bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Therapeutic Effects of Conditioned Media from Cultured Dental Pulp Stem Cells on Diabetic Polyneuropathy
Authors: MAKINO ERIKO , NAKAMURA NOBUHISA , MIYABE MEGUMI , ITO MIZUHO , KANADA SAKI , HATA MASAKI , SAIKI TOMOKAZU , KAMIYA HIDEKI , NAKAMURA JIRO , MIYAZAWA KEN , GOTO SHIGEMI , MATSUBARA TATSUAKI , NARUSE KEIKO
Published: June 2018

Stem cell transplantation is expected to become a novel therapy for diabetic polyneuropathy. Dental pulp stem cells (DPSC) are an attractive cell source because they can be easily isolated from teeth extracted for general orthodontic reasons. We reported earlier that DPSC transplantation was effective for diabetic polyneuropathy. However, most of the transplanted DPSCs from this study are gone from the transplanted site and the mechanism of cell transplantation may have been due to the abundant secreted factors from stem cells. We confirmed that conditioned media from DPSCs (DPSC-CM) ameliorated diabetic polyneuropathy. We, therefore, examined the mechanism of therapeutic effects of DPSC-CM on diabetic polyneuropathy.

DPSCs were isolated and cultured from the mandibular incisors of 6-week-old male Sprague-Dawly (SD) rats. Diabetes was induced at 6-weeks by administering STZ. DPSC-CM was administered to the unilateral hindlimb skeletal muscles of both the diabetic and normal rats 8 weeks after the administration of STZ, and the measurements were performed 4 weeks after DPSC-CM administration. Administration of DPSC-CM significantly improved the delay of the sciatic nerve motor/sensory conduction velocity and reduced sciatic nerve blood flow in diabetic rats. TNF-α and CD68 gene expression in the sciatic nerves tended to increase in the diabetic group, which showed a decreasing trend by administration of DPSC-CM. Capillary density in the hindlimb skeletal muscle was decreased in diabetic rats. DPSC-CM significantly increased capillary/muscle ratio in the hindlimb skeletal muscles in the diabetic rats. It was revealed that intramuscular administration of DPSC-CM was effective for diabetic polyneuropathy at least in part by improving nerve/muscle blood flow and suppressing inflammation. These results indicate that DPSC-CM could be a novel therapy for diabetic polyneuropathy.

Disclosure

E. Makino: None. N. Nakamura: None. M. Miyabe: None. M. Ito: None. S. Kanada: None. M. Hata: None. T. Saiki: None. H. Kamiya: Other Relationship; Self; MSD K.K., Ono Pharmaceutical Co., Ltd., Sanofi K.K., AstraZeneca, Astellas Pharma KK, Eli Lilly and Company, Novartis Pharma K.K., Dainippon Sumitomo Pharma Co., Ltd, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd. J. Nakamura: Other Relationship; Self; Astellas Pharma US, Inc., AstraZeneca, Ono Pharmaceutical Co., Ltd., MSD K.K., Kyowa Hakko Kirin Co., Ltd., Kowa Pharmaceuticals America, Inc., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly and Company, Novartis Pharma K.K., Pfizer Inc.. K. Miyazawa: None. S. Goto: None. T. Matsubara: None. K. Naruse: None.
Monounsaturated Fatty Acids Prevent Saturated Fatty Acid–Induced Impairment of Mitochondrial Trafficking in Dorsal Root Ganglion Sensory Neurons
Authors: RUMORA AMY , LOGRASSO GIOVANNI , HAIDAR JULIA A. , DOLKOWSKI JUSTIN , LENTZ STEPHEN I. , FELDMAN EVA L.
Published: June 2018

Diabetic neuropathy (DN) is a common complication of type 2 diabetes characterized by peripheral nerve damage and sensory loss. Dorsal root ganglion (DRG) sensory neurons require axonal mitochondrial transport to produce axonal ATP for neuronal function. In DN, DRG neurons exhibit axonal mitochondrial dysfunction and bioenergetic failure. A correlation between DN progression and dyslipidemia suggests that increased plasma saturated fatty acids (FAs) and decreased unsaturated FAs may play a role in the progression of DN. In this study, we evaluated the effect of saturated FA palmitate and monounsaturated FA oleate on mitochondrial trafficking and mitochondrial function in DRG neurons. Primary DRG neurons were treated with physiological concentrations of palmitate, oleate, and oleate/palmitate mixtures. The impact of these treatments was assessed by measuring mitochondrial motility and mitochondrial membrane depolarization using TMRM staining. Treatment with 62.5 μM to 250 μM palmitate induced a significant and dose-dependent decrease in axonal mitochondrial transport whereas oleate treatments from 31.25 to 250 μM did not alter the percentage of motile mitochondria. Palmitate treatments also resulted in a reduction of mitochondrial membrane potential in DRG neurons treated with 125 to 250 μM palmitate. Conversely, DRG neurons treated with 125 to 250 μM oleate maintained their mitochondrial membrane potential. Based on the differential effects of oleate and palmitate, we next evaluated whether oleate supplementation could prevent palmitate-induced inhibition of mitochondrial trafficking. Mixtures of oleate/palmitate at 1:1 or 2:1 molar ratios prevented palmitate-induced decreases in mitochondrial trafficking and mitochondrial membrane depolarization. These results indicate that monounsaturated FAs prevent saturated FA induced mitochondrial dysfunction in DRG neurons associated with dyslipidemia and DN.

