bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Related to the High Prevalence of Diabetic Kidney Disease in Ecuador-Update for Health Policy Makers
Authors: GUADALUPE MARIANA E. , ALVAREZ CONDO GRACIELA B. , VERA LORENTI FANNY E. , PAZMIÑO GOMEZ BETTY J. , RODAS NEIRA EDGAR I. , VERON DOLORES , CERCADO ALICIA G. , VILLEGAS GUILLERMO A. , TUFRO ALDA , VERON DELMA
Published: June 2018

Type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) are prevalent diseases in South America. Identification of factors associated to DKD is key to design appropriate regional health policies. We characterized DKD in 1663 adults (99% Confidence level, 1.4% margin of error) recruited from the general population of the Ecuadorian coast between 2014 and 2017 (46±14 years of age, 64% of them were women). Framed in our prospective, observational and cross-sectional study (NCT02237352) we evaluated demographic data, personal and family history, BMI, blood pressure (BP), plasma glucose (PG), HbA1c, creatinine (cr) and microalbuminuria (μAlb). T2DM was defined as peoples with clinical diagnosis of T2DM, being on insulin or oral hypoglycemic treatment, fasting PG ≥126 mg/dl, random glucose ≥200 mg/dl and HbA1c ≥6.5%. Subjects were deemed to have DKD when they presented μAlb ≥30 mg/gr-cr and/or estimated glomerular filtration rate ˂60 ml/min/1.73m2.

Results: Our study shows that the prevalence of DKD in the Ecuadorian coast was 9.3% (95% CI, 8%-11%) with 19.5% of the persons not knowing their T2DM status. The factors significantly different comparing DKD vs. non-DKD subjects (P<0.05) were: Female 71.4% (CI 95%, 64% -78%) vs. 57.4% (95% CI, 61%-66%); age 58±9 vs. 45±14 years; BMI 29.5±4.9 vs. 27.7±5.3 Kg/m2; systolic BP 133.5±20.9 vs. 119.4±16.8 mmHg; diastolic BP 82.9±13.4 vs. 75.4±12 mmHg; PG 197.3±103.6 vs. 98.4±41.5 mg/dl; HbA1c 8.8±2.6 vs. 5.7±1.3%; personal history of gestational diabetes (GD) 7.3% (95% CI, 3%-14%) vs. 2.4% (95% CI, 2%-4%) and overweight newborn children (ONBC) 30.9% (95% CI, 23%-41%) vs. 14.7% (95% CI, 13%- 17%).

Conclusion: Female gender, age, BMI, BP, PG, HbA1c, history of ONBC and GD all are factors linked to DKD in the Ecuadorian coast that should be considered to design meaningful health policies, to address the currently high prevalence of DKD. The amount of people unknowing their diagnosis of T2DM among folks with DKD suggests emphasizing the screening of T2DM.

Disclosure

M.E. Guadalupe: None. G.B. Alvarez Condo: None. F.E. Vera Lorenti: None. B.J. Pazmiño Gomez: None. E.I. Rodas Neira: None. D. Veron: None. A.G. Cercado: None. G.A. Villegas: None. A. Tufro: None. D. Veron: None.
Levels of Connective Tissue Growth Factor (CTGF) Predict Development of Kidney Dysfunction in Type 2 Diabetes-The VADT Study
Authors: HUNT KELLY J. , JAFFA MIRAN A. , GARRETT SARA M. , LUTTRELL DEIRDRE K. , LIPSON KENNETH E. , LOPES-VIRELLA MARIA F. , LUTTRELL LOUIS M. , JAFFA AYAD A. ,   VADT INVESTIGATORS
Published: June 2018

Connective tissue growth factor (CTGF) is a member of the CCN family of matricellular proteins that has been implicated in the inflammatory process, response to injury and wound healing. An emerging role of CTGF is that of a profibrotic factor implicated in the development of kidney disease. Our objective was to determine the role of CTGF as a predictor of macroalbuminuria (ACR ≥300µg/mg twice) and chronic kidney disease (CKD) stage 3 (GFR <60ml/min twice) and stage 4 (GFR <30ml/min once or twice) in the VADT cohort. Levels of CTGF were measured in 952 VADT patients, a median of 1.9 years after entry into the study. Participants were followed for a median of 3.8 years for renal outcomes. CTGF categories were defined as below the detectable limit (i.e., referent, 54.5%), lower half of detectable values (i.e., 22.8%) and upper half of detectable values (22.7%). Odds ratios (ORs) for kidney endpoints in relation to CTGF categories were calculated by logistic regression. Even with adjustment for baseline ACR levels, individuals in the highest compared to lowest CTGF category were at higher risk of macroalbuminuria [OR=3.21 (95% CI: 1.37, 7.53)]. In contrast, CTGF was predictive of incident stage 3 and stage 4 CKD only when baseline GFR levels were not adjusted for. Our study indicates that high levels of CTGF are associated with and predict future kidney dysfunction in patients with type 2 diabetes.

Disclosure

K.J. Hunt: None. M.A. Jaffa: None. S.M. Garrett: None. D.K. Luttrell: None. K.E. Lipson: Employee; Self; FibroGen, Inc.. Stock/Shareholder; Self; AbbVie Inc., Abbott, Becton, Dickinson and Company, Bristol-Myers Squibb Company, General Electric, Gilead Sciences, Inc., Medtronic, Nestlé, Novartis AG, Oracle, Pfizer Inc., Quest Diagnostics. Consultant; Spouse/Partner; Diabesen. M.F. Lopes-Virella: None. L.M. Luttrell: None. A.A. Jaffa: None.
The Risk Factors for Rapid Decline of Renal Function in Japanese Patients with Diabetes Mellitus
Authors: MATSUHISA MUNEHIDE , MORI HIROYASU , OHISHI MAMI , ISHIZU MASASHI , SUZUKI REIKO , TAKIKAWA INEKO , TANIGUCHI SATOSHI , TAMAKI MOTOYUKI , AKEHI YUKO , KURAHASHI KIYOE , YOSHIDA SUMIKO , ENDO ITSURO , AIHARA KEN-ICHI , FUNAKI MAKOTO , KURODA AKIO
Published: June 2018

Background: To prevent the end-stage renal failure, it is important to identify the high-risk patients with rapid decline of renal function (RDRF).

