bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Pioglitazone on Endothelial Function, Insulin Sensitivity, and Glucose Control in Subjects With Coronary Artery Disease and New-Onset Type 2 Diabetes
Authors: Sourij Harald , Zweiker Robert , Wascher Thomas C.
Published: May 2006

OBJECTIVE—About one of five patients with coronary artery disease (CAD) suffers from previously unknown, predominantly postprandial type 2 diabetes. In the process of atherogenesis and the subsequent increased cardiovascular mortality of diabetic patients, endothelial dysfunction is suspected to play an important role, and it is observed in diabetic as well as insulin-resistant states. Thus, the aim of our study was to investigate the effect of pioglitazone on endothelial dysfunction, insulin sensitivity, and glucose control in newly detected type 2 diabetic patients with CAD.

RESEARCH DESIGN AND METHODS—We investigated 42 patients (39 men and 3 women, age 60.25 ± 7.5 years, HbA1c 6.1 ± 0.5%) with manifest CAD and newly detected type 2 diabetes. A randomized, double-blind, placebo-controlled, parallel study with pioglitazone (30 mg/day for 12 weeks) was performed. At study entry and end, we performed an oral glucose tolerance test and measurements of endothelial dysfunction by photoplethysmographic pulse wave analysis.

RESULTS—Endothelial dysfunction was severely impaired at baseline in both groups. After 12 weeks, endothelial dysfunction was significantly better in the pioglitazone group (change of reflection index 6.5 ± 5.1 vs. 1.6 ± 2.9%, P = 0.002) compared with placebo. Insulin sensitivity, as assessed by homeostasis model assessment (2.20 ± 1.62 vs. 3.61 ± 1.87, P = 0.01), or the change of insulin sensitivity index from baseline to study end (0.021 ± 0.023 vs. −0.003 ± 0.012 μmol · kg−1 · min−1 per pmol/l, P = 0.0001) and β-cell function (57.42 ± 49.86 vs. 21.78 ± 18.54 mU/l per mmol/l, P = 0.0014) significantly improved in the pioglitazone group, with no change observed after placebo.

CONCLUSIONS—Pioglitazone improves endothelial dysfunction independently from the observed benefits on insulin sensitivity and β-cell function in patients with newly diagnosed type 2 diabetes and CAD.
Risk Scores for Type 2 Diabetes Can Be Applied in Some Populations but Not All
Authors: Glümer Charlotte , Vistisen Dorte , Borch-Johnsen Knut , Colagiuri Stephen ,   on behalf of the DETECT-2 Collaboration
Published: May 2006

OBJECTIVE—Risk scores based on phenotypic characteristics to identify individuals at high risk of having undiagnosed diabetes have been developed in Caucasian populations. The impact of known risk factors on having undiagnosed type 2 diabetes differs between populations from different ethnic origin, and risk scores developed in Caucasians may not be applicable to other ethnic groups. This study evaluated the performance of one risk score in nine populations of diverse ethnic origin.

RESEARCH DESIGN AND METHODS—Data provided by centers from around the world to the DETECT-2 project were used. The database includes population-based surveys with information on at least 500 people without known diabetes having a 75-g oral glucose tolerance test. To date, 52 centers have contributed data on 190,000 individuals from 34 countries. In this analysis, nine cross-sectional studies were selected representing diverse ethnic and regional backgrounds. The risk score assessed uses information on age, sex, blood pressure treatment, and BMI.

RESULTS—This analysis included 29,758 individuals; 1,805 individuals had undiagnosed diabetes. The performance of the risk score varied widely, with sensitivity, specificity, and percentage needing further testing ranging between 12 and 57%, 72 and 93%, and 2 and 25%, respectively, with the worse performance in non-Caucasian populations. This variation in performance was related to differences in the association between prevalence of undiagnosed diabetes and components of the risk score.

CONCLUSIONS—A typical risk score developed in Caucasian populations cannot be applied to other populations of diverse ethnic origins.
Altered D-Chiro-Inositol Urinary Clearance in Women With Polycystic Ovary Syndrome
Authors: Baillargeon Jean-Patrice , Diamanti-Kandarakis Evanthia , Ostlund Richard E. , Apridonidze Teimuraz , Iuorno Maria J. , Nestler John E.
Published: May 2006

OBJECTIVE—Evidence suggests that some actions of insulin are effected by inositolphosphoglycan (IPG) mediators. We hypothesize that a deficiency in D-chiro-inositol (DCI) and/or a DCI-containing IPG (DCI-IPG) may contribute to insulin resistance in humans.

