bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-Response Effect of Pioglitazone on Insulin Sensitivity and Insulin Secretion in Type 2 Diabetes
Authors: Miyazaki Yoshinori , Matsuda Masafumi , DeFronzo Ralph A. 
Published: March 2007

OBJECTIVE—To investigate the dose-response effects of pioglitazone on glycemic control, insulin sensitivity, and insulin secretion in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—A total of 58 diet-treated patients with type 2 diabetes (aged 54 ±1 years; 34 men and 24 women; BMI 31.5± 0.6 kg/m2) were randomly assigned to receive placebo (n=11) or 7.5 mg (n=13), 15 mg (n=12), 30 mg (n=11), or 45 mg (n=11) of pioglitazone per day for 26 weeks. Before and after 26 weeks, subjects underwent a 75-g oral glucose tolerance test (OGTT).
RESULTS—Patients treated with 7.5 or 15 mg/day of pioglitazone had no change in fasting plasma glucose (FPG) and fasting plasma insulin (FPI) concentrations or in plasma glucose (PG) and insulin concentrations during the OGTT. Patients treated with 30 and 45 mg/day of pioglitazone, respectively, had significant decreases from placebo in HbA1c (Δ=−2.0 and −2.9%), FPG (Δ=−66 and −97 mg/dl), and mean PG during OGTT (Δ=−84 and −107 mg/dl). Fasting plasma insulin decreased significantly in the 45-mg/day pioglitazone group, but the mean plasma insulin during the OGTT did not change. The insulinogenic index (Δ area under the curve [AUC] insulin/ΔAUC glucose) during the OGTT increased significantly in the 30- and 45-mg/day pioglitazone groups (0.13± 0.03 to 0.27± 0.05, P &lt; 0.05). From the OGTT, we previously have derived a composite whole-body insulin sensitivity index (ISI) that correlates well with that measured directly with the insulin clamp technique. Whole-body ISI [ISI=10,000 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\sqrt{(FPG{\times}FPI){\times}(\overline{PG}{\times}\overline{PI})}\) \end{document}, where P̅G̅ and P̅I̅ equal mean plasma glucose and insulin concentrations during OGTT] increased significantly in patients treated with 30 mg (1.8± 0.3 to 2.5± 0.3, P &lt; 0.05) or 45 mg (1.6± 0.2 to 2.7± 0.6, P &lt; 0.05) per day of pioglitazone. In the basal state, the hepatic ISI [k/(FPG × FPI)[k/(FPG × FPI)], which agrees closely with that measured directly with tritiated glucose, increased in patients treated with 30 mg (0.13± 0.02 to 0.21± 0.03, P &lt; 0.05) and 45 mg (0.11± 0.02 to 0.24± 0.06, P &lt; 0.05) per day of pioglitazone. Significant correlations between the dose of pioglitazone and the changes in HbA1c (r=−0.58), FPG (r=−0.47), mean PG during the OGTT (r=−0.46), insulinogenic index (r=0.34), hepatic ISI (r=0.44), and whole-body ISI (r=0.36) were observed.
CONCLUSIONS—Pioglitazone improves glycemic control through the dose-dependent enhancement of β-cell function and improved whole-body and hepatic insulin sensitivity.
α-Tocopherol Supplementation Decreases Plasminogen Activator Inhibitor-1 and P-Selectin Levels in Type 2 Diabetic Patients
Authors: Devaraj Sridevi , Chan Alberto V. Cabo , Jialal Ishwarlal 
Published: March 2007