Aim: We intended to clarify the risk factors for RDRF in Japanese patients with diabetes.

Methods: One hundred sixteen out-patients with diabetes (type 1/2, 38/78; M/F, 60/56; age 60.1±12.3 years; BMI, 25.3±4.8; HbA1c, 7.3±1.0%; eGFR, 68±22mL/min/1.73m2) were enrolled in this study, and were followed for one year. We defined RDRF as more than 20% of annual decline of eGFR. The sodium intake was estimated from the urine sodium excretion from early morning urine specimen according to previous report (J Hum Hypertens. 2002). The visceral fat area (VFA) was determined by the impedance method (HDS-2000, Omron Healthcare, Japan)

Results: 8.6% of participants were matched to the criteria of RDRF. In subjects with RDRF, the energy intake (45.6±10.6 kcal/kg BW/day), sodium intake (12.5±1.8 g/day), VFA (157±51 cm2) and prevalence of hypertension (100%) were higher than those without RDRF. Annual decline of eGFR was significantly correlated with the stage of diabetic nephropathy, VFA, systolic and diastolic blood pressure, urinary albumin excretion rate, triglyceride, and daily intake of energy, sodium and protein (p<0.05). The logistic regression analysis revealed that the independent determinants of RDRF were energy intake, sodium intake, and visceral fat area. In addition, the Receiver Operating Characteristic (ROC) analysis revealed that the cut-off values of these parameters were 46.8kcal/ kg BW/ day of energy intake (AUC 0.84, p<0.01), 11.8g/day of sodium intake (AUC 0.90, p<0.01), and 117cm2 of visceral fat area (AUC 0.88, p<0.01).

Conclusion: Visceral obesity, and high intake of energy and sodium contributed to rapid decline of renal function in Japanese patients with diabetes. Body weight management with adequate energy and sodium intake, therefore, may contribute to prevent progression of diabetic kidney disease.

Disclosure

M. Matsuhisa: None. H. Mori: None. M. Ohishi: None. M. Ishizu: None. R. Suzuki: None. I. Takikawa: None. S. Taniguchi: None. M. Tamaki: None. Y. Akehi: None. K. Kurahashi: None. S. Yoshida: None. I. Endo: None. K. Aihara: None. M. Funaki: Research Support; Self; Otsuka Holdings Co., Ltd., The Knowledge Cluster from the Ministry of Education, Science, and Culture of Japan. Board Member; Self; Mechanogenic C.C.. A. Kuroda: None.
Structure Equation Modeling Analysis of Risk Factors and the Pathway Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes
Authors: LEE TAO-CHUN , CHUNG FU-MEI
Published: June 2018

Background: Diabetes mellitus is the most common cause of chronic kidney disease (CKD), however, the inter-relationships and pathogenetic mechanisms among risk factors are still largely unknown.Structural equation models (SEMs)was applied to test a hypothesis model of causal pathways related to CKD in patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 3,395 subjects with T2DM were enrolled in this study. A hypothesized SEM was applied to assess associations between demographic data, diabetic self-management behaviors, diabetes control,life style, psycho-social, chronic inflammation factors, anthropometric, and metabolic variables simultaneously and the risk of CKD.

Results: Seven baseline factors including demographic data (-0.075), white blood cell count (0.084), high blood pressure (0.144), WHO 5 well-being index (-0.082), diabetes control (0.099), triglyceride(0.091) and uric acid (0.282) levels had direct effects on the risk of CKD. The final model could explain 26%of the variability in baseline CKD status. The pathway associated with CKD was further confirmed by SEM analysis showing that the same direct and specific indirect factors as in baseline CKD status analysis contributed to the risk of CKD at 12 months of follow-up. The final model could explain 31%of the variability in the risk of CKD at 12 months of follow-up.

Conclusions: This study is the first to investigate associations between factors obtained from real world daily practice and CKD status simultaneously, and delineate the pathway and inter-relationships of the risk factors contributing to the pathogenesis of CKD in patients with T2DM.

Disclosure

T. Lee: None. F. Chung: None.
Clinical Characteristics and Outcomes in Patients Admitted with Diabetic Ketoacidosis (DKA) and End-Stage Renal Disease (ESRD)
Authors: GALINDO RODOLFO J. , PASQUEL FRANCISCO J. , TSEGKA KATERINA G. , CARDONA SAUMETH , DHRUV NEIL , VELLANKI PRIYATHAMA , FAYFMAN MAYA , HAW J. SONYA , MIGDAL ALEXANDRA , NAIR SHAILESH , WANG HEQIONG , UMPIERREZ GUILLERMO E.
Published: June 2018

Management of patients with diabetic ketoacidosis (DKA) and end stage renal disease (ESRD) is challenging. We used data (ICD-9/10 codes and clinical) from the Emory Clinical Data Warehouse from 1/1/2006-12/31/2016 to determine the clinical presentation and outcomes of patients with DKA. DKA was confirmed with admission bicarbonate <18 mEq/L, beta-hydroxybutyrate >3 mmol/L, and pH < 7.3, during the first encounter. ESRD was defined as glomerular filtration rate <15 mL/min/1.73 m2. Among 681 patients admitted with DKA (45±18 years, 51% female); there were 65 (9.5%) and 616 (90.5%) patients with and without ESRD, respectively. On admission, patients with ESRD were older, more likely to be female, and had admission blood glucose, potassium and osmolality higher than patients without ESRD, Table. Patients with ESRD had longer length-of-stay (LOS); however, there were no differences in admission anion gap, pH, time-to-correction of hyperglycemia, hypoglycemia and hypokalemia rates, or hospital mortality between groups. About one in every ten patients admitted with DKA has ESRD. Patients with DKA and ESRD were older, presented with more severe hyperglycemia and had longer LOS; however, response to therapy and mortality was similar to patients without ESRD.DKA with ESRD n: 65 (9.5%)DKA without ESRD n: 616 (90.5%)p-valueAge, years57.4 ± 15.243.7 ± 17.40.001Female, n (%)41 (63)3(50)0.04BMI, mean (kg/m2)29.6± 9.227.2 ± 7.50.033HbA1c, %9.9 ± 2.611.7 ± 2.80.003BG, mg/dl753.6 ± 441585 ± 2500.003Anion Gap, mEq/L22.9 ± 722.8 ± 60.95Bicarbonate, mmol/L12.0 ± 411.5 ± 3.90.26Effective Osm, mOsm/kg303.9 ± 23296.7 ± 170.02Sodium, mmol/L131.0 ± 7132.1 ± 60.12Beta-hydroxybutyrate, mmol/L5.0 ± 3.16.3 ± 2.50.02Admission potassium, mEq/L5.7 ± 1.45.1 ± 1.1<0.001Time to BG < 250 mg/dl, minutes372.1 ± 279415 ± 2260.79Hospital mortality, n (%)2 (3)11 (2)0.36LOS, median days (Q1, Q3)8 (5, 16)3 (2, 5)<0.001Hypoglycemia <70 mg/dl, n (%)10 (15)77 (13)0.56Hypokalemia < 3.0 mEq/L, n (%)16 (25)126 (20)0.43

