bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic β-Cell Function and Immune Responses to Insulin After Administration of Intranasal Insulin to Humans At Risk for Type 1 Diabetes
Authors: Harrison Leonard C. , Honeyman Margo C. , Steele Cheryl E. , Stone Natalie L. , Sarugeri Elena , Bonifacio Ezio , Couper Jennifer J. , Colman Peter G. 
Published: March 2007

OBJECTIVE—Mucosal administration of insulin retards development of autoimmune diabetes in the nonobese diabetic mouse model. We conducted a double-blind crossover study in humans at risk for type 1 diabetes to determine if intranasal insulin was safe, in particular did not accelerate β-cell destruction, and could induce immune effects consistent with mucosal tolerance.RESEARCH DESIGN AND METHODS—A total of 38 individuals, median age 10.8 years, with antibodies to one or more pancreatic islet antigens (insulin, GAD65, or tyrosine phosphatase-like insulinoma antigen 2) were randomized to treatment with intranasal insulin (1.6 mg) or a carrier solution, daily for 10 days and then 2 days a week for 6 months, before crossover. The primary outcome was β-cell function measured as first-phase insulin response (FPIR) to intravenous glucose at 0, 6, and 12 months and then yearly; the secondary outcome was immunity to islet antigens, measured monthly for 12 months.RESULTS—No local or systemic adverse effects were observed. Diabetes developed in 12 participants with negligible β-cell function at entry after a median of 1.1 year. Of the remaining 26, the majority had antibodies to two or three islet antigens and FPIR greater than the first percentile at entry, as well as β-cell function that generally remained stable over a median follow-up of 3.0 years. Intranasal insulin was associated with an increase in antibody and a decrease in T-cell responses to insulin.CONCLUSIONS—Results from this pilot study suggest that intranasal insulin does not accelerate loss of β-cell function in individuals at risk for type 1 diabetes and induces immune changes consistent with mucosal tolerance to insulin. These findings justify a formal trial to determine if intranasal insulin is immunotherapeutic and retards progression to clinical diabetes.
Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 2 Diabetes
Authors: Hollander Priscilla A. , Blonde Lawrence , Rowe Richard , Mehta Adi E. , Milburn Joseph L. , Hershon Kenneth S. , Chiasson Jean-Louis , Levin Seymour R. ,   for the Exubera Phase III Study Group
Published: March 2007

OBJECTIVE— Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections.
RESEARCH DESIGN AND METHODS— Patients were randomized to 6 months’ treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA1c from baseline to the end of study.
RESULTS— HbA1c decreased similarly in the inhaled (−0.7%) and subcutaneous (−0.6%) insulin groups (adjusted treatment group difference: −0.07%, 95% CI −0.32 to 0.17). HbA1c &lt;7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24–4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82–0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group.
CONCLUSIONS— Inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen.
Plantar Fat-Pad Displacement in Neuropathic Diabetic Patients With Toe Deformity
Authors: Bus Sicco A. , Maas Mario , Cavanagh Peter R. , Michels Robert P. J. , Levi Marcel 
Published: March 2007