RESEARCH DESIGN AND METHODS—To assess this possibility in polycystic ovary syndrome (PCOS), we determined insulin sensitivity (Si by frequently sampled intravenous glucose tolerance test), plasma and urinary DCI and myo-inositol (MYO) levels (by gas chromatography/mass spectrometry), and the release of insulin and DCI-IPG during the oral glucose tolerance test (area under the curve [AUC]) in 23 women with PCOS and 26 normal women.

RESULTS—Women with PCOS were heavier than control subjects (P = 0.002 for BMI), but also had decreased Si (P < 0.001) and increased AUCinsulin (P < 0.001) compared with normal women, even when corrected for BMI. The urinary clearance of DCI (uClDCI) was increased almost sixfold in PCOS compared with normal women (P = 0.001), but not MYO clearance (P = 0.10). uClDCI correlated inversely with Si when all women were analyzed together (n = 49, r = −0.50, P < 0.001) and was one of the three best independent parameters predicting Si. Finally, the ratio of AUCDCI-IPG to AUCinsulin was decreased threefold in women with PCOS (P < 0.001).

CONCLUSIONS—uClDCI is inversely correlated with insulin sensitivity in women and is a strong independent predictor of insulin resistance in multivariate models. PCOS, which is characterized by insulin resistance, is associated with a selective increase in uClDCI and impaired DCI-IPG release in response to insulin. These findings are consistent with a defect in tissue availability or utilization of DCI in PCOS that may contribute to the insulin resistance of the syndrome.
Prevalence of Diabetes and Impaired Glucose Tolerance in 64-Year-Old Swedish Women
Authors: Brohall Gerhard , Behre Carl-Johan , Hulthe Johannes , Wikstrand John , Fagerberg Björn
Published: May 2006

OBJECTIVE—The purpose of this study was to describe the prevalence of diabetes and impaired glucose tolerance (IGT) in middle-aged women and to examine the variability and practical use of the oral glucose tolerance test (OGTT) in the screening for IGT and diabetes.

RESEARCH DESIGN AND METHODS—All 64-year-old women living in Göteborg, Sweden, were invited to take part in a screening examination (n = 4,856). Of these, 82% (n = 3,998) responded and 53% (n = 2,595) participated and underwent anthropometric measurements and a 75-g standardized OGTT that was repeated within 2 weeks in those not showing normal glucose tolerance (NGT).

RESULTS—The prevalences of known and new diabetes, IGT at both OGTTs, and impaired fasting glucose were 4.7, 4.8, 14.4, and 6.4%, respectively. Half of the women with diabetes were previously undiagnosed, and 37% of the diagnoses were based on OGTT and diabetes 2-h values at both or one of the two examinations. Women with IGT at both OGTTs, in comparison with those with one impaired and one normal OGTT, had higher BMI, waist girth, and blood pressure. More than 40% of the women showed impaired glucose metabolism.

CONCLUSIONS—Among these women, the prevalence of undetected diabetes was high and repeated OGTTs were needed to identify and not misclassify a considerable proportion of patients. The degree of glucose tolerance impairment and the number of abnormal OGTTs were directly associated with occurrence of components of the metabolic syndrome.
Cardiac Autonomic Neuropathy Predicts Cardiovascular Morbidity and Mortality in Type 1 Diabetic Patients With Diabetic Nephropathy
Authors: Astrup Anne Sofie , Tarnow Lise , Rossing Peter , Hansen Birgitte V. , Hilsted Jannik , Parving Hans-Henrik
Published: May 2006

OBJECTIVE—Cardiac autonomic neuropathy (CAN) has been associated with a poor prognosis in patients with diabetes. Because CAN is common in patients with diabetic nephropathy, we evaluated the predictive value of CAN in type 1 diabetic patients with and without diabetic nephropathy.

RESEARCH DESIGN AND METHODS—In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy and a matched group of 191 patients with long-standing type 1 diabetes and normoalbuminuria were followed for 10.1 years (range 0.0–10.3 years). At baseline, CAN was assessed by heart rate variation (HRV) during deep breathing. HRV was evaluated as a predictor of the primary end point: cardiovascular morbidity and mortality. As secondary end points, all-cause mortality and the influence of HRV on progression of diabetic nephropathy (decline in glomerular filtration rate [GFR]) was evaluated.

