bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Falls, Risk Factors for Falls, and Fall-Related Fractures in Individuals With Diabetes and a Prior Foot Ulcer
Authors: Wallace Carolyn , Reiber Gayle E. , LeMaster Joseph , Smith Douglas G. , Sullivan Katrina , Hayes Shane , Vath Christy 
Published: March 2007

OBJECTIVE—To describe the incidence of falls, risk factors for falls, and the frequency of fall-related fractures in a cohort of individuals with diabetes and a prior foot ulcer.
RESEARCH DESIGN AND METHODS—A total of 400 individuals with diabetes and a prior foot ulcer were recruited from two western Washington State health care organizations and followed prospectively for 2 years. Diabetes, demographic, and health information was collected at baseline, 1 year, and 2 years. Data on falls were collected at baseline, 4 weeks, and every 17 weeks thereafter. Medical records were abstracted to confirm fall-related morbidity.
RESULTS—The average age of the study population was 62 years, with 77% male and 23% female. Approximately 32% had fixed foot deformities, 58% had insensate feet, and 76% had comorbid conditions. Of the participants, 252 (64%) reported at least one fall during the 2-year study period. The overall incidence of falls in this cohort was 1.25 falls/person-year (95% CI 1.17–1.33). For the 164 participants (41%) who reported two or more falls, a BMI ≥30 kg/m2, the presence of one or more comorbid conditions, and insensate feet increased the risk. Two or more falls of any type were associated with a higher fracture risk. Although women were not at significantly greater risk for falls than men, their fracture incidence was 3.6 times higher.
CONCLUSIONS—Falls are very common in individuals with diabetes and prior foot ulcers. A small percentage of falls resulted in fractures. The risk of a fall-related fracture was significantly higher in women than in men. Increased attention to falls and fall prevention is indicated for diabetes care providers.
Effects of Tadalafil on Erectile Dysfunction in Men With Diabetes
Authors: Sáenz de Tejada Iñigo , Anglin Greg , Knight James R. , Emmick Jeffrey T. 
Published: March 2007

OBJECTIVE—To evaluate the efficacy and safety of tadalafil taken as needed before sexual activity by men with diabetes and erectile dysfunction (ED).
RESEARCH DESIGN AND METHODS—Men with type 1 or type 2 diabetes and a minimum 3-month history of ED were randomly allocated to one of three groups: placebo (n = 71), tadalafil 10 mg (n = 73), or tadalafil 20 mg (n = 72) taken up to once daily for 12 weeks. Changes from baseline in mean scores on the erectile function domain of the International Index of Erectile Function (IIEF) and changes from baseline in the proportion of “yes” responses to question 2, “Were you able to penetrate?,” and 3, “Were you able to complete intercourse?,” of the Sexual Encounter Profile were coprimary outcome measures.
RESULTS—A total of 191 (88%) of 216 patients completed the study. Treatment with tadalafil significantly improved all primary efficacy variables, regardless of baseline HbA1c level. Therapy with tadalafil also significantly improved a number of secondary outcome measures, including changes in other IIEF domains, individual IIEF questions, and percentage of positive responses to a global assessment question measuring erection improvement. Treatment with tadalafil did not alter mean HbA1c levels. Tadalafil was well tolerated, with headache and dyspepsia being the most frequent adverse events with active treatment.
CONCLUSIONS—Tadalafil therapy significantly enhanced erectile function and was well tolerated by men with diabetes and ED.
Diabetes in Ontario
Authors: Hux Janet E. , Ivis Frank , Flintoft Virginia , Bica Adina 
Published: March 2007

OBJECTIVE—Accurate information about the magnitude and distribution of diabetes can inform policy and support health care evaluation. We linked physician service claims (PSCs) and hospital discharge abstracts (HDAs) to determine diabetes prevalence and incidence.
RESEARCH DESIGN AND METHODS—A retrospective cohort was constructed using administrative data from the national HDA database, PSCs for Ontario (population 11 million), and registries carrying demographics and vital statistics. All HDAs and PSCs bearing a diagnosis of diabetes (ICD9-CM 250) were selected for 1991–1999. Two previously reported algorithms for identification of diabetes were applied as follows: “1-claim” (any HDA or PSC showing diabetes) and “2-claim” (one HDA or two PSCs within 2 years showing diabetes). Incident cases were defined as individuals who met the criteria for diabetes for the first time after at least 2 years of observation. For validation, diagnostic data abstracted from primary care charts (n=3,317) of 57 randomly selected physicians were linked to the administrative data cohort, and sensitivity and specificity were calculated.
RESULTS—In 1998, 696,938 individuals met the 1-claim criteria and 528,280 met the 2-claim criteria. Sensitivity for diabetes was 90 and 86%; for the 1- and 2-claim algorithms, specificity was 92 and 97%, respectively, and positive predictive values were 61 and 80%, respectively. Using the 2-claim algorithm, the all-age prevalence increased from 3.2% in 1993 to 4.5% in 1998 (6.1% in adults). Incidence remained stable.
CONCLUSIONS—Administrative data can be used to establish population-based incidence and prevalence of diabetes. Diabetes prevalence is increasing in Ontario and is considerably higher than self-reported rates.
The Gly972Arg Polymorphism in Insulin Receptor Substrate-1 Is Associated With Decreased Birth Weight in a Population-Based Sample of Brazilian Newborns
Authors: Bezerra Rosângela M.N. , de Castro Vagner , Sales Teresa , Passini Renato , Marba Sergio T.M. , Saad Sara T.O. , Saad Mario J.A. 
Published: March 2007

