bluuebunny/crossref_metadata_2025 huggingface dataset:
A Danish Diabetes Risk Score for Targeted Screening
Authors: Glümer Charlotte , Carstensen Bendix , Sandbæk Annelli , Lauritzen Torsten , Jørgensen Torben , Borch-Johnsen Knut
Published: March 2007

OBJECTIVE—To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing.

RESEARCH DESIGN AND METHODS—A population-based sample (Inter99 study) of 6,784 individuals aged 30–60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression.

RESULTS—The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (P < 0.05) associated with the presence of previously undiagnosed diabetes. The area under the receiver operating curve was 0.804 (95% CI 0.765–0.838) for the first half of the Inter99 population, 0.761 (0.720–0.803) for the second half of the Inter99 population, and 0.803 (0.721–0.876) for the ADDITION pilot study. The sensitivity, specificity, and percentage that needed subsequent testing were 76, 72, and 29%, respectively. The false-negative individuals in the risk score had a lower absolute risk of ischemic heart disease compared with the true-positive individuals (11.3 vs. 20.4%; P < 0.0001).

CONCLUSIONS—We developed a questionnaire to be used in a stepwise screening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.
Renin Angiotensin Aldosterone System Blockade and Renal Disease in Patients With Type 2 Diabetes
Authors: Chan Juliana C.N. , Wat Nelson M.S. , So Wing-Yee , Lam Karen S.L. , Chua Chin-Teong , Wong Kok-Seng , Morad Zaki , Dickson Tania Z. , Hille Darcy , Zhang Zhongxin , Cooper Mark E. , Shahinfar Shahnaz , Brenner Barry M. , Kurokawa Kiyoshi ,   on behalf of the Asian RENAAL Study Investigators
Published: March 2007

OBJECTIVE—Asia is predicted to have the largest population of patients with diabetes who are at high risk for renal disease. In the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, ∼17% of patients were Asians. In this subgroup analysis, we examined the characteristics, response, and adherence to treatment of the Asian population, as well as their baseline predictors of risk of renal end points.

RESEARCH DESIGN AND METHODS—A total of 252 Asian patients were enrolled in the RENAAL study, which compared losartan (50 mg titrated to 100 mg) to placebo in addition to conventional antihypertensive medications in type 2 diabetic patients with nephropathy. Mean follow-up was 3.2 years. The effect of losartan therapy on renal and cardiovascular outcomes was examined, and baseline predictors of risk were determined using a Cox proportional hazards model with prespecified baseline covariates.

RESULTS—Losartan reduced the risk of the primary composite end point composed of a doubling of serum creatinine, end-stage renal disease, or all-cause mortality in Asian patients by 35% (P = 0.02). No difference between losartan and placebo was observed for the cardiovascular composite outcomes. Losartan reduced the level of proteinuria by 47% (P < 0.001) and rate of decrease in renal function by 31% (0.0074). Discontinuations were lower in the losartan-treated patients. The strongest baseline predictors of risk of renal end points were proteinuria (hazard ratio 1.42, P < 0.0001) and low Hb (0.81, P < 0.0001).

CONCLUSIONS—In this subgroup analysis of the RENAAL study, losartan conferred significant renal benefits and was well tolerated in Asian patients with type 2 diabetes and clinical nephropathy. Baseline proteinuria and low Hb were strong predictors of risk of renal outcomes.
The Effect of Vitamin Therapy on the Progression of Coronary Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women
Authors: Levy Andrew P. , Friedenberg Paula , Lotan Rachel , Ouyang Pamela , Tripputi Mark , Higginson Lyall , Cobb Frederick R. , Tardif Jean-Claude , Bittner Vera , Howard Barbara V.
Published: March 2007

OBJECTIVE—Antioxidant trials have not demonstrated efficacy in slowing cardiovascular disease but could not rule out benefit for specific patient subgroups. Antioxidant therapy reduces LDL oxidizability in haptoglobin 1 allele homozygotes (Hp 1-1), but not in individuals with the haptoglobin 2 allele (Hp 2-1 or Hp 2-2). We therefore hypothesized that haptoglobin type would be predictive of the effect of vitamin therapy on coronary atherosclerosis as assessed by angiography.

RESEARCH DESIGN AND METHODS—We tested this hypothesis in the Women’s Angiographic Vitamin and Estrogen (WAVE) trial, a prospective angiographic study of vitamins C and E with or without hormone replacement therapy (HRT) in postmenopausal women. Haptoglobin type was determined in 299 women who underwent baseline and follow-up angiography. The annualized change in the minimum luminal diameter (MLD) was examined in analyses stratified by vitamin use, haptoglobin type, and diabetes status.

RESULTS—We found a significant benefit on the change in MLD with vitamin therapy as compared with placebo in Hp 1-1 subjects (0.079 ± 0.040 mm, P = 0.049). This benefit was more marked in diabetic subjects (0.149 ± 0.064 mm, P = 0.021). On the other hand, there was a trend toward a more rapid decrease in MLD with vitamin therapy in Hp 2-2 subjects, which was more marked in diabetic subjects (0.128 ± 0.057 mm, P = 0.027). HRT had no effect on these outcomes.

