bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in the Pattern of Antibiotic Prescription Profile and Recurrence Rate for Possible Urinary Tract Infections in Women With and Without Diabetes
Authors: Schneeberger Caroline , Stolk Ronald P. , DeVries J. Hans , Schneeberger Peter M. , Herings Ron M. , Geerlings Suzanne E.
Published: June 2008

OBJECTIVE—Women with diabetes have a high incidence and complication rate of urinary tract infections (UTIs). Our aims were to compare current treatment strategies with respect to recurrence rates in women with diabetes with those without diabetes.

RESEARCH DESIGN AND METHODS—We used a Dutch registration database containing pharmacy dispensing data. A total of 10,366 women with diabetes (17.5% premenopausal) (aged ≤55 years) and 200,258 women without diabetes (68% premenopausal) who received a first course of trimethoprim, nitrofurantoin, fosfomycin, or norfloxacin between January 1999 and January 2006 were included. We compared short (≤5 days) with long (>5 days) prescriptions and norfloxacin with trimethoprim, nitrofurantoin, and fosfomycin. A recurrence was defined as a second prescription for one of the above-mentioned agents or a first with amoxicillin (clavulanic acid), fluoroquinolones, or trimethoprim/sulfamethoxazole between 6 and 30 days after inclusion.

RESULTS—Premenopausal women with diabetes more often received a long (26.5 vs. 19.2%; P < 0.001) treatment with norfloxacin (10.7 vs. 6.2%; P < 0.001) but still had a higher recurrence rate (16.1 vs. 12.2%; P = 0.003) compared with those without diabetes. Similarly, postmenopausal women with diabetes more often received a longer (32.8 vs. 28.8%; P < 0.001) treatment with norfloxacin (15.2 vs. 12.7%; P < 0.001) but had a higher recurrence rate (19.1 vs. 16.4%; P < 0.001) compared with those without diabetes.

CONCLUSIONS—Despite the fact that patients with diabetes more often received longer and more potent initial treatment than patients without diabetes, pre- and postmenopausal women with diabetes more often had recurrences of their UTIs.
Trends in High-Risk HLA Susceptibility Genes Among Colorado Youth With Type 1 Diabetes
Authors: Vehik Kendra , Hamman Richard F. , Lezotte Dennis , Norris Jill M. , Klingensmith Georgeanna J. , Rewers Marian , Dabelea Dana
Published: June 2008

OBJECTIVE—Type 1 diabetes is associated with a wide spectrum of susceptibility and protective genotypes within the HLA class II system. It has been reported that adults diagnosed with youth-onset type 1 diabetes more recently have been found to have fewer classical high-risk HLA class II genotypes than those diagnosed several decades ago. We hypothesized that such temporal trends in the distribution of HLA-DR, DQ genotypes would be evident, and perhaps even stronger, among 5- to 17-year-old Hispanic and non-Hispanic white (NHW) youth diagnosed with type 1 diabetes in Colorado between 1978 and 2004.

RESEARCH DESIGN AND METHODS—HLA-DR, DQ was typed using PCR and sequence-specific oligonucleotide hybridization in 100 youth diagnosed during the period of 1978–1988 and 264 diagnosed during 2002–2004. Logistic regression was used to adjust for confounders and assess temporal trends.

RESULTS—The frequency of the highest-risk genotype (DRB1*03-DQB1*02/DRB1*04-DQB1*03) was higher (39%) in children diagnosed during the period 1978–1988 than in those diagnosed during 2002–2004 (28%). A similar pattern was observed in NHWs and Hispanics.

CONCLUSIONS—We found that high-risk HLA genotypes are becoming less frequent over time in youth with type 1 diabetes of NHW and Hispanic origin. This temporal trend may suggest that increasing environmental exposure is now able to trigger type 1 diabetes in subjects who are less genetically susceptible.
Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes
Authors: Gallego Patricia H. , Craig Maria E. , Duffin Anthony C. , Bennetts Bruce , Jenkins Alicia J. , Hofer Sabine , Lam Albert , Donaghue Kim C.
Published: June 2008

OBJECTIVE— In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro- and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107C>T, in type 1 diabetes.

RESEARCH DESIGN AND METHODS—This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment–length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate.

RESULTS—Median (interquartile range) age was 15.4 (13.5–17.3) years, and diabetes duration was 7.6 (4.9–10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (>1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p.Leu54Met polymorphism (odds ratio 3.84 [95% CI 1.49–9.82], P = 0.005); BMI (percentile) (1.02 [1.01–1.03], P = 0.007); systolic blood pressure (percentile) (1.01 [1.00–1.02], P = 0.03); and male sex (3.29 [1.98–5.46], P < 0.001).

CONCLUSIONS—Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT.
Association Between Renal Failure and Foot Ulcer or Lower-Extremity Amputation in Patients With Diabetes
Authors: Margolis David J. , Hofstad Ole , Feldman Harold I.
Published: June 2008

OBJECTIVE—The objective of this study was to evaluate the association between foot ulcers (DFU) and lower-extremity amputation (LEA) and chronic kidney disease (CKD) in patients with diabetes.

RESARCH DESIGN AND METHODS—This was a retrospective cohort study of individuals enrolled between 2002 and 2006 who were aged ≥35 years, had a history of diabetes, and were cared for in general practice. The physicians participated in The Health Information Network of the U.K.

