bluuebunny/crossref_metadata_2025 huggingface dataset:
Naringenin Prevents Dyslipidemia, Apolipoprotein B Overproduction, and Hyperinsulinemia in LDL Receptor–Null Mice With Diet-Induced Insulin Resistance
Authors: Mulvihill Erin E. , Allister Emma M. , Sutherland Brian G. , Telford Dawn E. , Sawyez Cynthia G. , Edwards Jane Y. , Markle Janet M. , Hegele Robert A. , Huff Murray W.
Published: July 2009

OBJECTIVE

The global epidemic of metabolic syndrome and its complications demands rapid evaluation of new and accessible interventions. Insulin resistance is the central biochemical disturbance in the metabolic syndrome. The citrus-derived flavonoid, naringenin, has lipid-lowering properties and inhibits VLDL secretion from cultured hepatocytes in a manner resembling insulin. We evaluated whether naringenin regulates lipoprotein production and insulin sensitivity in the context of insulin resistance in vivo.

RESEARCH DESIGN AND METHODS

LDL receptor–null (Ldlr−/−) mice fed a high-fat (Western) diet (42% calories from fat and 0.05% cholesterol) become dyslipidemic, insulin and glucose intolerant, and obese. Four groups of mice (standard diet, Western, and Western plus 1% or 3% wt/wt naringenin) were fed ad libitum for 4 weeks. VLDL production and parameters of insulin and glucose tolerance were determined.

RESULTS

We report that naringenin treatment of Ldlr−/− mice fed a Western diet corrected VLDL overproduction, ameliorated hepatic steatosis, and attenuated dyslipidemia without affecting caloric intake or fat absorption. Naringenin 1) increased hepatic fatty acid oxidation through a peroxisome proliferator–activated receptor (PPAR) γ coactivator 1α/PPARα-mediated transcription program; 2) prevented sterol regulatory element–binding protein 1c–mediated lipogenesis in both liver and muscle by reducing fasting hyperinsulinemia; 3) decreased hepatic cholesterol and cholesterol ester synthesis; 4) reduced both VLDL-derived and endogenously synthesized fatty acids, preventing muscle triglyceride accumulation; and 5) improved overall insulin sensitivity and glucose tolerance.

CONCLUSIONS

Thus, naringenin, through its correction of many of the metabolic disturbances linked to insulin resistance, represents a promising therapeutic approach for metabolic syndrome.
Generation of Novel Single-Chain Antibodies by Phage-Display Technology to Direct Imaging Agents Highly Selective to Pancreatic β- or α-Cells In Vivo
Authors: Ueberberg Sandra , Meier Juris J. , Waengler Carmen , Schechinger Wolfgang , Dietrich Johannes W. , Tannapfel Andrea , Schmitz Inge , Schirrmacher Ralf , Köller Manfred , Klein Harald H. , Schneider Stephan
Published: July 2009

OBJECTIVE

Noninvasive determination of pancreatic β-cell mass in vivo has been hampered by the lack of suitable β-cell–specific imaging agents. This report outlines an approach for the development of novel ligands homing selectively to islet cells in vivo.

RESEARCH DESIGN AND METHODS

To generate agents specifically binding to pancreatic islets, a phage library was screened for single-chain antibodies (SCAs) on rat islets using two different approaches. 1) The library was injected into rats in vivo, and islets were isolated after a circulation time of 5 min. 2) Pancreatic islets were directly isolated, and the library was panned in the islets in vitro. Subsequently, the identified SCAs were extensively characterized in vitro and in vivo.

RESULTS

We report the generation of SCAs that bind highly selective to either β- or α-cells. These SCAs are internalized by target cells, disappear rapidly from the vasculature, and exert no toxicity in vivo. Specific binding to β- or α-cells was detected in cell lines in vitro, in rats in vivo, and in human tissue in situ. Electron microscopy demonstrated binding of SCAs to the endoplasmatic reticulum and the secretory granules. Finally, in a biodistribution study the labeling intensity derived from [125I]-labeled SCAs after intravenous administration in rats strongly predicted the β-cell mass and was inversely related to the glucose excursions during an intraperitoneal glucose tolerance test.

CONCLUSIONS

Our data provide strong evidence that the presented SCAs are highly specific for pancreatic β-cells and enable imaging and quantification in vivo.
Change in the Distribution of Albuminuria According to Estimated Glomerular Filtration Rate in Pima Indians With Type 2 Diabetes
Authors: Pavkov Meda E. , Mason Clinton C. , Bennett Peter H. , Curtis Jeffrey M. , Knowler William C. , Nelson Robert G.
Published: July 2009

OBJECTIVE

We examined secular trends in the frequency distribution of albuminuria and estimated glomerular filtration rate (eGFR) in subjects with type 2 diabetes in 1982–1988 and 2001–2006, two periods associated with major changes in the management of diabetes.

RESEARCH DESIGN AND METHODS

The cross-sectional study included Pima Indians ≥15 years old with type 2 diabetes and measures of serum creatinine and urinary albumin-to-creatinine ratios (ACR). The continuous probability density distributions of ACR and eGFR were compared for the two time periods. eGFR was calculated using the Modification of Diet in Renal Disease Study equation.

RESULTS

The overall standardized distribution of ACR shifted toward lower values between time periods (P = 0.001), whereas the standardized distribution of eGFR did not (P = 0.45). In the first period, eGFR was <60 ml/min per 1.73 m2 in 6.5% of the 837 subjects. Of these, 9.3% had normal ACR, 7.4% had microalbuminuria, and 83.3% had macroalbuminuria. In the second period, the prevalence of low eGFR was similar (6.6% of the 1,310 subjects). Among those with low eGFR, normal ACR prevalence doubled to 17.2%, microalbuminuria prevalence nearly tripled to 19.5%, and macroalbuminuria prevalence declined to 63.2%. Twice as many subjects in the second period received antihypertensive medicines and 30% more received hypoglycemic medicines than in the first period.

