bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of B-Type Natriuretic Peptide (BNP) as a Screen for Left Ventricular Dysfunction in Patients With Diabetes
Authors: Epshteyn Victoria , Morrison Katherine , Krishnaswamy Padma , Kazanegra Radmila , Clopton Paul , Mudaliar Sunder , Edelman Steven , Henry Robert , Maisel Alan
Published: March 2007

OBJECTIVE—Routine screening of diabetic patients with echocardiography is not feasible due to its limited availability and high cost. B-type natriuretic peptide (BNP) is secreted from the left ventricle in response to pressure overload and is elevated in both systolic and diastolic dysfunction.

RESEARCH DESIGN AND METHODS—BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication for echocardiography (CIE) (n = 172) and those without clinical indication for echocardiography (no-CIE) (n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP.

RESULTS—The 91 patients with no-CIE with echos had similar BNP levels (83 ± 16 pg/ml) to the 215 patients with no-CIE without echos (63 ± 10, P = 0.10). Patients with CIE and subsequent abnormal left ventricular function (n = 112) had a mean BNP concentration of 435 ± 41 pg/ml, compared with those with no-CIE, but had abnormal left ventricular function on echo (n = 32) (161 ± 40 pg/ml). Twenty-one of 32 patients with no-CIE but with abnormal left ventricular function had diastolic dysfunction (BNP 190 ± 60pg/ml). A receiver-operating characteristic (ROC) curve revealed that the area under the curve was 0.91 for CIE patients and 0.81 for no-CIE patients (P < 0.001). For those with no congestive heart failure (CHF) symptoms, BNP levels showed a high negative predictive value (91% for BNP values <39 pg/ml), while in those patients who had a CIE, BNP levels showed a high positive predictive value for the detection of left ventricular dysfunction (96% with BNP levels >90 pg/ml).

CONCLUSIONS—BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction.
Contribution of Abnormal Insulin Secretion and Insulin Resistance to the Pathogenesis of Type 2 Diabetes in Myotonic Dystrophy
Authors: Perseghin Gianluca , Caumo Andrea , Arcelloni Cinzia , Benedini Stefano , Lanzi Roberto , Pagliato Emanuela , Sereni Lucia Piceni , Testolin Giulio , Battezzati Alberto , Comi Giancarlo , Comola Mauro , Luzi Livio
Published: March 2007

OBJECTIVE—Myotonic dystrophy (MyD), the most common adult form of muscular dystrophy, is often complicated by diabetes. MyD is dominantly inherited and is due to heterozygosity for a trinucleotide repeat expansion mutation in a protein kinase gene able to induce derangement of RNA metabolism responsible of an aberrant insulin receptor expression.

RESEARCH DESIGN AND METHODS—To assess insulin sensitivity and secretion before the onset of diabetes, we studied 10 MyD patients, 10 offspring of type 2 diabetes (OFF), and 10 healthy subjects with no family history of diabetes (control subjects) with dual X-ray energy absorption, euglycemic-hyperinsulinemic clamp (40 mU/[m2 · min]) combined with infusion of [6,6-d2]-glucose and oral glucose tolerance test (OGTT).

RESULTS—MyD had reduced lean body mass, but peripheral insulin sensitivity was not different to that of control subjects in contrast to OFF, which showed insulin resistance. Insulin secretion, obtained by deconvolution of OGTT data, was also shown to be comparable with that of OFF and control subjects (index of β-cell function = Φ; P = 0.91) even if increased parameters of insulin secretion were found during the first 30 min (Φ30; P = 0.05) of the oral glucose challenge. Fasting plasma proinsulin concentrations (P = 0.01) and the ratio to insulin (P = 0.01) were increased in MyD patients. The proinsulin levels also failed to be suppressed during the clamp and showed exaggerated response after the OGTT. Increased proinsulin levels were shown to be peculiar of MyD patients when compared with OFF.

CONCLUSIONS—In nondiabetic, young MyD patients, insulin sensitivity was preserved, and an increased early secretory response to oral glucose was detected. Abnormal plasma proinsulin levels in the fasting state, during the clamp, and during the OGTT were shown to be secretory dysfunctions peculiar of MyD patients and may be more important than insulin resistance in determining the high risk to develop diabetes in these patients.
Lifestyle Modification Improves Endothelial Function in Obese Subjects With the Insulin Resistance Syndrome
Authors: Hamdy Osama , Ledbury Sarah , Mullooly Cathy , Jarema Catherine , Porter Satoko , Ovalle Kerry , Moussa Amr , Caselli Antonella , Caballero A. Enrique , Economides Panayiotis A. , Veves Aristidis , Horton Edward S.
Published: March 2007

OBJECTIVE—Endothelial dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro- and the microcirculation in obese subjects with IRS.

RESEARCH DESIGN AND METHODS—We studied 24 obese subjects (9 men and 15 women, age 49.3 ± 1.9 years, BMI 36.7 ± 0.94 kg/m2, mean ± SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen.

