bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, Autoimmune, and Genetic Characteristics of Adult-Onset Diabetic Patients With GAD Autoantibodies in Japan (Ehime Study)
Authors: Takeda Haruyo , Kawasaki Eiji , Shimizu Ikki , Konoue Etsushi , Fujiyama Masao , Murao Satoshi , Tanaka Kiyonobu , Mori Kennichi , Tarumi Yoshinao , Seto Isamu , Fujii Yasuhisa , Kato Kenichi , Kondo Shiori , Takada Yasuharu , Kitsuki Nobuaki , Kaino Yukikazu , Kida Kaichi , Hashimoto Naotake , Yamane Yukio , Yamawaki Takashi , Onuma Hiroshi , Nishimiya Tatsuya , Osawa Haruhiko , Saito Yasushi , Makino Hideichi 
Published: March 2007

OBJECTIVE—To characterize the clinical, autoimmune, and genetic features in Japanese adult-onset diabetic patients with GAD autoantibodies.
RESEARCH DESIGN AND METHODS—GAD autoantibodies (GADab) were screened in 4,980 diabetic patients with age of onset &gt;20 years in the hospital-based Ehime Study, and the GADab-positive (GADab+) patients were then divided into two groups according to their insulin secretion and compared with nondiabetic subjects. The insulin-deficient state was defined as &lt;0.33 nmol/l serum C-peptide (CPR) at 2 h postprandial or 6 min after a 1-mg glucagon load.
RESULTS—GADab was detected in 188 (3.8%) of the 4,980 diabetic patients tested. Of these patients, 72 (38.3%) were classified as insulin deficient, 97 (51.6%) were classified as non–insulin deficient, and 19 (10.1%) were unclassified. The GADab+ insulin-deficient patients were characterized by young age at onset of diabetes, low BMI, low maximum BMI, and high levels of HbA1c. The prevalence of IA-2 autoantibodies and thyrogastric autoantibodies in the GADab+ insulin-deficient patients were significantly higher than those in the GADab+ non–insulin-deficient patients (P &lt; 0.05). GADab+ patients with insulin deficiency had increased frequencies of HLA DRB1*0405-DQB1*0401, *0802-*0302, and *0901-*0303 haplotypes, whereas the frequency of only HLA DRB1*0405-DQB1*0401 was increased in the case of GADab+ non–insulin-deficient patients. Of note is the fact that the GADab+ non–insulin-deficient group did not differ from healthy control subjects with respect to type 1 diabetes protective haplotype HLA DRB1*1502-DQB1*0601. A total of 13% of the GADab+ patients with diabetes had genotypes comprising the DRB1*1501-DQB1*0602 or *1502-*0601 and were characterized by old age at onset of diabetes, high BMI, resistance to the insulin-deficient state, low titer of GADab, and low frequency of other organ-specific autoantibodies.
CONCLUSIONS—We conclude that GADab+ non–insulin-deficient patients differ from GADab+ patients with insulin deficiency with respect to clinical characteristics, humoral autoimmunity to other organ-specific autoantibodies, as well as HLA class II genes.
Effect of Orlistat in Overweight and Obese Patients With Type 2 Diabetes Treated With Metformin
Authors: Miles John M. , Leiter Lawrence , Hollander Priscilla , Wadden Thomas , Anderson James W. , Doyle Michael , Foreyt John , Aronne Louis , Klein Samuel 
Published: March 2007

OBJECTIVE—The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—A 1-year multicenter, randomized, double-blind, placebo-controlled trial of 120 mg orlistat t.i.d. (n = 249) or placebo (n = 254) combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes.
RESULTS—After 1 year of treatment, mean (±SE) weight loss was greater in the orlistat than in the placebo group (−4.6 ± 0.3% vs. −1.7 ± 0.3% of baseline wt, P &lt; 0.001). Orlistat treatment caused a greater improvement in glycemic control than placebo, as evidenced by a greater reduction in serum HbA1c, adjusted for changes in metformin and sulfonylurea therapy (−0.90 ± 0.08 vs. −0.61 ± 0.08, P = 0.014); a greater proportion of patients achieving decreases in HbA1c of ≥0.5 and ≥1.0% (both P &lt; 0.01); and a greater reduction in fasting serum glucose (−2.0 ± 0.2 vs. −0.7 ± 0.2 mmol/l, P = 0.001). Compared with the placebo group, patients treated with orlistat also had greater decreases in total cholesterol, LDL cholesterol, and systolic blood pressure (all P &lt; 0.05). Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo (83 vs. 62%, P &lt; 0.05), more subjects in the placebo group withdrew prematurely from the study than in the orlistat group (44 vs. 35%, P &lt; 0.05).
CONCLUSIONS—Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control, serum lipid levels, and blood pressure in obese patients with type 2 diabetes who are being treated with metformin.
Development of a Prediction Equation for Insulin Sensitivity From Anthropometry and Fasting Insulin in Prepubertal and Early Pubertal Children
Authors: Huang Terry T.-K. , Johnson Maria S. , Goran Michael I. 
Published: March 2007

