bluuebunny/crossref_metadata_2025 huggingface dataset:
464-P: Visceral Adiposity Index Identifies Both Type 2 Diabetes Mellitus and Prediabetes Better than Established Indices of Visceral Obesity in a Pad Cohort
Authors: ZIERFUSS BERNHARD , HOEBAUS CLEMENS , HERZ CARSTEN T. , KOPPENSTEINER RENATE , SCHERNTHANER GERIT-HOLGER
Published: June 2019

T2DM is a major risk factor for cardiovascular morbidity and mortality in PAD. Clinical assessment of patients at risk for the development of T2DM remains challenging. Visceral obesity is a known risk factor of T2DM, but there is no consensus for a clinically applicable measurement. This study aimed to investigate the potential association of a novel visceral obesity parameter, visceral adiposity index (VAI), with dysglycemia (prediabetes and T2DM) in comparison to established indices in a PAD cohort. 366 patients with diagnosed PAD (defined by an ABI<0.9 and Fonaine stage) were enrolled into this cross-sectionally designed study. All patients without known T2DM underwent screening with an OGTT. T2DM and prediabetes (PRE - IFG and IGT) were defined according to the ADA criteria. VAI was calculated according to the Amato formula. The cohort consisted of 43 patients with normal glucose tolerance (NGT), 159 patients with PRE and 164 patients with manifest T2DM. VAI was significantly higher in T2DM and PRE against NGT (median 2.33, IQR 1.35-3.44; 1.95, 1.26-2.86; 1.41, 1.18-2.41; p=0.006). In a multivariable binary logistic regression model adjusted for age, gender, LDL-C, serum creatinine, systolic blood pressure, smoking status and CRP the odds ratio for the highest VAI tertile for dysglycemia was 3.34 (95% confidence interval 1.38-8.06), 1.9 (1.07-3.38) for T2DM and 2.65 (1.05-6.68) for PRE alone. The same model for dysglycemia was significant, but weaker, for BMI above 25 kg/m2(2.27, 1.11-4.66) and waist circumference (WC) >80cm in female and >94cm in male patients (2.38, 1.01-5.62), but not significant for waist-hip ratio (WHR) >0.85 in female and >0.9 in male patients (2.24, 0.91-5.52). BMI, WC and WHR models neither predicted T2DM nor PRE (data not shown). Higher VAI values are associated with different states of dysglycemia alone and combined in a PAD cohort. In these patients VAI is superior to more common parameters of obesity.

Disclosure

B. Zierfuss: None. C. Hoebaus: None. C.T. Herz: None. R. Koppensteiner: None. G. Schernthaner: None.
47-LB: Readmission and Comprehension of Diabetes (DM) Education at Discharge
Authors: PINKHASOVA DIANA , SWAMI JANYA , PATEL NEETI , DONIHI AMY , SIMINERIO LINDA M. , FRENCH ESRA KARSLIOGLU , DELISI KRISTIN , HLASNIK DEBORAH S. , RUBIN DANIEL J. , KORYTKOWSKI MARY T.
Published: June 2019

Hospitalized patients with DM are at high risk for early readmission. Improving inpatient education and discharge (DC) processes are proposed interventions for reducing this risk.

We examined the contribution of blood glucose (BG) 48 hr prior to DC (nadir, peak, STD, CV) and patient comprehension (PC) of instructions for home DM management following DC to risk for 30d readmission.

Insulin treated non-critically ill patients with DM (N=202) were recruited. Diabetes Early Readmission Risk Indicators (DERRI) were calculated for each participant, who were contacted within 48 hr of DC to complete a PC Questionnaire (PCQ).

Of 126 participants [age mean (STD) 61(12) years, BMI 32.9 (9.6) kg/m2, A1c 8.0 (2.2%), 45% women, 22% black, 85% type 2DM] who completed the PCQ, 42 (33%) required clarification of misunderstood DC instructions. PC scores were negatively correlated with BG STD (-0.17, 95% CI:-0.32,-0.02) and CV (-0.38, -0.7, -0.05).

There was no difference in median (25ile, 75ile) PC scores between patients with and without 30d readmission (79 (67, 93%) vs.83 (71,100%), p=0.19); however, there were more readmissions in those with PC scores <100% compared to scores of 100% (n = 34) (29% vs. 15%, OR=2.4, 95% CI: 0.83, 6.88).

Among all 202 participants, median DERRI scores were higher in the 25% with 30d readmission (27 (24, 30)) than those without (19 (20, 24), p = 0.002).

In summary, these results demonstrate deficiencies in the hospital DC process as demonstrated by the need for clarification of information in >30% of patients following DC. It is possible that this corrected information may have served as an intervention to reduce readmission risk. PC scores were negatively associated with glycemic variability preceding DC and scores <100% were associated with a higher risk for readmission. DERRI scores were strongly associated with risk for 30d readmissions, representing the first prospective external validation of this tool. These results support proposals to improve the DC process and post-DC follow-up of patients with DM.

Disclosure

D. Pinkhasova: None. J. Swami: None. N. Patel: None. A. Donihi: None. L.M. Siminerio: None. E. Karslioglu French: None. K. Delisi: None. D.S. Hlasnik: None. D.J. Rubin: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. M.T. Korytkowski: None.

Funding

National Institutes of Health (UL1-TR-001857)
473-P: Identification of Novel Genes Participating in Diabetic Macrovascular Complications by DNA Methylation Modulation
Authors: LIAO YUNFEI , CHEN LULU , ZENG TIANSHU
Published: June 2019

Diabetic vascular complications contribute to the increased morbidity and mortality of diabetic patients. However, the mechanism of diabetic macrovascular complication remains unclear.

Objective: We intend to unleash the role of DNA methylation modification in the pathological process of diabetic macrovascular complication and identify the potential biomarkers that could be beneficial for early intervention.

