bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Trandolapril and Its Fixed-Dose Combination With Verapamil on Proteinuria in Normotensive Adults With Type 2 Diabetes
Authors: Rubio-Guerra Alberto Francisco , Arceo-Navarro Adalberto , Vargas-Ayala German , Rodriguez-Lopez Leticia , Lozano-Nuevo Jose Juan , Gomez-Harper Carlos Treviño 
Published: March 2007

OBJECTIVE—To compare the effect of fixed-dose trandolapril-verapamil (FDTV) with that of trandolapril on proteinuria in normotensive, type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—A total of 60 normotensive, type 2 diabetic patients with 24-h proteinuria &gt;300 mg were randomly assigned to two groups for open-label treatment. One group received 2 mg trandolapril/180 mg verapamil FDTV once daily; the other group received 2 mg trandolapril once daily. Study drugs were administered for 6 months in both groups. Creatinine clearance and 24-h urinary protein excretion were measured at the beginning and the end of the study. Patients were evaluated monthly for blood pressure, fasting blood glucose level, heart rate, and adverse events. Statistical analysis was performed using ANOVA.
RESULTS—Both groups experienced a statistically significant (P &lt; 0.005) mean decrease in mean proteinuria from baseline: FDTV ([mean ± SD] 1,200 ± 200 to 540 ± 79 mg; P &lt; 0.001) and trandolapril (1,105 ± 212 to 750.9 ± 134 mg; P &lt; 0.005). A significantly greater reduction from baseline in proteinuria was observed in the FDTV group compared with the trandolapril group. Patients who received trandolapril experienced a statistically significant (P &lt; 0.05) decrease in mean creatinine clearance (91.1 ± 3.4 to 75.3 ± 3 ml/min; P &lt; 0.05) compared with patients who received FDTV (88.3 ± 3.6 to 82.9 ± 3.5 ml/min; P &gt; 0.05). Final fasting blood glucose was significantly lower in the FDTV group (139 ± 19) compared with the trandolapril group (154 ± 22; P &lt; 0.001). No significant differences were observed between the two groups in mean baseline or final measurements of blood pressure, mean heart rate, or frequency of adverse events.
CONCLUSIONS—Our results suggest that FDTV is more effective than trandolapril in reducing proteinuria in normotensive, type 2 diabetic patients. This effect on proteinuria is not related with blood pressure reduction.
Reductions in Plasma Cytokine Levels With Weight Loss Improve Insulin Sensitivity in Overweight and Obese Postmenopausal Women
Authors: Ryan Alice S. , Nicklas Barbara J. 
Published: March 2007

OBJECTIVE—The purpose of this study was to determine whether improvements in insulin sensitivity with weight loss are mediated by changes in inflammation in obese, postmenopausal women.
RESEARCH DESIGN AND METHODS—We studied 58 sedentary, overweight, and obese (BMI 33 ± 1 kg/m2, means ± SEM) postmenopausal (58 ± 1 year) women at baseline and 37 women who completed 6 months of weight loss induced by diet and exercise. The women underwent 3-h hyperinsulinemic-euglycemic clamps (40 mU · m−2 · min−1) to determine glucose utilization (M). Insulin sensitivity was determined as M/I, the amount of glucose metabolized per unit of plasma insulin (I). Visceral adipose tissue (VAT) and plasma concentrations of C-reactive protein (CRP), cytokines interleukin (IL)-6, and tumor necrosis factor (TNF)-α, as well as their soluble receptors, were measured.
RESULTS—At baseline, CRP concentration was a predictor of both glucose utilization and insulin sensitivity, independent of adiposity, race, and aerobic fitness (M: partial r = −0.30, P = 0.03, and M/I: partial r = −0.32, P = 0.02). Weight loss resulted in significant reductions in body weight, fat mass, VAT, and fasting glucose and insulin levels (P &lt; 0.05). Both glucose utilization and insulin sensitivity increased by 16% (P &lt; 0.05). CRP, IL-6, and soluble TNF receptor (sTNFR)-1 concentrations decreased (P &lt; 0.05), but concentrations of TNF-α, sTNFR-2, and soluble IL-6 receptor (IL-6sR) did not change. In stepwise regression models to predict changes in glucose homeostasis, changes in VAT and sTNF-R1 independently predicted changes in glucose utilization (r = −0.49 and cumulative r = −0.64, P &lt; 0.01), while changes in VAT and IL-6 were both independent predictors of changes in insulin sensitivity (r = −0.57 and cumulative r = −0.68, P &lt; 0.01).
CONCLUSIONS—Improvements in glucose metabolism with weight loss programs are independently associated with decreases in cytokine concentrations, suggesting that a reduction in inflammation is a potential mechanism that mediates improvements in insulin sensitivity.
Incidence of Lower-Extremity Amputation in American Indians
Authors: Resnick Helaine E. , Carter Elizabeth A. , Sosenko Jay M. , Henly Susan J. , Fabsitz Richard R. , Ness Frederick K. , Welty Thomas K. , Lee Elisa T. , Howard Barbara V. 
Published: March 2007

