bluuebunny/crossref_metadata_2025 huggingface dataset:
565-P: Serum 25-Hydroxy Vitamin D Levels in Relation to Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes
Authors: ZHANG LEI , GU YAN , YANG YUXIU , ZHU YAMEI , YIN XIAOYAN , DONG YANHU
Published: June 2019

Vitamin D deficiency is not only related to bone-related diseases but also associated with cardiovascular disease, diabetes, cancer and autoimmune diseases. Previous studies show that vitamin D deficiency increases risk of diabetic peripheral neuropathy (DPN). Data is limited among Chinese patients with type 2 diabetes. In this cross-sectional study, we enrolled 5362 patients (2359 men and 3003 women aged 30 to 89 years) with type 2 diabetes from Jan 1, 2016 to Oct 31, 2018. Serum 25-hydroxyvitamin D (25(OH)D) level was measured by electrochemiluminescence assay. Vitamin D deficiency was defined as Serum 25(OH)D level < 20 ng/mL according to the Endocrine Society Clinical Practice Guideline 2011. Diabetic peripheral neuropathy was diagnosed by motor/sensory nerve conduction velocity. Patients with diabetic peripheral neuropathy had lower serum 25(OH)D concentration (16.81±3.83 ng/mL vs. 18.05±4.11 ng/mL, P<0.05) compared with those without neuropathy. The prevalence of vitamin D deficiency was higher in patient with neuropathy than those without the complication (83.2% vs. 71.4%, P<0.05). We did not find gender difference on the prevalence of vitamin D deficiency. In the logistical regression model, Vitamin D deficiency was associated with increased risk of diabetic neuropathy, after adjustment of age, gender, duration of diabetes, smoking, body mass index, systolic blood pressure, fasting glucose, HbA1c, fasting C-peptide, total cholesterol, and microalbuminuria, the corresponding odds ratio was 1.76 (95% CI 1.05-3.37) (P<0.05). Vitamin D deficiency, a common hypovitaminosis in Chinese patients with type 2 diabetes, is independently associated with increased risk for diabetic peripheral neuropathy. Whether vitamin D supplementation improves diabetic peripheral neuropathy deserves further study.

Disclosure

L. Zhang: None. Y. Gu: None. Y. Yang: None. Y. Zhu: None. X. Yin: None. Y. Dong: None.
576-P: Prevalence of Vitamin B12 Deficiency and Clinical Neuropathy with Metformin Use in Type 2 Diabetes Mellitus Patients
Authors: KOTHIWALE VEERAPPA , CHAFEKAR NAHUSH D. , BABALICHE PRAKASH , CHOUGULE NIKHIL A.
Published: June 2019

Background and Objectives: Metformin is a cornerstone in the treatment of type 2 DM (type 2 diabetes mellitus) and is used as 1st line therapy. Studies showed that an average of 10-30% of patients on metformin for longer duration and at higher dosage had Vit. B12 deficiency. Sr.(Serum) Vit. B12 levels were studied and correlated with presence of peripheral neuropathy in type 2 DM patients on long term Metformin, attending OPD of our hospital.

Methods: 100 consecutive type 2 DM patients on Metformin for >3 years, aged >18 years attending OPD of the Dept. of Medicine from 1st January - 31st December 2017, were included in our study after the informed consent. Estimation of Sr. Vit. B12 levels was done and correlated with monofilament testing in all the study participants and metformin doses of 1 gm/day and >1 gm/day were classified.

Results: In our study, 35% of Diabetic patients on Metformin had Vit. B12 deficiency with mean 168.2 ± 17.9 pg/ml which also correlated with the abnormalities in the monofilament testing, graded on a scale of 1-10, 1 being severe peripheral neuropathy and 10 being normal. The mean monofilament score was found to be 6 out of 10. The remaining 65% had a mean Vit. B12 level of 502.3 ± 16.8 and a mean monofilament score of 8 out of 10. Total mean Vit. B12 level was found to be 619.2. By applying Chi square test as test of significance, odds of positive outcome for monofilament test in Vit. B12 deficient person is 25.5 and p value is significant (P<0.001). Degree of dosage of metformin did not have any significant correlation with Sr. Vit. B12 levels and monofilament score. We also found evidence of Megaloblastic anemia in study participants, with 29% of patients having high MCV with a mean of 98.4 ± 2.1 fl, and dimorphic (23%) and macrocytic (6%) picture on peripheral smear. The mean Hb range was 11.1 to 14.0 g/dL.

Conclusion: There is higher prevalence of Vit. B12 deficiency and linear correlation with peripheral neuropathy with long term Metformin use in type 2 DM patients which needs to be diagnosed and treated.

Disclosure

V. Kothiwale: None. N.D. Chafekar: None. P. Babaliche: None. N.A. Chougule: None.
578-P: Evaluation of Autonomic Function and Its Relation to Glucose Variability, Insulin Resistance, and Oxidative Stress in Prediabetes
Authors: DIMOVA RUMYANA , CHAKAROVA NEVENA , KIRILOV GEORGI , GROZEVA GRETA , TANKOVA TSVETALINA
Published: June 2019

Aim: The present study assesses the relation between cardiovascular autonomic function and some indexes of glycose variability, insulin resistance and oxidative stress in prediabetes.

Material and Methods: A total of 50 subjects - 12 males, mean age 55.6±9.7 years, mean BMI 28.4±6.4 kg/m2, divided into 2 groups according to glucose tolerance: 32 subjects with prediabetes and 18 subjects with normal glucose tolerance (NG) were included. Glucose tolerance was assessed by OGTT in accordance with WHO 2006 criteria. Plasma glucose was measured by hexokinase method and immunoreactive insulin - by immuno-chemiluminescence method at fasting, 120-minute and 180-minute during the test; and also oxLDL and 5-Nitrotyrosine - by ELISA method at fasting and 120-minute during the test. Indirect indexes of insulin resistance - HOMA-IR and insulin sensitivity - OGIS were calculated. HbA1c was assessed by immuno-turbidimetric, NGSP certified method. Continuous glucose monitoring was performed with blind sensor for professional use - FreeStyle Libre Pro - for a mean period of 13.6 ± 2.3 days.