RESULTS—During the follow-up, 79 patients (40%) with nephropathy reached the combined primary end point vs. 19 patients (10%) with normoalbuminuria (log-rank test, P < 0.0001). The unadjusted hazard ratio (HR) for reaching the primary end point when having an abnormal HRV (≤10 bpm) measured at baseline compared with a normal HRV was 7.7 (range 1.9–31.5; P = 0.004) in patients with nephropathy. Similarly in the normoalbuminuric patients, the unadjusted HR was 4.4 (1.4–13.6; P = 0.009). In patients with nephropathy, abnormal HRV was significantly associated with fatal and nonfatal cardiovascular disease after adjustment for cardiovascular risk factors. The adjusted HR for reaching the primary end point in a patient with nephropathy and an abnormal HRV was 6.4 (1.5–26.3, P = 0.010), as compared with a normal HRV. The unadjusted HR for dying when having an abnormal HRV compared with a normal HRV was 3.3 (95% CI 1.0–10.7; P = 0.043) in patients with diabetic nephropathy. After adjustment for confounding factors, the impact of HRV on all-cause mortality in patients with nephropathy was no longer significant (P = 0.293). There was no relationship between abnormal HRV and rate of decline in GFR.

CONCLUSIONS—HRV is an independent risk factor for cardiovascular morbidity and mortality in type 1 diabetic patients with nephropathy.
Improved Prandial Glucose Control With Lower Risk of Hypoglycemia With Nateglinide Than With Glibenclamide in Patients With Maturity-Onset Diabetes of the Young Type 3
Authors: Tuomi Tiinamaija , Honkanen Elina H. , Isomaa Bo , Sarelin Leena , Groop Leif C.
Published: May 2006

OBJECTIVE—To study the effect of the short-acting insulin secretagogue nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3), which is characterized by a defective insulin response to glucose and hypersensitivity to sulfonylureas.

RESEARCH DESIGN AND METHODS—We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. After an overnight fast, they received on three randomized occasions placebo, 1.25 mg glibenclamide, or 30 mg nateglinide before a standard 450-kcal test meal and light bicycle exercise for 30 min starting 140 min after the ingestion of the first test drug.

RESULTS—Insulin peaked earlier after nateglinide than after glibenclamide or placebo (median [interquartile range] time 70 [50] vs. 110 [20] vs. 110 [30] min, P = 0.0002 and P = 0.0025, respectively). Consequently, compared with glibenclamide and placebo, the peak plasma glucose (P = 0.031 and P < 0.0001) and incremental glucose areas under curve during the first 140 min of the test (P = 0.041 and P < 0.0001) remained lower after nateglinide. The improved prandial glucose control with nateglinide was achieved with a lower peak insulin concentration than after glibenclamide (47.0 [26.0] vs. 80.4 [71.7] mU/l; P = 0.023). Exercise did not induce hypoglycemia after nateglinide or placebo, but after glibenclamide six patients experienced symptomatic hypoglycemia and three had to interrupt the test.

CONCLUSIONS—A low dose of nateglinide prevents the acute postprandial rise in glucose more efficiently than glibenclamide and with less stimulation of peak insulin concentrations and less hypoglycemic symptoms.
Testing the Accelerator Hypothesis
Authors: Dabelea Dana , D’Agostino Ralph B. , Mayer-Davis Elizabeth J. , Pettitt David J. , Imperatore Giuseppina , Dolan Larry M. , Pihoker Catherine , Hillier Teresa A. , Marcovina Santica M. , Linder Barbara , Ruggiero Andrea M. , Hamman Richard F. ,   for the SEARCH for Diabetes in Youth Study Group
Published: May 2006

OBJECTIVE—The “accelerator hypothesis” predicts that fatness is associated with an earlier age at onset of type 1 diabetes. We tested the hypothesis using data from the SEARCH for Diabetes in Youth study.

RESEARCH DESIGN AND METHODS—Subjects were 449 youth aged <20 years at diagnosis who had positive results for diabetes antibodies measured 3–12 months after diagnosis (mean 7.6 months). The relationships between age at diagnosis and fatness were examined using BMI as measured at the SEARCH visit and reported birth weight, both expressed as SD scores (SDSs).