OBJECTIVE—The aim of this study was to quantify the association between claw/hammer toe deformity and changes in submetatarsal head (sub-MTH) fat-pad geometry in diabetic neuropathic feet.
RESEARCH DESIGN AND METHODS—Thirteen neuropathic diabetic subjects (mean age 56.2 years) with toe deformity, 13 age- and sex-matched neuropathic diabetic control subjects without deformity, and 13 age- and sex-matched healthy control subjects without deformity were examined. From high-resolution sagittal plane magnetic resonance images of the second and third ray of the foot, toe angle (a measure of deformity), sub-MTH fat-pad thickness, and subphalangeal fat-pad thickness were measured. The ratio of these thicknesses was used to indicate fat-pad displacement.
RESULTS—Sub-MTH fat pads were significantly thinner (2.5 ± 1.3 vs. 6.0 ± 1.4 mm, P &lt; 0.001) and subphalangeal fat pads significantly thicker (9.1 ± 1.9 vs. 7.6 ± 1.2 mm, P &lt; 0.005) in the neuropathic group with deformity compared with neuropathic control subjects. As a result, thickness ratio was substantially smaller in the deformity group: 0.28 ± 0.14 vs. 0.79 ± 0.14 in neuropathic control subjects (P &lt; 0.001). A significant correlation of 0.85 was present between toe angle and thickness ratio (P &lt; 0.001). No significant differences were found between neuropathic and healthy control subjects.
CONCLUSIONS—This study shows a distal displacement and subsequent thinning of the sub-MTH fat pads in neuropathic diabetic patients with toe deformity and suggests that, as a result, the capacity of the tissue in this region to reduce focal plantar pressure is severely compromised. This condition is likely to increase the risk of plantar ulceration in these patients.
β-Cell Dysfunction in Classic Transient Neonatal Diabetes Is Characterized by Impaired Insulin Response to Glucose but Normal Response to Glucagon
Authors: Valerio Giuliana , Franzese Adriana , Salerno Mariacarolina , Muzzi Gianluca , Cecere Gaetano , Temple Karen I. , Shield Julian P. 
Published: March 2007

OBJECTIVE—To investigate β-cell function and the long-term health of four case subjects presenting with chromosome 6–associated transient neonatal diabetes (TND).
RESEARCH DESIGN AND METHODS—Two unrelated case subjects presenting with paternal uniparental isodisomy of chromosome 6 (UPD6) and two siblings with a paternally inherited duplication of 6q24 were studied. Three case subjects presented with neonatal diabetes that recurred at 4–17 years, while diabetes was incidentally discovered in the other case subject at 14 years of age. β-Cell function was investigated after diabetes relapse by means of an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and glucagon tests. The quantitative insulin sensitivity check index (QUICKI) was calculated from fasting blood samples as an estimate of insulin sensitivity.
RESULTS—β-Cell function was investigated at diabetes relapse in two case subjects: the insulin response to both an OGTT and IVGTT was low, whereas the basal levels of C-peptide were normal. No evidence of insulin resistance was found. Residual β-cell function was further explored by a glucagon test in all subjects at the age of 16–28 years and was found to be normal. Final height was within the normal percentiles, whereas one case, who had been poorly controlled since puberty, presented with diabetes-related microvascular complications.
CONCLUSIONS—In patients with chromosome 6–associated TND, the β-cell is preserved and able to secrete insulin through the stimulatory G protein pathway while exhibiting a specific defect of insulin secretion after glucose stimulation. This form of diabetes can be managed with insulin or diet, although new therapeutic agents (glucagon-like synthetic analogs) may prove useful in the future. Lack of treatment leads to long-lasting hyperglycemia without the risk of ketoacidosis but associated with microangiopathy in adult life.
Stiffness and Impaired Blood Flow in Lower-Leg Arteries Are Associated With Severity of Coronary Artery Calcification Among Asymptomatic Type 2 Diabetic Patients
Authors: Tsuchiya Masanobu , Suzuki Eiji , Egawa Katsuya , Nishio Yoshihiko , Maegawa Hiroshi , Inoue Shinji , Mitsunami Kenichi , Morikawa Shigehiro , Inubushi Toshiro , Kashiwagi Atsunori 
Published: March 2007