Results: There was a significantly decreased parasympathetic tone during deep breathing test (p=0.009) and sympathetic tone at rest (p=0.021) and during Valsalva maneuver test (p=0.026) in prediabetes. Sympathetic activity was related to the standard deviation of glycemic excursions in prediabetes (F [1,31]=7.91, p=0.018); whilst parasympathetic activity was related to J-index and % time spent in glycemic range >7.8 mmol/l in prediabetes (F [1,31]=7.20, p=0.004) and with CONGA index in NGT (F [1,18]=6.75, p=0.025). No significant correlation between autonomic tone and the assessed markers of insulin resistance and oxidative stress was established.

Conclusions: The autonomic tone has been found to be declined in prediabetes. Glucose variability is probably an additional risk factor for autonomic dysfunction at these early stages of glucose intolerance.

Disclosure

R. Dimova: None. N. Chakarova: None. G. Kirilov: None. G. Grozeva: None. T. Tankova: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. Speaker's Bureau; Self; Lilly Diabetes, Novo Nordisk A/S, Servier.
579-P: Prevalence of and Risk Factors for Peripheral Neuropathy in Chinese Patients with Diabetes: A Multicenter Cross-Sectional Study
Authors: PAN QI
Published: June 2019

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, and its progression significantly worsens the patient’s quality of life. This study investigated the prevalence and risk factors associated with DPN in a large sample of Beijing individuals with type 1 and 2 diabetes, as well as compared the diagnostic methods for DPN. A total of 2,048 diabetic patients from 13 centers in Beijing were assessed for DPN through questionnaires and examination. Patients were divided into DPN group and suspected DPN/non-DPN group. The demographic, clinical and biological characteristics between the two groups were compared. Binary logistic regression analysis was performed to identify potential variables associated with DPN in diabetic patients. The diagnostic methods for DPN were also compared. Among the 2,048 diabetic patients, 73 cases of type 1 diabetes mellitus, 1,975 cases of type 2 diabetes were included in this study. Among them, 714 (34.86%) were identified with DPN, 537 (26.22%) were suspected of having DPN, and 797 (38.92%) were identified without DPN. Patient’s age, duration of diabetes, and diabetic retinopathy were the significant independent risk factor for DPN among patients with type 2 diabetes. The odds ratio (OR) was 1.439 (95% confidence interval (CI): 1.282-1.616, P < 0.001), 1.297 (95% CI: 1.151-1.462, P < 0.001), and 0.637 (95% CI: 0.506-0.802, P < 0.001), respectively. Ankle reflex, temperature sensation plus vibration sensation are the best screening test for patients with type 1 and 2 diabetes. The Youden indexes were 62.2 and 69.8%, respectively. The prevalence rates of DPN in the Chinese patients with type 1 and type 2 diabetes in Beijing were 21.92 and 35.34%, respectively. Patient’s age, duration of diabetes, and diabetic retinopathy are the independent risk factors for DPN.

Disclosure

Q. Pan: None.
58-OR: The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Transiently Delays Gastric Emptying Similarly to a Selective Long-Acting GLP-1 Receptor Agonist
Authors: URVA SHWETA , NAUCK MICHAEL A. , COSKUN TAMER , CUI XUEWEI , HAUPT AXEL , BENSON CHARLES , LOGHIN CORINA
Published: June 2019

A long-acting GLP-1 receptor agonist (RA) transiently delays gastric emptying (GE). We investigated the GE effect of a novel dual GIP and GLP-1 RA, tirzepatide (TZP), compared to that of a selective GLP-1 RA in nonclinical and clinical studies. No effect on GE was seen with GIP RA alone in mice. Combination of GIP RA with GLP-1 RA or a dual agonist, TZP, did not delay GE more than GLP-1 RA alone. The effect of TZP on GE was evaluated in a Phase 1 study, comprising 4 week multiple ascending dose (MAD; N=35) QW in healthy subjects and 4-week proof of concept (PoC) (N=53) in patients with T2DM. In MAD, TZP was administered QW at fixed doses of 0.5, 1.5, 4.5 mg, and a titration dose of 5-5-8-10 mg. A selective GLP-1 RA, dulaglutide (dula), 1.5 mg QW was also included. In PoC, TZP was administered QW at fixed doses of 0.5 mg and 5 mg, and at titration doses of 5-5-10-10 mg and 5-5-10-15 mg. Acetaminophen (APAP) was administered on Day -1 (prior to TZP or dula), at 24 hours after the first (Day 2) and fourth (Day 23) doses to coincide with peak TZP or dula exposure. Impact of TZP on GE was evaluated using APAP Cmax, AUC, and tmax, compared to placebo (PL). Baseline adjusted Cmax of APAP (ratio to Day -1) was used to compare the GE effect of TZP with that of dula. APAP Cmax decreased by approximately 50% and tmax was delayed by an hour after the first TZP dose (doses >1.5 mg), suggesting a delay in GE while AUC was not notably altered. Evaluation of APAP PK after the first and fourth doses of the fixed dose regimen of TZP showed that impact of TZP on GE was maximized after first dose (Day 2 vs. PL), and showed complete tachyphylaxis after repeated dosing (Day 23 vs. PL). Similarly, in the titration cohort, impact of TZP on GE was significant after the first dose. However, incomplete tachyphylaxis was observed after 4 weeks of TZP administration due to the titration regimen. Impact of the fixed doses of TZP on GE was comparable to that of a selective GLP 1 RA (dula).