RESULTS—Univariately, BMI SDS was not related to age at diagnosis. In multiple linear regression, adjusted for potential confounders, a significant interaction was found between BMI SDS and fasting C-peptide (FCP) on onset age (P < 0.0001). This interaction remained unchanged after additionally controlling for number and titers of diabetes antibodies. An inverse association between BMI and age at diagnosis was present only among subjects with FCP levels below the median (<0.5 ng/ml) (regression coefficient −7.9, P = 0.003). A decrease of 1 SDS in birth weight (639 g) was also associated with an ∼5-month earlier age at diagnosis (P = 0.008), independent of sex, race/ethnicity, current BMI, FCP, and number of diabetes antibodies.

CONCLUSIONS—Increasing BMI is associated with younger age at diagnosis of type 1 diabetes only among those U.S. youth with reduced β-cell function. The intrauterine environment may also be an important determinant of age at onset of type 1 diabetes.
Periodontal Changes in Children and Adolescents With Diabetes
Authors: Lalla Evanthia , Cheng Bin , Lal Shantanu , Tucker Sid , Greenberg Ellen , Goland Robin , Lamster Ira B.
Published: May 2006

OBJECTIVE—To evaluate the level of oral disease in children and adolescents with diabetes.

RESEARCH DESIGN AND METHODS—Dental caries and periodontal disease were clinically assessed in 182 children and adolescents (6–18 years of age) with diabetes and 160 nondiabetic control subjects.

RESULTS—There were no differences between case and control subjects with respect to dental caries. Children with diabetes had significantly higher plaque and gingival inflammation levels compared with control subjects. The number of teeth with evidence of attachment loss (the hallmark of periodontal disease) was significantly greater in children with diabetes (5.79 ± 5.34 vs. 1.53 ± 3.05 in control subjects, unadjusted P < 0.001). When controlling for age, sex, ethnicity, gingival bleeding, and frequency of dental visits, diabetes remained a highly significant correlate of periodontitis, especially in the 12- to 18-year-old subgroup. In the case group, BMI was significantly correlated with destruction of connective tissue attachment and bone, but duration of diabetes and mean HbA1c were not.

CONCLUSIONS—Our findings suggest that periodontal destruction can start very early in life in diabetes and becomes more prominent as children become adolescents. Programs designed to promote periodontal disease prevention and treatment should be provided to young patients with diabetes.
Effects of Intravenous Nicorandil Before Reperfusion for Acute Myocardial Infarction in Patients With Stress Hyperglycemia
Authors: Ishii Hideki , Ichimiya Satoshi , Kanashiro Masaaki , Amano Tetsuya , Matsubara Tatsuaki , Murohara Toyoaki
Published: May 2006

OBJECTIVE—Stress hyperglycemia increases the risk of mortality and poor outcomes in patients with acute myocardial infarction (AMI). We aimed to assess effects of intravenous nicorandil administered before reperfusion on AMI patients with stress hyperglycemia.

RESEARCH DESIGN AND METHODS—This study consisted of 158 consecutive first AMI patients with stress hyperglycemia who underwent percutaneous coronary intervention (PCI) within 24 h from the onset. They were randomly assigned to receive 12 mg of nicorandil (n = 81) or a placebo (n = 77) intravenously just before reperfusion. Stress hyperglycemia was defined as a blood glucose level ≥10 mmol/l (180 mg/dl). We examined various aspects of epicardial flow and microvascular function as immediate data and major adverse cardiac events (MACEs) (coronary heart disease death or unplanned readmission due to congestive heart failure) as late-phase data.

RESULTS—The incidence of slow flow after PCI was lower in the nicorandil group (13.6 vs. 27.3%, P < 0.04). ST segment resolution >50% was observed in 70.4 and 53.2% on nicorandil and placebo, respectively (P < 0.03). Patients treated with nicorandil had a lower peak creatine kinase level (3,137 ± 2,577 vs. 4,333 ± 3,608, P < 0.02). Upon Kaplan-Meier analysis, 5 years’ freedom from MACEs was 86.4% in the nicorandil group and 74.0% in the placebo (P < 0.05).