Methods: We screened for differentially methylated genes by methylated DNA immunoprecipitation chip (MeDIP-chip) in diabetic patients. The validation of MeDIP-chip was performed by methylation-specific PCR (MSP). Furthermore, we investigated the expressions of the aberrantly methylated genes and their functions in the model of diabetic mice.

Results: Serval aberrantly methylated genes have been explored, including phospholipase C beta 1 (PLCB1), cam kinase I delta (CAMK1D), and dopamine receptor D5 (DRD5) which participated in calcium signaling pathway. Meanwhile, vascular endothelial growth factor B (VEGFB), placental growth factor (PLGF), fatty acid transport protein 3 (FATP3), coagulation factor II thrombin receptor (F2R), and fatty acid transport protein 4 (FATP4) which participated in vascular endothelial growth factor receptor (VEGFR) signaling pathway, were also been found. After MSP and gene expression validation in peripheral blood of patients, PLCB1, PLGF, FATP4, and VEGFB were corroborated. Combining with the detection of fatty acid uptake by radionuclide tracing, DNA methylation regulated VEGFR signaling pathway was demonstrated to mediate the lipid deposition in aortas of diabetic mice.

Conclusions: Our study identifies novel biomarkers and therapeutic targets in diabetic macrovascular complications. DNA methylation in VEGFR signaling pathway might play an important role in diabetic macrovascular complications.

Disclosure

Y. Liao: None. L. Chen: None. T. Zeng: None.

Funding

National Natural Science Foundation of China
482-P: Linagliptin Induces M2 Macrophage Polarization and Suppresses Progression of Atherosclerosis in High-Fat-Fed ApoE-Deficient Mice
Authors: NISHIDA SHUHEI , MATSUMURA TAKESHI , SENOKUCHI TAKAFUMI , ISHII NORIO , MURAKAMI-NISHIDA SAIKO , YAMADA SARIE , MORITA YUTARO , WADA TOSHIAKI , MOTOSHIMA HIROYUKI , KONDO TATSUYA , ARAKI EIICHI
Published: June 2019

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors suppressed the progression of atherosclerosis in atherosclerotic mouse models. However, exact mechanism has been unclear. In this study, we investigated whether linagliptin suppressed progression of atherosclerosis in high fat diet (HFD)-fed apolipoprotein-E-deficient (ApoE KO) mice via anti-inflammatory effects on macrophages.

Methods: HFD-fed ApoE KO mice were treated orally with linagliptin (10 mg/kg/day). After 8 weeks of treatment, whole aorta and aortic sinus were stained with Oil red O, or anti-4-Hydroxynonenal (4-HNE) and anti-F4/80 antibodies. Mouse bone marrow-derived macrophages were used in vitro study. Intracellular ROS generation was evaluated by H2DCF-DA assay. Expression of iNOS, MCP-1, TNF-α, arginase-1, Mgl2 and Ym1 mRNA, and macrophage polarization were evaluated by real-time RT-PCR and FACS scan, respectively.

Results: There were no significant differences on food intake, body weight, blood glucose levels between each group, but cholesterol concentrations in VLDL and LDL particle were lower in linagliptin group. Oil-Red-O staining demonstrated that size of atherosclerotic lesions was decreased in linagliptin group. The 4-HNE-positive area and number of macrophages in plaques were decreased, and mRNA expression of arginase-1, Mgl2 and Ym1 in the aorta were higher in linagliptin groups than those in control groups. Linagliptin suppressed ROS generation, increased mRNA expression of arginase-1, Mgl2 and Ym1, and ameliorated LPS+IFNγ-induced reduction of M2 macrophages.

Conclusion: This study suggests that linagliptin suppresses the progression of atherosclerosis in HFD-fed apoE KO mice. Moreover, linagliptin suppresses ROS generation and increases the polarization of M2 macrophages. These findings may indicate the beneficial effects of linagliptin for the prevention of diabetic macrovascular complications.

Disclosure

S. Nishida: None. T. Matsumura: None. T. Senokuchi: None. N. Ishii: None. S. Murakami-Nishida: None. S. Yamada: None. Y. Morita: None. T. Wada: None. H. Motoshima: None. T. Kondo: None. E. Araki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Novo Nordisk Inc., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi.
486-P: Hyperglycemia Promotes Epigenetic Priming of RELA/p65 Gene in Cord Blood-Derived CD34+ Stem Cells and Their Differentiation into Proinflammatory CD16 Myeloid Cell Population
Authors: VINCI MARIA CRISTINA , VIGORELLI VERA , GENOVESE STEFANO , POMPILIO GIULIO
Published: June 2019

Background: Diabetic patients are characterized by a systemic pro-inflammatory state and an increased propensity to develop atherosclerosis. Since epigenetic mechanisms are known to be involved in the regulation of inflammatory genes of vascular cells under diabetic conditions, we hypothesized that uncontrolled hyperglycemia may epigenetically skew circulating CD34+ progenitors towards an inflammatory phenotype.

Results: We investigated the impact of hyperglycemia on the epigenetic makeup of NFkB gene, a gate-keeper of the inflammatory control of CD34+ cells, and on the differentiation into myeloid progenitors. CD34+ cells exposed to high glucose (HG) showed a significant reduction of the repressive epigenetic modification H3K9me3 on RELA/p65 gene encoding for nuclear factor NF-kappa-B p65 subunit. This epigenetic alteration coincided with an increased recruitment of RNA polymerase II at level of p65 promoter and with a significant transcription up-regulation. Interestingly, the KAT2B/PCAF gene, an histone acetyltransferase implicated in NFkB-p65 acetylation and nuclear stabilization, was also overexpressed. Consistently, HG-CD34+ cells showed higher acetylation of NFkB in the lysine-310 and increased expression and secretion of the NFkB-p65 target cytokines, TNFα and IL6. Moreover, in vitro differentiation of HG-CD34+ cells into myeloid lineage generated higher level of pro-inflammatory CD16+ and CD14+ CD16+ monocyte subsets when compared to the normoglycemic counterpart.