OBJECTIVE—Type 2 diabetic subjects have an increased propensity to premature atherothrombosis. α-Tocopherol (AT), a potent antioxidant, has anti-inflammatory properties at high doses. The aim of the study was to test the effect of natural (RRR)-AT supplementation (1,200 IU/day) on markers of thrombosis, plasminogen activator inhibitor-1 (PAI-1), and soluble P-selectin (sP-selectin) in type 2 diabetic patients with and without macrovascular complications (MVCs) compared with matched control subjects.
RESEARCH DESIGN AND METHODS—The volunteers comprised type 2 diabetic patients with (n=23) and without (n=24) MVCs and matched control subjects (n=25). Plasma levels of PAI-1 and P-selectin were assayed at baseline, after 3 months of supplementation, and after a 2-month washout phase.
RESULTS—Both diabetic groups had significantly increased levels of PAI-1 compared with control subjects (P &lt; 0.025), whereas only type 2 diabetic patients with MVCs had significantly elevated levels of sP-selectin compared with control subjects. AT supplementation significantly lowered levels of PAI-1 and sP-selectin in all three groups. The reduction in PAI-1 levels with AT supplementation was significantly greater in type 2 diabetic patients with MVCs than in those without MVCs (P=0.005).
CONCLUSIONS—Thus, AT therapy decreases markers of thrombosis in diabetic patients and control subjects and could be an adjunctive therapy in the prevention of atherosclerosis.
Comorbidities and Impairments Explaining the Association Between Diabetes and Lower Extremity Disability
Authors: Volpato Stefano , Blaum Caroline , Resnick Helaine , Ferrucci Luigi , Fried Linda P. , Guralnik Jack M. 
Published: March 2007

OBJECTIVE—To elucidate the role of diabetes-related impairments and comorbidities in the association between diabetes and physical disability, this study examined the association between diabetes and lower extremity function in a sample of disabled older women.
RESEARCH DESIGN AND METHODS—Cross-sectional analysis of 1,002 women (aged ≥65 years) enrolled in the Women’s Health and Aging Study (one-third most disabled of the total community-dwelling population). Diabetes and other medical conditions were ascertained by standard criteria that used multiple sources of information. Functional status was assessed using self-reported and objective performance measures.
RESULTS—Women with diabetes were significantly more likely to have cardiovascular diseases, peripheral nerve dysfunction, visual impairment, obesity, and depression. After adjustment for age, women with diabetes had a greater prevalence of mobility disability (odds ratio [OR] 1.85, 95% CI 1.12–3.06), activities of daily living disability (1.61, 1.06–2.43), and severe walking limitation (2.34, 1.56–3.50), and their summary mobility performance score (0–12 scale based on balance, gait speed, chair stands) was 1.4 points lower than in nondiabetic women (P &lt; 0.001). Peripheral artery disease, peripheral nerve dysfunction, and depression were the main individual contributing factors; however, none of these conditions alone fully explained the association between diabetes and disability. Conversely, only after adjusting for all potential mediators was the relationship between diabetes and disability reduced to a large degree.
CONCLUSIONS—Even among physically impaired older women, diabetes is associated with a major burden of disability. A wide range of impairments and comorbidities explains the diabetes-disability relationship, suggesting that the mechanism for such an association is multifactorial.
A Prospective, Randomized Comparison of the Metabolic Effects of Pioglitazone or Rosiglitazone in Patients With Type 2 Diabetes Who Were Previously Treated With Troglitazone
Authors: Khan Mehmood A. , St. Peter John V. , Xue Jay L. 
Published: March 2007

OBJECTIVE—To characterize potential differences in glycemic control, plasma lipid level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone or rosiglitazone.RESEARCH DESIGN AND METHODS—After a 2-week washout from TROG, 186 patients were randomly assigned to receive either pioglitazone (PIO) or rosiglitazone (ROSI). Weight, HbA1c, and fasting lipid profile were documented before discontinuing TROG and at 4 months after starting either pioglitazone or rosiglitazone. Secondarily, the effect of concurrent medications on study outcomes was assessed.RESULTS—A total of 127 patients completed follow-up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA1c between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA1c from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of ∼2.0 kg. Thiazolidinedione and HMG-CoA reductase inhibitor therapy had significant and independent effects on lipid profile (P &lt; 0.005). Significant improvements in lipid profile were noted in the PIO group (P &lt; 0.01), whereas none were detected with conversion to ROSI. Specifically, the PIO group experienced an average decrease in total cholesterol of ∼20 mg/dl.CONCLUSIONS—Differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted.
Control of Cardiovascular Risk Factors in Patients With Diabetes and Hypertension at Urban Academic Medical Centers
Authors: McFarlane Samy I. , Jacober Scott J. , Winer Nathaniel , Kaur Jasjeet , Castro Jonathan P. , Wui MaryLou A. , Gliwa Agnes , Von Gizycki Hans , Sowers James R. 
Published: March 2007

