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  • American Diabetes Association  (11)
  • 1
    Online Resource
    Online Resource
    Highly Angiogenic, Nonthrombogenic Bone Marrow Mononuclear Cell–Derived Spheroids in Intraportal Islet Transplantation
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. 3 ( 2018-03-01), p. 473-485
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. 3 ( 2018-03-01), p. 473-485
    Abstract: Highly angiogenic bone marrow mononuclear cell–derived spheroids (BM-spheroids), formed by selective proliferation of the CD31+CD14+CD34+ monocyte subset via three-dimensional (3D) culture, have had robust angiogenetic capacity in rodent syngeneic renal subcapsular islet transplantation. We wondered whether the efficacy of BM-spheroids could be demonstrated in clinically relevant intraportal islet transplantation models without increasing the risk of portal thrombosis. The thrombogenic potential of intraportally infused BM-spheroids was compared with that of mesenchymal stem cells (MSCs) and MSC-derived spheroids (MSC-spheroids). The angiogenic efficacy and persistence in portal sinusoids of BM-spheroids were examined in rodent syngeneic and primate allogeneic intraportal islet transplantation models. In contrast to MSCs and MSC-spheroids, intraportal infusion of BM-spheroids did not evoke portal thrombosis. BM-spheroids had robust angiogenetic capacity in both the rodent and primate intraportal islet transplantation models and improved posttransplant glycemic outcomes. MRI and intravital microscopy findings revealed the persistence of intraportally infused BM-spheroids in portal sinusoids. Intraportal cotransplantation of allogeneic islets with autologous BM-spheroids in nonhuman primates further confirmed the clinical feasibility of this approach. In conclusion, cotransplantation of BM-spheroids enhances intraportal islet transplantation outcome without portal thrombosis in mice and nonhuman primates. Generating BM-spheroids by 3D culture prevented the rapid migration and disappearance of intraportally infused therapeutic cells.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db17-0705
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 2
    Online Resource
    Online Resource
    1140-P: Efficacy and Safety of Evogliptin in Patients with Type 2 Diabetes: A Multicenter, Active-Controlled, Randomized Study with Open Label Extension (EVERGREEN Study)
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Background and Aims: Evogliptin is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. We investigated the efficacy and safety of Evogliptin compared with linagliptin in patients with type 2 diabetes (T2D). Materials and Methods: A total of 207 untreated patients with T2D (mean age, 56.1±10.4 years; body mass index, 26.1±3.4 kg/m2) who had HbA1c 7.0-10.0%, prior to the screening were randomized 1:1 for 5 mg Evogliptin (n=102) or 5 mg linagliptin (n=105) once daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint included the change in mean amplitude of glycemic excursion (MAGE) assessed by 72-hour continuous glucose monitoring. In the extended study for another 12 weeks, open-label treatment with Evogliptin 5 mg qd was conducted in both groups; Evogliptin/Evogliptin group (n=95) and Linagliptin/Evogliptin group (n=92). Results: After 12 weeks of treatment, the mean changes in HbA1c of Evogliptin group and linagliptin group were −0.85% and −0.75%, respectively; the between-group difference was -0.10% (95% confidence interval, −0.32-0.11%), demonstrating non-inferiority, meeting the pre-specified margin of 0.40%. The changes in MAGE were −24.6 mg/dL in the Evogliptin group and −16.7 mg/dL in the linagliptin group, which were significantly lower compared with baseline values in both groups. In the Evogliptin/Evogliptin group at week 24, the mean changes from baseline in HbA1c was −0.94%, achieving HbA1c & lt;7.0% in 80.2% of patients. The incidence and types of adverse events including hypoglycemic events, were comparable between the two groups for 24 weeks. Conclusion: In this study, once-daily evoglipitin 5 mg treatment significantly decreased HbA1c levels by 0.94% at week 24 and improved glycemic variability without any serious adverse events in Korean patients with T2D (ClinicalTrials.gov Identifier: NCT02974504). Disclosure S. Lim: None. G. Kim: None. H. Kwon: None. I. Park: None. K. Ahn: None. C. Park: None. S. Kwon: None. H. Kim: None. S. Park: None. S. Kim: None. M. Moon: None. E. Kim: None. C.H. Chung: None. K. Won: None. K. Park: None. M. Kim: None. D. Chung: None. C. Lee: None. T. Kim: None. M. Lee: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1140-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 3
