR) data and followed them through 6/30/2018. Patient demographics, CVD risk factors, medical history, and medication use were ascertained from the EHR. Age- and sex-adjusted all-cause mortality and incidence rates of myocardial infarction (MI) and heart failure (HF) were estimated by race/ethnicity. Hazard ratios were estimated using multivariable Cox proportional hazards models. We identified 135,199 patients with incident T2DM (mean±SD age: 58±13 years, 48% female, and median follow-up 6 years). 36% were white, 35% Hispanic, 12% Asian, and 12% black. All-cause mortality and incidence of MI and HF were highest among whites followed by blacks (Table). These findings suggest that improving access to quality care may help reduce racial/ethnic health disparities among patients with T2DM.

Disclosure

J. An: Research Support; Self; Merck & Co., Inc. G.A. Nichols: Research Support; Self; Amarin Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC., Merck Sharp & Dohme Corp. L. Qian: None. R. Wei: None. T. Harrison: None. M.A. Munis: None. Z. Li: None. T. Weiss: Employee; Self; Merck & Co., Inc. K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. S. Rajpathak: None. K. Reynolds: Research Support; Self; Amarin Corporation, Amgen Inc., Merck Sharp & Dohme Corp., Novartis AG.
428-P: Heart Failure (HF) and Its Risk Factors in Long-Duration Type 1 Diabetes (T1D)
Authors: GUO JINGCHUAN , COSTACOU TINA , ORCHARD TREVOR J.
Published: June 2019

To assess HF incidence in childhood onset, T1D, and its risk factors, we used 25 year follow-up data from the Epidemiology of Diabetes Complications Study (n=644, baseline age and T1D duration 27 and 19 years respectively). HF was determined by clinic exams, hospitalization, and/or self-reports. In a separate analysis, serum NT-proBNP (electrochemiluminescence immunoassay) was measured in the earliest available sample (n=572; HF diagnostic cutoff of 450 pg/mL). Hazard ratios (HR) per 1 s.d. increase in risk factor levels were estimated with Cox models.

Forty-one (6.3%) HF cases (3 baseline prevalent and 38 incident) were identified during follow-up. The 5.9% (38/642) cumulative incidence of HF yielded an incidence density of 2.97/1000 person-years. In the overall population (and not including NT-proBNP), allowing for a wide range of potential baseline confounders (sex, T1D duration, smoke, BMI, hypertension, HbA1c, lipids, WBC, eGFR and albumin excretion), T1D duration (HR=1.7, p=0.003), ever smoking (HR=2.4, p=0.02) and non-HDLc (HR=1.4, p=0.04) were strongly associated with incident HF after backward elimination.

In the sub analysis of 572 participants with NT-proBNP, 21 had values >450 pg/mL, 85.6% (18) of whom had end stage renal disease (ESRD) including 3 with concurrent HF. In those without ESRD at the time of NT-proBNP testing (n=551), NT-proBNP significantly predicted incident HF (32 clinically defined events, HR=1.7, p=0.03). Although in a backward elimination model (removal criterion: p≥ 0.2), allowing for other risk factors, NT-proBNP (HR=1.5, p=0.09) became marginal, it was retained in this final model along with T1D duration (HR=1.8, p=0.003), ever smoking (HR=2.6, p=0.01) and non-HDLc (HR=1.4, p=0.05).

HF incidence in this long-duration T1D cohort is increased compared to the general population with similar age (e.g., incidence=0.97/1000 pyrs). Diabetes duration, smoking and non-HDLc are strong risk factors of HF; while in those without ESRD, NT-proBNP is a moderate predictor.