OBJECTIVE—We studied the association between the Gly972Arg polymorphism in insulin receptor substrate-1 (IRS-1) and birth weight in a population-based sample of Brazilian newborns.
RESEARCH DESIGN AND METHODS—We studied 194 newborn children with adequate gestational age to identify the association between the Gly972Arg polymorphism and birth weight using PCR—restriction fragment length polymorphism analysis.
RESULTS—The data showed that the birth weight was lower in the newborns with the Gly972Arg polymorphism in IRS-1 compared with control subjects (3,141 ±31.8 vs. 3,373 ±80.3 g, P &lt; 0.008). The results also showed that the frequency of this polymorphism was increased in newborns with a birth weight &lt;3,000 g (P=0.041).
CONCLUSIONS—These results suggest that the genotype Gly972Arg may influence birth weight, reinforcing the hypothesis that genetically determined insulin resistance and/or reduced insulin secretion can result in impaired insulin-mediated growth in the fetus.
Elevated Remnant-Like Particle Cholesterol and Triglyceride Levels in Diabetic Men and Women in the Framingham Offspring Study
Authors: Schaefer Ernst J. , McNamara Judith R. , Shah Paulesh K. , Nakajima Katsuyuki , Cupples L. Adrienne , Ordovas Jose M. , Wilson Peter W.F. 
Published: March 2007

OBJECTIVE—Remnants of triglyceride-rich lipoproteins are thought to be atherogenic. A new antibody-based assay allows for the isolation of remnant-like particles (RLPs) from plasma or serum, and the subsequent measurement of RLP cholesterol (RLPC) and triglycerides (RLPTGs). We hypothesized that diabetic patients would have higher remnant levels than nondiabetic patients.
DESIGN AND METHODS—We compared RLPC and RLPTG levels of diabetic subjects (68 women, 121 men) participating in the Framingham Heart Study with those of nondiabetic subjects (1,499 women, 1,357 men).
RESULTS—Mean RLPC values for diabetic women were 106% higher than those for nondiabetic women (0.367 ± 0.546 mmol/l [14.2 ± 21.1 mg/dl] vs. 0.179 ± 0.109 mmol/l [6.9 ± 4.2 mg/dl]; P &lt; 0.0001), and RLPTG values for diabetic women were 385% higher than those for nondiabetic women (1.089 ± 2.775 mmol/l [93.1 ± 245.6 mg/dl] vs. 0.217 ± 0.235 mmol/l [19.2 ± 20.8 mg/dl]; P &lt; 0.0001). Similar but less striking differences were observed in diabetic men, who had mean RLPC values 28% higher than those seen in nondiabetic men (0.285 ± 0.261 mmol/l [11.0 ± 10.1 mg/dl] vs. 0.223 ± 0.163 mmol/l [8.6 ± 6.3 mg/dl]; P &lt; 0.001) and mean RLPTG values 70% higher than those seen in nondiabetic men (0.606 ± 1.019 mmol/l [53.6 ± 90.2 mg/dl] vs. 0.357 ± 0.546 mmol/l [31.6 ± 48.3 mg/dl]; P &lt; 0.001). Moreover, diabetic men and women had significantly higher total triglycerides and lower HDL cholesterol levels than nondiabetic subjects.
CONCLUSIONS—The data indicate that RLP particles are elevated in diabetic subjects. To achieve optimal reduction of risk for cardiovascular disease, treatment of elevated RLP values, along with the control of LDL cholesterol levels, should be considered.
Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of a Single-Dose of NN2211, a Long-Acting Glucagon-Like Peptide 1 Derivative, in Healthy Male Subjects
Authors: Elbrønd Bodil , Jakobsen Grethe , Larsen Søren , Agersø Henrik , Jensen Lisbeth Bjerring , Rolan Paul , Sturis Jeppe , Hatorp Vibeke , Zdravkovic Milan 
Published: March 2007