RESULTS—The presence of DFU or LEA and estimated glomerular filtration rate (eGFR) were evaluated in 90,617 individuals with a median time of observation of 2.4 years. Of these individuals 378 had an LEA and 2,619 had a DFU. CKD (eGFR <60 ml/min per 1.73 m2) was noted in 23,350 (26%) individuals in our cohort. For the development of DFU compared with our reference group (group 1 [eGFR ≥60 ml/min per 1.73 m2]), the hazard ratio (HR) for group 2 (eGFR ≥30 and <60 ml/min per 1.73 m2) was 1.85 (95% CI 1.71–2.01) and for group 3 (eGFR <30 ml/min per 1.73 m2) was 3.92 (3.23–4.75) (all P < 0.001). For LEA, the HR for group 2 was 2.08 (1.68–2.58) and for group 3 was 7.71 (5.29–11.26) (all P < 0.001).

CONCLUSIONS—In this observational study, there is a strong association between stage of CKD and DFU or LEA that is probably not just related to the presence of peripheral arterial disease. Individuals with even moderate CKD (eGFR <60 ml/min per 1.73 m2) have an increased risk for DFU and LEA.
Evaluation of a Systems Navigator Model for Transition From Pediatric to Adult Care for Young Adults With Type 1 Diabetes
Authors: Van Walleghem Norma , MacDonald Catherine A. , Dean Heather J.
Published: June 2008

OBJECTIVES— To determine whether a systems navigator service, The Maestro Project, could increase medical surveillance for young adults with type 1 diabetes who transfer from pediatric to adult care.

RESEARCH DESIGN AND METHODS— There were two cohorts of participants: 1) a younger group (aged 18 years, n = 82) who had the assistance of the navigator as they graduated from pediatric care and 2) an older group (aged 19–25 years) who were transferred to adult care without this initial support but later enrolled in the program.

RESULTS— Of the older group (who did not have initial access to the navigator), 40% dropped out of adult medical care, compared with a dropout rate of 11% for the younger group, who had access to the navigator at the time of transfer from pediatric care.

CONCLUSIONS— The systems navigator helped improve medical surveillance for both groups, although there was no evidence of improved short-term medical outcomes.
Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome
Authors: Hutchison Samantha K. , Harrison Cheryce , Stepto Nigel , Meyer Caroline , Teede Helena J.
Published: June 2008

OBJECTIVE—Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating insulin resistance in overweight women with PCOS.

RESEARCH DESIGN AND METHODS—At baseline, 38 overweight women (BMI >27 kg/m2) with PCOS and 17 weight-matched control subjects were compared. Women with PCOS were then randomly assigned to 6 months of a higher-dose oral contraceptive pill (OCP) (35 μg ethinyl estradiol/2 mg cyproterone acetate) or metformin (1 g b.i.d.). Outcome measures were insulin resistance (total insulin area under the curve) on an oral glucose tolerance test, RBP4, and metabolic/inflammatory markers.

RESULTS—Overweight women with PCOS were more insulin resistant than control subjects, yet RBP4 levels were not different in women with PCOS versus those in control subjects (35.4 ± 4.3 vs. 28.9 ± 3.1 μg/ml, P = 0.36). RBP4 correlated with cholesterol and triglycerides but not with insulin resistance. Metformin improved insulin resistance by 35%, whereas the OCP worsened insulin resistance by 33%. However, RBP4 increased nonsignificantly in both groups (43.7 ± 6.3 vs. 42.6 ± 5.5 μg/ml, P = 0.92).

CONCLUSIONS—Overweight women with PCOS were more insulin resistant than control subjects, but this finding was not reflected by RBP4 levels. RBP4 correlated with lipid levels but not with insulin resistance markers. RBP4 levels did not change when insulin resistance was reduced by metformin or increased by the OCP. These data suggest that RBP4 is not a useful marker of insulin resistance in PCOS but may reflect other metabolic features of this condition.
Weight Loss Strategies Associated With BMI in Overweight Adults With Type 2 Diabetes at Entry Into the Look AHEAD (Action for Health in Diabetes) Trial
Authors: Raynor Hollie A. , Jeffery Robert W. , Ruggiero Andrea M. , Clark Jeanne M. , Delahanty Linda M. ,   for the Look AHEAD (Action for Health in Diabetes) Research Group
Published: June 2008

OBJECTIVE—Intentional weight loss is recommended for those with type 2 diabetes, but the strategies patients attempt and their effectiveness for weight management are unknown. In this investigation we describe intentional weight loss strategies used and those related to BMI in a diverse sample of overweight participants with type 2 diabetes at enrollment in the Look AHEAD (Action for Health in Diabetes) clinical trial.

RESEARCH DESIGN AND METHODS—This was a cross-sectional study of baseline weight loss strategies, including self-weighing frequency, eating patterns, and weight control practices, reported in 3,063 women and 2,082 men aged 45–74 years with BMI ≥25 kg/m2.

RESULTS—Less than half (41.4%) of participants self-weighed ≥1/week. Participants ate breakfast 6.0 ± 1.8 days/week, ate 5.0 ± 3.1 meals/snacks per day, and ate 1.9 ± 2.7 fast food meals/week. The three most common weight control practices (increasing fruits and vegetables, cutting out sweets, and eating less high-carbohydrate foods) were reported by ∼60% of participants for ≥20 weeks over the previous year. Adjusted models showed that self-weighing less than once per week (B = 0.83), more fast food meals consumed per week (B = 0.14), and fewer breakfast meals consumed per week (B = −0.19) were associated (P < 0.05) with a higher BMI (R2 = 0.24).

