bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Differences in Adipose Tissue Metabolism in Women
Authors: Tchernof André , Bélanger Chantal , Morisset Anne-Sophie , Richard Christian , Mailloux Jacques , Laberge Philippe , Dupont Pierre
Published: May 2006

Studies comparing adipose tissue metabolism in central versus peripheral fat depots have generated equivocal data. We examined whether regional differences in abdominal subcutaneous and omental adipose tissue metabolism in women exist and whether they persist across the spectrum of body fatness and abdominal adiposity values. We measured adipocyte size; lipoprotein lipase (LPL) activity; and basal, isoproterenol-, forskolin-, and dibutyryl cAMP–stimulated lipolysis in adipose tissue or mature adipocytes isolated from the omental and subcutaneous fat depots in a sample of 55 healthy women undergoing elective gynecological surgery. Measures of body fat mass and body fat distribution were also obtained by dual-energy X-ray absorptiometry and computed tomography. Subcutaneous adipocytes were significantly larger than omental adipocytes (P < 0.0001). LPL activity expressed as a function of cell number was significantly higher in subcutaneous versus omental adipose tissue (P < 0.0001). Basal, isoproterenol-stimulated, dibutyryl cAMP–stimulated (10−3 mol/l) and forskolin-stimulated (10−5 mol/l) lipolysis (expressed as a function of cell number) were all significantly higher in subcutaneous versus omental adipocytes (P < 0.05 to P < 0.0001). However, the response of omental adipocytes to lipolytic stimuli tested (fold increase over basal level) was significantly greater in magnitude compared with subcutaneous adipocytes (P < 0.01). These differences were relatively constant across total body fat mass and visceral adipose tissue area tertiles. In conclusion, compared with adipocytes from the omental fat compartment, subcutaneous adipocytes are larger, have higher LPL activity, and are more lipolytic on an absolute basis, which may reflect a higher fat storage capacity in this depot in women. In contrast, omental adipocytes display greater relative responsiveness to both adrenergic receptor–and postreceptor-acting agents compared with subcutaneous adipocytes. Overall and visceral obesity have only minor effects on regional differences in adipose tissue metabolism.
Zonulin Upregulation Is Associated With Increased Gut Permeability in Subjects With Type 1 Diabetes and Their Relatives
Authors: Sapone Anna , de Magistris Laura , Pietzak Michelle , Clemente Maria G. , Tripathi Amit , Cucca Francesco , Lampis Rosanna , Kryszak Deborah , Cartenì Maria , Generoso Maddalena , Iafusco Dario , Prisco Francesco , Laghi Francesca , Riegler Gabriele , Carratu Romano , Counts Debra , Fasano Alessio
Published: May 2006

Zonulin, a protein that modulates intestinal permeability, is upregulated in several autoimmune diseases and is involved in the pathogenesis of autoimmune diabetes in the BB/Wor animal model of the disease. To verify the association between serum zonulin levels and in vivo intestinal permeability in patients with type 1 diabetes, both parameters were investigated in different stages of the autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal serum zonulin levels, as compared with age-matched control subjects. The increased zonulin levels correlated with increased intestinal permeability in vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while no changes were detected in ZO1 and occludin genes expression. When tested in serum samples collected during the pre–type 1 diabetes phase, elevated serum zonulin was detected in 70% of subjects and preceded by 3.5 ± 0.9 years the onset of the disease in those patients who went on to develop type 1 diabetes. Combined, these results suggest that zonulin upregulation is associated with increased intestinal permeability in a subgroup of type 1 diabetic patients. Zonulin upregulation seems to precede the onset of the disease, providing a possible link between increased intestinal permeability, environmental exposure to non–self antigens, and the development of autoimmunity in genetically susceptible individuals.
Consumption of Both Resistant Starch and β-Glucan Improves Postprandial Plasma Glucose and Insulin in Women
Authors: Behall Kay M. , Scholfield Daniel J. , Hallfrisch Judith G. , Liljeberg-Elmståhl Helena G.M.
Published: May 2006

OBJECTIVE—Consumption of a meal high in resistant starch or soluble fiber (β-glucan) decreases peak insulin and glucose concentrations and areas under the curve (AUCs). The objective was to determine whether the effects of soluble fiber and resistant starch on glycemic variables are additive.