CONCLUSIONS—The relative benefit or harm of vitamin therapy on the progression of coronary artery stenoses in women in the WAVE study was dependent on haptoglobin type. This influence of haptoglobin type seemed to be stronger in women with diabetes.
Association of Triglyceride–to–HDL Cholesterol Ratio With Heart Rate Recovery
Authors: Shishehbor Mehdi H. , Hoogwerf Byron J. , Lauer Michael S.
Published: March 2007

OBJECTIVE—Insulin resistance is associated with autonomic dysfunction. An attenuated decrease in heart rate after exercise (or heart rate recovery [HRR]) predicts all-cause mortality and is believed to reflect decreased parasympathetic activity. Utilizing triglyceride/HDL cholesterol concentration as a marker of insulin resistance, we sought to assess the association between insulin resistance and HRR.

RESEARCH DESIGN AND METHODS—Our study population included 4,963 healthy adults who participated in the Lipid Research Clinics Prevalence Study and underwent exercise testing. HRR was considered abnormal if it did not drop ≥42 bpm 2 min after completion of exercise. Fasting blood specimens were drawn.

RESULTS—Individuals in the highest quartile of triglyceride/HDL cholesterol had a significantly higher prevalence of abnormal HRR (40 vs. 30%, multivariable-adjusted prevalence ratio 1.18, 95% CI 1.01–1.39; P = 0.04). As a continuous variable, an increase in 1 SD of triglyceride–to–HDL cholesterol ratio was associated with a greater likelihood of an abnormal HRR, even after adjusting for >20 covariates (adjusted OR 1.16, 95% CI 1.07–1.25; P < 0.001). During 12 years of follow-up, there were 284 deaths. In age- and sex-adjusted analysis, participants with an abnormal HRR and high triglyceride–to–HDL cholesterol ratio had significantly higher mortality than those with a normal HRR and high triglyceride–to–HDL cholesterol ratio (hazard ratio = 1.49, 95% CI 1.08–2.04; P = 0.015).

CONCLUSIONS—HRR is associated with triglyceride–to–HDL cholesterol ratio and identifies patients with insulin resistance who are at increased risk of death.
The Role of Limited Joint Mobility in Diabetic Patients With an At-Risk Foot
Authors: Zimny Stefan , Schatz Helmut , Pfohl Martin
Published: March 2007

OBJECTIVE—To assess the role of limited joint mobility (LJM) in causing abnormal high plantar pressures in the forefoot of diabetic patients with an at-risk foot.

RESEARCH DESIGN AND METHODS—A total of 70 type 1 or type 2 diabetic patients and 30 control subjects participated in this cross-sectional study. Thirty-five diabetic patients with an at-risk foot, defined as a foot with neuropathy but without ulceration or previous ulceration, and 35 diabetic control subjects without neuropathy were selected for the subgroups. Joint mobility was assessed in the foot at the ankle and metatarsophalangeal I (first MTP) joints. Using the FastScan plantar pressure analyzer, the pressure-time integrals (PTIs) as dynamic variables were measured in each foot. The clinical assessment included standard measures of peripheral neuropathy.

RESULTS—The mobility at the ankle and first MTP joint were significantly reduced in the foot-at-risk group compared with the diabetic control group and the control subjects (P < 0.0001). The PTIs were significantly higher in the foot-at-risk group compared with the two other groups (P < 0.0001). There was a strong inverse correlation between the mobility of the ankle or first MTP joint and the PTI of the diabetic patients (r = −0.67, P < 0.0001, and r = −0.71, P < 0.0001, respectively). The vibration perception threshold was positively correlated with the PTI of the diabetic patients (r = 0.44, P = 0.0001).

CONCLUSIONS—Diabetic patients with an at-risk foot have reduced joint mobility and elevated PTIs on the plantar forefoot, placing them at risk for subsequent ulceration. Therefore, LJM may be a possible factor in causing high plantar pressures and may contribute to foot ulceration in the susceptible neuropathic at-risk foot.
Gestational Diabetes
Authors: Moses Robert G. , Mackay Maria T.
Published: March 2007

OBJECTIVE—To assess the relationship between leg length and glucose tolerance in pregnancy.

RESEARCH DESIGN AND METHODS—The leg length and leg-to-height percentage were prospectively determined on 161 glucose-tolerant women during pregnancy and 61 women with gestational diabetes mellitus (GDM).

RESULTS—Women with GDM were a mean of 2.8 cm shorter than women who were glucose tolerant, due entirely to their leg lengths being a mean of 3.2 cm shorter. With respect to the 2-h result on the glucose tolerance test (GTT), there were negative correlations for height (r = −0.161, P = 0.017), leg length (r = −0.266, P < 0.0005), and the leg-to-height percentage (r = −0.294, P < 0.0005). The correlation between the leg-to-height percentage and the 2-h result on the GTT remained significant after adjustment for age (r = −0.252, P < 0.0005) and for age and BMI (r = −0.224, P = 0.001).

CONCLUSIONS—Women with GDM are shorter than glucose-tolerant women and have a lower leg-to-height percentage. Consideration of short stature as a risk factor for GDM is not valid without taking into account the leg-to-height percentage.
Global Prevalence of Diabetes
Authors: Wild Sarah , Roglic Gojka , Green Anders , Sicree Richard , King Hilary
Published: March 2007

OBJECTIVE—The goal of this study was to estimate the prevalence of diabetes and the number of people of all ages with diabetes for years 2000 and 2030.

RESEARCH DESIGN AND METHODS—Data on diabetes prevalence by age and sex from a limited number of countries were extrapolated to all 191 World Health Organization member states and applied to United Nations’ population estimates for 2000 and 2030. Urban and rural populations were considered separately for developing countries.

