bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive Oxygen Species as a Signal in Glucose-Stimulated Insulin Secretion
Authors: Pi Jingbo , Bai Yushi , Zhang Qiang , Wong Victoria , Floering Lisa M. , Daniel Kiefer , Reece Jeffrey M. , Deeney Jude T. , Andersen Melvin E. , Corkey Barbara E. , Collins Sheila
Published: June 2007

One of the unique features of β-cells is their relatively low expression of many antioxidant enzymes. This could render β-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-l-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for β-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function.
Differentiation of Affinity-Purified Human Pancreatic Duct Cells to β-Cells
Authors: Yatoh Shigeru , Dodge Rikke , Akashi Tomoyuki , Omer Abdulkadir , Sharma Arun , Weir Gordon C. , Bonner-Weir Susan
Published: June 2007

To test whether pancreatic duct cells are in vitro progenitors, they were purified from dispersed islet-depleted human pancreatic tissue using CA19-9 antibody. The purified fraction was almost entirely CK19+ with no insulin+ cells, whereas the unpurified cells (crude duct) were 56% CK19+ and 0.4% insulin+ of total cells (0.7% of CK19+ cells). These cells were expanded as monolayers, aggregated under serum-free conditions, and transplanted into normoglycemic NOD/SCID mice. In crude duct grafts, insulin+ cells increased to 6.1% of CK19+ cells. Purified duct cells had slow expansion and poor aggregation, as well as engraftment. The addition of 0.1% cultured stromal cells improved these parameters. These stromal cells contained no CK19+ cells and no insulin by either quantitative RT-PCR or immunohistochemistry; stromal cell aggregates and grafts contained no insulin+ cells. Aggregation of purified duct plus stromal preparations induced insulin+ cells (0.1% of CK19+ cells), with further increase to 1.1% in grafts. Insulin mRNA mirrored these changes. In these grafts, all insulin+ cells were in duct-like structures, while in crude duct grafts, 85% were. Some insulin+ cells coexpressed duct markers (CK19 and CA19-9) and heat shock protein (HSP)27, a marker of nonislet cells, suggesting the transition from duct. Thus, purified duct cells from adult human pancreas can differentiate to insulin-producing cells.
SORCS1: A Novel Human Type 2 Diabetes Susceptibility Gene Suggested by the Mouse
Authors: Goodarzi Mark O. , Lehman Donna M. , Taylor Kent D. , Guo Xiuqing , Cui Jinrui , Quiñones Manuel J. , Clee Susanne M. , Yandell Brian S. , Blangero John , Hsueh Willa A. , Attie Alan D. , Stern Michael P. , Rotter Jerome I.
Published: June 2007

OBJECTIVE—A small number of susceptibility genes for human type 2 diabetes have been identified by candidate gene analysis or positional cloning. Genes found to influence diabetes or related traits in mice are likely to be susceptibility genes in humans. SorCS1 is the gene identified as responsible for the mouse chromosome 19 T2dm2 quantitative trait locus for fasting insulin levels, acting via impaired insulin secretion and increased islet disruption in obese females. Genes that impair compensatory insulin secretion in response to obesity-induced insulin resistance may be particularly relevant to human diabetes. Thus, we sought to determine whether variation in the human SORCS1 gene was associated with diabetes-related traits.

RESEARCH DESIGN AND METHODS—We assessed the contribution of variation in SORCS1 to human insulin–related traits in two distinct Mexican-American cohorts. One cohort (the Mexican-American Coronary Artery Disease [MACAD] cohort) consisted of nondiabetic individuals, allowing assessment of genetic association with subclinical intermediate insulin-related traits; the second cohort (the San Antonio Family Diabetes Study [SAFADS]) contained individuals with diabetes, allowing association analyses with overt disease.

RESULTS—We first found association of SORCS1 single nucleotide polymorphisms and haplotypes with fasting insulin levels and insulin secretion in the MACAD cohort. Similar to our results in the mice, the genetic association was strongest in overweight women. We then observed association with diabetes risk and age at diagnosis in women of the SAFADS cohort.

CONCLUSIONS—Identification of SORCS1 as a novel gene affecting insulin secretion and diabetes risk is likely to provide important insight into the biology of obesity-induced type 2 diabetes.
CD36-Facilitated Fatty Acid Uptake Inhibits Leptin Production and Signaling in Adipose Tissue
Authors: Hajri Tahar , Hall Angela M. , Jensen Dalan R. , Pietka Terri A. , Drover Victor A. , Tao Huan , Eckel Robert , Abumrad Nada A.
Published: June 2007