OBJECTIVE—To clarify whether stiffness and impaired blood flow in lower-leg arteries are associated with severity of coronary artery calcification among asymptomatic diabetic patients.
RESEARCH DESIGN AND METHODS—We enrolled 102 asymptomatic type 2 diabetic patients with no history of cardiovascular complications consecutively admitted to our hospital. Agatston coronary artery calcium (CAC) score, as a marker of coronary artery calcification, was obtained using electron-beam computed tomography. Total flow volume and resistive index, as an index of vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Brachial-ankle pulse-wave velocity (PWV), as an index of distensibility in the lower-extremity arteries, was also measured using an automatic device.
RESULTS—When the patients were grouped according to CAC scores of 0–10 (n = 54), 11–100 (n = 25), and &gt;100 (n = 23), those with the highest scores, which is considered to show possible coronary artery disease, showed the highest brachial-ankle PWV (P &lt; 0.001) and resistive index (P &lt; 0.001) and the lowest total flow volume (P &lt; 0.001) among the groups. Simple linear regression analyses showed that both brachial-ankle PWV (r = 0.508, P &lt; 0.001) and resistive index (r = 0.500, P &lt; 0.001) were positively correlated and total flow volume (r = −0.528, P &lt; 0.001) was negatively correlated with the log-transformed CAC score. Receiver operator characteristic curve analyses indicated that 1,800 cm/s for brachial-ankle PWV, 1.03 for resistive index, and 70 ml/min for total flow volume were diagnostic values for identifying patients with the highest scores.
CONCLUSIONS—Quantitatively assessed stiffness and impaired blood flow in lower-leg arteries may help identify diabetic patients with possible coronary artery disease.
What is a Normal Glucose Value?
Authors: Piché Marie-Éve , Arcand-Bossé Jean-Francois , Després Jean-Pierre , Pérusse Louis , Lemieux Simone , Weisnagel S. John 
Published: March 2007

OBJECTIVE—To evaluate differences in indexes of plasma glucose/insulin homeostasis and cardiovascular disease risk factors among subjects with normal fasting glucose (NFG), impaired fasting glucose, or glucose intolerance. Although individuals with fasting plasma glucose (FPG) concentrations &gt;5.4 mmol/l but &lt;6.1 mmol/l have been shown to have an increased risk of developing type 2 diabetes over 5 years, little is known about glucose metabolism abnormalities in this population.
RESEARCH DESIGN AND METHODS—We compared insulin secretion and insulin sensitivity using several indexes derived from an oral glucose tolerance test (OGTT) in 668 subjects from the Quebec Family Study who had varying degrees of FPG.
RESULTS—There was a progressive decline in indexes of β-cell function and insulin sensitivity when moving from NFG to type 2 diabetes. Compared with subjects with low NFG (FPG &lt;4.9 mmol/l), subjects with high NFG (FPG 5.3–6.1 mmol/l) were more insulin resistant (P &lt; 0.01), had higher insulin and C-peptide responses during an OGTT (P &lt; 0.05), and had reduced insulin secretion (corrected for insulin resistance). Subjects with high NFG were also characterized by higher plasma triglyceride levels and reduced HDL cholesterol concentrations and by a smaller LDL particle size. All these differences remained significant, even after adjustment for age, sex, BMI, and waist circumference. In addition, subjects with mid NFG (FPG 4.9–5.3 mmol/l) were characterized by impaired insulin secretion, decreased insulin sensitivity, higher triglyceride concentrations, and lower HDL cholesterol concentrations compared with subjects with low NFG.
CONCLUSIONS—Independent of age, sex, and adiposity, there are differences in indexes of plasma glucose/insulin homeostasis and in cardiovascular risk factors among subjects with low, mid, and high NFG, suggesting the presence, in the upper normal glucose range, of abnormalities in glucose homeostasis, which may predispose to type 2 diabetes.
Reduced Hospitalizations and Death Associated With Influenza Vaccination Among Patients With and Without Diabetes
Authors: Heymann Anthony D. , Shapiro Yonaton , Chodick Gabriel , Shalev Varda , Kokia Ehud , Kramer Eyal , Shemer Joshua 
Published: March 2007

