bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women
Authors: Hittel Dustin S. , Berggren Jason R. , Shearer Jane , Boyle Kristen , Houmard Joseph A. 
Published: October 2008

OBJECTIVE—Obesity is associated with endocrine abnormalities that predict the progression of insulin resistance to type 2 diabetes. Because skeletal muscle has been shown to secrete proteins that could be used as biomarkers, we characterized the secreted protein profile of muscle cells derived from extremely obese (BMI 48.8 ± 14.8 kg/m2; homeostasis model assessment [HOMA] 3.6 ± 1.0) relative to lean healthy subjects (BMI 25.7 ± 3.2 kg/m2; HOMA 0.8 ± 0.2).RESEARCH DESIGN AND METHODS—We hypothesized that skeletal muscle would secrete proteins that predict the severity of obesity. To test this hypothesis, we used a “bottom-up” experimental design using stable isotope labeling by amino acids in culture (SILAC) and liquid chromatography/mass spectometry/mass spectometry (LC-MS/MS) to both identify and quantify proteins secreted from cultured myotubes derived from extremely obese compared with healthy nonobese women.RESULTS—Using SILAC, we discovered a 2.9-fold increase in the secretion of myostatin from extremely obese human myotubes. The increased secretion and biological activity of myostatin were validated by immunoblot (3.16 ± 0.18, P &lt; 0.01) and a myoblast proliferation assay using conditioned growth medium. Myostatin was subsequently shown to increase in skeletal muscle (23%, P &lt; 0.05) and plasma (35%, P &lt; 0.05) and to correlate (r2 = 0.6, P &lt; 0.05) with the severity of insulin resistance.CONCLUSIONS—Myostatin is a potent antianabolic regulator of muscle mass that may also play a role in energy metabolism. These findings show that increased expression of myostatin in skeletal muscle with obesity and insulin resistance results in elevated circulating myostatin. This may contribute to systemic metabolic deterioration of skeletal muscle with the progression of insulin resistance to type 2 diabetes.
Effects of the Selective Serotonin Reuptake Inhibitor Fluoxetine on Counterregulatory Responses to Hypoglycemia in Individuals With Type 1 Diabetes
Authors: Briscoe Vanessa J. , Ertl Andrew C. , Tate Donna B. , Davis Stephen N. 
Published: October 2008

OBJECTIVE—Previous work has demonstrated that chronic administration of the serotonin reuptake inhibitor (SSRI) fluoxetine augments counterregulatory responses to hypoglycemia in healthy humans. However, virtually no information exists regarding the effects of fluoxetine on integrated physiological counterregulatory responses during hypoglycemia in type 1 diabetes. Therefore, the specific aim of this study was to test the hypothesis that 6-week use of the SSRI fluoxetine would amplify autonomic nervous system (ANS) counterregulatory responses to hypoglycemia in individuals with type 1 diabetes.RESEARCH DESIGN AND METHODS—Eighteen type 1 diabetic patients (14 men/4 women aged 19–48 years with BMI 25 ± 3 kg/m2 and A1C 7.0 ± 0.4%) participated in randomized, double-blind 2-h hyperinsulinemic (9 pmol · kg−1 · min−1)-hypoglycemic clamp studies before and after 6 weeks of fluoxetine administration (n = 8) or identical placebo (n = 10). Glucose kinetics was determined by 3-tritiated glucose. Muscle sympathetic nerve activity (MSNA) was determined by microneurography.RESULTS—Hypoglycemia (2.8 ± 0.1 mmol/l) and insulinemia (646 ± 52 pmol/l) were similar during all clamp studies. ANS, neuroendocrine, and metabolic counterregulatory responses remained unchanged in the placebo group. However, fluoxetine administration significantly (P &lt; 0.05) increased key ANS (epinephrine, norepinephrine, and MSNA), metabolic (endogenous glucose production and lipolysis), and cardiovascular (systolic blood pressure) counterregulatory responses during hypoglycemia.CONCLUSIONS—This study has demonstrated that 6-week administration of the SSRI fluoxetine can amplify ANS and metabolic counterregulatory mechanisms during moderate hypoglycemia in patients with type 1 diabetes. These data also suggest that the use of fluoxetine may be useful in increasing epinephrine responses during hypoglycemia in clinical practice.
Depression: An Important Comorbidity With Metabolic Syndrome in a General Population
Authors: Dunbar James A. , Reddy Prasuna , Davis-Lameloise Nathalie , Philpot Benjamin , Laatikainen Tiina , Kilkkinen Annamari , Bunker Stephen J. , Best James D. , Vartiainen Erkki , Kai Lo Sing , Janus Edward D. 
Published: October 2008