    Online Resource
    Online Resource
    1280-P: Higher Triglyceride–Glucose Index Is Associated with a Higher Risk of Cardiovascular Disease in Patients with Type 1 Diabetes
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: The triglyceride-glucose (TyG) index has been linked to cardiovascular disease in diabetic or nondiabetic patients. However, it remains unclear whether elevated TyG index is associated with a high risk of cardiovascular disease in patients with type 1 diabetes. We enrolled 14,553 adults with type 1 diabetes with a mean follow-up of 7.52 years using the National Health Insurance Database in Korea between January 2009 and December 2015. We exclude patients who have other etiology of diabetes, cancer, and underlying cardiovascular disease. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2] and categorized into four quartiles. The primary outcome is the hospitalization due to cardiovascular disease. Cox proportional hazards models were used to estimate adjusted hazard ratios. We found that the TyG index is positively associated with cardiovascular disease and all-cause mortality. Compared to Q1, the aHRs(95%CI) for the hospitalization due to cardiovascular disease of Q2, Q3, Q4 were 1.26(1.13-1.41), 1.38(1.24-1.54), 1.84(1.65-2.04). Furthermore, compared to Q1, the aHRs (95%Cl) for the all-cause mortality of Q2,3,4 were 1.19(1.05-1.35), 1.28(1.13-1.45),1.64(1.45-1.85). In conclusion, elevated TyG index was associated with a higher risk of cardiovascular disease and all-cause mortality in patients with type 1 diabetes. Disclosure R. Oh: None. S. Cho: None. S. Kim: None. J. Kim: None. G. Kim: None. J. Kim: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-1280-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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  • 4
    Online Resource
    Online Resource
    Protective Effect of NecroX-7 on Islets against Oxidative Stress and Inflammation
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Oxidative stress generated during islet isolation, culture, and transplantation causes islet cell damage mediated by hypoxia, reactive oxygen species (ROS) and inflammatory responses. We investigated the protective effects of NecroX-7, a novel ROS scavenger, during isolation and/or culture of islets. For ex vivo studies, islets from heterozygote human islet amyloid polypeptide (hIAPP+/-) mice and C57BL/6J mice were isolated by collagenase with and without supplementation with 20 uM of NecroX-7. Supplementation with NecroX-7 provided markedly increased islet viability and ATP contents, and attenuated ROS, transcription of c-Jun N-terminal kinases, high mobility group box-1 (HMGB1) and proinflammatory cytokines including interleukin-1beta (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-a). Transplantation of islets, which is derived from islet isolation method using supplementation with NecroX-7, into syngeneic subrenal subcapsular of hIAPP+/- mice also improved post-transplant blood glucose levels. Also, NecroX-7 protected RINm5F cells from t-BHP-induced and serum deprivation induced toxicity in in vitro culture by dose-dependent manner from 0.1 uM to 20 uM. Supplementation of medium with NecroX-7 during serum-deprived culture condition also improved impaired viability and serum deprivation-induced ROS in islets from hIAPP+/- mice by dose-dependent manner from 0.1 uM to 20 uM. These findings suggest that NecroX-7 supplementation during the islet isolation and/or culture process suppressed inflammatory responses and ROS induced by serum deprivation and provides a potential benefit to improve post-transplantation outcomes. Disclosure Y. Kwon: None. H. Lee: None. H. Kim: None. G. Kim: None. S. Jin: None. M. Lee: None. J. Kim: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1744-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 5
    Online Resource
    Online Resource
    Synergistic Effect of Islet Magnetic Resonance Imaging Using Direct Linking of Ferumoxytol to Surface of PEGylated Islet