RESULTS—This intervention resulted in 6.6 ± 1% reduction in body weight (P < 0.001) and significant improvement of insulin sensitivity index (2.9 ± 0.36 vs. 1.9 ± 0.33 [10−4 · min−1 · (μU ml−1)], P < 0.001). FMD significantly improved (12.9 ± 1.2% vs. 7.9 ± 1.0%, P < 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 ± 7.7 vs. 265.6 ± 9.3 ng/ml, P = 0.018 and 36.2 ± 3.6 vs. 48.6 ± 3.9 ng/ml, P = 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R2 = 0.47, P = 0.001).

CONCLUSIONS—We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance.
Progression to Overt Nephropathy in Type 2 Diabetes
Authors: Bruno Graziella , Merletti Franco , Biggeri Annibale , Bargero Giuseppe , Ferrero Stefania , Pagano Gianfranco , Perin Paolo Cavallo
Published: March 2007

OBJECTIVE—The first sign of diabetic nephropathy is microalbuminuria, but its predictive role of progression to overt nephropathy in type 2 diabetes has not yet been clarified. The aims of this study were to assess during 7 years of follow-up the incidence rate of overt nephropathy and the predictive role of microalbuminuria and other baseline variables (blood pressure, lipids, fibrinogen, uric acid, smoking, and HbA1c cumulative average during follow-up).

RESEARCH DESIGN AND METHODS—A prospective population-based study was performed in Casale Monferrato, Italy, including 1,253 type 2 diabetic patients recruited at baseline (1991–1992), 765 with normoalbuminuria (albumin excretion rate [AER] <20 μg/min) and 488 with microalbuminuria (AER 20–200 μg/min). All measurements were centralized. A nested case-control study within the cohort was performed, selecting four control subjects, frequency matched for age and attained individual time of follow-up with each case. Conditional regression analysis was performed to assess variables independently associated with risk of progression to overt nephropathy.

RESULTS—Of 1,253 total patients, 1,103 (88.0%) were included in the follow-up examination (median 5.33 years); their age and duration of disease at baseline were 68.4 ± 10.5 years and 10.4 ± 6.6 years, respectively. Cases of overt nephropathy were 202, giving an incidence rate of 37.0/1,000 person-years (95% CI 32.3–42.6). In conditional logistic regression analyses, microalbuminuria provided a 42% increased risk with respect to normoalbuminuria (95% CI 0.98–2.06), independently of duration of diabetes, hypertension, and systolic blood pressure. Other variables independently associated with progression to overt nephropathy were HbA1c cumulative average (P = 0.002), apolipoprotein B (P = 0.013), fibrinogen (P = 0.02), and HDL cholesterol (P = 0.03).

CONCLUSIONS—Of type 2 diabetic patients, 3.7% progress every year to overt nephropathy. Microalbuminuria is associated with a 42% increased risk of progression to overt nephropathy. Other independent predictors are HbA1c, HDL cholesterol, apolipoprotein B, and fibrinogen.
Biologic and Quality-of-Life Outcomes From the Mediterranean Lifestyle Program
Authors: Toobert Deborah J. , Glasgow Russell E. , Strycker Lisa A. , Barrera Manuel , Radcliffe Janice L. , Wander Rosemary C. , Bagdade John D.
Published: March 2007

OBJECTIVE—Few multiple lifestyle behavior change programs have been designed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes. This study tested the effectiveness of the Mediterranean Lifestyle Program (MLP), a comprehensive lifestyle self-management program (Mediterranean low–saturated fat diet, stress management training, exercise, group support, and smoking cessation), in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Postmenopausal women with type 2 diabetes (n = 279) were randomized to either usual care (control) or treatment (MLP) conditions. MLP participants took part in an initial 3-day retreat, followed by 6 months of weekly meetings, to learn and practice program components. Biological end points were changes in HbA1c, lipid profiles, BMI, blood pressure, plasma fatty acids, and flexibility. Impact on quality of life was assessed.

RESULTS—Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA1c, BMI, plasma fatty acids, and quality of life at the 6-month follow-up. Patterns favoring intervention were seen in lipids, blood pressure, and flexibility but did not reach statistical significance.

CONCLUSIONS—These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinically significant improvements in glycemic control, some coronary heart disease risk factors, and quality of life.
Out-of-Pocket Costs and Diabetes Preventive Services
Authors: Karter Andrew J. , Stevens Mark R. , Herman William H. , Ettner Susan , Marrero David G. , Safford Monika M. , Engelgau Michael M. , Curb J. David , Brown Arleen F. ,   The TRIAD Study Group
Published: March 2007

OBJECTIVE—Despite the increased shifting of health care costs to consumers, little is known about the impact of financial barriers on health care utilization. This study investigated the effect of out-of-pocket expenditures on the utilization of recommended diabetes preventive services.

RESEARCH DESIGN AND METHODS—This was a survey-based observational study (2000–2001) in 10 managed care health plans and 68 provider groups across the U.S. serving ∼180,000 patients with diabetes. From 11,922 diabetic survey respondents, we studied the occurrence of self-reported annual dilated eye exams and diabetes health education and among insulin users, daily self-monitoring of blood glucose (SMBG). Conditional probabilities were estimated for outcomes at each level of self-reported out-of-pocket expenditure by using hierarchical logistic regression models with random intercepts.