Disclosure

R.J. Galindo: None. F.J. Pasquel: Consultant; Self; Merck Sharp & Dohme Corp., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc.. K.G. Tsegka: None. S. Cardona: None. N. Dhruv: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. M. Fayfman: None. J. Haw: None. A. Migdal: None. S. Nair: None. H. Wang: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..
A Magnetic Resonance Imaging Volumetry Study of Regional Brain Atrophy in Diabetic Peripheral Neuropathy
Authors: SELVARAJAH DINESH , HEIBERG-GIBBONS FRANCESCA , WILKINSON IAIN D. , GANDHI RAJIV , TESFAYE SOLOMON
Published: June 2018

Aims: Diabetic neuropathy (DN) is a serious complication which was hitherto considered a disease of the peripheral nervous system. In this study we sought to investigate in detail changes in brain morphometry in DN. The aim of this study was to identify regional brain volume changes that were specific to DN (painful and painless DN)

Methods: 102 patients with diabetes (34 No-DN, 34 Painless DN and 34 Painful DN) and 34 healthy volunteers underwent detailed clinical and neurophysiological assessments. All subjects underwent 3-dimensional T1-weighted brain MRI (3.0T, Philips). Brain volume analysis was performed using SIENAX (www.fmrib.ox.ac.uk/fsl) and Freesurfer (http://surfer.nmr.mgh.harvard.edu/).

Results: Groups were matched for age and gender. Total brain volume was significantly lower painful DN [1401.7 (10.7)ml] and painless DN [1393.5 (69.6)ml]) compared to HV [1457.2(79.2)ml] and No DN [1437.2(60.9)ml]; ANOVA p=<0.01). Total grey matter volume was significantly lower in painful DN [713.9(67.1)ml] and painless DN [717.2(42.4)ml] compared to controls (HV [758.4(46.5)]; p=<0.01; No DN [747.3(41.1)]; p=0.015). There were no significant differences in white matter (ANOVA p=0.18) and CSF (ANOVA p=0.23) volumes. Painful DN subjects had significantly lower cortical thickness in the right postcentral gyrus [1.83(0.14)mm vs. HV 1.91(0.13)mm]; (p=0.02); left precentral gyrus [2.31(0.16)mm vs. HV [2.39(0.12)mm]; (p=0.02) and no DN [2.38(0.14)mm]; (p=0.04); and left insula [2.81(0.15)mm] vs. HV [2.97(0.14)mm] p=<0.01).

Conclusion: This is the largest cohort study of brain volume changes in subjects with DN examined to date. We have demonstrated significant reduction in grey matter volume in painful and painless DN subjects. In painful DN this is localised within the somatomotor cortex and insula. These findings highlight significant CNS involvement in DN that provides clues to the pathogenesis of this condition.

Disclosure

D. Selvarajah: None. F. Heiberg-Gibbons: None. I.D. Wilkinson: None. R. Gandhi: None. S. Tesfaye: Speaker's Bureau; Self; Pfizer Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Wörwag Pharma GmbH & Co. KG.
Impaired Hemodynamic Response to Thermal Pain in Painful Diabetic Neuropathy
Authors: GREIG MARNI , WILKINSON IAIN D. , SELVARAJAH DINESH , SHILLO PALLAI RAPPAI , GANDHI RAJIV , TESFAYE SOLOMON
Published: June 2018

Objective: Painful diabetic peripheral neuropathy (painful-DPN) causes distressing neuropathic pain that is only partially responsive to treatment. A better understanding of CNS correlates of painful-DPN is vital to develop more effective therapeutics. The aim of this study was to measure cerebral perfusion of the pain processing areas of the brain using MR-Dynamic Susceptibility Contrast (MR-DSC) imaging at rest and under experimental pain condition.

Methods: 55 T1DM subjects (20 painful-DPN, 23 painless-DPN, 13 no-DPN) and 19 Healthy Volunteers (HV); underwent detailed clinical and neurophysiological assessment (NISLL+7 tests of nerve function; DN4 questionnaire). MR images were obtained at 3T using a MR-DSC, T2*-weighted technique (TR/TE=1250/35ms; 72 dynamics) to assess the passage of a bolus of intravenous gadolinium-chelate through cerebral vascular bed. Subjects were scanned at baseline and during 90s of heat-pain applied to the right lateral thigh (non-neuropathic area). The time-to-peak (TTP) concentration of gadolinium in regions of interest (ROI): right and left thalamus, right and left sensory cortices (RSC and LSC), was measured.

Results: At baseline, although the mean TTP (s) in the ROIs was shorter in the painful-DPN group [e.g., RT: M (SD): 9.22 (1.13) vs. HV 9.83 (0.99), no-DPN 9.59 (0.90), painless-DPN 9.94 (0.97)] this was not statistically significant (p=0.058). However the ΔTTP in response to thermal pain was significantly different between the groups LT (p=0.021), RT (p=0.003), LSC (p=0.009), RSC (p=0.008). Whilst HV respond to thermal pain by shortening the TTP in ROI the painful-DPN group do the reverse (p<0.05).