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Purpose: We previously reported the feasibility of islet magnetic resonance imaging (MRI) using ferumoxytol, which is the only clinically-available ultrasmall superparamagnetic iron oxide. However, the labeling efficacy was not sufficient for its clinical use in islet transplantation. We aimed to evaluate the feasibility of islet MRI using direct linking of ferumoxytol to islet surface through PEGylation. Method: Islets were labeled by surface modification with up to 4% PEG-heparin-ferumoxytol. We compared islet function and viability of control islets and ferumoxytol-heparin-PEGylated islets. Efficacy of labeling with ferumoxytol-heparin-PEGylation and ferumoxytol alone was assessed in both ex vivo and in vivo models. Results: Labeling of islets with up to 2% PEG-heparin-ferumoxytol did not derange ex vivo islet viability and function. The T2* relaxation time was optimal when islets were labeled with 1 to 4% PEG-heparin-ferumoxytol. The labeling intensity in the ex vivo MRI of ferumoxytol-heparin-PEGylated islets was stronger than islets labeled with ferumoxytol alone. In syngeneic renal subcapsular islet transplantation, labeling with ferumoxytol-heparin-PEGylation showed better in vivo labeling efficacy than that of islets labeled with ferumoxytol alone. After labeling with ferumoxytol-heparin-PEGylation, there was a correlation between the total area of visualized islets and the transplanted islet mass in syngeneic mouse intraportal islet transplantation, and the visibility was also confirmed in the preliminary analysis of non-human primate intraportal islet transplantation model. Conclusion: Direct linking of ferumoxytol to islet surface through PEGylation improved the labeling efficacy and it could be used for the islet MRI in clinical islet transplantation. Disclosure H. Lee: None. Y. Kwon: None. H. Kim: None. M.R. Haque: None. G. Kim: None. S. Jin: None. M. Lee: None. Y. Byun: None. J. Kim: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1745-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 6
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    Online Resource
    The Association between Urinary N-Acetyl-ß-D-Glucosaminidase and Cardiovascular Autonomic Neuropathy in Patients with Diabetes
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Background: Cardiovascular autonomic neuropathy (CAN) is a microvascular complication of diabetes, which involves autonomic nerve fibers innervating the heart and vessels, resulting in increased cardiovascular morbidity and mortality. Previous studies reported that diabetic CAN is related to microalbuminuria. However, it is unclear whether CAN is related with urinary N-acetyl-β-D-glucosaminidase (uNAG), which was suggested as an early marker of renal tubular injury in diabetic nephropathy recently. Methods: Cross-sectional data of 1052 patients with diabetes were analyzed who had tests for uNAG and autonomic function test at outpatient clinic. The presence and severity of CAN were assessed by the five autonomic function tests. Results: The association between uNAG and the presence of CAN in patients with type 1 diabetes (T1D) (n=161) was significant in multivariate analysis (OR 1.20, 95% CI 1.03-39; p = 0.018) after correction of variables including age, duration of diabetes, glycemic index and albuminuria, but it was insignificant in patients with type 2 diabetes (T2D) (n=891). Among quartile groups divided by uNAG levels, prevalence of CAN was significantly increased across with higher quartiles of uNAG level only in patients with T1D (p = 0.013). The association between uNAG and the total CAN score, assessed as the severity of CAN, was significant in both patients with T1D (p = 0.033) and T2D (p = 0.006) in multivariate analyses. Conclusion: Elevated uNAG is associated with the prevalence of CAN only in patients with T1D, and it is also related to the severity of CAN in both patients with T1D and T2D. It suggests that elevated uNAG might be a potential marker for the development and progression of CAN in patients with diabetes. Disclosure M. Choi: None. J. Jun: None. G. Kim: None. S. Jin: None. K. Hur: None. M. Lee: None. J. Kim: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-572-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 7
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    Online Resource
    Large Relative Skeletal Muscle Mass May Protect against Diabetes Irrespective of Glycometabolic Parameters
