bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary NGAL and KIM-1 Are Significantly Elevated in Young Adults (YA) with Type 1 (T1D) and Type 2 (T2D) Diabetes
Authors: SHEANON NICOLE M. , MOTTL AMY K. , DAGOSTINO RALPH , SUERKEN CYNTHIA , AFKARIAN MARYAM , DABELEA DANA , IMPERATORE GIUSEPPINA , MARCOVINA SANTICA M. , PETTITT DAVID J. , SAYDAH SHARON , DOLAN LAWRENCE M. 
Published: June 2018

Urinary (U) neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are markers of renal tubular injury. Whether NGAL and KIM-1 are elevated in early diabetic kidney disease (DKD) is not known. We performed a pilot study to compare the U concentrations (C) of NGAL and KIM-1 in YA with T1D or T2D from the SEARCH registry and healthy controls (n 45 in each group). The YA with diabetes were selected based on age at dx &gt; 10 years and duration &gt;8 years and were randomly selected across the quartiles of eGFR with similar age, gender and ethnicity. T1D (age 21 ± 2 years; duration 9.6 ± 1.0 years; HbA1c 9.3 ± 2.1% eGFR 126 ± 19 mL/min/1.73m2, UACR 11 ± 16 µg/mg), T2D (age 24 ± 3 years, duration 9.8 ± 1.2 years, HbA1c 8.5 ± 3.0%, eGFR 128 ± 21 mL/min/1.73m2, UACR 38 ± 71 µg/mg), controls (age 23 ± 3 years). In each group 50% were female, 41% white, 43% AA, and 16% Hisp. NGAL and KIM-1 were significantly elevated in T1D and T2D compared with controls (p &lt; 0.001, p&lt; 0.007). Although there was a trend for a greater UC of NGAL in T2D than T1D and a greater UC of KIM-1 in T1D than T2D, these differences were not statistically significant. Elevated UC of NGAL and KIM-1 are present in YA with T1D and T2D suggesting the presence of tubular damage early in the course of diabetes. Further investigation will determine if these markers can be used to assess the natural history of tubular injury or monitor therapeutic intervention in DKD.

Disclosure
N.M. Sheanon: None. A.K. Mottl: None. R. Dagostino: Consultant; Self; Teva Pharmaceutical Industries Ltd., Acelity, RedHill Biopharma, Edwards Lifesciences. C. Suerken: None. M. Afkarian: None. D. Dabelea: None. G. Imperatore: None. S.M. Marcovina: None. D.J. Pettitt: None. S. Saydah: None. L.M. Dolan: None.
Effect of Thiazolidinediones on Renal Outcomes in Diabetic Patients with Microalbuminuria or Macroalbuminuria-A Systematic Review and Meta-analysis
Authors: QIN YAO , WANG XING , ZHANG MEI 
Published: June 2018

Introduction: Diabetic nephropathy (DN), has recently become the leading cause of end-stage renal disease (ESRD) in most countries, recent studies suggest that thiazolidinediones (TZDs) have renal benefits. The aim of this meta-analysis was to assess the effect of TZDs on renal outcomes in type 2 diabetic patients with microalbuminuria or macroalbuminuria.
Methods: Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched from 1991 to September 2017. Randomized controlled trials (RCTs) were selected to evaluate the impact of TZDs on urinary albumin, protein excretion, eGFR or Scr in diabetic patients. Weighted (WMDs) and standardized mean differences (SMDs) were used for changes in urine albumin or protein excretion, eGFR and Scr between the TZDs and control groups.
Results: 26 RCTs (9 with rosiglitazone and 17 with pioglitazone) involving 8129 patients with type 2 diabetes were included in this review. Meta-analysis of RCTs showed that in patients with baseline normo- and/or microalbuminuria, the WMD of proportional changes between the TZDs and control groups in urinary albumin excretion was -64.77% (95% CI, -75.60 to -53.94) and the WMD of changes in albumin-creatinine ratio was -24.94% (95% CI, -38.83 to -11.05). Overall, in participants with normo- and/or microalbuminuria, TZDs treatment was associated with a significant decrease in urinary albumin excretion (SMD, -0.91 units of standard deviation [SD]; 95% CI, -1.19 to -0.64). Similarly, TZDs were associated with a significant decrease in urinary protein excretion in patients with macroalbuminuria (SMD, -1.units of SD; 95% CI, -1.86 to -0.27). However, TZDs treatment couldn’t effectively improve eGFR or the level of Scr in diabetic patients whether with microalbuminuria or macroalbuminuria.
Conclusions: Treatment with TZDs can benefit patients with early diabetic nephropathy in absence of renal dysfunction.