RESULTS—Conditional probabilities of utilization (95% CI) varied by expenditure for dilated eye exam [no cost 78% (75–82), copay 79% (75–82), and full price 70% (64–75); P < 0.0001]; diabetes health education [no cost 29% (23–36), copay 29% (23–36), and full price 19% (14–25); P < 0.0001]; and daily SMBG [no cost 75% (68–81), copay 68% (60–75), and full price 59% (49–68); P < 0.0001]. Extensive adjustment for patient factors had no discernible effect on the estimates or their significance, and cost-utilization relationships were similar across income levels and other patient characteristics.

CONCLUSIONS—Benefit packages structured to derive greater fiscal contribution from the health plan membership result in suboptimal use of diabetes preventive services and may thus lead to poorer clinical outcomes, greater future costs, and lower health plan quality ratings.
A Comparison of Postprandial and Preprandial Administration of Insulin Aspart in Children and Adolescents With Type 1 Diabetes
Authors: Danne Thomas , Aman Jan , Schober Edith , Deiss Dorothee , Jacobsen Judith L. , Friberg Hans Henrik , Jensen Lars Hein ,   the ANA 1200 Study Group
Published: March 2007

OBJECTIVE—The aim of this study was to compare the glycemic control of preprandial versus postprandial injections of the new rapid-acting insulin analogue aspart in children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Forty-two children (aged 6–12 years) and 34 adolescents (13–17 years) were randomized to preprandial (immediately before meal start) and postprandial (immediately after a meal or a maximum of 30 min after meal start) treatment with insulin aspart (at least thrice daily) as part of a basal/bolus regimen in a multicenter study with an open labeled, two-period cross-over design (6-week periods). Of this group, 49% were boys, 55% were aged ≤13 years, and duration of diabetes was 4.4 years (range 1.0–9.4).

RESULTS—Glycemic control for postprandial treatment was not worse than preprandial treatment as assessed by fructosamine week 0 vs. 6 (mean ± SD, preprandial 367 ± 74 vs. 378 ± 90 μmol/l; postprandial 383 ± 83 vs. 385 ± 77 μmol/l) and HbA1c (preprandial 7.9 ± 1.3 vs. 8.0 ± 1.5%; postprandial 8.0 ± 1.4 vs. 8.3 ± 1.5%, P = 0.14). The only statistically significant finding from the seven-point blood glucose profiles and derived parameters between preprandial and postprandial treatment was a lower postprandial glucose level 120 min after breakfast (mean ± SEM, −2.08 ± 0.74 mmol/l, P = 0.016). The relative risk of hypoglycemia (blood glucose <3.9 mmol/l) preprandially to postprandially was not significantly different (mean 1.1; 95% CI 0.91–1.35; P = 0.31). Overall treatment satisfaction was equally high for both regimens with both patients and parents.

CONCLUSIONS—Although preprandial administration of insulin aspart is generally preferable, this study shows that in children and adolescents, postprandial administration of insulin aspart is a safe and effective alternative.
Antiatherogenic Effect of Pioglitazone in Type 2 Diabetic Patients Irrespective of the Responsiveness to Its Antidiabetic Effect
Authors: Satoh Noriko , Ogawa Yoshihiro , Usui Takeshi , Tagami Tetsuya , Kono Shigeo , Uesugi Hiroko , Sugiyama Hiroyuki , Sugawara Akira , Yamada Kazunori , Shimatsu Akira , Kuzuya Hideshi , Nakao Kazuwa
Published: March 2007

OBJECTIVE—Thiazolidinediones (TZDs), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily for 3 months) (n = 70) and the untreated control group (n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone.

RESULTS—The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA1c levels and increased plasma adiponectin concentrations relative to the control group (P < 0.01). It also significantly decreased CRP and PWV (P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing <1% of reduction in HbA1c (n = 30) and responders showing >1% of reduction (n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism.

CONCLUSIONS—This study represents the first demonstration of the antiatherogenic effect of pioglitazone in both nonresponders and responders with respect to its antidiabetic effect and suggests that pioglitazone can exert its antiatherogenic effect independently of its antidiabetic effect.
Weight, Adiposity, and Physical Activity as Determinants of an Insulin Sensitivity Index in Pima Indian Children
Authors: Bunt Joy C. , Salbe Arline D. , Harper Inge T. , Hanson Robert L. , Tataranni P. Antonio
Published: March 2007

OBJECTIVE—To determine whether measures of physical activity are related to an insulin sensitivity index ([ISI] 104/fasting insulin × glucose) independent of weight or adiposity in children.

RESEARCH DESIGN AND METHODS—We conducted a longitudinal study of 90 Pima Indian children (39 boys and 51 girls) at 5 and 10 years of age measuring adiposity (dual-energy X-ray absorptiometry), physical activity behavior (questionnaire: number of activities per week [ACT], average hours per week [TIME]), and energy expenditure (doubly labeled water: physical activity level [PAL]).

