bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ileum-Specific Transgenic Expression of Human Chimeric Intestinal Alkaline Phosphatase (IAP) Attenuates Western Diet (WD)–Induced Barrier Dysfunction and Glucose Intolerance
Authors: HE HONGLIANG , GHOSH SIDDHARTHA S. , YANNIE PAUL J. , WANG JING , GHOSH SHOBHA 
Published: June 2018

Intestinal epithelial cell derived IAP dephosphorylates/detoxifies bacterial endotoxin LPS in the gut lumen. We have earlier demonstrated that improvement of intestinal barrier function was accompanied by an increase in IAP activity. Herein, we developed IAP transgenic mice where expression of human chimeric IAP is under the control of intestine specific villin promoter. As shown in Panel A, compared to non-transgenic wild type (WT) littermates, IAP expression (identified by c-myc tag) was noted in colon, ileum jejunum and duodenum of IAP-transgenic (IAPTg) mice. IAP was almost uniformly expressed along the length of the ileum (Panel B) and while IAP activity reduced from proximal P1 segment to distal P9 segment in WT mice, this activity was maintained in the IAPTg mice (Panel C). Dietary challenge with WD impaired glucose tolerance in WT mice and this intolerance was attenuated in IAPTg mice (Panels D and E). Significant decrease in fecal zonulin, a marker for intestinal barrier dysfunction, in WD fed IAPTg mice (Panel F) and a corresponding decrease in translocation of oral 4kDa FITC dextran to plasma (Panel G) suggests that IAP overexpression improves intestinal barrier function. Thus, targeted increase in IAP activity represents a novel strategy to improve WD induced intestinal dysfunction and glucose intolerance.

Disclosure
H. He: None. S.S. Ghosh: None. P.J. Yannie: None. J. Wang: None. S. Ghosh: None.
Simple Screening for Glucose Intolerance Based on Myoinositol Levels in Self-Collected Urine Samples at Home
Authors: TAKAKADO MISAKI , TAKATA YASUNORI , KAWAMURA RYOICHI , OSAWA HARUHIKO 
Published: June 2018

Background: Urinary myoinositol (UMI) is a molecule with a structure similar to D-glucose. In the presence of hyperglycemia, reabsorption of MI in the renal tubules is inhibited by urinary glucose (UG), resulting in high concentrations of MI excreted into the urine. Unlike UG, UMI is highly stable at room temperature (RT) for over a week. Therefore, we conducted a study to establish a simple screening method for glucose intolerance (GI) based on UMI levels in self-collected pre- and postprandial urine samples at home.
Methods: First, to diagnose GI, we performed a 75gOGTT at the hospital in 115 volunteers without a past history of diabetes (DM). Within a week, each volunteer collected urine samples before and 2h after consuming the test meal (500kcal, energy bar) at home, and these samples were shipped to a single laboratory at RT. UMI was measured using an enzymatic method.
Results: To assess the usefulness of UMI for screening GI (IGT+DM), we performed statistical analyses using receiver-operating characteristic (ROC) curve. It revealed that the area under the curve of ROC (AUCROC) for 2h-postprandial UMI/creatinine (Cr) was 0.74 for diagnostic accuracy of GI (IGT+DM). The optimal cut-off was 27 mg/gCr with a sensitivity of 60%, and a specificity of 81%. For diagnostic accuracy of DM, AUCROC for 2h-postprandial UMI/Cr was 0.83, with a sensitivity of 80%, and a specificity of 74% at the cut-off value of 27 mg/gCr.
Conclusions: UMI measurement of urine samples self-collected at home may be a non-invasive, inexpensive, and valuable screening method for GI. This strategy may be suitable for subjects in area with limited access to medical care including developing countries, and could be the first step towards further medical examinations such as blood glucose (OGTT when required), and HbA1c.

Disclosure
M. Takakado: None. Y. Takata: None. R. Kawamura: None. H. Osawa: None.
Differential Effects of Birth Weight on Early-Onset Type 2 Diabetes in Adolescents and Young Adults
Authors: OLAIYA MUIDEEN T. , SINHA MADHUMITA , HANSON ROBERT L. , KOBES SAYUKO , NELSON ROBERT , KNOWLER WILLIAM C. 
Published: June 2018