Leptin plays an important role in regulating energy expenditure in response to food intake, but nutrient regulation of leptin is incompletely understood. In this study using in vivo and in vitro approaches, we examined the role of fatty acid uptake in modulating leptin expression and production. Leptin levels are doubled in the CD36-null mouse, which has impaired cellular fatty acid uptake despite a 40% decrease in fat mass. The CD36-null mouse is protected from diet-induced weight gain but not from that consequent to leptin deficiency. Leptin secretion in the CD36-null mouse is strongly responsive to glucose intake, whereas a blunted response is observed in the wild-type mouse. This indicates that leptin regulation integrates opposing influences from glucose and fatty acid and loss of fatty acid inhibition allows unsuppressed stimulation by glucose/insulin. Fatty acid inhibition of basal and insulin-stimulated leptin release is linked to CD36-facilitated fatty acid flux, which is important for fatty acid activation of peroxisome proliferator–activated receptor γ and likely contributes to the nutrient sensing function of adipocytes. Fatty acid uptake also may modulate adipocyte leptin signaling. The ratio of phosphorylated to unphosphorylated signal transducer and activator of transcription 3, an index of leptin activity, is increased in CD36-null fat tissue disproportionately to leptin levels. In addition, expression of leptin-sensitive fatty acid oxidative enzymes is enhanced. Targeting adipocyte CD36 may offer a way to uncouple leptin production and adiposity.
The Hemoglobin Glycation Index Is Not an Independent Predictor of the Risk of Microvascular Complications in the Diabetes Control and Complications Trial
Authors: Lachin John M. , Genuth Saul , Nathan David M. , Rutledge Brandy N.
Published: June 2007

The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy aimed at improved glucose control markedly reduced the risk of diabetes complications compared with conventional therapy. The principal determinant of risk was the history of glycemia. Recently, McCarter et al. (Diabetes Care 27:1259–1264, 2004) have presented analyses of the publicly available DCCT data using their hemoglobin glycation index (HGI), which is computed as the difference between the observed HbA1c (A1C) and that predicted from the level of blood glucose. In their analyses, the HGI level was a significant predictor of progression of retinopathy and nephropathy in the DCCT, which the authors claimed to support the hypothesis that the biological propensity for glycation, so-called biological variation in glycation, is another mechanism that determines risk of complications. However, we have criticized these analyses and conclusions because, from statistical principles, the glycation index must be positively correlated with the A1C level and thus may simply be a surrogate for A1C. Herein, we present the statistical properties of the glycation index to document its high correlation with A1C. We then replicate the analyses of McCarter et al. using both the HGI and the A1C together. Analyses show conclusively that the glycation index is not an independent risk factor for microvascular complications and that the effect of the glycation index on risk is wholly explained by the associated level of A1C. The HGI should not be used to estimate risk of complications or to guide therapy.
TCF7L2 Polymorphisms Modulate Proinsulin Levels and β-Cell Function in a British Europid Population
Authors: Loos Ruth J.F. , Franks Paul W. , Francis Richard W. , Barroso Inês , Gribble Fiona M. , Savage David B. , Ong Ken K. , O'Rahilly Stephen , Wareham Nicholas J.
Published: June 2007

Rapidly accumulating evidence shows that common T-cell transcription factor (TCF)7L2 polymorphisms confer risk of type 2 diabetes through unknown mechanisms. We examined the association between four TCF7L2 single nucleotide polymorphisms (SNPs), including rs7903146, and measures of insulin sensitivity and insulin secretion in 1,697 Europid men and women of the population-based MRC (Medical Research Council)-Ely study. The T-(minor) allele of rs7903146 was strongly and positively associated with fasting proinsulin (P = 4.55 × 10−9) and 32,33 split proinsulin (P = 1.72 × 10−4) relative to total insulin levels; i.e., differences between T/T and C/C homozygotes amounted to 21.9 and 18.4% respectively. Notably, the insulin-to-glucose ratio (IGR) at 30-min oral glucose tolerance test (OGTT), a frequently used surrogate of first-phase insulin secretion, was not associated with the TCF7L2 SNP (P > 0.7). However, the insulin response (IGR) at 60-min OGTT was significantly lower in T-allele carriers (P = 3.5 × 10−3). The T-allele was also associated with higher A1C concentrations (P = 1.2 × 10−2) and reduced β-cell function, assessed by homeostasis model assessment of β-cell function (P = 2.8 × 10−2). Similar results were obtained for the other TCF7L2 SNPs. Of note, both major genes involved in proinsulin processing (PC1, PC2) contain TCF-binding sites in their promoters. Our findings suggest that the TCF7L2 risk allele may predispose to type 2 diabetes by impairing β-cell proinsulin processing. The risk allele increases proinsulin levels and diminishes the 60-min but not 30-min insulin response during OGTT. The strong association between the TCF7L2 risk allele and fasting proinsulin but not insulin levels is notable, as, in this unselected and largely normoglycemic population, external influences on β-cell stress are unlikely to be major factors influencing the efficiency of proinsulin processing.
Incretin Levels and Effect Are Markedly Enhanced 1 Month After Roux-en-Y Gastric Bypass Surgery in Obese Patients With Type 2 Diabetes
Authors: Laferrère Blandine , Heshka Stanley , Wang Krystle , Khan Yasmin , McGinty James , Teixeira Julio , Hart Allison B. , Olivan Blanca
Published: June 2007

OBJECTIVE— Limited data on patients undergoing Roux-en-Y gastric bypass surgery (RY-GBP) suggest that an improvement in insulin secretion after surgery occurs rapidly and thus may not be wholly accounted for by weight loss. We hypothesized that in obese patients with type 2 diabetes the impaired levels and effect of incretins changed as a consequence of RY-GBP.

