bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil Heterogeneity Effects on Solute Breakthrough Sampled with Suction Cups: Numerical Simulations
Authors: Weihermüller Lutz , Kasteel Roy , Vereecken Harry
Published: July 2006

Porous cups are widely used to extract soil solution for monitoring solute transport; however, it is not always clear how soil heterogeneity influences solute breakthrough sampled by suction cups. The objective of this study was to evaluate the influence of soil heterogeneity on the breakthrough of solute extracted by suction cups. We conducted numerical simulations using the HYDRUS‐2D code. Local‐scale heterogeneity in hydraulic properties was generated using Miller–Miller scaling theory. Results of the simulations show that effective transport parameters derived from the measured breakthrough curves in the suction cups depended on the location of the suction cup in the heterogeneous flow field. Mean pore water velocities obtained from suction cup measurements ranged by a factor of 1.6 and dispersivities by a factor of 1.5 for the different heterogeneous structures. As a consequence, the arrival time (first moment) of the tracer plume derived from suction cup measurements was accelerated or delayed compared with the homogeneous case. Mass recoveries and suction cup sampling areas were also influenced by the underlying structure. The applied suction in the cup as well as the suction cup sampling area were found to have important effects on the mean pore water velocity, dispersivity, and mass recovery. The effect of variation in applied suction was analyzed using reference point data taken from 10 locations in the undisturbed flow field. Contrary to the general assumption that solute spreading measured with suction cups depends only on the mean pore water velocity, our results show that solute spreading is also influenced by (i) the suction cup sampling area and the deformation of streamlines to the cup, and (ii) the flow channels that are sampled. The numerical simulations indicate that the number of suction cups required for calculating a mean breakthrough curve in the chosen heterogeneous flow field must to be >20.
Preschoolers' Imaginative Play as Precursor of Narrative Consciousness
Authors: Singer Jerome L. , Singer Dorothy G.
Published: July 2006

Can the early childhood play of preschoolers foreshadow the form and complexity of adult ongoing consciousness? The beginnings of make-believe play in children from about two years of age are reviewed starting with transitional objects, play with soft toys, or imaginary playmates. The roles of pretending and story-telling play are next examined and their contribution not only to sheer enjoyment but to an array of cognitive, social, and emotional skills are considered. We discuss the contribution of adults as nurturers and enhancers of such play. We turn finally to the aspects of adult consciousness: wakeful perception; identification, labeling, and encoding; guided imagery, mental trial actions, and playfulness. The features of childhood play may be seen to foreshadow an array of functions of ongoing conscious thought, especially its narrative components and, following Baars' theory, its role as a “theater” for prioritizing, decision-making, contextualizing, and creativity.
Dreams of Truck Drivers: A Test of the Continuity Hypothesis of Dreaming
Authors: Schredl Michael , Funkhouser Arthur , Arn Nicole
Published: July 2006

Empirical studies largely support the continuity hypothesis of dreaming. The present study investigated the frequency and emotional tone of dreams of truck drivers. On the one hand, the findings of the present study partly support the continuity regarding the time spent with driving/being in the truck and driving dreams and, on the other hand, a close relationship was found between daytime mood (feelings of stress, job satisfaction) and dream emotions, i.e., different dream characteristics were affected by different aspects of daytime activity. The results, thus, indicate that it is necessary to define very clearly how this continuity is to be conceptualized. The approach of formulating a mathematical model (cf. [1]) should be adopted in future studies in order to specify the factors and their magnitude in the relationship between waking and dreaming.
Self-Perceived High Intuitiveness: An Initial Exploration
Authors: Rogers Paul , Wiseman Richard
Published: July 2006

This article presents the results of an exploratory and qualitative examination of the beliefs, experiences and alleged abilities of 50 individuals claiming to be highly intuitive. Participants offered three distinct mechanisms to explain how their intuition works—psychological, psychic, and spiritual. They reported relying on intuition mainly to judge the personality of strangers and predict the outcome of future events. Most could not recall instances of their intuitive judgments failing, and believed it was always wise to act on an intuition. Almost all reported believing that the onset of intuition was uncontrollable, but could be enhanced by becoming more receptive to one's “gut feelings.” These results are discussed in terms of developing a more detailed and ecologically valid understanding of intuition.
Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis in Diabetic LDL Receptor–Deficient Mice
Authors: Zang Mengwei , Xu Shanqin , Maitland-Toolan Karlene A. , Zuccollo Adriana , Hou Xiuyun , Jiang Bingbing , Wierzbicki Michel , Verbeuren Tony J. , Cohen Richard A.
Published: July 2006

Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMP-activated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor–deficient mice (DMLDLR−/−). In HepG2 hepatocytes, polyphenols, including resveratrol (a major polyphenol in red wine), apigenin, and S17834 (a synthetic polyphenol), increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC), and they increased activity of AMPK with 200 times the potency of metformin. The polyphenols also prevented the lipid accumulation that occurred in HepG2 cells exposed to high glucose, and their ability to do so was mimicked and abrogated, respectively, by overexpression of constitutively active and dominant-negative AMPK mutants. Furthermore, treatment of DMLDLR−/− mice with S17834 prevented the decrease in AMPK and ACC phosphorylation and the lipid accumulation in the liver, and it also inhibited hyperlipidemia and the acceleration of aortic lesion development. These studies 1) reveal that inactivation of hepatic AMPK is a key event in the pathogenesis of hyperlipidemia in diabetes, 2) point to a novel mechanism of action of polyphenols to lower lipids by activating AMPK, and 3) emphasize a new therapeutic avenue to benefit hyperlipidemia and atherosclerosis specifically in diabetes via activating AMPK.
Systemic Immune Mediators and Lifestyle Changes in the Prevention of Type 2 Diabetes
Authors: Herder Christian , Peltonen Markku , Koenig Wolfgang , Kräft Ilka , Müller-Scholze Sylvia , Martin Stephan , Lakka Timo , Ilanne-Parikka Pirjo , Eriksson Johan G. , Hämäläinen Helena , Keinänen-Kiukaanniemi Sirkka , Valle Timo T. , Uusitupa Matti , Lindström Jaana , Kolb Hubert , Tuomilehto Jaakko ,   for the Finnish Diabetes Prevention Study Group
Published: July 2006

The Finnish DPS (Diabetes Prevention Study) demonstrated that lifestyle intervention, aimed at increasing physical activity, improving diet, and decreasing body weight, reduced the incidence of type 2 diabetes in individuals with overweight and impaired glucose tolerance by 58%. Here, we studied which immunological markers at baseline predicted subsequent type 2 diabetes and whether there are immunologically defined subsets of subjects who are more or less responsive to the protective effects of lifestyle intervention. We randomly assigned 522 participants to a control group (n = 257) or a lifestyle intervention group (n = 265). Immunological parameters at baseline included high-sensitivity C-reactive protein (CRP), serum amyloid A, interleukin-6, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage migration inhibitory factor (MIF), and soluble intercellular adhesion molecule. In the control group, CRP was the best immunological predictor for progression to overt type 2 diabetes. In the intervention group, progression to type 2 diabetes was significantly higher in subjects with the highest RANTES concentrations and was lower in subjects with the highest MIF levels. Ratios of RANTES to MIF in the upper tertile were highly predictive of incident type 2 diabetes in the intervention group (P = 0.006), whereas the association was less pronounced in the control group (P = 0.088). Thus, systemic concentrations of immune mediators appear to be associated with the progression to type 2 diabetes and the prevention of type 2 diabetes by lifestyle changes.
Free Fatty Acids Inhibit Insulin Signaling–Stimulated Endothelial Nitric Oxide Synthase Activation Through Upregulating PTEN or Inhibiting Akt Kinase
Authors: Wang Xing Li , Zhang Lin , Youker Keith , Zhang Ming-Xiang , Wang Jian , LeMaire Scott A. , Coselli Joseph S. , Shen Ying H.
Published: July 2006

In metabolic syndrome, a systemic deregulation of the insulin pathway leads to a combined deregulation of insulin-regulated metabolism and cardiovascular functions. Free fatty acids (FFAs), which are increased in metabolic syndrome, inhibit insulin signaling and induce metabolic insulin resistance. This study was designed to examine FFAs’ effects on vascular insulin signaling and endothelial nitric oxide (NO) synthase (eNOS) activation in endothelial cells. We showed that FFAs inhibited insulin signaling and eNOS activation through different mechanisms. While linoleic acid inhibited Akt-mediated eNOS phosphorylation, palmitic acid appeared to affect the upstream signaling. Upregulation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) activity and transcription by palmitic acid mediated the inhibitory effects on insulin signaling. We further found that activated stress signaling p38, but not Jun NH2-terminal kinase, was involved in PTEN upregulation. The p38 target transcriptional factor activating transcription factor (ATF)-2 bound to the PTEN promoter, which was increased by palmitic acid treatment. In summary, both palmitic acid and linoleic acid exert inhibitory effect on insulin signaling and eNOS activation in endothelial cells. Palmitic acid inhibits insulin signaling by promoting PTEN activity and its transcription through p38 and its downstream transcription factor ATF-2. Our findings suggest that FFA-mediated inhibition of vascular insulin signaling and eNOS activation may contribute to cardiovascular diseases in metabolic syndrome.
Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States
Authors: Lee Yun S. , Kim Woo S. , Kim Kang H. , Yoon Myung J. , Cho Hye J. , Shen Yun , Ye Ji-Ming , Lee Chul H. , Oh Won K. , Kim Chul T. , Hohnen-Behrens Cordula , Gosby Alison , Kraegen Edward W. , James David E. , Kim Jae B.
Published: July 2006

Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat–fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3′ kinase–independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.
Increased Malonyl-CoA Levels in Muscle From Obese and Type 2 Diabetic Subjects Lead to Decreased Fatty Acid Oxidation and Increased Lipogenesis; Thiazolidinedione Treatment Reverses These Defects
Authors: Bandyopadhyay Gautam K. , Yu Joseph G. , Ofrecio Jachelle , Olefsky Jerrold M.
Published: July 2006