RESULTS—In cross-sectional analyses, ACT was correlated with ISI at 5 years of age (r = 0.24, P = 0.02) and at 10 years of age (r = 0.21, P = 0.05), but these relationships were not independent of weight or adiposity. PAL was correlated with ISI at 10 years of age (r = 0.39, P = 0.03) but was not independent of weight or adiposity. Longitudinally, ISI decreased from 5 to 10 years of age, and increases in weight and adiposity were associated with decreases in ISI (r = −0.51 and −0.41, respectively; both P < 0.0001). ACT decreased from 5 to 10 years of age, but children who had smaller decreases in ACT had smaller decreases in ISI, independent of increases in weight or adiposity (partial r = 0.22, P = 0.04 adjusted for either weight or adiposity).

CONCLUSIONS—These data suggest that early establishment and maintenance of an active lifestyle can have a beneficial effect on ISI that is partially independent of changes in weight or adiposity. This is particularly relevant considering the current epidemics of both obesity and type 2 diabetes in children.
Do Measures of Body Fat Distribution Provide Information on the Risk of Type 2 Diabetes in Addition to Measures of General Obesity?
Authors: Tulloch-Reid Marshall K. , Williams Desmond E. , Looker Helen C. , Hanson Robert L. , Knowler William C.
Published: March 2007

OBJECTIVE—To investigate which anthropometric measurements of obesity best predict type 2 diabetes in a population of Pima Indians and whether additional information on diabetes risk could be obtained by combining measures of general obesity with measures of body fat distribution.

RESEARCH DESIGN AND METHODS—We conducted a prospective study of 624 men and 990 nonpregnant women >18 years of age without diabetes. Subjects were followed a mean of 5.25 years for the development of type 2 diabetes (using 1997 American Diabetes Association criteria).

RESULTS—A total of 322 new cases of type 2 diabetes (107 men and 215 women) were diagnosed during follow-up. Baseline obesity measurements were highly correlated and predicted diabetes in proportional hazards models adjusted for age. BMI had the highest hazard ratio in men and women, with age-adjusted hazard ratios per SD of 1.73 (95% CI 1.44–2.07) and 1.67 (1.45–1.91), respectively. According to receiver-operating characteristic analysis, BMI and waist-to-height ratio were the best predictors of diabetes in men, while in women BMI, waist-to-height ratio, waist circumference, and waist-to-thigh ratio were the best predictors. The predictive abilities of models containing BMI were not significantly improved by including other measures of general obesity or measures of the body fat distribution.

CONCLUSIONS—Throughout its range, BMI was an excellent predictor of type 2 diabetes risk in Pima Indians and was not significantly improved by combining it with other measures of general adiposity or body fat distribution.
A Meta-Analysis of the Association Between Childhood Type 1 Diabetes and Atopic Disease
Authors: Cardwell Chris R. , Shields Mike D. , Carson Dennis J. , Patterson Chris C.
Published: March 2007

OBJECTIVE—To review the published literature and perform a meta-analysis summarizing the evidence in support of an inverse association between type 1 diabetes and the atopic disorders: asthma, eczema, and allergic rhinitis in children.

RESEARCH DESIGN AND METHODS—MEDLINE, Web of Science, and PubMed were searched to identify relevant studies. These were assessed on quality criteria, and odds ratios (ORs) and 95% CIs were calculated for each study from the reported prevalences of atopy in children with diabetes and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in findings between studies.

RESULTS—Twenty-five studies were identified. Heterogeneity in the findings from different studies was evident but was considerably reduced when the asthma and rhinitis analyses were restricted to those studies judged to be of adequate design. The meta-analysis revealed an inverse association between asthma and type 1 diabetes, but the finding only attained significance when analysis was restricted to the studies of adequate design (OR 0.82, 95% CI 0.68–0.99). In this subset an association of similar magnitude was observed between eczema and type 1 diabetes (0.82, 0.62–1.10) although this failed to attain statistical significance, and heterogeneity between studies was still present. There was little evidence of an association between rhinitis and type 1 diabetes (0.97, 0.82–1.16) in this subset of studies.

CONCLUSIONS—Our analysis suggests that there is a small but significant reduction in the prevalence of asthma in children with type 1 diabetes, but the findings for the other atopic diseases are less conclusive.
Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension
Authors: Winkler Karl , Konrad Thomas , Füllert Stefanie , Friedrich Isolde , Destani Ramadan , Baumstark Manfred W. , Krebs Kristin , Wieland Heinrich , März Winfried
Published: March 2007

OBJECTIVE—The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension.

RESEARCH DESIGN AND METHODS—We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 ± 0.8 mmol/l; HDL cholesterol, 1.1 ± 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5–7.1) were studied at baseline and on treatment.

RESULTS—At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 >250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 ± 0.30 to 20.13 ± 0.33 nm (P < 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 ± 0.0024 to 1.0371 ± 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol.

CONCLUSIONS—The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.
Activity Patterns of Patients With Diabetic Foot Ulceration
Authors: Armstrong David G. , Lavery Lawrence A. , Kimbriel Heather R. , Nixon Brent P. , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—To evaluate the activity of patients with diabetic foot ulcerations and their adherence to their pressure off-loading device.

RESEARCH DESIGN AND METHODS—We enrolled 20 subjects treated for neuropathic diabetic foot wounds corresponding to University of Texas grade 1 stage A. All were off-loaded using a removable cast walker (RCW). We recorded the total activity (measured in activity steps per day) taken on a waist-worn computerized accelerometer. We subsequently correlated this to activity recorded on an RCW-mounted accelerometer, which was not readily accessible to the patient.