RESULTS—The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. The urban population in developing countries is projected to double between 2000 and 2030. The most important demographic change to diabetes prevalence across the world appears to be the increase in the proportion of people >65 years of age.

CONCLUSIONS—These findings indicate that the “diabetes epidemic” will continue even if levels of obesity remain constant. Given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.
Insulin Detemir Offers Improved Glycemic Control Compared With NPH Insulin in People With Type 1 Diabetes
Authors: Home Philip , Bartley Paul , Russell-Jones David , Hanaire-Broutin Hélène , Heeg Jan-Evert , Abrams Pascale , Landin-Olsson Mona , Hylleberg Birgitte , Lang Hanne , Draeger Eberhard ,   on behalf of the Study to Evaluate the Administration of Detemir Insulin Efficacy, Safety and Suitability (Steadiness) Study Group
Published: March 2007

OBJECTIVE—Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration.

RESEARCH DESIGN AND METHODS—People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDetmorn+bed) or at a 12-h interval (IDet12h). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart.

RESULTS—With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet12h vs. NPH, −1.5 mmol/l [95% CI −2.51 to −0.48], P = 0.004; IDetmorn+bed vs. NPH, −2.3 mmol/l (−3.32 to −1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDetmorn+bed group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference −0.18% [−0.34 to −0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet12h vs. NPH, −0.8 kg [−1.44 to −0.24], P = 0.006; IDetmorn+bed vs. NPH, −0.6 kg [−1.23 to −0.03], P = 0.040).

CONCLUSIONS—Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person’s needs.
Effect of Diabetes on Long-Term Mortality Following Contemporary Percutaneous Coronary Intervention
Authors: Wilson Sean R. , Vakili Babak A. , Sherman Warren , Sanborn Timothy A. , Brown David L.
Published: March 2007

OBJECTIVE—Diabetic patients are known to have reduced long-term survival following percutaneous transluminal coronary angioplasty compared with nondiabetic patients. However, it is unknown whether this survival disadvantage has persisted in the era of contemporary percutaneous coronary intervention (PCI) techniques, which include the widespread use of stents and the availability of platelet glycoprotein (GP) IIb/IIIa inhibitors.

RESEARCH DESIGN AND METHODS—Three hospitals in New York City contributed prospectively defined data on 4,284 patients undergoing PCI. The primary end point was all-cause mortality following hospital discharge for PCI.

RESULTS—Hypertension, renal insufficiency, and renal failure requiring dialysis were all more common in diabetic patients, whereas active smoking was less frequent. Congestive heart failure on admission was more common in diabetic than nondiabetic patients (7.7 vs. 4.0%, P < 0.001). Stents were placed in 78% of nondiabetic patients and 75% of diabetic patients (P = 0.045). Platelet GP IIb/IIIa antagonists were administered to 23% of nondiabetic and 24% of diabetic patients (P = NS). At a mean follow-up of 3 years, mortality was 8% among nondiabetic patients and 13% for diabetic patients (P < 0.001). After adjustment for differences in baseline characteristics between nondiabetic and diabetic patients, diabetes remained a significant independent hazard for late mortality (hazard ratio 1.462, 95% CI 1.169–1.828; P = 0.001).

CONCLUSIONS—Following contemporary PCI, diabetic patients continue to have worse survival than nondiabetic patients.
Connective Tissue Growth Factor Is Increased in Plasma of Type 1 Diabetic Patients With Nephropathy
Authors: Roestenberg Peggy , van Nieuwenhoven Frans A. , Wieten Lotte , Boer Peter , Diekman Theo , Tiller Anna M. , Wiersinga Wilmar M. , Oliver Noelynn , Usinger William , Weitz Stephen , Schlingemann Reinier O. , Goldschmeding Roel
Published: March 2007

OBJECTIVE—Connective tissue growth factor (CTGF) is strongly upregulated in fibrotic disorders and has been hypothesized to play a role in the development and progression of diabetes complications. The aim of the present study was to investigate the possible association of plasma CTGF levels in type 1 diabetic patients with markers relevant to development of diabetes complications.

RESEARCH DESIGN AND METHODS—Plasma CTGF levels (full-length and NH2-terminal fragments) were determined in 62 well-characterized patients with type 1 diabetes and in 21 healthy control subjects. Correlations of these plasma CTGF levels with markers of glycemic control, platelet activation, endothelial activation, nephropathy, and retinopathy were investigated.

RESULTS—Elevated plasma NH2-terminal fragment of CTGF (CTGF-N) levels were detected in a subpopulation of type 1 diabetic patients and were associated with diabetic nephropathy. Stepwise regression analysis revealed contribution of albuminuria, creatinine clearance, and duration of diabetes as predictors of plasma CTGF-N level. Elevation of plasma CTGF-N levels in patients with retinopathy was probably due to renal comorbidity.

CONCLUSIONS—Plasma CTGF-N levels are elevated in type 1 diabetic patients with nephropathy and appear to be correlated with proteinuria and creatinine clearance. Further studies will be needed to determine the relevance of plasma CTGF as a clinical marker and/or pathogenic factor in diabetic nephropathy.
Can We Apply the National Cholesterol Education Program Adult Treatment Panel Definition of the Metabolic Syndrome to Asians?
Authors: Tan Chee-Eng , Ma Stefan , Wai Daniel , Chew Suok-Kai , Tai E.-Shyong
Published: March 2007

OBJECTIVE—Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population.

