bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Perception for Developing Diabetes
Authors: Walker Elizabeth A. , Mertz C.K. , Kalten Maria R. , Flynn James
Published: March 2007

OBJECTIVE—To assess personal risk perceptions for developing diabetes among practicing physicians.

RESEARCH DESIGN AND METHODS—Little is known about comparative risk perceptions concerning diabetes among medical experts. We administered the new Risk Perception Survey for Developing Diabetes to 535 nondiabetic physicians. The participants were 86% male, had a mean age of 49 years, and were 66% white and 24% Asian. Almost 37% were considered at higher risk for developing diabetes based on self-reported risk factors. Over 91% of respondents were either internal medicine or family medicine physicians.

RESULTS—Of the four subscales, Comparative Disease Risk and Environmental Risk indicated moderate risk perceptions, whereas Personal Control scores indicated a robust sense of control over developing diabetes. Optimistic Bias scores showed a tendency toward participants’ being optimistic that they were less likely to develop diabetes. Based on self-reported risk factor categories, a comparison of scores between physicians at higher risk (n = 196) and those at lower risk (n = 313) for developing diabetes showed greater comparative disease risk perception among the higher risk physicians (P < 0.01), as well as greater perception of diabetes risk (P < 0.001). Nearly 50% of higher risk physicians, however, reported an optimistic bias that they were less likely to develop diabetes than other people of their same age and sex. Women (n = 75) reported greater perception of environmental risks than men (P < 0.001). Asian respondents (n = 126) reported greater perception of environmental risk (P < 0.001) and greater worry about developing diabetes (P < 0.0001) than white respondents (n = 355). Regression analyses showed that scores for nondiabetes comparative disease risks (0.39) and level of optimistic bias (0.31) were predictive of diabetes risk perception (P < 0.0001).

CONCLUSIONS—The data gathered on physicians’ perception of their personal risk for developing diabetes and other comparative risk judgments provided an expert comparison for future analyses of at-risk or lay individuals’ perceptions of diabetes risk. Effective communication of diabetes risk among physicians, patients, and the general public relies on knowledge of and sensitivity to group differences in these perceptions.
Effect of Dalteparin on Healing of Chronic Foot Ulcers in Diabetic Patients With Peripheral Arterial Occlusive Disease
Authors: Kalani Majid , Apelqvist Jan , Blombäck Margareta , Brismar Kerstin , Eliasson Björn , Eriksson Jan W. , Fagrell Bengt , Hamsten Anders , Torffvit Ole , Jörneskog Gun
Published: March 2007

OBJECTIVE—Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers.

RESEARCH DESIGN AND METHODS—A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5,000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1) who healed with intact skin; 2) in whom the study ulcer was improved, unchanged, or impaired; or 3) who were amputated above or below the ankle level, as compared with control subjects.

RESULTS—Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided χ2 test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area ≥50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased ≥50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 ± 8 weeks in the dalteparin group compared with 16 ± 7 weeks in placebo group (NS).

CONCLUSIONS—The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.
Continuous Subcutaneous Insulin Infusion and Multiple Daily Injection Therapy Are Equally Effective in Type 2 Diabetes
Authors: Raskin Philip , Bode Bruce W. , Marks Jennifer B. , Hirsch Irl B. , Weinstein Richard L. , McGill Janet B. , Peterson Gregory E. , Mudaliar Sunder R. , Reinhardt Rickey R.
Published: March 2007

OBJECTIVE—Compare the efficacy, safety, and patient satisfaction of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy for patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 132 CSII-naive type 2 diabetic patients were randomly assigned (1:1) to CSII (using insulin aspart) or MDI therapy (bolus insulin aspart and basal NPH insulin) in a multicenter, open-label, randomized, parallel-group, 24-week study. Efficacy was assessed with HbA1c and eight-point blood glucose (BG) profiles. Treatment satisfaction was determined with a self-administered questionnaire. Safety assessments included adverse events, hypoglycemic episodes, laboratory values, and physical examination findings.