OBJECTIVE—To test the utility of homeostasis model assessment (HOMA) in predicting insulin sensitivity [×10− 4 min−1/(μIU/ml)] in children and to develop and compare two new prediction equations for insulin sensitivity in children using demographic and anthropometric measures in the presence or absence of fasting insulin.
RESEARCH DESIGN AND METHODS—We studied 156 white and African-American children with complete data (mean age 9.7 ± 1.8 years, 87.8% Tanner Stage 1 or 2). For development of new equations, two-thirds of the children were randomly assigned to a development group, whereas the remaining children were assigned to a cross-validation group.
RESULTS—A modified HOMA equation accurately predicted insulin sensitivity, but its utility is similar to fasting insulin alone. Demographic and anthropometric measures alone did not predict insulin sensitivity accurately, even when precise measures of body composition were included in the prediction model. Ethnicity, calf skinfold, and fasting insulin together explained 73% of the variance in insulin sensitivity and accurately predicted insulin sensitivity. The regression of measured versus predicted insulin sensitivity in the cross-validation group was not significantly different from the line of identity (P &gt; 0.05). Mean difference between measured and predicted insulin sensitivity was also not significant (P &gt; 0.05). Some bias was apparent, particularly in white boys.
CONCLUSIONS—Ethnicity, calf skinfold, and fasting insulin can accurately predict insulin sensitivity with greater precision than HOMA or fasting insulin alone (R2 = 0.73). Future studies, however, are needed to examine whether a universal equation is possible. A cross-validated prediction equation may be useful in population-based studies when complex measures of insulin sensitivity are not available.
Aggressive Lipid Lowering Does Not Improve Endothelial Function in Type 2 Diabetes
Authors: van Venrooij Francine V. , van de Ree Marcel A. , Bots Michiel L. , Stolk Ronald P. , Huisman Menno V. , Banga J. D. ,   on behalf of the DALI Study Group
Published: March 2007

OBJECTIVE—Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might be an effective method to improve endothelial function in these patients.
RESEARCH DESIGN AND METHODS—A randomized, double-blind, placebo-controlled trial was completed to study the effect of 30 weeks’ administration of atorvastatin 10 mg and 80 mg on endothelial function, as assessed by B-mode ultrasound of the brachial artery, in 133 patients with type 2 diabetes without a history of cardiovascular disease.
RESULTS—Patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction; mean flow-mediated vasodilation (SD) was 3.16% (3.56), and mean response on sublingual nitroglycerin was 6.58% (6.04). Despite substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent vasodilatation was found (P &gt; 0.8).
CONCLUSIONS—We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease. Aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction.
Survival in Patients With Type 2 Diabetes in a Swedish Community
Authors: Östgren Carl Johan , Lindblad Ulf , Melander Arne , Råstam Lennart 
Published: March 2007

