bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistin-Like Molecule-β Inhibits SGLT-1 Activity and Enhances GLUT2-Dependent Jejunal Glucose Transport
Authors: Krimi Rim Belharbi , Letteron Philippe , Chedid Pia , Nazaret Corinne , Ducroc Robert , Marie Jean-Claude 
Published: June 2009

OBJECTIVE
An increased expression of RELM-β (resistin-like molecule-β), a gut-derived hormone, is observed in animal models of insulin resistance/obesity and intestinal inflammation. Intestinal sugar absorption is modulated by dietary environment and hormones/cytokines. The aim of this study was to investigate the effect of RELM-β on intestinal glucose absorption.

RESEARCH DESIGN AND METHODS
Oral glucose tolerance test was performed in mice and rats in the presence and the absence of RELM-β. The RELM-β action on glucose transport in rat jejunal sacs, everted rings, and mucosal strips was explored as well as downstream kinases modulating SGLT-1 and GLUT2 glucose transporters.

RESULTS
Oral glucose tolerance test carried out in rodents showed that oral administration of RELM-β increased glycemia. Studies in rat jejunal tissue indicated that mucosal RELM-β promoted absorption of glucose from the gut lumen. RELM-β had no effect on paracellular mannitol transport, suggesting a transporter-mediated transcellular mechanism. In studies with jejunal mucosa mounted in Ussing chamber, luminal RELM-β inhibited SGLT-1 activity in line with a diminished SGLT-1 abundance in brush border membranes (BBMs). Further, the potentiating effect of RELM-β on jejunal glucose uptake was associated with an increased abundance of GLUT2 at BBMs. The effects of RELM-β were associated with an increased amount of protein kinase C βII in BBMs and an increased phosphorylation of AMP-activated protein kinase (AMPK).

CONCLUSIONS
The regulation of SGLT-1 and GLUT2 by RELM-β expands the role of gut hormones in short-term AMPK/protein kinase C mediated control of energy balance.
Association of 18 Confirmed Susceptibility Loci for Type 2 Diabetes With Indices of Insulin Release, Proinsulin Conversion, and Insulin Sensitivity in 5,327 Nondiabetic Finnish Men
Authors: Stančáková Alena , Kuulasmaa Teemu , Paananen Jussi , Jackson Anne U. , Bonnycastle Lori L. , Collins Francis S. , Boehnke Michael , Kuusisto Johanna , Laakso Markku 
Published: June 2009

OBJECTIVE
We investigated the effects of 18 confirmed type 2 diabetes risk single nucleotide polymorphisms (SNPs) on insulin sensitivity, insulin secretion, and conversion of proinsulin to insulin.

RESEARCH DESIGN AND METHODS
A total of 5,327 nondiabetic men (age 58 ± 7 years, BMI 27.0 ± 3.8 kg/m2) from a large population-based cohort were included. Oral glucose tolerance tests and genotyping of SNPs in or near PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, LOC387761, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B were performed. HNF1B rs757210 was excluded because of failure to achieve Hardy-Weinberg equilibrium.

RESULTS
Six SNPs (TCF7L2, SLC30A8, HHEX, CDKN2B, CDKAL1, and MTNR1B) were significantly (P &lt; 6.9 × 10−4) and two SNPs (KCNJ11 and IGF2BP2) were nominally (P &lt; 0.05) associated with early-phase insulin release (InsAUC0–30/GluAUC0–30), adjusted for age, BMI, and insulin sensitivity (Matsuda ISI). Combined effects of these eight SNPs reached −32% reduction in InsAUC0–30/GluAUC0–30 in carriers of ≥11 vs. ≤3 weighted risk alleles. Four SNPs (SLC30A8, HHEX, CDKAL1, and TCF7L2) were significantly or nominally associated with indexes of proinsulin conversion. Three SNPs (KCNJ11, HHEX, and TSPAN8) were nominally associated with Matsuda ISI (adjusted for age and BMI). The effect of HHEX on Matsuda ISI became significant after additional adjustment for InsAUC0–30/GluAUC0–30. Nine SNPs did not show any associations with examined traits.

CONCLUSIONS
Eight type 2 diabetes–related loci were significantly or nominally associated with impaired early-phase insulin release. Effects of SLC30A8, HHEX, CDKAL1, and TCF7L2 on insulin release could be partially explained by impaired proinsulin conversion. HHEX might influence both insulin release and insulin sensitivity.
Human Brain Glycogen Metabolism During and After Hypoglycemia
Authors: Öz Gülin , Kumar Anjali , Rao Jyothi P. , Kodl Christopher T. , Chow Lisa , Eberly Lynn E. , Seaquist Elizabeth R. 
Published: June 2009

OBJECTIVE
We tested the hypotheses that human brain glycogen is mobilized during hypoglycemia and its content increases above normal levels (“supercompensates”) after hypoglycemia.