RESULTS—HbA1c values decreased similarly for both groups from baseline (8.2 ± 1.37% for CSII, 8.0 ± 1.08% for MDI) to end of study (7.6 ± 1.22% for CSII, 7.5 ± 1.22% for MDI). The CSII group showed a trend toward lower eight-point BG values at most time points (only significant 90 min after breakfast; 167 ± 48 vs. 192 ± 65 mg/dl for CSII and MDI, respectively; P = 0.019). A total of 93% of CSII-treated subjects preferred the pump to their previous injectable insulin regimen for reasons of convenience, flexibility, ease of use, and overall preference. Safety assessments were comparable for both treatment groups.

CONCLUSIONS—Insulin aspart in CSII therapy provided efficacy and safety comparable to MDI therapy for type 2 diabetes. Patients with type 2 diabetes can be trained as outpatients to use CSII and prefer CSII to injections, indicating that pump therapy should be considered when initiating intensive insulin therapy for type 2 diabetes.
Relationships of Plasma Interleukin-18 Concentrations to Hyperhomocysteinemia and Carotid Intimal-Media Wall Thickness in Patients With Type 2 Diabetes
Authors: Aso Yoshimasa , Okumura Ki-ichi , Takebayashi Kohzo , Wakabayashi Sadao , Inukai Toshihiko
Published: March 2007

OBJECTIVE—We compared plasma interleukin (IL)-18 concentrations in patients with type 2 diabetes with those in age-matched control subjects and investigated whether plasma IL-18 was associated with plasma total homocysteine (tHcy) concentration or carotid intimal-media wall thickness (IMT), an early marker of atherosclerosis, in these patients.

RESEARCH DESIGN AND METHODS—We measured plasma IL-18 in 103 type 2 diabetic patients and 45 age-matched control subjects. We also measured patients’ plasma tHcy and serum high-sensitivity C-reactive protein (hs-CRP). IMT was evaluated for both common carotid arteries.

RESULTS—Plasma IL-18 was significantly higher in diabetic patients than in control subjects (203 ± 153 vs. 118 ± 37 pg/ml, P < 0.001). High IL-18 was defined as equaling or exceeding the mean + 2 SD of plasma IL-18 in control subjects (192 pg/ml). Patients with high IL-18 showed a greater carotid IMT than those with normal IL-18. Carotid plaques were more numerous in diabetic patients with high IL-18 than in those with normal IL-18. Plasma tHcy concentrations were significantly higher in patients with high IL-18 than in those with normal IL-18. Univariate and multivariate analyses showed a strong independent association between tHcy and IL-18. Plasma IL-18 also correlated positively with serum hs-CRP.

CONCLUSIONS—In patients with type 2 diabetes, plasma IL-18 concentrations are greater than in nondiabetic subjects. Plasma IL-18 is an independent determinant of plasma tHcy, which is linked independently with atherosclerotic carotid wall thickening.
Diabetic Retinopathy
Authors: Brown Jonathan Betz , Pedula Kathryn L. , Summers Kent H.
Published: March 2007

OBJECTIVE—To measure the extent to which modern intensified risk factor control has lessened the duration-specific prevalence of diabetic retinopathy and, therefore, has decreased the risk of blindness in Americans with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Intensified control of blood glucose and blood pressure has prevented diabetic retinopathy in randomized controlled trials. There is as yet no confirmation that subsequent treatment intensification in the community has had the same result. We identified all 6,993 members of a health maintenance organization, Kaiser Permanente Northwest (KPNW), who, in 1997–1998, had dilated retinal examinations and verifiable data of diagnosis of type 2 diabetes. We plotted prevalence by time since diagnosis for background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR) and compared these results to identically derived 1980–1982 results from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). We estimated multivariate predictive models.

RESULTS—Mean (± SD) HbA1c in KPNW was 7.84 ± 1.26% versus 10.37% (standardized) in the WESDR. KPNW blood pressure averaged 138.6 ± 13.8/79.5 ± 7.4 mmHg compared with 147.0/79.0 in the WESDR. BDR was much less prevalent in KPNW, but PDR prevalence appeared unchanged. BDR preceded diagnosis in 20.8% of the WESDR subjects but only 2.0% of KPNW subjects. However, in both populations, the first cases of PDR appeared similarly, soon after diagnosis.