Disclosure

S. Urva: None. M.A. Nauck: Advisory Panel; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sun Pharma. T. Coskun: Employee; Self; Eli Lilly and Company. X. Cui: Employee; Self; Eli Lilly and Company. A. Haupt: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Lilly Diabetes. C. Benson: Employee; Self; Eli Lilly and Company. C. Loghin: Employee; Self; Eli Lilly and Company.
593-P: Diabetes Enhances Translation of the mRNA Encoding CD40 in Müller Glia to Promote Retinal Inflammation
Authors: DIERSCHKE SADIE K. , TORO ALLYSON , MILLER WILLIAM P. , DENNIS MICHAEL D.
Published: June 2019

This study investigated the hypothesis that diabetes-induced hyperglycemia promotes retinal inflammation by augmenting translation of the immune costimulatory molecule CD40. In response to diabetes, Müller glia initiate retinal inflammation via activation of CD40. CD40 activation in Müller glia leads to ATP release, stimulation of P2X7 purinergic receptors on microglia/macrophages, and their subsequent release of inflammatory cytokines. Increased CD40 expression is a common feature of inflammatory diseases driven by CD40. Indeed, CD40 protein expression is elevated in Müller glia of diabetic mice, yet the mechanisms responsible for this increase have not been fully explored. In microglia/macrophages, inflammatory cytokines enhance CD40 gene transcription via cis-elements in the CD40 promoter. However, cytokine-mediated CD40 transcriptional upregulation is not sufficient to explain a model wherein retinal inflammation is initiated by CD40 expression in Müller glia. A recent genome-wide functional screening revealed that the untranslated region of the mRNA encoding CD40 was capable of promoting translation independent of the mRNA m7GTP cap. Our laboratory has previously demonstrated that diabetes-induced hyperglycemia promotes O-GlcNAcylation of the translational repressor 4E-BP1, leading to enhanced cap-independent mRNA translation. In the present study, in vivo translation of the CD40 mRNA was enhanced in Müller glia of STZ-diabetic RiboTag mice concomitant with increased protein O-GlcNAcylation. Enhanced O-GlcNAcylation was sufficient to promote CD40 mRNA translation in both retina and cells in culture, and O-GlcNAcylation-induced CD40 mRNA translation was ablated by 4E-BP deletion. In the retina of diabetic 4E-BP-deficient mice, CD40 translation and retinal pathology were normalized. Thus, therapeutic approaches targeting diabetes-induced defects in mRNA translation may be beneficial for preventing diabetic retinopathy progression.

Disclosure

S.K. Dierschke: None. A. Toro: None. W.P. Miller: None. M.D. Dennis: None.

Funding

American Diabetes Association/Pathway to Stop Diabetes (1-14-INI-04 to M.D.D.)
598-P: Lower Hematocrit Is Predictive of Treatment-Required Eye Diseases in Japanese Patients with Diabetes Mellitus
Authors: YAMAMOTO MASAHIKO , FUJIHARA KAZUYA , OSAWA TAEKO , HARADA MAYUKO , ISHIZAWA MASAHIRO , SUZUKI HIROSHI , ISHIGURO HAJIME , SEIDA HIROYASU , YAMANAKA NAUTA , MATSUBAYASHI YASUHIRO , SONE HIROHITO
Published: June 2019

Hematological markers such as hematocrit (Hct), hemoglobin (Hb) or red blood cell (RBC) count were reported to be associated with the development of diabetic retinopathy with conflicting results. Moreover, which of these markers is the best to predict incident retinopathy remains unknown. To clarify this, we utilized ICD-10 and medical treatment codes from a nationwide claims database that included 7,182 participants (1,490 women, mean age 50.8 y, HbA1c 6.9%, mean follow-up period 5.5y) classified as having diabetes mellitus or vision-threatening treatment-required diabetic eye diseases (TRDED). Multivariate Cox regression model was used to identify predictors of TRDED. During the study period, 177 patients developed TRDED (4.5/1000 person-years). Cox analysis demonstrated that the lower Hcts were significant predictors TRDED and lower Hcts were more predictive than lower RBC counts. The Hb level was not significantly associated with TRDED. Hazard ratios (HRs) per 1 standard deviation (SD) increase in Hct, RBC count and Hb for incident TRDED were 0.792 (95% confidence interval [CI], 0.666-0.942), 0.874(0.765-0.998), and 0.861 (0.725-1.023) as continuous variables, respectively. The interaction between Hct and RBC count was not statistically significant. Multivariate tertile analysis also revealed that a lower Hct was more predictive of TRDED (HR 2.03 [95% CI, 1.33-3.08] for the bottom [≤43.4%] vs. the top [≥46.7%] tertile [P value = 0.001]) than lower RBC counts (HR 1.54 [95% CI, 0.99-2.38] for the bottom [≤468×104/m3] vs. the top [≥507×104/m3] [P value = 0.054]). These findings demonstrated that lower Hcts were significant predictor of vision-threatening retinopathy for people with diabetes and more useful than the RBC count or Hb. Association of the influence of these three markers on severe retinopathy awaits further investigation.

Disclosure

M. Yamamoto: None. K. Fujihara: None. T. Osawa: None. M. Harada: None. M. Ishizawa: None. H. Suzuki: None. H. Ishiguro: None. H. Seida: None. N. Yamanaka: None. Y. Matsubayashi: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
6-OR: Estimated Glucose Disposal Rate and Major Vascular Events in Type 1 Diabetes: A 10-Year Follow-Up Study
Authors: GAROFOLO MONIA , GUALDANI ELISA , GIANNARELLI ROSA , ARAGONA MICHELE , CAMPI FABRIZIO , LUCCHESI DANIELA , DANIELE GIUSEPPE , MICCOLI ROBERTO , FRANCESCONI PAOLO , PRATO STEFANO DEL , PENNO GIUSEPPE
Published: June 2019