Disclosure
Y. Qin: None. X. Wang: None. M. Zhang: None.
Glycemic Fluctuation and the Risk of Hypoglycemia Unawareness Associated with Hemodialysis in Type 2 Diabetic Renal Failure
Authors: HAYASHI AKINORI , MOMOZONO AKARI , KAWAI SAYUKI , MASAKI TSUGUTO , YOSHINO SONOMI , OGAWA AKIFUMI , TAKANO KOJI , SHICHIRI MASAYOSHI 
Published: June 2018

Despite the high-risk of asymptomatic hypoglycemia associated with hemodialysis (HD) using glucose-free dialysate, presence of dialysate glucose is believed to prevent intradialytic hypoglycemia. However, exact glycemic fluctuation profiles and frequency of asymptomatic hypoglycemia during HD remain unappreciated. Using continuous glucose monitoring, we evaluated glycemic excursions in 63 type 2 diabetic HD patients (44 male, HbA1c 6.4±1.2%) treated with a dialysate containing either 100, 125 or 150 mg/dL glucose. Average sensor glucose level (SGL) at start of HD after 7.2±5.0 U bolus insulin and breakfast was 187.9±56.2 mg/dL. SGL showed gradual and sustained decrease during HD irrespective of the dialysate glucose levels (Figure). SGL nadir reached below the dialysate glucose levels in 23 of 37 patients treated with dialysate containing 100 mg/dL glucose, in 14 of 17 patients with 125 mg/dL and in all 9 patients with 150 mg/dL. Fourteen of all 63 patients (22%) presented with HD-related hypoglycemia as defined by SGL &lt;63 mg/dL during HD or immediately after HD up until the next meal. All hypoglycemic episodes revealed asymptomatic.
In conclusion, type 2 diabetic HD patients present a high-risk of HD-related hypoglycemia unawareness despite the use of dialysate containing 100-150 mg/dL glucose. SGL may fall well below the dialysate glucose level toward the end of HD.

Disclosure
A. Hayashi: None. A. Momozono: None. S. Kawai: None. T. Masaki: None. S. Yoshino: None. A. Ogawa: None. K. Takano: None. M. Shichiri: None.
Artificial Intelligence Predicts Progress of Diabetic Kidney Disease-Novel Prediction Model Construction with Big Data Machine Learning
Authors: MAKINO MASAKI , ONO MASAKI , ITOKO TOSHINARI , KATSUKI TAKAYUKI , KOSEKI AKIRA , KUDO MICHIHARU , HAIDA KYOICHI , KURODA JUN , YANAGIYA RYOSUKE , SUZUKI ATSUSHI 
Published: June 2018

Background: Diabetic kidney diseases (DKD) including diabetic nephropathy is the most frequent cause of hemodialysis (HD), and more precise prediction model could be useful to early intervention of DKD.
Methods: We constructed new prediction model for DKD by using artificial intelligence (AI) based on electronic medical records (EMRs). From EMRs of 64,059 diabetes patients who visited our hospital, we extracted a variety of features. This model uses the stage of nephropathy as labels, and predicts whether the stage 1 patients will move up their stage after 180 days.
Results: AI constructed new prediction model by big data machine learning. First, AI extracted raw features in past 6 months at reference period, and selected 22 factors. Then, time series data analysis using convolutional autoencoder was conducted to find time series patterns relating to 6-month DKD aggravation. AI then constructed the prediction model with 17raw features as well as time series and text as secondary features using logistic regression. Finally, AI predicted DKD aggravation with 0.74 AUC score at maximum. Furthermore, DKD aggravation group had significantly higher incidence of HD than non-aggravation group in 10 years.
Conclusion: The new prediction model by AI could detect progress of DKD, which could contribute to more effective and accurate intervention to reduce HD.