OBJECTIVE—To explore risk factors for all-cause mortality in patients with type 2 diabetes treated in primary care.
RESEARCH DESIGN AND METHODS—A prospective population-based study of 400 patients with type 2 diabetes who consecutively completed an annual checkup in primary care in Skara, Sweden, during 1992–1993. Vital status was ascertained to year 2000. Baseline characteristics as predictors for mortality were analyzed by Cox regression and expressed as relative risks (RRs), with 95% CIs.
RESULTS—During a mean follow-up time of 5.9 years, 131 patients died (56 deaths per 1,000 patients per year). In both sexes, all-cause mortality was predicted by HbA1c (by 1%; RR 1.14, 95% CI 1.01–1.27), and by LDL-to-HDL cholesterol ratios (1.15, 1.00–1.32). Increased mortality was also seen with prevalent hypertension (1.72, 1.21–2.44), microalbuminuria (1.87, 1.27–2.76), and previous cardiovascular disease (1.70, 1.15–2.50). Subanalyses revealed that increased mortality related to HbA1c was restricted to hypertensive patients with type 2 diabetes (1.23, 1.04–1.47). Serum triglycerides (by 1 mmol/l) predicted all-cause mortality in women (1.25, 1.06–1.47).
CONCLUSIONS—Poor glucose and lipid control and hypertension predicted all-cause mortality. Survival was also predicted by prevalent microalbuminuria and by previous cardiovascular disease. Confirming results from clinical trials, this population-based study has implications for primary and secondary prevention.
Thyroid Autoimmunity in Children and Adolescents With Type 1 Diabetes
Authors: Kordonouri Olga , Klinghammer Albrecht , Lang Egbert B. , Grüters-Kieslich Annette , Grabert Matthias , Holl Reinhard W. ,   On behalf of the DPV-Initiative of the German Working Group for Pediatric Diabetology
Published: March 2007

OBJECTIVE—To investigate thyroid autoimmunity in a very large nationwide cohort of children and adolescents with type 1 diabetes.
RESEARCH DESIGN AND METHODS—Data were analyzed from 17,749 patients with type 1 diabetes aged 0.1–20 years who were treated in 118 pediatric diabetes centers in Germany and Austria. Antibodies to thyroglobulin (anti-TG) and thyroperoxidase (anti-TPO) were measured and documented at least once in 7,097 patients. A total of 49.5% of these patients were boys, the mean age was 12.4 years (range 0.3–20.0 years), and the mean duration of diabetes was 4.5 years (range 0.0–19.5 years). A titer exceeding 100 units/ml or 1:100 was considered significantly elevated.
RESULTS—In 1,530 patients, thyroid antibody levels were elevated on at least one occasion, whereas 5,567 were antibody-negative during the observation period. Patients with thyroid antibodies were significantly older (P &lt; 0.001), had a longer duration of diabetes (P &lt; 0.001), and developed diabetes later in life (P &lt; 0.001) than those without antibodies. A total of 63% of patients with positive antibodies were girls, compared with 45% of patients without antibodies (P &lt; 0.001). The prevalence of significant thyroid antibody titers increased with increasing age; the highest prevalence was in the 15- to 20-year age group (anti-TPO: 16.9%, P &lt; 0.001; anti-TG: 12.8%, P &lt; 0.001). Thyroid-stimulating hormone (TSH) levels were higher in patients with thyroid autoimmunity (3.34 μU/ml, range 0.0–615.0 μU/ml) than in control subjects (1.84 μU/ml, range 0.0–149.0 μU/ml) (P &lt; 0.001). Even higher TSH levels were observed in patients with both anti-TPO and anti-TG (4.55 μU/ml, range 0.0–197.0 μU/ml).
CONCLUSIONS—Thyroid autoimmunity seems to be particularly common in girls with diabetes during the second decade of life and may be associated with elevated TSH levels, indicating subclinical hypothyroidism.
Is Insulin Sensitivity a Causal Intermediate in the Relationship Between Alcohol Consumption and Carotid Atherosclerosis?
Authors: Cooper Daniel E. , Goff David C. , Bell Ronny A. , Zaccaro Dan , Mayer-Davis Elizabeth J. , Karter Andrew J. 
Published: March 2007