Estimated Glucose Disposal Rate (eGDR), a validated tool to estimate insulin sensitivity (IS) in T1DM [eGDR = 21.158 - (0.09 x WC, cm) - (3.47 x hypertension, yes = 1) - (0.551 x HbA1c, %)], has been associated to all-cause death. The relationship between eGDR and major vascular (CV) events was evaluated in 736 T1DM enrolled in an observational, single-centre study over a 10-year follow-up. Incidence of CV and coronary events were obtained by interrogating hospital discharge registers. Mean eGDR was 7.51±2.26 (M±SD) mg/kg/min (median 8.26; IQR 5.53-9.29). According to the “Swedish National Diabetes Register,” eGDR was stratified in: C1: ≥8.0 (N. 399, 54.2%, ref); C2: 6.0-7.99 (N. 121, 16.4%); C3: 4.0-5.99 (N. 144, 19.6%) and C4: <4.0 mg/kg/min (N. 72, 9.8%). Compared to C1, C2-4 showed a worse risk profile. A total of 49 CV events (defined as first of MI, stroke, coronary, carotid or peripheral revascularization) occurred over a follow-up of 10.38±2.88 years (6.7%, 6.42 x1000 PYs). By Kaplan-Meier, incidence increased across eGDR categories: C1, 2.3%; C2, 4.1% (HR [95% CI] 1.79 [0.60-5.35]); C3, 11.8% (5.68 [2.53-12.75]); C4, 25.0% (12.76 [5.73-28.43], p<0.0001). After adjustment for multiple confounders, risk of CV events was significantly increased in C4 (5.18 [2.11-12.72], p<0.0001). Further adjustment for variables strictly related to IS (HDL, triglycerides, ACR) did not exclude C4 eGDR as an independent covariate. Over a follow-up of 10.47±2.74 years, 35 coronary events (first of MI or coronary revascularization) occurred (4.8%; 4.54 x 1000 PYs). Incidence increased across eGDR categories: C1, 2.3%; C2, 0.8% (0.35 [0.04-2.76]); C3, 7.6% (3.65 [1.51-8.81]); C4, 19.4% (9.64 [4.17-22.30], p<0.0001). After adjustment for multiple confounders, risk of coronary events was significantly increased in C4 (4.78 [1.90-12.04], p=0.001). Even so after further adjustment for variables strictly related to IS. Thus, in our T1DM, eGDR was a long-term independent predictor of vascular events.

Disclosure

M. Garofolo: None. E. Gualdani: None. R. Giannarelli: None. M. Aragona: None. F. Campi: None. D. Lucchesi: None. G. Daniele: None. R. Miccoli: None. P. Francesconi: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. G. Penno: None.
608-P: High er Level of Angiopoietin-Like Protein-2 Is Associated with Diabetic Macular Edema in Patients with Type 2 Diabetes Mellitus
Authors: ZHANG NING , AN YAXIN , YIN RUILI , ZHAO DONG
Published: June 2019

Background: Diabetic macular edema (DME) is characterized by hyperpermeability of retinal blood vessels and subsequent formation of hard exudates and macular edema. ANGPTL2 is associated with microvascularization and angiopoiesis, so we investigate the relationship between ANGPTL2 and occurrence of DME.

Methods: 222 patients with type 2 diabetic patients were enrolled and divided into 3 groups with matched gender, age and BMI: 1) DM group: patients without diabetic retinopathy (DR) and DME, 2) DR without DME group, and 3) DR with DME group. All subjects were performed optical coherence tomography scanning (OCT) and fundus photography. ANGPTL2 was measured by Elisa. We analyzed the OCT values of concentric circles of macular central fovea with average diameters of 1 mm (R1), 3 mm (R3) and 6 mm (R6) to diagnose DME. Multivariable regression analysis was performed to estimate association between ANGPTL2 and DME.

Results: Values of duration of diabetes, fasting C-peptide, postprandial C-peptide 1h, CRP, history of cataract and Statins treatment showed significant differences among three groups (p<0.05). ANGPTL2 levels in DM, DR without DME, DR with DME groups were 3.55±1.56, 3.68±1.59, 4.45±1.8ng/ml, respectively (P=0.012). In multivariable linear regression, Angplt2 was significantly different among three groups after adjustment for age, gender, BMI, glycosylated hemoglobin, ALT, AST, GGT, and fasting C peptide (P=0.023).

Conclusions: Our findings suggest that ANGPTL2 is higher in patients both with DR and DME. Increased level of ANGPTL2 may take part in the progression of diabetic macular edema in type 2 diabetes mellitus.

Disclosure

N. Zhang: None. Y. An: None. R. Yin: None. D. Zhao: None.
609-P: Effect of Rosuvastatin on Lipoprotein Sphingolipids in Patients with Type 2 Diabetes
Authors: KELLY CLARE B. , HAMMAD SAMAR M. , KLEIN RICHARD L. , LOPES-VIRELLA MARIA F. , GOSMANOVA ALBINA , LEYVA MISTI J. , ASTON CHRISTOPHER E. , LYONS TIMOTHY
Published: June 2019

Statin therapy reduces cardiovascular risk in type 2 diabetes (T2DM), partly by improving dyslipidemia, and partly through ‘pleiotropic’ effects. Sphingolipids, including ceramides, are amphiphilic components of lipoprotein surface monolayers. Sphingolipids regulate lipoprotein surface fluidity, and include key signaling molecules: ceramides are specifically associated with apoptosis and risk for premature coronary heart disease. Effects of statins on the sphingolipid content of lipoproteins are poorly defined.

Using liquid chromatography/electrospray ionization-tandem mass spectrometry, we determined fasting plasma concentrations of individual ceramides (Cer), sphingomyelins (SM), and glycosphingolipids (hexosyl- and lactosyl-Cer) in plasma from 19 men and 21 women with T2DM, before and after treatment with rosuvastatin (10 mg/day, 6 weeks). Exclusion criteria were use of ‘statins’ in the preceding 6 months, and any current use of lipid-modifying agents. Using existing lipoprotein compositional data, we calculated effects of rosuvastatin therapy on non-HDL sphingolipid content.

Results: Rosuvastatin reduced total cholesterol (C) (by 33%), triglycerides (20%), LDL-C (49%), and non-HDL particle number (34%); HDL-C was unaffected. It decreased total SM (15%), Cer (29%), and hexosyl- (30%) and lactosyl- (34%) Cer, independent of gender. Assuming HDL composition was unaffected, rosuvastatin reduced non-HDL SM by 42% and Cer by 61%: these reductions remained significant after correction for non-HDL-C and/or non-HDL lipoprotein surface area.