RESULTS—There were a mean 1,219.1 ± 821.2 activity units (steps) taken per patient per day. Patients logged significantly more daily activity units with the protective RCW off than with it on (873.7 ± 828.0 vs. 345.3 ± 219.1, P = 0.01). This amounts to only 28% of total daily activity recorded while patients were wearing their RCW. Although a total of 30% of the patients in the study recorded more daily activity units while wearing the device, this subset most adherent to their off-loading regimen still only wore the device for a total of 60% of their total daily activity.

CONCLUSIONS—Subjects with diabetic foot ulcerations appear to wear their off-loading devices for only a minority of steps taken each day. This may partially explain the poor results reported from many trials of agents designed to help speed the healing of these wounds. Control of this important aspect of care with less easily removable devices may increase the prevalence of healing.
The Performance of a Risk Score as a Screening Test for Undiagnosed Hyperglycemia in Ethnic Minority Groups
Authors: Spijkerman Annemieke M.W. , Yuyun Matthew F. , Griffin Simon J. , Dekker Jacqueline M. , Nijpels Giel , Wareham Nicholas J.
Published: March 2007

OBJECTIVE—To assess the performance of the Cambridge Risk Score (CRS) to predict undiagnosed hyperglycemia in Caribbean and South Asian people living in the U.K.

RESEARCH DESIGN AND METHODS—The CRS uses routinely available data from primary care records to identify people at high risk for undiagnosed type 2 diabetes. The sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve for the CRS cut point of 0.199 were 77, 72, and 80% (95% CI 68–91), respectively. The risk score was calculated for 248 Caribbean and 555 South Asian participants aged 40–75 years in the 1999 Health Survey for England. Undiagnosed hyperglycemia was considered present if fasting plasma glucose was ≥7.0 mmol/l or HbA1c was ≥6.5%. Sensitivity, specificity, and predictive values were calculated for various cut points of the risk score, and ROC curves were constructed.

RESULTS—The area under the ROC curve was 67% (59–76) and 72% (67–78) for Caribbeans and South Asians, respectively. The optimal cut point in Caribbean participants was 0.236, sensitivity was 63% (46–77), and specificity was 63% (56–69). In the South Asian population, the optimal cut point was and 0.127, sensitivity was 69% (60–78), and specificity was 64% (60–69).

CONCLUSIONS—The CRS, using routinely available data, can be used in a strategy to detect undiagnosed hyperglycemia in Caribbean and South Asian populations. The existence of ethnic group–specific cut points must be further established in future studies.
Depressive Symptoms and Risk of Type 2 Diabetes in Women
Authors: Arroyo Cassandra , Hu Frank B. , Ryan Louise M. , Kawachi Ichiro , Colditz Graham A. , Speizer Frank E. , Manson JoAnn
Published: March 2007

OBJECTIVE—To explore the relationship between depressive symptoms and incidence of type 2 diabetes in women.

RESEARCH DESIGN AND METHODS—We conducted an analysis of 72,178 female nurses aged 45–72 years who did not have diagnosed diabetes and who answered the Medical Outcomes Study 36-Item Short-Form Health Status Survey (SF-36) at baseline in 1992. We calculated relative risks (RR) of type 2 diabetes for women with presence of depressive symptoms (i.e., Five-Item Mental Health Index [MHI-5] score >52).

RESULTS—During 4 years of follow-up (282,317 person-years), 973 incident cases of type 2 diabetes were documented. Age-adjusted RR of developing type 2 diabetes for women with presence of depressive symptoms was 1.55 (95% CI 1.27–1.90). Additional adjustment for BMI resulted in a RR of developing type 2 diabetes of 1.36 (1.11–1.67). The multivariate RR of developing type 2 diabetes was 1.22 (1.00–1.50). After excluding women diagnosed with diabetes between 1992 and 1994, 472 incident cases of type 2 diabetes were documented for the follow-up period from 1994 to 1996 (148,889 person-years). The multivariate RR of developing type 2 diabetes for women with depressive symptoms was 1.29 (0.96–1.72).

CONCLUSIONS—Our data suggest that depressive symptoms are associated with a modest increase in the risk of type 2 diabetes.
Clinical Decisions Regarding HbA1c Results in Primary Care
Authors: Parnes Bennett L. , Main Deborah S. , Dickinson L. Miriam , Niebauer Linda , Holcomb Sherry , Westfall John M. , Pace Wilson D.
Published: March 2007

OBJECTIVE—To describe decisions made by primary care providers on elevated HbA1c results and their reasons for not intensifying therapy.

RESEARCH DESIGN AND METHODS—In this cross-sectional study, a provider survey was administered in two practice-based research networks when HbA1c results were reviewed on all nonpregnant patients >18 years old with type 2 diabetes. Univariate and Mantel-Hantel analyses assessed associations between patient characteristics and clinical decisions.