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Background: Skeletal muscle mass was negatively associated with the prevalence of diabetes in previous cross-sectional studies. The aim of the study was to investigate the impact of baseline relative skeletal muscle mass on the development of diabetes in a large population-based 7-year longitudinal study. Methods: A total of 18,269 individuals who underwent medical health check-up examination in a university-affiliated tertiary hospital without diabetes were included. Skeletal muscle mass was estimated by bioelectrical impedance analysis and presented as appendicular skeletal muscle mass (ASM) / body mass index (BMI). We analyzed hazard ratio for developing diabetes associated with ASM/BMI using Cox regression models and evaluated the effects of preexisting impaired fasting glucose (IFG). Results: Compared to subjects in the lowest baseline sex-specific ASM/BMI tertile, those in the highest ASM/BMI tertile were significantly associated with a decreased adjusted HR (AHR=0.69, 95% CI=0.59-0.81, P & lt;0.001) for incident diabetes after adjusting for age, family history of diabetes, smoking status, regular exercise, metabolic syndrome, and CRP. The reduction in the risk of developing diabetes was also significant in the highest tertile of sex-specific ASM/BMI tertile in the presence (AHR=0.81, 95% CI=0.68-0.97, P & lt;0.001) and in the absence of IFG (AHR=0.51, 95% CI=0.39-0.67, P & lt;0.001) compared to the lowest tertile. Conclusion: The large relative skeletal muscle mass has a potential preventive effect on developing diabetes, independently of glycometabolic parameters. In particular, in subjects with IFG who are at high risk for diabetes, larger relative skeletal muscle mass may provide a substantial benefit to prevent diabetes. Disclosure G. Kim: None. M. Choi: None. S. Jin: None. M. Lee: None. J. Kim: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1541-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 8
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    Circulating Netrin-1 as a Novel Biomarker for Impaired Fasting Glucose and Newly Diagnosed Type 2 Diabetes Mellitus
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Aims/Hypothesis: Netrin-1 has been introduced as a neuronal guidance cue, acting as a chemoattractant and chemorepulsive force during axonal migration. In recent studies, netrin-1 was shown to play various roles including tissue regeneration and modulation of inflammatory action. Inflammation is one of the major contributing factors in the development of insulin resistance and type 2 diabetes (T2DM). However, little is known about the possible relationship between serum netrin-1 and the risk of T2DM. Therefore, we investigated the association between levels of netrin-1 and glycometabolic parameters. Methods: Serum samples were collected from a total of 218 individuals (41 normal controls, 85 subjects with impaired fasting glucose (IFG) and 92 subjects with newly diagnosed T2DM). Clinical and biochemical parameters were assessed after receiving consent. Netrin-1 levels were determined by commercial enzyme-linked immunosorbent assay. Spearman correlation analyses and multivariable-adjusted linear regression analyses were conducted to examine the relationship between serum netrin-1 levels and glycometabolic parameters. Results: Serum netrin-1 level in subjects with IFG or T2DM was significantly higher than in normal control subjects (mean netrin-1 level; normal, IFG and T2DM; 275.9, 436.6 and 441.0 pg/mL, respectively; p for trend & lt;0.001). Serum netrin-1 levels had a significant positive correlation with fasting glucose, HbA1c, HOMA-IR, AST and ALT. Meanwhile, statistically inverse correlation was found between netrin-1 and HDL cholesterol and eGFR levels. In addition, Serum netrin-1 was independently associated with the presence of IFG or T2DM after adjusting covariates and potential confounders. In terms of the AUC, serum netrin-1 levels presented an AUC of 0.784 for the prediction of IFG or T2DM. Conclusions/Interpretation: Our results suggest that netrin-1 may be a new biomarker for early detection for IFG or T2DM (Clinical trial no. NCT02650830). Disclosure H. Jung: None. J. Bae: None. E. Han: None. G. Kim: None. J. Lee: None. S. Kim: None. B. Lee: None. E. Kang: None. C. Ahn: None. B. Cha: None. Y. Lee: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1535-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 9
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    Online Resource
    An Integrated Digital Health Care Platform for Diabetes Management With AI-Based Dietary Management: 48-Week Results From a Randomized Controlled Trial
    American Diabetes Association ; 2023