Conclusions: In T2DM, rosuvastatin lowers not only the number of non-HDL particles, but also the sphingolipid, and especially the Cer, content of each particle. This effect is independent of gender, potentially anti-atherogenic, and may represent a new pleiotropic effect of statins. Further studies are needed to confirm these findings in isolated lipoprotein classes, and to determine mechanism(s).

Disclosure

C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. A. Gosmanova: None. M.J. Leyva: None. C.E. Aston: None. T. Lyons: None.
61-LB: Voluntary Wheel-Running Improves Dynamic Glucose Disposal in Diet-Induced Obese Mice: A Stable-Isotope Approach
Authors: ALLERTON TIMOTHY , KOWALSKI GREG M. , FLOYD ELIZABETH , STEPHENS ELIZABETH
Published: June 2019

Methods such as the hyperinsulinemic-euglycemic clamp have demonstrated improved insulin sensitivity in exercise-trained mice, but fail to recapitulate a dynamic physiological route of glucose metabolism. Therefore, we sought to test the effect of exercise (voluntary wheel running; VWR) on postprandial glucose dynamics by using a stable isotope labelled oral glucose tolerance test (SI-OGTT) incorporating complimentary deuterium glucose tracers at 1:1 ratio (2-2H-glucose and 6-6 2H-glucose; 2g/kg lean body mass) to distinguish between endogenous glucose concentrations (index of EGP; tracer less glucose) and meal (load) derived glucose which provides an index of whole-body glucose disposal. SI-OGTT was performed in C57/BL6J mice after 8 weeks on a high fat diet (45% fat). Mice were then randomized to either a wheel running cage (n=13, HFD Ex) or normal cage (n=13, HFD Sed) while maintaining the HFD for 4 weeks before performing a SI-OGTT. HFD Ex mice demonstrated improvements in whole blood glucose total AUC that was attributed primarily to a reduction in the endogenous glucose concentration (tracer less glucose) AUC. HFD Ex mice also demonstrated significantly lower 2-2H-glucose and 6-6 2H-glucose tracer excursions. Serum insulin levels measured at 0 and 15-minutes post glucose gavage were significantly elevated in the HFD Sed mice, whereas HFD Ex mice demonstrated the expected reduction at both time points. Overall, VWR appears to have improved postprandial hepatic insulin sensitivity and increased whole-body glucose disposal. Finally, these results demonstrate the benefits of VWR on hepatic insulin sensitivity by combining a more physiological route of glucose administration (oral glucose) with the resolution of stable isotope tracers. We clearly demonstrate the SI-OGTT to be a sensitive and cost-effective method to measure exercise adaptations in DIO-mice, which only requires as little as 2 µl of tail blood.

Disclosure

T. Allerton: None. G.M. Kowalski: None. E. Floyd: None. J.M. Stephens: None.

Funding

National Center for Complementary and Integrative Health (T32AT004094 to T.A.); Office of Dietary Supplements (P50AT002776)
61-OR: ADA Presidents' Select Abstract: Characterization of Beta-Cell Function with Autoantibodies, Islet Pathology, and Genetics after 50 Years of Insulin Dependence
Authors: YU MARC GREGORY , PEZZOLESI MARCUS G. , KEENAN HILLARY A. , POBER DAVID M. , HE ZHIHENG , TINSLEY LIANE J. , DORIA ALESSANDRO , BONNER-WEIR SUSAN , KING GEORGE L.
Published: June 2019

Characterization of persistent beta-cell function in response to metabolic stimuli with HLA and monogenic genotypes and pancreatic morphology in a large group of people with long duration of type 1 diabetes (T1D) has not been reported. In the Joslin Medalist Study (“Medalists”), which enrolled people with ≥50 years of T1D (n=1019), we determined whether significant associations exist between beta-cell function, autoantibodies (AAb), islet morphology, and genetic risks for T1D and monogenic diabetes. In this cohort, 32% exhibited C-peptide>0.05 ng/mL while 44% had GAD/IA2 AAb. In those with mixed meal tolerance test (MMTT, n=516), 6% responded with doubling of baseline C-peptide, without a related change in AAb status. Longitudinally (n=181, over a median of 4 years), C-peptide levels increased in 12% (n=22) and decreased in 37% (n=67). Among those with repeated MMTT, 5% (3/56) and 16% (9/56) had similar waxing and waning responses, respectively. Postmortem examination of 68 Medalist pancreases showed that all contained scattered insulin-positive cells, with three categories: A) only scattered singlets/doublets (n=9); B) scattered plus few insulin-positive cells in some islets (n=45); and C) scattered plus some lobes with islets having many insulin-positive cells (n=14). 30 Medalists with baseline C-peptide ≥0.1 ng/mL underwent a hyperglycemic/arginine clamp, to which 47% responded. Genetic screen for monogenic diabetes on all Medalists studied with the clamp showed 10 exhibiting monogenic variants, with HLA-/AAb- and HLA+/AAb- Medalists responding most to stimuli.

In summary, these results show that all Medalists retained insulin-positive beta-cells, with many responding to metabolic stimuli even after 50 years of T1D. Medalists are heterogeneous with respect to beta-cell function and many with HLA+ diabetes risk alleles also have monogenic variants, indicating the importance of genetic testing for clinically-diagnosed T1D.

Disclosure

M. Yu: None. M.G. Pezzolesi: None. H.A. Keenan: Employee; Self; Sanofi Genzyme. D.M. Pober: None. Z. He: None. L.J. Tinsley: None. A. Doria: Research Support; Self; Sanofi-Aventis. S. Bonner-Weir: Advisory Panel; Spouse/Partner; Semma Therapeutics, Inc. G.L. King: Research Support; Self; Sanofi.

