bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Differences in Fasting Glucose and Glucose Tolerance on the Hyperbolic Relationship Between Insulin Sensitivity and Insulin Responses
Authors: Utzschneider Kristina M. , Prigeon Ronald L. , Carr Darcy B. , Hull Rebecca L. , Tong Jenny , Shofer Jane B. , Retzlaff Barbara M. , Knopp Robert H. , Kahn Steven E. 
Published: May 2006

OBJECTIVE—To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance.
RESEARCH DESIGN AND METHODS—We studied 219 healthy subjects (88 male and 131 female subjects, aged 26–75 years) with fasting plasma glucose (FPG) &lt;6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the latter a measure of intravenous glucose tolerance.
RESULTS—Si and AIRg were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG &lt;5.56 mmol/l vs. IFG, FPG 5.56–6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was left shifted in the IFG compared with NFG group (P &lt; 0.001) and was progressively more left shifted with decreasing Kg (P &lt; 0.001), consistent with decreasing β-cell function. These changes were not observed for the curves relating Si and fasting insulin, suggesting that in the fasting state β-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (Si × AIRg) was calculated as a measure of β-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG.
CONCLUSIONS—The inverse relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a hyperbolic relationship, a decrease in β-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.
Triple Therapy in Type 2 Diabetes
Authors: Rosenstock Julio , Sugimoto Danny , Strange Poul , Stewart John A. , Soltes-Rak Erika , Dailey George ,   on behalf of the Insulin Glargine 4014 Study Investigators
Published: May 2006

OBJECTIVE—To evaluate the efficacy and safety of add-on insulin glargine versus rosiglitazone in insulin-naïve patients with type 2 diabetes inadequately controlled on dual oral therapy with sulfonylurea plus metformin.
RESEARCH DESIGN AND METHODS—In this 24-week multicenter, randomized, open-label, parallel trial, 217 patients (HbA1c [A1C] 7.5–11%, BMI &gt;25 kg/m2) on ≥50% of maximal-dose sulfonylurea and metformin received add-on insulin glargine 10 units/day or rosiglitazone 4 mg/day. Insulin glargine was forced-titrated to target fasting plasma glucose (FPG) ≤5.5–6.7 mmol/l (≤100–120 mg/dl), and rosiglitazone was increased to 8 mg/day any time after 6 weeks if FPG was &gt;5.5 mmol/l.
RESULTS—A1C improvements from baseline were similar in both groups (−1.7 vs. −1.5% for insulin glargine vs. rosiglitazone, respectively); however, when baseline A1C was &gt;9.5%, the reduction of A1C with insulin glargine was greater than with rosiglitazone (P &lt; 0.05). Insulin glargine yielded better FPG values than rosiglitazone (−3.6 ± 0.23 vs. −2.6 ± 0.22 mmol/l; P = 0.001). Insulin glargine final dose per day was 38 ± 26 IU vs. 7.1 ± 2 mg for rosiglitazone. Confirmed hypoglycemic events at plasma glucose &lt;3.9 mmol/l (&lt;70 mg/dl) were slightly greater for the insulin glargine group (n = 57) than for the rosiglitazone group (n = 47) (P = 0.0528). The calculated average rate per patient-year of a confirmed hypoglycemic event (&lt;70 mg/dl), after adjusting for BMI, was 7.7 (95% CI 5.4–10.8) and 3.4 (2.3–5.0) for the insulin glargine and rosiglitazone groups, respectively (P = 0.0073). More patients in the insulin glargine group had confirmed nocturnal hypoglycemia of &lt;3.9 mmol/l (P = 0.02) and &lt;2.8 mmol/l (P &lt; 0.05) than in the rosiglitazone group. Effects on total cholesterol, LDL cholesterol, and triglyceride levels from baseline to end point with insulin glargine (−4.4, −1.4, and −19.0%, respectively) contrasted with those of rosiglitazone (+10.1, +13.1, and +4.6%, respectively; P &lt; 0.002). HDL cholesterol was unchanged with insulin glargine but increased with rosiglitazone by 4.4% (P &lt; 0.05). Insulin glargine had less weight gain than rosiglitazone (1.6 ± 0.4 vs. 3.0 ± 0.4 kg; P = 0.02), fewer adverse events (7 vs. 29%; P = 0.0001), and no peripheral edema (0 vs. 12.5%). Insulin glargine saved $235/patient over 24 weeks compared with rosiglitazone.
CONCLUSIONS—Low-dose insulin glargine combined with a sulfonylurea and metformin resulted in similar A1C improvements except for greater reductions in A1C when baseline was ≥9.5% compared with add-on maximum-dose rosiglitazone. Further, insulin glargine was associated with more hypoglycemia but less weight gain, no edema, and salutary lipid changes at a lower cost of therapy.
Sleep Duration as a Risk Factor for the Development of Type 2 Diabetes
Authors: Yaggi H. Klar , Araujo Andre B. , McKinlay John B. 
Published: May 2006

