bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Efficacy of Orlistat Therapy in Overweight and Obese Patients With Insulin-Treated Type 2 Diabetes
Authors: Kelley David E. , Bray George A. , Pi-Sunyer F. Xavier , Klein Samuel , Hill James , Miles John , Hollander Priscilla 
Published: March 2007

OBJECTIVE—Weight loss improves glycemic control, lipid profiles, and blood pressure in patients with type 2 diabetes. However, successful long-term weight loss is difficult for these patients, particularly those treated with insulin. The aim of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on weight loss, glycemic control, and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—This study was a 1-year multicenter, randomized, double-blind, placebo-controlled trial of orlistat (120 mg three times a day) or placebo combined with a reduced-calorie diet in overweight or obese adults (BMI 28–40 kg/m2) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA1c 7.5–12.0%). Outcome measurements included changes in body weight, glycemic control, blood pressure, and serum lipids.
RESULTS—After 1 year, the orlistat group lost significantly more weight (−3.89 ± 0.3% of baseline body weight, means ± SE) than the placebo group (−1.27 ± 0.3%, P &lt; 0.001). Orlistat treatment, compared with placebo, produced greater decreases in HbA1c (−0.62 ± 0.08 vs. −0.27 ± 0.08%, P = 0.002), fasting serum glucose (−1.63 ± 0.3 vs. −1.08 ± 0.3 mmol/l, P = 0.02), and the required doses of insulin and other diabetic medications. Orlistat also produced greater improvements than placebo in serum total cholesterol (P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and LDL/HDL ratio (P = 0.01).
CONCLUSIONS—Orlistat therapy produces clinically significant weight loss, with improvements in glycemic control and cardiovascular disease risk factors, in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy.
Elimination of Dietary Gluten Does Not Reduce Titers of Type 1 Diabetes-Associated Autoantibodies in High-Risk Subjects
Authors: Hummel Michael , Bonifacio Ezio , Naserke Heike E. , Ziegler Anette G. 
Published: March 2007

OBJECTIVE—Removal of the dietary wheat protein gluten protects against autoimmune diabetes in animal models. Furthermore, elimination of dietary gluten reduces the frequency of type 1 diabetes in patients with celiac disease. Herein we test the hypothesis that gluten is the driving antigen for type 1 diabetes-associated islet autoimmunity.RESEARCH DESIGN AND METHODS—Seven autoantibody-positive, first-degree relatives of patients with type 1 diabetes were placed on a gluten-free diet for 12 months followed by gluten reexposure for 12 months. Gliadin antibodies as well as the diabetes-related antibodies insulin autoantibody (IAA), GAD antibody (GADA), and tyrosin phosphatase IA2 antibody (IA-2A) were measured every 3 months; oral glucose tolerance tests were performed every 6 months. Changes in autoantibody titers were compared with those observed in a matched historical cohort.RESULTS—A reduction in IgG gliadin antibody titers was observed during the gluten-free period, but titers of diabetes-associated autoantibodies changed independently of gluten exposure. Type 1 diabetes-associated islet autoantibody levels at the end of the gluten-free diet period were not significantly different from those before commencement of the diet (P = 0.2) or at the end of the gluten reexposure period (P = 0.4). Changes in individual subjects were identified, but no differences were noted between the gluten-free and the gluten re-exposure periods, and the changes were similar to those observed in the historical control cohort (P = 1.0). Major titer reductions (&gt;50%) in the gluten-free period were observed in only one subject for all antibodies. Type 1 diabetes developed in this subject and in a second subject during the gluten reexposure period.CONCLUSIONS—The findings do not support the hypothesis that gluten is a driving antigen in type 1 diabetes.
A Longitudinal Study of the Effects of a Gluten-Free Diet on Glycemic Control and Weight Gain in Subjects With Type 1 Diabetes and Celiac Disease
Authors: Amin Rakesh , Murphy Nuala , Edge Julie , Ahmed Marion L. , Acerini Carlo L. , Dunger David B. 
Published: March 2007