OBJECTIVE—There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a sample representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components.
RESEARCH DESIGN AND METHODS—Three cross-sectional surveys including clinical health measures were completed in rural regions of Australia during 2004–2006. A stratified random sample (n = 1,690, response rate 48%) of men and women aged 25–84 years was selected from the electoral roll. Metabolic syndrome was defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale and psychological distress by the Kessler 10 measure.
RESULTS—Metabolic syndrome was associated with depression but not psychological distress or anxiety. Participants with the metabolic syndrome had higher scores for depression (n = 409, mean score 3.41, 95% CI 3.12–3.70) than individuals without the metabolic syndrome (n = 936, mean 2.95, 95% CI 2.76–3.13). This association was also present in 338 participants with the metabolic syndrome and without diabetes (mean score 3.37, 95% CI 3.06–3.68). Large waist circumference and low HDL cholesterol showed significant and independent associations with depression.
CONCLUSIONS—Our results show an association between metabolic syndrome and depression in a heterogeneous sample. The presence of depression in individuals with the metabolic syndrome has implications for clinical management.
Effect of Parental Type 2 Diabetes on Offspring With Type 1 Diabetes
Authors: Thorn Lena M. , Forsblom Carol , Wadén Johan , Söderlund Jenny , Rosengård-Bärlund Milla , Saraheimo Markku , Heikkilä Outi , Hietala Kustaa , Pettersson-Fernholm Kim , Ilonen Jorma , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: October 2008

OBJECTIVE—The purpose of this study was to study the association between a parental history of type 2 diabetes and the metabolic profile as well as the presence of the metabolic syndrome and diabetes complications in patients with type 1 diabetes.
RESEARCH DESIGN AND METHODS—This was a cross-sectional study design in 1,860 patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study (620 patients with and 1,240 age-matched patients without a parental history of type 2 diabetes). Information on parental history was received from the type 1 diabetic offspring by a standardized questionnaire.
RESULTS—Patients with type 1 diabetes and a positive parental history of type 2 diabetes had a higher prevalence of the metabolic syndrome (44 vs. 38%; P = 0.013) and a metabolic profile related to insulin resistance (higher BMI, larger waist circumference, and higher triglycerides, A1C, and insulin dose per kilogram) and also had a later onset of type 1 diabetes (17.2 ± 9.2 vs. 16.1 ± 8.9 years; P = 0.008), which was also confirmed in the publicly available Diabetes Control and Complications Trial data set. In contrast, no association was observed with blood pressure, diabetes complications, or HLA genotype distribution. Parental history of type 2 diabetes was independently associated with age at onset of type 1 diabetes (odds ratio 1.02 [95% CI 1.01–1.03]), BMI (1.07 [1.02–1.12]), triglycerides (1.18 [1.03–1.35]), and insulin dose per kilogram (1.63 [1.04–2.54]).
CONCLUSIONS—Parental history of type 2 diabetes is associated with a later onset of type 1 diabetes, the metabolic syndrome, and a metabolic profile related to insulin resistance.
Increased Matrix Metalloproteinase-9 Predicts Poor Wound Healing in Diabetic Foot Ulcers
Authors: Liu Yu , Min Danqing , Bolton Thyra , Nubé Vanessa , Twigg Stephen M. , Yue Dennis K. , McLennan Susan V. 
Published: October 2008