OBJECTIVE—There are national mandates to reduce blood pressure (BP) to &lt;130/85 mmHg, LDL cholesterol to &lt;100 mg/dl, and HbA1c to &lt;7% and to institute aspirin therapy in patients with diabetes. The objective of this study was to determine the proportion of patients in urban institutions with diabetes and hypertension who meet these treatment goals.
RESEARCH DESIGN AND METHODS—Using American Diabetes Association (ADA) guidelines, we evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics.
RESULTS—Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9%) had type 2 diabetes, and 26.7% met the target blood pressure of 130/85 mmHg. A total of 35.5% met the goal LDL cholesterol level of &lt;100 mg/dl, 26.7% had an HbA1c &lt;7%, and 45.6% were on antiplatelet therapy. Only 3.2% of patients met the combined ADA goal for BP, LDL cholesterol, and HbA1c.
CONCLUSIONS—Optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in our present health care systems.
Interpersonal Predictors of HbA1c in Patients With Type 1 Diabetes
Authors: Ciechanowski Paul S. , Hirsch Irl B. , Katon Wayne J. 
Published: March 2007

OBJECTIVE—Research suggests that increased collaboration and satisfaction in the patient-provider relationship is associated with better outcomes in patients with diabetes. In adults, an interpersonal style characterized by low trust of others and excessive self-reliance is known as “dismissing attachment style.” We hypothesized that diabetic patients with dismissing attachment style, due to a decreased ability to collaborate with providers and others, would have significantly higher HbA1c levels than patients with secure attachment style.
RESEARCH DESIGN AND METHODS—From 276 adult tertiary care patients with type 1 diabetes, we obtained mean HbA1c levels over the prior year and assessed patient attachment style, demographics, and clinical characteristics. We used χ2 tests and logistic regression to determine whether attachment style was associated with HbA1c levels.
RESULTS—We found that 62% of patients with dismissing attachment style had mean HbA1c levels ≥8% compared with 34% of patients with secure attachment style (P = 0.002). After adjusting for demographics, diabetes severity, medical comorbidity, and depression, dismissing attachment style remained significantly associated with HbA1c levels ≥8%, compared with secure attachment style (odds ratio 2.5, 95% CI 1.1–6.0).
CONCLUSIONS—We have found that dismissing attachment style is associated with a higher risk for poor glycemic control. This has relevance from a population-based perspective because ∼25% of the general population has a dismissing attachment style. Attachment style is easily measured using self-report instruments and may inform clinicians how to work with patients who are less engaged in the health care relationship.
Five-Week, Low–Glycemic Index Diet Decreases Total Fat Mass and Improves Plasma Lipid Profile in Moderately Overweight Nondiabetic Men
Authors: Bouché Clara , Rizkalla Salwa W. , Luo Jing , Vidal Hubert , Veronese Annie , Pacher Nathalie , Fouquet Caroline , Lang Vincent , Slama Gérard 
Published: March 2007