CONCLUSIONS—Regular self-weighing and breakfast consumption, along with infrequent consumption of fast food, were related to lower BMI in the Look AHEAD study population.
Rosiglitazone and Risk of Cancer
Authors: Monami Matteo , Lamanna Caterina , Marchionni Niccolò , Mannucci Edoardo
Published: June 2008

OBJECTIVE—Despite experimental data suggesting a protective effect of peroxisome proliferator–activated receptor-γ agonists with respect to malignancies, results of available epidemiological studies on the incidence of cancer in rosiglitazone-treated patients are not univocal. The aim of this meta-analysis of randomized clinical trials is to assess the effect of rosiglitazone on the incidence of cancer.

RESEARCH DESIGN AND METHODS—Randomized clinical trials of rosiglitazone with duration of >24 weeks were retrieved through Medline and from the GlaxoSmithKline Web site, which reports main results of all trials sponsored by GlaxoSmithKline; incident malignancies were retrieved from the summary of serious adverse events. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% CI. Considering differences in the duration of follow-up among treatment arms in some of the trials, we also calculated the incidence of cancer in rosiglitazone and control groups.

RESULTS—Eighty trials, enrolling 16,332 and 12,522 patients in the rosiglitazone and comparator groups, respectively, were retrieved. Rosiglitazone was not associated with a significant modification of the risk of cancer (OR 0.91 [95% CI 0.71–1.16], P = 0.44). The incidence of malignancies was significantly lower in rosiglitazone-treated patients than in control groups (0.23 [0.19–0.26] vs. 0.44 [0.34–0.58] cases/100 patient-years; P < 0.05).

CONCLUSIONS—The use of rosiglitazone appears to be safe in terms of incidence of cancer, whereas its possible protective effect needs to be further investigated.
Effect of Supervised Progressive Resistance-Exercise Training Protocol on Insulin Sensitivity, Glycemia, Lipids, and Body Composition in Asian Indians With Type 2 Diabetes
Authors: Misra Anoop , Alappan Narendra K. , Vikram Naval K. , Goel Kashish , Gupta Nidhi , Mittal Kanchan , Bhatt Suryaprakash , Luthra Kalpana
Published: June 2008

OBJECTIVE—To evaluate the effect of supervised progressive resistance-exercise training (PRT) protocol on insulin sensitivity, glycemia (blood glucose and A1C levels), lipids, and body composition in Asian Indians with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Thirty patients with type 2 diabetes underwent 12 weeks of PRT of six muscle groups (two sets, 10 repetitions each). The subjects were evaluated with detailed anthropometry and with measurements of the disappearance of glucose per unit time (K) during the short insulin tolerance test (KITT) for assessment of insulin sensitivity; of fasting blood glucose, A1C, lipids, and high-sensitivity C-reactive protein (hsCRP); of total body fat, regional fat, and lean body mass by dual-energy X-ray absorptiometry; and of cross-sectional skeletal muscle area of upper arm and thigh by computed tomography scan.

RESULTS—Insulin sensitivity improved significantly from mean ± SD KITT 1.22 ± 0.73 to 2.13 ± 0.75 (P < 0.0001) after the intervention. Significant decline (mean difference ± SD) from baseline was recorded in levels of the following parameters: A1C (0.54 ± 0.4%, P < 0.001), fasting blood glucose (2.7 ± 2.2 mmol/l, P < 0.001), total cholesterol (0.39 ± 0.7 mmol/l, P = 0.003), serum triglycerides (0.39 ± 0.5 mmol/l, P < 0.001), and truncal and peripheral subcutaneous adipose tissue compartments (SCAT) (P < 0.001). However, no significant changes were noticed in BMI or levels of total body fat, truncal fat, lean body mass, cross-sectional skeletal muscle area of the extremities, or hsCRP levels.

CONCLUSIONS—Moderate-intensity PRT for 3 months resulted in significant improvement in insulin sensitivity, glycemia, lipids, and truncal and peripheral SCAT in patients with type 2 diabetes. Resistance training should be an integral part of exercise regimen in Asian Indians with type 2 diabetes.
Diminished Alveolar Microvascular Reserves in Type 2 Diabetes Reflect Systemic Microangiopathy
Authors: Chance William W. , Rhee Chanhaeng , Yilmaz Cuneyt , Dane D. Merrill , Pruneda M. Lourdes , Raskin Philip , Hsia Connie C.W.
Published: June 2008

OBJECTIVE—Alveolar microvascular function is moderately impaired in type 1 diabetes, as manifested by restriction of lung volume and diffusing capacity (DLCO). We examined whether similar impairment develops in type 2 diabetes and defined the physiologic sources of impairment as well as the relationships to glycemia and systemic microangiopathy.

RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted at a university-affiliated diabetes treatment center and outpatient diabetes clinic, involving 69 nonsmoking type 2 diabetic patients without overt cardiopulmonary disease. Lung volume, pulmonary blood flow (Q̇), DLCO, membrane diffusing capacity (measured from nitric oxide uptake [DLNO]), and pulmonary capillary blood volume (VC) were determined at rest and exercise for comparison with those in 45 healthy nonsmokers as well as with normal reference values.

RESULTS—In type 2 diabetic patients, peak levels of oxygen uptake, Q̇ and DLCO, DLNO, and VC at exercise were 10–25% lower compared with those in control subjects. In nonobese patients (BMI <30 kg/m2), reductions in DLCO, DLNO, and VC were fully explained by the lower lung volume and peak Q̇, but these factors did not fully explain the impairment in obese patients (BMI >30 kg/m2). The slope of the increase in VC with respect to Q̇ was reduced ∼20% in patients regardless of BMI, consistent with impaired alveolar-capillary recruitment. Functional impairment was directly related to A1C level, retinopathy, neuropathy, and microalbuminuria in a sex-specific manner.