CONCLUSIONS—Earlier diagnosis and more aggressive control of blood glucose and blood pressure decreased the duration-adjusted prevalence of background, but not of sight-threatening proliferative retinopathy. More population-based research is needed to replicate and explain this unexpected finding. Detecting and treating PDR should not be neglected on the assumption that risk-factor control has minimized its prevalence.
Magnesium Intake and Risk of Type 2 Diabetes in Men and Women
Authors: Lopez-Ridaura Ruy , Willett Walter C. , Rimm Eric B. , Liu Simin , Stampfer Meir J. , Manson JoAnn E. , Hu Frank B.
Published: March 2007

OBJECTIVE—To examine the association between magnesium intake and risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We followed 85,060 women and 42,872 men who had no history of diabetes, cardiovascular disease, or cancer at baseline. Magnesium intake was evaluated using a validated food frequency questionnaire every 2–4 years. After 18 years of follow-up in women and 12 years in men, we documented 4,085 and 1,333 incident cases of type 2 diabetes, respectively.

RESULTS—After adjusting for age, BMI, physical activity, family history of diabetes, smoking, alcohol consumption, and history of hypertension and hypercholesterolemia at baseline, the relative risk (RR) of type 2 diabetes was 0.66 (95% CI 0.60–0.73; P for trend <0.001) in women and 0.67 (0.56–0.80; P for trend <0.001) in men, comparing the highest with the lowest quintile of total magnesium intake. The RRs remained significant after additional adjustment for dietary variables, including glycemic load, polyunsaturated fat, trans fat, cereal fiber, and processed meat in the multivariate models. The inverse association persisted in subgroup analyses according to BMI, physical activity, and family history of diabetes.

CONCLUSIONS—Our findings suggest a significant inverse association between magnesium intake and diabetes risk. This study supports the dietary recommendation to increase consumption of major food sources of magnesium, such as whole grains, nuts, and green leafy vegetables.
Intensive Therapy With Inhaled Insulin via the AERx Insulin Diabetes Management System
Authors: Hermansen Kjeld , Rönnemaa Tapani , Petersen Astrid Heide , Bellaire Shannon , Adamson Ulf
Published: March 2007

OBJECTIVE—To compare the glycemic control of inhaled insulin via the AERx insulin diabetes management system (iDMS) with that of subcutaneous (SC) insulin, both combined with NPH insulin at bedtime, in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—The AERx iDMS uses a liquid insulin formulation to achieve flexible precise mealtime dosing (with increments corresponding to 1 IU administered subcutaneously) and ensures insulin delivery only when the breathing technique is optimal. This trial in patients with type 2 diabetes compared the glycemic control (HbA1c) achieved by inhaled insulin administered via AERx iDMS with that using SC insulin. This was a randomized, 12-week, open-label, parallel, multicenter, multinational trial in 107 nonsmoking patients with type 2 diabetes (mean age 59 years, mean duration of diabetes 11.9 years). Patients were randomized to receive either inhaled fast-acting human insulin via AERx iDMS immediately before meals or SC fast-acting human insulin administered 30 min before meals, both in combination with evening NPH insulin.

RESULTS—Baseline and demographic characteristics were similar between the two groups. There was no statistically significant difference in HbA1c between the AERx and SC groups after 12 weeks of treatment (7.84 ± 0.77 vs. 7.76 ± 0.77%, P = 0.60). Fasting serum glucose was significantly lower in the AERx group compared with the SC group by the end of the trial (8.9 ± 3.8 vs. 10.8 ± 3.7 mmol/l, P = 0.01) with a similar NPH dose in the two groups (0.23 vs. 0.23 IU/kg, P = 0.93). There were no statistically significant differences between the two groups in the intra-subject variability of fasting or prandial blood glucose increment. Adverse events were similar in the two groups. No major safety concerns were raised during the trial.