CONCLUSIONS—Adjunctive therapy with administration of intravenous nicorandil before reperfusion on AMI patients with stress hyperglycemia significantly improves epicardial flow and prevents the occurrence of severe microvascular reperfusion injury, resulting in better outcomes in these patients.
Lifestyle Intervention Is Associated With Lower Prevalence of Urinary Incontinence
Authors: Brown Jeanette S. , Wing Rena , Barrett-Connor Elizabeth , Nyberg Leroy M. , Kusek John W. , Orchard Trevor J. , Ma Yong , Vittinghoff Eric , Kanaya Alka M. ,   for the Diabetes Prevention Program Research Group
Published: May 2006

OBJECTIVE—Diabetes is associated with increased urinary incontinence risk. Weight loss improves incontinence, but exercise may worsen this condition. We examined whether an intensive lifestyle intervention or metformin therapy among overweight pre-diabetic women was associated with a lower prevalence of incontinence.

RESEARCH DESIGN AND METHODS—We analyzed data from the Diabetes Prevention Program, a randomized controlled trial in 27 U.S. centers. Of the 1,957 women included in this analysis, 660 (34%) were randomized to intensive lifestyle therapy, 636 (32%) to metformin, and 661 (34%) to placebo with standard lifestyle advice. The main outcome measure was incontinence symptoms by frequency and type by a validated questionnaire completed at the end-of-trial visit (mean 2.9 years).

RESULTS—The prevalence of total (stress or urge) weekly incontinence was lower among women in the intensive lifestyle group (38.3%) than those randomized to metformin (48.1%) or placebo (45.7%). This difference was most apparent among women with stress incontinence (31.3% for intensive lifestyle group vs. 39.7% for metformin vs. 36.7% for placebo, P = 0.006). Changes in weight accounted for most of the protective effect of the intensive lifestyle intervention on stress incontinence.

CONCLUSIONS—Less-frequent urinary incontinence may be a powerful motivator for women to choose lifestyle modification to prevent diabetes.
Does Measurement Site for Visceral and Abdominal Subcutaneous Adipose Tissue Alter Associations With the Metabolic Syndrome?
Authors: Kuk Jennifer L. , Church Timothy S. , Blair Steven N. , Ross Robert
Published: May 2006

OBJECTIVE—To determine whether the associations between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and the metabolic syndrome are altered depending on measurement site for VAT and ASAT and the definition used to identify the metabolic syndrome.

RESEARCH DESIGN AND METHODS—Total VAT and ASAT volume was derived using ∼37 contiguous computed tomography (CT) images from T10–T11 to L5–S1 in 85 men. CT images obtained at eight intervertebral locations (e.g., L4–L5, L3–L4, etc.) were used to determine the associations between partial volumes (single images) and metabolic syndrome. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Logistic regression was used to calculate the odds ratio (OR) per SD increase in adipose tissue.

RESULTS—For total and all partial volumes, VAT was more strongly associated with metabolic syndrome than ASAT independent of metabolic syndrome criteria. The OR (per SD) for NCEP metabolic syndrome was higher for total VAT volume (OR = 7.26) and for the partial volumes at T12–L1 (7.46) and L1–L2 (8.77) than those at the L4–L5 level (3.94). The OR for metabolic syndrome (∼2.6) was not substantially different among the ASAT measures. A similar pattern of association was observed using the IDF metabolic syndrome criteria.

CONCLUSIONS—The measurement site for VAT, but not for ASAT, has a substantial influence on the magnitude of the association with both metabolic syndrome definitions. However, because VAT remained significantly associated with metabolic syndrome regardless of measurement site, the clinical interpretation was unaltered by measurement protocol or metabolic syndrome definition.
Abdominal Adiposity Is a Stronger Predictor of Insulin Resistance Than Fitness Among 50–95 Year Olds
Authors: Racette Susan B. , Evans Ellen M. , Weiss Edward P. , Hagberg James M. , Holloszy John O.
Published: May 2006

OBJECTIVE—Physical inactivity and increased adiposity contribute to insulin resistance; less is known, however, about the relative contributions of these factors in older adults. The aim of this study was to determine whether cardiovascular fitness, whole-body adiposity, or abdominal adiposity is the strongest predictor of insulin resistance into old age.