Conclusions: These results suggest that elevated glucose exposure might epigenetically prime CD34+ cells for a pro-inflammatory response as well as skew CD34+ cell differentiation into inflammatory cell lineages.

Disclosure

M. Vinci: None. V. Vigorelli: None. 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. G. Pompilio: None.

Funding

Ricerca Finalizzata, Ministero della Salute (PE-2011-02348537)
5-LB: Improving Diabetes Prevention with Benefit-Based Tailored Treatment: Disseminating Individualized Risk Estimates
Authors: CIEMINS ELIZABETH L. , POWELSON JILL E. , NELSON JASON P. , COLANGELO FRANCIS R. , CUDDEBACK JOHN K. , KENT DAVID M.
Published: June 2019

Objective: Implement in an electronic health record (EHR) a predictive model for people with prediabetes that provides individualized benefit estimates for taking metformin or participating in the Diabetes Prevention Program (DPP). This model stratifies people with prediabetes by the potential to reduce their risk of progression to diabetes based on regression models developed directly on the DPP trial and recalibrated to Optum data. With 1/3 of adults having prediabetes, health systems need a way to prioritize.

Study Design: Pre/post implementation study including provider and patient surveys and data on use of the predictive model. The model estimates risk of progression to diabetes with usual care, the DPP, or metformin, based on 11 demographic, biometric and diagnosis variables available in the EHR.

Population Studied: Patients with prediabetes at 10 pilot primary care clinics, where providers access the model via an EHR click and the data elements are automatically populated from the EHR.

Principal Findings: The predictive model was used on 68% (n=2,304) of patients with prediabetes between 5/1/18 and 1/31/19. A total of 43% of patients were classified as high-risk, 54% as moderate-risk, and 4% as low-risk. Treatment - either referrals to the DPP or prescriptions for metformin - was provided for 63% of high-risk, 15% of moderate-risk, and 4% of low-risk patients. DPP referrals and metformin prescriptions for these high-risk patients increased substantially after implementation of the calculator (DPP: 0% to 44%; Metformin: 2% to 19%).

Conclusions: A predictive model, embedded in the EHR, that predicts individual patient risk for developing diabetes at the point of care improved treatment for patients with prediabetes. Use of individualized risk estimates resulted in the prioritization of treatment for patients at greatest risk of developing type 2 diabetes.

Disclosure

E.L. Ciemins: None. J.E. Powelson: None. J.P. Nelson: None. F.R. Colangelo: None. J.K. Cuddeback: None. D.M. Kent: None.

Funding

Patient-Centered Outcomes Research Institute
501-P: ROCK2 Activation Accelerates Podocyte Injury in Diabetic Kidney Disease
Authors: MATOBA KEIICHIRO , KAWANAMI DAIJI , TAKEDA YUSUKE , NAGAI YOSUKE , UTSUNOMIYA KAZUNORI
Published: June 2019

Podocyte apoptosis is a key pathological finding in the progression of diabetic kidney disease. Here we demonstrate that Rho-kinase (ROCK) mediates transforming growth factor β (TGF-β)-induced podocyte apoptosis. Mechanistically, ROCK regulates Notch ligand induction via the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) but not Smad pathways. Consistently, the ROCK inhibitor fasudil suppressed albuminuria and the urinary excretion of nephrin in type 2 diabetic db/db mice and attenuated podocyte apoptosis. The expression of Notch ligand and apoptosis markers such as Bax and cyclin-dependent kinase inhibitor 1A (CDKN1A) was decreased in podocytes derived from fasudil-treated db/db mice. In order to elucidate the isoform-specific roles of ROCK, we knocked down ROCK1 and ROCK2 separately using siRNA duplexes. Importantly, Notch ligand expression was specifically regulated by ROCK2 but not ROCK1. In renal tissue, ROCK2 was expressed mainly in nucleus of glomerular cells, tubules, and vascular walls in wild type mice. Podocyte colocalization was revealed by immunofluorescence of ROCK2 and nephrin, indicating the involvement of ROCK2 in diabetic podocytopathy. The present study provides evidence that ROCK plays a key role in podocyte apoptosis. ROCK2 may be an attractive therapeutic target for diabetic kidney disease.

Disclosure

K. Matoba: Research Support; Self; Daiichi Sankyo Company, Limited, Novo Nordisk Inc., Sanofi, Shionogi & Co., Ltd., Takeda Pharmaceutical Company Limited. D. Kawanami: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Y. Takeda: None. Y. Nagai: None. K. Utsunomiya: None.

Funding

Japan Society for the Promotion of Science; Uehara Memorial Foundation; Japan Diabetes Society; Ichiro Kanehara Foundation; MSD Life Science Foundation; Yokoyama Foundation
510-P: Protection of Kidney and Pancreas in Diabetes via Rescuing Disruption of STRA6-Retinol Cascade by SGLT2 Inhibitor, not Sulfonylurea
Authors: SHIN SHYI-JANG
Published: June 2019

Sodium glucose co-transporter 2 (SGLT2) inhibitors have been proved to be beneficial for cardiovascular and renal outcome in diabetic patients. Our study demonstrated that disruption of intracellular retinol signaling is associated with diabetic nephropathy. Retinoid homeostasis, regulated by RBP4/STRA6/CRBP1/LRAT/RARs pathway, is also very crucial in cell biological function of pancreas and islets. This study aimed to demonstrate whether SGLT2 inhibitor or sulfonylurea could protect pancreas and kidney from diabetes-related injury. Diabetic db/db mice were treated with empagliflozin or glibenclamide for 4 weeks at their age of 8 weeks. This study analyzed RBP4/STRA6/CRBP1/LRAT/RARs signals and p-JNK, caspase in both pancreas and kidney, and functional markers of pancreatic β-cells (insulin, MafA, Pdx1, and NKX6.1) in pancreas of wild type, db/db, glibenclamide-treated db/db and empagliflozin-treated db/db mice. Significant reduction of insulin, MafA, Pdx1 and NKX6.1 protein and mRNA in pancreas of db/db mice were found and could be rescued in empagliflozin-treated db/db mice, but not in glibenclamide-treated db/db mice. STRA6, CRBP1, LRAT and RARβ protein and mRNA levels were reduced, while p-JNK and caspase expression increased in pancreas and kidneys of db/db mice. These changes were recovered in empagliflozin-treated db/db mice, but not in glibenclamide-treated db/db mice. The concentration of retinol, and retinoic acid, measured by HPLC, were also conserved in pancreas of empagliflozin-treated db/db mice, not in glibenclamide-treated db/db mice.