OBJECTIVE—To describe the longitudinal growth characteristics and glycemic control in type 1 diabetic children diagnosed with celiac disease and started on a gluten-free diet (GFD).
RESEARCH DESIGN AND METHODS—Data on growth and glycemic control for 11 case subjects diagnosed with celiac disease (cd+ group) and started on a GFD were collected prospectively, and two control subjects without celiac disease matched for age, sex, and duration of diabetes (cd− group) were selected for comparison.
RESULTS—In the period between diagnosis of type 1 diabetes and start of a GFD in the cd+ compared with the cd− group, BMI standard deviation score (SDS) was lower (–0.2 vs. 0.7, P = 0.015), as was HbA1c (8.9 vs. 9.8%, P = 0.002). In a regression model the cd+ group had lower BMI SDS (P &lt; 0.001) and lower HbA1c (P = 0.04), independent of other variables. On a GFD, BMI SDS increased by 12 months in the cd+ group and then was no different than the cd− group (1.1 vs. 1.0, P = 0.11), whereas HbA1c improved further within case subjects compared with pre-GFD (8.9 vs. 8.3%, P = 0.002). On a GFD, case subjects in contrast to control subjects showed no deterioration in HbA1c during the years of puberty (8.3 vs. 10.0%, P = 0.022)
CONCLUSIONS—In children with type 1 diabetes, untreated celiac disease resulted in lower BMI SDS and lower HbA1c. Recovery of BMI SDS with a GFD was associated with further improvement in HbA1c as compared with pre-GFD, with no expected deterioration in glycemic control during puberty. These apparent clinical benefits need confirming by larger studies.
Elevated Risk of Cardiovascular Disease Prior to Clinical Diagnosis of Type 2 Diabetes
Authors: Hu Frank B. , Stampfer Meir J. , Haffner Steven M. , Solomon Caren G. , Willett Walter C. , Manson JoAnn E. 
Published: March 2007

OBJECTIVE—To examine whether the risk of cardiovascular disease (CVD) is elevated before clinical diagnosis of type 2 diabetes in women.RESEARCH DESIGN AND METHODS—A total of 117,629 female nurses aged 30–55 years who were free of diagnosed CVD at baseline were recruited in 1976 and followed for 20 years.RESULTS—A total of 1,508 women had diagnosed type 2 diabetes at baseline in 1976. During 20 years of follow-up, 110,227 women remained free of diabetes diagnosis and 5,894 women developed type 2 diabetes. During 2.2 million person-years of follow-up, we documented 1,556 new cases of myocardial infarction (MI), 1,405 strokes, 815 fatal coronary heart disease (CHD), and 300 fatal strokes. Among women who developed type 2 diabetes during follow-up, the age-adjusted RRs of MI were 3.75 (95% CI 3.10–4.53) for the period before the diagnosis and 4.57 (3.87–5.39) for the period after the diagnosis, compared with women who remained free of diabetes diagnosis. The multivariate RRs further adjusting for BMI, smoking, and other cardiovascular risk factors were 3.17 (2.61–3.85) and 3.97 (3.35–4.71). The risk of stroke was also significantly elevated before diagnosis of diabetes (multivariate RR = 2.30 [1.76–2.99]). Further adjustment for history of hypertension or hypercholesterolemia did not appreciably alter the results.CONCLUSIONS—Our data indicate a substantially elevated risk of CVD before clinical diagnosis of type 2 diabetes in women. These findings suggest that aggressive management of cardiovascular risk factors is warranted in individuals at increased risk for diabetes.
Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes
Authors: Desouza Cyrus , Parulkar Akhil , Lumpkin David , Akers Donald , Fonseca Vivian A. 
Published: March 2007

OBJECTIVE—Flow-mediated dilatation (FMD), induced by occlusion of the brachial artery, is an index of nitric oxide-dependent endothelial function that is impaired in patients with type 2 diabetes. Sildenafil (Viagra) is an inhibitor of phosphodiesterase 5 (PDE-5), which is used for management of erectile dysfunction in a broad range of patients, including those with type 2 diabetes. Its effects on endothelial function in these patients have not been previously assessed.RESEARCH DESIGN AND METHODS—We assessed the acute and prolonged effects of a low dose of sildenafil (25 mg) on FMD in patients with type 2 diabetes. We performed a double-blind, placebo-controlled cross-over trial in 16 patients (14 of whom completed the study) with type 2 diabetes who had erectile dysfunction without overt clinical heart disease.RESULTS—In these patients, the mean ± SD brachial artery diameter (BAD) measured by ultrasound was 4.33 ± 0.6 mm. After inducing FMD, the BAD increased 8% to 4.66 ± 0.6 mm (P = 0.2). One hour after oral administration of sildenafil 25 mg, FMD increased the BAD significantly by 15% to 4.99 ± 0.5 mm (P ≤ 0.01), whereas it did not change with placebo (4.6 ± 0.6 mm, P = 0.1). After treatment with sildenafil 25 mg daily for 2 weeks and testing 24 h after the last dose, the mean FMD was 14% (P = 0.01). In contrast, the mean FMD with placebo was 9% (P = 0.45).CONCLUSIONS—We conclude that acute and prolonged sildenafil treatment has a favorable effect on brachial artery flow-mediated dilatation that persists for at least 24 h after the last dose. Further investigation is needed to determine whether this prolonged effect has clinical implications in patients with type 2 diabetes.
Heterogeneity in the Relationship Between Ethnicity, BMI, and Fasting Insulin
Authors: Palaniappan Latha P. , Carnethon Mercedes R. , Fortmann Stephen P. 
Published: March 2007