OBJECTIVE—The primary objective of the present study was to investigate the safety, tolerability, and pharmacokinetics of a single dose of NN2211, a long-acting glucagon-like peptide 1 (GLP-1) derivative, in healthy male subjects. The secondary objective was to investigate the pharmacodynamics of NN2211.
RESEARCH DESIGN AND METHODS—In a double-blind, randomized dose, escalation, placebo-controlled study, healthy male subjects were enrolled at eight consecutive dose levels (1.25, 2.5, 5.0, 10.0, 12.5, 15.0, 17.5, and 20.0 μg/kg) with eight subjects per dose level at a 3:1 active:placebo randomization. After subcutaneous dosing with NN2211, 48-h pharmacokinetic, and 24-h glucose, insulin and glucagon profiles were assessed. In addition, three subjects at each dose level were randomly assigned (one placebo/two active) to an intravenous glucose tolerance test (IVGTT) 9 h after the dose (corresponding to the time to maximal plasma concentration of NN2211).
RESULTS—After subcutaneous administration, the half-life of NN2211 was found to be 11–15 h. Overall, although there were no statistically significant differences compared with placebo in the area under the curve (0–9 h for insulin or glucagon), there was a borderline- significant lowering of glucose levels (P = 0.066). During the IVGTT, there was a statistically significant increase in insulin secretion (P = 0.0002), but there was no significant effect on glucagon levels. Although no significant effect was observed on glucose levels during the IVGTT, there was a dose-dependent increase in the glucose disappearance constant. Whereas no serious adverse events were observed, there was a higher incidence of adverse events after active treatment compared with placebo treatment (notably headache, dizziness, nausea, and vomiting).
CONCLUSIONS—This study provides evidence that NN2211 has a pharmacokinetic profile consistent with once-daily dosing in humans.
Pupil Signs of Sympathetic Autonomic Neuropathy in Patients With Type 1 Diabetes
Authors: Pittasch Daniel , Lobmann Ralf , Behrens-Baumann Wolfgang , Lehnert Hendrik 
Published: March 2007

OBJECTIVE—Pupillary autonomic neuropathy is considered an early sign of the development of systemic autonomic neuropathy. Sympathetic denervation is related to the duration of diabetes and the development of systemic autonomic dysfunction. We investigated pupil responsiveness to directly and indirectly acting sympathomimetics in type 1 diabetic patients with and without long-term complications, defined as cardiac autonomic neuropathy (CAN), peripheral sensomotor neuropathy, retinopathy, and nephropathy, and in healthy subjects.
RESEARCH DESIGN AND METHODS—A total of 47 randomly chosen type 1 diabetic patients and 20 healthy subjects were selected for this study. Patients were divided into groups determined by whether they had long-term diabetic complications. Pharmacological tests were performed with cocaine 4%, epinephrine 1%, and pholedrine 5% eye drops. Horizontal pupil diameter (HPD) was measured at the beginning of the pharmacological tests and at defined time points after instillation of the eye drops.
RESULTS—Statistical analysis showed a significantly smaller HPD in the patients before instillating eye drops (P = 0.011). In particular, the HPD was significantly smaller in the patient group without CAN when compared with healthy subjects (P = 0.004). Maximal cocaine reaction was diminished in the complication group (P &lt; 0.001). Epinephrine test, visual acuity, ocular pressure, and HbA1c did not differ in patients with or without long-term complications. The noncomplication group showed no significant differences in pupillary responses as compared with healthy subjects. The complication group showed a smaller HPD (P = 0.022), reduced pupillary responses in the cocaine (P = 0.037) and pholedrine tests (P &lt; 0.001), and anisocor pupil sizes after instillation of the eye drops (P = 0.034).
CONCLUSIONS—Our results clearly show that sympathetic denervation does exist in the pupil of diabetic patients and that it can be rapidly assessed using the cocaine test. These data and the results of the epinephrine test suggest a mixed pre- and postganglionic dysfunction of the sympathetic plexus. The significant smaller HPD in patients without CAN compared with that of healthy subjects could be a sign for early involvement of the pupil function before cardiac manifestation of systemic autonomic diabetic neuropathy.
Effect of Long-Term Exposure to Insulin Lispro on the Induction of Antibody Response in Patients With Type 1 or Type 2 Diabetes
Authors: Fineberg S. Edwin , Huang Jie , Brunelle Rocco , Gulliya K. S. , Anderson James H. 
Published: March 2007