In conclusion, this study indicates that empagliflozin, but not glibenclamide, exerts protective effects on pancreas and kidneys from diabetes through retrieving the disruption of STRA6-retinol signals in db/db mice.

Disclosure

S. Shin: None.

Funding

Taiwan Ministry of Science and Technology
52-LB: Insulin Cost-Saving Estimate for Injection Technique (IT) Training in Subjects Injecting into Lipohypertrophy (LH)
Authors: CHEN LIMING , XING QIULING , LI JING , ZHOU JIANXIN , HOU YUE , YUE NING , YUAN YI
Published: June 2019

Background: LH with prevalence of 53.1% [1] among diabetic population in China, is one of the most common clinical complications related to injection therapy. IT training includes rotation of injection sites, adjustment of doses, stop needle reuse, etc. is an education intervention for those diabetic patients injecting into LH.

Objective: This study aims to assess the effect of IT training on Total Daily Dose (TDD) of insulin for those diabetic patients injecting into LH and estimate the related insulin cost savings.

Methods: A 6-month prospective randomized controlled trial carried out in 210 diabetic patients with LH in Tianjin. Patients in intervention group (n=106) were given IT training including avoiding injections into LH, reducing TDD by 10-20%, rotating injection sites, and stopping needle reuse. Patients in control group (n=104) kept their injection habits. The annual cost of insulin in China were calculated with the TDD, unit cost of insulin, the population of insulin therapy and insulin adherence rate. Unit costs of insulin was 0.25 RMB/IU [2], 9 million insulin injecting patients and 42% insulin therapy adherence in China [1] (the exchange rate is 1 USD =6.617 RMB in 2018). The discount rate was set as 3%.

Results: The TDD for the control group and intervention group were 45.31(21.83) IU and 47.08(20.62) IU at 0 month and 45.06(21.29) IU and 40.53(19.97) IU at 6 months respectively. Patients in intervention group had a significant TDD decrease at 6.84 IU per day (P<0.05) after 6 months training. However, the TDD for control group only decreased at 0.91 IU per day. The estimated annual cost of decrease of insulin uptake because of IT training is approximately 1.37 billion RMB (207.0 million USD).

Conclusion: IT training in patients with LH can significantly reduce the insulin uptake and then saving medical expenditure both from the patient and the healthcare sectors’ perspective. Thus, the IT training should be applied in a greater population with insulin therapy in China.

Disclosure

L. Chen: Research Support; Self; Becton, Dickinson and Company. Q. Xing: Research Support; Self; Becton, Dickinson and Company. J. Li: Research Support; Self; Becton, Dickinson and Company. J. Zhou: Research Support; Self; Becton, Dickinson and Company. Y. Hou: Employee; Self; Becton, Dickinson and Company. N. Yue: Employee; Self; Becton, Dickinson and Company. Y. Yuan: Employee; Self; Becton, Dickinson and Company.

Funding

Becton, Dickinson and Company
526-P: Dapagliflozin Improves the Urinary CKD273 Proteomic Score When Added to Renin-Angiotensin Blockade in Patients with Type 2 Diabetes and Nephropathy
Authors: PERSSON FREDERIK , EICKHOFF MIE K. , MISCHAK HARALD , FRIMODT-MOLLER MARIE , ROSSING PETER
Published: June 2019

Objective: Evaluating effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on the urinary CKD273 proteomic score in patients with type 2 diabetes (T2D) and albuminuria.

Methods: A double-blinded, randomized, placebo-controlled, crossover trial of 12 weeks dapagliflozin (10 mg) or matching placebo added to standard care. Patients included (n=40) had T2D and albuminuria (UACR≥30 mg/g). At baseline and end of treatment periods HbA1C was measured, spot urine for urinary proteomics and three consecutive morning spot urines for albuminuria were collected and 24h blood pressure and 51Cr-EDTA (GFR) were performed. Urine proteomic patterns was evaluated using the CKD273 score. To determine high-risk or low risk of diabetic kidney disease a previously defined cut off of 0.154 was used. Results were compared using mixed model analysis adjusted for age, sex, systolic blood pressure, HbA1c, albuminuria and GFR. Chi-square analysis was used to examine change in risk category based on proteomics.

Results: Baseline values for the 36 participants completing the study: Geometric mean urinary albumin creatinine ratio (UACR) = 147 (IQR 82-330) mg/g, mean eGFR = 84 ml/minute/1.73 m2 (SD±19.3), HbA1c = 73 mmol/mol (SD±15) and 24h blood pressure = 147/82 mmHg (SD±12.0/8.1). Dapagliflozin reduced UACR by 44% (95% CI 17-78%, p<0.01), GFR by 10.6 (6-15) ml/minute/1.73m2 (p<0.01), HbA1c by 7.4 (5-10) mmol/mol (p<0.01) and 24h blood pressure by 4.1/2.9 mmHg (p=0.058/p<0.01). The CKD273 proteomic score improved from mean 0.457 with -0.217 (p<0.01) and renal risk category improved from 72% at high risk to 47% after dapagliflozin (p=0.032).

Conclusions: Dapagliflozin added to standard care in T2D patients with albuminuria significantly reduced the urinary CKD273 proteomic score and renal risk. This indicates a possible direct beneficial effect on the kidneys, which may explain part of the renal benefit of SGLT2i seen in clinical trials.