OBJECTIVE—Short-term partial sleep restriction results in glucose intolerance and insulin resistance. The purpose of this study was to assess the long-term relationship between sleep duration and the incidence of clinical diabetes.
RESEARCH DESIGN AND METHODS—A cohort of men from the Massachusetts Male Aging Study without diabetes at baseline (1987–1989) were followed until 2004 for the development of diabetes. Average number of hours of sleep per night was grouped into the following categories: ≤5, 6, 7, 8, and &gt;8 h. Incidence rates and relative risks (RRs) were calculated for the development of diabetes in each sleep duration category. Those reporting 7 h of sleep per night served as the reference group. Multivariate analysis was performed using Poisson regression.
RESULTS—Men reporting short sleep duration (≤5 and 6 h of sleep per night) were twice as likely to develop diabetes, and men reporting long sleep duration (&gt;8 h of sleep per night) were more than three times as likely to develop diabetes over the period of follow-up. Elevated risks remained essentially unchanged after adjustment for age, hypertension, smoking status, self-rated health status, education, and waist circumference (RR 1.95 [95% CI 0.95–4.01] for ≤5 h and 3.12 [1.53–6.37] for &gt;8 h). RRs were altered considerably for the two extreme sleep groups when adjusted for testosterone (1.51 [0.71–3.19] for ≤5 h and 2.81 [1.34–5.90] for &gt;8 h), suggesting that the effects of sleep on diabetes could be mediated via changes in endogenous testosterone levels.
CONCLUSIONS—Short and long sleep durations increase the risk of developing diabetes, independent of confounding factors. Sleep duration may represent a novel risk factor for diabetes.
Chromium Treatment Has No Effect in Patients With Poorly Controlled, Insulin-Treated Type 2 Diabetes in an Obese Western Population
Authors: Kleefstra Nanne , Houweling Sebastiaan T. , Jansman Frank G.A. , Groenier Klaas H. , Gans Rijk O.B. , Meyboom-de Jong Betty , Bakker Stephan J.L. , Bilo Henk J.G. 
Published: May 2006

OBJECTIVE—Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific populations of patients with type 2 diabetes. The aim of this study was to determine the effect of chromium treatment on glycemic control in a Western population of insulin-dependent patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—In this 6-month double-blind study, patients with an HbA1c (A1C) &gt;8% and insulin requirements of &gt;50 units/day were randomly assigned to receive treatment with placebo or 500 or 1,000 μg chromium daily in the form of chromium picolinate. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, and insulin requirements.
RESULTS—In this per-protocol analysis (n = 46), the decrease in A1C was approximately equal across the three groups (0.4%). All patients had a BMI &gt;25 kg/m2. No differences were found in the secondary end points. We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile.
CONCLUSIONS—There is no evidence that high-dose chromium treatment is effective in obese Western patients with type 2 diabetes.
Long-Term Effects of a Diabetes and Pregnancy Program
Authors: Feig Denice S. , Cleave Barbara , Tomlinson George 
Published: May 2006