OBJECTIVE—To determine the long-term effects of insulin lispro on inducing lispro-specific, insulin-specific, and cross-reactive (reactive with both insulin lispro and human insulin) antibodies.
RESEARCH DESIGN AND METHODS—A multinational, multicenter combination of controlled and noncontrolled, open-label studies of 4.5 years’ duration was designed to evaluate the long-term immunologic profile of subcutaneously administered insulin lispro. A total of 1,221 patients (men and women; 12–81 years of age) with type 1 or type 2 diabetes were enrolled. Circulating anti-insulin antibodies were measured using radioimmunoassays.
RESULTS—Insulin-specific and lispro-specific antibody responses were within the background noise levels of the assays. Significant elevations of antibody were confined to a cross-reactive antibody response. Antibody levels resulting from prior exposure to long- and short-acting insulins changed little after transfer to insulin lispro and remained within or near the baseline levels. De novo exposure to insulin lispro resulted in increases in cross-reactive but not insulin- or lispro-specific antibody levels. Cross-reactive insulin antibodies developed more readily in patients with type 1 diabetes than in those with type 2 diabetes. Long-term antibody responses tended to decrease over time and returned to baseline or near-baseline levels by the end of the long-term studies. No evidence of an anamnestic antibody response could be found in individuals treated intermittently with insulin lispro.
CONCLUSIONS—The immunogenic profile of patients treated with insulin lispro was comparable to that of patients treated with recombinant human insulin. Inductions of significant levels of specific or cross-reactive antibodies were not observed in patients who had received insulin previously. No significant antibody-dependent increases in insulin dosage requirements were noted in these patients. The incidence of insulin allergy was not different from that in patients treated with recombinant regular human insulin.
Predictive Properties of Impaired Glucose Tolerance for Cardiovascular Risk Are Not Explained by the Development of Overt Diabetes During Follow-Up
Authors: Qiao Qing , Jousilahti Pekka , Eriksson Johan , Tuomilehto Jaakko 
Published: March 2007

OBJECTIVE—To evaluate the relationship of impaired glucose tolerance (IGT) at baseline to coronary heart disease (CHD) incidence, and cardiovascular disease (CVD) and total mortality at follow-up, and to analyze whether the relationship is independent of the subsequent development of diabetes during follow-up.
RESEARCH DESIGN AND METHODS—A baseline screening survey for diabetes was performed in 1987 using a 2-h 75-g oral glucose tolerance test. A total of 1,234 men and 1,386 women aged 45–64 years, who were free of diabetes at baseline, were followed up for 10 years. During the follow-up, 153 subjects had an incident CHD event, 224 died, and 100 deaths were due to cardiovascular causes. Multivariate adjusted (adjusted for age, sex, waist-to-hip ratio, systolic blood pressure, cholesterol, HDL cholesterol, and smoking) hazard ratio (HR) was estimated using Cox regression analysis.
RESULTS—In subjects who had IGT at baseline and who did not progress to diabetes during the follow-up, the multivariate adjusted HR (95% CI) was 1.49 (0.95–2.34) for CHD incidence, 2.34 (1.42–3.85) for CVD mortality, and 1.65 (1.13–2.40) for all-cause mortality.
CONCLUSIONS—Baseline IGT was an independent risk predictor for cardiovascular morbidity and mortality and for total mortality, which was not confounded by the subsequent development of overt diabetes.
Progression of Coronary Artery Calcification in Type 1 Diabetes
Authors: Snell-Bergeon Janet K. , Hokanson John E. , Jensen Lisa , MacKenzie Todd , Kinney Gregory , Dabelea Dana , Eckel Robert H. , Ehrlich James , Garg Satish , Rewers Marian 
Published: March 2007