Conclusion: Subjects with painful-DPN have a paradoxical increase in TTP, indicating that chronic neuropathic pain state may result in a failure to mount a hemodynamic response to external pain and descending inhibition. This novel finding may serve as an objective marker of painful-DPN, and in the future may facilitate the development of novel treatments.

Disclosure

M. Greig: None. I.D. Wilkinson: None. D. Selvarajah: None. P. Shillo: None. R. Gandhi: None. S. Tesfaye: Speaker's Bureau; Self; Pfizer Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Wörwag Pharma GmbH & Co. KG.
Suppression of Neuropathy Development in Diabetic Rage-Deficient Mice Is Associated with Absence of M1/M2 Macrophage Skewing in the Sciatic Nerve
Authors: OSONOI SHO , MIZUKAMI HIROKI , OGASAWARA SAORI , TAKAHASHI KAZUHISA , SANGO KAZUNORI , YAGIHASHI SOROKU
Published: June 2018

Infiltrating macrophage (Mφ) into sciatic nerve (SN) is assumed one of the pathogenesis of diabetic polyneuropathy (DPN). In particular, skewing infiltrating Mφ toward pro-inflammatory (M1) Mφ, but not anti-inflammatory (M2) Mφ, possibly contributes to dysfunction of SN in diabetic state. However, the impacts of Mφ into dorsal root ganglia (DRG) in DPN are not yet well explored. For this purpose, male C57BL/6 mice (W) and receptor for AGEs (RAGE) null mice (R) were recruited and rendered diabetic (D) with STZ injection. After 8 weeks, nerve conduction velocity (NCV) and tail flick test were performed. Subsequently, mice were sacrificed to dissect SN and DRG, which were evaluated in the pathology and mRNA expression by qPCR. WD showed significant delay of NCV and increase in threshold for thermal sensation (p<0.01), while those were maintained in RD. Pathological analysis elucidated decrease in the average size of cell bodies in the DRG neuron of WD compared to W (p<0.01), as well as the expression of CGRP in DRG neurons (p<0.01). RD maintained neuronal cell size and CGRP expression. Significant increase in infiltration of Iba-I positive Mφ emerged in SN of WD compared to W (p<0.05). The increase was more robust, composed mostly of M2 in RD than WD (p<0.01). No increase of Mφ infiltration was identified in DRG of diabetic groups. The expression of iNOS (a marker for M1) was increased in SN of WD compared to W (p < 0.01), but not in that of RD. The expression of Arg1 (a marker for M2) was significantly increased in SN of RD compared to WD (p < 0.01). However, no changes of iNOS and Arg1 expression were detected in DRG. Our results suggest that proinflammatory changes in distal nerve elicits systematic sensory neuropathy in diabetes and correction of M1φ/M2φ imbalance may be beneficial for its prevention.

Disclosure

S. Osonoi: None. H. Mizukami: Research Support; Self; Sanwa Kagaku Kenkyusho Co., Ltd., Mitsubishi Tanabe Pharma Corporation. S. Ogasawara: None. K. Takahashi: None. K. Sango: None. S. Yagihashi: None.
Clinical Application of Photoacoustic Imaging to the Evaluation of Diabetic Polyneuropathy
Authors: YAGIHASHI SOROKU
Published: June 2018

Objective evaluation of peripheral nerve function and pathology is essential for the early diagnosis and determination of clinical staging of diabetic polyneuropathy (DPN). To this end, we attempted to apply the photoacoustic imaging (PAI) to clinical diagnosis of DPN and characterization of background pathology. PAI is the imaging system for the dual ultrasound detection of the specific tissues or organs and released signals from the same tissues irradiated with laser light with specific wave length. For the application of PAI to DPN, we selected the median (MN) and sural nerves (SN) for the evaluation and applied laser light to these nerves for the detection of signals from hemoglobin. With this method, PAI enables depiction of nerve bundle cross sectional area (NA), and hemoglobin distribution, thereby blood volume (BV), vascular area (VA) or caliber at the arteriolar/venular levels. In this study, 12 healthy control subjects (C) and 54 diabetic patients (DM) with (n=30) or without DPN (n=24) were subjected to PAI examination. DPN was confirmed by Japanese study group criteria. Correlation analysis was also conducted between PAI data and clinical staging of DPN. We found significant increases of NA 14% in MN and 18% in SN in DM compared to C, and trends of increases in NA toward advanced DPN. There was also a trend of increase in VA in DM with advanced DPN although there was no significant difference between C and DM. Compared to C, BV in SN was increased 12% in DM, but it was decreased in DM with DPN compared to those without DPN. These findings indicated that expanded nerve bundle area with decreased BV was characteristic in DPN. Our results suggest that endoneurial edema of nerve bundles, epi- and perineurial fibrosis and congestion with endoneurial ischemia may contribute to the development of DPN. We consider that PAI is a new and valuable method for the clinical application to DPN.

Disclosure

S. Yagihashi: None.
hBMSC-TERT in Cutaneous Diabetic Wound—Histological Analysis and Metalloproteinases
Authors: LEAL ÂNGELA M.
Published: June 2018

Diabetes (DM) is associated with micro- and macrovascular complications and impaired wound healing which leads to the formation of chronic lesions. Mesenchymal stem cells exert anti-inflammatory and secretory actions and their use in chronic lesions has obtained a high success rate, improving the healing process. In the present study, we have evaluated the effects of the use of a lineage of human mesenchymal cells obtained from bone marrow cells and immortalized by the enzyme telomerase (hBMSC-TERT), in wound healing in diabetics and their possible mechanism as regulators of MMPs. Male Wistar rats were divided into 6 groups (n = 8): Control without injury, Control with injury, Control with injury + hBMSC-TERT, Diabetics without injury, Diabetics with injury, Diabetics with injury + hBMSC-TERT. DM was induced by intraperitoneal injection of streptozotocin (60 mg/kg) and cutaneous lesions were performed in the dorsal region with the use of a punch (6 mm). Three weekly subcutaneous injections of hBMSC-TERT (1x106) into the lesion were performed. Thirteen days after the last injection, euthanasia and the collection of cutaneous tissue were performed for histological analysis (hematoxylin-eosin) and MMP-2 activity determination by gelatin zymography. The presence of fibroblasts and inflammatory infiltrate was significantly lower (p <0.05) in infused diabetic animals when compared to those non-infused, indicating an improvement of the healing process in the diabetic group treated with hBMSC-TERT. The diabetic animals infused with hBMSC-TERT showed improvement in the healing process with respect to the amount and organization of collagen when compared to diabetic animals that did not receive an infusion of hBMSC-TERT. The levels of pro MMP-2 were significantly higher in Control with injury group than in Control group treated with hBMSC-TERT and in diabetic animals.