OBJECTIVE—To determine whether the association of BMI and fasting insulin is modified by ethnicity.
RESEARCH DESIGN AND METHODS—Non-Hispanic black (black), non-Hispanic white (white), and Mexican-American men and women aged 20–80 years from the Third National Health and Nutrition Examination Survey (1988–1994) were included in this study. Linear regression models with an interaction term were used to test whether ethnicity modified the association between BMI and fasting insulin.
RESULTS—Fasting insulin was 19, 26, 20, and 19% higher in black women than white women with BMI levels of &lt;22, 22–24, 25–27, and 28–30 kg/m2, respectively. These differences between black and white women converged at BMI levels &gt;30 kg/m2. Mexican-American women had fasting insulin levels that were 17, 22, 20, and 16% higher than those of white women at BMI levels of 25–27, 28–30, 31–33, and &gt;34 kg/m2, respectively, but were not different in individuals with BMI levels &lt;25 kg/m2. Adjusting for established risk factors did not attenuate these associations in women. Differences in fasting insulin among men were not as apparent.
CONCLUSIONS—These findings suggest that the effect of obesity on insulin sensitivity is different for Americans in ethnic minorities. In black subjects, fasting insulin is higher at lean weight when compared with white and Mexican-American subjects. In Mexican-American subjects, fasting insulin is higher in overweight individuals when compared with white and black subjects. These findings are more pronounced in women than in men. This result reinforces the importance of designing prevention programs that are tailored to meet the needs of specific populations. Investigation of possible explanations for these differences seems warranted.
Diabetes Contributes to Cholesterol Metabolism Regardless of Obesity
Authors: Simonen Piia P. , Gylling Helena K. , Miettinen Tatu A. 
Published: March 2007

OBJECTIVE—To investigate cholesterol metabolism in obesity with and without diabetes.
RESEARCH DESIGN AND METHODS—We performed cross-sectional metabolic studies in obese individuals with and without type 2 diabetes. The study population consisted of 16 obese (BMI &gt;30 kg/m2) diabetic subjects with a mean age of 52 ± 2 years (SE) and 16 nondiabetic control subjects of similar age and weight. Cholesterol absorption efficiency was measured with peroral dual isotopes and cholesterol synthesis with sterol balance.
RESULTS—Serum total cholesterol did not differ between the groups, but LDL and HDL cholesterol were significantly lower and VLDL cholesterol and serum total and VLDL triglycerides were higher in the diabetic group than in the control group. Cholesterol absorption efficiency was 29 ± 1% in diabetic subjects vs. 42 ± 2% in the control subjects (P &lt; 0.01). Cholesterol synthesis was higher (17 ± 1 vs. 14 ± 1 mg · kg−1 · day−1; P &lt; 0.05) and neutral sterol and bile acid excretion and cholesterol turnover tended to be higher in the diabetic group than in the control group. Blood glucose was positively related to cholesterol synthesis in the diabetic group (r = +0.663, P &lt; 0.01) and in the control group (r = +0.590, P &lt; 0.05), suggesting that the higher blood glucose level, the higher the cholesterol synthesis. In addition, blood glucose was significantly positively related to fecal neutral sterol excretion in both groups.
CONCLUSIONS—Cholesterol absorption efficiency was lower and cholesterol synthesis was higher in obese subjects with diabetes than in those without diabetes, suggesting that diabetes modulates cholesterol metabolism more than obesity alone.
Prognostic Value of Dobutamine-Atropine Stress Myocardial Perfusion Imaging in Patients With Diabetes
Authors: Schinkel Arend F.L. , Elhendy Abdou , van Domburg Ron T. , Bax Jeroen J. , Vourvouri Eleni C. , Sozzi Fabiola B. , Valkema Roelf , Roelandt Jos R.T.C. , Poldermans Don 
Published: March 2007