Disclosure

J. Guo: None. T. Costacou: None. T.J. Orchard: Consultant; Self; Boehringer Ingelheim International GmbH.

Funding

National Institutes of Health
433-P: Serum Ceramides and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events in Patients with Peripheral Artery Disease
Authors: LEIHERER ANDREAS , MUENDLEIN AXEL , SAELY CHRISTOPH H. , LAAKSONEN REJO , LAAPERI MITJA , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , FRAUNBERGER PETER , BAUMGARTNER IRIS , DREXEL HEINZ , DOPHEIDE JÖRN F.
Published: June 2019

Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently emerged as predictors of cardiovascular outcomes in coronary artery disease patients. However, their power to predict cardiovascular events in patients with peripheral artery disease (PAD) is unknown and is addressed in the present study. We measured the serum concentrations of the above mentioned ceramides in a cohort of 380 patients with sonographically proven PAD, of whom 107 had type 2 diabetes (T2DM). Prospectively, we recorded 221 cardiovascular events over a mean follow-up time of 6.3±2.3 years. Cardiovascular event risk was higher in T2DM patients than in those who did not have diabetes (69 vs. 52%, p=0.001). The ceramides Cer(18:1/16:0) and Cer(18:1/24:1) and the respective ratios Cer(18:1/16:0)/Cer(18:1/24:0) and Cer(18:1/24:1)/Cer(18:1/24:0) were significant predictors of cardiovascular events both univariately and after multivariate adjustment including the presence of T2DM (Figure). Conversely, T2DM predicted cardiovascular events independently from the investigated ceramides (adjusted HR 1.76 [1.31-2.35], p<0.001). We conclude that the investigated ceramides and T2DM are mutually independent predictors of cardiovascular events in PAD patients.

Disclosure

A. Leiherer: None. A. Muendlein: None. C.H. Saely: None. R. Laaksonen: None. M. Laaperi: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. I. Baumgartner: None. H. Drexel: None. J.F. Dopheide: None.
434-P: Diabetes in Patients with Pancreatic Cancer: Relationship of Tumor Grade with Glycemic Control
Authors: BOEDDEKER JAN STEFFEN , BURKART VOLKER , STRASSBURGER KLAUS , GORETZKI PETER E. , KNOEFEL WOLFRAM TRUDO , MOEBIUS CHRISTIAN , HINSCH NORA , ESPOSITO IRENE , RODEN MICHAEL , MUESSIG KARSTEN
Published: June 2019

Diseases of the exocrine pancreas can result in impaired function of the endocrine pancreas with disturbed glucose homeostasis and ultimately overt diabetes mellitus. In diabetes which develops secondary to pancreatic carcinoma (type 3c diabetes or diabetes of the exocrine pancreas, DEP), the relationship between disturbed glycemic control and carcinoma is not fully understood. We hypothesized that the severity of pancreatic carcinoma positively associates with the degree of impairment of glycemic control. In 92 patients with potentially resectable pancreas neoplasm without diabetes (NOD, n=53, age 67±2 years, BMI 24.8±0.5 kg/m2), DEP (n=20, 71±3 years, 25.3±1.0 kg/m2) or preexisting type 2 diabetes (T2D, n=19, 71±3 years, 27.1±0.8 kg/m2), preoperative fasting glucose, insulin and HbA1c were measured. Pancreatic carcinoma was assessed by TNM classification and tumor grading. Patients with DEP or T2D had higher fasting glycemia (135±9 vs. 142±11 mg/dl), HbA1c (55±3 vs. 58±3 mmol/mol) and insulin resistance, as assessed by homeostatic model assessment for insulin resistance (HOMA-IR) (4.1±1.0 vs. 3.7±0.5), than NOD patients (88±2 mg/dl, 38±1 mmol/mol, 2.0 ± 0.3; all p<0.01). Tumor grading revealed that patients with tumor grade G3 had higher levels of fasting glucose (124±36 mg/dl) and HbA1c (53±2 mmol/mol) compared to patients with non-malignant neoplastic lesions (103±38 mg/dl, 42±2 mmol/mol; all p<0.01). Distribution patterns of tumor grades differed between DEP and T2D (p<0.05) and NOD (p<0.001), respectively. Particularly, the prevalence of G3 tumors was higher in DEP (79%) than in T2D (33%) or NOD patients (16%). Tumor stages did not relate to glycemic control.

In conclusion, patients with pancreas carcinoma exhibit a higher diabetes prevalence, which relates to higher tumor grades but not stages.