RESEARCH DESIGN AND METHODS—Ten normal-weight (43.5 years of age, BMI 22.0 kg/m2) and 10 overweight women (43.3 years of age, BMI 30.4 kg/m2) consumed 10 tolerance meals in a Latin square design. Meals (1 g carbohydrate/kg body wt) were glucose alone or muffins made with different levels of soluble fiber (0.26, 0.68, or 2.3 g β-glucan/100 g muffin) and three levels of resistant starch (0.71, 2.57, or 5.06 g/100 g muffin).

RESULTS—Overweight subjects had plasma insulin concentrations higher than those of normal-weight subjects but maintained similar plasma glucose levels. Compared with low β-glucan–low resistant starch muffins, glucose and insulin AUC decreased when β-glucan (17 and 33%, respectively) or resistant starch (24 and 38%, respectively) content was increased. The greatest AUC reduction occurred after meals containing both high β-glucan–high resistant starch (33 and 59% lower AUC for glucose and insulin, respectively). Overweight women were somewhat more insulin resistant than control women.

CONCLUSIONS—Soluble fiber appears to have a greater effect on postprandial insulin response while glucose reduction is greater after resistant starch from high-amylose cornstarch. The reduction in glycemic response was enhanced by combining resistant starch and soluble fiber. Consumption of foods containing moderate amounts of these fibers may improve glucose metabolism in both normal and overweight women.
Diet of Adolescents With and Without Diabetes
Authors: Helgeson Vicki S. , Viccaro Laura , Becker Dorothy , Escobar Oscar , Siminerio Linda
Published: May 2006

OBJECTIVE—To compare the dietary intake of adolescents with type 1 diabetes with that of adolescents without diabetes matched on age, sex, and year in school and to compare the diets of both groups with recommendations.

RESEARCH DESIGN AND METHODS—Participants were 132 adolescents with type 1 diabetes, recruited from Children’s Hospital of Pittsburgh, and 131 adolescents without diabetes ranging in age from 10.70 to 14.21 years. Dietary intake was assessed with three 24-h recall interviews with each participant and one parent. Percentage of calories from protein, carbohydrates, and total fat; amount of each type of fat; and amount of cholesterol, fiber, and sugar were calculated as averages across 3 days.

RESULTS—Adolescents with diabetes took in less total energy than recommended. The percentage of calories from carbohydrates and protein were within recommendations for adolescents with and without diabetes, but adolescents with diabetes exceeded the recommended fat intake. The diet of adolescents with diabetes consisted of a greater percentage of fat and protein and a smaller percentage of carbohydrates relative to adolescents without diabetes. Adolescents without diabetes consumed more sugar, while adolescents with diabetes took in more of all components of fat than adolescents without diabetes. Male subjects with diabetes had an especially high intake of saturated fat.

CONCLUSIONS—Adolescents with type 1 diabetes consume fewer calories from carbohydrates but more calories from fat than adolescents without diabetes and exceed the recommended levels of fat intake. These findings are of concern given the risk that type 1 diabetes poses for cardiovascular disease.
Sexual Function and Endocrine Profile in Fertile Women With Type 1 Diabetes
Authors: Salonia Andrea , Lanzi Roberto , Scavini Marina , Pontillo Marina , Gatti Elisa , Petrella Giovanna , Licata Giada , Nappi Rossella E. , Bosi Emanuele , Briganti Alberto , Rigatti Patrizio , Montorsi Francesco
Published: May 2006

OBJECTIVE—Aims of this study were 1) to assess sexual function and endocrine profile among fertile type 1 diabetic women during the follicular and luteal phases of the menstrual cycle, 2) to compare these results with those obtained among healthy fertile women who served as control subjects, and 3) to explore the correlations between sexual function and endocrine milieu among patients and control subjects during the follicular and luteal phases of the menstrual cycle.

RESEARCH DESIGN AND METHODS—Fifty fertile women with type 1 diabetes and 47 healthy control subjects completed a semistructured medical interview and filled in self-administered validated instruments to evaluate sexual function, depression, and sexual distress. Venous blood samples were drawn to measure glycated hemoglobin and an endocrine profile during either the follicular or the luteal phase of the menstrual cycle.