OBJECTIVE—To define incidence and predictors of nontraumatic lower-extremity amputation (LEA) in a diverse cohort of American Indians with diabetes.
RESEARCH DESIGN AND METHODS—The Strong Heart Study is a study of cardiovascular disease and its risk factors in 13 American-Indian communities. Data on the presence/absence of amputations were collected at each of three serial examinations (1989–1992, 1993–1995, and 1997–1999) by direct examination of the lower extremity. The logistic regression model was used to quantify the relationship between risk of LEA and potential risk factors, including diabetes duration, HbA1c, peripheral arterial disease, and renal function.
RESULTS—Of the 1,974 individuals with diabetes and without prevalent LEA at baseline, 87 (4.4%) experienced an LEA during 8 years of follow-up, and a total of 157 anatomical sites were amputated among these individuals. Amputation of toes was most common, followed by below-the-knee and above-the-knee amputations. Age-adjusted odds of LEA were higher among individuals with unfavorable combinations of risk factors, such as albuminuria and elevated HbA1c. Multivariable modeling indicated that male sex, renal dysfunction, high ankle-brachial index, longer duration of diabetes, less than a high school education, increasing systolic blood pressure, and HbA1c predicted LEA risk.
CONCLUSIONS—The 8-year cumulative incidence of LEA in American Indians with diabetes is 4.4%, with marked differences in risk by sex, educational attainment, renal function, and glycemic control.
Male Sex Increases the Risk of Autoimmunity but not Type 1 Diabetes
Authors: Krischer Jeffrey P. , Cuthbertson David D. , Greenbaum Carla ,   the Diabetes Prevention Trial-Type 1 Study Group
Published: March 2007

OBJECTIVE—The goal of this study was to explore the role of sex on the prevalence of autoantibodies, protective genetic subtypes, β-cell function, and the incidence of type 1 diabetes in a population of first- and second-degree relatives of patients with type 1 diabetes (probands). We examined both the effect of the sex of the individual screened as well as the effect of the sex of the individual’s proband on diabetes risk variables tested.
RESEARCH DESIGN AND METHODS—The Diabetes Prevention Trial-Type 1 has screened 93,188 relatives of type 1 diabetic patients from February 1994 to January 2002. After observing that more men than women were islet cell autoantibody (ICA) positive for the group as a whole, we further explored the role of sex by detailed analysis of variables in this population.
RESULTS—Our data suggest only an influence of sex on the type 1 diabetes disease process. After adjustment for race, age, and relationship to proband, male sex was associated with the appearance of autoimmunity, i.e., the presence of ICA and having two or more antibodies. There was no effect of sex on the presence of other autoantibodies, insulin secretion, results of oral glucose tolerance test, or development of diabetes.
CONCLUSIONS—Our finding that male sex conveys an independent increased risk for development of ICA and multiple antibodies, while at the same time finding no difference with respect to the development of diabetes, suggests that male relatives with the known risk factor of ICA are less likely than comparable female relatives to progress to overt disease, that the pathogenesis of type 1 diabetes among men is slower compared with women, or that women develop diabetes manifesting different antibody responses.
Impact of Degree of Obesity on Surrogate Estimates of Insulin Resistance
Authors: Kim Sun H. , Abbasi Fahim , Reaven Gerald M. 
Published: March 2007