CONCLUSIONS—Alveolar microvascular reserves are reduced in type 2 diabetes, reflecting restriction of lung volume, alveolar perfusion, and capillary recruitment. This reduction correlates with glycemic control and extrapulmonary microangiopathy and is aggravated by obesity.
Clinical Application of 1,5-Anhydroglucitol Measurements in Patients with Hepatocyte Nuclear Factor-1α Maturity-Onset Diabetes of the Young
Authors: Skupien Jan , Gorczynska-Kosiorz Sylwia , Klupa Tomasz , Wanic Krzysztof , Button Eric A. , Sieradzki Jacek , Malecki Maciej T.
Published: June 2008

OBJECTIVE—1,5-anhydroglucitol (1,5-AG) is a short-term marker of metabolic control in diabetes. Its renal loss is stimulated in hyperglycemic conditions by glycosuria, which results in a lowered plasma concentration. As a low renal threshold for glucose has been described in hepatocyte nuclear factor-1α (HNF-1α) maturity-onset diabetes of the young (MODY), the 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in patients with HNF-1α MODY and in type 2 diabetic subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1α MODY.

RESEARCH DESIGN AND METHODS—We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 type 2 diabetic patients and 47 nondiabetic control subjects. The 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). Receiver operating characteristic (ROC) curve analysis was used to evaluate 1,5-AG as a screening marker for HNF-1α MODY.

RESULTS—The mean 1,5-AG plasma concentration in diabetic HNF-1α mutation carriers was 5.9 μg/ml, and it was lower than that in type 2 diabetic patients (11.0 μg/ml, P = 0.003) and in nondiabetic control subjects (23.9 μg/ml, P < 0.00005). The ROC curve analysis revealed 85.7% sensitivity and 80.0% specificity of 1,5-AG in screening for HNF-1α MODY at the criterion of <6.5 μg/ml in patients with an A1C level between 6.5 and 9.0%.

CONCLUSIONS—1,5-AG may be a useful biomarker for differential diagnosis of patients with HNF-1α MODY with a specific range of A1C, although this requires further investigation. However, the clinical use of this particle in diabetic HNF-1α mutation carriers for metabolic control has substantial limitations.
Trends in Diabetes, High Cholesterol, and Hypertension in Chronic Kidney Disease Among U.S. Adults: 1988–1994 to 1999–2004
Authors: Fox Caroline S. , Muntner Paul
Published: June 2008

OBJECTIVE—The prevalence of chronic kidney disease (CKD) increased among U.S. adults from 1988–1994 to 1999–2004. We sought to explore the importance of trends in risk factors for CKD over time

RESEARCH DESIGN AND METHODS—The prevalence of cigarette smoking, obesity, hypertension, high cholesterol, and diabetes among U.S. adults with stage 3 CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m2) and albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g), separately, were determined for 1988–1994 and 1999–2004 using data from serial National Health and Nutrition Examination Surveys. The prevalence ratios (PRs) for stage 3 CKD and albuminuria by the presence of these risk factors were compared across survey periods.

RESULTS—The PR for CKD declined between 1988–1994 and 1999–2004 for obesity (PR 1.51 and 1.14 for 1988–1994 and 1999–2004, respectively; P for change = 0.010), hypertension (PR 2.60 and 1.70; P for change = 0.005), and high cholesterol (PR 1.58 and 1.20; P for change = 0.028). However, for diagnosed diabetes, the PR remained unchanged (1.64 and 1.62; P for change = 0.898). Similar results were observed for undiagnosed diabetes (PR of CKD 1.38 and 1.50; P for change = 0.373). The association of cigarette smoking was similar in each time period. Besides obesity, for which the association remained stable over time, similar patterns were observed for the PR of albuminuria.

CONCLUSIONS—In terms of CKD, improvements in hypertension and high cholesterol management have been offset by both diagnosed and undiagnosed diabetes. Further increases in CKD may occur if diabetes continues to increase.
Epidermal Innervation in Type 1 Diabetic Patients
Authors: Boucek Petr , Havrdova Terezia , Voska Ludek , Lodererova Alena , He Lan , Saudek Frantisek , Lipar Kvetoslav , Adamec Milos , Sommer Claudia
Published: June 2008

OBJECTIVE—To assess the effect of normoglycemia following simultaneous pancreas/kidney transplantation (SPK) on neurological function and intraepidermal nerve fiber density (IENFD) in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—We performed vibration perception threshold (VPT) testing and autonomic function testing (AFT) and assessed IENFD in skin biopsies from the lower thigh and upper calf in 14 healthy control subjects and 18 patients with type 1 diabetes at the time of and at 21–40 (median 29) months post SPK.

RESULTS—At baseline, significantly increased VPTs, pathological AFT results, and severe reduction in IENFD were present in SPK recipients. After SPK, an increase of IENFD in the thigh of more than one epidermal nerve fiber per millimeter was noted in three patients (median 4.1, range 1.9–10.2), but changes were not significant for the group as a whole.

CONCLUSIONS—We conclude that either irreversible nerve damage might be present in some SPK recipients or that longer periods of normoglycemia might be needed to allow nerve regeneration.
Burden and Rates of Treatment and Control of Cardiovascular Disease Risk Factors in Obesity
Authors: Molenaar Esther A. , Hwang Shih-Jen , Vasan Ramachandran S. , Grobbee Diederick E. , Meigs James B. , D'Agostino Ralph B. , Levy Daniel , Fox Caroline S.
Published: June 2008

OBJECTIVE— Obesity is associated with an increased risk for cardiovascular disease (CVD). We sought to determine rates of treatment and control of CVD risk factors among normal weight, overweight, and obese individuals in a community-based cohort.