RESEARCH DESIGN AND METHODS—We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese, Malay, and Asian-Indian ethnicity aged 18–69 years. Receiver operating characteristic analysis suggested that waist circumference >80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with and without the modified waist circumference criteria.

RESULTS—In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18–30 years to 31.0% in those aged 60–69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P < 0.001) and Asian Indians (prevalence 28.8% in Asian-Indians, 24.2% in Malays, and 14.8% in Chinese; P < 0.001).

CONCLUSIONS— NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely to exist between populations across Asia.
Does the Association of Habitual Physical Activity With the Metabolic Syndrome Differ by Level of Cardiorespiratory Fitness?
Authors: Franks Paul W. , Ekelund Ulf , Brage Søren , Wong Man-Yu , Wareham Nicholas J.
Published: March 2007

OBJECTIVE—Cardiovascular fitness (Vo2max) and physical activity are both related to risk of metabolic disease. It is unclear, however, whether the metabolic effects of sedentary living are the same in fit and unfit individuals. The purpose of this study was, therefore, to describe the association between physical activity and the metabolic syndrome and to test whether fitness level modifies this relationship.

RESEARCH DESIGN AND METHODS—Physical activity was measured objectively using individually calibrated heart rate against energy expenditure. Vo2max was predicted from a submaximal exercise stress test. Fat mass and fat-free mass (FFM) were calculated using impedance biometry. A metabolic syndrome score was computed by summing the standardized values for obesity, hypertension, hyperglycemia, insulin resistance, hypertriglyceridemia, and the inverse level of HDL cholesterol and was expressed as a continuously distributed outcome. To correct for exposure measurement error, a random subsample (22% of cohort) re-attended for three repeat measurements in the year following the first assessment.

RESULTS—The relationship of Vo2max (ml O2 · kgFFM−1 · min−1) and the metabolic syndrome score was of borderline significance after adjusting for age, sex, physical activity, and measurement error (β = −0.58, P = 0.06). The magnitude of the association between physical activity (kJ · d–1 · kgFFM−1) and the metabolic syndrome was more than three times greater than for Vo2max (standardized β = −1.83, P = 0.0042). Vo2max, however, modified the relationship between physical activity energy expenditure and metabolic syndrome (P = 0.036).

CONCLUSIONS—This study demonstrates a strong inverse association between physical activity and metabolic syndrome, an association that is much steeper in unfit individuals. Thus, prevention of metabolic disease may be most effective in the subset of unfit inactive people.
Effect of Apolipoprotein E4 Allele on Plasma LDL Cholesterol Response to Diet Therapy in Type 2 Diabetic Patients
Authors: Saito Mieko , Eto Masaaki , Nitta Hayami , Kanda Yukiko , Shigeto Makoto , Nakayama Katsura , Tawaramoto Kazuhito , Kawasaki Fumiko , Kamei Shinji , Kohara Kenji , Matsuda Masafumi , Matsuki Michihiro , Kaku Kohei
Published: March 2007

OBJECTIVE—The aim of this study was to investigate the effect of apolipoprotein (apo)E4 allele on plasma LDL cholesterol response to calorie-restricted diet therapy in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Twenty-four diabetic patients with the apoE3/3 genotype and 11 diabetic patients with the apoE4/3 genotype were recruited. Participants were hospitalized for calorie-restricted diet therapy (25.0 kcal · kg body wt−1 · day−1) for 14 days. Body weight, fasting plasma glucose (FPG) levels, and plasma lipid levels on hospital days 1 and 14 were compared between the two apoE genotype groups.

RESULTS—There were no significant differences in baseline FPG levels, HbA1c levels, BMI, and plasma levels of total cholesterol, triglyceride, and HDL cholesterol between the two apoE genotype groups, but baseline plasma levels of LDL cholesterol were significantly higher in the apoE4/3 group than in the apoE3/3 group. Body weight decreased slightly and FPG levels decreased significantly after diet therapy in both apoE genotype groups. In the apoE3/3 group, only plasma levels of triglyceride decreased significantly after diet therapy, whereas in the apoE4/3 group, plasma levels of triglyceride, total cholesterol, and LDL cholesterol decreased significantly after diet therapy. The decrease (percentage of change) in total cholesterol (−16.3 vs. −6.6%) and LDL cholesterol (−15.6 vs. −0.7%) after diet therapy was significantly greater in the apoE4/3 group than in the apoE3/3 group.

CONCLUSIONS—Calorie-restricted diet therapy is more effective in reducing plasma LDL cholesterol in type 2 diabetic patients with the apoE4 allele.
Mortality and Predictors of Mortality in a Cohort of Brazilian Type 2 Diabetic Patients
Authors: Salles Gil F. , Bloch Katia V. , Cardoso Claudia R.L.
Published: March 2007

OBJECTIVE—To investigate mortality rates and predictors of mortality in Brazilian type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A prospective follow-up study was carried out with 471 type 2 diabetic outpatients. Primary end points were all-cause, diabetes-related, and cardiovascular deaths. Excess mortality in this cohort was evaluated by calculating standardized mortality ratios (SMRs) in relation to those of the Rio de Janeiro population. Predictors of mortality were assessed by Kaplan-Meier survival curves and by uni- and multivariate Cox survival analyses.