CONCLUSIONS—In patients with type 2 diabetes, preprandial inhaled insulin via AERx iDMS is as effective as preprandial SC insulin injection in achieving glycemic control with similar tolerability.
Effect of Weight Loss on Cardiac Synchronization and Proinflammatory Cytokines in Premenopausal Obese Women
Authors: Marfella Raffaele , Esposito Katherine , Siniscalchi Mario , Cacciapuoti Federico , Giugliano Francesco , Labriola Domenico , Ciotola Myriam , Di Palo Carmen , Misso Lucio , Giugliano Dario
Published: March 2007

OBJECTIVE—Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss.

RESEARCH DESIGN AND METHODS—Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women.

RESULTS—Compared with nonobese women, obese women had increased concentrations of CRP (P < 0.01), TNF-α (P < 0.01), IL-6 (P < 0.01), and IL-18 (P < 0.01). Moreover, obese women had a higher myocardial performance index (P < 0.02) and lower transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02), and ejection fraction (P < 0.05), indicating ventricular dyssynchrony. Concentrations of CRP, TNF-α, and IL-6 were related to anthropometric indexes of obesity and to echocardiographic parameters of ventricular dyssynchrony. After 1 year of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. This was associated with reduction of cytokine (P < 0.01) and CRP (P < 0.02) concentrations and with improvement of echocardiographic parameters of ventricular dyssynchrony, which correlated with changes in adiposity, particularly visceral adiposity.

CONCLUSIONS—In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women.
Opportunistic Screening for Diabetes in Routine Clinical Practice
Authors: Ealovega Mark W. , Tabaei Bahman P. , Brandle Michael , Burke Ray , Herman William H.
Published: March 2007

OBJECTIVE—Since 1997, the American Diabetes Association has recommended that nondiabetic individuals ≥45 years of age be screened for diabetes at least every 3 years. We sought to characterize the frequency, methods, and results of diabetes screening in routine clinical practice.

RESEARCH DESIGN AND METHODS—We studied opportunistic screening in nondiabetic members of a health maintenance organization ≥45 years of age who were assigned to a large, integrated, academic health care delivery system. Screening was defined as the first glucose, HbA1c, or oral glucose tolerance test (OGTT) performed between 1 January 1998 and 31 December 2000. Chart review was performed to determine the prevalence of diabetes risk factors and to describe follow-up.

RESULTS—Of 8,286 nondiabetic patients ≥45 years of age, 69% (n = 5,752) were screened. The frequency of screening was greater in patients with one or more primary care visits and increased with age. Women were more likely to be screened than men, and patients with at least one diabetes risk factor were more likely to be screened than those without risk factors. Random plasma glucose was the most common screening test (95%). Four percent (n = 202) of those screened had abnormal results. Only 38% (n = 77) of those with abnormal results received appropriate follow-up, and 17% (n = 35) were diagnosed with diabetes within 6 months of screening. The yield of screening was very low (0.6%, 35 of 5,752).

CONCLUSIONS—Despite frequent screening and appropriate targeting of high-risk patients, follow-up of patients with abnormal results is uncommon and the yield of screening is low. Interventions are needed to help physicians recognize and provide appropriate follow-up for patients with potentially abnormal random glucose levels.
Closing the Gap: Effect of Diabetes Case Management on Glycemic Control Among Low-Income Ethnic Minority Populations
Authors:   The California Medi-Cal Type 2 Diabetes Study Group
Published: March 2007

OBJECTIVE—Disparities exist in the diabetes health status of ethnic minority and/or low-income populations relative to other groups. A primary objective of diabetes management is to improve glycemic control. The feasibility of implementing intensive diabetes case management in disparate populations remains largely untested.

RESEARCH DESIGN AND METHODS—Clinical sites in three southern California counties serving low-income, ethnic minority populations participated in our study. We randomized 362 Medicaid (called Medi-Cal in California) recipients with type 2 diabetes for at least 1 year to intervention (diabetes case management) or control (traditional primary care treatment) groups. Fifty-five percent of participants were minorities. Participants with HbA1c levels less than 7.5%, serious diabetes-related complications, or other serious medical conditions were excluded. We assessed the effect of the intervention (ongoing diabetes case management added to primary care) on glycemic control using serial HbA1c measurements over several years.