OBJECTIVE—To assess whether the influenza vaccination of community-dwelling, diabetic, elderly individuals is associated with reduced rates of hospitalization and death.
RESEARCH DESIGN AND METHODS—In this outcome-research study, we compared mortality and hospitalization rates of 15,556 patients aged ≥65 years followed using a diabetes registry in a large health maintenance organization to that of 69,097 members not suffering from chronic disease who were considered as a reference group. The study outcomes included all-cause death and hospitalization in internal medicine or geriatric wards for any reason over winter and summer (control) periods.
RESULTS—Vaccination rates were 48.8 and 42.0% among patients with diabetes and the reference population, respectively. Influenza vaccination was associated with a 12.3% reduction in hospitalization rates for patients with diabetes compared with 23.0% in the reference group (P = 0.08). The reduction in hospitalization rates was similar in both sexes among patients with diabetes. In addition, there was a significant reduction in mortality for the vaccinated group of patients with diabetes when compared with the nonvaccinated group except for female patients aged ≥85 years.
CONCLUSIONS—The study results support the use of influenza vaccine among an elderly population. However, there does not appear to be an additional benefit for patients with diabetes.
Effect of Rosiglitazone Versus Insulin on the Pancreatic β-Cell Function of Subjects With Type 2 Diabetes
Authors: Ovalle Fernando , Bell David S.H. 
Published: March 2007

OBJECTIVE—In a previous study, we found observational evidence of improvement in β-cell function when rosiglitazone was added to a failing oral antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm our previous observations, we designed and performed a prospective, randomized, and controlled study.
RESEARCH DESIGN AND METHODS—A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months. At baseline and at 6 months, the following were performed: measurement of fasting plasma glucose, fasting proinsulin, and insulin levels; frequently sampled intravenous glucose tolerance test; and glucagon stimulation test for C-peptide.
RESULTS—Nine subjects were randomized to the addition of 8 mg rosiglitazone, and eight subjects were randomized to the addition of one injection of insulin (premixed 70/30) before their evening meal. The treatment groups were well matched for age, duration of diabetes, and BMI. Most important, the HbA1c was well matched between groups before treatment (8.7 ± 0.3 and 9.0 ± 0.3%; NS) and at the end of the 6 months (7.8 ± 0.5 and 7.8 ± 0.3%; NS). After 6 months, at the end of the study, there was a significant improvement in acute insulin response to glucose in the rosiglitazone group (+15.3 μIU · ml−1 · 10 min−1; P &lt; 0.001) that led to an increase in the disposition index from 0.18 at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study, the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36% (P = 0.03) but did not change significantly in the insulin treatment group.
CONCLUSIONS—Rosiglitazone, but not insulin, induced a recovery of pancreatic β-cell function, as evidenced by the restoration of the first-phase insulin response to glucose, improvement in the disposition index, and a decrease in the proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral antihyperglycemic therapy failed. This improvement was independent of the correction of glucotoxicity.
Direct Health Care Costs of Diabetic Patients in Spain
Authors: Oliva Juan , Lobo Félix , Molina Begoña , Monereo Susana 
Published: March 2007

OBJECTIVE—The goal of this study was to estimate the health care resources spent by type 1 and type 2 diabetic patients in Spain during the year 2002.
RESEARCH DESIGN AND METHODS—This is a cost-of-illness study focusing on direct health care costs estimated from primary and secondary sources of information. A prevalence of diabetes ranging from 5 to 6% of the adult population was determined. Total cost is composed of six items: insulin and oral hypoglycemic agents, other drugs, disposable and consumable goods (glucose test strips, needles, and syringes), hospitalization, primary care visits, and visits to endocrinologists and dialysis.
RESULTS—The estimated direct cost of diabetes in 2002 ranges from €2.4 to 2.67 billion. Hospital costs were the most (€933 million), followed by noninsulin, nonhypoglycemic agent drugs (€777–932 million). Much lower are the costs of insulin and oral hypoglycemic agents (€311 million), primary care visits (€181–272 million), specialized visits (€127–145 million), and disposable elements (€70–81 million). Expenditures for all drugs and consumable goods ranged between €1.16 and 1.3 billion, representing 48–49% of total cost, which is 15% higher than hospital costs.
CONCLUSIONS—The direct health care costs of diabetic patients are high (6.3–7.4% of total National Health System expenditure). Their average annual cost is €1,290–1,476. For individuals without diabetes, the average annual cost is €865.
Home Monitoring of Foot Skin Temperatures to Prevent Ulceration
Authors: Lavery Lawrence A. , Higgins Kevin R. , Lanctot Dan R. , Constantinides George P. , Zamorano Ruben G. , Armstrong David G. , Athanasiou Kyriacos A. , Agrawal C. Mauli 
Published: March 2007