OBJECTIVE—To determine whether women with pregestational diabetes obtained long-term benefits from an intensive diabetes management program during pregnancy.
RESEARCH DESIGN AND METHODS—Women with pregestational diabetes who had attended an intensive diabetes management program in pregnancy between 1991 and 1999 were interviewed regarding diabetes self-management behaviors and current glycemic control. A retrospective chart review was done to obtain information on self-management behaviors at entry to the program and at delivery and compared with the present.
RESULTS—Comparing entry to the program to delivery, all diabetes self-management behaviors improved significantly, including frequency of self-monitoring of blood glucose, frequency of insulin injections, and frequency and complexity of insulin dose adjustment (IDA). HbA1c (A1C) also improved significantly from entry to delivery (mean 0.073–0.060) (P &lt; 0.0001). Comparing entry to the present, frequency of insulin injections improved significantly (P = 0.0004), frequency of IDA improved significantly (P = 0.004), and complexity of IDA improved significantly (P = 0.0032). However, there was no significant change in frequency of self-monitoring of blood glucose (P = 0.766) from before pregnancy to the present, and A1C significantly worsened by 0.015 (P &lt; 0.0001, 95% CI 0.009–0.021) from entry to the program to the present.
CONCLUSIONS—Women participating in an intensive diabetes management program during pregnancy improve significantly from entry to delivery in diabetes self-management behaviors and glycemic control and, in the long term, retain some of these behaviors and knowledge. However, this is not reflected in an improved A1C level. This may be explained by the loss of contact with the diabetes care team and/or the discontinuation of frequent self-monitoring of blood glucose—a critical behavior necessary for achieving optimal glycemic control.
Vitamin D and Calcium Intake in Relation to Type 2 Diabetes in Women
Authors: Pittas Anastassios G. , Dawson-Hughes Bess , Li Tricia , Van Dam Rob M. , Willett Walter C. , Manson Joann E. , Hu Frank B. 
Published: May 2006

OBJECTIVE—The purpose of this study was to prospectively examine the association between vitamin D and calcium intake and risk of type 2 diabetes.RESEARCH DESIGN AND METHODS—In the Nurses’ Health Study, we followed 83,779 women who had no history of diabetes, cardiovascular disease, or cancer at baseline for the development of type 2 diabetes. Vitamin D and calcium intake from diet and supplements was assessed every 2–4 years. During 20 years of follow-up, we documented 4,843 incident cases of type 2 diabetes.RESULTS—After adjusting for multiple potential confounders, there was no association between total vitamin D intake and type 2 diabetes. However, the relative risk (RR) of type 2 diabetes was 0.87 (95% CI 0.75–1.00; P for trend = 0.04) comparing the highest with the lowest category of vitamin D intake from supplements. The multivariate RRs of type 2 diabetes were 0.79 (0.70–0.90; P for trend &lt;0.001) comparing the highest with the lowest category of calcium intake from all sources and 0.82 (0.72–0.92; P for trend &lt;0.001) comparing the highest with the lowest category of calcium intake from supplements. A combined daily intake of &gt;1,200 mg calcium and &gt;800 IU vitamin D was associated with a 33% lower risk of type 2 diabetes with RR of 0.67 (0.49–0.90) compared with an intake of &lt;600 mg and 400 IU calcium and vitamin D, respectively.CONCLUSIONS— The results of this large prospective study suggest a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes.
Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes
Authors: Vinik Aaron I. , Ullal Jagdeesh , Parson Henri K. , Barlow Patricia M. , Casellini Carolina M. 
Published: May 2006

OBJECTIVE—The purpose of this study was to determine the effect of 24 weeks of treatment with 45 mg/day pioglitazone on peripheral skin blood flow (SkBF) and skin nitric oxide (NO) production in vivo in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—This was a randomized, parallel, cross-over, double-blind, within- and between-subject study designed to compare vascular responses before and after treatment. We studied 12 subjects with type 2 diabetes (average age 58.6 ± 30.8 years, HbA1c 7.9 ± 00.4%, BMI 31.3 ± 1.2 kg/m2). SkBF was measured using laser Doppler techniques in response to ischemia reperfusion and local skin warming, and NO production was assessed in vivo using an amperometric NO meter inserted directly into the skin. These measurements were performed before treatment and at 6 and 24 weeks.
RESULTS—The SkBF response was not significantly improved after 24 weeks in either of the groups. NO production was significantly decreased in the pioglitazone-treated group in the basal condition (area under the curve 6.4 ± 1.0 vs. 2.8 ± 0.8, P &lt; 0.01), after local heat stimulation at 40°C (12.9 ± 2.2 vs. 5.7 ± 1.7, P &lt; 0.01), and after nociceptor stimulated flow with local heating at 44°C (36.4 ± 6.3 vs. 16.6 ± 3.4). Differences were not significant in the placebo-treated group.
CONCLUSIONS—Treatment of patients with type 2 diabetes with pioglitazone for 24 weeks reduced skin NO production, thus probably reducing nitrosative stress without a demonstrable effect on SkBF. Because nitrosative stress is considered to be a factor in the pathogenesis of neurovascular dysfunction, these findings warrant further investigation.
High Risk of Cardiovascular Disease in Patients With Type 1 Diabetes in the U.K.
Authors: Soedamah-Muthu Sabita S. , Fuller John H. , Mulnier Henrietta E. , Raleigh Veena S. , Lawrenson Ross A. , Colhoun Helen M. 
Published: May 2006