RESEARCH DESIGN AND METHODS— Participants free of CVD (n = 6,801; mean age 49 years; 54% women) from the Framingham Offspring and Third Generation cohorts who attended the seventh Offspring examination (1998–2001) or first Third Generation (2002–2005) examination were studied.

RESULTS— Obese participants with hypertension were more likely to receive antihypertensive treatment (62.3%) than normal weight (58.7%) or overweight (59.0%) individuals (P = 0.002), but no differences in hypertension control across BMI subgroups among participants with hypertension were observed (36.7% [normal weight], 37.3% [overweight], and 39.4% [obese]; P = 0.48). Rates of lipid-lowering treatment were higher among obese participants with elevated LDL cholesterol (39.5%) compared with normal weight (34.2%) or overweight (36.4%) participants (P = 0.02), but control rates among those with elevated LDL cholesterol did not differ across BMI categories (26.7% [normal weight], 26.0% [overweight], and 29.2% [obese]; P = 0.11). There were no differences in diabetes treatment among participants with diabetes across BMI groups (69.2% [normal weight], 50.0% [overweight], 55.0% [obese]; P = 0.54), but obese participants with diabetes were less likely to have fasting blood glucose <126 mg/dl (15.7%) compared with normal weight (30.4%) or overweight (20.7%) participants (P = 0.02).

CONCLUSIONS— These findings emphasize the suboptimal rates of treatment and control of CVD risk factors among overweight and obese individuals.
Association of Intrauterine Exposure to Maternal Diabetes and Obesity With Type 2 Diabetes in Youth
Authors: Dabelea Dana , Mayer-Davis Elizabeth J. , Lamichhane Archana P. , D'Agostino Ralph B. , Liese Angela D. , Vehik Kendra S. , Narayan K.M. Venkat , Zeitler Phillip , Hamman Richard F.
Published: June 2008

OBJECTIVE—Limited data exist on the association between in utero exposure to maternal diabetes and obesity and type 2 diabetes in diverse youth. These associations were explored in African-American, Hispanic, and non-Hispanic white youth participating in the SEARCH Case-Control Study.

RESEARCH DESIGN AND METHODS—A total of 79 youth with type 2 diabetes and 190 nondiabetic control youth aged 10–22 years attended a research visit. In utero exposures to maternal diabetes and obesity were recalled by biological mothers.

RESULTS—Youth with type 2 diabetes were more likely to have been exposed to maternal diabetes or obesity in utero than were nondiabetic control youth (P < 0.0001 for each). After adjusting for offspring age, sex, and race/ethnicity, exposure to maternal diabetes (odds ratio [OR] 5.7 [95% CI 2.4–13.4]) and exposure to maternal obesity (2.8 [1.5–5.2]) were independently associated with type 2 diabetes. Adjustment for other perinatal and socioeconomic factors did not alter these associations. When offspring BMI was added, the OR for the association between in utero exposure to obesity and type 2 diabetes was attenuated toward the null (OR 1.1 [0.5–2.4]). Overall, 47.2% (95% CI 30.9–63.5) of type 2 diabetes in youth could be attributed to intrauterine exposure to maternal diabetes and obesity.

CONCLUSIONS—Intrauterine exposures to maternal diabetes and obesity are strongly associated with type 2 diabetes in youth. Prevention efforts may need to target, in addition to childhood obesity, the increasing number of pregnancies complicated by obesity and diabetes.
Dietary Behaviors Predict Glycemic Control in Youth With Type 1 Diabetes
Authors: Mehta Sanjeev N. , Volkening Lisa K. , Anderson Barbara J. , Nansel Tonja , Weissberg-Benchell Jill , Wysocki Tim , Laffel Lori M.B. ,   for the Family Management of Childhood Diabetes Study Steering Committee
Published: June 2008

OBJECTIVE—To investigate the association between dietary adherence and glycemic control among youth with type 1 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a cross-sectional analysis of 119 youth aged 9–14 years (mean ± SD 12.1 ± 1.6 years) with diabetes duration ≥1 year (5.4 ± 3.1 years). Dietary adherence was assessed using the Diabetes Self-Management Profile diet domain. Higher score defined greater dietary adherence. Glycemic control was determined by A1C.

RESULTS—Dietary adherence score was inversely correlated with A1C (r = −0.36, P < 0.0001). In a multivariate model (R2 = 0.34, P < 0.0001), dietary adherence (P = 0.004), pump use (P = 0.03), and caregiver education (P = 0.01) were associated with A1C. A1C of youth in the lowest (9.0%) tertile of diet score was higher than A1C of youth in the middle (8.1%, P = 0.004) and upper (8.4%, P = 0.06) tertiles. Dietary adherence uniquely explained 8% of the variance in A1C in the model.

CONCLUSIONS—Greater dietary adherence was associated with lower A1C among youth with type 1 diabetes.
Cost-Effectiveness of Intensified Versus Conventional Multifactorial Intervention in Type 2 Diabetes
Authors: Gæde Peter , Valentine William J. , Palmer Andrew J. , Tucker Daniel M.D. , Lammert Morten , Parving Hans-Henrik , Pedersen Oluf
Published: June 2008

OBJECTIVE—To assess the cost-effectiveness of intensive versus conventional therapy for 8 years as applied in the Steno-2 study in patients with type 2 diabetes and microalbuminuria.