Disclosure

A. Rumora: None. G. LoGrasso: None. J.A. Haidar: None. J. Dolkowski: None. S.I. Lentz: None. E.L. Feldman: None.
Muscarinic Receptor Antagonist Improves Nerve Fiber Function in Subjects with Type 2 Diabetes and Peripheral Neuropathy
Authors: VINIK AARON I. , CALCUTT NIGEL A. , EDWARDS JOSHUA F. , WEAVER JESSICA R. , BAILEY MICHAEL D. , FERNYHOUGH PAUL , CUNDRA LINDSEY B. , FRIZZI KATIE E. , PARSON HENRI , CASELLINI CAROLINA M.
Published: June 2018

Degeneration of nerve fibers due to diabetic peripheral neuropathy (DPN) has been linked to mitochondrial dysfunction. Manipulation of mitochondrial dysfunction through antagonism of muscarinic receptors (MR) promotes neurite outgrowth in adult sensory neurons in vitro and provides neuroprotection in rodent models of DPN. The aim of the study was to assess the efficacy of MR antagonist topical 3% oxybutynin in structural and functional measures of nerve fiber function in subjects with type 2 diabetes (T2DM) and DPN. Pilot, randomized, placebo-controlled, double-blinded study in 40 subjects assessed at baseline and after 20 weeks of treatment with oxybutynin or placebo with the following: intraepidermal nerve fiber density (IENFD) on proximal and distal leg; neuropathy scores and quality of life (Norfolk QoL DN) questionnaire. Baseline demographic characteristics were similar between the treatment groups. IENFD improved significantly after 20 weeks for the treatment group. Neuropathy scores and Norfolk QoL DN also improved significantly in the treatment group (Table 1). No improvements were seen in the placebo group. In this study, oxybutynin proves to be efficacious in improving structural and functional measures of small fiber function, and quality of life in T2DM subjects. These results offer a promising novel therapeutic approach for DPN that needs to be explored further.

Disclosure

A.I. Vinik: None. N.A. Calcutt: Stock/Shareholder; Self; WinSanTor, Inc.. J.F. Edwards: None. J.R. Weaver: None. M.D. Bailey: None. P. Fernyhough: Stock/Shareholder; Self; WinSanTor, Inc.. L.B. Cundra: None. K.E. Frizzi: None. H. Parson: None. C.M. Casellini: None.
Insulin Resistance, Cardiovascular Autonomic Neuropathy, and Left Ventricular Hypertrophy in Patients with Congenital Generalized Lipodystrophy
Authors: FERNANDES VIRGINIA O. , PONTE CLARISSE M.M. , GURGEL MARIA HELANE C. , MONTENEGRO ANA PAULA D.R. , BATISTA LIVIA A.A. , LIBERATO CRISTIANE B.R. , D'ALVA CATARINA B. , MONTENEGRO RENAN M. ,   BRAZILIAN LIPODYSTROPHY STUDY GROUP (BRAZLIPO)
Published: June 2018

Congenital generalized lipodystrophy (CGL) subjects have a high prevalence of cardiovascular autonomic neuropathy (CAN) and cardiac complications, including left ventricular hypertrophy (LVH). This study aimed to analyze insulin resistance (IR), CAN severity and LVH association. A cross sectional study with 10 CGL patients and 20 healthy controls. We evaluated clinical and laboratory data, echocardiogram parameters, 3 spectral analysis components - high frequency (HF), low frequency (LF), and very low frequency (VLF) - of heart rate variability (HRV), sympathetic-vagal balance, time domains of HRV, corrected QT interval (cQT), and 4 cardiovascular reflexes tests (postural hypotension test, orthostatic, respiratory, and valsalva coefficients - 2 abnormal tests: clinic CAN, 1 abnormal test: incipient CAN, and postural hypotension: advanced CAN). In CGL group 50% had CAN (40% clinic and 10% incipient) and 40% LVH. There was inverse correlation between LVMI and HF (p=0,007), IVS and HF (p=0,013), and positive correlation between IVS and HOMA-IR (p=0,042), and BP drop (p=0,010). These suggest that IR may be involved in the severity of CAN and cardiac autonomic dysfunction in the pathophysiology of cardiovascular complications in these disease.

Disclosure

V.O. Fernandes: None. C.M.M. Ponte: None. M.C. Gurgel: None. A.D.R. Montenegro: None. L.A.A. Batista: None. C.B.R. Liberato: None. C.B. D'Alva: None. R.M. Montenegro: None.
Statins Decrease VEGF Expression in Retinal Pigment Epithelial Cells by Downregulation of Receptor for AGE (RAGE)
Authors: TSUJINAKA HIROKI , ITAYA-HIRONAKA ASAKO , YAMAUCHI AKIYO , SAKURAMOTO-TSUCHIDA SUMIYO , MAKINO MAI , SHOBATAKE RYOGO , MASUDA NAONORI , HIRAI HIROMASA , OGATA NAHOKO , TAKASAWA SHIN
Published: June 2018

Age-related macular degeneration (AMD) is one of the most important causes of blindness in the elderly patients. Statins, inhibitors for HMG-CoA reductase, are recently reported to be useful for decreasing the risk of wet-type AMD. However, the molecular mechanisms how statins reduce the risk of AMD remain unclear. In this study, we examined the effects of statins (atorvastatin and lovastatin) on the expression of VEGF and RAGE in human retinal pigment epithelial (RPE) cells. We used h1RPE7, human RPE cells, damaged by 20 µM hydroquinone (HQ)+300 µg/mL advanced glycation end-product (AGE) as an experimental AMD model. These cells were treated with atorvastatin (100 nM) or lovastatin (2 µM) for 24 hours. After the treatment, the expression of VEGF and RAGE was evaluated by real-time RT-PCR, and we found that the mRNA levels of VEGF and RAGE in the HQ+AGE treated cells were increased. The additions of statins significantly attenuated the HQ+AGE-induced VEGF and RAGE mRNA expression. We also measured the VEGF concentration in the cell culture medium by ELISA and found that it was markedly decreased by the addition of statins. In order to know the impact of RAGE on the VEGF expression, small interfering RNA (siRNA) for RAGE (siRAGE) was introduced into h1RPE7 cells by lipofection method and the VEGF expression was measured by real-time RT-PCR. The RT-PCR results show that siRAGE attenuated the up-regulation of VEGF in the HQ+AGE treated cells. The luciferase reporter assays for RAGE and VEGF transcription showed that the RAGE expression in the statin-treated cells was regulated at the transcriptional level, and that the VEGF expression in these cells was regulated by a post-transcriptional mechanism. These results indicate that statins attenuated the HQ+AGE-induced VEGF expression via decreasing RAGE expression. As VEGF is an important factor for the development of wet-type AMD, statins could decrease the risk of wet-type AMD and be a preventive medicine for diabetic patients.