Background: Type 2 diabetes mellitus (T2DM) is increasingly diagnosed in adolescents and young adults. However, the impact of birth weight (BW) on this early onset T2DM is not well quantified.
Methods: A longitudinal study of Southwestern American Indians, aged ≥ 5 years, was conducted from 1965-2007. Subjects who had a recorded BW and at least one research exam that included an OGTT were followed until they developed T2DM or their last exam before the age of 40 years, whichever came first. Age-sex-adjusted incidence rate of T2DM was computed and Poisson regression models were used to estimate the effect of BW on the incidence of T2DM, adjusted for sex, BMI z-score (fitted as time-varying), and maternal variables, such as the presence of diabetes during pregnancy. The effect of BW on T2DM was non-proportional over time, and in some regression models, the effect was non-linear (quadratic). Therefore, all analyses were stratified by decade of age at follow-up and BW was analyzed as quintiles.
Results: Among 4,275 subjects (52% females, median BW 3.45 kg), there were 728 incident cases of T2DM over a median follow-up of 20.6 years (7.5 cases per 1000 person-years). Incidence rates, stratified by decade of age at follow-up, were greater in females and in older age groups. In multivariable regression analyses, the effect of BW on T2DM risk varied by age group, showing a quadratic (U-shaped) effect at 10-19 years (P&lt;0.05) and a negative linear effect at older age intervals (20-29 years, P=0.015; 30-39 years, P&lt;0.001). We could not reliably estimate risk at 0-9 years because of few cases. Female sex, greater BMI z-score, and the presence of maternal diabetes in pregnancy added to the effect of BW on T2DM risk in all age groups.
Conclusions: Both low and high BWs increased the risk of T2DM in adolescence, but only the effect of low BW persisted into young adulthood. Effects of female sex, accelerated growth, or being the offspring of a diabetic pregnancy added to the effect of BW on the risk of early onset T2DM.

Disclosure
M.T. Olaiya: None. M. Sinha: None. R.L. Hanson: None. S. Kobes: None. R. Nelson: None. W.C. Knowler: None.
Metabolic Syndrome and Prediabetes Fail to Detect a High Prevalence of Early Insulin Resistance—The PREMIER Study
Authors: CISTOLA DAVID P. , DWIVEDI ALOK K. , ARD JAMY D. 
Published: June 2018

The PREMIER Study was a multi-center randomized controlled trial of lifestyle interventions in 810 nondiabetic subjects with elevated blood pressure. At baseline, one half of the cohort met the criteria for metabolic syndrome (MetS) and one third met the fasting glucose criterion for prediabetes (PreD). The purpose of the current analysis of PREMIER data was to quantify the sensitivity of the MetS criteria and cut points for detecting hyperinsulinemia and insulin resistance, defined here as fasting insulin ≥ 12 μIU/mL based on prior calibration against the euglycemic clamp. Insulin showed statistically significant bivariate correlations with 4 of the 5 MetS criteria in decreasing order of strength: waist circumference, fasting glucose, HDL-cholesterol and fasting triglycerides. By contrast, systolic and diastolic blood pressure, and total- and LDL-cholesterol did not correlate with fasting insulin. Logistic regression revealed that each MetS criterion, except blood pressure, had an independent contribution to hyperinsulinemia, even after correcting for age, race and gender. Receiver operator characteristic curves showed that the harmonized MetS cut points were non-optimal for detecting hyperinsulinemia. Specifically, the fasting triglyceride and glucose cut points were too high, while those for waist circumference were too low. Using the criteria for MetS and hyperinsulinemia, the subjects were divided into four metabolic subtypes. The subtype with hyperinsulinemia but not MetS represented 14.7% (95% CI 12.4-17.5) of the cohort. The prevalence of individuals with hyperinsulinemia that did not meet the criteria for MetS or PreD was surprisingly high at 12.7% (95% CI 10.3-15.1). This subtype is an important target for early intervention and diabetes prevention, but was not detected in this population using the current criteria for MetS or PreD. New screening strategies and metabolic health measures are needed to improve outcomes for diabetes prevention.

Disclosure
D.P. Cistola: None. A.K. Dwivedi: None. J.D. Ard: Consultant; Self; Nestlé. Research Support; Self; Nestlé, VIVUS, Inc..
The Visceral Adiposity Index Is a Significantly Stronger Predictor of Incident Diabetes in Men than in Women
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN DANIELA , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ 
Published: June 2018

