bluuebunny/crossref_metadata_2025 huggingface dataset:
Smad3 Deficiency in Mice Protects Against Insulin Resistance and Obesity Induced by a High-Fat Diet
Authors: Tan Chek Kun , Leuenberger Nicolas , Tan Ming Jie , Yan Yew Wai , Chen Yinghui , Kambadur Ravi , Wahli Walter , Tan Nguan Soon
Published: January 2011

OBJECTIVE

Obesity and associated pathologies are major global health problems. Transforming growth factor-β/Smad3 signaling has been implicated in various metabolic processes, including adipogenesis, insulin expression, and pancreatic β-cell function. However, the systemic effects of Smad3 deficiency on adiposity and insulin resistance in vivo remain elusive. This study investigated the effects of Smad3 deficiency on whole-body glucose and lipid homeostasis and its contribution to the development of obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS

We compared various metabolic profiles of Smad3-knockout and wild-type mice. We also determined the mechanism by which Smad3 deficiency affects the expression of genes involved in adipogenesis and metabolism. Mice were then challenged with a high-fat diet to study the impact of Smad3 deficiency on the development of obesity and insulin resistance.

RESULTS

Smad3-knockout mice exhibited diminished adiposity with improved glucose tolerance and insulin sensitivity. Chromatin immunoprecipitation assay revealed that Smad3 deficiency increased CCAAT/enhancer-binding protein β-C/EBP homologous protein 10 interaction and exerted a differential regulation on proliferator-activated receptor β/δ and proliferator-activated receptor γ expression in adipocytes. Focused gene expression profiling revealed an altered expression of genes involved in adipogenesis, lipid accumulation, and fatty acid β-oxidation, indicative of altered adipose physiology. Despite reduced physical activity with no modification in food intake, these mutant mice were resistant to obesity and insulin resistance induced by a high-fat diet.

CONCLUSIONS

Smad3 is a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes, suggesting that Smad3 may be a potential target for the treatment of obesity and its associated disorders.
Induction of Mixed Chimerism With MHC-Mismatched but Not Matched Bone Marrow Transplants Results in Thymic Deletion of Host-Type Autoreactive T-Cells in NOD Mice
Authors: Racine Jeremy , Wang Miao , Zhang Chunyan , Lin Chia-Lei , Liu Hongjun , Todorov Ivan , Atkinson Mark , Zeng Defu
Published: January 2011

OBJECTIVE

Induction of mixed or complete chimerism via hematopoietic cell transplantation (HCT) from nonautoimmune donors could prevent or reverse type 1 diabetes (T1D). In clinical settings, HLA-matched HCT is preferred to facilitate engraftment and reduce the risk for graft versus host disease (GVHD). Yet autoimmune T1D susceptibility is associated with certain HLA types. Therefore, we tested whether induction of mixed chimerism with major histocompatibility complex (MHC)-matched donors could reverse autoimmunity in the NOD mouse model of T1D.

RESEARCH DESIGN AND METHODS

Prediabetic wild-type or transgenic BDC2.5 NOD mice were conditioned with a radiation-free GVHD preventative anti-CD3/CD8 conditioning regimen and transplanted with bone marrow (BM) from MHC-matched or mismatched donors to induce mixed or complete chimerism. T1D development and thymic deletion of host-type autoreactive T-cells in the chimeric recipients were evaluated.

RESULTS

Induction of mixed chimerism with MHC-matched nonautoimmune donor BM transplants did not prevent T1D in wild-type NOD mice, although induction of complete chimerism did prevent the disease. However, induction of either mixed or complete chimerism with MHC-mismatched BM transplants prevented T1D in such mice. Furthermore, induction of mixed chimerism in transgenic BDC2.5-NOD mice with MHC-matched or -mismatched MHC II−/− BM transplants failed to induce thymic deletion of de novo developed host-type autoreactive T-cells, whereas induction of mixed chimerism with mismatched BM transplants did.

CONCLUSIONS

Induction of mixed chimerism with MHC-mismatched, but not matched, donor BM transplants re-establishes thymic deletion of host-type autoreactive T-cells and prevents T1D, with donor antigen-presenting cell expression of mismatched MHC II molecules being required.
Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
Authors: Briand Nolwenn , Le Lay Soazig , Sessa William C. , Ferré Pascal , Dugail Isabelle
Published: January 2011

OBJECTIVE

Defective caveolin-1 expression is now recognized as a cause of lipoatrophic diabetes in patients, due to primary caveolin gene mutations or secondary caveolin deficiency caused by PTRF/cavin gene defects. The goal of this study was to establish the relative contribution of endothelial cells and adipocytes, both highly expressing caveolin-1 to the lipoatrophic phenotype of mice with global caveolin-1 gene invalidation (Cav1-KO).

RESEARCH DESIGN AND METHODS

We compared adipose tissue development and metabolic phenotype of wild-type (WT), lipoatrophic Cav1-KO, and a murine model with specific rescue of caveolin-1 expression in endothelial cells (caveolin-1-reconstituted [Cav1-RC]).

RESULTS

Defective adipose tissue development, reduced adipocyte size, and global alteration in adipose tissue gene expression that characterize lipoatrophic caveolin-1 null mice were still observed in Cav1-RC, indicating a prominent role of adipocyte-derived caveolin in lipoatrophy. We also observed that Cav1-KO adipose tissue contained an increased proportion of infiltrated macrophages compared with control mice, mostly with an alternate activation M2 phenotype. In contrast with defective lipid storage and lipoatrophy, macrophage infiltration was normalized in Cav1-RC mice, pointing to caveolin-1-dependent endothelium permeability as the causing factor for adipose tissue macrophage infiltration in this model.