Disclosure

H. Tsujinaka: None. A. Itaya-Hironaka: None. A. Yamauchi: None. S. Sakuramoto-Tsuchida: None. M. Makino: None. R. Shobatake: None. N. Masuda: None. H. Hirai: None. N. Ogata: Research Support; Self; Alcon Japan, Bayer Yakuhin, Ltd., Santen Seyaku Co., Ltd., AMO, Otsuka Holdings Co., Ltd., HOYA Co., Ltd.. S. Takasawa: None.
Role of Xanthine Oxidoreductase from Mesenchymal Cells in Retinal Inflammation after Pericyte Breakdown
Authors: KUSHIYAMA AKIFUMI , KIKUCHI TAKAKO , YAMAZAKI HIROKI , YAMAMOTOYA TAKESHI , SAKODA HIDEYUKI , FUJISHIRO MIDORI , NAKATSU YUSUKE , UEMURA AKIYOSHI , SHIRAKURA TAKASHI , ASANO TOMOICHIRO , IWAMOTO YASUHIKO
Published: June 2018

Glycemic control is important for diabetic retinopathy (DR), but not sufficient for the inhibition after proliferative DR (PDR). Uric acid in the vitreous is reportedly increased in patients with DR, especially in the PDR. Here, the involvement of xanthine oxidoreductase (XO), responsible for uric acid production, in worsening DR was examined in both mouse model and co-cultured angiogenesis model. First, retinal pericytes were abolished by anti-PDGFRβ antibody injection to C57/Bl6 neonatal mouse at P1. Pericyte dropout from endothelial cells is reportedly early histological change in DR, and induces bleeding, abnormal angiogenesis, inflammation, and retinal detachment with rapid progression at P9-11. The expression of XO level in retina was increasing after pericyte breakdown, and was proportional to VEGF, and preceding the increase of TNFalpha. When 3.6mg/kg Febuxostat (Fbx), an XO inhibitor was injected at P7, widespread edema and retinal detachment/funnel-like deformation were dramatically improved by Fbx treatment at P11. ICAM-1+ cells surrounding edema and CD11b+ cells were reduced. Next, we performed a 3D culture sprouting assay using HUVEC spheroids in collagen gel co-cultured with human lung fibroblast (hLF) in fibrin gel. By Fbx treatment within the physiological concentration, the branch sprouting, cellular migration to the distal side and mitosis in branch stems were inhibited. ICAM-1 increase in HUVEC was observed with hLF co-culture but was suppressed by Fbx treatment. Finally, these effects of Fbx were not shown on HUVEC in planar culture. On the other hand, dissolution of fibrin by hLF was delayed directly due to Fbx. VEGF and PAI-1 expression from hLF and MMP-9 activity in medium were decreased by Fbx treatment.

In summary, XO inhibition improved retinal inflammation and injury after pericyte loss. These results suggest the role of humoral inflammatory factors from mesenchymal cells surrounding retinal vessels in the hyperpermeable state such as DR.

Disclosure

A. Kushiyama: Research Support; Self; Teijin Pharma Limited, Sanwa Kagaku Kenkyusho Co., Ltd., Kowa Pharmaceutical Co., Ltd, StaGen. Consultant; Self; RIZAP. T. Kikuchi: None. H. Yamazaki: None. T. Yamamotoya: None. H. Sakoda: None. M. Fujishiro: Research Support; Self; Johnson & Johnson Services, Inc.. Y. Nakatsu: None. A. Uemura: Research Support; Self; Daiichi Sankyo Company, Limited, Boehringer Ingelheim GmbH, KAN Research Institute, Inc. T. Shirakura: Employee; Self; Teijin Pharma Limited. T. Asano: Research Support; Self; Teijin Pharma Limited, Sanwa Kagaku Kenkyusho Co., Ltd., Sanofi K.K. Y. Iwamoto: Board Member; Self; Japan Diabetes Foundation.
High-Fat Diet/Palmitate–Induced ER Stress Promotes Protein O-GlcNAcylation in Retina and Retinal Muller Cells
Authors: DAI WEIWEI , TORO ALLYSON , DIERSCHKE SADIE K. , DENNIS MICHAEL D.
Published: June 2018

The incidence of type 2 diabetes, the most common cause of diabetic retinopathy (DR), is rapidly on the rise due to the overconsumption of calorie rich diets. Using an animal model of diet-induced obesity/pre-type 2 diabetes, we evaluated the mechanism responsible for increased O-GlcNAcylation of retinal proteins following consumption of a diet high in saturated fat (HFD), as dysregulated O-GlcNAcylation contributes to the development of DR. In the retina of mice fed a HFD for 4 weeks, increased O-GlcNAcylation was observed concomitant with markers of endoplasmic reticulum (ER) stress. Similarly, in TR-MUL retinal cells in culture, addition of the saturated fatty acid palmitate or the ceramide analog Cer6 to culture medium increased protein O-GlcNAcylation and ER stress. One potential mechanism whereby ER stress increases O-GlcNAcylation is by upregulating flux through the hexosamine biosynthetic pathway (HBP) via increased expression of the rate-limiting enzyme glutamine-fructose-6-phosphate amidotransferase (GFAT). In the retina of mice fed a HFD and in TR-MUL cells exposed to Cer6, mRNA and protein expression of GFAT2, but not GFAT1 were increased. Similarly, in TR-MUL cells treated with the ER stress inducer thapsigargin (TG) increased O-GlcNAcylation was observed concomitant with an increase in GFAT2. Alternatively, ER stress inhibitor prevented the effect. GFAT2 knockdown via siRNA attenuated O-GlcNAcylation induced by either TG or Cer6. The glial cell specific transcription factor OASIS (old astrocyte specifically-induced substance) plays a central role in coordinating the unfolded protein response. Unlike GFAT1, GFAT2 contains a putative binding site for OASIS. Both HFD and Cer6 increased OASIS expression, and OASIS was sufficient to promote GFAT2 expression and increase O-GlcNAcylation. Overall, the results support a model whereby HFD-induced ER stress acts to promote O-GlcNAcylation in retina through an OASIS/GFAT2-dependent mechanism.