CONCLUSIONS

The distribution of albuminuria changed significantly among diabetic Pima Indians over the past 20 years, as treatment with medicines to control hyperglycemia and hypertension increased. The distribution of eGFR, however, remained unchanged. Consequently, the frequency of chronic kidney disease characterized by normoalbuminuria and low eGFR doubled.
Effects of Exercise Training Intensity on Pancreatic β-Cell Function
Authors: Slentz Cris A. , Tanner Charles J. , Bateman Lori A. , Durheim Michael T. , Huffman Kim M. , Houmard Joseph A. , Kraus William E.
Published: July 2009

OBJECTIVE

Insulin resistance and β-cell dysfunction both are important contributors to the pathogenesis of type 2 diabetes. Exercise training improves insulin sensitivity, but its effects on β-cell function are less well studied.

RESEARCH DESIGN AND METHODS

Sedentary, overweight adults were randomized to control or one of three 8-month exercise programs: 1) low amount/moderate intensity, 2) low amount/vigorous intensity, or 3) high amount/vigorous intensity. Of 387 randomized, 260 completed the study and 237 had complete data. Insulin sensitivity (Si), acute insulin response to glucose (AIRg), and the disposition index (DI = Si × AIRg) were modeled from an intravenous glucose tolerance test.

RESULTS

Compared with control subjects, all three training programs led to increases in DI. However, the moderate-intensity group experienced a significantly larger increase in DI than either of the vigorous-intensity groups and through a different mechanism. The high-amount/vigorous-intensity group improved Si and had a compensatory reduction in AIRg, whereas the moderate-intensity group had a similar improvement in Si but almost no reduction in AIRg. Importantly, the inactive control group experienced a significant increase in fasting glucose.

CONCLUSIONS

To the extent that the DI accurately reflects β-cell function, we observed that both moderate- and vigorous-intensity exercise training improved β-cell function, albeit through distinct mechanisms. It is not clear which of these mechanisms is preferable for maintenance of metabolic health. While moderate-intensity exercise led to a larger improvement in DI, which may reflect a transition toward a more normal DI, longer-term investigations would be necessary to determine which was more effective at reducing diabetes risk.
Association Between Type of Dietary Fish and Seafood Intake and the Risk of Incident Type 2 Diabetes
Authors: Patel Pinal S. , Sharp Stephen J. , Luben Robert N. , Khaw Kay-Tee , Bingham Sheila A. , Wareham Nicholas J. , Forouhi Nita G.
Published: July 2009

OBJECTIVE

To investigate the association between fish and seafood intake and new-onset type 2 diabetes.

RESEARCH DESIGN AND METHODS

This was a population-based prospective cohort (European Prospective Investigation of Cancer [EPIC]-Norfolk) study of men and women aged 40–79 years at baseline (1993–1997). Habitual fish and seafood intake (white fish, oily fish, fried fish, and shellfish) was assessed using a semiquantitative food frequency questionnaire and categorized as less than one or one or more portions/week. During a median (interquartile range) follow-up of 10.2 (9.1–11.2) years, there were 725 incident diabetes cases among 21,984 eligible participants.

RESULTS

Higher total fish intake (one or more versus less than one portions/week) was associated with a significantly lower risk of diabetes (odds ratio [OR] 0.75 [95% CI 0.58–0.96]), in analyses adjusted for age, sex, family history of diabetes, education, smoking, physical activity, dietary factors (total energy intake, alcohol intake, and plasma vitamin C) and obesity (BMI and waist circumference). White fish and oily fish intakes were similarly inversely associated with diabetes risk, but the associations were not significant after adjustment for dietary factors (oily fish) or obesity (white fish). Fried fish was not significantly associated with diabetes risk. Consuming one or more portions/week of shellfish was associated with an increased risk of diabetes (OR 1.36 [1.02–1.81]) in adjusted analyses.

CONCLUSIONS

Total, white, and oily fish consumption may be beneficial for reducing risk of diabetes, reinforcing the public health message to consume fish regularly. Greater shellfish intake seems to be associated with an increased risk of diabetes, warranting further investigation into cooking methods and mechanisms.
Potential of Albiglutide, a Long-Acting GLP-1 Receptor Agonist, in Type 2 Diabetes
Authors: Rosenstock Julio , Reusch Jane , Bush Mark , Yang Fred , Stewart Murray ,   for the Albiglutide Study Group
Published: July 2009

OBJECTIVE

To evaluate the efficacy, safety, and tolerability of incremental doses of albiglutide, a long-acting glucagon-like peptide-1 receptor agonist, administered with three dosing schedules in patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapy.

RESEARCH DESIGN AND METHODS

In this randomized multicenter double-blind parallel-group study, 356 type 2 diabetic subjects with similar mean baseline characteristics (age 54 years, diabetes duration 4.9 years, BMI 32.1 kg/m2, A1C 8.0%) received subcutaneous placebo or albiglutide (weekly [4, 15, or 30 mg], biweekly [15, 30, or 50 mg], or monthly [50 or 100 mg]) or exenatide twice daily as an open-label active reference (per labeling in metformin subjects only) over 16 weeks followed by an 11-week washout period. The main outcome measure was change from baseline A1C of albiglutide groups versus placebo at week 16.

RESULTS

Dose-dependent reductions in A1C were observed within all albiglutide schedules. Mean A1C was similarly reduced from baseline by albiglutide 30 mg weekly, 50 mg biweekly (every 2 weeks), and 100 mg monthly (−0.87, −0.79, and −0.87%, respectively) versus placebo (−0.17%, P < 0.004) and exenatide (−0.54%). Weight loss (−1.1 to −1.7 kg) was observed with these three albiglutide doses with no significant between-group effects. The incidence of gastrointestinal adverse events in subjects receiving albiglutide 30 mg weekly was less than that observed for the highest biweekly and monthly doses of albiglutide or exenatide.