Disclosure

F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. M.K. Eickhoff: None. H. Mischak: Stock/Shareholder; Self; Mosaiques Diagnostics. M. Frimodt-Moller: None. P. Rossing: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. Other Relationship; Self; Novartis AG, Novo Nordisk A/S.

Funding

AstraZeneca
529-P: Hemoglobin Glycation Index Is Associated with Incident Chronic Kidney Disease in Subjects with Impaired Glucose Metabolism: A 10-Year Longitudinal Cohort Study
Authors: HUH JI HYE , KIM WONJIN , KIM MIN KYUNG
Published: June 2019

Objectives: We investigated associations between HGI and incident chronic kidney disease (CKD) in treatment naïve subjects with prediabetes or diabetes.

Methods: A prospective cohort study was conducted in 2,187 subjects with prediabetes or diabetes. The HGI was calculated as the measured HbA1c minus predicted HbA1c, which was calculated from the linear relationship between HbA1c and fasting plasma glucose levels. Incident CKD was defined as occurring if eGFR decreased to less than 60 mL/min per 1.73 m2 and decreased by more than 25% from baseline during follow-up. The hazard ratio (HR) for incident CKD was calculated using Cox models.

Results: The overall prevalence of CKD was 335 (15.3%) during the 10-year follow-up period. While the prevalences of CKD significantly increased from the first to third tertile of HGI, this phenomenon was not seen in HbA1c (Figure). In multivariate analysis, the highest HGI tertile group showed the highest adjusted HR for incident CKD (HR, 1.57; 95% CI, 1.06-2.34) and this was significant even after adjustment for HbA1c.

Conclusion: High HGI was associated with increased risk for incident CKD in treatment naïve subjects with prediabetes or diabetes. These finding suggest that HGI might provide additional information for predicting CKD in patients with impaired glucose tolerance independently of HbA1c levels.

Disclosure

J. Huh: None. W. Kim: None. M. Kim: None.
535-P: Relationship between Renal Capacities to Reabsorb Glucose and Kidney Disease in Patients with Diabetes
Authors: MATAR ODETTE , POTIER LOUIS , ABOULEKA YAWA , FUMERON FRÉDÉRIC , MOHAMMEDI KAMEL , HADJADJ SAMY , ROUSSEL RONAN , VELHO GILBERTO , MARRE MICHEL
Published: June 2019

Hyperglycemia can impair tubulo-glomerular balance and cause kidney disease by opening pre-glomerular resistances. Susceptibility to kidney disease is heterogeneous among diabetic patients, and renal capacities to reabsorb glucose may contribute to it. We studied if renal capacities to reabsorb glucose relate to kidney disease in diabetic patients. The diabetic patients attending over 6 months our tertiary referral center in Paris, France (where SGLT2 inhibitors are not available), were studied consecutively for their fractional glucose reabsorption (1-[urinary glucose x plasma creatinine]/[urinary creatinine x plasma glucose]) according to their glycemia (<6, 6-11, >11mM), and kidney disease (normo-, micro-, macroalbuminuria, and estimated Glomerular Filtration Rate (eGFR, CKP-EPI equation) >90, 90-60, 59-30, and <30-16 ml/min/1.73m2; patients with eGFR ≤15ml/min/1.73m2 were excluded). Of 637 participants, 106 displayed glycemia <6mM, 288 6-11mM, and 243 >11mM. Fractional glucose reabsorption was similar in participants with glycemia <6mM and 6-11mM: median 99.90 (interquartiles 99.60-99.94)%. It was lower in those with glycemia >11mM, proportional to kidney disease: normoalbuminuria (n=135) 93.50 (81.60-99.34)%, microalbuminuria (n=77) 96.56 (93.77-99.71)%, macroalbuminuria (n=31) 99.12 (94.20-99.64)% (p<0.001); eGFR >90ml/min/1.73m2 (n=111) 94.13 (82.34-98.58)%, 90-60ml/min/1.73m2 (n=72) 96.35 (87.81-99.75)%, 59-30ml/min/1.73m2 (n=46) 98.88 (92.19-99.78)%, <30-16 ml/min/1.73m2 (n=14), 99.11 (97.57-99.77)% (p<0.01). On multivariate analyses, fractional glucose reabsorption in participants with glycemia >11mM contributed independently to their urinary albumin excretions and eGFR values. Renal capacities to reabsorb glucose were linked to kidney disease in diabetic patients with glycemia >11mM. Inter-individual capacities to reabsorb glucose may contribute to kidney disease of diabetic patients.

Disclosure

O. Matar: None. L. Potier: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Sanofi. Y. Abouleka: None. F. Fumeron: None. K. Mohammedi: None. S. Hadjadj: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Servier. Research Support; Self; Bayer AG, Janssen Research & Development. Speaker's Bureau; Self; Abbott, Valbiotis. R. Roussel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. G. Velho: None. M. Marre: Advisory Panel; Self; Servier. Board Member; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S.
54-LB: Let’s Play! A Diabetes Education Board Game
Authors: CURL MICHELLE , POZEFSKY DIANE , JAIN NINA
Published: June 2019

Background: The adolescent years are challenging time for diabetes educators, medical providers and families with type 1 diabetes. We developed a unique board game to assess knowledge, increase dialogue, and provide education. The game curriculum utilizes Blooms taxonomy and focuses on the cognitive, affective and psycho-motor domains of educational learning. Game-based learning can enhance student/patient motivation and improve knowledge acquisition. Games also provide a safe format for the learner to try new experiences and gain insight from their successes and failures.

Objectives: To enhance dialogue among the diabetes educator, teenagers and parents regarding type 1 diabetes management. To assess players’ knowledge of diabetes and provide additional education and support.

Methods: Ninety parent-child dyads participated in the game over the course of 18 months. Thirty percent were teenage participants (13-17 yo). The game design encourages players to apply their skills and knowledge in simulated, real world scenarios. On every turn, players must use basic math skills to advance to the next challenge. The game focuses on the following diabetes self-management themes: glucose monitoring, physical activity, medication management, healthy eating, problem solving, exercise and sick day management.