CONCLUSIONS

This is the first report of a specific role for adipocyte caveolin expression in lipid storage. Our study also shows that endothelium caveolin critically participates in the control of macrophage extravasation from the blood into adipose tissue, therefore establishing distinct roles depending on topology of caveolin expression in different cell types of adipose tissue.
Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance
Authors: Hirvonen Jussi , Virtanen Kirsi A. , Nummenmaa Lauri , Hannukainen Jarna C. , Honka Miikka-Juhani , Bucci Marco , Nesterov Sergey V. , Parkkola Riitta , Rinne Juha , Iozzo Patricia , Nuutila Pirjo
Published: January 2011

OBJECTIVE

Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance.

RESEARCH DESIGN AND METHODS

We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling.

RESULTS

The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group.

CONCLUSIONS

We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance.
Rictor/mTORC2 Is Essential for Maintaining a Balance Between β-Cell Proliferation and Cell Size
Authors: Gu Yanyun , Lindner Jill , Kumar Anil , Yuan Weiping , Magnuson Mark A.
Published: January 2011

OBJECTIVE

We examined the role of Rictor/mammalian target of rapamycin complex 2 (mTORC2), a key component of the phosphotidylinositol-3-kinase (PI3K)/mTORC2/AKT signaling pathway, in regulating both β-cell mass and function.

RESEARCH DESIGN AND METHODS

Mice with β-cell–specific deletions of Rictor or Pten were studied to determine the effects of deleting either or both genes on β-cell mass and glucose homeostasis.

RESULTS

Rictor null mice exhibited mild hyperglycemia and glucose intolerance caused by a reduction in β-cell mass, β-cell proliferation, pancreatic insulin content, and glucose-stimulated insulin secretion. Islets from these mice exhibited decreased AKT-S473 phosphorylation and increased abundance of FoxO1 and p27 proteins. Conversely, Pten null (βPtenKO) mice exhibited an increase in β-cell mass caused by increased cellular proliferation and size. Although β-cell mass was normal in mice lacking both Rictor and Pten (βDKO), their β-cells were larger than those in the βPtenKO mice. Even though the β-cell proliferation rate in the βDKO mice was lower than in the βPtenKO mice, there was a 12-fold increase the phosphorylation of AKT-T308.

CONCLUSIONS

PI3K/AKT signaling through mTORC2/pAKT-S473 plays a key role in maintaining normal β-cell mass. The phosphorylation of AKT-S473, by negatively regulating that of AKT-T308, is essential for maintaining a balance between β-cell proliferation and cell size in response to proliferative stimuli.
Tests for Genetic Interactions in Type 1 Diabetes
Authors: Morahan Grant , Mehta Munish , James Ian , Chen Wei-Min , Akolkar Beena , Erlich Henry A. , Hilner Joan E. , Julier Cécile , Nerup Jørn , Nierras Concepcion , Pociot Flemming , Todd John A. , Rich Stephen S. ,   for the Type 1 Diabetes Genetics Consortium
Published: January 2011

OBJECTIVE

Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1 diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions.

RESEARCH DESIGN AND METHODS

To address this issue, the Type 1 Diabetes Genetics Consortium recruited 3,892 families, including 4,422 affected sib-pairs. After genotyping 6,090 markers, linkage analyses of these families were performed, using a novel method and taking into account factors such as genotype at known susceptibility loci.

RESULTS

Evidence for linkage was robust at the HLA and INS loci, with logarithm of odds (LOD) scores of 398.6 and 5.5, respectively. There was suggestive support for five other loci. Stratification by other risk factors (including HLA and age at diagnosis) identified one convincing region on chromosome 6q14 showing linkage in male subjects (corrected LOD = 4.49; replication P = 0.0002), a locus on chromosome 19q in HLA identical siblings (replication P = 0.006), and four other suggestive loci.

CONCLUSIONS

This is the largest linkage study reported for any disease. Our data indicate there are no major type 1 diabetes subtypes definable by linkage analyses; susceptibility is caused by actions of HLA and an apparently random selection from a large number of modest-effect loci; and apart from HLA and INS, there is no important susceptibility factor discoverable by linkage methods.
Serum Apolipoprotein AI and B Are Stronger Biomarkers of Diabetic Retinopathy Than Traditional Lipids
Authors: Sasongko Muhammad Bayu , Wong Tien Y. , Nguyen Thanh T. , Kawasaki Ryo , Jenkins Alicia , Shaw Jonathan , Wang Jie Jin
Published: January 2011

OBJECTIVE

To describe and compare the associations of serum lipoproteins and apolipoproteins with diabetic retinopathy.

RESEARCH DESIGN AND METHODS

This was a cross-sectional study of 224 diabetic patients (85 type 1 and 139 type 2) from a diabetes clinic. Diabetic retinopathy was graded from fundus photographs according to the Airlie House Classification system and categorized into mild, moderate, and vision-threatening diabetic retinopathy (VTDR). Serum traditional lipids (total, LDL, non–HDL, and HDL cholesterol and triglycerides) and apolipoprotein AI (apoAI), apolipoprotein B (apoB), and the apoB-to-apoAI ratio were assessed.