CONCLUSIONS

Weekly albiglutide administration significantly improved glycemic control and elicited weight loss in type 2 diabetic patients, with a favorable safety and tolerability profile.
Hypertriglyceridemic Waist Phenotype Predicts Increased Visceral Fat in Subjects With Type 2 Diabetes
Authors: Sam Susan , Haffner Steven , Davidson Michael H. , D'Agostino Ralph B. , Feinstein Steven , Kondos George , Perez Alfonso , Mazzone Theodore
Published: July 2009

OBJECTIVE

Greater accumulation of visceral fat is strongly linked to risk of cardiovascular disease. However, elevated waist circumference by itself does not always identify individuals with increased visceral fat.

RESEARCH DESIGN AND METHODS

We examined 375 subjects with type 2 diabetes from the CHICAGO cohort for presence of hypertriglyceridemic waist phenotype (waist circumference >90 cm in men or >85 cm in women, in conjunction with a plasma triglyceride concentration of ≥177 mg/dl) to determine its usefulness for identifying subjects with increased amounts of visceral fat. We divided subjects into three groups: group 1 (low waist circumference and low triglycerides; waist circumference ≤90 cm in men or ≤85 cm in women and triglyceride <177 mg/dl, n = 18), group 2 (high waist circumference and low triglycerides; waist circumference >90 cm in men or >85 cm in women and triglycerides <177 mg/dl, n = 230), and group 3 (high waist circumference and high triglycerides; waist circumference >90 cm in men or >85 cm in women and triglycerides ≥177 mg/dl, n = 127).

RESULTS

Subjects in group 3 had significantly higher visceral fat (P < 0.0001), A1C (P < 0.01), and coronary artery calcium (P < 0.05) compared with group 2, despite similar age, BMI, and waist circumference. The relationship of the phenotype to atherosclerosis, however, was attenuated by adjustment for HDL cholesterol, triglyceride-rich lipoprotein cholesterol, apolipoprotein B, or LDL particle number.

CONCLUSIONS

The presence of hypertriglyceridemic waist phenotype in subjects with type 2 diabetes identifies a subset with greater degree of visceral adiposity. This subset also has greater degree of subclinical atherosclerosis that may be related to the proatherogenic lipoprotein changes.
Transforming Growth Factor-β1 and Incident Type 2 Diabetes
Authors: Herder Christian , Zierer Astrid , Koenig Wolfgang , Roden Michael , Meisinger Christa , Thorand Barbara
Published: July 2009

OBJECTIVE

Subclinical inflammation leads to insulin resistance and β-cell dysfunction. This study aimed to assess whether levels of circulating transforming growth factor-β1 (TGF-β1)—a central, mainly immunosuppressive, and anti-inflammatory cytokine—were associated with incident type 2 diabetes.

RESEARCH DESIGN AND METHODS

We measured serum levels of TGF-β1 from 460 individuals with and 1,474 individuals without incident type 2 diabetes in a prospective case-cohort study within the population-based MONICA (MONItoring of Trends and Determinants in CArdiovascular Disease)/KORA (Cooperative Health Research in the Region of Augsburg) cohort.

RESULTS

Elevated TGF-β1 concentrations were associated with higher, not lower, risk for type 2 diabetes (age-, sex-, and survey-adjusted hazard ratios [95% CI] for increasing TGF-β1 tertiles: 1.0, 1.08 [0.83–1.42], and 1.41 [1.08–1.83]; Pfor trend = 0.012). Adjustment for BMI and metabolic and lifestyle factors had virtually no impact on the effect size.

CONCLUSIONS

Elevated serum concentrations of the cytokine TGF-β1 indicate an increased risk for type 2 diabetes. TGF-β1 may be upregulated to counterbalance metabolic and immunological disturbances preceding type 2 diabetes.
Heterogeneous Effects of Fructose on Blood Lipids in Individuals With Type 2 Diabetes
Authors: Sievenpiper John L. , Carleton Amanda J. , Chatha Sheena , Jiang Henry Y. , de Souza Russell J. , Beyene Joseph , Kendall Cyril W.C. , Jenkins David J.A.
Published: July 2009

OBJECTIVE

Because of blood lipid concerns, diabetes associations discourage fructose at high intakes. To quantify the effect of fructose on blood lipids in diabetes, we conducted a systematic review and meta-analysis of experimental clinical trials investigating the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol in type 1 and 2 diabetes.

RESEARCH DESIGN AND METHODS

We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of ≥7 days. Data were pooled by the generic inverse variance method and expressed as standardized mean differences with 95% CI. Heterogeneity was assessed by χ2 tests and quantified by I2. Meta-regression models identified dose threshold and independent predictors of effects.

RESULTS

Sixteen trials (236 subjects) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides and lowered total cholesterol under specific conditions without affecting LDL cholesterol or HDL cholesterol. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the reference carbohydrate was starch (mean difference 0.24 [95% CI 0.05–0.44]), dose was >60 g/day (0.18 [0.00–0.37]), or follow-up was ≤4 weeks (0.18 [0.00–0.35]). Piecewise meta-regression confirmed a dose threshold of 60 g/day (R2 = 0.13)/10% energy (R2 = 0.36). A total cholesterol–lowering effect without heterogeneity was seen only in type 2 diabetes under the following conditions: no randomization and poor study quality (−0.19 [−0.34 to −0.05]), dietary fat >30% energy (−0.33 [−0.52 to −0.15]), or crystalline fructose (−0.28 [−0.47 to −0.09]). Multivariate meta-regression analyses were largely in agreement.