Disclosure

W. Dai: None. A. Toro: None. S.K. Dierschke: None. M.D. Dennis: None.
FFAR1 Agonism Restores Insulin Secretion in Rodents, Human Islets, and Diabetic Monkeys
Authors: LIU JIANYING , LEE SEUNGHUN P. , MARTIN TONYA , RADY BRIAN , MEEGALLA SANATH , HUANG HUI , WINTERS MICHAEL P. , NORQUAY LISA D. , QI JENSON , DU FUYONG , NAWROCKI ANDREA R. , PLAYER MARK , POCAI ALESSANDRO
Published: June 2018

The free fatty acid receptor 1 (FFAR1) mediates fatty acid-induced insulin secretion from pancreatic β-cells. Numerous ligands have been investigated for their antidiabetic actions. The most advanced, fasiglifam (TAK-875), is a site 1 binding agonist that stimulates IPone and improves glycemic control in diabetic patients via glucose-dependent insulin secretion (GSIS). Recently, FFAR1 agonists were discovered that bind to site 3, stimulate IPone and cAMP and result in both insulin and glucagon-like peptide-1 (GLP-1) secretion.

We hypothesized that this novel pharmacology would lead to superior glucose lowering relative to fasiglifam in diabetic monkeys. A selective FFAR1 agonist (CpdA) was discovered that activates rodent, cynomolgus and human FFAR1 receptors in vitro, triggering similar IPone and cAMP production. Incubation with CpdA but not fasiglifam restored insulin secretion in human islets from diabetic donors. Cpd A stimulates GLP-1 secretion in wild type but not GPR40 knockout mice, additionaly, as well as stimulates insulin secretion in ZDF rats. The ability of CpdA to control blood glucose was evaluated in diabetic cynomolgus monkeys during an oral glucose tolerance test after a single dose and repeated dosing for 7 days. Notably, the restoration of insulin secretion elicited by CpdA in diabetic human islets was recapitulated in vivo in diabetic monkeys and resulted in superior acute and chronic improvement in glucose tolerance relative to fasiglifam.

In conclusion, administration of CpdA restores insulin secretion and produces robust improvement in glucose metabolism in diabetic rodents and monkeys. Thus, FFAR1 agonists represent a potential treatment for type 2 diabetes.

Disclosure

J. Liu: None. S.P. Lee: Employee; Self; Janssen Research & Development. T. Martin: Employee; Self; Janssen Research & Development. Stock/Shareholder; Self; Janssen Research & Development. B. Rady: Employee; Self; Janssen Research & Development. S. Meegalla: None. H. Huang: None. M.P. Winters: None. L.D. Norquay: Employee; Self; Janssen Research & Development. J. Qi: None. F. Du: None. A.R. Nawrocki: Employee; Self; Janssen Pharmaceuticals, Inc.. M. Player: None. A. Pocai: None.
Relationship between Nitrated High-Density Lipoproteins and Vascular Function in African-American Diabetic Patients
Authors: ADEDAYO AJIBOLA M. , ELUWOLE AYOBAMI , TEDLA FASIKA , KREMER ARYE , MASTROGIOVANNI NICOLE , ROSENBERG CARL , DREIZEN PAUL , LAROSA JOHN , SALCICCIOLI LOUIS , BOUTJDIR MOHAMED , BANERJI MARY ANN , BROWN CLINTON , SALIFU MORO , LAZAR JASON , BAKILLAH AHMED
Published: June 2018

Previous studies have shown that HDL isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of nitrated apolipoprotein AI (NT-apoAI). The significance of NT-apoAI in the pathogenesis of vascular diabetic complications is not well understood. We aimed to evaluate the relationship between plasma NT-apoAI and vascular function in African-Americans diabetic patients. 125 patients with type 2 diabetes were enrolled over a 6 months period. Levels of plasma NT-apoAI was quantified by enzyme-linked immunosorbent assays (ELISA). Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound image analysis. Patients population was divided in two groups (well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c >7.0%, N=71). Mean age 60±8 years; 64% female; 80% had hypertension; 90% had dyslipidemia and 15% had CKD. Mean HbA1c levels were 8.1±2.2% and duration of diabetes was 10.29±3.79 years. NT-apoAI was negatively correlated with levels of apoAI and VRI in well-controlled patients but not in poorly-controlled patients (r= -0.298, p=0.025 and r= -0.265, p=0.042; respectively). Multi-regression analysis revealed that NT-apoAI was independently associated with VRI, but neither with PWV nor CIMT, after adjustment for independent variables such as age, gender, weight, hypertension, stroke, smoking, duration of diabetes, dyslipidemia, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.001, p= 0.025; r2= 0.325 for the model). NT-apoAI, independently of other clinical variables, can predict microvascular dysfunction particularly in well-controlled diabetic patients. NT-apoAI could be used as marker to identify diabetic patients at risk of developing early vascular complications.

Disclosure

A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.
Relationship between the Triglyceride Glucose Index and the Presence and Fibrosis of Nonalcoholic Fatty Liver Disease in Korean Adults
Authors: KIM MIN KYUNG , KIM JUNG HYE , PARK KAHUI , LEE SANG BAE , NAM JI SUN , KANG SHINAE , PARK JONG SUK , AHN CHUL WOO , KIM YU SIK
Published: June 2018

Background: Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance. Insulin resistance is a well known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and liver fibrosis in subjects with NAFLD. Thus, we investigated the relationship between the TyG index and liver fibrosis in Korean adults.

Methods: In total, 5158 participants who underwent ultrasonography in a health promotion center were enrolled. Anthropometric profiles and multiple metabolic risk factors were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. NAFLD was diagnosed by ultrasonography, and degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS). Significant liver fibrosis was defined as NFS ≥ -1.5.

Results: All subjects were stratified into four groups based on their TyG indices. Significant differences were observed in metabolic parameters among the groups, and the prevalence of NAFLD and liver fibrosis by NFS significantly increased with increasing TyG index. When classifying the severity of NAFLD into three groups, there was a significant correlation between the severity of NAFLD and the TyG index. In the logistic regression analysis after adjustment for multiple risk factors, the odds ratio for the prevalence of liver fibrosis, when comparing the highest and lowest quartiles of the TyG index was 1.92 (95% CI: 1.46-2.53; P for trend < 0.01); the odds ratio for the prevalence of liver fibrosis, when comparing the highest and lowest quartiles of HOMA-IR was 2.92 (95% CI: 1.12-2.40; P for trend <0.01).