OBJECTIVE—A J-shaped association has been demonstrated between alcohol consumption and atherosclerosis. Insulin resistance, also a risk factor for atherosclerosis, has been shown to have a similar J-shaped association with alcohol intake. This raises the question of whether insulin sensitivity (SI) is a causal intermediate in the alcohol-atherosclerosis relationship.
RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study was a multicenter cohort study designed to investigate relationships among SI, risk factors for cardiovascular disease, and carotid artery atherosclerosis. Using regression analysis, we tested whether adjustment for SI attenuated the alcohol-atherosclerosis relationship observed at baseline.
RESULTS—A J-shaped association was observed between alcohol consumption and common carotid artery intimal medial thickness. The protective aspect of the alcohol-atherosclerosis relationship was attenuated by 25% after the adjustment for SI. However, an interaction was observed between alcohol consumption and glucose tolerance (GT) status. In comparison with never drinkers, all levels of alcohol consumption were associated with less atherosclerosis in participants with normal GT status. Participants with impaired GT status (but not diabetes) demonstrated a J-shaped alcohol-atherosclerosis association. All levels of alcohol consumption were associated with more atherosclerosis in participants with diabetes.
CONCLUSIONS—SI may be a causal intermediate at protective levels of alcohol intake, but an alcohol-GT interaction precluded a definitive conclusion. Moderate alcohol consumption may increase the risk of atherosclerosis in people with diabetes. These findings contrast with previous reports and do not support current recommendations regarding moderate alcohol consumption in people with diabetes. More research is needed to clarify this issue.
Intrinsic Muscle Atrophy and Toe Deformity in the Diabetic Neuropathic Foot
Authors: Bus Sicco A. , Yang Qing X. , Wang Jinghua H. , Smith Michael B. , Wunderlich Roshna , Cavanagh Peter R. 
Published: March 2007

OBJECTIVE—The objectives of this study were to compare intrinsic foot muscle cross-sectional area (CSA) in patients with diabetic polyneuropathy and nondiabetic control subjects and to examine the association between intrinsic muscle CSA and clawing/hammering of the toes in neuropathic feet.
RESEARCH DESIGN AND METHODS—High-resolution T2-weighted fast spin-echo images and parametric T2 multiple spin-echo images were acquired using multiple spin-echo magnetic resonance imaging (MRI) of frontal plane sections of the metatarsal region of the foot in a sample of eight individuals with diabetic polyneuropathy and eight age- and sex-matched nonneuropathic nondiabetic control subjects. The configuration of joints of the second toe was obtained using a three-dimensional contact digitizer.
RESULTS—Remarkable atrophy was found in all the intrinsic muscles of neuropathic subjects as compared with nondiabetic control subjects. Quantitative T2 analysis showed a 73% decrease in muscle tissue CSA distally in the neuropathic subjects. Muscle comprised only 8.3 ± 2.9% (means ± SD) of total foot CSA compared with 30.8 ± 3.9% in control subjects. No significant differences were found between the groups in the metatarso-phalangeal and proximal and distal interphalangeal joint angles of the second ray. Moreover, clawing/hammering of the toes was found in only two of eight neuropathic subjects.
CONCLUSIONS—Although sensory neuropathy is often emphasized in considerations of diabetic foot pathology, our results show that the consequences of motor neuropathy in the feet are profound in people with diabetes. This has implications for foot function and may play a significant role in postural instability. However, intrinsic muscle atrophy does not necessarily appear to imply toe deformity.
Association of Type and Duration of Diabetes With Erectile Dysfunction in a Large Cohort of Men
Authors: Bacon Constance G. , Hu Frank B. , Giovannucci Edward , Glasser Dale B. , Mittleman Murray A. , Rimm Eric B. 
Published: March 2007

OBJECTIVE—Differences in risk of erectile dysfunction (ED) by characteristics of diabetes among older men are not well understood. We examined the association of type and duration of diabetes with erectile function in men &gt;50 years of age in a large prospective cohort study.
RESEARCH DESIGN AND METHODS—Subjects included 31,027 men aged 53–90 years in the Health Professionals Follow-Up Study cohort. On a questionnaire mailed in 2000, participants rated their ability (without treatment) in the past 5 years to have and maintain an erection sufficient for intercourse. Men who reported poor or very poor function were considered to have ED. Diabetes information was ascertained via self-report and documented with supplementary medical data.
RESULTS—Men with diabetes had an age-adjusted relative risk (RR) of 1.32 (95% CI 1.3–1.4) for having ED compared with men without diabetes. In multivariable regression analyses, men with type 1 and type 2 diabetes were at a significantly higher risk for ED (type 1 diabetes RR = 3.0, 95% CI 1.5–5.9; type 2 diabetes RR = 1.3, 1.1–1.5) than nondiabetic men. Men with type 2 diabetes had an increasingly greater risk of ED with increased duration since diagnosis (trend test P value &lt;0.0001) (RR = 1.7, 95% CI 1.1–2.7, for men diagnosed &gt;20 years previously).
CONCLUSIONS—For men over age 50 years, increasing duration of diabetes was positively associated with increased risk of ED relative to nondiabetic subjects. This association persisted despite the higher prevalence of other comorbid conditions. ED prevention and diabetes management efforts are likely to go hand-in-hand.
Improvement of BMI, Body Composition, and Body Fat Distribution With Lifestyle Modification in Japanese Americans With Impaired Glucose Tolerance
Authors: Liao David , Asberry Pamela J. , Shofer Jane B. , Callahan Holly , Matthys Colleen , Boyko Edward J. , Leonetti Donna , Kahn Steven E. , Austin Melissa , Newell Laura , Schwartz Robert S. , Fujimoto Wilfred Y. 
Published: March 2007