RESULTS—During a median follow-up of 57 months (range 2–84 months), 121 (25.7%) patients died, 91 (75.2%) from diabetes-related causes and 44 (36.4%) from cardiovascular diseases. After adjusting for age and sex, the all-cause SMR was 3.36 (95% confidence interval [CI] 2.81–4.02) and the cardiovascular SMR was 3.28 (CI 2.44–4.41). In the Cox multivariate analysis, the predictors of mortality were older age, increased 24-h proteinuria, preexisting vascular disease, presence of frequent ventricular premature contractions and prolonged maximum heart rate−corrected QT interval on baseline electrocardiogram, and decreased serum HDL cholesterol. The use of β-blockers was a protective factor. In Kaplan-Meier curves, these variables were capable of distinguishing subgroups of patients with significantly different prognoses.

CONCLUSIONS—Brazilian type 2 diabetic patients had a more than threefold excess mortality than the general population, largely because of increased cardiovascular mortality risk. Several clinical, laboratory, and electrocardiographic predictors of mortality were identified that could possibly be modified to decrease the mortality burden of type 2 diabetes in Brazil.
Results of Blood Inflammatory Markers Are Associated More Strongly With Toe-Brachial Index Than With Ankle-Brachial Index in Patients With Type 2 Diabetes
Authors: Aso Yoshimasa , Okumura Ki-ichi , Inoue Teruo , Matsutomo Rika , Yoshida Noboru , Wakabayashi Sadao , Takebayashi Kohzo , Inukai Toshihiko
Published: March 2007

OBJECTIVE—Three blood markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and fibrinogen) were compared with markers of atherosclerotic cardiovascular disease (CVD) (history of stroke or cardiac ischemia and measured toe-brachial index [TBI]) to determine whether inflammatory markers are associated with atherosclerosis in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Of 103 patients with type 2 diabetes, 26 had CVD. TBI was plethysmographically determined in both great toes. Serum hsCRP was immunonephelometrically determined. Plasma IL-6 was measured by an enzyme immunoassay.

RESULTS—Both ABI and TBI were lower in diabetic patients with CVD than in those without CVD (1.05 ± 0.19 vs. 1.14 ± 0.09, P < 0.05, and 0.75 ± 0.20 vs. 0.95 ± 0.21, P < 0.001, respectively). By linear regression, right TBI but not right ABI showed a significant negative correlation with serum hsCRP (r = −0.372, P < 0.01) and plasma fibrinogen (r = −0.224, P < 0.05). Serum hsCRP was also negatively correlated with lower TBI, but not lower ABI. We found no significant correlation between plasma IL-6 and ABI or TBI.

CONCLUSIONS—TBI was strongly associated with CVD, serum hsCRP, and plasma fibrinogen. Of these inflammatory markers, serum hsCRP may be the most promising marker for vascular inflammation.
Relation Between Acanthosis Nigricans and Insulin Sensitivity in Overweight Hispanic Children at Risk for Type 2 Diabetes
Authors: Kobaissi Hassan A. , Weigensberg Marc J. , Ball Geoff D.C. , Cruz Martha L. , Shaibi Gabriel Q. , Goran Michael I.
Published: March 2007

OBJECTIVE—To investigate in a population of Hispanic children if 1) the presence of acanthosis nigricans (AN) is related to insulin sensitivity (Si) independent of adiposity and 2) scale scoring AN severity adds to the clinical estimation of insulin sensitivity, above and beyond the presence or absence AN alone.

RESEARCH DESIGN AND METHODS—The study population, 131 Hispanic overweight children (mean BMI percentile 97.0 ± 3.1, 72 boys, 59 girls, ages 8–13 years, mean Tanner stage 2.4 ± 1.5) with a family history of type 2 diabetes, underwent a physical examination of the neck to determine AN absence or presence (0–1), AN extent score (0–4 scale), AN texture score (0–3 scale), and an AN combined score (extent + texture; 0–7 scale). Si was measured by the frequently sampled intravenous glucose tolerance test and minimal modeling. Multivariate linear regression analysis was used to determine the role of BMI and AN in predicting Si.

RESULTS—BMI was the main predictor of Si, explaining ∼41% of the variance. The presence of AN explained an additional 4% of the variability in Si; scale scoring of AN extent or texture did not significantly improve the prediction.

CONCLUSIONS—Although AN is an independent risk factor for insulin resistance in overweight Hispanic children at risk for type 2 diabetes, body adiposity is the primary determinant of insulin sensitivity. In addition, scale scoring AN seems of minimal usefulness in clinically estimating the severity of insulin resistance over and above assessing the presence or absence of AN and calculating BMI.
Mortality in Diabetic and Nondiabetic Patients After Amputations Performed From 1990 to 1995
Authors: Tentolouris Nicholas , Al-Sabbagh Sameer , Walker Michael G. , Boulton Andrew J.M. , Jude Edward B.
Published: March 2007

OBJECTIVE—To compare survival rates after first amputation between patients with and without diabetes.

RESEARCH DESIGN AAND METHODS—We performed a retrospective study of all nontraumatic amputations performed at our center in the years 1990–1995 in patients with (n = 100) and without (n = 151) diabetes. Survival status was assessed from the first amputation until 31 December 2001.