Disclosure

J. Boeddeker: None. V. Burkart: None. K. Strassburger: None. P.E. Goretzki: None. W. Knoefel: None. C. Moebius: None. N. Hinsch: None. I. Esposito: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. K. Muessig: None.

Funding

German Ministry of Culture and Science of the State of North Rhine-Westphalia; German Federal Ministry of Health; German Federal Ministry of Education and Research; German Center for Diabetes Research
436-P: Comparison of the ASCVD and UK Prospective Diabetes Study Risk Engine with Carotid Intima Media Thickness and Brachial-Ankle Pulse Wave Velocity
Authors: HONG SANG MO , CHOI YUN MI , HONG EUN-GYOUNG
Published: June 2019

Object: We explored and compare the efficacy of ACC-AHA-atherosclerotic cardiovascular disease (ASCVD) risk score and UK Prospective Diabetes Study (UKPDS) risk engine with the presence of subclinical carotid and peripheral atherosclerosis in patients with type 2 diabetes(T2DM) patients.

Methods: We studied 746 T2DM patients aged 20 years and older, who visited Hallym University Dongtan Sacred Heart Hospital from Noember 2012 to June 2014. Carotid atherosclerosis was defined as carotid intima-media thickness (IMT) > 1mm or the presence of carotid artery plaque. Peripheral atherosclerosis was defined as over than 1750 cm/s of brachial-ankle pulse wave velocity (baPWV). Ten-year coronary heart disease (CHD) risk was determined using the ASCVD and UKPDS risk engine.

Results: The mean 10-year CHD risks of UKPDS and ASCVD were 13.9±13.0% and 12.7±13.3%, respectively. The prevalence of carotid atherosclerosis and peripheral atherosclerosis were 13.3% and 22.9%. The risk for carotid atherosclerosis and peripheral atherosclerosis increased 6.12 (95% CI 3.3-11.4) times and 10.0 (95% CI 5.9-17.1) times in high risk group (≥20% 10-year UKPDS risk) than low-risk group, respectively. The risk for carotid atherosclerosis and peripheral atherosclerosis increased 7.891 (95% CI 4.4-14.0) times and 15.6 (95% CI 9.2-26.2) times in high risk group (≥20% 10-year ASCVD-predicted coronary heart disease risk) than low-risk group, respectively. In multiple regression analysis with ASCVD and UKPDS risk for carotid atherosclerosis and peripheral atherosclerosis, only ASCVD risk were statically significant (all p<0.001).

Conclusion: Carotid atherosclerosis and peripheral atherosclerosis were prevalent in patients with T2DM and positively correlate d with 10-year CHD risk. In comparison of ASCVD and UKPDS risk engine, ASCVD risk engine was more proper in patients with T2DM.

Disclosure

S. Hong: None. Y. Choi: None. E. Hong: None.
441-P: Chitotriosidase Activity Is Inversely Associated with Diastolic Blood Pressure and HbA1c but Not with Arterial Stiffness in Patients with Type 2 Diabetes without Complications
Authors: D'ONOFRIO LUCA , LUORDI CECILIA , MIGNOGNA CARMEN , CARLONE ANGELA , MORETTI CHIARA , TARTAGLIONE LIDA , MADDALONI ERNESTO , LETO GAETANO , MAZZAFERRO SANDRO , BUZZETTI RAFFAELLA
Published: June 2019

Background and Aim: Chitotriosidase (Chit), a mammalian chitinases secreted by monocytes and epithelial cells, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. Aim of the study was to evaluate Chit activity as a precocious biomarker of arterial stiffness in T2D patients without overt vascular complications.

Methods: Arterial stiffness was measured by Cardio-Ankle Vascular Index (CAVI) in 174 T2D patients (mean±SD age=55±4 years, 103 men) without established diabetic complications. For this cross-sectional study, we measured Chit activity by electrochemiluminescent assay in the sera from the 41 patients with the lowest (L_CAVI) and the 42 patients with the highest (H_CAVI) CAVI values.