RESULTS—Type 1 diabetic women had decreased sexual function and increased sexual distress compared with control subjects during the luteal, but not the follicular, phase of the menstrual cycle. During the follicular phase, patients had lower estrogenic basal tone, lower “weak” androgen (namely Δ4-androstenedione and dehydroepiandrosterone sulfate) production, and lower free-triiodothyronine and free-thyroxine levels compared with control subjects. During the luteal phase, total testosterone levels were higher in patients than control subjects, while 17β-estradiol and progesterone levels were lower in patients than control subjects.

CONCLUSIONS—Among type 1 diabetic women, sexual function and sexual distress vary according to the phase of the menstrual cycle. This finding may have implications on the clinical assessment of sexual function in type 1 diabetic women.
Understanding Exercise Beliefs and Behaviors in Women With Gestational Diabetes Mellitus
Authors: Symons Downs Danielle , Ulbrecht Jan S.
Published: May 2006

OBJECTIVE—The purpose of this study was to examine the exercise beliefs and behaviors of postpartum women who had gestational diabetes mellitus (GDM) during a recent pregnancy.

RESEARCH DESIGN AND METHODS—Postpartum women with GDM (n = 28) completed a mail survey assessing their self-reported exercise beliefs (advantages, barriers, and important social influences) and behaviors.

RESULTS—We found that 1) the strongest perceived advantage of exercise during pregnancy was controlling blood glucose and postpartum it was controlling weight, 2) the most common barrier to exercise during pregnancy was fatigue and postpartum it was a lack of time, 3) women’s husband/partner most strongly influenced their exercise during pregnancy and postpartum, 4) women exercised more during the postpartum period than before or during pregnancy, and 5) the number of exercise advantages was positively associated with women’s pregnancy and postpartum exercise behavior.

CONCLUSIONS—To increase exercise behavior and reduce the risk of type 2 diabetes in women with GDM, researchers and health care professionals are encouraged to use women’s exercise beliefs, that is, advantages, social influences, and perceived barriers to exercise, as a framework for designing effective diabetes treatment and prevention programs.
Middle-Aged Premenopausal Women With Type 1 Diabetes Have Lower Bone Mineral Density and Calcaneal Quantitative Ultrasound Than Nondiabetic Women
Authors: Strotmeyer Elsa S. , Cauley Jane A. , Orchard Trevor J. , Steenkiste Ann R. , Dorman Janice S.
Published: May 2006

OBJECTIVE—To determine whether middle-aged premenopausal women with type 1 diabetes had more self-reported fractures and lower bone mineral density (BMD) compared with nondiabetic women.

RESEARCH DESIGN AND METHODS—Participants were premenopausal women aged 35–55 years with type 1 diabetes (n = 67; 32.2 ± 5.3 years duration) and without diabetes (n = 237). Total hip, femoral neck, whole-body, and spine BMD were measured by dual X-ray absorptiometry. Calcaneal broadband ultrasound attenuation (BUA) was assessed with quantitative ultrasound.

RESULTS—Women with type 1 diabetes were more likely to report a fracture after age 20 years compared with nondiabetic women (33.3 vs. 22.6%; age-adjusted odds ratio 1.89 [95% CI 1.02–3.49]). Type 1 diabetes was associated with lower total hip BMD (0.890 vs. 0.961 g/cm2; P < 0.001), femoral neck BMD (0.797 vs. 0.847 g/cm2; P = 0.001), whole-body BMD (1.132 vs. 1.165 g/cm2; P < 0.01), and lower calcaneal BUA (71.6 vs. 84.9 dB/MHz; P < 0.001) after multivariate adjustment. BMD was 3–8% lower in type 1 diabetic compared with control women and calcaneal BUA was 15% lower. Spine BMD and biomarkers of bone remodeling were not significantly different between groups. In the type 1 diabetic women, reduced monofilament detection and blindness were both associated with lower BMD.