RESEARCH DESIGN AND METHODS
We utilized in vivo 13C nuclear magnetic resonance spectroscopy in conjunction with intravenous infusions of [13C]glucose in healthy volunteers to measure brain glycogen metabolism during and after euglycemic and hypoglycemic clamps.

RESULTS
After an overnight intravenous infusion of 99% enriched [1-13C]glucose to prelabel glycogen, the rate of label wash-out from [1-13C]glycogen was higher (0.12 ± 0.05 vs. 0.03 ± 0.06 μmol · g−1 · h−1, means ± SD, P &lt; 0.02, n = 5) during a 2-h hyperinsulinemic-hypoglycemic clamp (glucose concentration 57.2 ± 9.7 mg/dl) than during a hyperinsulinemic-euglycemic clamp (95.3 ± 3.3 mg/dl), indicating mobilization of glucose units from glycogen during moderate hypoglycemia. Five additional healthy volunteers received intravenous 25–50% enriched [1-13C]glucose over 22–54 h after undergoing hyperinsulinemic-euglycemic (glucose concentration 92.4 ± 2.3 mg/dl) and hyperinsulinemic-hypoglycemic (52.9 ± 4.8 mg/dl) clamps separated by at least 1 month. Levels of newly synthesized glycogen measured from 4 to 80 h were higher after hypoglycemia than after euglycemia (P ≤ 0.01 for each subject), indicating increased brain glycogen synthesis after moderate hypoglycemia.

CONCLUSIONS
These data indicate that brain glycogen supports energy metabolism when glucose supply from the blood is inadequate and that its levels rebound to levels higher than normal after a single episode of moderate hypoglycemia in humans.
Relationships Between Circulating Metabolic Intermediates and Insulin Action in Overweight to Obese, Inactive Men and Women
Authors: Huffman Kim M. , Shah Svati H. , Stevens Robert D. , Bain James R. , Muehlbauer Michael , Slentz Cris A. , Tanner Charles J. , Kuchibhatla Maragatha , Houmard Joseph A. , Newgard Christopher B. , Kraus William E. 
Published: June 2009

OBJECTIVE
To determine whether circulating metabolic intermediates are related to insulin resistance and β-cell dysfunction in individuals at risk for type 2 diabetes.

RESEARCH DESIGN AND METHODS
In 73 sedentary, overweight to obese, dyslipidemic individuals, insulin action was derived from a frequently sampled intravenous glucose tolerance test. Plasma concentrations of 75 amino acids, acylcarnitines, free fatty acids, and conventional metabolites were measured with a targeted, mass spectrometry–based platform. Principal components analysis followed by backward stepwise linear regression was used to explore relationships between measures of insulin action and metabolic intermediates.

RESULTS
The 75 metabolic intermediates clustered into 19 factors comprising biologically related intermediates. A factor containing large neutral amino acids was inversely related to insulin sensitivity (SI) (R2 = 0.26). A factor containing fatty acids was inversely related to the acute insulin response to glucose (R2 = 0.12). Both of these factors, age, and a factor containing medium-chain acylcarnitines and glucose were inversely and independently related to the disposition index (DI) (R2 = 0.39). Sex differences were found for metabolic predictors of SI and DI.

CONCLUSIONS
In addition to the well-recognized risks for insulin resistance, elevated concentrations of large, neutral amino acids were independently associated with insulin resistance. Fatty acids were inversely related to the pancreatic response to glucose. Both large neutral amino acids and fatty acids were related to an appropriate pancreatic response, suggesting that these metabolic intermediates might play a role in the progression to type 2 diabetes, one by contributing to insulin resistance and the other to pancreatic failure. These intermediates might exert sex-specific effects on insulin action.
Postprandial Glucose Improves the Risk Prediction of Cardiovascular Death Beyond the Metabolic Syndrome in the Nondiabetic Population
Authors: Lin Hung-Ju , Lee Bai-Chin , Ho Yi-Lwun , Lin Yen-Hung , Chen Ching-Yi , Hsu Hsiu-Ching , Lin Mao-Shin , Chien Kuo-Liong , Chen Ming-Fong 
Published: June 2009

OBJECTIVE
With increasing evidence about the cardiovascular risk associated with postprandial nonfasting glucose and lipid dysmetabolism, it remains uncertain whether the postprandial glucose concentration increases the ability of metabolic syndrome to predict cardiovascular events.