Funding

Nunnally Foundation; Beatson Pledge Fund; National Institute of Diabetes and Digestive and Kidney Diseases
612-P: Eicosapentaenoic Acid (EPA) Inhibits Human HDL Oxidation in a Concentration-Dependent Manner at a Pharmacologic Dose In Vitro
Authors: SHERRATT SAMUEL , MASON R. PRESTON
Published: June 2019

Aim: Prescription eicosapentaenoic acid (EPA) reduced cardiovascular events in the REDUCE-IT study population, including patients with diabetes. As EPA has been previously shown to reduce LDL oxidation, we investigated if it may prevent HDL oxidation at a pharmacologic dose. Atheroprotective properties of HDL are compromised in patients with diabetes due to oxidative damage and glycation.

Methods: Isolated human HDL at 200 µg/mL was incubated with vehicle or EPA at levels that match plasma concentrations (∼10 µM) at 4 g/d. All samples were subjected to oxidation over 6 hour under low and high glucose (200 mg/dL) conditions.

Results: EPA inhibited HDL oxidation in a highly dose- and time-dependent manner. At lower concentrations (≤ 3.5 µM), EPA inhibited oxidation until 4 hour or less. At higher concentrations (>7.0 µM), EPA inhibited HDL oxidation 6 hour. At 10.0 µM, EPA inhibited HDL oxidation by 80% (p<0.001) at 6 hour. Large effect shifts were observed with relatively small concentration shifts, with the critical concentration shifts being time-dependent. Similar antioxidant effects were observed with hyperglycemia.

Conclusions: These data support concentration-dependent antioxidant effects for EPA that require pharmacologic concentrations for sustained activity. These effects of EPA may provide one potential mechanism for cardiovascular benefits in patients with diabetes.

Disclosure

S. Sherratt: None. R. Mason: Consultant; Self; Amarin Corporation. Research Support; Self; Amarin Corporation, Amgen Inc., Novartis AG, Pfizer Inc. Speaker's Bureau; Self; Pfizer Inc.
616-P: Long-Term Statin Persistence Is Poor among High-Risk Patients with Baseline Diabetes: A Real-World Administrative Claims Analysis
Authors: TOTH PETER P. , PHILIP SEPHY , HULL MICHAEL , GRANOWITZ CRAIG B.
Published: June 2019

Background: Statin persistence has been poor for over 2 decades, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking, particularly in patients with diabetes.

Methods: This retrospective administrative claims analysis (Optum Research Database) analyzed long-term data on statin persistence in patients with high CV risk by diabetes and triglycerides (TG). Patients aged ≥45 years with diabetes and/or atherosclerotic CV disease with an index date and statin prescription filled in 2010 were included. Patients with TG ≥150 mg/dL were propensity-matched to a comparator cohort with TG <150 mg/dL and high-density lipoprotein cholesterol >40 mg/dL. Cohorts were followed for ≥6 months to March 2016.

Results: In the elevated-TG and comparator cohorts (each n=23,181), mean follow-up was 41.4 and 42.5 months, mean age was 62.2 and 62.6 years, and 49.7% and 49.5% were female, respectively. In patients with and without baseline elevated-TG and/or baseline diabetes, statin persistence was poor, with ≤21% remaining on a prescription fill for index statin at 5 years (Figure).

Conclusions: Statin persistence remains poor, particularly in patients with high CV risk, elevated TG, and diabetes. Better public health programs and patient education initiatives on the benefits of statins and the danger of statin discontinuation are needed.

Disclosure

P.P. Toth: Consultant; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novo Nordisk Inc. Speaker's Bureau; Self; Amarin Corporation, Amgen Inc., Merck & Co., Inc., Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi US. S. Philip: Employee; Self; Amarin Corporation. Stock/Shareholder; Self; Amarin Corporation. M. Hull: None. C.B. Granowitz: Employee; Self; Amarin Pharma Inc. Stock/Shareholder; Self; Amarin Pharma Inc.
618-P: Effect of Liraglutide Combined with Human Umbilical Cord Mesenchymal Stem Cells on Liver Injury of T2DM with NAFLD Rats by Mediating Toll-Like Receptor 4/Nuclear Factor-kappa B Signaling Pathway and Oxidative Stress
Authors: CHEN PIN
Published: June 2019

Objective: To observe the effect of liraglutide combined with human umbilical cord mesenchymal stem cells on type 2 diabetes mellitus with nonalcoholic fatty liver disease rats liver injury. And then to investigate relation of the effect on the liver injury between the toll-like receptor 4/nuclear factor-kappa B inflammatory signal pathway and oxidative stress mechanism.

Methods: Animal model establishment and experimental grouping and intervention: The rats were randomly selected and divided into the following four groups: T2DM with NAFLD model group, hUC-MSCs treatment group, Liraglutide treatment group, Liraglutide combined with hUC-MSCs treatment group.

Results: 1. Rat serum levels of TNF-α, IL-6, 8-OHdG and SOD: Compared with MC+LIRA group, the levels of TNF-α, IL-6 and 8-OHdG were decreased in MC+LIRA+hUC-MSCs group (P <0.05), SOD was increased (P<0.05). 2. Pathological changes of rats liver tissue:Compared with MC+LIRA group, the NAS score were decreased in MC+LIRA+hUC-MSCs group (P <0.05).3. Expression of TLR4 and NF-κB mRNA in rat liver tissue: Compared with MC+hUC-MSCs group, the expression of TLR4 and NF-κB mRNA were significantly decreased in MC+LIRA group and MC+LIRA+hUC-MSCs group (P<0.05). Compared with MC+LIRA group, the expression of TLR4 and NF-κB mRNA were decreased in MC+LIRA+hUC-MSCs group (P <0.05).

Conclusion: The mechanism of liraglutide combined with human umbilical cord mesenchymal stem cells on type 2 diabetes mellitus with nonalcoholic fatty liver disease is closely related to the down-regulation of TLR4/NF-κB inflammation pathway and oxidative stress.