RESULTS

Diabetic retinopathy was present in 133 (59.4%) individuals. After adjustment for age, sex, diabetes duration, A1C, systolic blood pressure, and diabetes medications, the HDL cholesterol level was inversely associated with diabetic retinopathy (odds ratio 0.39 [95% CI 0.16–0.94], highest versus lowest quartile; Ptrend = 0.017). The ApoAI level was inversely associated with diabetic retinopathy (per SD increase, 0.76 [95% CI 0.59–0.98]), whereas apoB (per SD increase, 1.31 [1.02–1.68]) and the apoB-to-apoAI ratio (per SD increase, 1.48 [1.13–1.95]) were positively associated with diabetic retinopathy. Results were similar for mild to moderate diabetic retinopathy and VTDR. Traditional lipid levels improved the area under the receiver operating curve by 1.8%, whereas apolipoproteins improved the area by 8.2%.

CONCLUSIONS

ApoAI and apoB and the apoB-to-apoAI ratio were significantly and independently associated with diabetic retinopathy and diabetic retinopathy severity and improved the ability to discriminate diabetic retinopathy by 8%. Serum apolipoprotein levels may therefore be stronger biomarkers of diabetic retinopathy than traditional lipid measures.
Higher Plasma Levels of Advanced Glycation End Products Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes
Authors: Nin Johanna W. , Jorsal Anders , Ferreira Isabel , Schalkwijk Casper G. , Prins Martin H. , Parving Hans-Henrik , Tarnow Lise , Rossing Peter , Stehouwer Coen D.
Published: January 2011

OBJECTIVE

To investigate the associations of plasma levels of advanced glycation end products (AGEs) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, and arterial stiffness.

RESEARCH DESIGN AND METHODS

We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, pentosidine and other biomarkers were measured at baseline. The median follow-up duration was 12.3 (interquartile range 7.6–12.5) years.

RESULTS

During the course of follow-up, 82 individuals (24.2%) died; 85 (25.1%) suffered a fatal (n = 48) and/or nonfatal (n = 53) CVD event. The incidence of fatal and nonfatal CVD and of all-cause mortality increased with higher baseline levels of AGEs independently of traditional CVD risk factors: hazard ratio (HR) = 1.30 (95% CI = 1.03–1.66) and HR = 1.27 (1.00–1.62), respectively. These associations were not attenuated after further adjustments for markers of renal or endothelial dysfunction, low-grade inflammation, or arterial stiffness.

CONCLUSIONS

Higher levels of AGEs are associated with incident fatal and nonfatal CVD as well as all-cause mortality in individuals with type 1 diabetes, independently of other risk factors and of several potential AGEs-related pathophysiological mechanisms. Thus, AGEs may explain, in part, the increased cardiovascular disease and mortality attributable to type 1 diabetes and constitute a specific target for treatment in these patients.
HbA1c in Nondiabetic Dutch Infants Aged 8–12 Months
Authors: Jansen Hanneke , Huiting Haika G. , Scholtens Salome , Sauer Pieter J.J. , Stolk Ronald P.
Published: January 2011

OBJECTIVE

An international committee of experts recommended using HbA1c for diagnostic testing for diabetes. Little is known about normal values of HbA1c in infants. The aim of this study is to describe the distribution of HbA1c in 8- to 12-month-old nondiabetic infants.

RESEARCH DESIGN AND METHODS

HbA1c was measured in 86 infants participating in the Groningen Expert Center for Kids with Obesity (GECKO)-Drenthe birth cohort study. Anthropometric measurements were performed at Well Baby Clinics. Data on parents and children were collected prospectively using questionnaires.

RESULTS

HbA1c was normally distributed with a mean (SD) HbA1c level of 5.38% (0.24), range 4.8–6.0% or 35.29 mmol/mol (2.65), range 29.1–42.1 mmol/mol. Age, sex, birth weight, duration of breastfeeding, anthropometric measurements, and maternal BMI were not associated with HbA1c.

CONCLUSIONS

We found a normal distribution of HbA1c with a relatively high mean HbA1c of 5.38%. No significant association between risk factors for type 2 diabetes and HbA1c levels was found.
Factors Predictive of Severe Hypoglycemia in Type 1 Diabetes
Authors:   Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group
Published: January 2011

OBJECTIVE

Identify factors predictive of severe hypoglycemia (SH) and assess the clinical utility of continuous glucose monitoring (CGM) to warn of impending SH.

RESEARCH DESIGN AND METHODS

In a multicenter randomized clinical trial, 436 children and adults with type 1 diabetes were randomized to a treatment group that used CGM (N = 224), or a control group that used standard home blood glucose monitoring (N = 212) and completed 12 months of follow-up. After 6 months, the original control group initiated CGM while the treatment group continued use of CGM for 6 months. Baseline risk factors for SH were evaluated over 12 months of follow-up using proportional hazards regression. CGM-derived indices of hypoglycemia were used to predict episodes of SH over a 24-h time horizon.

RESULTS

The SH rate was 17.9 per 100 person-years, and a higher rate was associated with the occurrence of SH in the prior 6 months and female sex. SH frequency increased eightfold when 30% of CGM values were ≤70 mg/dL on the prior day (4.5 vs. 0.5%; P < 0.001), but the positive predictive value (PPV) was low (<5%). Results were similar for hypoglycemic area under the curve and the low blood glucose index calculated by CGM.

CONCLUSIONS

SH in the 6 months prior to the study was the strongest predictor of SH during the study. CGM-measured hypoglycemia over a 24-h span is highly associated with SH the following day (P < 0.001), but the PPV is low.
Glycemic Control and Health Disparities in Older Ethnically Diverse Underserved Adults With Diabetes
Authors: Weinstock Ruth S. , Teresi Jeanne A. , Goland Robin , Izquierdo Roberto , Palmas Walter , Eimicke Joseph P. , Ebner Susana , Shea Steven ,   The IDEATel Consortium
Published: January 2011

OBJECTIVE

The Informatics for Diabetes Education and Telemedicine (IDEATel) project randomized ethnically diverse underserved older adults with diabetes to a telemedicine intervention or usual care. Intervention participants had lower A1C levels over 5 years. New analyses were performed to help better understand this difference.