RESULTS—A total of 483 surveys were completed by at least 88 providers at 19 clinics. Most patients were female (62.5%), mean age was 60 years, and 28.6% were Hispanic. The overall action rate on HbA1c results ≥7% (n = 294) was 70.7%. Patients who were black or had Medicare without medication insurance had lower rates of action on HbA1c ≥7 and ≥8%, respectively (P < 0.05). The most common reasons providers reported for inaction were “patient improving/doing well,” “competing demands,” and “hypoglycemic risk.”

CONCLUSIONS—Primary care providers generally adhere to national glycemic control guidelines, although there may be disparities in black patients and patients without medication insurance coverage. A variety of reasons were given when control was not intensified.
Inflammation and Glucose Intolerance
Authors: Wolf Myles , Sauk Jenny , Shah Anand , Vossen Smirnakis Karen , Jimenez-Kimble Ricardo , Ecker Jeffrey L. , Thadhani Ravi
Published: March 2007

OBJECTIVE—Increased leukocyte count is a marker of inflammation that has been associated with the development of type 2 diabetes in prospective studies. Although gestational diabetes mellitus (GDM) and type 2 diabetes share certain pathophysiological mechanisms, few studies have examined inflammation and risk of GDM.

RESEARCH DESIGN AND METHODS—We prospectively examined routine leukocyte counts collected at the first prenatal visit in a cohort of 2,753 nulliparous euglycemic women, 98 (3.6%) of whom were later diagnosed with GDM. Subjects were divided into quartiles of leukocyte count, and the results of third-trimester glucose screening tests and the incidence of GDM among these quartiles were compared. Logistic regression was used to calculate univariate and multivariable-adjusted relative risks (RRs) of GDM according to leukocyte quartiles.

RESULTS—Leukocyte counts were increased among women who subsequently developed GDM compared with those who remained free of GDM (10.5 ± 2.2 vs. 9.2 ± 2.2 × 103 cells/ml; P < 0.01). There was a linear increase in postloading mean glucose levels (P for trend <0.01), the area under the glucose tolerance test curves (P for trend <0.01), and the incidence of GDM (quartile 1, 1.1; quartile 2, 2.5; quartile 3, 4.2; and quartile 4, 6.4%; P for trend <0.01) with increasing leukocyte quartiles. In the multivariable-adjusted analysis, the linear trend in the RR of GDM with increasing leukocyte quartiles remained statistically significant (quartile 1, reference; quartile 2, RR 2.3 [95% CI 0.9–5.7]; quartile 3, 3.3 [1.4–7.8]; quartile 4, 4.9 [2.1–11.2]; P for trend <0.01).

CONCLUSIONS—Increased leukocyte count early in pregnancy is independently and linearly associated with the results of GDM screening tests and the risk of GDM. Although overlap in the leukocyte count distributions precludes it from being a clinically useful biomarker, these data suggest that inflammation is associated with the development of GDM and may be another pathophysiological link between GDM and future type 2 diabetes.
White Blood Cell Count Is Associated With Macro- and Microvascular Complications in Chinese Patients With Type 2 Diabetes
Authors: Tong Peter C. , Lee Ka-Fai , So Wing-Yee , Ng Margaret H. , Chan Wing-Bun , Lo Matthew K. , Chan Norman N. , Chan Juliana C.
Published: March 2007

OBJECTIVES—There are close associations among raised white blood cell (WBC) count, coronary heart disease, and metabolic syndrome in the general population. The association between WBC count and vascular complications of diabetes has not been explored. We carried out a cross-sectional cohort study to determine the association between WBC count and the presence of macro- and microvascular complications in type 2 diabetes.

RESEARCH DESIGN AND METHODS—In this study, 3,776 patients with type 2 diabetes and normal WBC count (3.5–12.5 × 109/l) underwent a comprehensive assessment of complications and cardiovascular risk factors based on the European DiabCare protocol. Demographic and anthropometric parameters were recorded. Metabolic profiles, including complete blood picture and urinary albumin excretion, were measured.

RESULTS—Patients with higher WBC counts (categorized into quintiles) had adverse metabolic profiles as evidenced by higher blood pressure, BMI, HbA1c, fasting plasma glucose, LDL cholesterol, triglycerides, and urinary albumin excretion, but lower HDL cholesterol (all P <0.001 for trend). The prevalence of macro- and microvascular complications increased in a dosage-related manner with WBC count. After adjustments for smoking and other known cardiovascular risk factors, a 1-unit (1 × 109/l) increment of WBC count was associated with a 15.8% (95% CI 9.3–22.6; P < 0.001) and 12.3% increase (5.8–19.1; P < 0.001) in the prevalence of macro- and microvascular complications, respectively.

CONCLUSIONS—Elevated WBC count, even within the normal range, is associated with both macro- and microvascular complications in type 2 diabetes. Chronic inflammation, as indicated by a higher WBC count, may play a linkage role in the development of macro- and microvascular complications in diabetes.
The Prevalence of the Metabolic Syndrome Among Arab Americans
Authors: Jaber Linda A. , Brown Morton B. , Hammad Adnan , Zhu Qian , Herman William H.
Published: March 2007

OBJECTIVE—To estimate the prevalence of the metabolic syndrome in Arab Americans by age, sex, and BMI and to examine the association between insulin resistance and each of the components of the metabolic syndrome.