The visceral adiposity index (VAI) is a validated tool for the evaluation of visceral adiposity, using waist circumference, serum triglycerides, age and gender to diagnose this metabolic abnormality. We aimed at investigating the power of the VAI to predict diabetes incidence in men and in women. We prospectively recorded diabetes incidence in a large consecutive cohort of 1282 patients undergoing coronary angiography for the evaluation of established or suspected coronary artery disease who did not have diabetes at baseline. The VAI was calculated according to the Amato formula; diabetes was diagnosed according to ADA criteria. At baseline, the VAI score did not differ significantly between men (n=845) and women (230±199 vs. 238±239; p=0.247). Prospectively, 133 patients newly developed diabetes during a follow-up period of 3.7±0.9 years; diabetes incidence did not differ significantly between men and women (13.3 vs. 9.8%; p=0.093. The VAI significantly predicted incident diabetes in men but not in women both univariately (standardized odds ratios (ORs) of 1.71 [1.40-2.10]; p&lt;0.001 and 1.09 [0.81-1.49]; p=0.565, respectively) and after multivariate adjustment (standardized adjusted ORs 1.56 [1.24-1.97]; p&lt;0.001 and 1.[0.75-1.46]; p=0.790, respectively). An interaction term VAI x gender was statistically significant (p=0.017), indicating that the VAI was a significantly stronger predictor of diabetes incidence among men than women. We conclude that the VAI is a significantly stronger predictor of diabetes incidence in men than in women.

Disclosure
C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin: None. B. Larcher: None. A. Mader: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
Clinical Importance of One-Hour Plasma Glucose in Relation to Diabetes and Metabolic Syndrome in an Obese Population
Authors: HAVERALS LIEN , VAN DESSEL KRISTOF P.S. , VERRIJKEN AN , DIRINCK EVELINE L. , PEIFFER FRIDA W. , GAAL LUC VAN , BLOCK CHRISTOPHE DE 
Published: June 2018

Introduction: Type 2 diabetes mellitus (T2DM) is increasingly prevalent and associated with increased morbi/mortality. In Caucasian obese subjects we investigated a possible link between 1-hour plasma glucose (1HrPG), diabetes and the metabolic syndrome (MetS).
Methods: Overweight and obese patients were consecutively included from the obesity clinic. ROC-curves were used to compare the diagnostic sensitivity and specificity of 1HrPG vs. fasting plasma glucose (FPG), 2HrPG, and HbA1c to diagnose diabetes, using American Diabetes Association criteria.
Results: We included 2439 patients (72% female) [mean age 43±13 years, median BMI 37.3 (33.7-41.3) kg/m²]. Diabetes was diagnosed in 9.8% and prediabetes in 33.8% of subjects. Exactly 1262 (51,7%) had a 1HrPG ≥155 mg/dL. These subjects were more insulin-resistant (p&lt;0.001), had a higher waist (p&lt;0.001), visceral adipose tissue (VAT) (p&lt;0.001), systolic blood pressure (p&lt;0.001), worse lipid profile (p&lt;0.001), and higher plasminogen activator inhibitor-1 (PAI-1) [p&lt;0.001] than subjects with 1HrPG &lt;155mg/dL. MetS was present in 64.1% of the subjects with 1HrPG ≥155 mg/dL vs. 42.5% of subjects with a 1HrPG &lt;155 mg/dL (p&lt;0.001). In the group with 1HrPG ≥155 mg/dL only 32.6% had a normal glucose tolerance (NGT) while 18.5% was diagnosed with T2DM and 48.9% had prediabetes, compared to 81.7% NGT, 0.6% T2DM and 17.7% prediabetes in subjects with a 1HrPG &lt; 155 mg/dL (p&lt;0.001). In the group with NGT 412 subjects (30,0%) had a 1HrPG ≥155 mg/dL. These subjects showed higher HOMA-IR (p=0.008), VAT (p&lt;0.001), blood pressure (p&lt;0.001), worse lipid profile (p=0.001) than those with a 1HrPG&lt;155 mg/dl, indicating its clinical relevance. For diabetes, the ROC area under the curve for 2HrPG was 0.928, compared to 1HrPG (0.764), Hba1c (0.752) and, FPG (0.600).
Conclusion: This study supports the need for detection of subjects with higher 1HrPG values. being at risk for development of T2DM, MetS and cardiovascular disease.

Disclosure
L. Haverals: None. K.P.S. Van Dessel: None. A. Verrijken: None. E.L. Dirinck: None. F.W. Peiffer: None. L. Van Gaal: Advisory Panel; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Speaker's Bureau; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Research Support; Self; EU (Hepadip & Resolve consortium) and National Research Funds. C. De Block: None.
Glucose Variability of Individuals without Diabetes Using a Long-Term Continuous Glucose Monitoring System
Authors: DEISS DOROTHEE , ABTAHI TAHMID , RASTOGI RAVI , KELLEY E. L. 
Published: June 2018