OBJECTIVE—To evaluate the role of adiposity in the relationship between specific and surrogate estimates of insulin-mediated glucose uptake (IMGU) in a large nondiabetic population.
RESEARCH DESIGN AND METHODS—Healthy volunteers were classified by BMI into normal weight (&lt;25.0 kg/m2, n = 208), overweight (25.0–29.9 kg/m2, n = 168), and obese (≥30.0 kg/m2, n = 109) groups. We then assessed how differences in BMI affect the correlation between steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide, glucose, and insulin (a specific measure of IMGU) and five surrogate estimates: fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and area under the curve for insulin in response to oral glucose (I-AUC).
RESULTS—Correlation coefficients (r values) between SSPG and surrogate measures of IMGU were all significant (P &lt; 0.05), but the magnitude varied between BMI groups: normal weight: fasting plasma glucose 0.20, fasting plasma insulin 0.33, HOMA-IR 0.36, QUICKI −0.33, and I-AUC 0.69; overweight: fasting plasma glucose 0.19, fasting plasma insulin 0.55, HOMA-IR 0.55, QUICKI −0.54, and I-AUC 0.72; and obese: fasting plasma glucose 0.40, fasting plasma insulin 0.56, HOMA-IR 0.60, QUICKI −0.61, and I-AUC 0.69.
CONCLUSIONS—The relationship between direct and surrogate estimates of IMGU varies with BMI, with the weakest correlations seen in the normal-weight group and the strongest in the obese group. In general, I-AUC is the most useful surrogate estimate of IMGU in all weight groups. Fasting plasma insulin, HOMA-IR, and QUICKI provide comparable information about IMGU. Surrogate estimates of IMGU based on fasting insulin and glucose account for no more than 13% of the variability in insulin action in the normal-weight group, 30% in the overweight group, and 37% in the obese group.
Adiponectin and Leptin Concentrations May Aid in Discriminating Disease Forms in Children and Adolescents With Type 1 and Type 2 Diabetes
Authors: Morales Alba , Wasserfall Clive , Brusko Todd , Carter Carolyn , Schatz Desmond , Silverstein Janet , Ellis Tamir , Atkinson Mark 
Published: March 2007

OBJECTIVE—The incidence of pediatric type 2 diabetes has recently seen an alarming increase. To improve our understanding of pediatric type 2 diabetes and identify markers that discriminate these subjects from those with type 1 diabetes, we performed a multivariant analysis associating serum adiponectin and leptin levels with anthropometrical parameters and disease state.
RESEARCH DESIGN AND METHODS—Samples from children and adolescents with type 1 diabetes (n = 41) and type 2 diabetes (n = 17) and from nondiabetic individuals of similar age from the general population (n = 43) were investigated. An analysis included the parameters of matching for BMI and Tanner stage. Receiver-operator characteristic (ROC) curves were established to assess these analytes’ association with disease.
RESULTS—Contrary to studies of adult type 1 diabetes, adiponectin levels in our pediatric type 1 diabetic subjects (10.2 μg/ml [95% CI 8.6–11.7]) did not differ from those of healthy control subjects (10.6 μg/ml [9.2–12.0]; P = NS). Children with type 2 diabetes (5.5 μg/ml [4.8–6.2]) had significantly lower adiponectin levels than both of those groups. Conversely, type 2 diabetic subjects showed marked elevations in serum leptin concentrations (24.3 ng/ml [17.1–31.5]) compared with healthy control subjects (2.7 ng/ml [1.3–4.1]; P &lt; 0.001) and type 1 diabetic subjects (5.1 ng/ml [3.5–6.7]; P &lt; 0.001). Importantly, each of the properties ascribed to pediatric type 2 diabetes was present when the comparison was restricted to healthy children or type 1 diabetic patients whose BMI was &gt;85th percentile or who had Tanner stage 4 and 5. The evaluation of adiponectin-to-leptin ratios revealed a striking difference between children with type 1 diabetes (6.3 [3.8–8.8]) and type 2 diabetes (0.3 [0.2–0.5]; P &lt; 0.001).
CONCLUSIONS—In pediatric diabetes, where diagnosis of disease is often difficult, these studies suggest that the adiponectin-to-leptin ratio may provide additional help in the discrimination between type 1 and type 2 diabetes.
A Prospective Study of Red Meat Consumption and Type 2 Diabetes in Middle-Aged and Elderly Women
Authors: Song Yiqing , Manson JoAnn E. , Buring Julie E. , Liu Simin 
Published: March 2007