OBJECTIVE—To evaluate whether a 5-week low–glycemic index (LGI) diet versus a high–glycemic index (HGI) diet can modify glucose and lipid metabolism as well as total fat mass in nondiabetic men.
RESEARCH DESIGN AND METHODS—In this study, 11 healthy men were randomly allocated to 5 weeks of an LGI or HGI diet separated by a 5-week washout interval in a crossover design.
RESULTS—The LGI diet resulted in lower postprandial plasma glucose and insulin profiles and areas under the curve (AUCs) than the HGI diet. A 5-week period of the LGI diet lowered plasma triacylglycerol excursion after lunch (AUC, P &lt; 0.05 LGI vs. HGI). These modifications were associated with a decrease in the total fat mass by ∼700 g (P &lt; 0.05) and a tendency to increase lean body mass (P &lt; 0.07) without any change in body weight. This decrease in fat mass was accompanied by a decrease in leptin, lipoprotein lipase, and hormone-sensitive lipase RNAm quantities in the subcutaneous abdominal adipose tissue (P &lt; 0.05).
CONCLUSIONS—We concluded that 5 weeks of an LGI diet ameliorates some plasma lipid parameters, decreases total fat mass, and tends to increase lean body mass without changing body weight. These changes were accompanied by a decrease in the expression of some genes implicated in lipid metabolism. Such a diet could be of benefit to healthy, slightly overweight subjects and might play a role in the prevention of metabolic diseases and their cardiovascular complications.
Inhibition of Dipeptidyl Peptidase IV Improves Metabolic Control Over a 4-Week Study Period in Type 2 Diabetes
Authors: Ahrén Bo , Simonsson Erik , Larsson Hillevi , Landin-Olsson Mona , Torgeirsson Hlin , Jansson Per-Anders , Sandqvist Madeléne , Båvenholm Peter , Efendic Suad , Eriksson Jan W. , Dickinson Sheila , Holmes David 
Published: March 2007

OBJECTIVE—Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1–degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.
RESEARCH DESIGN AND METHODS—A total of 93 patients (61 men and 32 women), aged 64 ± 9 years (means ± SD) and with BMI 27.3 ± 2.7 kg/m2, entered the study. Fasting blood glucose was 8.5 ± 1.5 mmol/l, and HbA1c was 7.4 ± 0.7%. Before and after treatment with NVP DPP728 at 100 mg × 3 (n = 31) or 150 mg × 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).
RESULTS—Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P &lt; 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA1c was reduced to 6.9 ± 0.7% in the combined active treatment groups (P &lt; 0.001). Laboratory safety and tolerability was good in all groups.
CONCLUSIONS—We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
UKPDS 59: Hyperglycemia and Other Potentially Modifiable Risk Factors for Peripheral Vascular Disease in Type 2 Diabetes
Authors: Adler Amanda I. , Stevens Richard J. , Neil Andrew , Stratton Irene M. , Boulton Andrew J. M. , Holman Rury R. ,   for the U.K. Prospective Diabetes Study Group
Published: March 2007

OBJECTIVE—To determine the role of hyperglycemia in prospective analyses of peripheral vascular disease (PVD) in type 2 diabetes, taking into account other potential risk factors.
RESEARCH DESIGN AND METHODS—Potential risk factors for the development of PVD were examined in 3,834 of 5,102 individuals enrolled in the U.K. Prospective Diabetes Study (UKPDS) without PVD at diagnosis of diabetes, followed for 6 years, and for whom relevant data were available. PVD was defined as two of the following: ankle-arm blood pressure index &lt;0.8, absence of both dorsalis pedis and posterior tibial pulses to palpation in one or both legs, and intermittent claudication. Logistic regression was used to estimate the association between potential risk factors measured 3–4 months after diagnosis of diabetes and incident PVD. The prevalence of PVD at 3-year intervals to 18 years was determined.
RESULTS—Hyperglycemia, assessed as HbA1c, was associated with an increased risk for incident PVD, independent of other risk factors including age, increased systolic blood pressure, reduced HDL cholesterol, smoking, prior cardiovascular disease, peripheral sensory neuropathy, and retinopathy. Each 1% increase in HbA1c was associated with a 28% increased risk of PVD (95% CI 12–46), and each 10-mmHg increase in systolic blood pressure with a 25% increase in risk (95% CI 10–43).
CONCLUSIONS—Hyperglycemia, as well as smoking, dyslipidemia, and blood pressure are potentially modifiable risk factors for the development of PVD.
Delayed Gastric Emptying and Gastric Autoimmunity in Type 1 Diabetes
Authors: De Block Christophe E.M. , De Leeuw Ivo H. , Pelckmans Paul A. , Callens Dirk , Máday Emöke , Van Gaal Luc F. 
Published: March 2007