RESEARCH DESIGN AND METHODS—Subjects included 407 men and women aged 50–95 years (means ± SD 69 ± 11 years). Insulin resistance was estimated using the insulin sensitivity index (ISI) of Matsuda and DeFronzo [ISI = 10,000/square root of (fasting glucose × fasting insulin) × (mean glucose × mean insulin during an oral glucose tolerance test); lower ISI = greater insulin resistance]. Fitness was determined with a treadmill maximal oxygen consumption (Vo2max) test. Whole-body adiposity measures included BMI and percent fat by dual-energy X-ray absorptiometry or hydrodensitometry; abdominal adiposity was estimated by waist circumference.

RESULTS—Waist circumference was the strongest independent correlate of ISI (r = −0.52, P < 0.0001), explaining 28% of the variance when controlling for sex, BMI, percent fat, and Vo2max. BMI (r = −0.45), percent fat (r = −0.40), and Vo2max (r = 0.22) independently predicted ISI (all P < 0.0001); however, after controlling for waist circumference, only Vo2max remained significant (r = 0.13, P = 0.009).

CONCLUSIONS—Adiposity and fitness continue to be significant predictors of insulin sensitivity into old age, with abdominal obesity being the most important single factor. These findings support the measurement of waist circumference to assess health risk among older adults.
Low Ankle-Brachial Pressure Index Predicts Increased Risk of Cardiovascular Disease Independent of the Metabolic Syndrome and Conventional Cardiovascular Risk Factors in the Edinburgh Artery Study
Authors: Wild Sarah H. , Byrne Christopher D. , Smith Felicity B. , Lee Amanda J. , Fowkes F. Gerald R.
Published: May 2006

OBJECTIVE—To investigate whether a low ankle-brachial pressure index (ABI) predicts increased risk of cardiovascular disease (CVD) independent of the metabolic syndrome and conventional cardiovascular risk factors.

RESEARCH DESIGN AND METHODS—The Edinburgh Artery Study is a population-based cohort study in which subjects were followed up until their death or for ∼15 years. Low ABI at baseline was defined as <0.9; subjects with ABI >1.4 (n = 13) were excluded from the analyses. We used a modified version of the definition of the metabolic syndrome published in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, replacing waist circumference criteria with BMI criteria. Data on relevant parameters were available for 1,467 men and women ages 55–74 years at baseline. Cox proportional hazards models were used to study cardiovascular morbidity and mortality before and after adjusting for potential confounding factors.

RESULTS—We determined that 25% of the study population had the metabolic syndrome and that a low ABI was more prevalent among people with than without the metabolic syndrome (24 vs. 15%; P < 0.001). During the follow-up period, there were 226 deaths from CVD and 462 nonfatal cardiovascular events. The hazard ratio (95% CI) for low ABI after adjusting for age, sex, baseline CVD, diabetes, smoking status, LDL cholesterol, and metabolic syndrome was 1.5 (1.1–2.1) for CVD mortality and 1.5 (1.2–1.8) for all CVD outcomes.

CONCLUSIONS—Low ABI is associated with increased risk of CVD independent of the metabolic syndrome and other major CVD risk factors.
Does Albuminuria Predict Cardiovascular Outcomes on Treatment With Losartan Versus Atenolol in Patients With Diabetes, Hypertension, and Left Ventricular Hypertrophy?
Authors: Ibsen Hans , Olsen Michael H. , Wachtell Kristian , Borch-Johnsen Knut , Lindholm Lars H. , Mogensen Carl E. , Dahlöf Björn , Snapinn Steven M. , Wan Ying , Lyle Paulette A.
Published: May 2006

OBJECTIVE—Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events.

RESEARCH DESIGN AND METHODS—In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR.

RESULTS—Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were ∼33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR.

CONCLUSIONS—Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials.
Trend in the Prevalence of the Metabolic Syndrome and Its Impact on Cardiovascular Disease Incidence
Authors: Lorenzo Carlos , Williams Ken , Hunt Kelly J. , Haffner Steven M.
Published: May 2006

OBJECTIVE—With the current obesity epidemic, one would expect a prevalence increase in the metabolic syndrome. Therefore, in the San Antonio Heart Study, a population-based study with worsening obesity, we examined the metabolic syndrome and its effect on incident cardiovascular disease (CVD).

RESEARCH DESIGN AND METHODS—We enrolled 5,158 subjects in two cohorts: 1979–1982 and 1984–1988. We reexamined 3,682 (71.4%) subjects in 1987–1990 (cohort 1) and 1991–1996 (cohort 2) and assessed a 7.5-year incidence of CVD in 4,635 (90.0%) participants. We used the metabolic syndrome definition of the National Cholesterol Education Program–Adult Treatment Panel III.