Increased accumulation of fatty acids and their derivatives can impair insulin-stimulated glucose disposal by skeletal muscle. To characterize the nature of the defects in lipid metabolism and to evaluate the effects of thiazolidinedione treatment, we analyzed the levels of triacylglycerol, long-chain fatty acyl-coA, malonyl-CoA, fatty acid oxidation, AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), malonyl-CoA decarboxylase, and fatty acid transport proteins in muscle biopsies from nondiabetic lean, obese, and type 2 subjects before and after an euglycemic-hyperinsulinemic clamp as well as pre–and post–3-month rosiglitazone treatment. We observed that low AMPK and high ACC activities resulted in elevation of malonyl-CoA levels and lower fatty acid oxidation rates. These conditions, along with the basal higher expression levels of fatty acid transporters, led accumulation of long-chain fatty acyl-coA and triacylglycerol in insulin-resistant muscle. During the insulin infusion, muscle fatty acid oxidation was reduced to a greater extent in the lean compared with the insulin-resistant subjects. In contrast, isolated muscle mitochondria from the type 2 subjects exhibited a greater rate of fatty acid oxidation compared with the lean group. All of these abnormalities in the type 2 diabetic group were reversed by rosiglitazone treatment. In conclusion, these studies have shown that elevated malonyl-CoA levels and decreased fatty acid oxidation are key abnormalities in insulin-resistant muscle, and, in type 2 diabetic patients, thiazolidinedione treatment can reverse these abnormalities.
Temporal Dynamics of Tyrosine Phosphorylation in Insulin Signaling
Authors: Schmelzle Katrin , Kane Susan , Gridley Scott , Lienhard Gustav E. , White Forest M.
Published: July 2006

The insulin-signaling network regulates blood glucose levels, controls metabolism, and when dysregulated, may lead to the development of type 2 diabetes. Although the role of tyrosine phosphorylation in this network is clear, only a limited number of insulin-induced tyrosine phosphorylation sites have been identified. To address this issue and establish temporal response, we have, for the first time, carried out an extensive, quantitative, mass spectrometry-based analysis of tyrosine phosphorylation in response to insulin. The study was performed with 3T3-L1 adipocytes stimulated with insulin for 0, 5, 15, and 45 min. It has resulted in the identification and relative temporal quantification of 122 tyrosine phosphorylation sites on 89 proteins. Insulin treatment caused a change of at least 1.3-fold in tyrosine phosphorylation on 89 of these sites. Among the responsive sites, 20 were previously known to be tyrosine phosphorylated with insulin treatment, including sites on the insulin receptor and insulin receptor substrate-1. The remaining 69 responsive sites have not previously been shown to be altered by insulin treatment. They were on proteins with a wide variety of functions, including components of the trafficking machinery for the insulin-responsive glucose transporter GLUT4. These results show that insulin-elicited tyrosine phosphorylation is extensive and implicate a number of hitherto unrecognized proteins in insulin action.
Liver-Specific Inhibition of ChREBP Improves Hepatic Steatosis and Insulin Resistance in ob/ob Mice
Authors: Dentin Renaud , Benhamed Fadila , Hainault Isabelle , Fauveau Véronique , Foufelle Fabienne , Dyck Jason R.B. , Girard Jean , Postic Catherine
Published: July 2006

Obesity is a metabolic disorder often associated with type 2 diabetes, insulin resistance, and hepatic steatosis. Leptin-deficient (ob/ob) mice are a well-characterized mouse model of obesity in which increased hepatic lipogenesis is thought to be responsible for the phenotype of insulin resistance. We have recently demonstrated that carbohydrate responsive element–binding protein (ChREBP) plays a key role in the control of lipogenesis through the transcriptional regulation of lipogenic genes, including acetyl-CoA carboxylase and fatty acid synthase. The present study reveals that ChREBP gene expression and ChREBP nuclear protein content are significantly increased in liver of ob/ob mice. To explore the involvement of ChREBP in the physiopathology of hepatic steatosis and insulin resistance, we have developed an adenovirus-mediated RNA interference technique in which short hairpin RNAs (shRNAs) were used to inhibit ChREBP expression in vivo. Liver-specific inhibition of ChREBP in ob/ob mice markedly improved hepatic steatosis by specifically decreasing lipogenic rates. Correction of hepatic steatosis also led to decreased levels of plasma triglycerides and nonesterified fatty acids. As a consequence, insulin signaling was improved in liver, skeletal muscles, and white adipose tissue, and overall glucose tolerance and insulin sensitivity were restored in ob/ob mice after a 7-day treatment with the recombinant adenovirus expressing shRNA against ChREBP. Taken together, our results demonstrate that ChREBP is central for the regulation of lipogenesis in vivo and plays a determinant role in the development of the hepatic steatosis and of insulin resistance in ob/ob mice.
Altered Skeletal Muscle Subsarcolemmal Mitochondrial Compartment During Catch-Up Fat After Caloric Restriction
Authors: Crescenzo Raffaella , Lionetti Lillà , Mollica Maria Pina , Ferraro Marialuisa , D’Andrea Elvira , Mainieri Davide , Dulloo Abdul G. , Liverini Giovanna , Iossa Susanna
Published: July 2006