Disclosure

P. Chen: None.
621-P: Cardiovascular Mortality and Orthostatic Hypotension in Type 2 Diabetic Patients (T2D) with Lower Limb Lesions—Italian Diabetic Patients' Association-Section of Treviso Project
Authors: SAMBATARO MARIA , SAMBADO LUISA , SPINETTI GAIA , SEGANFREDDO ELENA , TREVISIOL ENRICA , MARCON MARIALISA , STEFANI PIERO MARIA , FURLAN ANNA , CACCIATORE MATILDE , PACCAGNELLA AGOSTINO
Published: June 2019

Introduction: Neuroischemic (NI) diabetic foot (DF) is an advanced complication leading to limb amputations and cardiac mortality. We contributed to demonstrate that bone marrow (BM) T2D neuropathy impairs vascular regenerative hematopoietic cell mobilization. We here hypothesize that autonomic neuropathy (DAN) and pathological orthostatic hypotension (reducing systolic and diastolic blood pressure -BP at least 30 and 10 mm Hg) convert to cardiovascular death in T2D patients with NI-DF.

Subjects and Methods: We performed DAN and postural hypotension tests in 204 surgical-treated neuropathic T2D without (87 N) or with (117 NI) critical limb ischemia (pO2 <30 mm Hg). In peripheral blood (PB) (204) and BM (65) samples we evaluated: percentage of haematopoietic precursor CD34+, VEGF receptor KDR+ (PreC) and neurokinin-1 receptor on BM-CD34+ cells (BM-NK1R+preC) by flow cytometry; circulating P substance neuropeptide by ELISA.

Results: We observed 46 NI cardiac deaths (DD) and 158 alive patients (AD) after prospective 5 years. DD were older but comparable for diabetes age, BMI, HbA1c, post-revascularization oximetry and TUC lesion grade. All T2D had autonomic failure but only DD were orthostatically hypotensive (-BP -35±2 and -21± 3 mm Hg p<0.01 vs. AD) with different BM/PB preC incremental ratio (8.8±4 vs. 1.5 ±0.3 106 events p<0.0003 vs. AD), similar circulating P levels, reduced BM-NK1R+preC (14.5±8.5 vs. 36.4±5 % p<0.04). Both -BP correlate with BM/PB preC (p< 0.04) but not with BM-NK1R+preC.

Conclusions: We prospectively confirm that autonomic failure impacts on vascular homeostasis and cardiac mortality in T2D with prevalent NI-DF. Now we demonstrate that pathological orthostatic hypotension, a simple clinical measure, could contribute to persistent ischemic bone marrow signal in neuroreceptor reduced BM-derived stem cells, worsening BM vascular regenerative capacity and cardiac performance.

Disclosure

M. Sambataro: None. L. Sambado: None. G. Spinetti: None. E. Seganfreddo: None. E. Trevisiol: None. M. Marcon: None. P. Stefani: None. A. Furlan: None. M. Cacciatore: None. A. Paccagnella: None.

Funding

Italian Diabetic Patients' Association of Treviso and Oderzo
641-P: Relationship of Sarcopenia and Microcirculation Assessed by Skin Perfusion Pressure in Patients with Type 2 Diabetes
Authors: JUNG CHANHEE , CHOI DUGHYUN , KIM CHUL-HEE , MOK JI OH
Published: June 2019

Sarcopenia is more prevalent in diabetes than controls and is related with higher cardiovascular events such as critical limb ischemia and mortality in T2DM. Microvascular dysfunction in diabetes plays a crucial role in the development of diabetic complications. Skin perfusion pressure (SPP) using laser Doppler technique is valuable in the evaluation of microcirculation function and limb ischemia. Although previous study reported that sarcopenia is independently associated with diabetic foot disease and even it is regarded as a chronic complication of T2DM, no studies have examined the relationship of sarcopenia and microcirculation. The current analysis is an attempt to evaluate the undisclosed relationship of sarcopenia and skin perfusion pressure. We analyzed the data of 188 patients with T2DM performing laser Doppler technique for measuring SPP. Sarcopenia was defined low appendicular muscle mass adjusted for height (Men <7 kg/m2, women < 5.7kg/m2) using bioelectrical impedance analysis. We divided into two groups based on SPP: ≤50 mmHg, >50 mmHg. SPP below 50 mmHg was considered as impaired microcirculation. The mean age and SPP of total subjects were 51 years and 72 mmHg. A total of 26 patients (13.8%) were diagnosed with impaired function of microcirculation in limb on SPP. The prevalence of sarcopenia in total subjects was 8%. The prevalence of sarcopenia increased significantly in SPP ≤50 mmHg group than in SPP >50 mmHg (23% vs. 5.3%, p=0.028). Significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (p=0.008). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 6.1 (95% CI =1.2-31.7) for having of SPP ≤50 mmHg even after adjustment for confounding factors (p=0.032). Our results suggest that the sarcopenia is significantly associated with the presence of impaired function of microcirculation on SPP in T2DM.

Disclosure

C. Jung: None. D. Choi: None. C. Kim: None. J. Mok: None.
642-P: Diagnosing Peripheral Neuropathy with a Remote Temperature Monitoring Mat
Authors: PETERSEN BRIAN J. , ZHOU MIN , BLOOM JONATHAN D. , ROTHENBERG GARY M. , ARMSTRONG DAVID
Published: June 2019

The aim of this study was to derive and validate a model to identify peripheral sensory neuropathy using remote temperature monitoring (RTM). We used data from a recent longitudinal study of a once-daily in-home RTM mat. Neurological status was assessed via 10g monofilament. We trained and cross-validated (repeated k-fold sampler) machine learning classifiers (support vector machine with radial basis function kernels). Accuracy was defined as the area under the receiver operator curve (AUC). We report on three final models that assess neuropathic status: (1) foot temperatures at the six plantar locations commonly used for RTM; (2) high-resolution foot temperature maps (thermograms); (3) high-resolution foot shape without associated temperatures. A total of 154 feet were included, of which 30 were insensate (19.5%). The AUCs of these three models were 0.78±0.13 (good), 0.92±0.07 (excellent), and 0.54±0.16 (poor), respectively. The results suggest the diagnostic usefulness of thermograms, which is supported by the fact that analysis feature importance of model 2 shows high diagnostic value for temperatures in the medial midfoot and distal toes. The latter is possibly due to vasodilation of the medial plantar artery, while the former can be explained by the progressive nature of neuropathy from distal to proximal. That model 3 had nearly no predictive value suggests that foot deformity secondary to motor neuropathy is not contributing diagnostic value. Interestingly, 22 feet showed neuropathic progression over the 34-week study. Results from model 1 reflected these changes when assessed at enrollment and at study completion for these feet. These results suggest the RTM mat may be useful for assessing peripheral neurological function and progression in patients with diabetes. These diagnostic models may also inform improved RTM standard and machine learning algorithms for predicting diabetic foot complications secondary to neuropathy.