RESULTS—At baseline, the metabolic syndrome was less prevalent in cohort 1 than in cohort 2: in men, 20.4 vs. 29.3% (P < 0.001); in women, 16.3 vs. 26.3% (P < 0.001). The prevalence increased in men and women of both Mexican-American and non-Hispanic white ethnic groups between 1979–1982 and 1991–1996 (P for trend <0.001 for each of the groups). There was an excess of incident CVD in cohort 2 relative to cohort 1 (odds ratio 1.37 [95% CI 1.02–1.84]) after adjustment for age, sex, ethnic origin, socioeconomic status, history of CVD, diabetes, total cholesterol, smoking, and family history of heart attack. Further adjustment for the metabolic syndrome reduced this difference (1.26 [0.93–1.71]) because the metabolic syndrome predicted incident CVD (1.58 [1.14–2.18]).

CONCLUSIONS—In San Antonio, Texas, an increase in the prevalence of the metabolic syndrome between 1979–1982 and 1984–1988 contributes to explain a higher CVD incidence.
The 10-s Maximal Sprint
Authors: Bussau Vanessa A. , Ferreira Luis D. , Jones Timothy W. , Fournier Paul A.
Published: May 2006

OBJECTIVE—To investigate whether a short maximal sprint can provide another means to counter the rapid fall in glycemia associated with moderate-intensity exercise in individuals with type 1 diabetes and therefore decrease the risk of early postexercise hypoglycemia.

RESEARCH DESIGN AND METHODS—In the study, seven male subjects with type 1 diabetes injected their normal insulin dose and ate their usual breakfast. When their postprandial glycemia fell to ∼11 mmol/l, they pedaled at 40% ˙Vo2peak for 20 min on a cycle ergometer then immediately engaged in a maximal 10-s cycling sprint (sprint trial) or rested (control trial); the sprint and rest trials were administered in a counterbalanced order.

RESULTS—Moderate-intensity exercise resulted in a significant fall (P < 0.05) in glycemia in both trials (means ± SE: 3.6 ± 0.5 vs. 3.1 ± 0.5 mmol/l for sprint and control, respectively). The subsequent short cycling sprint opposed a further fall in glycemia for 120 min, whereas in the absence of a sprint, glycemia decreased further (3.6 ± 1.22 mmol/l; P < 0.05) after exercise. The stabilization of glycemia in the sprint trial was associated with elevated levels of catecholamines, growth hormone, and cortisol. In contrast, these hormones remained at stable or near-stable levels in the control trial. Changes in insulin and free fatty acid levels were similar in the sprint and control trials.

CONCLUSIONS—These results suggest that after moderate-intensity exercise, it is preferable for young individuals with insulin-treated, complication-free type 1 diabetes to engage in a 10-s maximal sprint to acutely oppose a further fall in glycemia than to only rest. The addition of the sprint after moderate-intensity exercise provides another means to reduce the risk of hypoglycemia in active individuals with type 1 diabetes.
Effects of Pioglitazone Versus Glipizide on Body Fat Distribution, Body Water Content, and Hemodynamics in Type 2 Diabetes
Authors: Basu Ananda , Jensen Michael D. , McCann Frances , Mukhopadhyay Debabrata , Joyner Michael J. , Rizza Robert A.
Published: May 2006

OBJECTIVE—Pioglitazone, a peroxisome proliferator–activated receptor agonist and glipizide, an insulin secretagogue, are commonly used to treat type 2 diabetes. Our study was designed to examine the effects of pioglitazone versus glipizide on body water, body composition, and hemodynamic parameters in the presence of comparable glycemic control between groups.

RESEARCH DESIGN AND METHODS—We studied 19 diabetic subjects randomly assigned to either 45 mg pioglitazone (n = 8) or 10 mg (median dose) glipizide (n = 11) for 12 weeks. Body water content was measured with deuterated water, body composition by dual-energy X-ray absorptiometry and computed tomography, and cardiac output and systemic vascular resistance by acetylene rebreathing technique both before and after therapy.