Background: Prior investigations regarding glucose variability in nondiabetic subjects measured by continuous glucose monitoring (CGM) have been limited to only few weeks. Little is known about what defines healthy or pathologic glycemic variability. This study investigated “normal glycemia” under daily conditions using a long-term implantable CGM system in nondiabetic adults for 90 days.
Methods: 25 adult nondiabetic participants (10 Male, 15 Female, 17 participants &gt;45 years old) were inserted with the Eversense® CGM System (Senseonics Inc, MD). Participants were instructed to continuously wear the CGM system during the 90 day period and calibrate the system when prompted. Analysis was performed to estimate standardized measures of euglycemia (70-180 mg/dL), hypoglycemia (&lt;54, &lt;70 mg/dL), hyperglycemia (&gt;180, &gt;200 mg/dL) and glucose variability (Mean, SD, CV).
Results: Out of 25 participants, 5 had inadequate data for inclusion. Analysis showed the average glucose value of the nondiabetic participants was 102 mg/dL (SD=18 and CV=0.17). Average percent time spent in hypoglycemia &lt;54mg/dL was 0.14% and &lt;70mg/dL was 1.5%. Time spent in euglycemia 70-180 mg/dL was 98%. Time spent in hyperglycemia &gt;180 and &gt;200 mg/dL was 0.17% and 0.05%, respectively. 17 participants had at least one value &lt; 54mg/dL and 18 participants had glucose values &gt;180mg/dL with 11 subjects with glucose values &gt; 200mg/dL.
Conclusions: Glycemic variability recorded over extended period of time in participants without a diagnosis of diabetes showed similar results as observed by previous researchers over short duration with tight glycemic control. However, hypo- and hyperglycemic excursions are in some normoglycemic regarded individuals more frequent than suggested without CGM. Further analysis including meal challenge and fasting levels may provide guidance regarding expected values for persons without a diagnosis of diabetes and to set realistic target ranges for those with diabetes.

Disclosure
D. Deiss: Consultant; Self; Senseonics. Advisory Panel; Self; Abbott. Consultant; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Becton, Dickinson and Company. T. Abtahi: Other Relationship; Self; Senseonics. R. Rastogi: Employee; Self; Senseonics. E.L. Kelley: Employee; Self; Senseonics.
Exocrine Pancreatic Function as a Novel Biomarker in Pre-T1D
Authors: ROSS JAMES J. , WASSERFALL CLIVE , PERRY DANIEL J. , MCGRAIL KIERAN M. , POSGAI AMANDA L. , BRUSKO TODD M. , SCHATZ DESMOND , HALLER MICHAEL J. , ATKINSON MARK A. 
Published: June 2018

Recent studies demonstrated reduced serum trypsinogen levels as well as pancreatic weight/volume in patients with type 1 diabetes (T1D) and nondiabetic/autoantibody (AAb)-positive subjects. Histological defects including increased CD8+ T cell infiltration and elevated C4d deposition have been observed in the exocrine T1D pancreas. Like trypsinogen, amylase and lipase are produced by the exocrine pancreas and serve as more common markers of exocrine function. We hypothesized that amylase and lipase levels would be lower in patients with T1D as well as in subjects with multiple (i.e., ≥2) T1D-related AAb compared with controls. To test this, serum amylase and lipase levels were determined in 70 patients with recent-onset T1D (duration &lt;3 mo), 57 patients with established T1D (duration &gt;3 mo), 56 single AAb positive (1AAb+) subjects, 42 multiple AAb positive (≥2AAb+) subjects, 96 AAb negative (AAb-) relatives of T1D patients, and 110 AAb- control subjects. Amylase levels, which are independent of age (r = -0.02, P = 0.7), were significantly lower in patients with T1D (mean ± SD 39.98 ± 17.8 ng/mL; P &lt; 0.005) vs. AAb- subjects (47.40 ± 20.17 ng/mL). Lipase levels, which are positively correlated with age (r = 0.30, P &lt; 0.0001), were significantly lower in T1D patients (25.95 ± 21.ng/mL; P &lt; 0.001) as well as ≥2AAb+ subjects (22.59 ± 11.12 ng/mL; P &lt; 0.001) compared with 1AAb+ individuals (37.60 ± 16.79 ng/mL). These results provide further evidence that exocrine pancreas abnormalities exist in patients with T1D and ≥2AAb+ subjects considered to have early-stage T1D with high risk of progressing to clinical diagnosis. These data also support the possibility that an inherent or acquired defect in exocrine pancreas development and/or function may contribute to disease pathogenesis, but cause and effect cannot yet be ascertained. Importantly, these exocrine pancreas enzymes may serve as biomarkers of T1D to better predict disease progression and/or stratify patients according to etiology.