An accelerated rate of fat recovery (catch-up fat) and insulin resistance are characteristic features of weight recovery after caloric restriction, with implications for the pathophysiology of catch-up growth and weight fluctuations. Using a previously described rat model of weight recovery in which catch-up fat and skeletal muscle insulin resistance have been linked to suppressed thermogenesis per se, we investigated alterations in mitochondrial energetics and oxidative stress in subsarcolemmal (SS) and intermyofibrillar (IMF) skeletal muscle mitochondria. After 2 weeks of semistarvation followed by 1 week of refeeding, the refed rats show persistent and selective reductions in SS mitochondrial mass (assessed from citrate synthase activity in tissue homogenate and isolated mitochondria) and oxidative capacity. Furthermore, the refed rats show, in both SS and IMF muscle mitochondria, a lower aconitase activity (whose inactivation is an index of increased reactive oxygen species [ROS]), associated with higher superoxide dismutase activity and increased proton leak. Taken together, these studies suggest that diminished skeletal muscle mitochondrial mass and function, specifically in the SS mitochondrial compartment, contribute to the high metabolic efficiency for catch-up fat after caloric restriction and underscore a potential link between diminished skeletal muscle SS mitochondrial energetics, increased ROS concentration, and insulin resistance during catch-up fat.
An Open, Randomized, Parallel-Group Study to Compare the Efficacy and Safety Profile of Inhaled Human Insulin (Exubera) With Glibenclamide as Adjunctive Therapy in Patients With Type 2 Diabetes Poorly Controlled on Metformin
Authors: Barnett Anthony H. , Dreyer Manfred , Lange Peter , Serdarevic-Pehar Marjana ,   on behalf of the Exubera Phase III Study Group
Published: July 2006

OBJECTIVE—To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes.

RESEARCH DESIGN AND METHODS—We conducted an open-label, parallel, 24-week multicenter trial. Patients uncontrolled on metformin were randomized to adjunctive INH (n = 243) or glibenclamide (n = 233). Before randomization, patients were divided into two HbA1c (A1C) arms: ≥8 to ≤9.5% (moderately high) and >9.5 to ≤12% (very high). The primary efficacy end point was A1C change from baseline.

RESULTS—Mean adjusted A1C changes from baseline were −2.03 and −1.88% in the INH and glibenclamide groups, respectively; between-treatment difference −0.17% (95% CI −0.34 to 0.01; P = 0.058), consistent with the noninferiority criterion. In the A1C >9.5% arm, inhaled insulin demonstrated a significantly greater reduction in A1C than glibenclamide, between-treatment difference −0.37% (−0.62 to −0.12; P = 0.004). In the A1C ≤9.5% arm, between-treatment difference was 0.04% (−0.19 to 0.27; P = 0.733). Hypoglycemia (events per subject-month) was greater with INH (0.18) than glibenclamide (0.08), risk ratio 2.24 (1.58–3.16), but there were no associated discontinuations. Other adverse events, except increased cough in the INH group, were similar. At week 24, changes from baseline in pulmonary function parameters were small. Insulin antibody binding increased more with INH but did not have any associated clinical manifestations.

CONCLUSIONS—In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (>9.5%) was more effectively treated with the addition of INH.
A Risk Score for Predicting Incident Diabetes in the Thai Population
Authors: Aekplakorn Wichai , Bunnag Pongamorn , Woodward Mark , Sritara Piyamitr , Cheepudomwit Sayan , Yamwong Sukit , Yipintsoi Tada , Rajatanavin Rajata
Published: July 2006

OBJECTIVE—The objective of this study was to develop and evaluate a risk score to predict people at high risk of diabetes in Thailand.

RESEARCH DESIGN AND METHODS—A Thai cohort of 2,677 individuals, aged 35–55 years, without diabetes at baseline, was resurveyed after 12 years. Logistic regression models were used to identify baseline risk factors that predicted the incidence of diabetes; a simple model that included only those risk factors as significant (P < 0.05) when adjusted for each other was developed. The coefficients from this model were transformed into components of a diabetes score. This score was tested in a Thai validation cohort of a different 2,420 individuals.

RESULTS—A total of 361 individuals developed type 2 diabetes in the exploratory cohort during the follow-up period. The significant predictive variables in the simple model were age, BMI, waist circumference, hypertension, and history of diabetes in parents or siblings A cutoff score of 6 of 17 produced the optimal sum of sensitivity (77%) and specificity (60%). The area under the receiver-operating characteristic curve (AUC) was 0.74. Adding impaired fasting glucose or impaired glucose tolerance status to the model slightly increased the AUC to 0.78; adding low HDL cholesterol and/or high triglycerides barely improved the model. The validation cohort demonstrated similar results.

CONCLUSIONS—A simple diabetes risk score, based on a set of variables not requiring laboratory tests, can be used for early intervention to delay or prevent the disease in Thailand. Adding impaired fasting glucose or impaired glucose tolerance or triglyceride and HDL cholesterol status to this model only modestly improves the predictive ability.
Prepregnancy Care and Pregnancy Outcomes in Women With Type 1 Diabetes
Authors: Temple Rosemary C. , Aldridge Vivien J. , Murphy Helen R.
Published: July 2006

OBJECTIVE—The objective of this study was to examine the relationship between prepregnancy care, glycemic control, maternal hypoglycemia, and pregnancy outcomes in women with type 1 diabetes.

RESEARCH DESIGN AND METHODS—This was a prospective observational cohort study of women with type 1 diabetes who delivered from 1991 to 2002. Outcome measures were attendance at a clinic for prepregnancy care, maternal HbA1c (A1C) throughout pregnancy, maternal severe hypoglycemic episodes, macrosomia, preeclampsia, premature delivery (delivery before 37 weeks), very premature delivery (delivery before 34 weeks), spontaneous abortion, and adverse pregnancy outcome (defined as major malformation, stillbirth, and neonatal death).