Results: Compared with L_CAVI, H_CAVI patients were older (57±4years vs. 52±4years, p<0.01), had longer T2D duration (6±3years vs. 4±3years, p=0.02), higher diastolic blood pressure (DBP) (90±9 vs. 86±9mmHg, p=0.03), HbA1c (6,5±0,9% vs. 6,01±0,6%, p<0.01) and fasting blood glucose (130±29 vs. 117±27 mg/dL, p=0,024) values, lower BMI (28,5±4,2 vs. 32,3±7,2 kg/m2, p=0.01) and glomerular filtration rate (91,3±11,2 vs. 96,1±10,0mL/min/1.73m2, p=0.04). Chit activity was similar in L_CAVI and H_CAVI groups (11,6±5,6 vs. 14,0±8,3 nmol/mL/h respectively). Although, Chit was inversely related to DBP (r=-0.22; p <0.041) and HbA1c (r=-0.21; p=0.048) and directly related to albuminuria (r=0.22; p=0.04). No significant differences were found in systolic blood pressure, gender, lipid profile, calcium, urate, inflammatory markers between the two groups.

Conclusion: Arterial stiffness raises with age, metabolic control, DBP and impaired kidney function. Chit is also associated with DBP, metabolic control and kidney damage but did not result as a direct marker of arterial stiffness in T2D patients without established complications.

Disclosure

L. D'Onofrio: None. C. Luordi: None. C. Mignogna: None. A. Carlone: None. C. Moretti: None. L. Tartaglione: None. E. Maddaloni: Speaker's Bureau; Self; Merck & Co., Inc., Pikdare. G. Leto: None. S. Mazzaferro: None. R. Buzzetti: None.

Funding

Sapienza University of Rome (“Avvio alla ricerca 2016”)
443-P: Reduced Cardiorenal Function and In-Hospital Mortality in Patients with Type 2 Diabetes Mellitus and ST-Segment Elevation Myocardial Infarction
Authors: GENOVESE STEFANO , COSENTINO NICOLA , CAMPODONICO JENESS , DE METRIO MONICA , MOLTRASIO MARCO , RONDINELLI MAURIZIO , DE FERRARI GAETANO , MARENZI GIANCARLO
Published: June 2019

Background: ST-segment elevation myocardial infarction (STEMI) patients with diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients.

Methods: We included 5,152 STEMI patients treated with primary angioplasty. Left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were evaluated at hospital admission. The primary endpoint was in-hospital mortality. A composite of in-hospital mortality, cardiogenic shock, and acute kidney injury was the secondary endpoint.

Results: Eight-hundred-seventy-nine (17%) patients had DM. The incidence of LVEF≤40% (30% vs. 22%; P<0.001), eGFR≥60 ml/min/1.73m2 (27% vs. 18%; P<0.001), or both (12% vs. 6%; P<0.001) was higher in patients with DM. In-hospital mortality was higher in DM than in non-DM patients (6.1% vs. 3.5%; P=0.002) with an unadjusted OR of 1.81 (95% confidence interval [CI] 1.31-2.50; P=0.003). However, DM was no longer associated with an increased mortality risk after adjustment for cardiac and renal function (OR 1.03, 95% CI 0.68-1.56; P=0.89). A similar behavior was observed for the secondary endpoint, with an unadjusted OR for DM of 1.52 (95% CI 1.25-1.85; P<0.001) and an OR after adjustment for cardiac and renal function of 1.07 (95% CI 0.85-1.36; P=0.53).

Conclusion: The study indicates that the increased in-hospital mortality and morbidity of DM patients with STEMI is driven by the underlying cardio-renal dysfunction, rather than to the mere presence of DM.

Disclosure

S. Genovese: Advisory Panel; Self; Novartis Pharmaceuticals Corporation, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Hikma Pharmaceuticals. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Takeda Pharmaceutical Company Limited. N. Cosentino: None. J. Campodonico: None. M. De Metrio: None. M. Moltrasio: None. M. Rondinelli: Consultant; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Takeda Pharmaceutical Company Limited. G. De Ferrari: None. G. Marenzi: Speaker's Bureau; Self; Merck Sharp & Dohme Corp.

Funding

Centro Cardiologico Monzino