RESEARCH DESIGN AND METHODS
This was an observational study of 15,145 individuals aged 35–75 years without diabetes or cardiovascular diseases. Postprandial glucose was obtained 2 h after a lunch meal. Metabolic syndrome was diagnosed using the criteria of the U.S. National Cholesterol Education Program Adult Treatment Panel III. Cardiovascular and all-cause deaths were primary outcomes.

RESULTS
During a median follow-up of 6.7 years, 410 individuals died, including 82 deaths from cardiovascular causes. In a Cox model adjusting for metabolic syndrome status as well as age, sex, smoking, systolic blood pressure, LDL, and HDL cholesterol levels, elevated 2-h postprandial glucose increased the risk of cardiovascular and all-cause death (per millimole per liter increase, hazard ratio 1.26 [95% CI 1.11–1.42] and 1.10 [1.04–1.16], respectively), with significant trends across the postprandial glucose quintiles. Including 2-h postprandial glucose into a metabolic syndrome–included multivariate risk prediction model conferred a discernible improvement of the model in discriminating between those who died of cardiovascular causes and who did not (integrated discrimination improvement 0.4, P = 0.005; net reclassification improvement 13.4%, P = 0.03); however, the improvement was only marginal for all-cause death.

CONCLUSIONS
Given the risk prediction based on metabolic syndrome and established cardiovascular risk factors, 2-h postprandial glucose improves the predictive ability to identity nondiabetic individuals at increased risk of cardiovascular death.
A1C Underestimates Glycemia in HIV Infection
Authors: Kim Peter S. , Woods Christian , Georgoff Patrick , Crum Dana , Rosenberg Alice , Smith Margo , Hadigan Colleen 
Published: June 2009

OBJECTIVE
The objective of this study was to determine the relationship between A1C and glycemia in HIV infection.

RESEARCH DESIGN AND METHODS
We completed a prospective cross-sectional study of 100 HIV-infected adults with type 2 diabetes (77%) or fasting hyperglycemia (23%) with measured glucose, A1C, mean corpuscular volume (MCV), and fructosamine. A total of 200 HIV-uninfected type 2 diabetic subjects matched for key demographic characteristics served as control subjects.

RESULTS
Relative to the control subjects, A1C underestimated glucose by 29 ± 4 mg/dl in the HIV-infected subjects. Current nucleoside reverse transcriptase inhibitors (NRTIs), higher MCV and hemoglobin, and lower HIV RNA and haptoglobin were associated with greater A1C-glucose discordance. However, only MCV and current NTRI use, in particular abacavir, remained significant predictors in multivariate analyses. Fructosamine more closely reflected glycemia in the HIV-infected subjects.

CONCLUSIONS
A1C underestimates glycemia in HIV-infected patients and is related to NRTI use. Use of abacavir and increased MCV were key correlates in multivariate analyses. Fructosamine may be more appropriate in this setting.
Metformin for Obesity in Children and Adolescents: A Systematic Review
Authors: Park Min Hae , Kinra Sanjay , Ward Kirsten J. , White Billy , Viner Russell M. 
Published: June 2009

OBJECTIVE
To summarize the efficacy of metformin in reducing BMI and cardiometabolic risk in obese children and adolescents without diabetes.

RESEARCH DESIGN AND METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Double-blind RCTs of ≥6 months duration in obese subjects age ≤19 years without diabetes were included. Our primary outcomes of interest include changes in BMI and measures of insulin sensitivity.

RESULTS
Five trials met inclusion criteria (n = 320 individuals). Compared with placebo, metformin reduced BMI by 1.42 kg/m2 (95% CI 0.83–2.02) and homeostasis model assessment insulin of resistance (HOMA-IR) score by 2.01 (95% CI 0.75–3.26).

CONCLUSIONS
Metformin appears to be moderately efficacious in reducing BMI and insulin resistance in hyperinsulinemic obese children and adolescents in the short term. Larger, longer-term studies in different populations are needed to establish its role in the treatment of overweight children.
Quality of Diabetes Care for Immigrants in the U.S.
Authors: Dallo Florence J. , Wilson Fernando A. , Stimpson Jim P. 
Published: June 2009