OBJECTIVE—Delayed gastric emptying and/or gastrointestinal symptoms occur in 30–50% of diabetic patients. Known contributing factors are autonomic neuropathy and acute hyperglycemia, but the role of gastric autoimmunity has never been investigated, although 15–20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA status, autonomic nerve function, HbA1c, thyroid-stimulating hormone (TSH), Helicobacter pylori (HP), acid production, and gastric histology.
RESEARCH DESIGN AND METHODS—Gastric emptying of solids and liquids (measured by 13C-octanoic acid and 13C-glycine breath tests, respectively) was tested in euglycemic conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age 40 ± 15 years; mean HbA1c 7.8 ± 0.9%). Gastrointestinal symptoms, autonomic nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric histology, and acid secretion (pentagastrin) were assessed.
RESULTS—Solid gastric emptying was delayed in 40% and liquid emptying in 36% of patients. Gastric motility did not correlate with symptoms. PCA status, gastric morphology, and acid secretion were similar in those with and without gastroparesis. HbA1c level (β = 1.34, P = 0.011) was the only risk factor for delayed solid emptying in a logistic regression model testing HbA1c, autonomic nerve function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying time for liquids correlated with TSH level (r = 0.83, P &lt; 0.0001) and autonomic neuropathy score (r = −0.79, P = 0.001).
CONCLUSIONS—We found that ∼50% of type 1 diabetic patients studied had delayed gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. Metabolic control was worse in patients with delayed solid emptying.
Neurotrophic Factor Receptors in Epiretinal Membranes After Human Diabetic Retinopathy
Authors: Harada Takayuki , Harada Chikako , Mitamura Yoshinori , Akazawa Chihiro , Ohtsuka Kenji , Ohno Shigeaki , Takeuchi Shinobu , Wada Keiji 
Published: March 2007

OBJECTIVE—Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75NTR]; glial cell line–derived neurotrophic factor receptor-α1 [GFRα1] and GFRα2; and Ret) are involved in the formation of ERMs after PDR.
RESEARCH DESIGN AND METHODS—ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 ± 8 years with 17 ± 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 ± 18 years with 13 ± 4 years of diabetes were processed for immunohistochemical analysis.
RESULTS—Expressions of trkA, trkB, trkC, p75NTR, and Ret mRNAs were similar in both groups. In contrast, GFRα2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P &lt; 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFRα2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFRα1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects.
CONCLUSIONS—These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs.
Coronary Artery Disease and Carotid Artery Intima-Media Thickness in Japanese Type 2 Diabetic Patients
Authors: Mitsuhashi Naomi , Onuma Tomio , Kubo Sayaka , Takayanagi Naoko , Honda Motoe , Kawamori Ryuzo 
Published: March 2007

OBJECTIVE—To investigate the association between carotid atherosclerosis, measured as intima-media thickness (IMT), and cardiovascular morbidity in type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—We investigated the relationship between IMT and coronary artery disease (CAD) in 40 type 2 diabetic patients and 40 control subjects. Diabetic patients with CAD determined by coronary angiography were consecutively recruited, whereas the control subjects were recruited from among diabetic outpatients without CAD at the same institution. IMT was measured in both carotid arteries using B-mode ultrasonography.
RESULTS—Carotid IMT was significantly greater in the diabetic patients than in the control subjects (1.27 ± 0.07 vs. 1.03 ± 0.04 mm, P &lt; 0.05). IMT was associated with CAD by logistic regression analysis using all independent variables (P = 0.062). When the 40 patients with CAD were divided into a group of 20 patients with coronary artery bypass grafting (CABG) and another 20 patients without CABG, the IMT was significantly greater in the CABG group than in the non-CABG group (1.47 ± 0.11 vs. 1.07 ± 0.07 mm, P &lt; 0.05).
CONCLUSIONS—These results indicate that the presence of carotid atherosclerosis implies a high probability of coronary involvement in Japanese nonobese subjects with type 2 diabetes.