CONCLUSIONS

Pooled analyses demonstrated conditional triglyceride-raising and total cholesterol–lowering effects of isocaloric fructose exchange for carbohydrate in type 2 diabetes. Recommendations and large-scale future trials need to address the heterogeneity in the data.
Insulin-Based Versus Triple Oral Therapy for Newly Diagnosed Type 2 Diabetes
Authors: Lingvay Ildiko , Legendre Jaime L. , Kaloyanova Polina F. , Zhang Song , Adams-Huet Beverley , Raskin Philip
Published: July 2009

OBJECTIVE

Early use of insulin after diagnosis of type 2 diabetes is met with resistance because of associated weight gain, hypoglycemia, and fear of decreased compliance and quality of life (QoL).

RESEARCH DESIGN AND METHODS

In treatment-naive patients with newly diagnosed type 2 diabetes, insulin and metformin were initiated for a 3-month lead-in period, then patients were randomly assigned to insulin and metformin (insulin group) or metformin, pioglitazone, and glyburide (oral group) for 36 months. Hypoglycemic events, compliance, A1C, weight, QoL, and treatment satisfaction were assessed.

RESULTS

Of 29 patients randomly assigned into each group, 83% (insulin group) and 72% (oral group) completed this 3-year study. At study completion, A1C was 6.1 ± 0.6% (insulin group) versus 6.0 ± 0.8% (oral group). Weight increased similarly in both groups (P = 0.09) by 4.47 kg (95% CI 0.89–8.04 kg) (insulin group) and 7.15 kg (95% CI 4.18–10.13 kg) (orals group). Hypoglycemic events did not differ between groups (mild 0.51 event/person-month in the insulin group vs. 0.68 event/person-month in the orals group, P = 0.18 and severe 0.04 event/person-year in the insulin group vs. 0.09 event/person-year in the orals group, P = 0.53). Compliance, QoL, and treatment satisfaction were similar between groups, with 100% of patients randomly assigned to insulin willing to continue such treatment.

CONCLUSIONS

When compared with a clinically equivalent treatment regimen, insulin-based therapy is effective and did not cause greater weight gain or hypoglycemia nor decrease compliance, treatment satisfaction, or QoL. Insulin is safe, well-accepted, and effective for ongoing treatment of patients with newly diagnosed type 2 diabetes.
Maternal BMI Before Pregnancy, Maternal Weight Gain During Pregnancy, and Risk of Persistent Positivity for Multiple Diabetes-Associated Autoantibodies in Children With the High-Risk HLA Genotype
Authors: Rasmussen Trond , Stene Lars C. , Samuelsen Sven O. , Cinek Ondrej , Wetlesen Turid , Torjesen Peter A. , Rønningen Kjersti S.
Published: July 2009

OBJECTIVE

To assess whether maternal BMI before pregnancy and weight gain during pregnancy predicted the risk of islet autoimmunity in genetically susceptible children.

RESEARCH DESIGN AND METHODS

Of 46,939 newborns screened for the high-risk HLA genotype DR4-DQ8/DR3-DQ2, 1,003 were positive and 885 were followed with serial blood samples tested for autoantibodies to insulin, GAD, and insulinoma-associated protein 2 (IA2). The end point was defined as repeated positivity for two or three autoantibodies or the onset of type 1 diabetes (islet autoimmunity).

RESULTS

Thirty-six children developed islet autoimmunity, of whom 10 developed type 1 diabetes. Both maternal BMI ≥30 kg/m2 before pregnancy and maternal weight gain ≥15 kg predicted the increased risk of islet autoimmunity (hazard ratio [HR] 2.5, P = 0.023, and HR 2.5, P = 0.015, respectively), independent of maternal diabetes.

CONCLUSIONS

Maternal weight may predict risk of islet autoimmunity in offspring with a high genetic susceptibility for type 1 diabetes.
Hyperglycemia, Type 2 Diabetes, and Depressive Symptoms
Authors: Kivimaki Mika , Tabak Adam G. , Batty G. David , Singh-Manoux Archana , Jokela Markus , Akbaraly Tasnime N. , Witte Daniel R. , Brunner Eric J. , Marmot Michael G. , Lawlor Debbie A.
Published: July 2009

OBJECTIVE

To examine the recent suggestion that impaired fasting glucose may protect against depression, whereas a diagnosis of diabetes might then result in depression.

RESEARCH DESIGN AND METHODS

Cross-sectional analysis of 4,228 adults (mean age 60.7 years, 73.0% men) who underwent oral glucose tolerance testing and completed the Center for Epidemiologic Studies Depression scale (CES-D).

RESULTS

After adjustment for demographic factors, health behaviors, and clinical measurements (BMI, waist circumference, lipid profile, and blood pressure), there was a U-shaped association between fasting glucose and depression (Pcurve = 0.001), with elevated CES-D at low and very high glucose levels. This finding was replicable with 2-h postload glucose (P = 0.11) and A1C (P = 0.007).

CONCLUSIONS

The U-shaped association between blood glucose and CES-D, with the lowest depression risk seen among those in the normoglycemic range of A1C, did not support the hypothesized protective effect of hyperglycemia.
Diabetes Risk Perception and Intention to Adopt Healthy Lifest yles Among Primary Care Patients
Authors: Hivert Marie-France , Warner Ana Sofia , Shrader Peter , Grant Richard W. , Meigs James B.
Published: July 2009

OBJECTIVE

To examine perceived risk of developing diabetes in primary care patients.

RESEARCH DESIGN AND METHODS

We recruited 150 nondiabetic primary care patients. We made standard clinical measurements, collected fasting blood samples, and used the validated Risk Perception Survey for Developing Diabetes questionnaire.