    In:  Diabetes Care Vol. 46, No. 5 ( 2023-05-01), p. 959-966
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 46, No. 5 ( 2023-05-01), p. 959-966
    Abstract: We investigated the efficacy of an integrated digital health care platform with artificial intelligence (AI)–based dietary management in adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In this 48-week, open-label, randomized, multicenter clinical trial, overweight or obese adults with T2D were randomly assigned to one of three groups in a 1:1:1 ratio: group A received routine diabetes care; group B used the digital integrated health care platform by themselves; and group C used the platform with feedback from medical staff and intermittently applied personal continuous glucose monitoring. The primary end point was the difference of change in HbA1c from baseline to 24 weeks between groups A and B, while secondary end points included changes in HbA1c from baseline to 48 weeks and changes in body weight during follow-up. RESULTS A total of 294 participants were randomly assigned to group A (n = 99), B (n = 97), or C (n = 98). The decreases in HbA1c from baseline to 24 and 48 weeks in group B (−0.32 ± 0.58% to 24 weeks and −0.28 ± 0.56% to 48 weeks) and group C (−0.49 ± 0.57% to 24 weeks and −0.44 ± 0.62% to 48 weeks) were significantly larger than those in group A (−0.06 ± 0.61% to 24 weeks and 0.07 ± 0.78% to 48 weeks). Groups B and C exhibited greater weight loss than group A from baseline to 24 weeks, and group C demonstrated more weight loss than group A from baseline to week 48. CONCLUSIONS Among adults with T2D, use of an integrated digital health care platform with AI-driven dietary management resulted in better glycemia and more weight loss.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc22-1929
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
    detail.hit.zdb_id: 1490520-6
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  • 10
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    2061-P: Inflammation Status Is Independent Risk Factor for the Development of Metabolic Syndrome in Both Metabolically Healthy Obese and Nonobese Adults
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Objectives: The fact that metabolic syndrome is accompanied by a low-grade inflammation suggests inflammation may play an important role in the etiology. The aim of our study was to assess the association between heterogeneity of inflammation status and the incidence of metabolic syndrome (MetS) in the metabolically healthy persons who are either obese or nonobese. Methods: This longitudinal study included all metabolically healthy persons who underwent four or more follow-up comprehensive health examinations either annually or biennially from August 2006 through August 2013 at the Health Promotion Center at Samsung Medical Center, Seoul, Republic of Korea. Metabolic health was defined as absence of any component of the MetS except obesity. We defined obesity using the BMI, which is classified into categories of normal (18.0-22.9 kg/m2), overweight (23-24.9 kg/m2), and obesity (25 kg/m2). Hematological indices such as WBC count or its subtypes (neutrophils, lymphocytes, monocytes) and hsCRP were measured. The outcome was the 7-year cumulative incidence of MetS. Results: The person-years follow-up were 17,786 in normal weight, 10,376 in overweight, and 7,391 in obesity group. Baseline age, sex, physical activity, smoking, exercise, fasting plasma glucose, HbA1c, blood pressure, lipid profile, hematologic parameters, hsCRP were adjusted. Cox regression multivariate analysis resulted in neutrophil count ( & gt; 2,750/mm3) was associated with increased incidence of MetS in normal weight (HR 1.7; CI 1.29-2.35; p & lt;0.001), overweight (HR 1.59; CI 1.29-1.95; p & lt;0.001), and obesity (HR 1.26; CI 1.10-1.45; p & lt;0.001). Conclusion: This longitudinal analysis showed the neutrophil count is associated with the incidence of MetS in the metabolically heathy persons who are either obese or nonobese. Therefore, inflammatory status could be an independent risk factor for the development of metabolic syndrome irrespective of obesity. Disclosure K. Hur: None. M. Choi: None. S. Park: None. S. Lee: None. J. Ahn: None. J. Park: None. H. Park: None. G. Kim: None. S. Jin: None. J. Kim: None. M. Lee: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-2061-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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