Conclusion: There is a significant association between the TyG index and liver fibrosis of NAFLD, but HOMA-IR was superior to TyG index for predicting liver fibrosis in NAFLD patients.

Disclosure

M. Kim: None. J. Kim: None. K. Park: None. S. Lee: None. J. Nam: None. S. Kang: None. J. Park: None. C. Ahn: None. Y. Kim: None.
Prevalence of Lipid Abnormalities in Progressive Stages of Diabetes Mellitus
Authors: GUI BIN , SIAU EVAN , AMOROSA LOUIS F.
Published: June 2018

Prediabetes (PD) often exists in patients with coronary artery disease (CAD). This cross-sectional study aimed to uncover a link between measures of fat metabolism and lipid profiles with increasing stages of glucose intolerance which could promote premature CAD in PD.

Methods: Subjects from NHANES 2005-2012 without history of DM, dyslipidemia or medication for these disorders were matched by age and gender and categorized into normal group (HbA1c<5.7 and fasting plasma glucose<100mg/dl), PD group (6.5>HbA1c≥5.7 or 125mg/dl>fasting plasma glucose≥100mg/dl) and DM group (HbA1c≥6.5 or fasting plasma glucose≥125mg/dl). Body mass measures, plasma insulin level, lipid panel and hepatic steatosis were compared among 3 groups, using Chi-square and Wilcoxon rank sum test.

Results: From 29314 subjects in NHANES: 128 normal, 132 PD and 130 DM subjects were selected. Weight, BMI, waist circumference significantly increased within groups (all P<0.001) in parallel with hepatosteatosis, and consistent with increasing lipogenesis. LDL changes were distinctive being highest in PD group (P=0.0003).

Conclusions: Insulin values and progressive dyslipidemia correlated with increasing diabetes as expected, but the disparity between hepatic steatosis and LDL suggests an imbalance between lipogenesis and lipoprotein clearance resulting in higher LDL in PD; and a mechanism for early onset of diabetic induced atherogenesis.

Table 1Median and interquartile range or percentageNormal (1)PD (2)DM (3)P among groupsP (1) vs (2)P(2) vs (3)Total cholesterol204 (181-226)213 (194-249)2(182-245)0.010.0020.11LDL124 (99-141)146 (119-167)126 (100- 151)0.0003<0.00010.007Triglyceride104 (82 -139)117 (83-175)179 (131-243)<0.00010.13<0.0001HDL55 (42-69)49 (43-60)40 (34-48)<0.00010.16<0.0001Non-HDL-Cholesterol147 (126-170)167 (140-198)167 (135-196)<0.00010.00020.96Insulin7.24 (5.77-10.55)9.12 (7.28-12.59)15.22 (11.21-22.88)<0.00010.0002<0.0001Hepatic steatosis24.20%45.65%78.72%<0.00010.002<0.0001

Disclosure

B. Gui: None. E. Siau: None. L.F. Amorosa: None.
Longitudinal Changes in Depression and Glycemia in Adults with Type 1 Diabetes
Authors: TRIEF PAULA M. , FOSTER NICOLE C. , CHAYTOR NAOMI , HILLIARD MARISA E. , KITTELSRUD JULIE , JASER SARAH , MAJIDI SHIDEH , CORATHERS SARAH , BZDICK SUZAN , ADKINS DEANNA , WEINSTOCK RUTH S.
Published: June 2018

To assess change in depression over ≥4 years in adults with type 1 diabetes (T1D) and the association between change in depression and glycemic outcomes, we examined PHQ-8 data in adults in the T1D Exchange Clinic Registry with T1D duration ≥ 1 year (N= 2547; 57% female, 92% non-Hispanic white, year 1 age 43±16 years). PHQ-8 score ≥10 defined “depressed.” Linear regression was used to assess association of continuous outcomes and depression; logistic regression was used for categorical outcomes. At year 1/year 5, 9%/11% were depressed. In this sample, 126 (5%) had Persistent Depression (depressed at year 1 and year 5), 112 (4%) Resolved Depression (depressed at year 1, not at year 5), 148 (6%) New Year 5 Depression (not depressed at year 1, depressed at year 5), and 2161 (85%) Not Depressed at year 1/year 5. Of those depressed at year 1, 53% were depressed at year 5; of those not depressed at year 1, 6% were depressed at year 5. Participants with persistent depression/new year 5 depression had a significant increase (↑) in A1c [adj mean ↑ 0.5± 0.2/0.5± 0.2; adj mean 8.1±0.1 for both; adj P’s=0.001]; those not depressed at year 1/year 5 showed a trend in ↑A1c [0.3±0.1; adj mean 7.8±0.1; adj P=0.04]. Those with resolved depression did not show change in A1c [0.2±0.2; adj mean 7.7±0.2; adj P=0.28]. Those with persistent depression/new year 5 depression were more likely to report new year 5 DKA (DKA year 5 | no DKA year 1) than those not depressed at year 1/year 5 (adj P’s=0.03/0.04). There were trends for those with persistent depression to be more likely to report new year 5 severe hypoglycemia (SH) than those not depressed (11.1% vs. 4.8%); and for those with resolved depression to be less likely to report new year 5 SH (3.6 vs. 4.8%, adj P’s=0.09/0.11). Depression category was not associated with change in BMI (adj P=0.80). As a continuous variable, ↑in PHQ-8 was associated with ↑ in A1c (adj P<0.001), but not with new year 5 SH or BMI change (adj P>0.50). Depression (persistent or new year 5) has a negative impact on glycemic control over time. Adults with T1D should be screened and treated for depression.

Disclosure

P.M. Trief: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. N.C. Foster: None. N. Chaytor: None. M.E. Hilliard: None. J. Kittelsrud: None. S. Jaser: None. S. Majidi: None. S. Corathers: None. S. Bzdick: None. D. Adkins: None. R.S. Weinstock: Research Support; Self; Medtronic MiniMed, Inc., Mylan, Kowa Pharmaceuticals America, Inc., Diasome Pharmaceuticals, Inc., Calibra Medical, Dexcom, Inc., Ultradian Diagnostics LLC., JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases.
Study on the Effect of Cerium Oxide Nanocubes on Full-Thickness Cutaneous Wound Healing of Type 2 Diabetic Rats
Authors: HAN YANFEI , LI LINDONG , LIU YANJUN , WANG YOU , YAN CHUNHUA , SUN LINGDONG
Published: June 2018

Objective: To explore the effect and mechanism of cerium oxide nanocubes on the cutaneous wound healing of Goto-Kakizaki (GK) rats.