OBJECTIVE—We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-ß1 (TGF-ß1) with wound healing rate.
RESEARCH DESIGN AND METHODS—The ulcers were cleansed to remove exudates, and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1, and TGF-ß1.
RESULTS—At presentation, MMP-9 and the MMP-9–to–TIMP-1 ratio correlated inversely with the wound healing rate at 28 days (P &lt; 0.001). MMP-9 and the MMP-9–to–TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 who did not. The pro–MMP-9 concentration was predictive of healing within 12 weeks. Addition of cutoffs for TIMP-1 (&gt;480 pg/ml) and TGF-ß (&gt;115 pg/ml) further improved its predictive power (area under the curve 0.94).
CONCLUSIONS—These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1, and TGF-ß in wound fluid may help to identify ulcers at risk of poor healing.
Physical Activity May Facilitate Diabetes Prevention in Adolescents
Authors: Thomas Amy S. , Greene Lori F. , Ard Jamy D. , Oster Robert A. , Darnell Betty E. , Gower Barbara A. 
Published: October 2008

OBJECTIVE—The aim of this study was to examine the association of physical activity with glucose tolerance and resting energy expenditure (REE) among adolescents.
RESEARCH DESIGN AND METHODS—Subjects were 32 male and female adolescents aged 12–18 years. Intravenous glucose tolerance (Kg) and REE were assessed under inpatient conditions after an overnight fast. Kg was determined as the inverse slope of time versus (ln) glucose over minutes 8–19 of an intravenous glucose tolerance test. Physical activity was assessed over 8 days using accelerometry (counts per minute).
RESULTS—In multiple linear regression analysis, Kg was positively associated with total physical activity (TPA), moderate physical activity (MPA), and 5-min bouts of MPA. Similarly, REE was positively associated with TPA, MPA, and 5-min bouts of MPA.
CONCLUSIONS—In this population, physical activity was positively related to both glucose tolerance and REE. These results suggest that moderate activity may be beneficial in the prevention of diabetes in adolescent populations both through promoting efficient glucose disposal and through increasing energy expenditure.
Insulin Gene Mutations as Cause of Diabetes in Children Negative for Five Type 1 Diabetes Autoantibodies
Authors: Bonfanti Riccardo , Colombo Carlo , Nocerino Valentina , Massa Ornella , Lampasona Vito , Iafusco Dario , Viscardi Matteo , Chiumello Giuseppe , Meschi Franco , Barbetti Fabrizio 
Published: October 2008

OBJECTIVE—Heterozygous, gain-of-function mutations of the insulin gene can cause permanent diabetes with onset ranging from the neonatal period through adulthood. The aim of our study was to screen for the insulin gene in patients who had been clinically classified as type 1 diabetic but who tested negative for type 1 diabetes autoantibodies.
RESEARCH DESIGN AND METHODS—We reviewed the clinical records of 326 patients with the diagnosis of type 1 diabetes and identified seven probands who had diabetes in isolation and were negative for five type 1 diabetes autoantibodies. We sequenced the INS gene in these seven patients.
RESULTS—In two patients whose diabetes onset had been at 2 years 10 months of age and at 6 years 8 months of age, respectively, we identified the mutation GB8S and a novel mutation in the preproinsulin signal peptide (ASignal23S).
CONCLUSIONS—Insulin gene mutations are rare in absolute terms in patients classified as type 1 diabetic (0.6%) but can be identified after a thorough screening of type 1 diabetes autoantibodies.
Biophysical Correlates of Cognition Among Depressed and Nondepressed Type 2 Diabetic Patients
Authors: Elderkin-Thompson Virginia , Hellemann Gerhard , Gupta Rakesh K. , Kumar Anand 
Published: October 2008