RESULTS—There were 290 pregnancies, in which 110 (38%) women had prepregnancy care. The prepregnancy care group contained more primiparous women (54.7 vs. 40.6%; P = 0.021) and fewer smokers (9.4 vs. 28.7%; P < 0.0001). They registered earlier (6.6 vs. 8.3 weeks, P < 0.0001) and had a lower A1C at the initial visit (6.5% vs. 7.6%; P < 0.0001). Adverse pregnancy outcomes and very premature deliveries were significantly lower in women who received prepregnancy care (2.9 vs. 10.2%; P = 0.03 and 5.0 vs. 14.2%; P = 0.02, respectively). In contrast, between groups, there was no difference in A1C after 24 weeks or in the rates of macrosomia, preeclampsia, or maternal severe hypoglycemic episodes.

CONCLUSIONS—Prepregnancy care was associated with improved glycemic control in early pregnancy and significant reductions in adverse pregnancy outcome (malformation, stillbirth, and neonatal death) and very premature delivery. However, prepregnancy care failed to have an impact on glycemic control in later pregnancy or to reduce the risk of macrosomia and preeclampsia.
Health Behaviors Among Women of Reproductive Age With and Without a History of Gestational Diabetes Mellitus
Authors: Kieffer Edith C. , Sinco Brandy , Kim Catherine
Published: July 2006

OBJECTIVE—To estimate the prevalence of several health-related behaviors among women of reproductive age with and without a history of gestational diabetes mellitus (hGDM).

RESEARCH DESIGN AND METHODS—We performed a cross-sectional study using the 2001–2003 Behavioral Risk Factor Surveillance System, a national population-based random sample telephone survey. Participants were 177,420 women aged 18–44 years with and without self-reported hGDM. Outcome measures included meeting physical activity and fruit and vegetable guidelines, sedentary activity level, and current smoking.

RESULTS—Approximately 3% (n = 4,718) of women aged 18–44 years reported physician-diagnosed hGDM. Women with hGDM had higher BMIs, were significantly older, were less often educated or employed, and were more often Hispanic or African American, married, and living with children. Women with hGDM reported worse self-rated health than women without hGDM. In unadjusted and multivariate adjusted comparisons, there were no significant differences in levels of physical activity, fruit and vegetable consumption, or smoking among women with and without hGDM. However, women with hGDM who lived with children were significantly less likely to meet fruit and vegetable consumption guidelines (odds ratio 0.78 [95% CI 0.63–0.97]; P < 0.05) and more likely to smoke (1.21 [1.01–1.47]; P < 0.05) than their counterparts without hGDM.

CONCLUSIONS—Despite their elevated risk for future diabetes, women with hGDM who lived with children were less likely to meet fruit and vegetable consumption guidelines and more likely to smoke than women with children who did not have hGDM.
Chromium Picolinate Supplementation Attenuates Body Weight Gain and Increases Insulin Sensitivity in Subjects With Type 2 Diabetes
Authors: Martin Julie , Wang Zhong Q. , Zhang Xian H. , Wachtel Deborah , Volaufova Julia , Matthews Dwight E. , Cefalu William T.
Published: July 2006

OBJECTIVE—Chromium picolinate (CrPic) supplementation has been suggested to improve glycemia, but there are conflicting reports on efficacy. We sought to determine the effect of CrPic on insulin sensitivity, glycemic control, and body composition in subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Thirty-seven subjects with type 2 diabetes were evaluated. After baseline, subjects were placed on a sulfonylurea (glipizide gastrointestinal therapeutic system 5 mg/day) with placebo for 3 months. Subjects were then randomized in a double-blind fashion to receive either the sulfonylurea plus placebo (n = 12) or the sulfonylurea plus 1,000 μg Cr as CrPic (n = 17) for 6 months. Body composition, insulin sensitivity, and glycemic control were determined at baseline, end of the 3-month single-blind placebo phase, and end of study.

RESULTS—Subjects randomized to sulfonylurea/placebo, as opposed to those randomized to sulfonylurea/CrPic, had a significant increase in body weight (2.2 kg, P < 0.001 vs. 0.9 kg, P = 0.11), percent body fat (1.17%, P < 0.001 vs. 0.12%, P = 0.7), and total abdominal fat (32.5 cm2, P < 0.05 vs. 12.2 cm2, P < 0.10) from baseline. Subjects randomized to sulfonylurea/CrPic had significant improvements in insulin sensitivity corrected for fat-free mass (28.8, P < 0.05 vs. 15.9, P = 0.4), GHb (−1.16%, P < 0.005 vs. −0.4%, P = 0.3), and free fatty acids (−0.2 mmol/l, P < 0.001 vs. −0.12 mmol/l, P < 0.03) as opposed to sulfonylurea/placebo.

CONCLUSIONS—This study demonstrates that CrPic supplementation in subjects with type 2 diabetes who are taking sulfonylurea agents significantly improves insulin sensitivity and glucose control. Further, CrPic supplementation significantly attenuated body weight gain and visceral fat accumulation compared with the placebo group.
Is Self-Monitoring of Blood Glucose Appropriate for All Type 2 Diabetic Patients?
Authors: Davis Wendy A. , Bruce David G. , Davis Timothy M.E.
Published: July 2006

OBJECTIVE—We sought to determine whether self-monitoring of blood glucose (SMBG) is associated with better glycemic control in type 2 diabetes.