RESEARCH DESIGN AND METHODS—A Markov model was developed to incorporate event and risk data from Steno-2 and account Danish-specific costs to project life expectancy, quality-adjusted life expectancy (QALE), and lifetime direct medical costs expressed in year 2005 Euros. Clinical and cost outcomes were projected over patient lifetimes and discounted at 3% annually. Sensitivity analyses were performed.

RESULTS—Intensive treatment was associated with increased life expectancy, QALE, and lifetime costs compared with conventional treatment. Mean ± SD undiscounted life expectancy was 18.1 ± 7.9 years with intensive treatment and 16.2 ± 7.3 years with conventional treatment (difference 1.9 years). Discounted life expectancy was 13.4 ± 4.8 years with intensive treatment and 12.4 ± 4.5 years with conventional treatment. Lifetime costs (discounted) for intensive and conventional treatment were €45,521 ± 19,697 and €41,319 ± 27,500, respectively (difference €4,202). Increased costs with intensive treatment were due to increased pharmacy and consultation costs. Discounted QALE was 1.66 quality-adjusted life-years (QALYs) higher for intensive (10.2 ± 3.6 QALYs) versus conventional (8.6 ± 2.7 QALYs) treatment, resulting in an incremental cost-effectiveness ratio of €2,538 per QALY gained. This is considered a conservative estimate because accounting prescription of generic drugs and capturing indirect costs would further favor intensified therapy.

CONCLUSIONS—From a health care payer perspective in Denmark, intensive therapy was more cost-effective than conventional treatment. Assuming that patients in both arms were treated in a primary care setting, intensive therapy became dominant (cost- and lifesaving).
Risk of Glucose Intolerance and Diabetes in Hemipancreatectomized Donors Selected for Normal Preoperative Glucose Metabolism
Authors: Kumar Anjali F. , Gruessner Rainer W.G. , Seaquist Elizabeth R.
Published: June 2008

OBJECTIVE—Hemipancreatectomy (HPx) for the purpose of organ donation has been associated with a 25% risk of developing abnormal glucose tolerance or diabetes in the year after surgery. Since 1997, the University of Minnesota has imposed criteria to prevent potential donors with clinical features associated with an increased diabetes risk from undergoing HPx. We recently assessed glucose tolerance in hemipancreatectomized donors selected since the adoption of the new criteria to determine whether the risk of developing abnormal glucose tolerance was reduced below the 25% rate previously demonstrated.

RESEARCH DESIGN AND METHODS—Individuals who underwent HPx for the purpose of pancreas donation between 1997 and 2003 were contacted and interviewed about their health status. Those not taking diabetes medications were invited to undergo an assessment of their glucose tolerance.

RESULTS—Successful contact was made with 15 of 21 donors who underwent HPx during this period. Two donors reported use of oral diabetic medications and were not studied further. Of the remaining 13, 2 had impaired fasting glucose (fasting blood glucose 100–125 mg/dl), 1 had impaired glucose tolerance (2-h postglucose load blood glucose 140–199 mg/dl), and 3 displayed both. One donor met the diagnostic criteria for diabetes. Six donors had normal glucose values.

CONCLUSIONS—Despite the use of stringent criteria to exclude those at risk for developing abnormalities in glucose metabolism, 43% of healthy humans who underwent HPx between 1997 and 2003 have impaired fasting glucose, impaired glucose tolerance, or diabetes on follow-up. The current preoperative criteria are insufficient to predict those who will develop abnormal glucose metabolism after HPx.
Economic Benefits of Intensive Insulin Therapy in Critically Ill Patients
Authors: Sadhu Archana R. , Ang Alfonso C. , Ingram-Drake Leslie A. , Martinez Dorothy S. , Hsueh Willa A. , Ettner Susan L.
Published: June 2008

OBJECTIVE—The purpose of this study was to analyze the economic outcomes of a clinical program implemented to achieve strict glycemic control with intensive insulin therapy in patients admitted to the intensive care unit (ICU).

RESEARCH DESIGN AND METHODS—A difference-in-differences (quasi-experimental) study design was used to examine the associations of an intensive insulin therapy intervention with changes in hospital length of stay (ICU and total), costs (ICU and total), and mortality. Hospital administrative data were obtained for 6,719 adult patients admitted between 2003 and 2005 to one of five intervention or four comparison ICUs in a large academic medical center. Linear regression models with log transformations and appropriate retransformations were used to estimate length of stay (LOS) and costs; logistic regressions were used to estimate mortality.

RESULTS—After adjustment for observable patient characteristics and secular time trends, the intervention was consistently associated with lower average glucose levels and a trend toward shorter LOS, lower costs, and lower mortality. However, associations with resource use and outcomes were statistically significant in only ICU LOS, with an average reduction of 1.19 days of ICU care per admission. Other associations, although large in magnitude and in the hypothesized directions, were not estimated with sufficient precision to rule out other net effects. The associations with ICU days and costs were larger in magnitude than total days and costs.

CONCLUSIONS—A clinical team focused on hyperglycemia management for ICU patients can be a valuable investment with significant economic benefits for hospitals.
Lifetime Risk of Cardiovascular Disease Among Individuals With and Without Diabetes Stratified by Obesity Status in the Framingham Heart Study
Authors: Fox Caroline S. , Pencina Michael J. , Wilson Peter W.F. , Paynter Nina P. , Vasan Ramachandran S. , D’Agostino Ralph B.
Published: June 2008

OBJECTIVE—We assessed the lifetime risk of cardiovascular disease (CVD) among individuals with and without obesity and diabetes.