RESULTS—Altogether, 61% of the patients with and 54.3% of those without diabetes died 5.2 (4.5–5.8) and 5.3 (4.7–5.9) [mean (95% CI)] years after the first amputation, respectively (P = 0.80). Survival was not different between patients with and without diabetes after controlling for the level (major versus minor) (P = 0.67) or the cause (ischemia versus infection) of amputation (P = 0.72). No sex differences were found for survival in either study group. Independent predictors of mortality in the diabetic group were duration of diabetes (P = 0.05), history of stroke (P = 0.02), and serum creatinine level (P < 0.0001), while in the nondiabetic group independent predictors were history of stroke (P = 0.04), serum creatinine level (P = 0.005), and higher white blood cell count (P = 0.02). The peak incidence of amputations was observed in the decade of 67–76 years of age in both groups. Major amputations were more common among nondiabetic patients in all age-groups. Median hospital stay and postoperative complications were comparable between the two groups.

CONCLUSIONS—All-cause mortality is high after an amputation in both diabetic and nondiabetic patients. Mortality rates, hospital stay, and postoperative complications are not different between diabetic and nondiabetic amputees. No modifiable factors, with the exception of nephropathy, were found to improve survival in amputees. Peripheral vascular disease and neuropathy are the main cause of amputations; prevention, therefore, of these complications is warranted to prevent amputations and the subsequent high mortality.
Type 1 Diabetes Among Sardinian Children Is Increasing
Authors: Casu Anna , Pascutto Cristiana , Bernardinelli Luisa ,   the Sardinian IDDM Epidemiology Study Group, Songini Marco
Published: March 2007

OBJECTIVE—The Sardinian type 1 diabetes register represented the basis to determine the most recent trends and the age distribution of type 1 diabetes incidence among Sardinians <15 years of age during 1989–1999. Part of the data (1989–1998) has been already published by the EURODIAB Group with a lower completeness of ascertainment (87%). The geographical distribution of type 1 diabetes risk was also investigated.

RESEARCH DESIGN AND METHODS—The new cases of type 1 diabetes in children aged 0–14 years in Sardinia were prospectively registered from 1989 to 1999 according to the EURODIAB ACE criteria. The completeness of ascertainment calculated applying the capture-recapture method was 91%. Standardized incidence rates and 95% CI were calculated assuming the Poisson distribution. Trend of type 1 diabetes incidence was analyzed using the Poisson regression model. Maps of the geographical distribution of type 1 diabetes risk for the whole time period and separately for 1989–1994 and 1995–1999 were produced applying a Bayesian method.

RESULTS—A total of 1,214 type 1 diabetic patients were registered yielding to an overall age- and sex-standardized incidence rate of 38.8/100,000 (95% CI 36.7–41.1). There was a male excess with an overall male-to-female ratio of 1.4 (1.3–1.8). The increase of incidence during the 11 years analyzed was statistically significant (P = 0.002) with a yearly increasing rate of 2.8% (1.0–4.7). No evidence of an effect of age and sex on this trend has been found. The geographical distribution of type 1 diabetes relative risk (RR) showed that the highest risk areas are located in the southern and central-eastern part of the island and the lowest risk in the northeastern part, even if most of these differences were not statistically significant. This geographical distribution seemed to remain mainly the same between 1989–1994 and 1995–1999.

CONCLUSIONS—The homogeneity of diabetes risk and the increase of incidence over the age-groups in the Sardinian population stress the role of an environmental factor uniformly distributed among the genetically high-risk Sardinians.
Muscle Weakness and Foot Deformities in Diabetes
Authors: van Schie Carine H.M. , Vermigli Cristiana , Carrington Anne L. , Boulton Andrew
Published: March 2007

OBJECTIVE—To examine the relationships among muscle weakness, foot deformities, and peroneal and tibial nerve conduction velocity in diabetic and nondiabetic men.

RESEARCH DESIGN AND METHODS—A neuropathic and foot evaluation was undertaken in 10 nondiabetic control subjects (group C) and in 36 consecutive diabetic patients attending Diabetes Centre clinics, including 10 diabetic control subjects (group D), 15 diabetic neuropathic patients (group DN), and 11 diabetic patients with a history of ulceration (group DU). Neuropathy was defined as a peroneal motor nerve conduction <40 m/s. Muscle weakness was assessed in seven intrinsic and seven extrinsic muscles of the foot using a semiquantitative score (max score per muscle = 3). Foot deformities were assessed using a foot deformity score (max score = 3). A higher score indicated increased muscle weakness or more severe foot deformities. Muscle weakness and foot deformities were assessed without prior knowledge of patient and neuropathy status.

RESULTS—Peroneal and tibial nerve conduction velocity were associated with weakness in muscles innervated by, respectively, the peroneal and tibial nerve (r = −0.70 and r = −0.51, P < 0.01) and foot deformities (r = −0.60 and r = −0.59, P < 0.001). The DN and DU groups had more weakness in intrinsic and extrinsic muscles compared with the C and D groups. Muscles innervated by the tibial nerve had a greater proportional muscle weakness than those innervated by the peroneal nerve in the DN and DU groups. The DN and DU patients had more foot deformities (median food deformity score [interquartile range]) (3 [2–3] and 2 [2–3]) compared with D and C patients (0 [0–0.75] and 0 [0–0]).