Disclosure
M. Makino: Research Support; Spouse/Partner; THE DAI-ICHI LIFE INSURANCE COMPANY, LIMITED. Self. M. Ono: None. T. Itoko: Employee; Self; IBM. T. Katsuki: Employee; Self; IBM. A. Koseki: Employee; Self; IBM. M. Kudo: Employee; Self; IBM. K. Haida: Employee; Self; Daiichilife Insurance Company. J. Kuroda: Employee; Self; The Dai-ichi Life Insurance Company, Limited. R. Yanagiya: None. A. Suzuki: Research Support; Self; THE DAI-ICHI LIFE INSURANCE COMPANY, LIMITED.. Speaker's Bureau; Self; Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation. Research Support; Self; EA Pharma Co Ltd, Daiichi Sankyo Company, Limited, Chugai Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., MSD K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.
Interaction of Exocrine and Endocrine Pancreas in Obesity Ciliopathies
Authors: HOSTELLEY TIMOTHY L. , DUNLEAVEY JESSICA , ZAGHLOUL NORANN A. 
Published: June 2018

Ciliopathies are rare genetic disorders characterized by dysfunction in primary cilia. Two ciliopathies, Alström Syndrome and Bardet-Biedl Syndrome (BBS), are characterized by high rates of obesity. However, they have strikingly different rates of diabetes. The rate is much higher in Alström patients relative to BBS. To gain insight into genetic mechanisms for this discrepancy we performed whole transcriptome sequencing on zebrafish depleted of the Alström gene, alms1, or the BBS gene, bbs1. We identified gene expression changes and found 8 genes that were differentially expressed in opposite directions between the two models. Among these, several exocrine pancreas enzymes were downregulated in Alström and/or upregulated in BBS. Based on this, and our previous demonstration of β-cell mass changes in models of both disorders, we hypothesized that the expression of exocrine pancreas enzymes affects endocrine pancreas function. This might suggest that impaired β-cell function in Alström results from reduced expression of exocrine pancreas enzymes, while the opposite may be true in BBS. These findings also support a non-ciliary role for BBS and Alström genes as we found them to be expressed in the non-ciliated acinar cells. To test our hypothesis, we overexpressed each enzyme in transgenic zebrafish embryos, in which β-cells can be visualized. In control animals, overexpression of the exocrine pancreas enzymes significantly increased the number of β-cells, suggesting that these enzymes play a role in regulating β-cell mass and function. Overexpression could also rescue the loss of β-cells observed in animals depleted of alms1. We have also found that the inactive form of these enzymes are selectively taken up by β-cells in vitro and induce proliferation in cultured MIN6 β-cells. This suggests a direct interaction between the exocrine and endocrine pancreas. Taken together, these data support the possibility that exocrine pancreatic enzymes may play an important role in the modulation of β-cells in diabetes.

Disclosure
T.L. Hostelley: None. J. Dunleavey: None. N.A. Zaghloul: None.
Clinical Variables and Outcomes of Kidney Transplant Recipients with Type 2 Diabetes and New-Onset Diabetes after Transplantation in a Predominantly Minority Urban Population
Authors: ALEKSIC SANDRA , ANARAKI SARA ZAHEDPOUR , TSOMOS EFFIE , UPADHYAY LAXMI , JAPP EMILY , AJAIMY MARIA , AKALIN ENVER , ZONSZEIN JOEL 
Published: June 2018

Background: Minority populations remain at a high risk for type 2 diabetes (T2D) and its complications. In kidney transplant recipients T2D and new onset diabetes after transplant (NODAT) are associated with worse outcomes, but data from minority populations are limited. We aimed to characterize clinical variables and outcomes in a predominantly minority kidney transplant recipients with T2D and NODAT.
Methods: We performed a retrospective chart review of all recipients of kidney transplant in a large urban university center from June 01, 2012 until December 31, 2014. Individuals with type 1 diabetes or pancreas transplant were excluded. NODAT was defined by the ADA criteria.
Results: We included 304 individuals, 40% Hispanic and 41% non-Hispanic black. Fifty percent had T2D. During a median follow-up of 37 (22-52) months, 36% of the recipients without diabetes developed NODAT. Hispanics and non-Hispanic blacks less frequently remained without diabetes compared to non-Hispanic whites (27% vs. 29% vs. 51%, p=0.001). Individuals with T2D had higher BMI compared to NODAT and no diabetes (29.9±7.4 vs. 28.1±6.5 vs. 27.2±5.7kg/m2, p=0.007). Individuals with T2D and NODAT were older than those without diabetes (60.8±9.5 vs. 56.5±13 vs. 47.9±14 years, p&lt;0.0001), had more pretransplant cardiovascular disease (36 vs. 26 vs. 11%, p&lt;0.0001), more deceased-donor transplants (90 vs. 93 vs. 75%, p=0.0007), and had significantly higher proteinuria at 6, 12, and 24 months posttransplant, but no difference was found in serum creatinine, graft survival (94 vs. 94 vs. 93%, p=0.904) or patient survival (93 vs. 96 vs. 95%, p=0.708).
Conclusions: In a predominantly minority cohort there was a high rate of both T2D and NODAT with only less than one fifth of individuals without diabetes. In this high-risk population, there was no difference in patient or graft survival over a relatively short observational period.