OBJECTIVE—Caudate magnetization transfer (MT) ratios have indicated an abnormality in the macromolecular protein pool of diabetic patients. This study examined the relationship between MT ratios of the caudate and cognitive performance.
RESEARCH DESIGN AND METHODS—Diabetic patients, diabetic and depressed patients, and healthy comparison subjects completed magnetic resonance imaging and a neuropsychological battery. Magnetization transfer ratios of caudate and three comparison regions were computed. The neuropsychological battery was aggregated into a global index of cognitive function and correlated with MT ratios.
RESULTS—MT ratios of the caudate correlated with cognitive performance, and the correlations were stronger among diabetic patients than healthy control subjects. Comorbid depression increased the strength of the correlation compared with diabetes alone. Comparison regions showed no evidence of a diabetes effect on cognition.
CONCLUSIONS—One mechanism precipitating cognitive loss during diabetes appears to be associated with cellular changes occurring in the macromolecular protein pool of the caudate.
Adult Metabolic Syndrome and Impaired Glucose Tolerance Are Associated With Different Patterns of BMI Gain During Infancy
Authors: Fall Caroline H.D. , Sachdev Harshpal Singh , Osmond Clive , Lakshmy Ramakrishnan , Biswas Sushant Dey , Prabhakaran Dorairaj , Tandon Nikhil , Ramji Siddharth , Reddy K. Srinath , Barker David J.P. , Bhargava Santosh K. 
Published: October 2008

OBJECTIVE—The purpose of this study was to describe patterns of infant, childhood, and adolescent BMI and weight associated with adult metabolic risk factors for cardiovascular disease.
RESEARCH DESIGN AND METHODS—We measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III definition) in 1,492 men and women aged 26–32 years in Delhi, India, whose weight and height were recorded every 6 months throughout infancy (0–2 years), childhood (2–11 years), and adolescence (11 years–adult).
RESULTS—Men and women with metabolic syndrome (29% overall), any of its component features, or higher (greater than upper quartile) insulin resistance (homeostasis model assessment) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood, and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence but with lower BMI in infancy.
CONCLUSIONS—In this Indian population, patterns of infant BMI and weight gain differed for individuals who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders.
Differential Effects of Two Isoenergetic Meals Rich in Saturated or Monounsaturated Fat on Endothelial Function in Subjects With Type 2 Diabetes
Authors: Tentolouris Nicholas , Arapostathi Christina , Perrea Despoina , Kyriaki Despoina , Revenas Constantinos , Katsilambros Nicholas 
Published: October 2008

OBJECTIVE—To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes.
RESEARCH DESIGN AND METHODS—A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD).
RESULTS—FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 ± 2.5% and decreased after the SAFA-rich meal by 16.7 ± 6.0% (Δ = −11.5 ± 6.4%; P = 0.008).
CONCLUSIONS—Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.
Improved Carbohydrate Metabolism After Bariatric Surgery Raises Antioxidized LDL Antibody Levels in Morbidly Obese Patients
Authors: Garrido-Sánchez Lourdes , García-Almeida Jose M. , García-Serrano Sara , Cardona Isabel , García-Arnes Juan , Soriguer Federico , Tinahones Francisco J. , García-Fuentes Eduardo 
Published: October 2008

OBJECTIVE—Antioxidized LDL (anti-oxLDL) antibodies have recently been suggested to be protective against the development of diabetes. We measured the changes in anti-oxLDL antibody levels in the inverse situation of improvement in carbohydrate metabolism.
RESEARCH DESIGN AND METHODS—The study was undertaken in 73 morbidly obese individuals, 21 of whom had type 2 diabetes, before and 7 months after they underwent bariatric surgery and in 11 healthy, nonobese individuals. Measurements were made of the area under the curve of glucose (AUCGlu) by an intravenous glucose tolerance test and of oxidized LDL (oxLDL) and IgG and IgM anti-oxLDL antibodies.
RESULTS—The morbidly obese patients with diabetes had significantly higher levels of oxLDL compared with the morbidly obese patients with normal fasting glucose and the control subjects and significantly lower levels of IgM anti-oxLDL antibodies. An inverse correlation was found between the levels of oxLDL and IgM anti-oxLDL antibodies (r = −0.352, P = 0.012). Although the levels of IgG and IgM anti-oxLDL antibodies rose after surgery, this increase was only significant in the diabetic patients, who experienced an improvement in their metabolic profile. Different multiple linear regression models showed that the AUCGlu was the main factor explaining the behavior of the levels of oxLDL and anti-oxLDL antibodies.
CONCLUSIONS—We found a close association between carbohydrate metabolism and IgM anti-oxLDL antibodies, which were significantly reduced in the morbidly obese patients with diabetes. The improvement in carbohydrate metabolism after bariatric surgery led to a significant increase in the levels of IgG and IgM anti-oxLDL antibodies.
In Vivo Insulin Sensitivity and Secretion in Obese Youth
Authors: Bacha Fida , Gungor Neslihan , Lee SoJung , Arslanian Silva A. 
Published: October 2008