Methods: A total of 90 GK rats with full-thickness wounds were equally divided into three groups according to different treatments: normal saline (NS), recombinant human epidermal growth factor (rhEGF), and cerium oxide nanocubes solution (CONS). Two round cuts were made on the rats' dorsum from epidermis to the muscle layer. On days 3, 7, 10, 13, 16 and 21 post operation, five rats in each group were killed and made into specimens. Histological evaluation were conducted and the protein and mRNA levels of epidermal growth factor (EGF) and tumor necrosis factor (TNF-α) were analyzed with enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) technology. In addition, the levels of superoxide dismutase (SOD) and catalase (CAT) were detected by ELISA.

Results: Compared with the other two groups, the CONS-treated group had less inflammatory cell infiltration, more fibroblasts and smaller granulation tissue area in HE stained tissue micrographs. Meanwhile, Masson stained tissue micrographs showed thicker, more compact and more regular collagenous fiber. In CONS-treated rats, the wound healing rate on days 7 and 10 after surgery was significantly higher compared with other groups (p<0.05). On days 7, 10 and 13, the levels of TNF-α protein as well as TNF-α mRNA in the CONS-treated group were lower than in the NS-treated group (p<0.05). On days 7 and 10, SOD, CAT and EGF protein levels in the CONS-treated group were higher when compared to the NS-treated group (p<0.05), while the expression of EGF mRNA in the CONS-treated obviously increased from day 3 till day 13.

Conclusion: The mechanism of cerium oxide nanocubes promoting experimental diabetic wound healing may be related to reducing inflammatory reaction and promoting the synthesis of antioxidants and growth factors.

Disclosure

Y. Han: None. L. Li: None. Y. Liu: None. Y. Wang: None. C. Yan: None. L. Sun: None.
Diabetes Self-Management Education Program Effect on Glycemic Control and Insulin Dosing in Poor Diabetes Literacy Patients from Urban Areas in Mexico City—Therapeutic Education Underuse and Insulin Overuse
Authors: SILVA-TINOCO RUBÉN , MEZA DANIELA G. , MARTINEZ DAVID GARCIA , OROZCO JAVIER , ROMERO-IBARGUENGOITIA MARIA ELENA , DE LA TORRE-SALDAÑ VIRIDIANA A. , RAMOS GARCIA JESUS A. , DOLORES MARÍA C. , CUATECONTZI ENEDINA TERESA
Published: June 2018

Limited evidence exists on the efficacy of Diabetes Self-Management Education (DSME) in primary care urban population in low- and middle-income countries. This study evaluated the effect on glycemic control and insulin dosing in patients who attended an interdisciplinary educative structured program at Clínica Especializada en el Manejo de la Diabetes in México City-Iztapalapa in 2017. Intervention lasted 5 months and included individual and group sessions in a shared medical appointments model aimed at promoting self-care. In 252 patients with type 2 diabetes, diabetes literacy and self-care activities were assessed from the 10-item Spoken Knowledge in Low Literacy in Diabetes (SKILL-D, score 0-100) and the Summary of Diabetes Self-Care Activities (SDSCA, days/week), respectively. Women represented 67% and 59.6% had elementary or less education. Mean age was 55±10 years old, mean duration of diabetes was 13±8 years and 66% were on insulin treatment. SKILL-D and SDSCA scores increased from 22±19 to 80±16 and 2.5±1.4 to 4.7±1 days/week, respectively. HbA1c decreased from 9.3±2.1 to 6.7±1.1% (mean variation 2.5±2.1%; p<0.001) and daily total insulin dose decreased from 37±17 to 23±13 units (mean variation 13.5±14.7 units; p<0.001). Only in 22% another drug agent was added, in 18% insulin was discontinued and in 3% insulin started. Diabetes literacy and self-care activities were poor at the beginning of the study. This is a real-world study that showed that a non-pharmacological approach focused on promoting self-care, such as DSME, had in important effect on HbA1c reduction and insulin dosing in urban areas patients with low literacy, but also suggested an insulin over-prescription practice with lack of adherence/prescription to/of lifestyle interventions, before participation in this program.

Disclosure

R. Silva-Tinoco: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. D.G. Meza: None. D. Garcia Martinez: None. J. Orozco: None. M. Romero-Ibarguengoitia: None. V.A. De La Torre-Saldañ: None. J.A. Ramos Garcia: None. M.C. Dolores: None. E. Cuatecontzi: None.
Multidisciplinary Predialysis Team Education for Patients with Diabetic Nephropathy Reduced Cost for Admission at the Induction of Hemodialysis, and Subsequent Mortality
Authors: HITOMI MAMIKO , SATO TERUKO , MORIYA TATSUMI
Published: June 2018

Although a multidisciplinary individual team approach (MTA) has been thought to help prevent the progress of diabetic nephropathy (DN), its efficacy has not been fully examined. We compared the effect of an MTA on the hemodialysis (HD) course of 51 DN patients with that of 34 DN patients managed via a dietitian approach (DA) alone (total patients, n=85; male, n=58; age, 62±12 years; T2DM, n=81). In all cases, HD was initiated between January 2010 and May 2016. MTA staff members were doctors, dietitians, nurses, laboratory technologists, and pharmacists. Each intervention took 15-30 min at an outpatient clinic on the day of doctor visits. The team provided advice on nutrition, medication, medical exam, foot care, self-monitoring, and self-management. In the MTA group, the annual number of intervention sessions was higher, the cardiothoracic ratio was lower, and the cost per admission for HD induction was lower in comparison to the DA group (5.0±5.5/year vs.2.0±2.0/year, P=0.004; 53.1±6.6% vs. 57.3±7.4%, p=0.009; and 1.55±0.85 vs. 2.04±0.15 million JPY, p=0.029). Four patients in the MTA group and 9 in the DA group died during the observation period (likelihood ratio 5.381, p=0.020). A Kaplan-Meier survival analysis showed that the MTA group had superior patient survival (log rank p=0.009). The number of patients who underwent 24-h corrected urine tests 6 months before HD was higher in the MTA group (n=20 vs. n=5, likelihood ratio 6.281, p=0.025), while the urinary sodium excretion in 24 h urine collection was lower in the MTA group (8.2±2.2 g/day vs. 13.0±6.9, P=0.011).The stepwise regression analysis showed that the MTA and DA classifications mostly affected patient survival at the final observation (F=7.20, p=0.014).