OBJECTIVETo compare achievement of the American Diabetes Association diabetes care recommendations for U.S.- and foreign-born individuals with diabetes.RESEARCH DESIGN AND METHODSUsing the 2001–2006 Medical Expenditure Panel Surveys, we report estimates for receipt of a cholesterol test, routine checkup, influenza vaccination, eye examination, dental checkup, foot examination, and two or more A1C tests in 1 year for foreign- (n = 1,272) and U.S.-born (n = 5,811) individuals aged ≥18 years. We define a dichotomous variable representing full compliance with the above examinations. We provide descriptive characteristics of the sample and use multivariable analysis for each procedure with random effects logit regression.RESULTSCompared with U.S.-born individuals with diabetes, foreign-born individuals are younger, have lower education levels and income, are more likely to have public or no insurance, and are less likely to have a usual source of care. With adjustment for all potential confounders, foreign-born individuals are less likely to report having had an influenza vaccination (odds ratio 0.51 [95% CI 0.31–0.71]) or to be compliant with any one of the seven recommendations (0.64 [0.34–0.95]).CONCLUSIONSThese findings demonstrate that immigrants are less likely than U.S.-born individuals with diabetes to adhere to any one of seven diabetes care recommendations in general and, specifically, are less likely to report having received an influenza vaccination. Because immigrants are less likely to use health care, clinicians should take advantage of the office visit to effectively communicate to the patient the importance of receiving an influenza vaccination.
Randomized Comparison of Pramlintide or Mealtime Insulin Added to Basal Insulin Treatment for Patients With Type 2 Diabetes
Authors: Riddle Matthew , Pencek Richard , Charenkavanich Supoat , Lutz Karen , Wilhelm Ken , Porter Lisa 
Published: June 2009

OBJECTIVE
To compare the efficacy and safety of adding mealtime pramlintide or rapid-acting insulin analogs (RAIAs) to basal insulin for patients with inadequately controlled type 2 diabetes.

RESEARCH DESIGN AND METHODS
In a 24-week open-label, multicenter study, 113 patients were randomly assigned 1:1 to addition of mealtime pramlintide (120 μg) or a titrated RAIA to basal insulin and prior oral antihyperglycemic drugs (OADs). At screening, patients were insulin naive or had been receiving &lt;50 units/day basal insulin for &lt;6 months. The basal insulin dosage was titrated from day 1, seeking fasting plasma glucose (FPG) ≥70–&lt;100 mg/dl. Pramlintide and an RAIA were initiated on day 1 and week 4, respectively. The proportion of patients achieving A1C ≤7.0% without weight gain or severe hypoglycemia at week 24 was the primary end point.

RESULTS
More pramlintide- than RAIA-treated patients achieved the primary end point (30 vs. 11%, P = 0.018) with a similar dose of basal insulin. Pramlintide and an RAIA yielded similar mean ± SEM values for FPG and A1C at 24 weeks (122 ± 7 vs. 123 ± 5 mg/dl and 7.2 ± 0.2 vs. 7.0 ± 0.1%, respectively) and similar least squares mean reductions from baseline to end point (−31 ± 6 vs. −34 ± 6 mg/dl and −1.1 ± 0.2 vs. −1.3 ± 0.2%, respectively). RAIAs but not pramlintide caused weight gain (+4.7 ± 0.7 vs. +0.0 ± 0.7 kg, P &lt; 0.0001). Fewer patients reported mild to moderate hypoglycemia with pramlintide than with the RAIA (55 vs. 82%), but more patients reported nausea (21 vs. 0%). No severe hypoglycemia occurred in either group.

CONCLUSIONS
In patients taking basal insulin and OADs, premeal fixed-dose pramlintide improved glycemic control as effectively as titrated RAIAs. The pramlintide regimen sometimes caused nausea but no weight gain and less hypoglycemia.
Serum Lipopolysaccharide Activity Is Associated With the Progression of Kidney Disease in Finnish Patients With Type 1 Diabetes
Authors: Nymark Mariann , Pussinen Pirkko J. , Tuomainen Anita M. , Forsblom Carol , Groop Per-Henrik , Lehto Markku ,   on behalf of the FinnDiane Study Group
Published: June 2009

OBJECTIVE
The aim of the study was to investigate whether serum lipopolysaccharide (LPS) activities are associated with the progression of kidney disease in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS
For this prospective study, we chose 477 Finnish patients with type 1 diabetes, who were followed for 6 years. At the baseline visit, 239 patients had a normal albumin excretion rate (normoalbuminuria) and 238 patients had macroalbuminuria. Patients were further divided into nonprogressors and progressors based on their albumin excretion rate at follow-up. Eighty normoalbuminuric patients had developed microalbuminuria, and 79 macroalbuminuric patients had progressed to end-stage renal disease. Serum LPS activity was determined with the Limulus amoebocyte lysate chromogenic end point assay.