RESULTS

Patients with high perceived risk were more likely than those with low perceived risk to have a family history of diabetes (68 vs. 18%; P < 0.0001) and to have metabolic syndrome (53 vs. 35%; P = 0.04). However, patients with high perceived risk were not more likely to have intentions to adopt healthier lifestyle in the coming year (high 26.0% vs. low 29.2%; P = 0.69).

CONCLUSIONS

Primary care patients with higher perceived risk of diabetes were at higher actual risk but did not express greater intention to adopt healthier lifestyles. Aspects of health behavior theory other than perceived risk need to be explored to help target efforts in the primary prevention of diabetes.
Low LDL Cholesterol, Albuminuria, and Statins for the Risk of Cancer in Type 2 Diabetes
Authors: Yang Xilin , So Wing Yee , Ma Ronald C.W. , Ko Gary T.C. , Kong Alice P.S. , Zhao Hailu , Luk Andrea O.Y. , Lam Christopher W.K. , Ho Chung Shun , Tong Peter C.Y. , Chan Juliana C.N.
Published: July 2009

OBJECTIVE

LDL cholesterol <2.80 mmol/l was associated with increased cancer risk in type 2 diabetes. We explored the 1) interaction between low LDL cholesterol and albuminuria and 2) interaction between copresence of these two risk factors and statin use for cancer in type 2 diabetes.

RESEARCH DESIGN AND METHODS

We analyzed prospective data for 3,793 Chinese type 2 diabetic patients who remained naive for statin treatment and 1,483 patients in whom statin treatment was initiated during a median follow-up period of 5.24 years. All patients were free of cancer at baseline. Biological interactions were estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates biological interaction.

RESULTS

In 3,793 statin-naive type 2 diabetic patients, copresence of low LDL cholesterol and albuminuria increased cancer risk by 2.8-fold (hazard ratio 2.77 [95% CI 1.78–4.31]) with significant biological interactions (RERI 1.05 [0.04–2.06]; AP 0.38 [0.09–0.66]). In the whole cohort of 5,276 type 2 diabetic patients, there was interaction between nonuse of statins and copresence of low LDL cholesterol and albuminuria with increased cancer risk (RERI 2.87 [0.64–5.09] and AP 0.60 [0.29–0.90]). Statin nonusers with LDL cholesterol <2.80 mmol/l and albumunuria had a 4.9-fold risk of cancer compared with statin users with or without both risk factors.

CONCLUSIONS

In type 2 diabetes, there was interaction between low LDL cholesterol and albuminuria with increased cancer risks. The latter was attenuated in the presence of statin treatment.
Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome — meta-analysis
Authors: Medica Igor , Maver Ales , Augusto Goncalo , Peterlin Borut
Published: July 2009

Folate metabolism deficiency has been related to increased occurrence of maternal non-disjunction resulting in trisomy 21. Several polymorphisms in genes coding for folate metabolism enzymes have been investigated for association with the maternal risk of Down syndrome (DS) yielding variable results. We performed a meta-analysis of case-control studies obtained through the PubMed database. The studies on polymorphisms in the MTHFR, MTRR, MTR, RFC1 and CBS genes were included. The summary OR demonstrated a statistically significant increased risk of giving birth to a child with DS in mothers carrying the mutant allele of the MTHFR/C677T gene polymorphism (both genetic models) and in mothers homozygous for the mutant allele of the MTRR/A66G polymorphism (recessive genetic model). Analyses of other polymorphisms, MTHFR/A1298C, MTR/A2756G, RFC1/A80G, and CBS/844ins68, resulted in borderline or no statistical significance. In conclusion, our meta-analysis showed the significance of genetic alterations in the folate metabolism genes in maternal susceptibility to DS offspring. Our results suggest that the importance of folate supplementation to women in reproductive age in prevention of non-disjunction be revised. Further genetic studies on a combined effect of multiple folate metabolism genes is recommended. Additionally, more thorough studies on the haplotype analyses of genes is recommended as well, especially in populations that have not yet been investigated thus far.
Serum levels of resistin and hsCRP in women with PCOS
Authors: Çapoğlu İlyas , Erdem Fuat , Uyanık Abdullah , Turhan Hamdullah
Published: July 2009

Resistin has been associated with obesity and type 2 diabetes. The elevated serum resistin level in human diabetes is often associated with a pro-inflammatory milieu. In vitro data suggest that C-reactive protein (CRP) significantly increases resistin expression in cultured human PBMC, yet the relationship in vivo is largely unknown. The purpose of this study was to determine the concentrations of CRP and resistin in women with polycystic ovary syndrome (PCOS) and to clarify whether or not there are correlations between CRP and resistin levels that have not previously been studied in PCOS in the context of resistin. Serum resistin and hsCRP levels of forty-five women with PCOS were analyzed. Compared with the control group, women with PCOS had significantly higher serum concentrations of resistin (p=0.009). Women with PCOS had higher hsCRP levels compared with controls, but these differences were not statistically significant (p>0.05). There was no correlation between serum resistin and hsCRP levels (r=0.128, p=0.404). Our study suggests that resistin concentrations was not associated with hsCRP levels
Changes in antioxidative parameters in the kidney of rats subchronically intoxicated with chlorfenvinphos — an organophosphate insecticide
Authors: Łukaszewicz-Hussain Anna
Published: July 2009