RESEARCH DESIGN AND METHODS— Incretin (gastric inhibitory peptide [GIP] and glucagon-like peptide-1 [GLP-1]) levels and their effect on insulin secretion were measured before and 1 month after RY-GBP in eight obese women with type 2 diabetes and in seven obese nondiabetic control subjects. The incretin effect was measured as the difference in insulin secretion (area under the curve [AUC]) in response to an oral glucose tolerance test (OGTT) and to an isoglycemic intravenous glucose test.

RESULTS— Fasting and stimulated levels of GLP-1 and GIP were not different between control subjects and patients with type 2 diabetes before the surgery. One month after RY-GBP, body weight decreased by 9.2 ± 7.0 kg, oral glucose-stimulated GLP-1 (AUC) and GIP peak levels increased significantly by 24.3 ± 7.9 pmol · l−1 · min−1 (P < 0.0001) and 131 ± 85 pg/ml (P = 0.007), respectively. The blunted incretin effect markedly increased from 7.6 ± 28.7 to 42.5 ± 11.3 (P = 0.005) after RY-GBP, at which it time was not different from that for the control subjects (53.6 ± 23.5%, P = 0.284).

CONCLUSIONS— These data suggest that early after RY-GBP, greater GLP-1 and GIP release could be a potential mediator of improved insulin secretion.
Prognostic Impact of Metabolic Syndrome by Different Definitions in a Population With High Prevalence of Obesity and Diabetes
Authors: de Simone Giovanni , Devereux Richard B. , Chinali Marcello , Best Lyle G. , Lee Elisa T. , Galloway James M. , Resnick Helaine E. ,   for the Strong Heart Study Investigators
Published: June 2007

OBJECTIVE— This study analyzed which definition of the metabolic syndrome is more predictive of cardiovascular events in both diabetic and nondiabetic members of a population-based sample.

RESEARCH DESIGN AND METHODS— A 10-year, longitudinal follow-up of the Strong Heart Study cohort has been evaluated. The analysis included 3,945 participants (2,384 female) with complete data (1,700 with diabetes and 1,468 with arterial hypertension) for evaluation of metabolic syndrome. Those with prevalent cardiovascular disease were excluded (n = 287, of whom 127 were female). Prevalence of metabolic syndrome was assessed based on the World Health Organization (WHO), the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III, and International Diabetes Federation (IDF) definitions. The main outcome was 10-year incidence of combined fatal and nonfatal cardiovascular events, including stroke, coronary heart disease, and congestive heart failure.

RESULTS— Fatal and nonfatal cardiovascular events occurred in 1,120 participants. After adjusting for age, sex, and diabetes, metabolic syndrome by all definitions was significantly associated with higher incidence of cardiovascular events (all P < 0.0001). In nondiabetic individuals, incident cardiovascular event rates were about 30–40% higher in those with metabolic syndrome, without a significant difference among definitions (0.03 < P < 0.001), and remained significant in WHO and NCEP ATP III definitions even after further adjustment for obesity, hypertension, and low HDL cholesterol. In the diabetic group, metabolic syndrome risk for cardiovascular events was greatest using the WHO definition (P < 0.002 vs. other models).

CONCLUSIONS— In individuals without diabetes, metabolic syndrome is associated with incident cardiovascular disease, especially with WHO and NCEP ATP III definitions. Metabolic syndrome also predicts higher cardiovascular event rates in diabetic participants, a prediction that is greatest using the WHO definition.
Monounsaturated Fat–Rich Diet Prevents Central Body Fat Distribution and Decreases Postprandial Adiponectin Expression Induced by a Carbohydrate-Rich Diet in Insulin-Resistant Subjects
Authors: Paniagua J.A. , de la Sacristana A. Gallego , Romero I. , Vidal-Puig A. , Latre J.M. , Sanchez E. , Perez-Martinez P. , Lopez-Miranda J. , Perez-Jimenez F.
Published: June 2007

OBJECTIVE— Central obesity is associated with insulin resistance through factors that are not fully understood. We studied the effects of three different isocaloric diets on body fat distribution, insulin sensitivity, and peripheral adiponectin gene expression.

RESEARCH DESIGN AND METHODS— Eleven volunteers, offspring of obese type 2 diabetic patients with abdominal fat deposition, were studied. These subjects were considered insulin resistant as indicated by Matsuda index values <4 after an oral glucose tolerance test, and they maintained A1C <6.5% without therapeutic intervention. All subjects underwent three dietary periods of 28 days each in a crossover design: 1) diet enriched in saturated fat (SAT), 2) diet rich in monounsaturated fat (MUFA) (Mediterranean diet), and 3) diet rich in carbohydrates (CHOs).

RESULTS— Weight, body composition, and resting energy expenditure remained unchanged during the three sequential dietary periods. Using dual-energy X-ray absorptiometry we observed that when patients were fed a CHO-enriched diet, their fat mass was redistributed toward the abdominal depot, whereas periphery fat accumulation decreased compared with isocaloric MUFA-rich and high-SAT diets (ANOVA P < 0.05). Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P < 0.05).