Disclosure

B.J. Petersen: Employee; Self; Podimetrics. Stock/Shareholder; Self; Podimetrics. M. Zhou: None. J.D. Bloom: Employee; Self; Podimetrics. Stock/Shareholder; Self; Podimetrics. G.M. Rothenberg: Consultant; Self; Podimetrics. D. Armstrong: None.
65-OR: Effects of Treatment with Metformin and/or Sitagliptin on Beta-Cell Function and Insulin Resistance in Prediabetic Women with Previous Gestational Diabetes
Authors: BARONE SARA , DARDANO ANGELA , TURA ANDREA , KURUMTHODATHU JANCY J. , BERTOLOTTO ALESSANDRA , BIANCHI CRISTINA , GIUSTI LAURA , LACARIA EMILIA , ROMANO MATILDE , MICCOLI ROBERTO , PENNO GIUSEPPE , PRATO STEFANO DEL , DANIELE GIUSEPPE
Published: June 2019

Gestational diabetes (GDM) enhances the risk of type 2 diabetes (T2D) with 20-50% of women progressing to T2D within 10-years after pregnancy. Preventative strategies, including use of pharmacologic agents, are worth considering. We assessed, in a randomized double-blind study, the effect of 16-week therapy with sitagliptin (SITA, 100 mg qd), metformin (MET, 850 mg bid), and SITA+MET (50+850 mg bid) on beta-cell function and insulin sensitivity in women (n=40, age 30-49 y) with recent GDM and impaired glucose regulation (IGR: IFG and/or IGT). A 75gr OGTT and +125 mg/dl hyperglycemic clamp followed by 5 gr i.v. L-arginine were performed at baseline and study-end. Baseline characteristics were comparable in the 3 groups. At week 16, BMI declined in all groups (-1.2±0.2 Kg/m2; p<0.05). First phase(2-10 min) insulin secretion and arginine-stimulated C-peptide response increased with SITA+MET (1.0±0.2 to 1.3±0.3 ng/ml/min and 3.2±0.6 to 4.8±1.0 pmol/min, respectively, both p<0.05) while no changes occurred with MET and SITA. SITA+MET increased OGTT-based glucose sensitivity (55.7±11.3 to 108±56.2 pmol x min-1m-2 x mM-1; p=0.04) but no changes occurred with MET and SITA. No change occurred for rate sensitivity and potentiation factor in any group. SITA+MET increased insulin sensitivity (M/I: 2.2±0.5 to 4.6±1.3 mg/kg/min÷μIU/min/ml; p=0.04; OGIS: 351.9±11.4 to 375.7±9.6 ml x min-1m-2; p=0.08) but it was not affected by MET or SITA. Disposition Index increased with SITA+MET (10.8±1.1 to 13.6±1.6 μIU/ml/min÷mg/dl/min) and SITA (8.6±1.0 to 10.6±1.3; both p<0.05). Among SITA+MET women, 33% reverted to NGT compared to 14% with MET and 7% with SITA (p<0.05). This proof of concept study shows that SITA+MET is superior to SITA and MET monotherapy on beta-cell function and insulin sensitivity improvement in IGR women with previous GDM. It may offer a potential pharmacologic intervention to reduce risk of T2D in this high-risk population.

Disclosure

S. Barone: None. A. Dardano: None. A. Tura: None. J.J. Kurumthodathu: None. A. Bertolotto: Speaker's Bureau; Self; Abbott, Lilly Diabetes. C. Bianchi: None. L. Giusti: None. E. Lacaria: None. M. Romano: None. R. Miccoli: None. G. Penno: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. G. Daniele: None.
652-P: A Group-Based Food Monopoly-Style Game Improved Blood Glucose Control in Newly Diagnosed Type 2 Diabetes
Authors: WU YUEH CHU , WANG YU-MING , KORNELIUS EDY , HUANG CHIEN NING
Published: June 2019

Objective: The aim of this study was to compare the effectiveness of a Food Monopoly-style Game (FMG) on glycemic control in type 2 diabetes (T2DM), compared with usual care.

Methods: Newly diagnosed T2DM patients were randomly assigned to the FMG group (using a group interaction model of patient education) and a usual care group (using a traditional teaching model). Glycemic outcomes and behavior questionnaires were evaluated at 3 months.

Results: A total of 65 patients were enrolled (FMG group, n=32; usual care group, n=33) with a mean age of 52.9±11.2 years, diabetes duration of 0.7±0.4 years, and HbA1c level of 9.2±1.9%. FMG group patients had significantly greater HbA1c reduction at 3 months than that of usual care patients (-2.3 vs. -0.6%), respectively; p<0.001. SMBG (times/week) (+5.8±3.1) and physical activity (minutes/week) (+42.5 ±24.4) were higher in the FMG group, compared with the usual care group (p<0.001). The FMG group had a significantly greater percentage of patients who achieved HbA1c<7% at 3 months compared with the usual care group (62.5 vs. 0%, p<0.001).

Conclusions: Our data suggest that the FMG approach provided more effective education in poorly controlled T2DM compared with conventional patient education. Education tools, such as FMG, can be used to adjust patients' self-management behavior and enhance diabetes-related psychosocial self-efficacy.

Disclosure

Y. Wu: None. Y. Wang: None. E. Kornelius: None. C. Huang: None.