CONCLUSIONS—Lower BMD in premenopausal women with type 1 diabetes may substantially increase their risk of developing osteoporosis after menopause. Type 1 diabetic women should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause.
Association of Systemic Concentrations of Macrophage Migration Inhibitory Factor With Impaired Glucose Tolerance and Type 2 Diabetes
Authors: Herder Christian , Kolb Hubert , Koenig Wolfgang , Haastert Burkhard , Müller-Scholze Sylvia , Rathmann Wolfgang , Holle Rolf , Thorand Barbara , Wichmann H.-Erich
Published: May 2006

OBJECTIVE—Macrophage migration inhibitory factor (MIF) is a central cytokine in innate immunity. MIF expression can be regulated by glucose and insulin, but data on the association with type 2 diabetes are sparse. The aim of this study was to test whether MIF is associated with impaired glucose tolerance (IGT) and type 2 diabetes and whether these associations are independent of metabolic and immunological risk factors and to compare the associations of MIF and IGT/type 2 diabetes with those of C-reactive protein (CRP) and interleukin-6 (IL-6) with IGT/type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4 (KORA S4) is a population-based survey performed in Southern Germany (1999–2001). Of 1,653 participants aged 55–74 years, 236 patients with type 2 diabetes, 242 subjects with IGT, and 244 normoglycemic control subjects matched for age and sex were included in this cross-sectional study. Serum concentrations of MIF were measured by enzyme-linked immunosorbent assay.

RESULTS—Serum MIF concentrations are highly increased in individuals with IGT and type 2 diabetes. The associations of MIF with IGT and type 2 diabetes were independent of classical risk factors and of CRP and IL-6 and were much stronger before and after multivariate adjustment than the associations of CRP and IL-6 with IGT and type 2 diabetes.

CONCLUSIONS—Our data suggest that elevations of systemic MIF concentrations precede the onset of type 2 diabetes. This finding may be relevant because MIF has been reported to contribute to the development of type 2 diabetes–related diseases such as atherosclerosis and cancer.
Trends in Deliveries, Prenatal Care, and Obstetrical Complications in Women With Pregestational Diabetes
Authors: Feig Denice S. , Razzaq Asma , Sykora Kathy , Hux Jan E. , Anderson Geoff M.
Published: May 2006

OBJECTIVE—To describe recent trends in the proportion of deliveries in women with pregestational diabetes (PGD), their use of services, and diabetes-related obstetrical complications.

RESEARCH DESIGN AND METHODS—In this population-based retrospective cohort study, comprehensive administrative data were used to identify all women (with and without PGD) who gave birth in an Ontario, Canada, hospital from 1996 to 2001. Data on maternal complications and interventions were obtained from hospital discharge records; data on use of prenatal services were obtained from fee-for-service claims.

RESULTS—The proportion of deliveries in women with PGD increased steadily from 0.8% in 1996 to 1.2% in 2001 (P < 0.001). In 2001, women with PGD were more likely to be diagnosed with shoulder dystocia (adjusted odds ratio 2.00 [95% CI 1.55–2.58]), hypertension (4.13 [3.44–4.96]), and preeclampsia/eclampsia (4.44 [3.43–5.73]) and have higher rates of inductions (1.69 [1.52–1.88]) and caesarean sections (1.78 [1.60–1.98]) than women without PGD. In 2001, 50% of the women with PGD had a visit to a diabetes specialist during pregnancy and only 30% of women had claims for a prenatal retinal examination. Both of these rates have decreased over the study period.

CONCLUSIONS—Women with PGD now account for a larger proportion of deliveries. These women continue to have higher obstetrical complication and intervention rates than women without PGD and many do not receive recommended specialty care during pregnancy.
Cost-Effectiveness and Net Benefit of Enhanced Treatment of Depression for Older Adults With Diabetes and Depression
Authors: Katon Wayne , Unützer Jürgen , Fan Ming-Yu , Williams John W. , Schoenbaum Michael , Lin Elizabeth H.B. , Hunkeler Enid M.
Published: May 2006

OBJECTIVE—To determine the incremental cost-effectiveness and net benefit of a depression collaborative care program compared with usual care for patients with diabetes and depression.