OBJECTIVE—Exercise tolerance in patients with diabetes is frequently impaired due to noncardiac disease such as claudication and polyneuropathy. This study assesses the prognostic value of dobutamine stress myocardial perfusion imaging in patients with diabetes.
RESEARCH DESIGN AND METHODS—A total of 207 consecutive diabetic patients who were unable to undergo exercise stress testing underwent dobutamine-atropine stress myocardial perfusion imaging. Follow-up was successful in 206 of 207 (99.5%) patients. A total of 12 patients underwent early (&lt;60 days) revascularization and were excluded from the analysis. End points during follow-up were hard cardiac events, defined as cardiac death and nonfatal myocardial infarction.
RESULTS—Abnormal myocardial perfusion was detected in 125 (64%) patients. During 4.1 ± 2.4 years of follow-up, 73 (38%) deaths occurred, 36 (49%) of which were due to cardiac causes. Nonfatal myocardial infarction occurred in 7 (4%) patients, and 45 (23%) patients underwent late coronary revascularization. Cardiac death occurred in 2 of 69 (3%) patients with normal myocardial perfusion and in 34 of 125 (27%) patients with perfusion abnormalities (P &lt; 0.0001). A multivariable Cox proportional hazard model demonstrated that, in addition to clinical and stress test data, an abnormal scan had an incremental prognostic value for prediction of cardiac death (hazard ratio 7.2, 95% CI 1.7–30). The summed stress score was an important predictor of cardiac death; the hazard ratio was 1.2 (95% CI 1.07–1.34) per one-unit increment.
CONCLUSIONS—Dobutamine-atropine stress myocardial perfusion imaging provides additional prognostic information incremental to clinical data in patients with diabetes who are unable to undergo exercise stress testing.
l-Arginine: An Ultradian-Regulated Substrate Coupled With Insulin Oscillations in Healthy Volunteers
Authors: Schaefer Adrien , Simon Chantal , Viola Antoine , Piquard François , Geny Bernard , Brandenberger Gabrielle 
Published: March 2007

OBJECTIVE—Coupled oscillations of 50–110 min in insulin and glucose have been found previously in healthy men under continuous enteral nutrition. Because l-arginine induces insulin release as glucose does, we tested the hypothesis that l-arginine can also display such an ultradian rhythm.
RESEARCH DESIGN AND METHODS—Seven healthy male subjects participated in one experimental night during which blood was sampled every 10 min from 2300 to 0700. Plasma glucose, C-peptide, and l-arginine levels were measured simultaneously. The insulin secretion rate (ISR) was calculated from plasma C-peptide levels by a deconvolution procedure.
RESULTS—Plasma glucose followed the recognizable profiles, with oscillations closely linked to similar changes in the ISR. Pulse analysis of l-arginine profiles revealed significant oscillations linked to glucose and ISR oscillations, with the highest cross-correlation coefficients at time lag 0 ranging from 0.380 to 0.680 for glucose and l-arginine and from 0.444 to 0.726 for ISR and l-arginine (P &lt; 0.01). The mean period of l-arginine oscillations was 77.2 ± 6.2 min, and their mean amplitude was 19.9 ± 1.7%, similar to that of glucose (17.0 ± 1.9%), when expressed as the percentage of mean overnight levels.
CONCLUSIONS—This newly discovered ultradian rhythm of l-arginine and its coupling with glucose and ISR oscillations sheds new light on the regulation of l-arginine, the substrate of numerous metabolic pathways, including nitric oxide synthesis. These oscillations may be of significance in conditions of hyperinsulinemia or abnormal glucose tolerance.
Improving Diabetes Processes of Care in Managed Care
Authors: Ilag Liza L. , Martin Catherine L. , Tabaei Bahman P. , Isaman Deanna J. M. , Burke Ray , Greene Douglas A. , Herman William H. 
Published: March 2007

OBJECTIVE—To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practices.
RESEARCH DESIGN AND METHODS—Nine practices providing care to managed care patients were randomly assigned as intervention or comparison sites. Intervention-site subjects had Annual Diabetes Assessment Program (ADAP) assessments (HbA1c, blood pressure, lipids, smoking, retinal photos, urine microalbumin, and foot examination) at years 1 and 2. Comparison-site subjects had ADAP assessments at year 2. At Intervention sites, year 1 ADAP results were reviewed with subjects, mailed to providers, and incorporated into electronic medical records with guideline-generated suggestions for treatment and follow-up. Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessments. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models.
RESULTS—Of 284 eligible subjects, 103 of 173 (60%) at the Intervention sites and 71 of 111 (64%) at the comparison sites participated; 83 of 103 (81%) of the intervention-site subjects returned for follow-up at year 2. Performance of the six recommended assessments improved in intervention-site subjects at year 2 compared with year 1 (5.8 vs. 4.3, P = 0.0001) and compared with comparison-site subjects at year 2 (4.2, P = 0.014). No significant changes were noted in intermediate outcomes.
CONCLUSIONS—The ADAP significantly improved processes of care but not intermediate outcomes. Additional interventions are needed to improve intermediate outcomes.
Moderate Alcohol Consumption, Estrogen Replacement Therapy, and Physical Activity Are Associated With Increased Insulin Sensitivity
Authors: Greenfield Jerry R. , Samaras Katherine , Jenkins Arthur B. , Kelly Paul J. , Spector Tim D. , Campbell Lesley V. 
Published: March 2007