Results: Diabetes educators reported increased dialogue and teen engagement during diabetes education. Game play facilitated the assessment of teens’ knowledge, skills and emotional well-being. Based on this assessment, educators addressed the specific needs of each parent-child dyad. Educators also reported improved interdisciplinary communication. Pediatric endocrinologists reported an improved ability to individualize patients’ medical care based on the identified knowledge/skill deficits.

Conclusion: This diabetes board game has the potential to improve dialogue and guide education for each parent-child dyad.

Disclosure

M. Curl: None. D. Pozefsky: None. N. Jain: None.
540-P: Time Is an Independent Risk Factor for Diabetic Nephropathy in African Americans (AA) Compared with Caucasians
Authors: FERRARI ALDO DE , OVALLE FERNANDO
Published: June 2019

Background: AA have a higher prevalence of diabetic nephropathy (DN) than Caucasians. However, the prevalence of DN between AA and Caucasians as a function of time is less well understood.

Methods: We retrospectively reviewed the medical charts of 1211 adults who consecutively presented to our diabetes clinic from 2001-10. We collected data from their initial clinic visit. We defined DN as microalbuminuria >300 mg/g or GFR <60 mL/min/1.73m2. Primary objectives were to estimate the prevalence of DN among AA and Caucasians, estimate DN prevalence as a function of time since diabetes diagnosis, and determine risk factors associated with DN.

Findings: The prevalence of DN among AA and Caucasians was 32% and 19.6%, respectively. The prevalence of DN increased as a function of time for both AA and Caucasians, but was significantly higher among AA >10 years after diabetes diagnosis (Figure). In multivariable logistic regression, having hypertension (OR = 3.0, 95% CI 2.03 - 4.49), diabetes for >10 years (2.64, 1.91 - 3.68), A1c >8% (1.40, 1.01 - 1.96), and being AA (1.88, 1.32 - 2.66) were independently associated with DN. Diabetes subtype, BMI, and gender were not associated with DN.

Interpretation: Differences in DN prevalence between AA and Caucasians appear ∼10 after diabetes diagnosis, independent of A1c and hypertension control. AA may benefit from early prevention and aggressive risk factors control.

Disclosure

A. De Ferrari: None. F. Ovalle: Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk A/S.
549-P: Renal Outcome of Patients with Type 2 Diabetes Exhibiting Normoalbuminuric Renal Insufficiency
Authors: NISHIWAKI YUI , HANAI KO , BABAZONO TETSUYA
Published: June 2019

Recent studies have identified a unique subgroup of patients with type 2 diabetes exhibiting reduced renal function in spite of being normoalbuminuric; however, information is limited regarding the clinical course of these patient. Here, we evaluated renal outcome of patients with normoalbuminuric renal insufficiency. This was a single-center, historical cohort study. We studied 7,152 adult Japanese patients with type 2 diabetes (mean age: 61 years, men: 64%) who had never undergone renal replacement therapy (RRT). The subjects were classified into 6 groups based on the baseline estimated glomerular filtration rate (eGFR): ≥ 60 or < 60 mL/min/1.73 m2and urinary albumin-to-creatinine ratio: ACR (<30: normoalbuminuria, 30-299: microalbuminuria, or ≥ 300 mg/g: macroalbuminuria). Two separate endpoints were defined as follows: 1) ≥ 30% decline in eGFR from the baseline value or initiation of RRT, whichever came first, and 2) annual decline in eGFR, estimated using a linear mixed-effect model. During a median follow-up of 5.7 years, 1,374 patients reached the first endpoint. The adjusted hazard ratios (vs. patients with normal eGFR and normoalbuminuria [n= 3,881]) for patients with reduced eGFR and normoalbuminuria (n= 823), normal eGFR and microalbuminuria (n= 1,010), reduced eGFR and microalbuminuria (n= 508), normal eGFR and macroalbuminuria (n= 235), and reduced eGFR and microalbuminuria (n= 695) were 1.55, 2.74, 4.15, 10.00, and 29.02, respectively (all p< 0.001). The adjusted annual decline in eGFR (least square mean ± standard error) in patients with reduced eGFR and normoalbuminuria was 0.66 ± 0.10 mL/min/1.73 m2/year, which was significantly lower than those in other 5 groups (p< 0.001).

In conclusion, patients with type 2 diabetes manifesting normoalbuminuric renal insufficiency are likely to have a better kidney prognosis, with an extremely slow decline rate of renal function.

Disclosure

Y. Nishiwaki: None. K. Hanai: None. T. Babazono: None.
555-P: Poor Sleep Quality Linked to Decreased Brain Gray Matter Density in Type 2 Diabetes
Authors: CABRERA-MINO CRISTINA , ROY BHASWATI , WOO MARY A. , KUMAR RAJESH , CHOI SARAH E.
Published: June 2019

Background: Adults with type 2 diabetes mellitus (T2DM) frequently report poor sleep quality. However, the impact of poor sleep, which may exacerbate brain changes in T2DM patients, is unclear. Study aim was to evaluate sleep symptoms and the relationship between sleep quality and brain changes in T2DM using high-resolution magnetic resonance imaging (MRI) procedures.

Methods: Brain MRI images were collected from 17 T2DM patients (age 55.8 ± 7.0 years, 7 males) and 52 controls (age 55.7 ± 1.8 years, 32 males) using a 3.0-Tesla MRI scanner. Sleep symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI) and images evaluated using gray matter density (GMD) maps. Statistical analysis included partial correlations and ANCOVA (covariates: age, sex).

Results: T2DM patients showed worse sleep symptoms compared to controls (7.2 ± 4.0 vs. 3.6 ± 2.0; p<0.001). There were negative correlations between GMD (including frontal cortices, hippocampi, and cerebellum) and sleep quality (lower density in persons with higher PSQI/worse sleep) [left cerebellum GMD vs. PSQI, r = -0.742, p = 0.002; right GMD vs. PSQI, r = -0.722, p = 0.002].