RESEARCH DESIGN AND METHODS—This article describes a preplanned subgroup analysis of patients with diabetes from the Improving Mood-Promoting Access to Collaborative (IMPACT) randomized controlled trial. The setting for the study included 18 primary care clinics from eight health care organizations in five states. A total of 418 of 1,801 patients randomized to the IMPACT intervention (n = 204) versus usual care (n = 214) had coexisting diabetes. A depression care manager offered education, behavioral activation, and a choice of problem-solving treatment or support of antidepressant management by the primary care physician. The main outcomes were incremental cost-effectiveness and net benefit of the program compared with usual care.

RESULTS—Relative to usual care, intervention patients experienced 115 (95% CI 72–159) more depression-free days over 24 months. Total outpatient costs were $25 (95% CI −1,638 to 1,689) higher during this same period. The incremental cost per depression-free day was 25 cents (−$14 to $15) and the incremental cost per quality-adjusted life year ranged from $198 (144–316) to $397 (287–641). An incremental net benefit of $1,129 (692–1,572) was found.

CONCLUSIONS—The IMPACT intervention is a high-value investment for older adults with diabetes; it is associated with high clinical benefits at no greater cost than usual care.
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) <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 <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 < 0.001) and was progressively more left shifted with decreasing Kg (P < 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 >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 >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 >9.5%, the reduction of A1C with insulin glargine was greater than with rosiglitazone (P < 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 <3.9 mmol/l (<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 (<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 <3.9 mmol/l (P = 0.02) and <2.8 mmol/l (P < 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 < 0.002). HDL cholesterol was unchanged with insulin glargine but increased with rosiglitazone by 4.4% (P < 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 >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 (>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 >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 >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) >8% and insulin requirements of >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 >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 < 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 < 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 <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 <0.001) comparing the highest with the lowest category of calcium intake from supplements. A combined daily intake of >1,200 mg calcium and >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 <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 < 0.01), after local heat stimulation at 40°C (12.9 ± 2.2 vs. 5.7 ± 1.7, P < 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

Two 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

The 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.
Cover Picture: Multidimensional Large‐Amplitude Motion: Revealing Concurrent Tunneling Pathways in Molecules with Several Internal Rotors / The Glycine–Water Complex (Angew. Chem. Int. Ed. 21/2006)
Authors: Schnell Melanie , Grabow Jens‐Uwe , Alonso José L. , Cocinero Emilio J. , Lesarri Alberto , Sanz M. Eugenia , López Juan C.
Published: May 2006

Microsolvation of glycine has been studied by combining impulse supersonic‐jet Fourier‐transform microwave spectroscopy with laser ablation and the structure of the monohydrated complex derived from rotational spectra. Combining this method with theoretical considerations enables the internal dynamics of multiple large‐amplitude motions, such as in (CH3)3XCl (X=Si, Ge, Sn), to be revealed. For more details, see the Communications by J.‐U. Grabow and J. L. Alonso and co‐workers on pages 3465 and 3471 ff.
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

Loss 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

The 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

This 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.
Epidemiology of measles, mumps and rubella in Italy
Authors: GABUTTI G. , ROTA M. C. , SALMASO S. , BRUZZONE B. M. , BELLA A. , CROVARI P. , Serological Study group and the
Published: May 2006

A serosurvey for measles, mumps and rubella was conducted in Italy; incidence based on statutory notifications over the last three decades was also calculated. In Italy the diseases followed an endemic–epidemic pattern, with an incidence peak every 2–4 years, and had a limited reduction of incidence attributable to childhood immunization. Lower notification rates were observed in the Southern regions. This is possibly related to greater under notification in the South and is confirmed by our seroprevalence data. Incidence of measles and rubella and proportion of cases among young adults increased significantly in the three decades considered, but not for mumps. Serological data confirmed that these infections are still very frequent in Italy, without significant geographic variation in the country. In the age groups 2–4 and 5–9 years the percentage of individuals still susceptible to each virus was higher than 30%. The proportion of susceptible subjects older than 15 years was similar for the three infections (6·1, 11·7 and 8·8% for measles, mumps and rubella, respectively). The low vaccine coverage for rubella and measles in Italy has so far only partially affected the occurrence of the diseases. No impact of mumps vaccination is visible. The average number of deaths, for each disease, has decreased during the three study periods. Today the priority in Italy is to halt the progressive increase of the mean age of acquisition of the three infections, to eliminate differences in coverage among regions and to conform to European standards. This will be achieved through a combination of increasing MMR vaccine coverage before 2 years of age, implementing vaccination campaigns for low seroprevalence age groups, and/or introducing a second dose of MMR, depending on the level of current MMR coverage.
Die «Diagnose» im Lichte von Charles S. Peirce, Sherlock Holmes, Sigmund Freud und der modernen Neurobiologie
Authors: Adler
Published: May 2006