CONCLUSIONS— An isocaloric MUFA-rich diet prevents central fat redistribution and the postprandial decrease in peripheral adiponectin gene expression and insulin resistance induced by a CHO-rich diet in insulin-resistant subjects.
Prospective Study of Type 1 and Type 2 Diabetes and Risk of Stroke Subtypes
Authors: Janghorbani Mohsen , Hu Frank B. , Willett Walter C. , Li Tricia Y. , Manson Joann E. , Logroscino Giancarlo , Rexrode Kathryn M.
Published: June 2007

OBJECTIVE— The aim of this study was to examine the relationship between type 1 and type 2 diabetes and risk of stroke subtypes in women.

RESEARCH DESIGN AND METHODS— We followed 116,316 women aged 30–55 years in 1976 through 2002 for incidence of stroke. At baseline and through biennial follow-up, women were asked about their history and treatment of diabetes and other potential risk factors for stroke.

RESULTS— During 2.87 million person-years of follow-up, 3,463 incident strokes occurred. In multivariate analyses, the incidence of total stroke was fourfold higher in women with type 1 diabetes (relative risk [RR] 4.7 [95% CI 3.3–6.6]) and twofold higher among women with type 2 diabetes (1.8 [1.7–2.0]) than for nondiabetic women. The multivariate RR of ischemic stroke was increased sixfold (6.3 [4.0–9.8]) in type 1 diabetes and twofold (2.3 [2.0–2.6]) in type 2 diabetes. Risks for large-artery infarction and lacunar stroke were similar. Type 1 diabetes was also significantly associated with the risk of hemorrhagic stroke (3.8 [1.2–11.8]), but type 2 diabetes was not (1.0 [0.7–1.4]).

CONCLUSIONS— Both type 1 and type 2 diabetes are associated with substantially increased risks of total and most subtypes of stroke.
Six-Year Incidence of Proteinuria in Type 1 Diabetic African Americans
Authors: Roy Monique S. , Affouf Mahmoud , Roy Alec
Published: June 2007

OBJECTIVE— We sought to report the 6-year incidence of proteinuria and associated risk factors in African Americans with type 1 diabetes.

RESEARCH DESIGN AND METHODS— African Americans (n = 483) with type 1 diabetes were reexamined in a 6-year follow-up study. Proteinuria and creatinuria were measured in 4-h timed urine specimens obtained at initial and follow-up visits. Other evaluations included a structured clinical interview, ocular examination, masked grading of seven stereoscopic fundus photographs, blood pressure measurements, blood assays, and administration of the Beck Depression Inventory (BDI).

RESULTS— Over the 6-year period, 117 (42.9%) of the 473 patients at risk developed “any” proteinuria, defined as either microalbuminuria (26.0%) or overt (16.9%) proteinuria; 87 (23.5%) progressed from micro- or no albuminuria to overt proteinuria and 39 (8.7%) to end-stage renal disease; and 40 (20.6%) regressed. Peak incidence of any proteinuria occurred for patients who were 10–14 years of age or had 5–10 years of diabetes duration at baseline. Multiple regression analysis showed that baseline albumin excretion rate (AER), systemic hypertension, blood cholesterol, and high BDI depression scores were significant and independent risk factors for incidence of any proteinuria.

CONCLUSIONS— In African Americans with type 1 diabetes, the 6-year incidence of proteinuria is high, particularly among young patients and those with a relatively short duration of diabetes at baseline. Baseline AER is the strongest predictor for incidence of any proteinuria.
Asymmetric Dimethylarginine Predicts Cardiovascular Events in Patients With Type 2 Diabetes
Authors: Krzyzanowska Katarzyna , Mittermayer Friedrich , Wolzt Michael , Schernthaner Guntram
Published: June 2007

OBJECTIVE— Circulating concentrations of an endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are elevated in patients with increased cardiovascular risk. We hypothesized that ADMA predicts cardiovascular events and enhances risk prediction independent of established risk markers in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS— This prospective cohort study included 125 patients with type 2 diabetes. ADMA, l-arginine, high-sensitivity C-reactive protein (CRP), and routine clinical parameters were determined at baseline. First occurrence of cardiovascular events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, carotid revascularization, or all-cause mortality) was defined as a composite end point.

RESULTS— During a median follow-up of 21 (interquartile range 11–27) months, 84 events occurred in 48 patients. According to multivariate Cox regression analysis, patients with baseline ADMA or CRP in the highest tertile had a significantly increased hazard ratio for incident cardiovascular events compared with those with ADMA or CRP in tertile 1 (2.37 [95% CI 1.05–5.35], P = 0.038, and 3.63 [1.59–8.28], P = 0.002). Assessing the joint effect of ADMA and CRP revealed that patients with either ADMA or CRP or both in the highest tertile had increased hazard ratios for cardiovascular events compared with patients with neither ADMA nor CRP in the highest tertile before and after adjustment for possible confounders (hazard ratio 4.59 [95% CI 2.07–10.15], P < 0.001).

CONCLUSIONS— ADMA predicted cardiovascular events and enhanced the predictive role of CRP in patients with type 2 diabetes. ADMA therefore could improve cardiovascular risk assessment in patients with type 2 diabetes.
Central Obesity Is an Independent Risk Factor for Albuminuria in Nondiabetic South Asian Subjects
Authors: Chandie Shaw Prataap K. , Berger Stefan P. , Mallat Marko , Frölich Marijke , Dekker Friedo W. , Rabelink Ton J.
Published: June 2007

OBJECTIVE— South Asians have a high prevalence of central obesity. When the diagnosis of diabetes is made, they have a very high risk of developing renal failure. In the current study, we explored the hypothesis that central obesity is associated with the development of renal injury, before the manifestation of diabetes.