RESEARCH DESIGN AND METHODS

IDEATel randomized Medicare beneficiaries with diabetes (n = 1,665) to receive home video visits with a diabetes educator and upload glucose levels every 4–6 weeks or usual care (2000–2007). Annual measurements included BMI, A1C (primary outcome), and completion of questionnaires. Mixed-model analyses were performed using random effects to adjust for clustering within primary care physicians.

RESULTS

At baseline, A1C levels (mean ± SD) were 7.02 ± 1.25% in non-Hispanic whites (n = 821), 7.58 ± 1.78% in non-Hispanic blacks (n = 248), and 7.79 ± 1.68% in Hispanics (n = 585). Over time, lower A1C levels were associated with more glucose uploads (P = 0.02) and female sex (P = 0.002). Blacks, Hispanics, and insulin-users had higher A1C levels than non-Hispanic whites (P < 0.0001). BMI was not associated with A1C levels. Blacks and Hispanics had significantly fewer uploads than non-Hispanic whites over time. Hispanics had the highest baseline A1C levels and showed the greatest improvement in the intervention, but, unlike non-Hispanic whites, Hispanics did not achieve A1C levels <7.0% at 5 years.

CONCLUSIONS

Racial/ethnic disparities were observed in this cohort of underserved older adults with diabetes. The IDEATel telemedicine intervention was associated with improvement in glycemic control, particularly in Hispanics, who had the highest baseline A1C levels, suggesting that telemedicine has the potential to help reduce disparities in diabetes management.
No Loss of Chance of Diabetic Retinopathy Screening by Endocrinologists With a Digital Fundus Camera
Authors: Germain Natacha , Galusca Bodgan , Deb-Joardar Nilanjana , Millot Luc , Manoli Pierre , Thuret Gilles , Gain Philippe , Estour Bruno
Published: January 2011

OBJECTIVE

To compare the efficacy of the diabetic retinopathy (DR) screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of “loss of chance.”

RESEARCH DESIGN AND METHODS

In a cross-sectional study, 500 adult diabetic patients (1,000 eyes) underwent three-field retinal photography with a digital fundus camera following pupillary dilatation. Five endocrinologists and two ophthalmology residents underwent 40 h of training on screening and grading of DR and detection of associated retinal findings. A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists. Screening efficiency of endocrinologists was evaluated in terms of “loss of chance,” i.e., missed diagnoses that required ophthalmologist referrals.

RESULTS

The mean weighted κ of DR screening performed by endocronologists was similar to that of ophthalmology residents (0.65 vs. 0.73). Out of 456 DR eyes, both endocrinologists and ophthalmology residents misdiagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral. There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training.

CONCLUSIONS

The endocrinologist with specific training for DR detection using a three-field digital fundus camera with pupillary dilatation can perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.
Heart Rate Recovery After Exercise Is a Predictor of Silent Myocardial Ischemia in Patients With Type 2 Diabetes
Authors: Yamada Tomohide , Yoshitama Takashi , Makino Kunihiko , Lee Tetsuo , Saeki Fumihiko
Published: January 2011

OBJECTIVE

Slow heart rate recovery (HRR) predicts all-cause mortality. This study investigated the relationship between silent myocardial ischemia (SMI) and HRR in type 2 diabetes.

RESEARCH DESIGN AND METHODS

The study enrolled 87 consecutive patients with type 2 diabetes and no chest symptoms. They underwent treadmill exercise testing and single-photon emission computed tomography imaging with thallium scintigraphy. Patients with abnormal myocardial perfusion images also underwent coronary angiography.

RESULTS

SMI was diagnosed in 41 patients (47%). The SMI group showed slower HRR than the non–SMI group (18 ± 6 vs. 30 ± 12 bpm; P < 0.0001). HRR was significantly associated with SMI (odds ratio 0.83 [95% CI 0.75–0.92]; P = 0.0006), even after adjustment for maximal exercise workload, resting heart rate, maximum heart rate, rate pressure product, HbA1c, use of sulfonamides, and a history of cardiovascular disease.

CONCLUSIONS

HRR can predict SMI in patients with type 2 diabetes.
Proximal Neuropathic Lesions in Distal Symmetric Diabetic Polyneuropathy
Authors: Pham Mirko , Oikonomou Dimitrios , Bäumer Philipp , Bierhaus Angelika , Heiland Sabine , Humpert Per M. , Nawroth Peter P. , Bendszus Martin
Published: January 2011

OBJECTIVE

This study investigated high-resolution magnetic resonance neurography (MRN) in distal symmetric diabetic polyneuropathy (dPNP).

RESEARCH DESIGN AND METHODS

MRN comprised high-resolution transaxial imaging of peripheral nerves of the lower limbs in 20 patients with type 2 diabetes (10 with dPNP, type 2/dPNP[+], and 10 without dPNP, type 2/dPNP[−]), seven patients with type 1 diabetes (two with dPNP, type 1/dPNP[+], five without dPNP, type 1/dPNP[−]), and 10 nondiabetic control subjects. Intraneural T2 lesions, as the main diagnostic criterion of MRN, were detected visually by two independent observers and quantitatively by analysis of T2 contrast ratios.

RESULTS

Multifocal fascicular, symmetric intraneural T2 lesions occurred in the proximal trunks of sciatic nerves in four patients (three with type 2/dPNP[+] and one with type 1/dPNP[+]) but not in control subjects (type 2/dPNP[−], type 1/dPNP[−], nondiabetic control subjects), which was confirmed by quantitative analysis. Clinical severity was higher in patients with T2 lesions (neuropathy deficit score: 10 vs. 7.8; P = 0.05).