OBJECTIVE—Coronary artery disease (CAD) occurs earlier in life and is more often fatal in people with type 1 diabetes. This excess risk seems to be higher than in those with type 2 diabetes and is poorly explained by conventional risk factors. The role of glycemic control is controversial and has not been previously addressed in a prospective manner using a reliable marker for subclinical CAD, such as coronary artery calcification (CAC), measured by electron beam computed tomography (EBCT).
RESEARCH DESIGN AND METHODS—We measured CAC twice during an interval of 2.7 years in 109 men and women with type 1 diabetes (aged 22–50 years). Progression of CAC was found in 21 patients, based on change in the square root-transformed volume score.
RESULTS—In multiple logistic regression, CAC progression was associated with baseline hyperglycemia (odds ratio [OR] 7.11, 95% CI 1.38–36.6, P = 0.02), adjusted for the presence of CAC at baseline (P = 0.01), duration of diabetes (P = 0.02), sex (P = 0.09), and age (P = 0.27). There was also a significant interactive effect of higher insulin dose and higher BMI (P = 0.03).
CONCLUSIONS—In conclusion, in this young cohort with type 1 diabetes, suboptimal glycemic control (HbA1c &gt;7.5%) was a strong risk factor for progression of CAC. Insulin resistance may also play a role.
Prevalence of Delayed Gastric Emptying in Diabetic Patients and Relationship to Dyspeptic Symptoms
Authors: Samsom M. , Vermeijden J.R. , Smout A.J.P.M. , van Doorn E. , Roelofs J. , van Dam P.S. , Martens E.P. , Eelkman-Rooda S.J. , van Berge-Henegouwen G.P. 
Published: March 2007

OBJECTIVE—Data on the prevalence of abnormal gastric emptying in diabetic patients are still lacking. The relation between gastric emptying and dyspeptic symptoms assessed during gastric emptying measurement has not yet been investigated. The aim was to investigate the prevalence of delayed gastric emptying in a large cohort of unselected diabetic patients and to investigate the relation between gastric emptying and gastrointestinal sensations experienced in the 2 weeks before and during the test meal, prospectively.
RESEARCH DESIGN AND METHODS—Gastric emptying was evaluated in 186 patients (106 with type 1 diabetes, mean duration of diabetes 11.6 ± 11.3 years) using 100 mg 13C-enriched octanoic acid added to a solid meal.
RESULTS—Gastric emptying was significantly slower in the diabetic subjects than in the healthy volunteers (T50: 99.5 ± 35.4 vs. 76.8 ± 21.4 min, P &lt; 0.003; Ret120 min: 30.6 ± 17.2 vs. 20.4 ± 9.7%, P &lt; 0.006). Delayed gastric emptying was observed in 51 (28%) diabetic subjects. The sensations experienced in the 2 weeks before the test were weakly correlated with the sensation scored during the gastric emptying test. Sensations assessed during the gastric emptying test did predict gastric emptying to some extent (r = 0.46, P &lt; 0.0001), whereas sensations experienced in the previous 2 weeks did not.
CONCLUSIONS—This prospective study shows that delayed gastric emptying can be observed in 28% of unselected patients with diabetes. Upper gastrointestinal sensations scored during the gastric emptying tests do predict the rate of gastric emptying to some extent and sensation experienced during daily life does not.
Insulin Suppresses Plasma Concentration of Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9
Authors: Dandona Paresh , Aljada Ahmad , Mohanty Priya , Ghanim Husam , Bandyopadhyay Arindam , Chaudhuri Ajay 
Published: March 2007

OBJECTIVE—We recently demonstrated a potent anti-inflammatory and thus a potential antiatherogenic effect of insulin in human aortic endothelial cells and mononuclear cells at physiologically relevant concentrations. We have now further investigated the anti-inflammatory suppressive action of insulin on vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9. VEGF and MMP-9 play a central regulatory role in angiogenesis, contribute to the pathogenesis of proliferative retinopathy, and have also been found to accelerate atherosclerosis.
RESEARCH DESIGN AND METHODS—Insulin was infused (2 IU/h) in 5% dextrose (100 ml/h) and KCl (8 mmol/h) into 10 fasting, obese, nondiabetic subjects for 4 h. Subjects were also infused with 5% dextrose without insulin and with saline on two separate occasions. Blood samples were obtained at 0, 2, 4, and 6 h.
RESULTS—Plasma insulin concentrations increased from a basal level of 12.5 ± 2.2 to 28.2 ± 3.3 μU/ml at 2 h and 24.4 ± 3.7 μU/ml at 4 h after insulin infusion. VEGF concentration decreased from 307.2 ± 163.8 pg/ml (100%) at 0 h to 73.5 ± 20.9% of the basal level at 2 h and 67.1 ± 23.2% at 4h. Plasma MMP-9 concentrations decreased from 375 ± 196.3 ng/ml (100%) at 0 h to 83 ± 22% of the basal level at 2 h and to 82 ± 21% of the basal level at 4 h (P &lt; 0.05). Dextrose infusion alone did not change plasma VEGF concentration. However, plasma MMP-9 concentration increased significantly at 4 h following dextrose infusion alone (P &lt; 0.05). Saline infusions without insulin caused no alteration in glucose, insulin, VEGF, or MMP-9.
CONCLUSIONS—These observations may have implications for a potential antiretinopathic and antiatherosclerotic effect of insulin in the long term.