OBJECTIVE—To investigate 1) associations between environmental factors (alcohol consumption, hormone replacement therapy [HRT], and physical activity) and insulin resistance and secretion, independent of genetic influences; 2) the contribution of abdominal adiposity to these relationships; and 3) whether gene-environment interactions mediate these associations.
RESEARCH DESIGN AND METHODS—Reported effects of lifestyle factors on insulin resistance and secretion are inconsistent, possibly due to difficulty in dissecting environmental from genetic influences and to confounding by adiposity. We examined these relationships in 798 nondiabetic female twins. Insulin resistance and secretion were estimated by modified homeostasis model assessment (HOMA-R′ and HOMA-β′, respectively). Percent total body fat and percent central abdominal fat (CAF) were measured by dual-energy X-ray absorptiometry.
RESULTS—All categories of alcohol consumption were associated with lower insulin levels and HOMA-β′ than abstinence. Only moderate alcohol consumers (11–20 units/week) had lower HOMA-R′ than abstainers (−0.16 ± 0.09 vs. 0.14 ± 0.13 SD, P = 0.048). This difference was attenuated after controlling for percent CAF (P = 0.57), which was lower in moderate drinkers. Controlling for genetic and smoking effects in cotwin case-control analysis, monozygotic pairs discordant for alcohol consumption had greater within-pair differences in HOMA-R′ than concordant pairs (P = 0.02). Postmenopausal women using estrogen-only HRT had lower HOMA-R′ than non–HRT users (−0.33 ± 0.16 vs. 0.17 ± 0.08 SD, P = 0.003), even after controlling for percent CAF. Lower fasting glucose levels and insulin resistance and secretion indexes in physically active subjects were partly explained by lower abdominal adiposity.
CONCLUSIONS—Moderate alcohol consumption, estrogen replacement, and physical activity are associated with increased insulin sensitivity in female twins. The favorable effects of moderate alcohol consumption and physical activity on insulin sensitivity are partly mediated by lower abdominal adiposity.
Dose-Response Relationships of Inhaled Insulin Delivered via the Aerodose Insulin Inhaler and Subcutaneously Injected Insulin in Patients With Type 2 Diabetes
Authors: Kim Dennis , Mudaliar Sunder , Chinnapongse Sithipol , Chu Neelima , Boies Sarah M. , Davis Trent , Perera Ayesh D. , Fishman Robert S. , Shapiro David A. , Henry Robert 
Published: March 2007

OBJECTIVE—To compare the dose-response relationship following inhalation of regular insulin delivered via the Aerodose insulin inhaler with that following subcutaneously injected regular insulin in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—Twenty-four patients with type 2 diabetes (21 nonsmoking men, aged 36–80 years) each received two of three doses of 80, 160, or 240 units inhaled regular insulin, delivered via a clinical Aerodose insulin inhaler, and two of three corresponding doses of 8, 16, or 24 units by subcutaneous injection under isoglycemic clamp conditions on 4 separate study days in an incomplete block design study. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h.
RESULTS—Inhaled insulin exhibited significantly shorter time-to-peak insulin levels (Tmax 77 ± 66 vs. 193 ± 104 min, P &lt; 0.001) and time-to-peak metabolic effects (TGIRmax 240 ± 94 vs. 353 ± 60 min, P &lt; 0.001) compared with subcutaneously injected insulin. Comparison of total insulin absorption (insulin area under the curve [AUC]) versus total metabolic effect (GIR-AUC) from 0 to 8 h (group means) revealed overlapping dose-response relationships for both inhaled and subcutaneous injection treatments. Comparison of slopes revealed no significant differences between the inhaled and subcutaneous injection treatment groups (P = 0.6). No significant differences in either relative bioavailability or relative biopotency were found among doses, indicating a consistent subcutaneous injection-to-inhaled dosing conversion ratio among doses. No serious adverse events or clinically relevant changes in lung function were observed.
CONCLUSIONS—The overlapping dose-response curves of inhaled and subcutaneous treatments together with a consistent relative bioavailability and relative biopotency for inhaled insulin across doses suggest that the Aerodose insulin inhaler will deliver a pharmacologically predictable insulin dose to patients with diabetes similar to that observed following subcutaneous injection.