CONCLUSIONS—Important relationships have been shown between motor nerve conduction deficit and muscle weakness; however, it is still not clear whether abnormal nerve function, leading to a decrease in muscle strength, could be responsible for the development of foot deformities.
Relationship Between Adiponectin and Glycemic Control, Blood Lipids, and Inflammatory Markers in Men With Type 2 Diabetes
Authors: Schulze Matthias B. , Rimm Eric B. , Shai Iris , Rifai Nader , Hu Frank B.
Published: March 2007

OBJECTIVE—Adiponectin, synthesized in the adipose tissue, appears to play an important role in hyperglycemia and dyslipidemia, as well as in inflammatory mechanisms, which lead to a markedly increased atherosclerotic risk in diabetic subjects. However, previous studies did not evaluate the complex relationships between adiponectin and the array of metabolic abnormalities commonly observed in diabetes.

RESEARCH DESIGN AND METHODS—To examine the associations between plasma levels of adiponectin and HbA1c, blood lipids, and inflammatory markers, we obtained blood samples from 741 participants in the Health Professionals Follow-up Study with a diagnosis of type 2 diabetes.

RESULTS—Plasma adiponectin levels were positively correlated with HDL cholesterol and negatively correlated with triglycerides, apolipoprotein B-100 (apoB100), C-reactive protein (CRP), and fibrinogen. These associations were not appreciably altered after controlling for lifestyle exposures, medical conditions, and obesity-associated variables. A 10-μg/ml higher level of plasma adiponectin was associated with lower HbA1c (−0.21% points, P = 0.001), triglycerides (−0.39 mmol/l, P < 0.001), apoB100 (−0.04 g/l, P < 0.001), CRP (−0.51 mg/l, P = 0.003), and fibrinogen (−0.53 μmol/l, P < 0.001) and higher HDL cholesterol (0.13 mmol/l, P < 0.001). Associations between adiponectin and inflammatory markers were furthermore independent of HbA1c and HDL cholesterol, suggesting that the anti-inflammatory properties of adiponectin are not mediated by potential effects on glycemic control and blood lipids. Our results were consistent among obese and nonobese men.

CONCLUSIONS—Our study supports the hypothesis that increased adiponectin levels might be associated with better glycemic control, better lipid profile, and reduced inflammation in diabetic subjects. Measures that increase adiponectin levels might be valuable targets for decreasing the atherosclerotic risk present in diabetes.
Quinapril, an ACE Inhibitor, Reduces Markers of Oxidative Stress in the Metabolic Syndrome
Authors: Khan Bobby V. , Sola Srikanth , Lauten Wright B. , Natarajan Rama , Hooper W. Craig , Menon Rekha G. , Lerakis Stamatios , Helmy Tarek
Published: March 2007

OBJECTIVE—Patients with the metabolic syndrome often have abnormal levels of proinflammatory and pro-oxidative mechanisms within their vasculature. We sought to determine whether the ACE inhibitor quinapril regulates markers of oxidative stress in the metabolic syndrome.

RESEARCH DESIGN AND METHODS—Forty patients with the metabolic syndrome were randomized in a double-blind manner to either the ACE inhibitor quinapril (20 mg/day) or matching placebo for 4 weeks. Serum markers of vascular oxidative stress were measured.

RESULTS—After 4 weeks of therapy, serum 8-isoprostane was reduced by 12% in the quinapril group when compared with placebo (quinapril, 46.7 ± 1.0; placebo, 52.7 ± 0.9 pg/ml; P = 0.001). Erythrocyte superoxide dismutase activity increased 35% in the quinapril group when compared with placebo (quinapril, 826.3 ± 17.1; placebo, 612.3 ± 6.9 units/g Hb; P < 0.001). In addition, lag time to oxidation of LDL, a marker of oxidative stress, was increased by 48% in the quinapril group when compared with placebo (quinapril 89.2 ± 9.2 vs. placebo 60.1 ± 12.3 min; P < 0.001). Therapy with quinapril was well tolerated.

CONCLUSIONS—The addition of the ACE inhibitor quinapril reduces markers of vascular oxidative stress and may attenuate the progression of the pathophysiology seen in the metabolic syndrome.
Plasma Adiponectin, Insulin Sensitivity, and Subclinical Inflammation in Women With Prior Gestational Diabetes Mellitus
Authors: Winzer Christine , Wagner Oswald , Festa Andreas , Schneider Barbara , Roden Michael , Bancher-Todesca Dagmar , Pacini Giovanni , Funahashi Tohru , Kautzky-Willer Alexandra
Published: March 2007

OBJECTIVE—Women with prior gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes and associated vasculopathy. Because increased fat mass and inflammatory processes are angiopathic risk factors, the relationship between insulin sensitivity, parameters of subclinical inflammation, and plasma concentrations of adipocytokines was investigated in pGDM both at 3 months and 12 months after delivery.

RESEARCH DESIGN AND METHODS—Insulin sensitivity (through a frequently sampled intravenous glucose tolerance test) and plasma concentrations of ultrasensitive C-reactive protein (CRP), adiponectin, plasminogen activator inhibitor (PAI)-1, tumor necrosis factor-α, leptin, and interleukin-6 were measured in 89 pGDM (BMI 26.9 ± 0.5 kg/m2, age 32 ± 0.5 years) and in 19 women with normal glucose tolerance during pregnancy (NGT) (23.7 ± 0.9 kg/m2, 31 ± 1.3 years).