In conclusion, the MTA provided good clinical and economic results for DN patients through improved self-management and an improved clinical course, even when implemented after the initiation of HD.

Disclosure

M. Hitomi: None. T. Sato: None. T. Moriya: None.
Novel Approach to Sarcopenia in Diabetic Patients Treated with GLP-1 Receptor Agonists (GLP-1RA)
Authors: IKEJIMA SHIN , KONDO SEIYA , SAKAI TAKENORI , TANIAI HISANORI , TAKAHASHI TOMOMI , UMEZU JUNKO , ISEKA MAMI , INOUE MAYA , NISHIHARA HARUMI , MURATA KAZUYA , HIRAI AIZAN
Published: June 2018

Background: It is expected that GLP-1 Receptor Agonists (GLP-1RA) have not only glucose lowering effect but also weight loss and protection of diabetic kidney disease. On the other hand, sarcopenia and frailty is becoming important, because elderly diabetic patients increase in Japan. In the present study, we report about falling risk, dietary surveys and exercise therapy of diabetic patients treated with GLP-1RA.

Methods: The questionnaire was tested in type 2 diabetic outpatients treated with GLP-1RA at our hospital (mean age 65.7 years). The control group was the diabetic outpatient treated without GLP-1RA in nearly the same age range (mean age 63.6 years). We measured hand grip strength and one-leg standing (OLS) time. Participants were defined as patients with a high risk of falling, If their hand grip strength was ≤30kg(male) or ≤20kg(female) and their OLS time was <20s. Especially if their OLS time was <5s, defined as patients with a severe high risk of falling. We also analyzed their dietary surveys in three days. Finally, we planned original exercise program to patients with a high risk of falling, and investigated the effect of this exercise every month.

Result: A total of 194 cases (male, 61%; female, 39 %) were included in this study. The prevalence of patients with a high risk falling was 36.1%. In patients treated with GLP-1RA (92 cases) and without GLP-1RA (102 cases), the prevalence of patients with a high risk falling was 45.7% and 27.5%. In patient treated with GLP-1RA, the prevalence of patients with severe high risk falling was 27.5% in liraglutide group (51 cases) and was 36.6% in dulaglutide group (41 cases). Dietary surveys and the effect of exercise program are on-going.

Conclusion: These findings show that type 2 diabetic patients treated with GLP-1RA are high risk group of falling compared with patients treated without GLP-1RA. Therefore, in use of GLP-1RA, we should be careful of sarcopenia and frailty involves in weight loss and muscle atrophy. Exercise and diet therapy are important.

Disclosure

S. Ikejima: None. S. Kondo: None. T. Sakai: None. H. Taniai: None. T. Takahashi: None. J. Umezu: None. M. Iseka: None. M. Inoue: None. H. Nishihara: None. K. Murata: None. A. Hirai: None.
Weight Loss among Adults with Type 2 Diabetes Participating in the Diabetes Prevention Program
Authors: CARPENEDO DOROTA , BROKAW SARAH M. , TYSK SONJA , FERNANDES JESSIE , HELGERSON STEVEN D. , HARWELL TODD S. ,   MONTANA DIABETES PREVENTION PROGRAM STUDY GROUP
Published: June 2018

Evidence suggests substantial weight loss may be associated with remission of T2DM. We assessed weight loss in adults with T2DM participating in an intensive lifestyle intervention using the National Diabetes Prevention Program (DPP) curriculum. While enrollment was targeted toward adults at high-risk for T2DM, adults with T2DM who were referred by their primary care provider and received medical clearance to participate were also permitted to enroll in the DPP (N = 105). Seventy percent of these participants were female; the mean age and baseline BMI were 59.2 years (SD 8.9) and 38.7 kg/m2 (SD 7.7), respectively. The mean number of core sessions and total sessions (22 total sessions) completed by participants was 12.1 (SD 3.8) and 14.5 (SD 5.5). Sixty percent of participants achieved the physical activity goal of ≥150 minutes of moderate physical activity. Forty-six percent and 28% of participants achieved ≥5% and ≥7% weight loss respectively. Results from the multiple logistic regression models indicated that participants who self-monitored their fat intake consistently and met the physical activity goal were more likely to achieve the 7% weight loss goal and participants who self-monitored their fat intake consistently were more likely to achieve ≥5% weight loss (Table). Our findings suggest that many persons with T2DM can achieve substantial weight loss through participation in DPP lifestyle intervention.Table. Factors independently associated with achieving seven percent and five percent weight loss among participants with T2DM enrolled in the Montana Diabetes Prevention Program, 2008-2016.Achieved 7% weight lossat 4 monthsAchieved 5% weight lossat 4 monthsAdjusted Odds Ratio (95% CI)PAdjusted Odds Ratio (95% CI)PAge (years)60+0.82 (0.27-2.5)0.720.79 (0.27-2.32)0.6736-591.0Reference1.0ReferenceSexFemale1.(0.31-3.55)0.930.41 (0.13-1.33)0.14Male1.0Reference1.0ReferenceBaseline BMI (kg/m2)25.0-29.91.41 (0.29-6.93)0.690.69 (0.14-3.37)0.5330.0-34.91.04 (0.28-3.82)0.851.31 (0.39-4.47)0.5035.0+1.0Reference1.0ReferenceCore Self-monitored fat (weeks)14-165.67 (1.67-27.55)0.024.21 (1.07-16.57)0.027-132.07 (0.44-9.74)0.811.34 (0.39-4.63)0.410-61.0Reference1.0ReferencePhysical activity goalMet2.92 (0.86-9.88)0.082.76 (0.97-7.84)0.06Unmet1.0Reference1.0Reference*95% CI – Ninety-five percent confidence interval.