CONCLUSIONS

For the first time, proximal neuropathic lesions of dPNP are reported in vivo. This supports that accumulation of proximal, multifocal fascicular injury may be important in disease progression.
Islet Autoantibody Seroconversion in the DPT-1 Study
Authors: Vehik Kendra , Haller Michael J. , Beam Craig A. , Schatz Desmond A. , Wherrett Diane K. , Sosenko Jay M. , Krischer Jeffrey P. ,   DPT-1 Study Group
Published: January 2011

OBJECTIVE

Although type 1 diabetes autoimmunity frequently begins in childhood, little is known about the relationship between age and autoimmunity development. Our aim was to determine the timing of seroconversion to diabetes-associated autoantibody (DAA) positivity and risk in first- and second-degree relatives of patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Study subjects were identified through the Diabetes Prevention Trial-Type 1 (DPT-1). Children 3–18 years of age (n = 42,447) were screened for DAAs; 1,454 were ICA positive (≥10 JDF units), 1,758 were GAD65 positive, and 899 were ICA512 positive at the time of initial screening. Subjects who were initially antibody negative (n = 39,212) were recalled for rescreening, and 11,813 returned for rescreening.

RESULTS

DAA seroconversion occurred in 469 (4%) children; 258 seroconverted to ICA, 234 to GAD65, and 99 to ICA512. The median time to seroconversion was 2 years. The 2-year risk for DAAs was highest in early childhood. For each 1-year increase in age in this cohort, the risk of any autoantibody seroconversion (HR 0.95, 95% CI 0.92–0.97) decreased by 5%, and for any two autoantibodies risk decreased by 13% (0.87, 0.82–0.93).

CONCLUSIONS

Risk of autoantibody seroconversion among children followed in DPT-1 is age dependent. Younger children have the highest risk for DAAs, with the majority of children seroconverting by 13 years of age (75%). This suggests that annual screenings should be started in early childhood and continued through early adolescence to identify the majority of subjects at risk for type 1 diabetes and eligible for prevention trials.
Maternal Glucose Concentration During Pregnancy Predicts Fat and Lean Mass of Prepubertal Offspring
Authors: Chandler-Laney Paula C. , Bush Nikki C. , Rouse Dwight J. , Mancuso Melissa S. , Gower Barbara A.
Published: January 2011

OBJECTIVE

Intrauterine exposure to high maternal glucose is associated with excess weight gain during childhood, but it is not clear whether the excess weight represents increased fat or lean mass. The purpose of this study was to examine the relationship between maternal glucose concentrations during pregnancy and offspring body composition. A secondary goal was to examine whether the association between maternal glucose and children’s body fat was independent of energy intake, energy expenditure, or physical activity.

RESEARCH DESIGN AND METHODS

Children aged 5–10 years and their biological mothers (n = 27) were recruited. Maternal glucose concentration 1 h after a 50-g oral glucose load, used to screen for gestational diabetes mellitus at 24–28 weeks gestation, was retrieved from medical records. Children underwent dual-energy X-ray absorptiometry to measure body composition, indirect calorimetry to measure resting energy expenditure (REE), accelerometry to measure physical activity, and three 24-h diet recalls to measure energy intake.

RESULTS

Maternal glucose concentration during pregnancy was positively associated with children’s lean mass (P < 0.05) and adiposity (fat mass adjusted for lean mass; P < 0.05). The association between maternal glucose and children’s adiposity was independent of children’s REE, percent of time spent physically active, and energy intake (P < 0.001).

CONCLUSIONS

Intrauterine exposure to relatively high maternal glucose is associated with greater lean mass and adiposity among prepubertal offspring. Further research is needed to examine the mechanisms by which maternal glucose concentrations during pregnancy influence children’s body composition.
Endotoxemia Is Associated With an Increased Risk of Incident Diabetes
Authors: Pussinen Pirkko J. , Havulinna Aki S. , Lehto Markku , Sundvall Jouko , Salomaa Veikko
Published: January 2011

OBJECTIVE

Diabetes is accompanied with a chronic low-grade inflammation, which may in part be mediated by endotoxins derived from Gram-negative bacteria.

RESEARCH DESIGN AND METHODS

We investigated in a population-based cohort whether endotoxemia is associated with clinically incident diabetes. The serum endotoxin activity was measured by limulus assay from the FINRISK97 cohort comprising 7,169 subjects aged 25–74 years and followed up for 10 years.

RESULTS

Both the subjects with prevalent diabetes (n = 537) and those with incident diabetes (n = 462) had higher endotoxin activity than the nondiabetic individuals (P < 0.001). The endotoxin activity was significantly associated with increased risk for incident diabetes with a hazard ratio 1.004 (95% CI 1.001–1.007; P = 0.019) per unit increase resulting in a 52% increased risk (P = 0.013) in the highest quartile compared with the lowest one. The association was independent of diabetes risk factors: serum lipids, γ-glutamyl transferase, C-reactive protein, BMI, and blood glucose. Furthermore, the association of endotoxemia with an increased risk of incident diabetes was independent of the metabolic syndrome as defined either by the National Cholesterol Educational Program-Adult Treatment Panel III or the International Diabetes Federation. Endotoxin activity was linearly related (P < 0.001) to the number of components of the metabolic syndrome.