RESEARCH DESIGN AND METHODS—Participants were drawn from the original and offspring cohorts of the Framingham Heart Study. Lifetime (30-year) risk of CVD was assessed using a modified Kaplan-Meier approach adjusting for the competing risk of death, beginning from age 50 years.

RESULTS—Over 30 years, the lifetime risk of CVD among women with diabetes was 54.8% among normal-weight women and 78.8% among obese women. Among normal-weight men with diabetes, the lifetime risk of CVD was 78.6%, whereas it was 86.9% among obese men.

CONCLUSIONS—The lifetime risk of CVD among individuals with diabetes is high, and this relationship is further accentuated with increasing adiposity.
Periodontal Disease and Incident Type 2 Diabetes
Authors: Demmer Ryan T. , Jacobs David R. , Desvarieux Moïse
Published: June 2008

OBJECTIVE—Type 2 diabetes and periodontal disease are known to be associated, but the temporality of this relationship has not been firmly established. We investigated whether baseline periodontal disease independently predicts incident diabetes over two decades of follow-up.

RESEARCH DESIGN AND METHODS—A total of 9,296 nondiabetic male and female National Health and Nutrition Examination Survey (NHANES I) participants aged 25–74 years who completed a baseline dental examination (1971–1976) and had at least one follow-up evaluation (1982–1992) were studied. We defined six categories of baseline periodontal disease using the periodontal index. Of 7,168 dentate participants, 47% had periodontal index = 0 (periodontally healthy); the remaining were classified into periodontal index quintiles. Incident diabetes was defined by 1) death certificate (ICD-9 code 250), 2) self-report of diabetes requiring pharmacological treatment, or 3) health care facility stay with diabetes discharge code. Multivariable logistic regression models assessed incident diabetes odds across increasing levels of periodontal index in comparison with periodontally healthy participants.

RESULTS—The adjusted odds ratios (ORs) for incident diabetes in periodontal index categories 1 and 2 were not elevated, whereas the ORs in periodontal index categories 3 through 5 were 2.26 (95% CI 1.56–3.27), 1.71 (1.0–2.69), and 1.50 (0.99–2.27), respectively. The OR in edentulous participants was 1.30 (1.00–1.70). Dentate participants with advanced tooth loss had an OR of 1.70 (P < 0.05) relative to those with minimal tooth loss.

CONCLUSIONS—Baseline periodontal disease is an independent predictor of incident diabetes in the nationally representative sample of NHANES I.
Adipokines and Incident Type 2 Diabetes in an Aboriginal Canadian Population
Authors: Ley Sylvia H. , Harris Stewart B. , Connelly Philip W. , Mamakeesick Mary , Gittelsohn Joel , Hegele Robert A. , Retnakaran Ravi , Zinman Bernard , Hanley Anthony J.G.
Published: June 2008

OBJECTIVE—The aim of this study was to investigate associations of adiponectin, leptin, C-reactive protein (CRP), interleukin (IL)-6, and serum amyloid A (SAA), individually or in combinations, with risk of incident type 2 diabetes in an Aboriginal Canadian population.

RESEARCH DESIGN AND METHODS—Of the 606 Sandy Lake Health and Diabetes Project cohort subjects who were free of diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments. Concentrations of fasting adiponectin, leptin, CRP, IL-6, SAA, and covariates were measured at baseline. Fasting glucose and a 75-g oral glucose tolerance test were obtained at baseline and follow-up to determine incident type 2 diabetes, defined as clinically diagnosed type 2 diabetes or as fasting plasma glucose ≥7.0 mmol/l or 2-h postload plasma glucose ≥11.1 mmol/l at follow-up.

RESULTS—Low adiponectin, high leptin, and low adiponectin-to-leptin ratio at baseline were associated with increased risk of incident type 2 diabetes after adjustment for age, sex, triglycerides, HDL cholesterol, hypertension, and impaired glucose tolerance (odds ratio 0.63 [95% CI 0.48–0.83], 1.50 [1.02–2.21], and 0.54 [0.37–0.77], respectively). When the models were additionally adjusted for waist circumference or BMI, however, only low adiponectin remained significantly associated with increased incident diabetes (0.68 [0.51–0.90]). Combinations of leptin, CRP, IL-6, and/or SAA with adiponectin, assessed using either the ratio or joint effects, did not improve diabetes prediction.

CONCLUSIONS—Low baseline adiponectin is associated with increased risk of incident type 2 diabetes independent of leptin, CRP, IL-6, SAA, and metabolic syndrome variables including obesity.
Assessment of Aortic Pulse Wave Velocity and Cardiac Diastolic Function in Subjects With and Without the Metabolic Syndrome
Authors: Roes Stijntje D. , Alizadeh Dehnavi Reza , Westenberg Jos J.M. , Lamb Hildo J. , Mertens Bart J.A. , Tamsma Jouke T. , de Roos Albert
Published: June 2008

OBJECTIVE—To evaluate the influence of lipid and glucose metabolism in the metabolic syndrome on aortic pulse wave velocity (PWV) and left ventricular (LV) diastolic function using magnetic resonance imaging (MRI).

RESEARCH DESIGN AND METHODS—Aortic PWV and LV diastolic function were assessed using MRI in 16 subjects with the metabolic syndrome and 16 subjects without the metabolic syndrome matched for age, waist circumference, and blood pressure. The groups were compared using the unpaired t test or Mann-Whitney U test, and linear regression analysis was applied.

RESULTS—Aortic PWV was increased and LV diastolic function was decreased in subjects with compared with those without the metabolic syndrome. HDL cholesterol was independently associated with aortic PWV (R = −0.470, P < 0.01) and LV diastolic function (R = −0.421, P = 0.02).