Disclosure

D. Carpenedo: None.S.M. Brokaw: None.S. Tysk: None.J. Fernandes: None.S.D. Helgerson: None.T.S. Harwell: None.
Provider Experience Drives Clinical Decision Making in T2DM—Insights from Realistic Training Simulations
Authors: ROBINSON KATIE , ESGRO ROBERT A. , SEIFERT DOUGLAS
Published: June 2018

Rationale: Given the vast number of individual clinical scenarios and treatment options for patients with T2DM, clinical decision making is challenging. However, there is little evidence regarding the patient and provider characteristics that drive treatment selection.

Methods: Vindico Medical Education and Syandus partnered to create a virtual clinical training environment designed to identify and address drivers of treatment selection for patients with T2DM. The program featured three learner-centric clinical scenarios and evaluated participants in real-time, providing immediate, conversational feedback on the appropriateness of their decisions.

Results: For a newly-diagnosed patient with T2DM in need of treatment beyond metformin monotherapy, most providers selected an appropriate add-on agent with a preference for oral compounds [22% DPP-4 inhibitor, 26% SGLT2 inhibitor, 27% sulfonylurea (SU), 6% thiazolidinedione (TZD)], with the remainder selecting a GLP-1 RA (19%). The preference for oral agents persisted in a simulation of a patient with newly-diagnosed heart failure of which there were two most appropriate options based on patient characteristics (SGLT2 inhibitor, 63%; 37% GLP-1 RA 37%). Notably, when several classes of therapy were appropriate, providers with more clinical experience prefer newer agents (e.g., SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 RAs) vs. older agents (e.g., TZDs and SUs).

Conclusion: Providers prefer to treat patients with oral antidiabetes medications. More experienced providers prefer newer antidiabetes medications vs. their less-experienced colleagues, demonstrating the need for targeted education to junior providers on newer treatment options. Realistic clinical training simulations are an impactful tool to both educate providers on optimal clinical decision-making and identify drivers of clinical decision-making toward improved patient care.

Disclosure

K. Robinson: None. R.A. Esgro: None. D. Seifert: None.
Are Complications Preventable with Periodic Education via Telemedicine? A Study of 414 Compliant T2D Patients Followed Up for 19 Years
Authors: KESAVADEV JOTHYDEV , SHANKAR ARUN , DAVID ASHWIN , KRISHNAN GOPIKA , AJAI NEETHU A. , SANAL GEETHU , AJITH JAYSREE , JAYANTHI SOUMYA , RAMACHANDRAN LAKSHMY , JOTHYDEV SUNITHA
Published: June 2018

Background: Despite availability of many new diabetes therapies, outcomes still remain very poor, with majority developing debilitating vascular complications. Landmark trials have demonstrated, complications could be prevented if patients keep achieving A1c, BP and cholesterol targets. Diabetes Tele Management System (DTMS®), a sophisticated software integrated with multidisciplinary team was initiated in our centre since 1998 for customised titration of medications, diabetes education (DE) and behavioural modifications through virtual consultations (VC) precluding frequent physical visits (PV).

Aim: To assess long-term impact of DTMS® over 19 years,in successfully averting complications in T2D.

Methods: Patients enrolled in DTMS® and adhering to customised VC, with follow-up data available for 19 years were de-identified. Subjects: n 414, baseline:age 50.10±9.22y, males 60.09%, T2D duration 11.44±6.85y Inclusion criteria: VC ≥ 1 in 3 mths, PV ≥ 1 in 3y, and attended group DE ≥ 1 in 3y. Exclusion criteria: CKD (4and5).

Results: Change from baseline at 19th y: A1c= -0.68%, LDL=-60.3 mg/dl, creatinine= 0.04 mg/dl, SBP/DBP= -7.2/-8.66 mmHg. New onset CKD= 0.24%, CAD/CVA=2.4%, deaths=3.86%. Average PV frequency 2.04/y, VC 1.2/month.

Conclusion: Vascular complications could be successfully prevented, in 93.5% of the T2D subjects followed up for 19 years via tele-management program.

Disclosure

J. Kesavadev: Advisory Panel; Self; Novo Nordisk India Private Limited. Speaker's Bureau; Self; Novo Nordisk India Private Limited. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; MSD. Speaker's Bureau; Self; MSD. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. A. Shankar: None. A. David: None. G. Krishnan: None. N.A. Ajai: None. G. Sanal: None. J. Ajith: None. S. Jayanthi: None. L. Ramachandran: None. S. Jothydev: None.
A Meta-analysis of Real-World Observational Studies on the Impact of Flash Glucose Monitoring on Glycemic Control as Measured by HbA1c
Authors: SEIBOLD ALEXANDER , WELSH ZOE K. , ELLS SARA , SCHLAEGER CHRISTOF
Published: June 2018

Flash glucose monitoring is proven in randomized clinical trials to reduce the amount of time that people with type 1 or type 2 diabetes spend in hypoglycemia, with glucose below 3.9 mmol/L (70 mg/dL). Here we report a meta-analysis of real world observational studies on the impact of flash glucose monitoring on glycemic control as measured by HbA1c. A series of 17 studies were identified as reporting longitudinal HbA1c data in a total 1338 participants with type 1 (n=1112) or type 2 diabetes (n=226) using the FreeStyle Libre flash glucose monitoring system. Data included observations on children, adolescents and adults. The studies were reported in peer-reviewed published manuscripts, congress poster presentations and in-press data.

Meta-analysis of change in HbA1c was performed using trial as a random effect and weighting with the inverse of the within trial variance. Overall mean change in HbA1c was -0.56, 95% CI (-0.76, -0.36), with substantial heterogeneity between trials (I2=92.6%). Meta-regression was performed with the covariate initial HbA1c and treating trial as a random effect (Figure). No significant differences were detected based on length of study, type of diabetes (type 1 vs. type 2) or children vs. adults.

Disclosure

A. Seibold: Employee; Self; Abbott. Stock/Shareholder; Self; Abbott. Z.K. Welsh: Employee; Self; Abbott. Stock/Shareholder; Self; Abbott, AbbVie Inc. S. Ells: Employee; Self; Abbott. Stock/Shareholder; Self; Abbott. C. Schlaeger: Employee; Self; Abbott. Stock/Shareholder; Self; Roche Pharma.