RESEARCH DESIGN AND METHODS—We studied a representative, cross-sectional, population-based sample of 542 Arab Americans aged 20–75 years. The metabolic syndrome was defined by Adult Treatment Panel III (ATP III) and World Health Organization (WHO) diagnostic criteria. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR).

RESULTS—The age-adjusted prevalence of the metabolic syndrome was 23% (95% CI 19–26%) by the ATP III definition and 28% (24–32%) by the WHO definition. Although the prevalence increased significantly with age and BMI in both sexes by both definitions, differences in estimates were noted. With ATP III, the age-specific rates were similar for men and women aged 20–49 years but were significantly higher for women aged ≥50 years. With WHO, rates were higher for men than women aged 20–49 years and similar for those aged ≥50 years. The most common component of the metabolic syndrome in men and women was low HDL cholesterol with the ATP III and the presence of glucose intolerance and HOMA-IR with the WHO. Strong associations between HOMA-IR and individual components of the metabolic syndrome were observed. After fitting a model with HOMA-IR as the outcome, waist circumference, triglyceride level, and fasting plasma glucose level were significantly associated with HOMA-IR.

CONCLUSIONS—The metabolic syndrome is common among Arab Americans and is related to modifiable risk factors.
Concept, Strategies, and Feasibility of Noninvasive Insulin Delivery
Authors: Cefalu William T.
Published: March 2007

OBJECTIVE—To comprehensively review the progress to date on the development of alternative routes for insulin delivery.

RESEARCH DESIGN AND METHODS—Study data were collected through a Medline review.

RESULTS—Proof of principle has been established for many routes of administration including dermal, nasal, oral, buccal, and pulmonary insulin delivery.

CONCLUSIONS—Of all the approaches to date, pulmonary delivery appears to be most feasible. Ongoing phase III studies will ultimately determine safety, tolerability, and efficacy before approval for clinical use.
Effects of Moderate Weight Loss and Orlistat on Insulin Resistance, Regional Adiposity, and Fatty Acids in Type 2 Diabetes
Authors: Kelley David E. , Kuller Lewis H. , McKolanis Therese M. , Harper Patricia , Mancino Juliet , Kalhan Satish
Published: March 2007

OBJECTIVE—Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss–dependent and –independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O).

RESEARCH DESIGN AND METHODS—Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (−10.3 ± 1.3 vs. −8.9 ± 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis.

RESULTS—Weight loss resulted in substantial improvement (P < 0.001) in HbA1c (−1.6 ± 0.3 vs. −1.0 ± 0.4%; NS between groups). IS improved significantly more with orlistat (Δ2.2 ± 0.4 vs. Δ1.2 ± 0.4 mg · min−1 · kg−1 fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Δ–154 ± 22 vs. Δ–51 ± 33 μmol/l; P < 0.05), insulin-suppressed FFA (Δ–119 ± 23 vs. Δ–87 ± 34 μmol/l; P < 0.05), and fasting plasma glucose (FPG; −62 ± 9 vs. −32 ± 8 mg/dl; P = 0.02). Changes in HbA1c were correlated with ΔIS (r = −0.41; P < 0.01) but not with weight loss per se.

CONCLUSIONS—At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS.
Dietary Magnesium Intake in Relation to Plasma Insulin Levels and Risk of Type 2 Diabetes in Women
Authors: Song Yiqing , Manson JoAnn E. , Buring Julie E. , Liu Simin
Published: March 2007

OBJECTIVE—Higher intake of magnesium appears to improve glucose and insulin homeostasis; however, there are sparse prospective data on the association between magnesium intake and incidence of type 2 diabetes.

RESEARCH DESIGN AND METHODS—In the Women’s Health Study, a cohort of 39,345 U.S. women aged ≥45 years with no previous history of cardiovascular disease, cancer, or type 2 diabetes completed validated semiquantitative food frequency questionnaires in 1993 and were followed for an average of 6 years. We used Cox proportional hazard models to estimate multivariate relative risks (RRs) of type 2 diabetes across quintiles of magnesium intake compared with the lowest quintile. In a sample of 349 apparently healthy women from this study, we measured plasma fasting insulin levels to examine their relation to magnesium intake.

RESULTS—During 222,523 person-years of follow-up, we documented 918 confirmed incident cases of type 2 diabetes. There was a significant inverse association between magnesium intake and risk of type 2 diabetes, independent of age and BMI (P = 0.007 for trend). After further adjustment for physical activity, alcohol intake, smoking, family history of diabetes, and total calorie intake, the multivariate-adjusted RRs of diabetes from the lowest to highest quintiles of magnesium intake were attenuated at 1.0, 1.06, 0.81, 0.86, and 0.89 (P = 0.05 for trend). Among women with BMI ≥25 kg/m2, the inverse trend was significant; multivariate-adjusted RRs were 1.0, 0.96, 0.76, 0.84, and 0.78 (P = 0.02 for trend). Multivariate-adjusted geometric mean insulin levels for overweight women in the lowest quartile of magnesium intake was 53.5 compared with 41.5 pmol/l among those at the highest quartile (P = 0.03 for trend).