Chlorfenvinphos is an organophosphate insecticide, posing a risk to those who are professionally involved in its production and use in agriculture, as well as to the general population. Organophosphates (OPs) are the class of insecticides, whose primary target is acetylcholinesterase (AChE) that hydrolyzes acetylcholine, a major neurotransmitter at the central and peripheral neuronal synapses. Moreover, many authors postulate that these compounds, both in acute and chronic intoxication, change the activities of antioxidative enzymes, thus leading to the enhancement of lipid peroxidation in many tissues. In the current study, animals received once a day, intragastrically with a stomach tube, 0.1ml/100g of olive oil (control groups) and oil solution of chlorfenvinphos at a dose of 0.02LD50 (0.3 mg/kg b. w.) — the experimental groups. The animals were sacrificed on day 14 or on day 28 of exposure. In the kidneys of rats, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) as well as reduced glutathione level (GSH) were determined. Chlorfenvinphos administration resulted in increased activities of antioxidative enzymes in the kidney of rats. Renal activities of SOD, GPx and GR were more pronounced on day 28 of chlorfenvinphos exposure than on day 14. The kidney reduced glutathione level (GSH) did not change in comparison to the control level. The current experimental findings indicate that subchronic administration of chlorfenvinphos leads to an adaptive response in the kidney of rats and this response is mostly due to reduced glutathione level and glutathione metabolism.
Risk factors for vancomycin-resistant enteroccocci colonization in infants in neonatal intensive care unit
Authors: Devrim Ilker , Genel Ferah , Atlihan Füsun , Özbek Erhan , Gülfidan Gamze
Published: July 2009

We aimed to evaluate the risk factors for VRE colonization in neonatal intensive care units. In December 2007, we identified a neonate with VRE infection (urinary tract infection and we performed blood and stool cultures for VRE until the last colonized patient was discharged from our clinic. All the neonates hospitalized in NICU during December 2007 to January 2008. Active surveillance cultures for VRE fecal carriage was carried out in neonatal intensive care unit. Resistance to vancomycin was detected by the E-test method. Epidemiological data was recorded for all patients included in the study and was used for the risk factors. Totally 54 infants in NICU were screened for VRE colonization. Totally 11 infants (20%) were colonized with vancomycin-resistant enterococci. The average duration of all antimicrobial therapy was significantly longer in colonized patients. The infants who were hospitalized for more than 10 days were found to be significantly more colonized with VRE when compared to the infants with shorter hospital stay (p<0.05). There were no statistically significant differences between VRE colonized and non-colonized infants in respect to sex, to third generation cephalosporin usage, glycopeptide usage, presence of prematurity, presence of mechanical ventilation(p> 0.05). The premature infants and the mature infants were under risk of VRE colonization. Longer duration of hospitalization and antimicrobial usage were the prominent risk factors. Since infants in neonatal intensive care units were under risk of infections, periodic active surveillance cultures should be combined with logical antimicrobial therapy.
Effects of an EE/CA compared with EE/CA-metformin on serum ADMA levels in women with polycystic ovary syndrome
Authors: Kebapcilar Levent , Yuksel Arif , Bozkaya Giray , Taner Cuneyt , Kebapcilar Ayse , Bilgir Oktay , Alacacioglu Ahmet , Sari Ismail
Published: July 2009

To determine the effects of EE/CA (Ethinylestradiol/ Cyproterone Acetate) and EE/CA-metformin treatments on the asymmetric dimethylarginine (ADMA) levels in women with PCOS (Polycystic Ovary Syndrome). Among 43 patients diagnosed with PCOS, one study arm (n=22) was administered (35 µg EE, 2mg CA) and the other (n=21) was administered (35 µg EE, 2mg CA plus 1700mg metformin). Serum ADMA, lipid profile, androgens, insulin, and HOMA-IR (Homeostatic Model Assessment of Insulin Resistance ) values were assessed prior to treatment and after 3 months of therapy. A significant reduction in ADMA levels relative to pre-treatment in the EE/CA+metformin group (1.2±0.4 vs 0.95±0.4, p=0.016) compared to the EE/CA group (1.0±0.5 vs 1.03±0.4, p >0.05). Andogens, insulin and HOMA-IR levels decreased in both treatment groups. All lipid profiles significantly improved in-group EE/CA+metformin while no significant decrease was observed in TG and HDL-cholesterol levels in EE/CA group. Post-treatment levels of HDL-C levels correlated significantly with the reducing ADMA levels in the EE/CA+metformin group (P=0.005, r= 0.602). Adding metformin to EE/CA therapy in PCOS may beneficial endothelium effects associated with reduction of ADMA levels.
Taxane-based adjuvant chemotherapy in node positive, early stage Turkish breast cancer patients
Authors: Alacacioglu Ahmet , Zengel Baha , Denecli Ali
Published: July 2009

Adjuvant chemotherapy decreases the risk of breast cancer recurrence in patients with breast cancer. In addition, it increases the rate of survival. Therefore, various chemotherapy regimens are administered in the treatment of breast cancer. The efficacy of taxane-based adjuvant chemotherapies has been demonstrated in various trials. This trial was designed to retrospectively evaluate the efficacy of taxane-based chemotherapies in lymph node-positive, early-stage Turkish breast cancer patients. 29 patients receiving TAC regimen and 29 patients receiving AC+P regimen were evaluated. 6 courses of TAC regimen were administered every 3 weeks (docetaxel 75 mg/m2, doxorubicine 50 mg/m2, cyclophosphamide 500 mg/m2). The other patient group was administered AC+P regimen (4 courses of doxorubicin 60mg/m2, cyclophosphamide 600 mg/m2 combination every 2 weeks, followed by paclitaxel 175 mg/m2 for 4 courses every 2 weeks). The 1-year, 2-year and 3-year disease-free survival (DFS) rates were 96.3%, 81.1% and 72.8% respectively. No significant difference was detected in DFS between premenopausal and postmenopausal patients on the taxane regimen (p=0.82). There was no significant difference in DFS between estrogen or progesterone receptor positive and negative patients (p=0.46). Disease-free survival of patients receiving TAC and AC+P adjuvant chemotherapy regimen was compared. The follow-up period of patients on AC+P chemotherapy was longer than those receiving TAC (AC+P mean 38.6±12.8 months, TAC mean 17.1±5.4 months). No significant difference was observed upon evaluation of both treatment arms with respect to DFS (p=0.92). In conclusion, this trial once more demonstrated that taxane-based adjuvant chemotherapy was effective and safe in lymph node-positive, early-stage Turkish breast cancer patients.
Accuracy of quantitative ultrasound parameters in the diagnosis of osteoporosis
Authors: Pais Raluca , Campean Remus , Simon Siao-Pin , Bolosiu Calin , Muntean Laura , Bolosiu Horatiu
Published: July 2009