Die diagnostische Hypothesenbildung ist eine causa ficta, eine Annahme, geeignete Erscheinungen zu erklären, die aber noch nicht als einzig mögliche und gültige Erklärung des Sachverhaltes erwiesen ist. Als ein Beispiel für eine diagnostische Hypothesenbildung wird ein Hauff-Märchen geschildert. Die Hauptfigur entwickelt ihre Hypothese aufgrund von Zeichen. Es gibt ikonische, indexikalische und symbolische Zeichen. Bei S. Peirce entsteht die Hypothese durch Abduktion, bei Conan Doyle's Sherlock Holmes durch «Versenkung», bei S. Freud durch «Gleichschwebende Aufmerksamkeit». Alle drei Verfahren sind sehr ähnlich. Die neurobiologischen Strukturen und Funktionskreise, die diesen Vorgängen entsprechen, werden beschrieben, insbesondere das sog. «emotional-implizite» Gedächtnis. Die besprochene Art der Hypothesenfindung ist für den Arzt bedeutsam.
Predicting spring discharge of the Susquehanna River from a winter synoptic climatology for the eastern United States
Authors: Miller W. D. , Kimmel D. G. , Harding L. W.
Published: May 2006

Seasonal and interannual variations of freshwater flow strongly influence estuarine processes, exemplified by plankton biomass and productivity. The main tributary feeding Chesapeake Bay, the Susquehanna River, has shown threefold variability of spring flow in the last 52 years. The magnitude of spring discharge from the Susquehanna River is associated with the frequency and type of weather patterns transiting the eastern United States during winter and is related to the precipitation stored in the basin as snow and ice. Large‐scale indices of climate variability, such as El Niño–Southern Oscillation and the North Atlantic Oscillation, have not proven to be strong predictors of freshwater flow in the Mid‐Atlantic. We developed a synoptic climatology as an alternative way to quantify and classify regional weather, focusing on the types and frequency of occurrence of patterns we identified for winter. This approach was used to predict freshwater flow in spring and explained 54% of the variance of spring discharge after extreme outliers were removed. Responses of Chesapeake Bay plankton to contrasting years of weather pattern frequencies and associated freshwater flow were examined to illustrate ecosystem response to climatic forcing.
Use of suppression subtractive hybridization to examine the accessory genome of the Liverpool cystic fibrosis epidemic strain of Pseudomonas aeruginosa
Authors: Smart Catherine H. M. , Walshaw Martin J. , Hart C. Anthony , Winstanley Craig
Published: May 2006

The Liverpool epidemic strain (LES) of Pseudomonas aeruginosa has been highly successful at colonizing cystic fibrosis (CF) patients throughout the UK, has replaced previously established strains in CF patients, has caused infections of non-CF parents of CF patients, and can cause greater morbidity in CF than other strains of P. aeruginosa. Using suppression subtractive hybridization (SSH) to identify strain-specific sequences, a diagnostic test for the LES based on PCR amplification of SSH sequence PS21 had previously been developed. In this study, the SSH sequence database of LES was substantially increased, using both extension of previous sequences and new rounds of subtraction. Of 92 SSH sequences identified as present in the LES but absent from strain PAO1, 25 were assessed for prevalence amongst a strain panel consisting mainly of LES and non-LES CF isolates. Preliminary analysis of genome sequence data indicated that all SSH sequences that were LES specific or found only rarely in other strains of P. aeruginosa were present on one of three contigs. All of the SSH sequences screened were either unstable amongst LES isolates or were not completely LES specific. Rare false positives were found with the PS21 test. The authors suggest that a second PCR assay designed to detect SSH sequence LESF9 can be used to confirm the identity of the most prevalent CF epidemic lineage in the UK.