In conclusion, the data indicate that hBMSC-TERT may become an important therapeutic tool.

Disclosure

Â.M. Leal: None.
Persistent C-Peptide Levels and Proliferative Retinopathy in Childhood-Onset Type 1 Diabetes (T1D)
Authors: WILLIAMS KATHERINE , COSTACOU TINA , BECKER DOROTHY J. , ORCHARD TREVOR J.
Published: June 2018

Persistent C-peptide levels may protect against complications in T1D. To test this hypothesis, 185 subjects from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a 30-year prospective study of childhood onset (<17 years) T1D, had serum C-peptide levels measured by Mercodia ultra-sensitive ELISA at their 25 year exam. Eighteen (9.7%) subjects had detectable C-peptide levels. Those with and without detectable C-peptide did not differ in age (51.8 vs. 51.1 years, p=0.70), age of onset (9.7 vs. 8.1 years, p=0.12), diabetes duration (42.1 vs. 43.0 years, p=0.61), or HbA1c at either baseline (8.1 vs. 8.5%, p=0.22) or 25 years (7.8 vs. 7.8%, p=0.91). In those with detectable C-peptide, non-HDL cholesterol levels were lower at baseline (104.4 vs. 124.1 mg/dl, p=0.01), but not 25 years (112.6 vs. 119.5 mg/dl, p=0.44) and pump use was marginally lower at 25 years (31.2% vs. 55.3%, p=0.07). Proliferative retinopathy was lower in those with detectable C-peptide levels (33.5% vs. 55.1%, p=0.08) and this difference remained marginally significant (p=0.08) after controlling for duration of T1D, HbA1c and non-HDL cholesterol. No significant differences in overt nephropathy (5.6% vs. 22.7%, p=0.13), peripheral neuropathy (61.1% vs. 77.2%, p=0.15), or renal failure (0 vs. 4.2%, p=1.00) were found between the two groups when analyzed separately. When those with either retinopathy or nephropathy were combined, those with detectable C-peptide levels had lower rates of these complications (33.3% vs. 58.1%, p=0.045). This association remained significant in logistic regression after controlling for duration of diabetes and HbA1c with a statistically significant odds ratio 0.39 (95% CI: 0.08-0.94). When those with neuropathy were added to the overall microvascular complication group, no significant differences were found (p=0.13). These findings are consistent with the hypothesis that proliferative retinopathy and possibly nephropathy in T1D may be influenced by persistent C-peptide secretion.

Disclosure

K. Williams: None. T. Costacou: None. D.J. Becker: None. T.J. Orchard: None.
Impact of Vitamin B6 Intake on the Risk of Diabetic Retinopathy—Analysis from Multicenter Prospective Study of Japanese Patients with Type 2 Diabetes
Authors: HORIKAWA CHIKA , AIDA REI , TANAKA SHIRO , YOSHIMURA YUKIO , KAWASAKI RYO , MORIYA TATSUMI , ARAKI ATSUSHI , SONE HIROHITO
Published: June 2018

Vitamin B6 has been expected to prevent the progression of diabetic retinopathy. Previous studies reported that treatment with vitamin B6 protected against capillary dropout in a mouse model of diabetes and low serum vitamin B6 levels were associated with retinal vein occlusion in healthy individuals. However, data on this topic in patients with diabetes are sparse. As part of a nationwide cohort study we investigated the relationship between vitamin B6 intake and the incidence of diabetic retinopathy in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c≥6.5%. The present analysis was conducted among 22Japanese patients with type 2 diabetes from outpatient clinics in 59 university and general hospitals in Japan. Analyzed were 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of a diabetic retinopathy event. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean vitamin B6 intake in quartiles ranged from 0.9 to 2.0 mg/day and half of participants had vitamin B6 intake less than the recommended dietary allowance according to dietary reference intakes in Japan (males 1.4 mg/day; females 1.2 mg/day). Patients in higher quartiles included those with significantly high energy, vegetable, meat and fish intakes (p for trend< 0.01, < 0.01, < 0.01, and < 0.01, respectively). After adjusting for confounders, hazard ratios for diabetic retinopathy in the 2nd, 3rd, and 4th quartiles of vitamin B6 intake compared with the 1st quartile were 1.2 (95% confidence interval 0.8-1.7, p=0.36), 0.9 (0.6-1.3, p=0.51), and 0.51 (0.31-0.88, p=0.01), respectively. We clarified that the decreased incidence of diabetic retinopathy in Japanese patients with type 2 diabetes was associated with high vitamin B6 intake.

Disclosure

C. Horikawa: None. R. Aida: None. S. Tanaka: None. Y. Yoshimura: None. R. Kawasaki: None. T. Moriya: None. A. Araki: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
Knowledge, Attitudes, and Practices Related to Diabetes Eye Complications among Diabetes Mellitus Patients at a Referral Hospital in Zimbabwe
Authors: SITHOLE MELLISA , MATIMBA ALICE , WOODWARD RICHMOND
Published: June 2018

Information related to knowledge, attitudes, and practices of people with diabetes is especially important in resource-limited settings such as Zimbabwe, where medications to treat diabetes are costly and capacity to treat complications is limited, making observance of appropriate self-care practices that may delay or prevent complications vital to patient and public health. As a start to understanding the level of knowledge of diabetes eye complications, attitudes towards self-care practices, and utilization of available health care resources among diabetes patients, we conducted face-to-face interviews with 189 diabetes patients (133 female, 56 male, mean age 62.7 years) attending a referral hospital in Zimbabwe’s second largest city. A structured questionnaire was administered to each patient to document knowledge, attitudes, and practices that had 13, 11, and 12 questions in each section respectively. Knowledge results revealed the total knowledge score of diabetes and associated eye complications is associated with patients' self-report of seeing clearly or not, indicating patients not seeing all the time have a higher score then patients self-reporting they do see clearly all the time, x2=24.5815, df=11, p=0.0105. Attitude results revealed 74% of participants viewed consulting a pharmacist as a very important health care step compared to 96% who viewed consulting a physician as a very important health care step. Results indicating patients with diabetes who see clearly have less knowledge about diabetes and related eye complications suggests that reinforcing self-care steps should be directed towards this group. At the same time, patient attitude results suggest this gap could be filled by emphasizing the role of pharmacists in fostering good diabetes self-care practices and providing education for individuals with diabetes, especially early in the course of disease before vision impairment may occur.