OBJECTIVE—The aim of this study was to prospectively assess the relation between red meat intake and incidence of type 2 diabetes.
RESEARCH DESIGN AND METHODS—Over an average of 8.8 years, we evaluated 37,309 participants in the Women’s Health Study aged ≥45 years who were free of cardiovascular disease, cancer, and type 2 diabetes and completed validated semiquantitative food frequency questionnaires in 1993.
RESULTS—During 326,876 person-years of follow-up, we documented 1,558 incident cases of type 2 diabetes. After adjusting for age, BMI, total energy intake, exercise, alcohol intake, cigarette smoking, and family history of diabetes, we found positive associations between intakes of red meat and processed meat and risk of type 2 diabetes. Comparing women in the highest quintile with those in the lowest quintile, the multivariate-adjusted relative risks (RRs) of type 2 diabetes were 1.28 for red meat (95% CI 1.07–1.53, P &lt; 0.001 for trend) and 1.23 for processed meat intake (1.05–1.45, P = 0.001 for trend). Furthermore, the significantly increased diabetes risk appeared to be most pronounced for frequent consumption of total processed meat (RR 1.43, 95% CI 1.17–1.75 for ≥5/week vs. &lt;1/month, P &lt; 0.001 for trend) and two major subtypes, which were bacon (1.21, 1.06–1.39 for ≥2/week vs. &lt;1/week, P = 0.004 for trend) and hot dogs (1.28, 1.09–1.50 for ≥2/week vs. &lt;1/week, P = 0.003 for trend). These results remained significant after further adjustment for intakes of dietary fiber, magnesium, glycemic load, and total fat. Intakes of total cholesterol, animal protein, and heme iron were also significantly associated with a higher risk of type 2 diabetes.
CONCLUSIONS—Our data indicate that higher consumption of total red meat, especially various processed meats, may increase risk of developing type 2 diabetes in women.
Oral Antihyperglycemic Medication Nonadherence and Subsequent Hospitalization Among Individuals With Type 2 Diabetes
Authors: Lau Denys T. , Nau David P. 
Published: March 2007

OBJECTIVE—This study examines the association between oral antihyperglycemic medication nonadherence and subsequent hospitalization among individuals with type 2 diabetes.
RESEARCH DESIGN AND METHODS—Using administrative claims data (2000–2001) from a managed care organization in the Midwestern U.S., this study analyzed 900 enrollees, aged 18 years and over, with type 2 diabetes who were taking oral antihyperglycemic agents both years but who did not use insulin. Nonadherence was defined as a medication possession ratio (MPR) &lt;80%. Multivariate logistic regression analyses were performed where hospitalization in 2001 was regressed on nonadherence to the oral antihyperglycemic drug regimen in 2000, while controlling for nonadherence to drugs for hypertension and dyslipidemia and for hospitalization in 2000, age, sex, intensity of the diabetes drug regimen, and comorbidities.
RESULTS—The proportion of enrollees who were nonadherent to the antihyperglycemic drug regimen in 2001 was 28.9%, whereas 18.8 and 26.9% were nonadherent to antihypertensive and lipid-modifying drugs, respectively. The increase in the hospitalization rate for 2001 was most apparent where the antihyperglycemic MPR for 2000 dropped to &lt;80%. Enrollees who were nonadherent to oral diabetes medications in 2000 were at higher risk of hospitalization in 2001 (odds ratio 2.53; 95% CI 1.38–4.64), whereas nonadherence to drugs for hypertension and dyslipidemia were not significantly associated with hospitalization.
CONCLUSIONS—Patients with type 2 diabetes who do not obtain at least 80% of their oral antihyperglycemic medications across 1 year are at a higher risk of hospitalization in the following year.
Effect of High-Dose Vitamin E on Insulin Resistance and Associated Parameters in Overweight Subjects
Authors: Manning Patrick J. , Sutherland Wayne H.F. , Walker Robert J. , Williams Sheila M. , de Jong Sylvia A. , Ryalls Anne R. , Berry Elizabeth A. 
Published: March 2007

OBJECTIVE—Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals.
RESEARCH DESIGN AND METHODS—Eighty overweight individuals (BMI &gt;27 kg/m2) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months.
RESULTS—Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased. These changes were not apparent at 6 months. Plasma ALT concentrations declined significantly throughout the study period.
CONCLUSIONS—In conclusion, these findings indicate that vitamin E improves oxidative stress and hepatocellular function. Although insulin resistance also improves, this effect appears transient.
Temporary Preservation of β-Cell Function by Diazoxide Treatment in Childhood Type 1 Diabetes
Authors: Örtqvist Eva , Björk Elisabeth , Wallensteen Måna , Ludvigsson Johnny , Åman Jan , Johansson Calle , Forsander Gun , Lindgren Fredrik , Berglund Lars , Bengtsson Mats , Berne Christian , Persson Bengt , Karlsson F. Anders 
Published: March 2007