RESEARCH DESIGN AND METHODS—We used cross-sectional and longitudinal data from type 2 diabetic participants in the observational, community-based Fremantle Diabetes Study (FDS) who reported SMBG status at study entry (n = 1,286) and annual reviews over 5 years (n = 531).

RESULTS—At study entry, 70% of patients performed SMBG, with a median of four tests per week (interquartile range two to seven). Patients with shorter diabetes duration; who were attending diabetes education, diabetes-related clinics, or medical specialists; who were taking insulin with or without oral hypoglycemic agents (OHAs); and who were self-reporting hypoglycemic events were more likely to use SMBG. Both cross-sectional and longitudinal FDS data showed that HbA1c (A1C) was not significantly different between SMBG users and nonusers, either overall or within diabetes treatment groups (diet, OHAs, and insulin with or without OHAs). There was also no independent cross-sectional relationship between A1C and SMBG frequency. The average annual societal cost of using SMBG (in year 2000 Australian dollars [A$], excluding glucometers) was A$162 per type 2 diabetic patient or A$51 million when projected to the Australian diagnosed type 2 diabetic population.

CONCLUSIONS—Neither SMBG testing nor its frequency was associated with glycemic benefit in type 2 diabetic patients regardless of treatment. Our data did not include methods of SMBG delivery and application, factors that require further assessment in the evaluation of SMBG utility in non–insulin-treated type 2 diabetes. SMBG may be still of value in the identification and prevention of hypoglycemia and in dose adjustment in insulin-treated patients.
Normotensive Women With Type 2 Diabetes and Microalbuminuria Are at High Risk for Macrovascular Disease
Authors: Zandbergen Adrienne A.M. , Sijbrands Eric J. , Lamberts Steven W. , Bootsma Aart H.
Published: July 2006

OBJECTIVE—The excess risk of macrovascular disease and death associated with diabetes seems higher in women than in men. The pathogenesis for this risk difference has not been fully elucidated. We investigated whether female sex was associated with macrovascular disease and death, independently of known risk factors related to type 2 diabetes, nephropathy, or retinopathy in normotensive patients with type 2 diabetes and microalbuminuria.

RESEARCH DESIGN AND METHODS—We conducted a prospective, prolonged follow-up study of a subgroup of 67 diabetic patients (46 men and 21 women) without established cardiovascular disease who participated in a larger clinical trial. Data were collected on current and past health, medication use, blood pressure, renal function, and HbA1c during the follow-up period of 4.7 ± 0.8 (means ± SE) years. The end point was a composite of death, cardiovascular disease, cerebrovascular events, and peripheral artery disease.

RESULTS—Of the women, eight (38.1%) met the end point compared with six (13.4%) of the men (P = 0.02 for difference in event-free survival). The hazard ratio of women relative to men was 3.19 (95% CI 1.11–9.21), which further increased after adjusting for age, systolic blood pressure, BMI, smoking, total-to-HDL cholesterol ratio, urinary albumin excretion, and retinopathy.

CONCLUSIONS—In our study population of normotensive patients with type 2 diabetes and microalbuminuria, female sex was associated with increased risk of fatal and nonfatal cardiovascular disease, independent of the classical cardiovascular risk factors, the severity of nephropathy or presence of retinopathy, or health care utilization.
A Low-Fat Vegan Diet Improves Glycemic Control and Cardiovascular Risk Factors in a Randomized Clinical Trial in Individuals With Type 2 Diabetes
Authors: Barnard Neal D. , Cohen Joshua , Jenkins David J.A. , Turner-McGrievy Gabrielle , Gloede Lise , Jaster Brent , Seidl Kim , Green Amber A. , Talpers Stanley
Published: July 2006

OBJECTIVE—We sought to investigate whether a low-fat vegan diet improves glycemic control and cardiovascular risk factors in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Individuals with type 2 diabetes (n = 99) were randomly assigned to a low-fat vegan diet (n = 49) or a diet following the American Diabetes Association (ADA) guidelines (n = 50). Participants were evaluated at baseline and 22 weeks.

RESULTS—Forty-three percent (21 of 49) of the vegan group and 26% (13 of 50) of the ADA group participants reduced diabetes medications. Including all participants, HbA1c (A1C) decreased 0.96 percentage points in the vegan group and 0.56 points in the ADA group (P = 0.089). Excluding those who changed medications, A1C fell 1.23 points in the vegan group compared with 0.38 points in the ADA group (P = 0.01). Body weight decreased 6.5 kg in the vegan group and 3.1 kg in the ADA group (P < 0.001). Body weight change correlated with A1C change (r = 0.51, n = 57, P < 0.0001). Among those who did not change lipid-lowering medications, LDL cholesterol fell 21.2% in the vegan group and 10.7% in the ADA group (P = 0.02). After adjustment for baseline values, urinary albumin reductions were greater in the vegan group (15.9 mg/24h) than in the ADA group (10.9 mg/24 h) (P = 0.013).

CONCLUSIONS—Both a low-fat vegan diet and a diet based on ADA guidelines improved glycemic and lipid control in type 2 diabetic patients. These improvements were greater with a low-fat vegan diet.
Longitudinal Study of New and Prevalent Use of Self-Monitoring of Blood Glucose
Authors: Karter Andrew J. , Parker Melissa M. , Moffet Howard H. , Spence Michele M. , Chan James , Ettner Susan L. , Selby Joe V.
Published: July 2006

OBJECTIVE—We sought to assess longitudinal association between self-monitoring of blood glucose (SMBG) and glycemic control in diabetic patients from an integrated health plan (Kaiser Permanente Northern California).