RESULTS—The mean duration of follow-up was 25.3 months. HbA1c decreased substantially in both groups from an average of 9.54–7.66% (a reduction of 1.88%) in the intervention group and from an average of 9.66–8.53% (a reduction of 1.13%) in the control group. This improvement was sustained throughout the study. The reduction in HbA1c was consistently greater in the intervention group at each time point (P < 0.001), ranging between 0.65 at 6 months and 0.87 at study end.

CONCLUSIONS—Diabetes case management, added to primary care, substantially improved glycemic control compared with the control group. Diabetes case management can help reduce disparities in diabetes health status among low-income ethnic populations.
The Impact of a Decade of Changing Treatment on Rates of Severe Hypoglycemia in a Population-Based Cohort of Children With Type 1 Diabetes
Authors: Bulsara Max K. , Holman C. D’Arcy J. , Davis Elizabeth A. , Jones Timothy W.
Published: March 2007

OBJECTIVE—To determine the impact of changes to treatment on the incidence of severe hypoglycemia and its risk factors in a large population-based cohort of children with type 1 diabetes.

RESEARCH DESIGN AND METHODS—The cohort consisted of 1,335 children (age at entry 9.5 ± 4.3 years [mean ± SD], range 0–18), yielding 6,928 patient-years of data. The mean follow-up period was 4.7 ± 3.1 years (range 0–10.7). Prospective assessment of severe hypoglycemia (an event leading to loss of consciousness or seizure) and associated clinical factors and outcomes was made between 1992 and 2002. Patients were reviewed every 3 months. Data were analyzed using the negative binomial regression model.

RESULTS—A total of 944 severe events were recorded. The incidence of severe hypoglycemia increased significantly by 29% per year for the first 5 years but appeared to plateau over the last 5 years. The overall average HbA1c significantly decreased (by 0.2% per year) over the whole follow-up period. An increased risk of severe hypoglycemia was associated with lower HbA1c, younger age, higher insulin dose, male sex, and lower parental socioeconomic status. Of insulin therapies, only pump treatment was associated with reduced rates of severe hypoglycemia.

CONCLUSIONS—Severe hypoglycemia remains a major problem for children and adolescents with type 1 diabetes. Recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycemia but further monitoring will be important.
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 <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 < 0.001) and subphalangeal fat pads significantly thicker (9.1 ± 1.9 vs. 7.6 ± 1.2 mm, P < 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 < 0.001). A significant correlation of 0.85 was present between toe angle and thickness ratio (P < 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 >100 (n = 23), those with the highest scores, which is considered to show possible coronary artery disease, showed the highest brachial-ankle PWV (P < 0.001) and resistive index (P < 0.001) and the lowest total flow volume (P < 0.001) among the groups. Simple linear regression analyses showed that both brachial-ankle PWV (r = 0.508, P < 0.001) and resistive index (r = 0.500, P < 0.001) were positively correlated and total flow volume (r = −0.528, P < 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 >5.4 mmol/l but <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 <4.9 mmol/l), subjects with high NFG (FPG 5.3–6.1 mmol/l) were more insulin resistant (P < 0.01), had higher insulin and C-peptide responses during an OGTT (P < 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 < 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 (>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.
Metabolic Syndrome as a Predictor of All-Cause and Cardiovascular Mortality in Type 2 Diabetes
Authors: Bruno Graziella , Merletti Franco , Biggeri Annibale , Bargero Giuseppe , Ferrero Stefania , Runzo Cristina , Prina Cerai Stefano , Pagano Gianfranco , Cavallo-Perin Paolo
Published: March 2007

OBJECTIVE—The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organization–defined metabolic syndrome, independent of conventional cardiovascular risk factors.

RESEARCH DESIGN AND METHODS—During the follow-up (1991–2001), 1,565 patients were regularly examined with centralized measurements of HbA1c. The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling.

RESULTS—At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6–77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16–7.33), independent of other risk factors.

CONCLUSIONS—We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components.