CONCLUSIONS

Both prevalent and incident diabetes were associated with endotoxemia, which may link metabolic disorders to inflammation. The results suggest that microbes play a role in the pathogenesis of diabetes.
Fasting Plasma Glucose and Hemoglobin A1c in Identifying and Predicting Diabetes
Authors: Wang Wenyu , Lee Elisa T. , Howard Barbara V. , Fabsitz Richard R. , Devereux Richard B. , Welty Thomas K.
Published: January 2011

OBJECTIVE

To compare fasting plasma glucose (FPG) and HbA1c in identifying and predicting type 2 diabetes in a population with high rates of diabetes.

RESEARCH DESIGN AND METHODS

Diabetes was defined as an FPG level ≥126 mg/dL or an HbA1c level ≥6.5%. Data collected from the baseline and second exams (1989–1995) of the Strong Heart Study were used.

RESULTS

For cases of diabetes identified by FPG ≥126 mg/dL, using HbA1c ≥6.5% at the initial and 4-year follow-up diabetes screenings (or in identifying incident cases in 4 years) among undiagnosed participants left 46% and 59% of cases of diabetes undetected, respectively, whereas for cases identified by HbA1c ≥6.5%, using FPG ≥126 mg/dL left 11% and 59% unidentified, respectively. Age, waist circumference, urinary albumin-to-creatinine ratio, and baseline FPG and HbA1c levels were common significant risk factors for incident diabetes defined by either FPG or HbA1c; triglyceride levels were significant for diabetes defined by HbA1c alone, and blood pressure and sibling history of diabetes were significant for diabetes defined by FPG alone. Using both the baseline FPG and HbA1c in diabetes prediction identified more people at risk than using either measure alone.

CONCLUSIONS

Among undiagnosed participants, using HbA1c alone in initial diabetes screening identifies fewer cases of diabetes than FPG, and using either FPG or HbA1c alone cannot effectively identify diabetes in a 4-year periodic successive diabetes screening or incident cases of diabetes in 4 years. Using both criteria may identify more people at risk. The proposed models using the commonly available clinical measures can be applied to assessing the risk of incident diabetes using either criterion.
Quality of Diabetes Care Predicts the Development of Cardiovascular Events: Results of the AMD-QUASAR Study
Authors: Rossi Maria C.E. , Lucisano Giuseppe , Comaschi Marco , Coscelli Carlo , Cucinotta Domenico , Di Blasi Patrizia , Bader Giovanni , Pellegrini Fabio , Valentini Umberto , Vespasiani Giacomo , Nicolucci Antonio ,   on behalf of the AMD-QUASAR Study Group
Published: January 2011

OBJECTIVE

The QUASAR (Quality Assessment Score and Cardiovascular Outcomes in Italian Diabetes Patients) study aimed to assess whether a quality-of-care summary score predicted the development of cardiovascular (CV) events in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

In 67 diabetes clinics, data on randomly selected patients were extracted from electronic medical records. The score was calculated using process and outcome indicators based on monitoring, targets, and treatment of A1C, blood pressure, LDL cholesterol, and microalbuminuria. The score ranged from 0 to 40.

RESULTS

Overall, 5,181 patients were analyzed; 477 (9.2%) patients developed a CV event after a median follow-up of 28 months. The incidence rate (per 1,000 person-years) of CV events was 62.4 in patients with a score of <15, 41.0 in those with a score between 20 and 25 and 36.7 in those with a score of >25.

Multilevel analysis, adjusted for clustering and case-mix, showed that the risk to develop a new CV event was 84% higher in patients with a score of <15 (incidence rate ratio [IRR] = 1.84; 95% confidence interval [CI] 1.29–2.62) and 17% higher in those with a score between 15 and 25 (IRR = 1.17; 95% CI 0.93–1.49) compared with those with a score of >25.

Mean quality score varied across centers from 16.5 ± 7.5 to 29.1 ± 6.3. When the score was tested as the dependent variable, it emerged that 18% of the variance in the score could be attributed to setting characteristics.

CONCLUSIONS

Our study documented a close relationship between quality of diabetes care and long-term outcomes. A simple score can be used to monitor quality of care and compare the performance of different centers/physicians.
The Prevalence and Predictors of an Abnormal Ankle-Brachial Index in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
Authors: Singh Premranjan P. , Abbott J. Dawn , Lombardero Manuel S. , Sutton-Tyrrell Kim , Woodhead Gail , Venkitachalam Lakshmi , Tsapatsaris Nicholas P. , Piemonte Thomas C. , Lago Rodrigo M. , Rutter Martin K. , Nesto Richard W. ,   BARI,   2D Study Group
Published: January 2011

OBJECTIVE

To examine ankle-brachial index (ABI) abnormalities in patients with type 2 diabetes and coronary artery disease (CAD).

RESEARCH DESIGN AND METHODS

An ABI was obtained in 2,240 patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. ABIs were classified as: normal, 0.91–1.3; low, ≤0.9; high, >1.3; or noncompressible artery (NC). Baseline characteristics were examined according to ABI and by multivariate analysis.

RESULTS

ABI was normal in 66%, low in 19%, and high in 8% of patients, and 6% of patients had NC. Of the low ABI patients, 68% were asymptomatic. Using normal ABI as referent, low ABI was independently associated with smoking, female sex, black race, hypertension, age, C-reactive protein, diabetes duration, and lower BMI. High ABI was associated with male sex, nonblack race, and higher BMI; and NC artery was associated with diabetes duration, higher BMI, and hypertension.