Conclusion: Adults with T2DM show reduced GMD negatively correlating with increased sleep disturbance symptoms. Potential mechanisms are unclear, but may involve altered glucose metabolism or hypoxic-induced processes. Efforts to improve sleep quality may help mitigate brain changes in T2DM patients.

Disclosure

C. Cabrera-Mino: None. B. Roy: None. M.A. Woo: None. R. Kumar: None. S.E. Choi: None.

Funding

National Institute of Nursing Research (1R01NR017190-01A1)
557-P: Impact of Extensive HbA1c Control on Major Microvascular Complications in Type 2 Diabetes Mellitus with Short Duration of Disease
Authors: TAVAKOLI MITRA , ISHIBASHI FUKASHI
Published: June 2019

The aim of this study was to investigate the impact of extensive HbA1c control on major microvascular complications including neuropathy, retinopathy and nephropathy in T2DM patients with short duration. Detailed Clinical (e.g., full Lipid profile test, BMI, Blood Pressure, eGFR), ophthalmic (e.g., Fundus Photography, Optical Coherence Topography (OCT), Corneal Confocal Microscopy (CCM)) and neurological examinations (e.g., symptoms, electrophysiology, quantitative sensory testing, Cardiac Autonomic Neuropathy tests) were performed in 76 patients with T2DM at baseline and after glycemic control (GC) with or without Extensive HbA1C control (EHC) over 4 years along with 48 controls with normal glucose tolerance (NGT) and 34 subjects with impaired glucose tolerance (IGT). The mean HbA1c levels during whole follow-up period were closely related with the improvement in neurological markers. The multiple regression analysis indicates that the changes in all Corneal Nerve markers (CNF) and neurophysiological measures were closely associated with the mean HbA1c level over whole follow-up period. Higher SD and CV of HbA1c levels were negatively associated with some CNF and neurophysiological measures. The high baseline HbA1c levels deteriorated many neurological markers. In this study patients with poorly controlled type 2 diabetes returned to IGT by normalizing HbA1c level for 2 years without hypoglycemia. Nephropathy reduced from 34.2% to 18.4%. However, the prevalence of retinopathy progressed from 7.9% at baseline to 13.2%. Prevalence of neuropathy reduced from 13.2% to 2.6%. Although improvement of neurological markers in this study was significant, but the changes were small. The intensive GC in T2DM with short duration is associated with a reduction in microvascular complications (mostly albuminuria). The normalized HbA1c levels are more effective than standard care for preventing the development of neuropathy, but not retinopathy.

Disclosure

M. Tavakoli: None. F. Ishibashi: None.
56-LB: HCP Information: Drowning in Resources, Lacking Confidence?
Authors: MCDERMOTT JAMES M. , LEVINE BRIAN , LACKNER JOHANNA , SHOGER ERIK , CLOSE KELLY L.
Published: June 2019

Objective: This study sought to identify gaps in diabetes care information resources for healthcare professionals (HCPs), as well as their confidence administering diabetes care.

Methods: In July 2018, a survey was delivered to 286 HCPs, including U.S. primary care physicians (PCPs), nurse practitioners (NPs), physician assistants (PAs), and certified diabetes educators (CDEs), to assess confidence in treating patients with diabetes, current use of diabetes information resources, and needs not met by existing resources. Survey respondents treated an average of at least 40 patients with diabetes per month.

Results: On average, HCPs are using 24 different resources to stay informed on developments in diabetes care. Over 60% of surveyed HCPs do not feel fully comfortable staying up to date with care guidelines and medication/technology advances, and 96% are interested in a consolidated diabetes information hub. Further, 59% of CDEs, 72% of PCPs, 84% of NPs, and 90% of PAs lack full confidence in their ability to help patients self-manage their diabetes. PAs have the lowest confidence in their ability to start every diabetes therapy and technology. Confidence among the other HCPs in initiating medications is high, though apart from CDEs, few are comfortable starting diabetes technology; only 17% of PAs, 32% of NPs, and 39% of PCPs are confident initiating CGM.

Conclusions: These results suggest that many HCPs lack confidence in their abilities to keep up with developments in diabetes and effectively help patients manage their diabetes. The availability of a consolidated diabetes information resource for HCPs has potential to enable better care delivery, improve outcomes, and reduce provider overwhelm.

Disclosure

J.M. McDermott: Other Relationship; Self; Various. B. Levine: Other Relationship; Self; Various. J. Lackner: None. E. Shoger: Other Relationship; Self; Abbott Laboratories, Ascensia Diabetes Care, Dexcom, Inc., Insulet Corporation, Medtronic, Sanofi, Senseonics, Tandem Diabetes Care, Valeritas, Inc. K.L. Close: Other Relationship; Self; Various diabetes companies.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
560-P: Thermal Indicators of Previously Undiagnosed Diabetic Peripheral Neuropathy
Authors: BURGE MARK R. , CALDER CHRISTOPHER STEWART , WIGDAHL JEFFREY , JOSHI VINAYAK , GUO XIAOSHAN , CARMICHAEL JUSTIN C. , SOLIZ PETER
Published: June 2019

Purpose: Neurological clinical exams, quantitative sensory tests (QST), and nerve conduction studies (NCS) have been reported to have low accuracy in diagnosing diabetic peripheral neuropathy (DPN). This study explores the use of infrared (thermal) video imaging to detect small and large fiber DPN.

Methods: 48 subjects with and 148 subjects without DPN were studied and compared to age-matched control subjects (n=84). All subjects’ feet were examined for sores, deformities, and other signs of disease, and patients with recent foot surgeries were excluded. Monofilament and vibration threshold testing ware performed on all subjects. Thermal videos were collected for all subjects, and NCS exams were performed on a subset of subjects. Thermal imaging followed a standard procedure: Imaging pre- and post-cooling to 2°C. A thermal classification model using thermal features extracted from the videos was developed with NCS as the reference standard to assess the performance of thermoregulation models.