OBJECTIVE—Impaired glucose tolerance (IGT) represents a pre-diabetic state. Controversy continues in regards to its pathophysiology. The aim of this study was to investigate the differences in insulin sensitivity (IS) and secretion in obese adolescents with IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes.
RESEARCH DESIGN AND METHODS—A total of 12 obese adolescents with NGT, 19 with IGT, and 17 with type 2 diabetes underwent evaluation of insulin sensitivity (3-h hyperinsulinemic [80mu/m2/min]–euglycemic clamp), first-phase insulin and second-phase insulin secretion (2-h hyperglycemic clamp), body composition, and abdominal adiposity. Glucose disposition index (GDI) was calculated as the product of first-phase insulin × insulin sensitivity.
RESULTS—Insulin-stimulated glucose disposal was significantly lower in subjects with type 2 diabetes compared with subjects with NGT and IGT, with no difference between the latter two. However, compared with youth with NGT, youth with IGT have significantly lower first-phase insulin and C-peptide levels and GDI (P = 0.012), whereas youth with type 2 diabetes have an additional defect in second-phase insulin. Fasting and 2-h glucose correlated with GDI (r = −0.68, P &lt; 0.001 and r = −0.73, P &lt; 0.001, respectively) and first-phase insulin but not with insulin sensitivity.
CONCLUSIONS—Compared with youth with NGT, obese adolescents with IGT have evidence of a β-cell defect manifested in impaired first-phase insulin secretion, with a more profound defect in type 2 diabetes involving both first- and second-phase insulin. GDI shows a significantly declining pattern: it is highest in NGT, intermediate in IGT, and lowest in type 2 diabetes. Such data suggest that measures to prevent progression or conversion from pre-diabetes to type 2 diabetes should target improvement in β-cell function.
A Randomized Trial of Low-Dose Aspirin in the Prevention of Clinical Type 2 Diabetes in Women
Authors: Pradhan Aruna D. , Cook Nancy R. , Manson JoAnn E. , Ridker Paul M. , Buring Julie E. 
Published: October 2008

OBJECTIVE—Subclinical inflammation is linked with the development of type 2 diabetes, and epidemiologic data suggest that this association may be stronger in women. Although small clinical studies have shown a prominent hypoglycemic effect of short-term high-dose aspirin, no randomized trials have directly evaluated the efficacy of aspirin in diabetes prevention at doses acceptable for use in routine clinical practice. We evaluated whether chronic low-dose aspirin prevents the development of clinical diabetes among initially healthy American women.
RESEARCH DESIGN AND METHODS—Subjects were enrolled in the Women's Health Study, a 10-year randomized double-blind, placebo-controlled trial of aspirin and vitamin E for primary prevention of cardiovascular disease and cancer. Between 1992 and 1995, 38,716 women aged ≥45 years and free of clinical diabetes were randomly assigned to either low-dose aspirin or placebo (median follow-up 10.2 years). Documented clinical type 2 diabetes was prospectively evaluated throughout the trial.
RESULTS—Among women randomly assigned to receive aspirin (n = 19,326) or placebo (n = 19,390), there was no statistically significant difference in the incidence of type 2 diabetes. There were 849 cases of diabetes in the aspirin group and 847 in the placebo group (rate ratio 1.01 [95% CI 0.91–1.11]). Stratification by diabetes risk factors including age, BMI, family history of diabetes, physical activity, A1C, and high-sensitivity C-reactive protein did not support a modulating effect of these variables. Analyses accounting for treatment duration and adherence similarly found no beneficial effects.
CONCLUSIONS—These data suggest that long-term low-dose aspirin does not prevent the development of clinical type 2 diabetes in initially healthy women.