OBJECTIVE—To estimate the absolute and relative risk of cardiovascular disease (CVD) in patients with type 1 diabetes in the U.K.
RESEARCH DESIGN AND METHODS—Subjects with type 1 diabetes (n = 7,479) and five age- and sex-matched subjects without diabetes (n = 38,116) and free of CVD at baseline were selected from the General Practice Research Database (GPRD), a large primary care database representative of the U.K. population. Incident major CVD events, comprising myocardial infarction, acute coronary heart disease death, coronary revascularizations, or stroke, were captured for the period 1992–1999.
RESULTS—The hazard ratio (HR) for major CVD was 3.6 (95% CI 2.9–4.5) in type 1 diabetic men compared with those without diabetes and 7.7 (5.5–10.7) in women. Increased HRs were found for acute coronary events (3.0 and 7.6 in type 1 diabetic men and women, respectively, versus nondiabetic subjects), coronary revascularizations (5.0 in men, 16.8 in women), and for stroke (3.7 in men, 4.8 in women). Type 1 diabetic men aged 45–55 years had an absolute CVD risk similar to that of men in the general population 10–15 years older, with an even greater difference in women.
CONCLUSIONS—Despite advances in care, these data show that absolute and relative risks of CVD remain extremely high in patients with type 1 diabetes. Women with type 1 diabetes continue to experience greater relative risks of CVD than men compared with those without diabetes.
Experimental Approaches for Controlling Current Flowing through Metal–Molecule–Metal Junctions
Authors: Tran E. , Duati M. , Ferri V. , Müllen K. , Zharnikov M. , Whitesides G. M. , Rampi M. A. 
Published: May 2006

AbstractTwo experimental approaches that enable control of current flow through metal–molecules–metal junctions are described. A number of studies using two‐electrode metal–molecules–metal junctions have shown that the current between the electrodes depends on the structures of the incorporated molecules. When a tunneling mechanism dominates electron transport through organic molecules, the molecules behave similar to resistors with resistivities that can be controlled by changing the structure. Incorporation of molecules with increasing conjugation into Hg‐based junctions increases the current flow dramatically. Alternatively, by using four‐electrode electrochemical junctions that allow the potential of the electrodes to be controlled with respect to the energy levels of the incorporated molecules, it is possible to change the mechanism of electron transfer and produce abrupt increases in the current flow. These signals, analogous to solid‐state diodes, are particularly significant for molecular electronics. Electrochemical junctions also permit prediction of the value of the applied potential at which the current will start taking off and to identify the mechanism of charge transport. New and recently published results obtained using junctions based on Hg electrodes in an “electrochemical” mode show that two junctions incorporating redox centers by different interactions behave as current switches, with the current flow dominated by different charge‐transport mechanisms.
Dlx homeobox gene control of mammalian limb and craniofacial development
Authors: Kraus Petra , Lufkin Thomas 
Published: May 2006