CONCLUSIONS—These findings support a protective role of higher intake of magnesium in reducing the risk of developing type 2 diabetes, especially in overweight women.
Diabetes and Outcome of Community-Acquired Pneumococcal Bacteremia
Authors: Thomsen Reimar W. , Hundborg Heidi H. , Lervang Hans-Henrik , Johnsen Søren P. , Sørensen Henrik T. , Schønheyder Henrik C.
Published: March 2007

OBJECTIVE—Patients with diabetes may carry a higher case fatality of invasive pneumococcal infection compared with nondiabetic patients due to decreased immunity, risk of metabolic derangement, or angiopathy. We conducted a population-based cohort study to assess the impact of diabetes on mortality within 90 days in patients with pneumococcal bacteremia.

RESEARCH DESIGN AND METHODS—All patients with community-acquired pneumococcal bacteremia in North Jutland County, Denmark, from January 1992 to December 2001 were retrieved from the County Bacteremia Registry. Using civil registry numbers, patients with diabetes were identified by record linkage with the County Prescription Database (for antidiabetic drugs) and the County Hospital Discharge Registry. Mortality within 90 days was determined through the Central Population Registry. Mortality rates were compared for diabetic and nondiabetic patients and adjusted for sex, age, and comorbidity.

RESULTS— Among 628 patients aged >15 years with community-acquired pneumococcal bacteremia, 63 (10.0%) had diabetes. The diabetic patients were slightly older (median age 71.7 years) than the nondiabetic patients (67.0 years), and the proportion of patients with comorbidity was higher in the diabetic group (59 vs. 46%). Mortality in diabetic patients compared with nondiabetic patients was 11.1 vs. 16.5% after 30 days and 16.0 vs. 19.5% after 90 days, respectively. After adjustment for sex, age, and comorbidity, the mortality rate ratio for diabetic patients was 0.6 (95% CI 0.3–1.2) compared with the nondiabetic patients.

CONCLUSIONS—Diabetic patients with community-acquired pneumococcal bacteremia appear not to have a higher case fatality than nondiabetic patients.
Organizational Factors Affecting the Adoption of Diabetes Care Management Processes in Physician Organizations
Authors: Li Rui , Simon Jodi , Bodenheimer Thomas , Gillies Robin R. , Casalino Lawrence , Schmittdiel Julie , Shortell Stephen M.
Published: March 2007

OBJECTIVE—To describe the extent of adoption of diabetes care management processes in physician organizations in the U.S. and to investigate the organizational factors that affect the adoption of diabetes care management processes.

RESEARCH DESIGN AND METHODS—Data are derived from the National Survey of Physician Organizations and the Management of Chronic Illness, conducted in 2000–2001. A total of 1,104 of the 1,590 physician organizations identified responded to the survey. The extent of adoption of four diabetes care management processes is measured by an index consisting of the organization’s use of diabetic patient registries, clinical practice guidelines, case management, and physician feedback. The ordinary least-squares model is used to determine the association of organizational characteristics with the adoption of diabetes care management processes in physician organizations. A logistic regression model is used to determine the association of organizational characteristics with the adoption of individual diabetes care management processes.

RESULTS—Of the 987 physician organizations studied that treat patients with diabetes, 48% either do not use any or use only one of the four diabetes care management processes. A total of 20% use two care management processes, and 32% use three or four processes. External incentives to improve quality, computerized clinical information systems, and ownership by hospitals or health maintenance organizations are strongly associated with the diabetes care management index and the adoption of individual diabetes care management processes.

CONCLUSIONS—Policies to encourage external incentives to improve quality and to facilitate the adoption of computerized clinical information technology may promote greater use of diabetes care management processes.
Aldose Reductase Inhibition by AS-3201 in Sural Nerve From Patients With Diabetic Sensorimotor Polyneuropathy
Authors: Bril Vera , Buchanan Robert A. ,   the AS-3201 Study Group
Published: March 2007

OBJECTIVE—The primary purpose of this investigation was to determine whether AS-3201, a new aldose reductase inhibitor, penetrates the sural nerve and inhibits sorbitol and fructose accumulation in patients with diabetic sensorimotor polyneuropathy (DSP). An additional aim was to determine whether any changes in nerve function would manifest with AS-3201 therapy.

RESEARCH DESIGN AND METHODS—Patients with mild to moderate DSP based on nerve conduction studies were randomized into one of three treatment groups in a double-blind fashion: placebo or AS-3201 at 5 or 20 mg/day. After 12 weeks of administration, the sural nerve was biopsied for measurement of sorbitol, fructose, and AS-3201.

RESULTS—At baseline, no important clinical, electrophysiological, or laboratory differences were found between the three groups. The nerve sorbitol concentration of 3.14 × 10−2 nmol/mg wet nerve in patients in the placebo group was inhibited by 65 and 84% in patients on AS-3201 at 5 and 20 mg/day, respectively (P < 0.001). Fructose levels were similarly inhibited. Sensory nerve conduction velocities improved by ≥1 m/s (P < 0.05).

CONCLUSIONS—AS-3201 penetrates the sural nerve and inhibits sorbitol accumulation in patients with DSP. Additional studies are needed to confirm the electrophysiological suggestion that AS-3201 delays progression or leads to regression of DSP.