Disclosure
J.J. Ross: None. C. Wasserfall: None. D.J. Perry: None. K.M. McGrail: None. A.L. Posgai: None. T.M. Brusko: Stock/Shareholder; Self; OneVax, LLC. Advisory Panel; Self; Caladrius Biosciences, Inc.. Consultant; Self; Merck & Co., Inc., Sanofi-Aventis. D. Schatz: None. M.J. Haller: None. M.A. Atkinson: Other Relationship; Self; Patent Issued.
The Progression of Hyperglycemia and Diabetes Before and After Lung Transplant
Authors: AKSHINTALA DIVYA , SCHEKER EVANA VALENZUELA , PELAEZ ANDRES , CHANDRASHEKARAN SATISH , MACHUCA TIAGO , LEEY JULIO A. 
Published: June 2018

Diabetes mellitus (DM) is a frequent complication of organ transplantion . The aim of the study was to determine the incidence and prevalence of DM after Lung Transplant (LTx).
Methods: Chart review of patients undergoing LTx at the University of Florida, Gainesville between 2013 and 2015. Variables such as diabetes status before and after LTx, glucose level (G) during first seven days after LTx, insulin therapy and other relevant factors were included.
Results: There were 81 LTx surgeries corresponding to 78 patients (3 had repeat LTX). Prior to LTx 14 patients had DM (5 CF), only 2 them were taking insulin, both had CF. G &gt;200 mg/dl and &lt;70mg/dl were observed in 71% (58/81) and 19% (16/81) patients during the first 7 days after LTx respectively. At LTx surgery discharge, 35% (29/81) were on insulin, 51% of them (15/29) on basal insulin alone or in combination. After 12m from LTx, 26 were on insulin, 69% of them (18/26) on basal insulin alone or in combination. Among those who had G&gt;200mg/dl within the first 7 days, only 19% (11/58) had been diagnosed of DM before LTX, and 45% of them (26/58) were taking DM medications 12 months after LTx, and 65% (17/26) were using basal insulin alone or in combination.
Conclusion: Inpatient hyperglycemia is very common after LTx. Use of insulin at discharge is a strong predictor for use of insulin 12m after LTX, indicating the need for close monitoring.
Characteristic1 month BEFORE LTx12 months AFTER LTxAge (SD)50.7 (16.8)xFemale41% (34/81)xBMI23.9 (4.0)25.2 (4.2)Diabetes Mellitus18 (14/78) Dx per PMH36% (28/78) Dx per medication listAny type of Insulin14% (2/14)32% (26/81)G &gt;200 mg/d first 7 d after LTx71% (58/81)xG &lt;70 mg/dl first 7 d after LTx19% (16/81)x

Disclosure
D. Akshintala: None. E. Valenzuela Scheker: None. A. Pelaez: None. S. Chandrashekaran: None. T. Machuca: None. J.A. Leey: None.
Different Course of the Microvascular Complications of Diabetes Mellitus in Kidney Transplant Recipients with Posttransplant Diabetes—A Longitudinal Study
Authors: LONDERO GAI THIZÁ M. , GIARETTA LUANA S. , MANFRO ROBERTO C. , CANANI LUIS H. , LAVINSKY DANIEL , LEITAO CRISTIANE B. , BAUER ANDREA 
Published: June 2018

Objective: This study assessed microvascular complications (MC) occurrence in renal posttransplant diabetes mellitus (PTDM).
Methods: Patients ≥ 5 years of PTDM were included from a cohort of 895 kidney recipients (KR) transplanted in 2000-2011. Diabetic retinopathy (DR) was evaluated by fundus photographs (FP) and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and eGFR. Distal polyneuropathy (DPN) was assessed by Michigan Protocol/monofilament foot exam. Ewing protocol identified cardiovascular autonomic neuropathy (CAN). Controls were KR transplanted in the same period but without PTDM (NPTDM).
Results: After 578 weeks, 135 (15%) KR developed PTDM, 64 with PTDM ≥ 5 years. None of PTDM KR presented DR at FP but thinning of inner retinal layers was observed with OCT (Figure 1). More than 60% of PTDM KR had DPN (OR 1.55; CI 1.26-1.91; p&lt;0.001). Frequency of CAN was similar between PTDM and NPTDM KR (p=0.26). During the 1st year and after 8.5±3.0 years of transplantation, eGFR and PCR did not differ between groups.
Conclusions: This is the first longitudinal study to assess MC in PTDM KR. A lower than expected prevalence as well as a different clinical course of the MC was observed. PTDM seems to be a unique type of DM and its consequences may be milder than expected in type 1 and type 2 DM.

Disclosure
T.M. Londero Gai: None. L.S. Giaretta: None. R.C. Manfro: None. L.H. Canani: None. D. Lavinsky: None. C.B. Leitao: None. A. Bauer: None.