OBJECTIVE—To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance (IGT).
RESEARCH DESIGN AND METHODS—This study compared the effects of an American Heart Association (AHA) step 2 diet (&lt;30% of total calories as fat, &lt;7% saturated fat, 55% carbohydrate, and &lt; 200 mg cholesterol daily) plus endurance exercise for 1 h three times a week (treatment group) with an AHA step 1 diet (30% of total calories as fat, 10% saturated fat, 50% carbohydrate, and &lt;300 mg cholesterol) plus stretching exercise three times a week (control group) on BMI, body composition (% fat), and body fat distribution at 6 and 24 months of follow-up in 64 Japanese American men and women with IGT, 58 of whom completed the study.
RESULTS—At 6 months, the treatment group showed significantly greater reduction in percent, body fat (−1.4 ± 0.4 vs. −0.3 ± 0.3%); BMI (−1.1 ± 0.2 vs. −0.4 ± 0.1 kg/m2); subcutaneous fat by computed tomography at the abdomen (−29.3 ± 4.2 vs. −5.7 ± 5.9 cm2), thigh (−13.2 ± 3.6 vs. −3.6 ± 3.0 cm2), and thorax (−19.6 ± 3.6 vs. −8.9 ± 2.6 cm2); and skinfold thickness at the bicep (−2.0 ± 0.6 vs. 1.1 ± 0.6 mm) and tricep (−3.7 ± 0.8 vs. −0.9 ± 0.6 mm), which continued despite moving to home-based exercise for the last 18 months.
CONCLUSIONS—Diet and endurance exercise improved BMI, body composition, and body fat distribution and, thus, may delay or prevent type 2 diabetes in Japanese Americans with IGT.
Fetal Overnutrition in Polynesian Pregnancies and in Gestational Diabetes May Lead to Dysregulation of the Adipoinsular Axis in Offspring
Authors: Simmons David , Breier Bernhard H. 
Published: March 2007

OBJECTIVE—To compare umbilical cord leptin concentrations in different ethnic groups and between pregnancies with and without gestational diabetes mellitus (GDM) in Auckland, New Zealand.
RESEARCH DESIGN AND METHODS—A cross-sectional study of 116 European, Polynesian, and South Asian women and their infants with and without GDM. Maternal metabolic measures were recorded at 36 weeks’ gestation, umbilical cord samples were collected at birth, and neonatal anthropometric measures were recorded 24 h after delivery.
RESULTS—Compared with Europeans and South Asians, samples of Polynesian umbilical cords had higher leptin concentrations (8.7 and 9.5 vs. 14.9 ng/ml, respectively; P = 0.026). Umbilical cord samples from pregnancies complicated by GDM had higher leptin concentrations than those from normal pregnancies (22.3 vs. 13.8 ng/ml, respectively; P = 0.022). Maternal leptin concentrations at 36 weeks were similar across ethnic groups and with and without GDM. Cord leptin correlated with birth weight, measures of fetal size, and cord insulin in normal pregnancies and those complicated by GDM. In multivariate analyses, cord leptin was related to birth weight (P &lt; 0.001), gestation at delivery (P = 0.038), and ethnic group (P = 0.017) in normal pregnancies and to birth weight (P &lt; 0.001), gestation at delivery (P &lt; 0.001), and sex (P = 0.003) but not maternal diabetes status (P = 0.909) in pregnancies complicated by GDM.
CONCLUSIONS—Offspring of Polynesian women are relatively hyperleptinemic, independent of birth size. Offspring of women with GDM are also relatively hyperleptinemic at birth, but this was associated with their increased birth weight. We speculate that this GDM-associated relative hyperleptinemia may be due to fuel-mediated teratogenesis affecting the adipoinsular axis, which in turn could also lead to leptin resistance and obesity in adult life. The reason for the ethnic difference in hyperleptinemia is unclear.