RESEARCH DESIGN AND METHODS— We invited first-degree nondiabetic relatives of South Asian type 2 diabetic patients for investigation of microalbuminuria and diabetes. Subjects who used antihypertensive or antidiabetic medication were excluded. We performed a glucose tolerance test according to the classic World Health Organization criteria. A total of 205 subjects were normoglycemic; we excluded 25 subjects because of impaired glucose tolerance, and 30 subjects were excluded because of de novo diabetes. Central obesity was measured by waist-to-hip ratio (WHR). Albuminuria was measured as albumin-to-creatinine ratio (ACR) in the early-morning urine.

RESULTS— Central obesity was independently related with albuminuria in the 205 normoglycemic subjects. We found no relation of fasting blood glucose or systolic blood pressure with albuminuria. Multivariate analysis for the presence of increased albuminuria (median ACR >0.31 mg/mmol) showed a relative risk of 4.1 for the highest versus the lowest tertile of WHR (P = 0.002).

CONCLUSIONS— Central obesity is an early and independent risk factor for increased albuminuria in normoglycemic South Asian subjects. This could explain the high incidence of diabetic renal disease in South Asians, probably by the mechanism of insulin resistance and endothelial dysfunction in the pre-diabetic state.
Elevated Cystatin C Concentration and Progression to Pre-Diabetes
Authors: Donahue Richard P. , Stranges Saverio , Rejman Karol , Rafalson Lisa B. , Dmochowski Jacek , Trevisan Maurizio
Published: June 2007

OBJECTIVE— We conducted a nested case-control investigation to examine whether elevated baseline concentrations of cystatin C predicted progression from normoglycemia to pre-diabetes over 6 years of follow-up from the Western New York Health Study.

RESEARCH DESIGN AND METHODS— In 2002–2004, 1,455 participants from the Western New York Health Study, who were free of type 2 diabetes and known cardiovascular disease at baseline (1996–2001), were reexamined. An incident case of pre-diabetes was defined as an individual with fasting glucose <100 mg/dl at the baseline examination and ≥100 and ≤125 mg/dl at the follow-up examination, thereby eliminating individuals with prevalent pre-diabetics. All case patients (n = 91) were matched 1:3 to control participants based on sex, race/ethnicity, and year of study enrollment. All control subjects had fasting glucose levels <100 mg/dl at both baseline and follow-up examinations. Cystatin C concentrations and the urinary albumin-to-creatinine ratio were measured from frozen (−196°C) baseline blood and urine samples. Serum creatinine concentrations were available from the baseline examination only.

RESULTS— Multivariate conditional logistic regression analyses adjusted for age, baseline glucose level, homeostasis model assessment of insulin resistance, BMI, hypertension, estimated glomerular filtration rate, cigarette smoking, and alcohol use revealed a significantly increased risk of progression to pre-diabetes among those with elevated baseline concentrations of cystatin C (odds ratio 3.28 [95% CI 1.43–7.54]) (upper quintile versus the remainder). Results of secondary analyses that considered high-sensitivity C-reactive protein, interleukin-6, E-selectin, or soluble intercellular adhesion molecule-1 did not alter these results.

CONCLUSIONS— These results suggest that cystatin C was associated with a threefold excess risk of progression to pre-diabetes in this population.
Alanine Aminotransferase and Directly Measured Insulin Sensitivity in a Multiethnic Cohort
Authors: Hanley Anthony J.G. , Wagenknecht Lynne E. , Festa Andreas , D'Agostino Ralph B. , Haffner Steven M.
Published: June 2007

OBJECTIVE— The objective of the present analysis was to evaluate the association of alanine aminotransferase (ALT) with directly measured insulin sensitivity (Si) in a large, multiethnic cohort of U.S. adults and to determine whether ALT adds to existing metabolic risk definitions in identifying subjects with insulin resistance.

RESEARCH DESIGN AND METHODS— Si was directly measured from frequently sampled intravenous glucose tolerance tests among 999 nondiabetic African-American, Hispanic, and non-Hispanic white subjects aged 40–69 years who were participating in the Insulin Resistance Atherosclerosis Study. Subjects also received an oral glucose tolerance test, and fasting insulin, ALT, and alcohol intake were determined.

RESULTS— ALT was associated with Si after adjustment for age, sex, ethnicity, impaired fasting glucose, triglycerides, HDL, blood pressure, and waist (clinical model) (P < 0.0001). The association remained significant after further adjustment for fasting insulin and impaired glucose tolerance (P = 0.004). In logistic regression analysis, elevated ALT (upper quartile) was associated with insulin resistance (lowest quartile of Si) after adjustment for age, sex, and ethnicity (odds ratio 3.0 [95% CI 2.2–4.1]). Elevated ALT was independently associated with insulin resistance when included in models with waist circumference, National Cholesterol Education Program criteria for metabolic syndrome, hypertriglyceridemic waist, elevated triglyceride-to-HDL ratio, or homeostasis model assessment of insulin resistance (HOMA-IR) (all P < 0.01). Finally, the addition of elevated ALT improved classification of insulin resistance by area under the receiver operating characteristic curve criteria for all models except HOMA-IR.