CONCLUSIONS

ABI abnormalities are common and often asymptomatic in patients with type 2 diabetes and CAD.
Use of Continuous Glucose Monitoring in Subjects With Type 1 Diabetes on Multiple Daily Injections Versus Continuous Subcutaneous Insulin Infusion Therapy
Authors: Garg Satish K. , Voelmle Mary K. , Beatson Christie R. , Miller Hayley A. , Crew Lauren B. , Freson Brandon J. , Hazenfield Rachel M.
Published: January 2011

OBJECTIVE

To compare use of continuous glucose monitoring in subjects with type 1 diabetes on multiple daily injection (MDI) therapy versus continuous subcutaneous insulin infusion (CSII) therapy for 6 months.

RESEARCH DESIGN AND METHODS

Sixty type 1 diabetic adults with similar baseline characteristics, using either MDI (n = 30) or CSII (n = 30) therapy, were enrolled in this 6-month prospective study. Subjects were instructed to wear the DexCom SevenPLUS continuous glucose monitor at all times throughout the study. All subjects were initially blinded from the continuous glucose monitoring (CGM) glucose data. After 4 weeks of blinded CGM use, the CGM was unblinded, making glucose data available to the patient. The CGM remained in the unblinded state for the remainder of the study (20 weeks). Clinic visits occurred every 4 weeks, at which time A1C values were collected and CGM data were downloaded.

RESULTS

Mean baseline (± SD) A1C was 7.61 (± 0.76) and 7.63 (± 0.68) for CSII and MDI, respectively (P > 0.05). Without any significant therapy change, A1C decrease at 12 weeks was similar in both groups (P = 0.03). When compared with the blinded phase, unblinded use of CGM was associated with similar but significant reductions in glycemic control and variability parameters. In addition, both therapy groups had similar changes in mean glucose and glucose variability indexes at 3 and 6 months (ITT analysis, P > 0.05). Predefined per protocol analysis (sensor use at least 6 days/week) showed greater improvement in time spent in target range glycemia, 3.9–10.0 mmol/L (70–180 mg/dL), in the CSII group.

CONCLUSIONS

We conclude that CGM provides similar benefits in glucose control for patients using MDI or CSII therapy.
Age-Related Blood Antioxidant Capacity in Men and Women
Authors: Hübner-Woźniak Elżbieta , Okecka-Szymańska Joanna , Stupnicki Romuald , Malara Marzena , Kozdroń Ewa
Published: January 2011

Age-Related Blood Antioxidant Capacity in Men and Women

The aim of the study was to assess the blood antioxidant capacity in men and women in relation to age. The subjects were 19 men (YM) and 19 women (YW) aged 25-32 years, and 11 men (OM) and 11 women (OW) aged 63-71 years, all sedentary. The following factors were determined: the activity of erythrocyte superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPX), catalase (CAT), total antioxidant status (TAS), as well as plasma retinol, α-tocopherol, uric acid and total protein concentrations. The sum of standardized activities of antioxidant enzymes was calculated to compare age-related changes in the total capacity of the erythrocyte antioxidant defense. No significant age-related changes in SOD activity were observed; mean CAT activity was higher in older women and men than in younger subjects. Mean activity of GPX was higher and that of GR lower in older subjects compared to the younger ones. The calculated total erythrocyte antioxidant enzyme capacity in younger and older subjects rendered similar values. No significant differences in plasma retinol and α-tocopherol concentrations in relation to sex or age were noted. The plasma total protein level was significantly lower in younger women and men compared to their older mates. It was concluded that the total erythrocyte enzymatic antioxidant capacity did not change with age. The results obtained clearly show that multiple factors may contribute to the ageing process.
Carrot (Daucus carota L.) In Vitro Regeneration
Authors: Rabiei Keramat , Polyakov Aleksey , Khodambashi Mahmood , Sharafova Olga , Kalashnikova Elena , Hooshmand Saadollah , Omidi Mansour
Published: January 2011

Carrot (Daucus carota L.) In Vitro Regeneration

Experiments were carried out for optimization of conditions for morphogenic callus production and regeneration of carrot (Daucus carota L.) using four cultivars cultivated in Iran. Hypocotyl segments were put on media supplemented with 0.2 mg·L-1 2,4-D for callus initiation and proliferation. Small portions of callus (25 mg) were cut and transferred to new media with different concentrations of 2,4-D including 0.2, 0.5 and 1 mg·L-1. MS (Murashige & Skoog 1962) and MSm (Masuda et al. 1981) media were used in the experiments to identify the differences between these two media according to callus, embryoid and plantlet production.

Obtained results showed that low level of 2,4-D (0.2 mg·L-1) was more effective in morphogenic callus production although higher amounts of it (0.5 mg·L-1 and 1 mg·L-1) caused more callus growth. Kinetin in concentration of 0.1 mg·L-1 was more effective for regeneration than BAP used in concentration 1 mg·L-1 especially according to embryoid production. MSm medium was more useful than MS for callus production and regeneration of carrot plantlets. Among tested cultivars Nantes Improved had more capability to produce viable plantlets.
Yielding of Asparagus Depending on Harvest Ending Date
Authors: Knaflewski Mikołaj , Krzesiński Włodzimierz , Gąsecka Monika , Stachowiak Jerzy
Published: January 2011

Yielding of Asparagus Depending on Harvest Ending Date

The field experiment focused on the determination of yielding of asparagus cv. ‘Thielim’ in relation to harvest duration: traditional (until June 20th), shortened (June 10th) and prolonged (30th June) harvests. The variation in harvest ending dates did not have a significant influence on the total, marketable and non-marketable yields as well as on the crown weight and the number of storage roots. However, the extension of harvest time until June 30th resulted in an increase in the number of spears in the total and marketable yields, accompanied by a decrease in their diameter. Also prolonging harvest affected negatively the summer stalk size. During harvest until June 10th asparagus plants probably did not use their full yielding potential, because of too short harvest time. It resulted in increased height, weight, light absorption of summer stalks, leaf area index (LAI) and the total of cross-section areas of summer stalks (PPPA) with no significant differences in yield.
Occurrence of Crioceris Spp. of Ten European Asparagus Cultivars Depending on Drip Irrigation
Authors: Lamparski Robert , Rolbiecki Roman , Piesik Dariusz , Pańka Dariusz
Published: January 2011