RESULTS
Serum LPS activity was significantly higher in the macroalbuminuric group than in the normoalbuminuric group (P &lt; 0.001). Notably, normoalbuminuric progressor patients had a significantly higher LPS activity at baseline than normoalbuminuric nonprogressor patients (median 49 [interquartile range 34–87] vs. 39 [29–54] EU/ml; P = 0.001). The normoalbuminuric progressor patients exhibited features of the metabolic syndrome with higher triglyceride concentrations and lower estimated glucose disposal rate. A high LPS-to-HDL ratio was associated with the progression of kidney disease in both groups. Insulin resistance (P &lt; 0.001) and serum LPS activity (P = 0.026) were independent risk factors of disease development, when A1C was removed from the regression analysis.

CONCLUSIONS
High serum LPS activity is associated with the development of diabetic nephropathy in Finnish patients with type 1 diabetes.
Evaluation of an immunoassay for determination of haptoglobin concentration in various biological specimens from swine
Authors: Gutiérrez Ana M. , Martínez-Subiela Silvia , Cerón Jose J. 
Published: June 2009

Abstract
Objective—To develop and evaluate an immunoassay based on time-resolved immunofluorometry (TR-IFM) for measurement of haptoglobin concentrations in samples of various body fluids of swine.
Animals—20 pigs without clinical signs of disease and seronegative for antibodies against major viruses that affect pigs and 30 pigs with clinical signs of disease.
Procedures—Haptoglobin concentrations were measured in samples of serum, saliva, and meat juice obtained from both groups of pigs to evaluate the ability of TR-IFM to differentiate between healthy and diseased pigs. Performance of TR-IFM was evaluated by means of its calibration curve and detection limit, analytic precision during routine operation, and linearity of results for serial dilutions for the 3 types of samples. In addition, performance of TR-IFM was compared with that of a commercial spectrophotometric assay.
Results—The TR-IFM assay involved only 1 step, and the results were obtained in 20 minutes, with good analytic sensitivity and reproducibility. The analytic limit of detection was 0.52 ng/mL. Intra-assay and interassay coefficients of variation ranged from 1.13% to 4.81% and 5.97% to 13.57%, respectively. The method yielded linear results for all sample types. Serum haptoglobin concentrations determined by use of TR-IFM and spectrophotometric assays were highly correlated (r = 0.96). Differences between healthy and diseased pigs with respect to median haptoglobin concentrations were significant for all types of samples.
Conclusions and Clinical Relevance—The 1-step TR-IFM assay accurately quantified haptoglobin concentrations in serum, saliva, and meat juice samples from swine and may be useful in laboratory and meat inspection settings.
Phase I evaluation of carboplatin by use of a dosing strategy based on a targeted area under the platinum concentration-versus-time curve and individual glomerular filtration rate in cats with tumors
Authors: Bailey Dennis B. , Rassnick Kenneth M. , Dykes Nathan L. , Pendyala Lakshmi 
Published: June 2009

Abstract
Objective—To determine whether a carboplatin dose calculation that is based on a targeted area under the concentration-versus-time curve (AUCTarget) and individual glomerular filtration rate (GFR) accurately predicts carboplatin-associated myelotoxicoses in tumor-bearing cats, and to determine the maximum tolerated AUCTarget.
Animals—32 cats with tumors.
Procedures—In each cat, plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid was measured to assess GFR. Carboplatin was administered IV. The dose was calculated by use of an equation as follows: Dose = AUCTarget × 2.6 × GFR × body weight. Initial AUCTarget was 2.0 min·mg·mL−1 and was increased in increments of 0.50 min·mg·mL−1 in cohorts of 3 cats. To assess myelotoxic effects, CBCs were performed weekly for ≥ 4 weeks. Following identification of the maximum tolerated AUCTarget, additional cats were treated at that AUCTarget and plasma platinum concentrations were measured in 6 cats.
Results—The AUCTarget values ranged from 2.0 to 3.0 min·mg·mL−1. Neutropenia was the dose-limiting toxicosis, and the maximum tolerated AUCTarget was 2.75 min·mg·mL−1. Nineteen cats received this dose of carboplatin; 13 became neutropenic, but only 1 developed severe neutropenia (< 500 neutrophils/μL), and none had neutropenia-associated clinical signs. In the cats that had plasma platinum concentration determined, the difference between AUCTarget and the measured value ranged from −0.23 to 0.31 min·mg·mL−1 (median, 0.20 min·mg·mL−1).
Conclusions and Clinical Relevance—In cats, carboplatin-associated myelotoxicoses were accurately and uniformly predicted by use of the proposed dosing strategy. The maximum tolerated AUCTarget for a single dose of carboplatin was 2.75 min·mg·mL−1.