Disclosure

M. Sithole: None. A. Matimba: None. R. Woodward: None.
A Whole-Grain Diet Confers Metabolic Advantages in Glucose Metabolism Compared to a Macronutrient-Matched, Refined-Grain Diet
Authors: MEY JACOB T. , HARI ADITHYA , GODIN JEAN-PHILIPPE , ROSS ALASTAIR , KIRWAN JOHN P.
Published: June 2018

Observational studies suggest diets high in whole grains (WG) may confer metabolic benefits over diets based on refined grains (RG) for overweight/obese individuals, thus preventing the development of type 2 diabetes (T2D). However clinical data have been inconclusive, in part due to metabolic heterogeneity. Therefore, we investigated a WG and RG diet in individuals at high risk (HR) or low risk (LR) of developing T2D based on 1 hour glycemic level during an OGTT (oral glucose tolerance test). We conducted a double-blind randomized crossover trial in 15 overweight/obese adults. Participants were administered a 4 hour, 75g OGTT and stratified as HR or LR of developing T2D (HR: 1 hour OGTT glucose (GLU) ≥155 mg/dl; LR: 1 hour OGTT GLU <155 mg/dl). Isocaloric WG and RG diets were provided for two 8 week periods with 10 week washout. Macronutrients were matched except for WG or RG (50g/1000 kcal). Fifteen subjects completed the trial, 10 HR (38±3 years, 33±2 kg/m2, 1 hour OGTT GLU 201±8 mg/dl) and 5 LR (38±4 years, 35±2 kg/m2, 1 hour OGTT GLU 126±5 mg/dl). Groups differed only by 1 hour OGTT (p<0.05). Weight loss was similar but only HR reached statistical significance (-2.1 kg, p<0.05). HR-WG improved insulin sensitivity (Matsuda Index, +21%, p<0.05). Further, HR-RG had a significant negative association between change in BMI and Matsuda Index vs. WG (r2=0.41, p<0.01). LR-RG reduced GLU clearance (iAUC 180 minutes, +27%, p<0.05 vs. WG). In agreement, LR-RG increased OGTT insulin (iAUC p<0.05 at 120, 180 and 240 minutes) and c-peptide (iAUC p<0.05 at 60 and 120 minutes). Interestingly, 1 hour OGTT GLU predicted change in waist circumference in WG (n=15, r2=0.36, p=0.02), suggesting those with more impaired GLU tolerance may acquire greater benefit from WG. We observed differential effects of a WG and RG diet in overweight/obese adults. These data suggest a WG diet may improve measures of glucose metabolism in individuals at high risk of developing T2D, whereas a RG diet may impair glucose metabolism in lower risk individuals.

Disclosure

J.T. Mey: None. A. Hari: None. J. Godin: Employee; Self; Nestlé. Employee; Spouse/Partner; Nestlé. A. Ross: None. J.P. Kirwan: None.
Ranibizumab-Induced Diabetic Retinopathy Improvement—Results from Patients at High Risk for Vision Loss in RIDE/RISE and Protocol S
Authors: HERSHBERGER VRINDA , HILL LAUREN F. , TUOMI LISA L. , GHANEKAR AVANTI
Published: June 2018

Purpose: To examine diabetic retinopathy (DR) outcomes in patients (pts) at high risk for negative outcomes using data from RIDE/RISE and Protocol S. In RIDE/RISE, pts with moderately severe to severe nonproliferative DR (NPDR) at baseline were assessed due to their high risk for progression to proliferative disease (ETDRS Report 12. Ophthalmology. 1991). In Protocol S, the majority of pts had proliferative DR (PDR) at baseline, which is associated with vision loss (Moss. Ophthalmology. 1998), and DR outcomes were assessed according to diabetic macular edema (DME) status at baseline.

Methods: In the randomized phase 3 RIDE (NCT00473382)/RISE (NCT00473330) studies, pts with DME (N = 759) received monthly ranibizumab (RBZ) (0.3 mg or 0.5 mg) or sham treatment through the month (M) 24 primary end point. In the randomized phase 3 Protocol S (NCT01489189) study, eyes with and without DME received either prompt pan-retinal photocoagulation or RBZ 0.5 mg (as needed after 3 monthly treatments) (N = 394 eyes). M24 DR outcomes are retrospectively evaluated herein.

Results: In RIDE/RISE, ∼ 30% of pts in each arm had high-risk NPDR at baseline (DR severity level 47/53) (35.9%, 30.0%, and 33.9% for RBZ 0.3 mg, RBZ 0.5 mg, and sham, respectively). A significant majority of these pts (78.4% and 81.1% of RBZ 0.3 mg- and 0.5 mg-treated, respectively) achieved ≥ 2-step DR improvement at M24 vs. only 11.6% of sham-treated pts (P < .0001). Notably, these rates of ≥ 2-step DR improvement with RBZ were more than 2 times higher than the overall population at M24 (37.2% and 35.9% for RBZ 0.3 mg and 0.5 mg, respectively) (Ip. Arch Ophthalmol. 2012). In Protocol S, 87% of eyes had PDR and 22% of eyes had DME at baseline. At M24, RBZ treatment resulted in ≥ 2-step DR improvement in eyes with (58.5%) and without (37.8%) DME at baseline.

Conclusions: RBZ treatment was effective at significantly improving DR in pts at high risk for DR-related vision loss, irrespective of baseline DME status.