Occurrence of Crioceris Spp. of Ten European Asparagus Cultivars Depending on Drip Irrigation

The influence of drip irrigation of 10 European asparagus cultivars on the occurrence of Crioceris duodecimpunctata (L.) and Crioceris asparagi (L.) was studied. We tested 5 German cultivars (‘Ravel’, ‘Rambo’, ‘Rally’, ‘Ramada’, ‘Rapsody’), 2 Spanish cv. (‘Cipres’ and ‘Plaverd’), 2 Dutch cv. (‘Backlim’ and ‘Grolim’) and French cv. ‘Orane’ in the field conditions. The field experiment was carried out in two consecutive years (2005-2006) at Kruszyn Krajeński near Bydgoszcz on a sandy soil. Adults and larvae of C. duodecimpunctata (twelvespotted asparagus beetles - T-SAB) and C. asparagi (common asparagus beetles - CAB) reached over 91% of all insects settled on asparagus summer stalks. The German cultivars ‘Rambo’ and ‘Rally’ were considerably settled by adults and larvae of T-SAB. The highest number of individuals (adults and larvae) of CAB on the Dutch cv. ‘Backlim’ were observed. However, German cv. ‘Rapsody’ were significantly less numerous (both CAB and T-SAB). Moreover Dutch cv. ‘Backlim’ was more occupied by adults and larvae of CAB in drip irrigation plots than all five tested German cultivars. Also adults and larvae of T-SAB as well as CAB often prefer drip irrigated asparagus summer stalks.
Effect of Rape and Mustard Seed Meals on Verticillium wilt of Pepper
Authors: Smolińska Urszula , Kowalska Beata , Kowalczyk Waldemar , Horbowicz Marcin
Published: January 2011

Effect of Rape and Mustard Seed Meals on Verticillium wilt of Pepper

The effect of plant material from Brassicaceae plants - the mustard seed meal and rapeseed meal, added to soil or peat substrate, on Verticillium wilt of pepper was evaluated in laboratory and greenhouse conditions. It was stated that the addition of these materials decreased infestation of pepper vascular vessels caused by Verticillium dahliae. The decomposition of rapeseed meal and mustard seed meal increased concentration of ammonia, the compound toxic to many pathogens. The increase of total bacteria, actinomycetes, spore forming bacteria were also observed. The materials from Brassicaceae plants positive influenced on plant development and chlorophyll content in pepper leaves.
Influence of Fungicide Treatment on Grey Mould of Cabbage
Authors: Survilienė Elena , Valiuškaitė Alma , Duchovskienė Laisvūnė , Kavaliauskaitė Danguolė
Published: January 2011

Influence of Fungicide Treatment on Grey Mould of Cabbage

The experiments were carried out in the Institute of Horticulture in 2008-2010. The study was supported by the Lithuanian State Science and Studies Foundation. The aim of this investigation was to establish the influence of fungicides applications to control grey mould in cabbages cultivars Kingston F1, Lennox F1 and Paradox F1 during storage. Three fungicide applications with active ingredients azoxystrobine at the rate of 200 g·ha-1 (Amistar 250 SC), boscalid at the rate of 267 g·ha-1 + pyraclostrobine at the rate of 67 g·ha-1 (Signum 33 WG), tebuconazole at the rate of 250 g·ha-1 (Folicur 250 EW), iprodione at the rate of 500 g·ha-1 (Rovral Aqua Flo) and fluopyram at the rate of 200 g·ha-1 + tebuconazole at the rate of 200 g·ha-1 (Bayer CropScience product) were made on second part of plant vegetation (growth stage by BBCH 41-46). After harvesting cabbage heads (20 units from every replication) were kept in a cold storage for four months after harvest. Obtained data showed that fungicide treatments allow for reducing the incidence of grey mould and reduced losses during the four-month storage period by average up 64.73-93.77%.
Chronic social stress increases nitric oxide-dependent vasorelaxation in normotensive rats
Authors: Puzserova Angelika , Bernatova Iveta
Published: January 2011

Chronic social stress increases nitric oxide-dependent vasorelaxation in normotensive rats

The aim of this study was to examine oxidative load and endothelium-dependent vasorelaxation in the serotonin pre-constricted femoral artery (FA) of Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding in the presence or absence of ascorbic acid (AsA) in working solution. Adult male rats were randomly divided into control (living space: 480 cm2/rat) or stressed (living space: 200 cm2/rat) groups for 8 weeks. Blood pressure and heart rate, determined using tail-cuff plethysmography, were not influenced by stress vs. control. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured in the left ventricle and liver (for assessment of oxidative load) and were found unchanged by chronic crowding. The nitric oxide (NO)-dependent component of endothelium-dependent relaxation was investigated in the FA using a wire myograph. In both the presence and absence of AsA, acetylcholine-induced relaxation of the FA of stressed rats significantly exceeded that of the controls, which was associated with an increase of the NO-dependent component. In conclusion, the data showed that chronic crowding did not produce oxidative stress in the organs investigated and indicate that elevation of NO production during chronic stress is an important way of adaptation, which may prevent normotensive rats from the development of stress-induced hypertension.