RESEARCH DESIGN AND METHODS—Longitudinal analyses of glycemic control among 1) 16,091 patients initiating SMBG (new-user cohort) and 2) 15,347 ongoing users of SMBG (prevalent-user cohort). SMBG frequency was based on pharmacy use (number of blood glucose test strips dispensed), and glycemic control was based on HbA1c (A1C). In the new-user cohort, ANCOVA models (pre- and posttest design) were used to assess the effect of initiating SMBG. In the prevalent-user cohort, repeated-measure, mixed-effects models with random-intercept and time-dependent covariates were used to assess changes in SMBG and A1C. All models were stratified by therapy (no medications, oral agents only, or insulin) and adjusted for baseline A1C, sociodemographics, insulin injection frequency, comorbidity index, medication adherence, smoking status, health care use, and provider specialty.

RESULTS—Greater SMBG practice frequency among new users was associated with a graded decrease in A1C (relative to nonusers) regardless of diabetes therapy (P < 0.0001). Changes in SMBG frequency among prevalent users were associated with an inverse graded change in A1C only among pharmacologically treated patients (P < 0.0001).

CONCLUSIONS—These observational findings are consistent with short-term benefits of initiating SMBG practice for all patients but continuing benefits only for pharmacologically treated patients. Differences in effectiveness between new versus prevalent users of SMBG have implications for guideline development and interpretation of observational outcomes data.
The atypical pattern of cell death in B16F10 melanoma cells treated with TNP-470
Authors: Okrój Marcin , Stawikowska Dorota , Słomińska Ewa , Myśliwski Andrzej , Bigda Jacek
Published: July 2006

TNP-470 is an acknowledged anti-angiogenic factor, and was studied clinically as an anti-cancer drug. We previously reported on an additional property of this molecule: the intracellular generation of reactive oxygen species in B16F10 melanoma cells. We showed that a massive generation of ROS occurred in the first few hours after treatment with TNP-470 and that this event was critical to subsequent cell death. In this study, we analyzed the process of cell death and noticed an atypical pattern of death markers. Some of these, such as DNA fragmentation or condensation of chromatin, were characteristic for programmed cell death, while others (the lack of phosphatidylserine flip-flop but permeability to propidium iodide, the maintenance of adhesion to the substratum, no change in mitochondrial transmembrane potential, no effect of the panspecific caspase inhibitor) rather suggested a necrotic outcome. We concluded that TNP-470 induced at least some pathways of programmed cell death. However, increasing damage to critical cell functions appears to cause a rapid switch into the necrotic mode. Our data is similar to that in other reports describing the action of ROS-generating agents. We hypothesize that this rapid programmed cell death/necrosis switch is a common scenario following free radical stress.
Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803
Authors: Ling Hui , Zhang Liang-Yun , Su Qi , Song Ying , Luo Zhao-Yang , Zhou Xiu , Zeng Xi , He Jie , Tan Hui , Yuan Jing-Ping
Published: July 2006

Diallyl disulfide (DADS) is a major constituent of garlic. Previously, we found that DADS both inhibited proliferation in human gastric cancer cells in vitro and in vivo, and induced G2/M arrest. In this study, we investigated whether this differentiation effect was induced by DADS in human gastric cancer MGC803 cells, and whether it was related to an alteration in ERK activity. The results showed that the growth of MGC803 cells was inhibited by DADS. Cells treated with DADS displayed a lower nucleocytoplasmic ratio and tended to form gland and intercellular conjunction structures. The ConA-mediated cell agglutination ratio and cells’ ALP specific activity decreased. In MGC803 cells, dye transfer was limited to a few cells neighbouring the dye-injected cell and to a depth of 1–2 layers beneath the scrape site. However, after treatment with DADS, the LY (Lucifer Yellow) was transferred to several cells immediately neighbouring the microinjected cell and to a depth of 2–4 cell layers from the scrape site. This indicated that DADS induced differentiation in MGC803 cells. Western blot analysis revealed that although DADS did not influence the quantity of ERK1/2 protein expressed, it did decrease its phosphorylation in a concentration-dependent manner, compared with the controls. At 30 mg·L−1, DADS inhibited the activation of ERK1/2 in 15–30 min. These results suggested that the DADS-induced differentiation of MGC803 cells involved an alteration of the ERK1/2 signaling pathway.
Cover Picture: Fabrication of Stable Low‐Density Silica Aerogels Containing Luminescent ZnS Capped CdSe Quantum Dots (Adv. Mater. 15/2006)
Authors: Sorensen L. , Strouse G. F. , Stiegman A. E.
Published: July 2006

Luminescent CdSe quantum dots 2.5 and 6.0 nm in diameter can be incorporated into low‐density silica aerogel matrices. In work reported by Stiegmann and co‐workers on p. 1965, aerogels are formed from the supercritical CO2 extraction of an alcogel containing quantum dots surface passivated with 3‐aminopropyltriethoxysilane. The resulting aerogels, shown on the cover, are low scattering and display intense, stable luminescence.
Mixing of components in two‐component aggregation
Authors: Matsoukas Themis , Lee Kangtaek , Kim Taehoon
Published: July 2006