Disclosure

V. Hershberger: None. L.F. Hill: Employee; Self; Genentech, Inc. L.L. Tuomi: Employee; Self; Genentech, Inc. A. Ghanekar: Employee; Self; Roche Pharma. Stock/Shareholder; Self; Roche Pharma.
Association between Metabolic Syndrome Components and Indices of Liver Steatosis and Stiffness by Transient Elastography in Patients with Type 2 Diabetes and Imaging-Confirmed Nonalcoholic Fatty Liver Disease
Authors: HUANG ZHIMIN , LEE CHI HO , FONG HO YI , LAM KAREN S.
Published: June 2018

Background and Aims: The index of liver steatosis, controlled attenuation parameter (CAP), is a relatively new introduction to Fibroscan, an established equipment for assessing liver fibrosis, in terms of liver stiffness measurement (LSM). The relationship between CAP and/or LSM and metabolic syndrome components in diabetic patients with nonalcoholic fatty liver disease (NAFLD) was unclear, and was addressed in this study.

Methods: A total of 224 patients with type 2 diabetes and NAFLD confirmed by ultrasonography were recruited. Anthropometric and serum biochemical parameters were collected. CAP and LSM were measured using transient elastography. The association between metabolic syndrome components and values of CAP and LSM was analyzed.

Results: The mean age of the patients was 57.9±10.2 years, their BMI was28.6± 5.5kg/m2, and the duration of diabetes was 16.6±8.3 years. Eighty-eight percent of the patients had hypertension, and 79.5% were on lipid-lowering drugs. The mean CAP was 309.3±57.9 dB/m, and median LSM was 7.9 (5.7, 10.4) kpa. There were significant rising trends in BMI, waist circumference, waist to hip ratio, white blood cell count, HbA1c, FPG, triglyceride, ALT, AST and LSM with escalating CAP tertiles, whereas age, HDL-c, AST/ALT ratio and plasma adiponectin decreased concomitantly (all p<0.05). There was a larger number of metabolic syndrome components clustering in the third as compared to the first tertile of CAP (p=0.027) and LSM (p=0.035). On the other hand, with an increasing number of metabolic syndrome components, the value of CAP (p=0.001) and LSM (p=0.025) increased accordingly.

Conclusion: CAP and LSM measured by transient elastography had a strong correlation with the clustering of metabolic syndrome components in NAFLD, even in patients with long-standing type 2 diabetes.

Disclosure

Z. Huang: None. C. Lee: None. H. Fong: None. K.S. Lam: None.
Reduction of Diabetes and Cardiovascular Risk in a Workforce after Digital Behavioral Counseling
Authors: BIRSE CHARLES E. , LAGIER ROBERT J. , CHEW PAUL , JASIK CAROLYN B. , MADERO ERICA N.
Published: June 2018

Background: We asked whether the integration of digital behavioral counseling with employer-sponsored annual biometric screening could reduce the risk of obesity-related chronic disease in a U.S. workforce.

Methods: We evaluated a cohort (n=113) who participated in an employer-sponsored annual wellness program with year-end biometric screening and enrolled in a digital behavioral counseling program. Individuals were included in the analysis if they participated in the wellness program in 2015, had prediabetes (fasting glucose (FG) 100 to 125mg/dL or Hb1Ac 5.7 to 6.4%) and a BMI ≥25 kg/m2 in 2016, and agreed to participate in a digital behavioral counseling program followed by year-end biometric screening in 2017.

Results: The participants were 75% women and 61% Caucasian, 28% African American. At the 2016 year-end biometric screening, which preceded digital behavioral counseling, the characteristics of the cohort (mean± sd) were age, 50.0±9.9 years; BMI, 37.1±8.6 kg/m2; Hb1Ac, 6.1±0.6%; and FG, 106.9±24.2 mg/dL. Following behavioral counseling, 28% of the participants lost 5% or more of body weight. Hb1Ac and FG levels both fell below prediabetic thresholds for 32% of the participants. Other biometric outcome measures improved (Table).

Conclusions: Digital behavioral counseling was effective in reducing risk for both diabetes and cardiovascular disease in a workforce cohort.Change in annual biometric screening resultsThe year preceding counseling (2015 to 2016)The year counseling received (2016 to 2017)P value (paired t-Test)BMI (kg/m2)+0.66-1.18<0.0001Hb1Ac (%)+0.06-0.220.001Fasting Glucose (mg/dL)+5.85-2.840.02Triglycerides (mg/dL)+12.0-17.20.0110-year ASCVD risk* (%)+1.83-0.480.01*Atherosclerotic Cardiovascular Disease risk (2013 ACC/AHA Cardiovascular Risk Guideline)

Disclosure

C.E. Birse: Employee; Self; Quest Diagnostics. Stock/Shareholder; Self; Quest Diagnostics. R.J. Lagier: Employee; Self; Quest Diagnostics. P. Chew: Employee; Self; Omada Health, Inc. C.B. Jasik: Employee; Self; Omada Health, Inc. E.N. Madero: Employee; Self; Omada Health, Inc..
ApoC-III Levels Correlate with Insulin Resistance and HbA1c in Familial Partial Lipodystrophy—Observations from the Broaden Study
Authors: MERAL RASIMCAN , DIGENIO ANDRES , NEIDERT ADAM H. , TAMI JOSEPH , ORAL ELIF A. ,   ON BEHALF OF THE BROADEN STUDY INVESTIGATORS
Published: June 2018

Familial Partial Lipodystrophy (FPLD) is a rare genetic disorder with selective loss of adipose tissue from the periphery with an increase in ectopic fat leading to severe hepatic insulin resistance, and hypertriglyceridemia. ApoC-III is a secreted liver glycoprotein associated with hypertriglyceridemia and insulin resistance. We inquired the relationship between lipid and other metabolic parameters with morphometric characteristics (including those of ectopic fat deposition) and circulating apoC-III levels in a cohort of FPLD patients who were screened for enrollment into the BROADEN study, a global trial to study efficacy of volanesorsen (an antisense mRNA apoC-III inhibitor). 28 patients are included in these analyses (age range, 28 to 65, mean 45 years; M/F, 7/21; all but one Caucasian). Table 1 shows the significant relationships observed using linear regression analyses between circulating ApoC-III levels and investigated parameters. These results reiterate the tight relationship between triglyceride levels and ApoC-III levels, and further demonstrate that circulating ApoC-III levels also correlate with insulin resistance, and HbA1c as well as important left ventricle morphometric parameters. It is plausible to hypothesize that a strategy to lower apoC-III levels may have additional benefits beyond lowering triglyceride levels.Table 1: Relationship of metabolic and echocardiogram parameters in FPLDParametersR2p-valuenParametersR2p-valuenTriglycerides* vs. ApoC-III0.63<0.00128LV end systolic diameter vs ApoC-III0.260.02719HOMA-IR* vs. ApoC-III0.190.01928LV end systolic diameter vs Triglycerides*0.250.03119HOMA-IR* vs. Triglycerides*0.150.04228Left ventricle outflow tract dimension vs ApoC-III0.220.04519Insulin* vs. ApoC-III0.140.04528Left ventricle outflow tract dimension vs Triglycerides*0.290.01719HbA1c** vs. ApoC-III0.230.03021* Parameter log-transformed**Subjects with HbA1c<6.4% excluded