CONCLUSIONS—Increased aortic PWV and decreased LV diastolic function is observed in subjects with the metabolic syndrome, regardless of blood pressure. Moreover, HDL cholesterol is independently associated with aortic PWV and LV diastolic function.
Adipose Tissue Lipolysis Is Upregulated in Lean and Obese Men During Acute Resistance Exercise
Authors: Chatzinikolaou Athanasios , Fatouros Ioannis , Petridou Anatoli , Jamurtas Athanasios , Avloniti Alexandra , Douroudos Ioannis , Mastorakos George , Lazaropoulou Christina , Papassotiriou Ioannis , Tournis Symeon , Mitrakou Asimina , Mougios Vassilis
Published: June 2008

OBJECTIVE—To investigate the effect of acute resistance exercise on adipose tissue triacylglycerol lipase activity (TGLA) in lean and obese men.

RESEARCH DESIGN AND METHODS—Nine lean and eight obese men performed 30 min of circuit resistance exercise. Adipose tissue and blood were sampled during exercise for TGLA, metabolite, and hormone determinations. Respiratory exchange ratio (RER) was measured throughout exercise.

RESULTS—Energy expenditure of exercise relative to body mass was higher in the lean and RER was higher in the obese men, suggesting lower fat oxidation. TGLA increased 18-fold at 5 min of exercise in the lean men and 16-fold at 10 min of exercise in the obese men. The delayed lipolytic activation in the obese men was reflected in serum nonesterified fatty acid and glycerol concentrations. Plasma insulin increased in the obese but did not change in the lean men.

CONCLUSIONS—Resistance exercise upregulated adipose tissue lipolysis and enhanced energy expenditure in lean and obese men, with a delayed lipolytic activation in the obese men.
Intake of Fruit, Vegetables, and Fruit Juices and Risk of Diabetes in Women
Authors: Bazzano Lydia A. , Li Tricia Y. , Joshipura Kamudi J. , Hu Frank B.
Published: June 2008

OBJECTIVE—The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 71,346 female nurses aged 38–63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported.

RESULTS—During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94–1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72–0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84–0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10–1.26]).

CONCLUSIONS—Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.
Preanalytical, Analytical, and Computational Factors Affect Homeostasis Model Assessment Estimates
Authors: Manley Susan E. , Luzio Stephen D. , Stratton Irene M. , Wallace Tara M. , Clark Penelope M.S.
Published: June 2008

OBJECTIVE—We investigated how β-cell function and insulin sensitivity or resistance are affected by the type of blood sample collected or choice of insulin assay and homeostatis model assessment (HOMA) calculator (http://www.dtu.ox.ac.uk).

RESEARCH DESIGN AND METHODS—Insulin was measured using 11 different assays in serum and 1 assay in heparinized plasma. Fasting subjects with normoglycemia (n = 12), pre-diabetes, i.e., impaired fasting glucose or impaired glucose tolerance (n = 18), or type 2 diabetes (n = 67) were recruited. Patients treated with insulin or those who were insulin antibody–positive were excluded. HOMA estimates were calculated using specific insulin (SI) or radioimmunoassay (RIA) calculators (version 2.2).

RESULTS—All glucose values were within model (HOMA) limits but not all insulin results, as 4.3% were <20 pmol/l and 1% were >300 pmol/l. β-Cell function derived from different insulin assays ranged from 67 to 122% (median) for those with normoglycemia (P = 0.026), from 89 to 138% for those with pre-diabetes (P = 0.990), and from 50 to 81% for those with type 2 diabetes (P < 0.0001). Furthermore, insulin resistance ranged from 0.8 to 2.0 (P = 0.0007), from 1.9 to 3.2 (P = 0.842), and from 1.5 to 2.9 (P < 0.0001), respectively. This twofold variation in HOMA estimates from the various insulin assays studied in serum may be significant metabolically. Insulin was 15% lower in heparinized plasma (used in the original HOMA study) compared with serum, which is now more commonly used. β-Cell function differed by 11% and insulin resistance by 15% when estimates derived from specific insulin were calculated using the RIA rather than the SI calculator.

CONCLUSIONS—To enable comparison of HOMA estimates among individuals and different research studies, preanalytical factors and calculator selection should be standardized with insulin assays traceable to an insulin reference method procedure.
Hyperinsulinemia in African-American Adolescents Compared With Their American White Peers Despite Similar Insulin Sensitivity
Authors: Hannon Tamara S. , Bacha Fida , Lin Yan , Arslanian Silva A.
Published: June 2008

OBJECTIVE—African-American (AA) children are hyperinsulinemic and insulin resistant compared with American white (AW) children. Previously, we demonstrated that insulin secretion relative to insulin sensitivity was ∼75% higher in AA compared with AW children, suggesting that hyperinsulinemia in AA children is not merely a compensatory response to lower insulin sensitivity. The aim of the present investigation was to assess whether glucose-stimulated insulin response is higher in AA versus AW adolescents who have comparable in vivo insulin sensitivity.

RESEARCH DESIGN AND METHODS—The hyperinsulinemic-euglycemic and hyperglycemic clamp techniques were utilized to assess first- and second-phase insulin secretion. Insulin secretion relative to insulin sensitivity was calculated as the glucose disposition index.

RESULTS—AA adolescents compared with their AW peers with comparable insulin sensitivity and body composition had higher first-phase insulin concentrations.

CONCLUSIONS—The quantitative relationship between insulin sensitivity and first-phase insulin appears to differ among AA and AW adolescents.