Quantitative ultrasound (QUS) is of increasing interest for evaluation of osteoporosis because, compared with dual-energy X-ray absorptiometry (DXA), it is portable, less expensive, and radiation-free. The aim of our study was to determine the sensitivity, specificity, and cut-off values of quantitative ultrasound parameters in identifying patients with osteoporosis compared to the World Health Organization (WHO) standard definition. We performed a cross-sectional investigational study of 73 subjects, and determined total hip and lumbar spine T-scores by dual-energy X-ray absorptiometry (DXA) (Prodigy Advance Lunar-GE). The QUS parameters (broadband ultrasound attenuation [BUA], speed of sound, bone mineral density, the stiffness index, and QUS T-score) were determined with Sahara Hologic equipment. The AUC was 0.81 (95% CI 0.67–0.95, p<0.05) for speed of sound (SOS) and 0.76 (95% CI 0.62–0.90, p<0.05) for BUA for the patients with DXA T-scores ≥ −1 DS; the cut-off values were 1542.2 meters per second for SOS and 63.3 dB/MHz for BUA. In patients with DXA T-scores ≤ − 2.5 DS, AUC was 0.80 (95% CI 0.70–0.90, p<0.05) for SOS, and 0.76 (95% CI 0.65–0.87, p<0.05) for BUA. The cut-off values were 1504.95 meters per second for SOS and 49.5 dB/MHz for BUA. Pearson correlation coefficients were positive and statistically significant (> 50%) for all QUS parameters in both groups, (2-tailed, p<0.05). QUS parameters correctly identified normal patients (false negative 34.21% and false positive 2.53%) and those with osteoporosis (false negative 8.55% and false positive 7.82%). The patients with QUS parameters between the cut-off values corresponding to DXA T-scores of −1 SD and − 2.5 SD should be further evaluated by DXA.
Platelet indices in patients with colorectal cancer
Authors: Karagöz Bülent , Sücüllü İlker , Sayan Özkan , Bilgi Oğuz , Tuncel Tolga , Filiz Ali , Yücel Ergün , Ozgun Alpaslan , Erikçi Alev , Alacacioğlu Ahmet , Kandemir Emin
Published: July 2009

The interaction between cancer cells and platelets has been known for a long time. Although platelet indices have been also investigated in several clinical settings, it has not been exactly demonstrated in cancer patients. We investigated platelet indices in colorectal cancer patients and compared with healthy subjects. Two hundred and twenty-one colorectal cancer patients and 110 healthy subjects were enrolled into the retrospective study. Data were obtained from computerized medical records of our hospital. Medical record review was performed for all patients regarding thrombocyte indices. Platelet count (325.000/mm3 ± 265.000/mm3 vs 267.000/mm3 ± 67.000/mm3; p=0.025; respectively) and plateletcrit (Pct) (0.25% ± 0.10 vs 0.21 ± 0.05; p<0.001; respectively) were increased in patients compared with healthy subjects while mean platelet volume (MPV) and platelet distribution width (PDW) were similar. The platelet indices were not related to existence of metastasis or acute abdomen. Platelet count and Pct, but not MPV and PDW, are elevated in colorectal cancer patients. Future studies that investigate platelet morphology, function, and putative role of platelets in tumorigenesis and metatasis should be established.
Prospective Controlled Trial of STAR Total Ankle Replacement versus Ankle Fusion: Initial Results
Authors: Saltzman Charles L. , Mann Roger A. , Ahrens Jeanette E. , Amendola Annunziato , Anderson Robert B. , Berlet Gregory C. , Brodsky James W. , Chou Loretta B. , Clanton Thomas O. , Deland Jonathan T. , DeOrio James K. , Horton Greg A. , Lee Thomas H. , Mann Jeffrey A. , Nunley James A. , Thordarson David B. , Walling Arthur K. , Wapner Keith L. , Coughlin Michael J.
Published: July 2009

Background:

Mobile-bearing ankle replacements have become popular outside of the United States over the past two decades. The goal of the present study was to perform a prospective evaluation of the safety and efficacy of a mobile-bearing prosthesis to treat end stage ankle arthritis. We report the results of three separate cohorts of patients: a group of Scandanavian Total Ankle Replacement (STAR) patients and a control group of ankle fusion patients (the Pivotal Study Groups) and another group of STAR total ankle patients (Continued Access Group) whose surgery was performed following the completion of enrollment in the Pivotal Study.

Materials and Methods:

The Pivotal Study design was a non-inferiority study using ankle fusion as the control. A non-randomized multi-centered design with concurrent fusion controls was used. We report the initial perioperative findings up to 24 months following surgery. For an individual patient to be considered an overall success, all of the following criteria needed to be met: a) a 40-point improvement in total Buechel-Pappas ankle score, b) no device failures, revisions, or removals, c) radiographic success, and d) no major complications. In the Pivotal Study (9/00 to 12/01), 158 ankle replacement and 66 arthrodesis procedures were performed; in the Continued Access Study (4/02 to 10/06), 448 ankle replacements were performed, of which 416 were at minimum 24 months post-surgery at time of the database closure.