Disclosure

R. Meral: None. A. Digenio: Employee; Self; Akcea Therapeutics. A.H. Neidert: None. J. Tami: Employee; Self; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Self; Ionis Pharmaceuticals, Inc. E.A. Oral: Advisory Panel; Self; Aegerion Pharmaceuticals. Research Support; Self; Aegerion Pharmaceuticals, Akcea Therapeutics. Advisory Panel; Self; Akcea Therapeutics. Research Support; Self; Ionis Pharmaceuticals, Inc., AstraZeneca. Other Relationship; Self; Aegerion Pharmaceuticals.
Analysis of the Association between PCSK9 Levels and Plasma Lipid Levels in Cameroonians with Type 2 Diabetes
Authors: CAMILLE B.M. , MBACHAM WILFRED F. , SOBNGWI EUGÈNE , MBANYA JEAN CLAUDE
Published: June 2018

Studies have shown that intensive LDL-lowering therapy results in a significant reduction in cardiovascular disease (CVD) risk and improved outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of LDL cholesterol (LDL-C) and an independent CVD risk marker. PCSK9 has additionally been related to CRP which is also a CVD risk marker. The emerging importance of the inhibition of PCSK9 for the treatment of hypercholesterolemia warrants investigations in different populations. This is the first study evaluating the association between PCSK9 and plasma lipid levels in Sub-Saharan Africa.

A Cross sectional analysis was conducted at a major hospital in Yaound9, Cameroon in a cohort of 82 participants (53% females) with median age of 51[42-58] years. There were 28 non-obese type 2 diabetes (T2D) patients with median known duration of diabetes of 3.08[1.06-6.50] years, matched for age and sex to 28 obese nondiabetic and 26 lean nondiabetic subjects. Serum PCSK9 levels were measured using sandwich ELISA method. PCSK9 and hs-CRP levels were significantly higher in obese and T2D subjects relative to the lean controls (p<0.001 and p =0.0respectively). BMI was an independent predictor for PCSK9 and hs-CRP levels and this association remained after adjustment for potential confounders. Lean female subjects had significantly higher PCSK9 levels than males (p=0.004) and positive correlation of PCSK9 with LDL-C and total cholesterol (r=0.4, p=0.048 and r=0.5, p=0.039 respectively). An association was not found between PCSK9 and plasma lipid levels in obese and type 2 diabetes subjects nor was it found between PCSK9 and hs-CRP.

Obese and type 2 diabetes subjects have higher PCSK9 and hs-CRP levels when compared to lean controls, suggesting that these metabolic states potentially impact PCSK9 levels in Cameroonian patients.

Disclosure

C.B.M. Mba: None. W.F. Mbacham: None. E. Sobngwi: None. J. Mbanya: Advisory Panel; Self; GlaxoSmithKline plc.. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi, Servier.
Gender and Risk of Cardiovascular Events in Patients with Diabetic Foot
Authors: ANICHINI ROBERTO , POLICARDO LAURA , FRANCESCONI PAOLO , FRANCIA PIERGIORGIO , DE BELLIS ALESSANDRA , GULISANO MASSIMO , SEGHIERI GIUSEPPE
Published: June 2018

In patients with diabetic foot (DF) the risk of developing cardiovascular events or renal failure is strongly increased. While DF is more frequent in males, it is yet unknown if there is a gender difference about cardiovascular events or renal failure incidence in patients with diabetic foot. The aim of this study was to evaluate the risk of hospitalization for cardiovascular events (ASCVD: heart attack, ischemic stroke or heart failure) or chronic renal failure (CKD), stratified by gender, in a population of diabetic patients living in Tuscany from 2012 to 2016. On the basis of administrative data bases, patients living in Tuscany at the 1st of January 2012 were divided into 2 subgroups: patients previously hospitalized for diabetic foot (ulcers, infections, major or minor amputations, gangrene or Charcot foot) and patients without history of hospitalization for diabetic foot. Data were collected from the regional hospitalization registry, and in the two groups the risk of developing ASCVD or CKD by the Cox regression corrected by age and comorbidities (Charlson Index of previous hospitalizations) separately in males and females was evaluated. 240238 patients with diabetes (121442 males, 118796 females) were identified. After the corrections made by age, sex and Charlson index, males showed a major risk of developing diabetic foot (DF): Odds Ratio (OR):2.018 (95% CI:1.901-2.141); p<0.0001.The corrected risk of hospitalization for ASCVD and CKD in patients with previous diagnosis of DF was higher in females [Hazard Ratio (HR):1.647 (1.470-1838)] than in males (HR:1.458 (1.348-1.574); p=0,04. In the population investigated, the risk of hospitalization for DF was two time higher in males, while, the risk of hospitalization for ASCVD corrected by confounding factors, in patients previously hospitalized for DF, was significantly higher in females.

Disclosure

R. Anichini: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation, Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company, AstraZeneca. Speaker's Bureau; Self; Merck & Co., Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Sanofi, Janssen Pharmaceuticals, Inc.. Research Support; Self; Grünenthal Group. L. Policardo: None. P. Francesconi: None. P. Francia: None. A. de Bellis: Speaker's Bureau; Self; Eli Lilly and Company, AstraZeneca, Novo Nordisk A/S. Research Support; Self; Grünenthal Group. M. Gulisano: None. G. Seghieri: None.