The problem of binary component aggregation with kernels that are independent of composition is considered. The bivariate distribution as the product of two distributions is studied, one that refers to the size of the aggregates, and one that describes the distribution of the component of interest (solute), and obtain the governing equations for all three. The distribution of solute within aggregates of size v has a steady‐state solution, that is independent of the size distribution: it is a Gaussian function whose mean and variance are both proportional to the aggregate size v. To quantify the degree of blending, the sum‐square X2, of the deviation of the amount solute from its mean, is studied. Two cases are identified for which X2 is constant during aggregation: (a) “partially mixed” seeds regardless of kernel; and (b) sum‐type kernels regardless of seed distribution. Simulations confirm the results for these two cases, and further indicate that in the general case, X2 is nearly constant. The degree of mixing is determined solely by the initial distribution of components, but does not depend on the kernel. Optimum initial conditions that minimize the time required to reach a desired level of homogeneity between components are identified. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Accelerated evolution of Protocadherin11X/Y: A candidate gene‐pair for cerebral asymmetry and language
Authors: Williams Nic A. , Close James P. , Giouzeli Maria , Crow Timothy J.
Published: July 2006

It has been argued that cerebral asymmetry (the “torque”) is the characteristic that defines the human brain and that morphological findings in psychosis are consistent with a deviation in this sex‐dependent dimension of brain growth. Evidence from sex chromosome aneuploidies and an association within families between sex and handedness is consistent with the presence of a determinant of cerebral asymmetry (a possible correlate of language) on the X and the Y chromosomes. During hominid evolution a 3.5 Mb translocation occurred from the ancestral X chromosome to the Y chromosome, resulting in duplication of the Protocadherin11X gene, such that it is represented on the X and Y chromosomes in man, whereas there is a single X‐linked gene in other mammals. We re‐date the duplicative translocation to 6 million years ago, that is, close to the chimpanzee–hominid bifurcation. Sequence comparisons with the chimpanzee, bonobo, gorilla, and orangutan indicate that in contrast to earlier purifying selection there has been accelerated change in the Protocadherin11X ectodomain as well as the Protocadherin11Y sequence in the hominid lineage since the duplication. The evolutionary sequence of events together with the prior case for an X‐Y homologous gene suggests that this gene‐pair is a candidate for the evolution of hominid‐specific characteristics including the sexual dimorphism of cerebral asymmetry, a putative correlate of language. © 2006 Wiley‐Liss, Inc.
Abnormalities of cholesterol metabolism in autism spectrum disorders
Authors: Tierney Elaine , Bukelis Irena , Thompson Richard E. , Ahmed Khalid , Aneja Alka , Kratz Lisa , Kelley Richard I.
Published: July 2006

Although Smith‐Lemli‐Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism [Tierney et al., 2001; Am J Med Genet 98:191‐200.], the incidence of SLOS and other sterol disorders among individuals with autism spectrum disorders (ASD) is unknown. This study investigated (1) the incidence of biochemically diagnosed SLOS in blood samples from a cohort of subjects with ASD from families in which more than one individual had ASD and (2) the type and incidence of other sterol disorders in the same group. Using gas chromatography/mass spectrometry, cholesterol, and its precursor sterols were quantified in 100 samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had sterol levels consistent with SLOS, 19 samples had total cholesterol levels lower than 100 mg/dl, which is below the 5th centile for children over age 2 years. These findings suggest that, in addition to SLOS, there may be other disorders of sterol metabolism or homeostasis associated with ASD. © 2006 Wiley‐Liss, Inc.
Knee pain, knee osteoarthritis, and the risk of fracture
Authors: Arden Nigel K. , Crozier Sarah , Smith Helen , Anderson Frazer , Edwards Christopher , Raphael Helen , Cooper Cyrus
Published: July 2006

Objective

Patients with osteoarthritis (OA) have increased bone mineral density; however, the association between knee OA and fracture is controversial. Few data exist on the association between knee pain and fracture. We examined the association of knee OA and knee pain with fracture and falls in elderly men and women.

Methods

The study group comprised 6,641 men and women ages ≥75 years who participated in a 3‐year randomized controlled trial of intramuscular vitamin D therapy. Patients completed a questionnaire about knee pain and OA. Fracture and fall data were collected prospectively every 6 months.

Results

Knee pain prevalence and a clinician diagnosis of knee OA were 35.2% and 6.8%, respectively. A total of 436 incident nonvertebral fractures were reported, and 3,992 patients sustained a fall. Prevalent knee pain was associated with an increased risk of falls (hazard ratio [HR] 1.26, 95% confidence interval [95% CI] 1.17–1.36) and hip fracture (HR 2.0, 95% CI 1.18–3.37). Increasing severity of knee pain was associated with a greater risk of falls and hip fracture. Clinician diagnosis of knee OA was associated with an increased risk of nonvertebral fractures (HR 1.61, 95% CI 1.09–2.36). The increased risk of fracture was not substantially reduced by adjusting for falls, but was attenuated by adjustment for the use of walking aids.

Conclusion

Patients with a clinical diagnosis of knee OA and with knee pain have an increased risk of nonvertebral and hip fracture. This is not explained by the increased risk of falls, but is more likely to be due to the severity of falls sustained. Knee pain and OA should be regarded as independent risk factors for fracture.