Results: Monofilament and vibration test results were compared with clinical diagnoses and had sensitivities of 52% and 57%, respectively. Sensitivity and specificity increase to 74% and 85% when the two tests were combined in an “either/or” decision. NCS was performed on 39 subjects: 11 control subjects, 12 subjects with clinical DPN, and 16 subjects with DM but without DPN. QST demonstrated a best sensitivity of 59% for the vibration test and a best individual specificity of 100% for the monofilament test when compared to NCS. When combined, QST demonstrated best overall sensitivity and specificity of 63% and 87%. The thermal model returned a sensitivity/specificity of 82%/94% and 91%/75% for different cut-points.

Conclusions: Thermal recovery modeling from a cold stimulus yielded superior agreement with clinical and NCS diagnoses as compared to QST in the detection of DPN. A thermal imaging device can be made that is feasible for use in clinics at a lower cost than NCS devices.

Disclosure

M.R. Burge: None. C.S. Calder: None. J. Wigdahl: None. V. Joshi: None. X. Guo: None. J.C. Carmichael: None. P. Soliz: Stock/Shareholder; Self; VisionQuest Biomedical LLC.

Funding

National Institutes of Health
561-P: Serum C-Peptide Concentrations Are Inversely Associated with Cardiovascular Autonomic Neuropathy in Type 2 Diabetic Individuals With and Without Renal Impairment Independently of Estimated Glomerular Filtration Rate
Authors: CHUNG JIN OOK , PARK SEON-YOUNG , CHO DONG HYEOK , CHUNG DONG JIN , CHUNG MIN YOUNG
Published: June 2019

Cardiovascular autonomic neuropathy (CAN) is a significant cause of cardiovascular morbidity and mortality in patients with type 2 DM. C-peptide is suggested as a bioactive peptide with protective roles on microangiopathy. However, due to renal metabolism of C-peptide, previous studies have been limited to diabetic patients without renal impairment. Serum C-peptide levels might be increased despite reduced beta cell function in patients with renal impairment. Therefore, we tested the hypothesis that C peptide would relate to the risk of CAN in patients with type 2 DM independently of renal function. A total of 1070 type 2 diabetic patients were investigated in this cross-sectional study. Prior dialysis or renal transplantation was excluded. CAN was diagnosed by a cardiovascular reflex test. Fasting C-peptide, 2-hour postprandial C-peptide, and ΔC-peptide levels were measured. The estimated glomerular filtration rate (eGFR) was calculated from CKD-EPI equation. In individuals with and without renal impairment, patients with CAN showed lower levels of fasting C-peptide, postprandial C-peptide and ΔC-peptide. In multivariate analysis, serum C-peptide levels were significantly associated with CAN (OR, 0.80; 95% CI, 0.67-0.96 for fasting C-peptide, p=0.014; OR, 0.78; 95% CI, 0.64-0.95 for postprandial C-peptide, p=0.013; OR, 0.80; 95% CI, 0.66-0.97 for ΔC-peptide, p=0.023) after adjustment for age, gender and other confounders including eGFR. Our results show that serum C-peptide levels are inversely associated with CAN in type 2 diabetic patients with and without renal impairment independently of eGFR. These findings might suggest the beneficial effects of serum C-peptide levels on CAN independently of eGFR.

Disclosure

J. Chung: None. S. Park: None. D. Cho: None. D. Chung: None. M. Chung: None.
562-P: The Effect of Vitamin D Supplementation on the Cytokines Levels in Patients with Type 2 Diabetes Mellitus and Diabetic Neuropathy
Authors: STEPANOVA ANNA P. , KARONOVA TATYANA L. , GALAGOUDZA MICHAEL , VASILEVA ELENA YU , JUDE EDWARD B.
Published: June 2019

Background: Inflammation plays an important role in the pathogenesis of diabetic neuropathy (DN) in patients with type 2 diabetes (DM2). It seems that vitamin D ((VitD) could be involved in this process, however, the relationship between VitD status and inflammatory markers has not been wildly studied.

Hypothesis: The aim was to study the association between VitD status and inflammatory markers in patients with DM2 and DN.

Methods: The single-centre randomized study included 62 subjects with DM2 and DN (more than 4 points according to NDS), HbA1c up to 9%. Antihyperglycemic treatment was stable during the study. Patients were randomized in two groups: 5000 IU (group I) and 40000 IU (group II) of cholecalciferol supplementation per week. Body mass index (BMI), glycated hemoglobin (HbA1c), serum 25(OH)D level, Interleukins 6, 10 (IL-6, IL-10) were determined at baseline and after 24 weeks of treatment. The correlation analysis was evaluated by Pearson test.

Results: Group I (n = 31, F16) and Group II (n = 31, F15) were matched for age, gender, BMI and baseline HbA1c levels. VitD insufficient/deficiency was revealed in 78% of diabetic patients with DN. After 6 months of VitD supplementation, the BMI, HbA1c and IL-6 levels significantly decreased, and 25(OH)D and IL-10 concentration increased only in Group II. We found associations between serum 25(OH)D and IL-6 (r = -0.912, p = 0.017) as well as IL-10 (r = 0.903, p = 0.014), and between HbA1c and IL-6 (r = 0.825, p = 0.031) and IL-10 (r = -0.897, p = 0.025) exclusively in Group II after treatment.

Conclusions: VitD supplementation in 40000 IU of cholecalciferol per week during 6 months was associated with improved vitamin D status, pro-inflammatory markers and better glycemic control in patients with DM2 and DN. Vitamin D supplementation in 5000 IU per week did not change vitamin D status and inflammatory markers in this population.

Disclosure

A.P. Stepanova: None. T.L. Karonova: None. M. Galagoudza: None. E.Y. Vasileva: None. E.B. Jude: None.