OBJECTIVE—To evaluate the effectiveness of at-home infrared temperature monitoring as a preventative tool in individuals at high risk for diabetes-related lower-extremity ulceration and amputation.
RESEARCH DESIGN AND METHODS—Eighty-five patients who fit diabetic foot risk category 2 or 3 (neuropathy and foot deformity or previous history of ulceration or partial foot amputation) were randomized into a standard therapy group (n = 41) or an enhanced therapy group (n = 44). Standard therapy consisted of therapeutic footwear, diabetic foot education, and regular foot evaluation by a podiatrist. Enhanced therapy included the addition of a handheld infrared skin thermometer to measure temperatures on the sole of the foot in the morning and evening. Elevated temperatures (&gt;4°F compared with the opposite foot) were considered to be “at risk” of ulceration due to inflammation at the site of measurement. When foot temperatures were elevated, subjects were instructed to reduce their activity and contact the study nurse. Study subjects were followed for 6 months.
RESULTS—The enhanced therapy group had significantly fewer diabetic foot complications (enhanced therapy group 2% vs. standard therapy group 20%, P = 0.01, odds ratio 10.3, 95% CI 1.2–85.3). There were seven ulcers and two Charcot fractures among standard therapy patients and one ulcer in the enhanced therapy group.
CONCLUSIONS—These results suggest that at-home patient self-monitoring with daily foot temperatures may be an effective adjunctive tool to prevent foot complications in individuals at high risk for lower-extremity ulceration and amputation.
Does the Metabolic Syndrome Improve Identification of Individuals at Risk of Type 2 Diabetes and/or Cardiovascular Disease?
Authors: Stern Michael P. , Williams Ken , González-Villalpando Clicerio , Hunt Kelly J. , Haffner Steven M. 
Published: March 2007

OBJECTIVE—The metabolic syndrome has been promoted as a method for identifying high-risk individuals for type 2 diabetes and cardiovascular disease (CVD). We therefore sought to compare this syndrome, as defined by the National Cholesterol Education Program, to the Diabetes Predicting Model and the Framingham Risk Score as predictors of type 2 diabetes and CVD, respectively.
RESEARCH DESIGN AND METHODS—A population-based sample of 1,709 initially nondiabetic San Antonio Heart Study (SAHS) participants were followed for 7.5 years, 195 of whom developed type 2 diabetes. Over the same time interval, 156 of 2,570 SAHS participants experienced a cardiovascular event. A population-based sample of 1,353 initially nondiabetic Mexico City Diabetes Study (MCDS) participants were followed for 6.5 years, 125 of whom developed type 2 diabetes. Baseline measurements included medical history, age, sex, ethnicity, smoking status, BMI, blood pressure, fasting and 2-h plasma glucose levels, and fasting serum total and HDL cholesterol and triglycerides.
RESULTS—The sensitivities for predicting diabetes with the metabolic syndrome were 66.2 and 62.4% in the SAHS and the MCDS, respectively, and the false-positive rates were 27.8 and 38.7%, respectively. The sensitivity and false-positive rates for predicting CVD with the metabolic syndrome in the SAHS were 67.3 and 34.2%, respectively. At corresponding false-positive rates, the two predicting models had significantly higher sensitivities and, at corresponding sensitivities, significantly lower false-positive rates than the metabolic syndrome for both end points. Combining the metabolic syndrome with either predicting model did not improve the prediction of either end point.
CONCLUSIONS—The metabolic syndrome is inferior to established predicting models for either type 2 diabetes or CVD.