CONCLUSIONS— ALT was associated with insulin resistance independently of conventional and more detailed metabolic measures. These findings suggest that the addition of ALT to existing clinically based metabolic risk definitions is an inexpensive way to improve the identification of subjects with insulin resistance.
Use of Maternal GHb Concentration to Estimate the Risk of Congenital Anomalies in the Offspring of Women with Prepregnancy Diabetes
Authors: Guerin Andrea , Nisenbaum Rosane , Ray Joel G.
Published: June 2007

OBJECTIVE— We sought to determine the absolute risk of having a congenital anomaly in relation to periconceptional GHb concentration among women with prepregnancy diabetes.

RESEARCH DESIGN AND METHODS— Two reviewers independently retrieved all cohort studies through a systematic literature search between January 1985 and May 2006. For each study, the absolute risk of having a pregnancy affected by a major or minor structural anomaly (diagnosed either antenatally or up to 28 days after conception) was calculated according to the number of SDs of GHb above the mean for nondiabetic, nonpregnant control subjects. A multilevel logistic-normal model was used to pool the data, which were expressed in tabular and graphic formats.

RESULTS— In seven cohort studies, there were 117 anomalies among 1,977 pregnancies. At a periconceptional GHb concentration 0 SD above normal, the absolute risk of a pregnancy affected by a congenital anomaly was ∼2% (95% CI 0.0–4.4). At 2 SD above normal, the risk was 3% (0.4–6.1), and at 8 SD it was ∼10% (2.3–17.8). For each 1-SD unit increase in GHb, the associated risk of a congenital malformation increased by an odds ratio of 1.2 (95% CI 1.1–1.4). The risk in relation to A1C followed the same pattern.

CONCLUSIONS— Using data from a limited number of published studies, a practical aid was developed to optimize use of the GHb and A1C concentrations for estimating the absolute risk of a congenital anomaly in the offspring of women with prepregnancy diabetes.
Telmisartan Shows an Equivalent Effect of Vitamin C in Further Improving Endothelial Dysfunction After Glycemia Normalization in Type 1 Diabetes
Authors: Ceriello Antonio , Piconi Ludovica , Esposito Katherine , Giugliano Dario
Published: June 2007

OBJECTIVE— Long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations of endothelial function by increased oxidative stress, even when glycemia is normalized.

RESEARCH DESIGN AND METHODS— In this study, 36 type 1 diabetic patients and 12 control subjects were enrolled. The diabetic patients were divided into three groups. The first group was treated for 24 h with insulin, achieving a near normalization of glycemia. After 12 h of this treatment, vitamin C was added for the remaining 12 h. The second group was treated for 24 h with vitamin C. After 12 h of this treatment, insulin was started, achieving a near normalization of glycemia for the remaining 12 h. The third group was treated for 24 h with both vitamin C and insulin, achieving near normalization of glycemia. The same protocols were performed after 1 month of telmisartan or placebo.

RESULTS— Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels. Telmisartan significantly improved basal endothelial function and decreased nitrotyrosine plasma levels. In patients treated with telmisartan, a near normalization of both flow-mediated vasodilation and oxidative stress was achieved when glycemia was normalized, whereas adding vitamin C infusion did not show further effect on endothelial function or nitrotyrosine plasma levels.

CONCLUSIONS— These data indicate that combining the normalization of glycemia with an antioxidant can normalize endothelial function in type 1 diabetic patients and that telmisartan works as an antioxidant like vitamin C.
A Sagnac-Michelson fibre optic interferometer: Signal processing for disturbance localization
Authors: Kondrat M. , Szustakowski M. , Pałka N. , Ciurapiński W. , Życzkowski M.
Published: June 2007

We present numerical and experimental results on a new generation fibre optic perimeter sensor based on a Sagnac and Michelson interferometers configuration. In particular, an original signal processing scheme is presented. The sensor can detect a potential intruder and determine its position along a protected zone. We propose a localization method that offers the inherent properties of both interferometers. After demodulation of the signals from both interferometers, the obtained amplitude characteristic of the Sagnac interferometer depends on a position of a disturbance along the interferometer, while amplitude characteristic of the Michelson interferometer does not depend on this position. So, quotient of both demodulated characteristics makes it possible to localize the disturbance. During investigations of a laboratory model of the sensor, it was possible to detect the position of the disturbance with a resolution of about 40 m along the 6-km-long sensor.
Analysis of noise properties of an optocoupler device
Authors: Konczakowska A. , Cichosz J. , Szewczyk A. , Stawarz B.
Published: June 2007

In the paper, localization of a source of random telegraph signal noise (RTS noise) in optocoupler devices of CNY 17 type was defined. The equivalent noise circuit in low frequency noise for these types of optocouplers was proposed.
Sensor properties of planar waveguide structures with grating couplers
Authors: Karasiński P.
Published: June 2007