AbstractThe Dlx homeobox gene family is of ancient origin and crucial for embryonic development in invertebrates and vertebrates. The Dlx proteins are thought to function as DNA‐binding transcriptional regulators, likely controlling large numbers of downstream effector genes. In mammals gene expression analysis of the six members of the Dlx gene family has been demonstrated in the nervous system, neural crest derivatives, branchial arches, and developing appendages. Through genetic approaches the Dlx genes have been implicated in patterning and development of the brain, craniofacial structures, and the axial and appendicular skeleton. Substantial functional redundancy within the Dlx gene family has prevented the analysis of single gene mutations from demonstrating the full developmental control exerted by the Dlx proteins. Here, we will discuss data from recent combined loss and gain‐of‐function genetic mutations, which have given greater insight into the role of Dlx homeobox genes in craniofacial, limb, and bone development. © 2006 Wiley‐Liss, Inc.
Gene expression analysis reveals a signature of estrogen receptor activation upon loss ofPtenin a mouse model of endometrial cancer
Authors: Lian Zenglin , De Luca Pasquale , Di Cristofano Antonio 
Published: May 2006

AbstractLoss ofPTENis the earliest detectable genetic lesion in the endometrioid subtype of endometrial cancer (EEC), a tumor thought to be associated with an increase in unopposed estrogen activity.Pten+/−mice develop endometrial neoplastic lesions with full penetrance, despite having normal estrogen levels. We have utilized oligonucleotide arrays to identify the alterations in gene expression patterns associated with loss ofPtenand consequent neoplastic transformation of the endometrium. We show that 487 and 330 genes are substantially up‐ and downregulated, respectively, inPten+/−mice. Several genes whose expression levels are impacted by loss ofPtenare associated with pathways and functions that are relevant to the transformation and progression processes. Strikingly, we found that the expression levels of over 100 genes known to be regulated by estrogen receptor alpha (ERα) are also altered in the neoplastic uterus fromPten+/−mice, thus mimicking a hyperestrogenic environment. These results provide in vivo evidence supporting the hypothesis that loss ofPtenand subsequent Akt activation result in the activation of several ERα‐dependent pathways that, mimicking increased estrogen signaling, may play a pivotal role in the neoplastic process. J. Cell. Physiol. 208: 255–266, 2006. © 2006 Wiley‐Liss, Inc.
Conductivity modification of proton conducting polymer gel electrolytes with the addition of fumed silica
Authors: Sharma Jitender Paul , Sekhon S. S. 
Published: May 2006

AbstractThe addition of nano size fumed silica to non aqueous proton conducting polymer gel electrolytes containing ammonium hexafluorophosphate (NH4PF6) has been found to modify the conductivity and viscosity behavior. Two maxima observed in the conductivity vs. fumed silica plot at very low concentrations have been explained to be due to an increase in free ion concentration with the dissociation of ion aggregates, and the formation of a high conducting interfacial layer between the particles of fumed silica and polymer gel electrolytes respectively. The change in free ion concentration has been monitored by pH measurements whereas change in mobility has been checked from viscosity measurements. The dissociation of ion aggregates with the addition of fumed silica has also been supported by FTIR results. The variation of conductivity and viscosity with temperature has also been studied and conductivity of nano dispersed gels does not show any change with time. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Buckling of a column on a Wieghardt foundation
Authors: Ruta G.C. , Elishakoff I. 
Published: May 2006

AbstractThis study considers the buckling of a uniform column on a Wieghardt elastic foundation. The column model incorporates both purely flexible, Bernoulli‐Euler, and shear‐deformable, Timoshenko, beams. Some comparisons with results reported in the existing literature are made, and numerical examples are evaluated to attempt shedding additional light on the problem.
The devil's in the details: genetic and phenotypic divergence between artificial and native populations of the endangered pupfish (Cyprinodon diabolis)
Authors: Wilcox J. L. , Martin A. P. 
Published: May 2006

AbstractPropagation of threatened or endangered species in artificial habitats is a common strategy for reducing the probability of extinction by demographic or stochastic forces. Differential selection, founder effects and genetic drift can conspire to cause artificial populations to differ irreversibly from native populations for characters important for fitness, thereby compromising conservation efforts. Here we show that artificial propagation of the endangered Devil's Hole pupfish Cyprinodon diabolis resulted in rapid divergence for phenotypic and genetic characteristics despite attempts to replicate key characteristics of the species' native habitat when designing the artificial environments. Although differences in behavior and morphology between the native pool population and the two artificial pools may reflect phenotypic plasticity, the results underscore the need to monitor and control (to the extent possible) closely the evolutionary process when propagating native species in artificial pools for multiple generations.