Results:

Major complications and need for secondary surgical intervention were more common in the Pivotal Study arthroplasty group than the Pivotal Study ankle fusion group. In the Continued Access Group, secondary procedures performed on these arthroplasty patients decreased by half when compared with the Pivotal Arthroplasty Group. When the Pivotal Groups were compared, treatment efficacy was higher for the ankle replacement group due to improvement in functional scores. Pain relief was equivalent between fusion and replacement patients. The hypothesis of non-inferiority of ankle replacement was met for overall patient success.

Conclusion:

By 24 months, ankles treated with STAR ankle replacement (in both the Pivotal and Continued Access Groups) had better function and equivalent pain relief as ankles treated with fusion. Level of Evidence: II, Prospective Controlled Comparative Surgical Trial
Recombinant Bone Morphogenetic Protein-2 (rhBMP-2) in High-Risk Ankle and Hindfoot Fusions
Authors: Bibbo Christopher , Patel Dipak V. , Haskell Michelle D.
Published: July 2009

Background:

The purpose of this study was to evaluate the effect of rhBMP-2 on bone healing in patients who undergo high-risk ankle & hindfoot fusions.

Materials & Methods:

Patients who underwent high-risk, elective ankle and hindfoot fusions treated with rhBMP-2 augmentation were reviewed for clinical outcomes and complications. A total of 112 fusion sites (69 patients) were reviewed for analysis. The mean age of the patients was 52 years (range, 21 to 84 years). There were 37 males (53%) and 32 females (47%). Forty-four patients (64%) were smokers and 13 patients (19%) were diabetic. A history of high-energy trauma was present in 47 (68%) patients and avascular necrosis of the talus was present in 22 patients (32%). Forty-five patients (65%) had multiple risk-factors. The exclusion criteria were peripheral vascular disease, infection, and patients who were not available for the usual follow-up protocol. Internal and/or external fixation was utilized for ankle and hindfoot fusions. Bone graft was used only for patients who had defects or malalignment. Postoperatively, nonweightbearing radiographs were taken every 2 to 4 weeks (3 views per site). When plain radiographic union was evident, a confirmatory CT scan was obtained.

Results:

Overall, 108 fusion sites went on to union (96% union rate) at a mean time of 11 weeks (as assessed by a CT scan) [ankle joint at 10 weeks; subtalar joint at 12.3 weeks; talonavicular joint at 12.7 weeks and calcaneocuboid joint at 10.9 weeks]. Different union times between ankle, subtalar, talonavicular, and calcaneocuboid joint were not significant ( p = 0.2571, Kruskal-Wallis Test Nonparametric ANOVA). All sites: [No graft] vs. [Autograft] vs. [Allograft]: p = 0.2421 (Kruskal-Wallis Test Nonparametric ANOVA), were not statistically significant. Complications included nonunion in 5 of 112 joints in 3 patients (4% joint nonunion rate; 4% patient nonunion rate) [subtalar joint, n = 2; talonavicular joint, n = 1; and calcaneocuboid joint, n = 1]. Two patients had wound complications and one other patient had a deep infection; all were successfully treated with local wound care, negative-pressure dressings and antibiotics.

Conclusion:

We believe rhBMP-2 is an effective adjunct for bone healing in patients who undergo high-risk ankle and hindfoot fusions. Low complication rates were observed in this study. Level of Evidence: IV, Retrospective Case Series
Correlation of Harris Mats, Physical Exam, Pictures, and Radiographic Measurements in Adult Flatfoot Deformity
Authors: Coughlin Michael J. , Kaz Ari
Published: July 2009

Introduction:

In many reports describing flatfoot deformities, the abnormality is described using observations from physical examination, radiographs, or foot imprints. Correlation of these measurements is often lacking, making determination of the magnitude of the deformity or its surgical correction difficult to quantify.

Material and Methods:

Weightbearing AP and lateral radiographs were obtained on 25 patients (39 feet) with a clinically apparent flatfoot deformity and an asymptomatic control group of 28 subjects (56 feet). Radiographs were examined for the lateral talometatarsal angle, the lateral talocalcaneal angle, calcaneal pitch, first metatarsocuneiform height, medial cuneiform -fifth metatarsal height, metatarsus primus elevatus, plantar gapping at the first metatarsocuneiform joint, the AP talonavicular coverage angle, and the metatarsus adductus angle. Harris mat imprints were obtained on each foot and measured for the magnitude of the flatfoot deformity. Physical examination included the subjective appearance to the examiner of the degree of pes planus (none, mild, moderate, severe), hindfoot valgus, and ankle range of motion. Photographs of the hindfoot were obtained in a standardized manner, and hindfoot valgus was measured from these photos and compared to the measured hindfoot valgus on the physical exam.

Results:

Statistically significant differences between the two groups were found in the lateral talometatarsal angle, lateral talocalcaneal angle, calcaneal pitch, first metatarsocuneiform height, the AP talonavicular coverage angle, Harris mat imprint score, subjective pes planus score, hindfoot valgus measurement from both photographs and physical examination, ankle range of motion (all with a p value less than 0.01), and the metatarsus adductus angle ( p = 0.019). No patient in the control group and 14 (36%) in the flatfoot group had evidence of plantar gapping at the first metatarsocuneiform joint. In the flatfoot group, statistically significant correlations were demonstrated between the Harris mat score and heel valgus as measured by photographic and physical examination, subjective pes planus grading by physical exam, the lateral talometatarsal angle, and the first metatarsocuneiform height.

Conclusion:

This study validates the use of the Harris mat imprint as an effective method of quantifying the magnitude of a flatfoot deformity. We also found a statistically significant decrease in ankle range of motion in the flatfoot group, indicating that tightness of the gastrocsoleus complex is part of the pathophysiology of flatfoot deformity. Level of Evidence: III, Case Control Study