The paper presents the results of theoretical analysis as well as the results of experimental research involving planar sensor structures with input grating couplers of the period Λ = 800 nm. In the theoretical part of the paper we discussed the influence of the parameters of a sensor structure on it sensitivities. The experimental part of the work presents the results of experimental research involving the influence of refractive index of the cover on the coupling characteristics of sensor structures with grating couplers. The full widths at half maximum (FWHM) were from 0.023° to 0.029°. For the investigated structures we estimated detection thresholds for the changes of refractive index of the cover and the changes of sensitive film thickness. It has been demonstrated that by the application of the elaborated structures we can detect minimal changes of the refractive index (Δnc)min = 2.1×10−6 when the refractive index of the cover nc = 1.333 and (Δnc)min = 1.0×10−6 when nc = 1515. For sensitive films of the thickness w < 100 nm, by using the elaborated structures, we can detect mean changes of the thickness along the values lower than 10−3 nm.
Prioritization of Low-Volume Pavement Sections for Maintenance by Using Fuzzy Logic
Authors: Chandran Shiju , Isaac Kuncheria P. , Veeraragavan A.
Published: June 2007

A pavement management system formulated according to the specific needs and resources of a highway agency should ensure satisfactory pavement performance with minimal maintenance cost. The success of a pavement management system depends on the pavement condition data, accuracy of the prediction of pavement performance, and project-and network-level rehabilitation planning. Of these, the most labor-intensive, time-consuming, and costly component is the collection of pavement condition data. The inventory data include roughness, skid resistance, and surface distresses. Although mechanical instruments are available for rapid collection of roughness and skid resistance data, the collection of distress data for low-volume rural roads is still manual and hence labor-intensive and time-consuming. Subjective rating techniques prove to be a solution to this problem, but their reliability is poor due to the subjectivity associated with them. Therefore, there is a need for a rapid and cost-effective yet reliable method for collecting pavement condition data. The Prime Minister's Gram Sadak Yojana is a project launched in India by the Government of India to provide all-weather road connectivity to rural habitations. The investment is around 600 billion rupees ($15 billion) during the period 2000–2007. As part of the project, road stretches are prioritized for maintenance and reconstruction by using the pavement condition index. The quantification of the severity and extent of data collected is affected by each panel member's perception and judgment. To deal effectively with the subjectivity associated with human judgment of distress severity and extent, mathematical techniques of fuzzy set were used. Fuzzy membership functions were formulated for severity, extent, and relative importance of each distress with respect to maintenance. Fuzzy condition indices were used to prioritize the pavement sections by suitable fuzzy ranking methods. The effectiveness of the method is established by ranking pavement sections.
Asset Valuation of Low-Volume Road Networks
Authors: De Solminihac Hernán E. , Hidalgo Priscila , Chamorro Alondra
Published: June 2007

Asset management is a systematic process of maintenance, modernization, and operation of infrastructure assets in an economically efficient way. For these reasons, asset management has been considered as an emerging concept applied in the area of transport management. Many countries have developed procedures to evaluate pavement infrastructure assets; however, these applications generally have focused on main interurban and urban roads. The objective of this paper is to present a methodology to determine the asset value of low-volume roads and to quantify the impact of maintenance policies on such asset value. As a case study, the proposed methodology was applied to the unpaved road network of Chile, considering different maintenance policies and their impact on the evolution of the road network asset value. A complete analysis that considered the impact of maintenance policies under different budgetary conditions was performed. The analysis was done by using the HDM-4 program, since it performs technical and economic valuations considering a reposition value method. Relationships close to linear were found between final asset value of the unpaved road network under a 20-year valuation. Results showed that medium levels of investment are needed to maintain the network asset value. A small increase of the initial asset value of a network is obtained with high levels of investment. Asset valuation is a good and simple tool that helps agencies during a first-level management process. However, it is not recommended on its own as an optimization tool for the allocation of resources, as social costs and benefits associated with each investment strategy need to be considered.
Correlation of California Bearing Ratio with Shear Strength Parameters
Authors: Gregory Garry H. , Cross Stephen A.
Published: June 2007

The California bearing ratio (CBR) test is still widely used in the design and analysis of pavements. The CBR test is relatively expensive and time consuming. A method is proposed for correlating CBR values with the undrained shear strength of clay soils, or the effective internal friction angle of noncohesive soils. Unconsolidated undrained triaxial tests on clays and quick drained-triaxial tests on sands can determine these parameters. These tests are much more economical and rapid than the CBR test. The correlation is based on foundation-bearing capacity theory. The configuration of the CBR test can be closely modeled in bearing capacity theory as a circular foundation with a surcharge. Actual test results are presented to support the correlations. The proposed method allows economical development of estimated CBR values from quick shear tests. The correlation between shear strength results and CBR has been established on the basis of a limited number of soil samples. Additional test results are needed to verify the correlation. In the interim, the proposed method should be used with good judgment and engineering experience to provide a quick method of determining sub-grade soil properties for pavement thickness design.
Guidelines to Engineering Analysis of Motorized Mixed Use on Low-Volume Roads in U.S. National Forests
Authors: Gililland Ed , Robbins Frank
Published: June 2007