RESULTS—pGDM showed lower (P < 0.0001) plasma adiponectin (6.7 ± 0.2 μg/ml) than NGT (9.8 ± 0.6 μg/ml) and a decreased (P < 0.003) insulin sensitivity index (Si) and disposition index (P < 0.03), but increased plasma leptin (P < 0.003), PAI-1 (P < 0.002), and CRP (P < 0.03). After adjustment for body fat mass, plasma adiponectin remained lower in pGDM (P < 0.004) and correlated positively with Si (P < 0.003) and HDL cholesterol (P < 0.0001) but negatively with plasma glucose (2-h oral glucose tolerance test [OGTT]) (P < 0.0001), leptin (P < 0.01), CRP (P < 0.007), and PAI-1 (P < 0.0001). On regression analysis, only HDL cholesterol, postload (2-h OGTT) plasma glucose, and Si remained significant predictors of plasma adiponectin, explaining 42% of its variability. Of note, adiponectin further decreased (P < 0.05) only in insulin-resistant pGDM despite unchanged body fat content and distribution after a 1-year follow-up.

CONCLUSIONS—Lower plasma adiponectin concentrations characterize women with previous GDM independently of the prevailing insulin sensitivity or the degree of obesity and are associated with subclinical inflammation and atherogenic parameters.
The Effect of Liraglutide, a Long-Acting Glucagon-Like Peptide 1 Derivative, on Glycemic Control, Body Composition, and 24-h Energy Expenditure in Patients With Type 2 Diabetes
Authors: Harder Helle , Nielsen Lene , Thi Tu D.T. , Astrup Arne
Published: March 2007

OBJECTIVE—Glucagon-like peptide (GLP)-1 is a gut hormone that exerts incretin effects and suppresses food intake in humans, but its therapeutic use is limited due to its short half-life. This was a randomized, double-blind, parallel-group, placebo-controlled trial investigating the effect of the long-acting GLP-1 derivative liraglutide (NN2211) on glycemic control, body weight, body composition, and 24-h energy expenditure in obese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Thirty-three patients (mean ± SD) aged 60.0 ± 9.5 years, with HbA1c 7.5 ± 1.2% and BMI 36.6 ± 4.1 kg/m2, were randomized to treatment with a single daily subcutaneous dose of 0.6 mg liraglutide (n = 21) or placebo (n = 12) for 8 weeks. In addition to weight and glycemic parameters, body composition was assessed by dual-energy X-ray absorptiometry (DEXA) scanning and 24-h energy expenditure in a respiratory chamber.

RESULTS—After 8 weeks, liraglutide reduced fasting serum glucose (liraglutide, −1.90 mmol/l, and placebo, 0.27 mmol/l; P = 0.002) and HbA1c (liraglutide, −0.33%, and placebo, 0.47%; P = 0.028) compared with placebo. No change in body weight was detected (liraglutide, −0.7 kg, and placebo, −0.9 kg; P = 0.756). There was a nonsignificant trend toward a decrease in total fat mass (liraglutide, −0.98%, and placebo, −0.12%; P = 0.088) and toward an increase in lean body mass (liraglutide, 1.02%, and placebo, 0.23%; P = 0.118) in the liraglutide group compared with the placebo group. Twenty-four-hour energy expenditure was unaffected by the treatment (liraglutide, −12.6 kJ/h, and placebo, −13.7 kJ/h; P = 0.799).

CONCLUSIONS—Eight weeks of 0.6-mg liraglutide treatment significantly improved glycemic control without increasing weight in subjects with type 2 diabetes compared with those on placebo. No influence on 24-h energy expenditure was detected.
Elevated Plasma Levels of Nt-proBNP in Patients With Type 2 Diabetes Without Overt Cardiovascular Disease
Authors: Magnusson Martin , Melander Olle , Israelsson Bo , Grubb Anders , Groop Leif , Jovinge Stefan
Published: March 2007

OBJECTIVE—The NH2-terminal portion of the precursor of brain natriuretic peptide (Nt-proBNP) has been reported to be elevated in left ventricular dysfunction. This peptide is a split product from the proBNP molecule, and its level in the circulation is not, as the mature BNP peptide, dependent on the peripheral number of BNP receptors. We aimed to test the hypothesis that asymptomatic left ventricular dysfunction (ALVD), as estimated by Nt-proBNP, would be more prevalent in patients with type 2 diabetes without overt cardiovascular disease in comparison with matched control subjects.

RESEARCH DESIGN AND METHODS—The study population consisted of 253 patients with type 2 diabetes and 230 matched control subjects aged 40–70 years without any overt heart disease from primary care centers in Western Finland and Southern Sweden. Nt-proBNP was measured in plasma by competitive enzyme immunosorbent assay.

RESULTS—Patients with type 2 diabetes were shown to have higher Nt-proBNP values (360.9 pmol/l [262.6–467.9]) than control subjects (302.7 pmol/l [215.4–419.2]) (P < 0.001). Nt-proBNP levels were independently related to diabetes after adjustment for age, sex, systolic and diastolic blood pressure, BMI, heart rate, drug treatment, serum creatinine, and cystatin C.

CONCLUSIONS—Our data suggest that the secretion of Nt-proBNP is increased in type 2 diabetic patients with no overt heart disease, suggesting that type 2 diabetes is associated with a higher prevalence of ALVD than hitherto thought. Nt-proBNP may thus serve as a screening instrument to select patients with type 2 diabetes who could benefit from an echocardiographical examination.