OBJECTIVE—We examined the effect of diazoxide, an ATP-sensitive K+ channel opener and inhibitor of insulin secretion, on β-cell function and remission in children at clinical onset of type 1 diabetes.
RESEARCH DESIGN AND METHODS—A total of 56 subjects (21 girls and 35 boys, age 7–17 years) were randomized to 3 months of active treatment (diazoxide 5–7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years.
RESULTS—Diazoxide decreased circulating C-peptide concentrations by ∼50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 ± 0.22 vs. 0.31 ± 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (−0.05 ± 0.24 vs. −0.18 ± 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 ± 0.20 and 0.20 ± 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent.
CONCLUSIONS—This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of β-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.
Diabetes Is the Strongest Risk Factor for Lower-Extremity Amputation in New Hemodialysis Patients
Authors: Speckman Rebecca A. , Frankenfield Diane L. , Roman Sheila H. , Eggers Paul W. , Bedinger Marjorie R. , Rocco Michael V. , McClellan William M. 
Published: March 2007

OBJECTIVE—End-stage renal disease (ESRD) patients, especially those with diabetes, have an increased risk of nontraumatic lower-extremity amputation (LEA). The present study aims to examine the association of demographic and clinical variables with the risk of hospitalization for LEA among incident hemodialysis patients.
RESEARCH DESIGN AND METHODS—The study population consisted of incident hemodialysis patients from the study years 1996–1999 of the ESRD Core Indicator/Clinical Performance Measures (CPM) Project. Cox proportional hazard modeling was used to identify factors associated with LEA.
RESULTS—Four percent (116 of 3,272) of noncensored incident patients had an LEA during the 12-month follow-up period. Factors associated with LEA included diabetes as the cause of ESRD or preexisting comorbidity (hazard ratio 6.4, 95% CI 3.4–12.0), cardiovascular comorbidity (1.8, 1.2–2.8), hemodialysis inadequacy (urea reduction ratio [URR] &lt;58.5% (1.9, 1.1–3.3), and lower serum albumin level (1.6, 1.1–2.3). Among patients with diabetes, hemodialysis inadequacy and cardiovascular comorbidity were risk factors for LEA (2.6, 1.4–4.8, and 1.7, 1.1–2.6, respectively).
CONCLUSIONS—These data suggest that diabetes is a potent risk factor for LEA in new hemodialysis patients. In ESRD patients with diabetes, a multipronged approach may reduce the rate of LEA. Potentially beneficial strategies include adherence to hemodialysis adequacy guidelines, aggressive treatment of cardiovascular comorbidities, and the utilization of LEA prevention strategies recommended for the general population of patients with diabetes.
Possible Impairment of Transcardiac Utilization of Adiponectin in Patients With Type 2 Diabetes
Authors: Furuhashi Masato , Ura Nobuyuki , Moniwa Norihito , Shinshi Yasuyuki , Kouzu Hidemichi , Nishihara Masahiro , Kokubu Nobuaki , Takahashi Toru , Sakamoto Ken-ichi , Hayashi Manabu , Satoh Naotoshi , Nishitani Takahiro , Shikano Yasukuni , Shimamoto Kazuaki 
Published: March 2007

OBJECTIVE—Adiponectin, an adipocyte-derived protein, has been suggested to enhance insulin sensitivity and prevent atherosclerosis. Circulating adiponecin levels are reduced in states of insulin resistance such as type 2 diabetes. We examined transcardiac utilization of adiponectin in patients with and without type 2 diabetes.
RESEARCH DESIGN AND METHODS—A total of 17 male type 2 diabetic patients and 17 male nondiabetic patients were investigated. Venous blood samples were taken to measure glucose and lipid variables. Blood samples for the measurement of adiponectin were collected simultaneously from the aortic root and coronary sinus. Angiographic semiquantitative stenosis score of coronary artery was also evaluated.
RESULTS—The adiponectin levels in both the aortic root and coronary sinus in the diabetic patients were significantly lower than those in the nondiabetic patients. The adiponectin level was significantly lower in the coronary sinus than in the aortic root in the nondiabetic patients, but there was no significant difference between adiponectin levels in the aortic root and coronary sinus in the diabetic patients. The total stenosis score, as an index of severity of coronary artery stenosis, was significantly higher in the diabetic patients than in the nondiabetic patients. The stenosis score was correlated with the degree of transcardiac utilization of adiponectin from the aortic root to coronary sinus in the nondiabetic patients but not in the diabetic patients.
CONCLUSIONS—Diabetic patients not only have a decreased adiponectin level in the basal state compared with nondiabetic patients but also have impaired utilization of adiponectin in the coronary artery and/or the heart, which may promote the development of atherosclerosis.