Disclosure
S. Aleksic: None. S. Zahedpour Anaraki: None. E. Tsomos: None. L. Upadhyay: None. E. Japp: None. M. Ajaimy: None. E. Akalin: None. J. Zonszein: Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc..
Effect of Carnosine Supplementation on Cardiometabolic Risk Factors in Obesity, Prediabetes, and Diabetes—A Meta-analysis of Randomized Controlled Trials
Authors: MENON KIRTHI ARAVIND , MOUSA AYA , COURTEN BARBORA DE 
Published: June 2018

The burden of diabetes is rapidly increasing in line with the growing obesity epidemic. Identification of simple and easily scalable interventions is therefore urgently needed. Carnosine (beta-alanyl-L-histidine), a dipeptide with anti-inflammatory, anti-oxidative, and anti-glycating properties, has been proposed as a potential strategy for the prevention of diabetes. However, previous studies examining the effects of carnosine on cardiometabolic risk factors have produced inconsistent results. Here, we present the first systematic review and meta-analysis examining the effects of carnosine supplementation on cardiometabolic risk factors. Electronic databases including Medline, CINAHL, EMBASE and EBM Reviews were searched to identify all randomized controlled trials (RCTs) comparing supplementation with carnosine vs. placebo, usual care or other interventions. In meta-analyses of five trials with 309 participants, carnosine-supplemented groups had lower HbA1c (mean difference (MD) [95% CI]= -0.5% [-0.4,-0.6], p&lt;0.001); fasting glucose (MD [95% CI]= -0.6 mmol/L [-1.1, -0.1], p=0.03); postprandial glucose (MD [95% CI]= -1.0 mmol/L [-1.4, -0.6], p&lt;0.001); triglycerides (MD [95% CI]= -0.4 mmol/L [-0.6, -0.3], p=0.005); and high-sensitivity C-reactive protein (MD [95% CI]= -0.4 mg/L [-0.6, -0.2], p&lt;0.001) compared with placebo. Low statistical heterogeneity was observed for all outcomes (I2=0-1%) except fasting glucose (I2=84%). However, heterogeneity in study design was an important limitation, including the different populations studied, and the use of varying doses of carnosine and mixed supplementation. Nevertheless, our findings suggest that carnosine may improve cardiometabolic risk factors and further well designed randomized controlled trials are needed to confirm these findings.

Disclosure
K. Aravind Menon: None. A. Mousa: None. B. de Courten: None.
Intrauterine Growth Retardation Induced Long-Term Gene Dysregulation Is Associated with Altered Histone Modifications in Rat Islets
Authors: LIEN YU-CHIN , WANG PAUL , SIMMONS REBECCA A. 
Published: June 2018

Intrauterine growth retardation (IUGR) is associated with the development of type 2 diabetes in adulthood. Although the underlying mechanisms remain unclear, permanent alterations in gene expression implicate epigenetics. Using a rat model of IUGR induced by bilateral uterine artery ligation at e18, we sought to determine if histone modifications are a potential mechanism for permanent IUGR-induced gene dysregulation. We assessed genome-wide histone modifications in islets from 2 and 10 week control and IUGR rats using ChIP-Seq. IUGR induced significant changes in enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in 2 week islets at 2181, 1482, and 4572 annotated genes, respectively. At 10 week there were far more changes in enrichment of these marks (9988, 3489, and 4355 genes, respectively). We then integrated our RNA-Seq transcriptome data obtained at the same ages and found that the expression levels of multiple genes in IUGR islets were correlated with changes in histone marks. In 10 week islets, the expression of 639, 355, and 400 genes correlated with changes in enrichment of H3K4me3, H3K27me3, and H3K27Ac, respectively; whereas in 2 week islets, only 43, 64, and 149 genes were correlated with enrichment of these marks. Interestingly, 6 genes in 10 week islets correlated with changes in all 3 histone marks, strongly suggesting that changes in gene expression were induced by histone modifications. Ingenuity pathway analysis of differential expressed genes that correlated with histone modifications revealed significant enrichment in pathways critical for normal islet function, such as cAMP-mediated signaling, immune function, axonal guidance, and VEGF family ligand-receptor interaction. Collectively, the present findings identify histone modification as a potential epigenetic mechanism that may contribute to long-term gene dysregulation and abnormal islet phenotype in IUGR animals.