In the past few decades, the availability and capability of off-highway vehicles (OHVs) have increased tremendously. On November 9, 2005, the U.S. Department of Agriculture (USDA) Forest Service published a final travel management regulation governing use of OHVs and other motor vehicles on National Forest System lands. The final rule requires individual national forests to designate those roads, trails, and areas open to motor vehicle use. For the USDA Forest Service to designate a road to be open for operation of both highway-legal and non-highway-legal vehicles at the same time (motorized mixed use), an engineering analysis must be performed. When motorized mixed-use designation is proposed for a road, a qualified engineer must determine whether that road can accommodate motorized mixed use, mitigation measures should be implemented before designation, or designation would be inappropriate. The guidelines that will be used by qualified engineers of the USDA Forest Service to analyze low-volume National Forest System roads are described, along with factors to be included in the analysis, possible mitigation measures, and documentation for motorized mixed-use analysis.
New Products Evaluation Program for Lower-Volume Local Roads
Authors: Gray Robert M. , Roback Jeffery G.
Published: June 2007

The Pennsylvania Department of Transportation (PennDOT) original and innovative program that introduces local governments to new products and processes through the use of its liquid fuels funds is presented, and other departments of transportation are encouraged to adapt it. Liquid fuels funds may be used on locally owned and maintained roads with approved PennDOT products and processes. PennDOT's Bureau of Municipal Services (BMS) initiated the program, the New Products Evaluation Program for Lower-Volume Local Roads, to give stakeholders a wider selection of quality products and processes to choose from. Pennsylvania maintains an interest in reducing costs for local governments by providing access to high-quality products that are eligible for liquid fuels funds expenditures. These products are designed for lower-volume roads rather than high-volume highways. PennDOT also initiated this streamlined program to allow manufacturers of innovative products and processes for lower-volume local roads to submit their applications to PennDOT for evaluation. The manufacturers contract with the testing facilities and are responsible for all costs incurred in the testing and evaluation process. The objectives of this program are to (a) increase the number of available high-quality new products and processes for low-volume local roads, (b) create strong communication channels among various stakeholders and BMS about new product offerings for low-volume local roads, (c) provide manufacturers with a more expedient process for testing their products locally, and (d) develop a products evaluation process that is more cost-effective for local governments and PennDOT.
Strategic Planning for Optimization of Road-Building Materials in Overberg District Municipality in South Africa
Authors: Van Zyl Gerrie , Fourie Gerhard , Henderson Mervyn
Published: June 2007

Maintaining gravel roads to an acceptable level with increasing traffic volumes and social and environmental needs on the one hand and decreasing budgets and availability of suitable material on the other hand requires innovation and long-term strategic planning to keep agency and road user costs as low as possible. These conditions were identified in the Overberg District of Western Cape Province in South Africa, where a huge backlog for regravelling of roads has developed because of limited funding and difficulties in obtaining suitable materials. District municipalities act as agents to the provincial government and are therefore responsible for the maintenance of provincial roads within their regions. The average gravel thickness of the gravel wearing course on divisional and main roads in Western Cape Province has dropped from more than 80 mm to less than 40 mm in the past 10 years. Intense involvement in the Overberg District Municipality (DM) with gravel road maintenance, upgrading, performance monitoring, the finding of suitable road-building materials, and approval for mining has led to the realization that existing strategies for gravel road maintenance are inadequate to deliver acceptable service to the road user and to ensure that available material sources are optimally used. From an evaluation of needs and constraints within the DM, several factors have been identified as important contributors in the long-term planning of road maintenance and material utilization. This resulted in (a) a subdivision of the area as based on material availability, land use, topography, climate, and so forth; (b) identification of life-cycle maintenance strategy categories; (c) alternative approaches for material source selection and longer-term usage; and (d) the introduction of initiatives that help to reduce material demand. The approach followed to optimize both material sources and service delivery to the road user and preservation of the environment is discussed.
Best Practices for Pavement Edge Maintenance
Authors: Lawson William D. , Hossain M. Shabbir
Published: June 2007

The problem of pavement edge drop-offs as a maintenance, safety, and liability issue for the Texas Department of Transportation (TxDOT) is discussed. The objectives for this 2-year research project—to identify and to communicate best practices effectively for pavement edge maintenance—were accomplished by capturing more than 3,700 years of institutional knowledge from maintenance leaders representing all 25 TxDOT districts. The research focuses on maintenance practices for naturally occurring edge drop-offs, with an emphasis on low-volume roads. The key factors causing edge drop-offs are narrow road width or absence of shoulders, traffic volume and type, and adverse environmental conditions. Tracy's law—“if you lose the edge, you lose the road”— provides a key perspective on meeting these challenges and points out that good edge maintenance strategy is important in achieving good roads and that without good edge maintenance, a district cannot achieve good roads. Edge maintenance practices and procedures fall into three broad categories: awareness, preventive maintenance, and edge repair techniques. Road widening, both in-house by using TxDOT forces and by formal contract, emerged as the ultimate practice for long-term treatment of edge problems. Districts use conventional, in-house-modified, and commercially manufactured equipment specifically dealing with pavement edge maintenance to address the edge drop-off issue. Because of the significant financial resources devoted to pavement edge maintenance, several tools are used to improve the planning and allocation of edge maintenance funds.