Disclosure
Y. Lien: None. P. Wang: None. R.A. Simmons: None.
Prevalence of Peripheral Neuropathy in Prediabetes
Authors:   UAZMAN ALAM, OF LIVERPOOL DIABETES AND ENDOCRINE RESEARCH GROUP,   UNIVERSITY, EARLY NEUROPATHY ASSESSMENT GROUP, MANCHESTER
Published: June 2018

Objectives: There are conflicting evidence regarding the relationship of peripheral neuropathy in prediabetes. Our aim was to determine the prevalence of peripheral neuropathy in prediabetes through a systematic literature review and meta-analysis.
Methods: Five electronic databases, namely MEDLINE, EMBASE, PubMed, Web of Science and Cochrane Central Register of Controlled Trials were searched for studies published up to October 2017. Original full studies were included that provided prevalence data for a population with prediabetes, who were over 18 years of age. Additional studies were identified from reference lists and two reviewers independently identified eligible studies on predefined inclusion criteria.
Results: In total, 1314 studies were identified after duplicates were removed and subsequently 1255 were excluded. Of the 59 remaining studies, 23 studies (n=6494) met the inclusion criteria for the meta-analysis. The pooled prevalence estimate of neuropathy in prediabetes was 18% (95% CI: 13-22%) with a marked level of heterogeneity (I2 = 97%). The high level of heterogeneity between studies was partly explained by the method of neuropathy assessment. Subgroup analyses based on the method of neuropathy assessment was evaluated and the prevalence was highly dependent on the method of assessment. The prevalence depending on the type of test used was: quantitative tests: 16% (95% CI: 3-30%, I2 = 95%), physical examination: 24% (95% CI: 7-40%, I2 = 83%), questionnaires: 8% (95% CI: 2 -13%, I2 = 57%) and combination(s) of the three: 18% (95% CI: 13- 24%, I2 = 97%).
Conclusions: There is a higher than expected prevalence of peripheral neuropathy in prediabetes. Future large, population based studies using accurate and quantitative means of identifying neuropathy are required and an internationally agreed definition as to what constitutes prediabetic neuropathy is required.

Disclosure
U. Alam: Speaker's Bureau; Self; Sanofi, Novo Nordisk A/S.
LXRs Protect DRG Neurons from High-Fat Diet–Induced ER Stress and Allodynia
Authors: AUBERT VIRGINIE 
Published: June 2018

Painful diabetic neuropathy (DN) affecting small sensory neurons is one of the most common complications of obesity and type 2 diabetes. While emerging clinical evidence demonstrates that DN is associated with dyslipidemia, the complex molecular and cellular neurobiology triggering the disease is unknown. Emerging evidence demonstrates the important contribution of complex pathways including endoplasmic reticulum stress and inflammation. Recent OMICs data analyzing peripheral nervous tissue (Dorsal root ganglia (DRG) and associated nerves) of obese individuals have also highlighted alterations in lipid nuclear receptors, which provide novel insight into the onset of DN. Liver X Receptors (LXR) α and β are nuclear transcription factors that respond to cholesterol or fatty acid metabolites. Nuclear LXRs control gene programs in liver cells, adipocytes, and macrophages to regulate lipid metabolism, inflammation and ER stress though the specific physiological role of LXRs in neurons is difficult to interpret given its broad tissue expression. Our tissue specific deletion model unmasks an important role of LXR in small sensory neurons in type 2 DN pathogenesis. Our results show that LXR deletion in sensory neurons worsens the hypersensitivity induced by a High fat Diet (HFD) associated with changes in DRG gene. In addition, treatment with the LXR agonist GW4965 improves the HFD-induced mechanical allodynia in vivo and protects mice DRG sensory neurons from lipid-induced ER stress in vitro and in vivo (ribo-tag model), further confirming a protective role for LXR in DN. Our data suggest that the lipid sensor LXRs in small sensory neurons could respond to dietary lipid to potentially maintain normal PNS function in the face of high-fat nutrition.

Disclosure
V. Aubert: None.