RESULTS—Pioglitazone increased (P < 0.001 from baseline) total body water (+2.4 ± 0.5 l) accounting for 75% of the total weight gain (+3.1 ± 2.0 kg) but did not alter vascular endothelial growth factor concentrations. Total abdominal (−32.2 ± 19 cm2) and visceral fat area (−16.1 ± 8 cm2) tended to decrease with pioglitazone but increased (P < 0.02 for differences between groups) with glipizide (+38.4 ± 17 cm2 abdominal; +19.1 ± 9 cm2 visceral). Pioglitazone tended to reduce (P = 0.05) diastolic (−8.4 ± 4 mmHg) and mean (−9.5 ± 5 mmHg; P = 0.08) blood pressure and reduced (P < 0.001) systemic vascular resistance (2,785 ± 336 vs. 2,227 ± 136 dynes/s per m2), while there were no differences in these parameters with glipizide. Neither therapy altered circulating catecholamine concentrations.

CONCLUSIONS—When pioglitazone and glipizide are given in doses sufficient to achieve equivalent glycemic control in people with type 2 diabetes, pioglitazone increases total body water, thereby accounting for the majority of weight gain, tended to decrease visceral and abdominal fat content and blood pressure, and reduces systemic vascular resistance.
Are Health Care Professionals Advising Patients With Diabetes or At Risk for Developing Diabetes to Exercise More?
Authors: Morrato Elaine H. , Hill James O. , Wyatt Holly R. , Ghushchyan Vahram , Sullivan Patrick W.
Published: May 2006

OBJECTIVE—With increased focus on the obesity and diabetes epidemics, and the clear benefit of exercise in disease prevention and management, this study determined the lifetime prevalence of health professional advice to exercise among individuals with or at risk for diabetes.

RESEARCH DESIGN AND METHODS—The Medical Expenditure Panel Survey is a nationally representative survey of the U.S. population. In the 2002 survey, 26,878 adults responded when asked about ever receiving health professional advice to exercise more. Information on sociodemographic characteristics and health conditions were self-reported. Type 2 diabetes risk factors were age ≥45 years, non-Caucasian ethnicity, physical inactivity, BMI ≥25 kg/m2, hypertension, and cardiovascular disease.

RESULTS—A total of 73% of adults with diabetes were told by a health professional to exercise more versus 31% of adults without diabetes. The proportion receiving advice increased as the number of diabetes risk factors increased until reaching similar rates as people with diabetes. After adjustment for sociodemographic and clinical factors, the strongest correlates of receiving advice were BMI and cardiovascular risk factors. Among respondents with diabetes, the likelihood of receiving advice did not vary by age, sex, education, or income level but was less likely in Hispanics.

CONCLUSIONS—Health professionals advised most patients with or at highest risk for diabetes to exercise, suggesting recognition of its importance for disease management. As risk factors declined, fewer patients were advised to exercise, suggesting missed opportunities for disease prevention. However, exercise has not increased proportional to exercise advice. The challenge remains converting patient awareness into behavior change.
Polymorphisms of the Protein Kinase C-β Gene (PRKCB1) Accelerate Kidney Disease in Type 2 Diabetes Without Overt Proteinuria
Authors: Araki Shin-ichi , Haneda Masakazu , Sugimoto Toshiro , Isono Motohide , Isshiki Keiji , Kashiwagi Atsunori , Koya Daisuke
Published: May 2006

OBJECTIVE—We investigated the contribution of PKC-β gene (PRKCB1) polymorphisms to diabetic kidney disease in a prospective observational follow-up study.

RESEARCH DESIGN AND METHODS—A total of 364 Japanese subjects with type 2 diabetes without overt proteinuria were enrolled during 1996–1998 and followed until 2004. Five single nucleotide polymorphisms (−1504C/T, −546C/G, −348A/G, −278C/T, and −238C/G) in the promoter region of PRKCB1 were genotyped. The end points were transition from stage to stage of diabetic nephropathy as a time-to-event outcome and the annual decline rate of estimated glomerular filtration rate (eGFR) as a slope-based outcome.

RESULTS—During the study (median 6 years), 34 of 364 subjects (9.3%) progressed. Kaplan-Meier estimation revealed that subjects with both T allele at −1054 C/T and G allele at −546 C/G polymorphisms frequently showed transition to advanced stages of diabetic nephropathy (P = 0.015). The annual change rate in eGFR in the subjects with both alleles was also significantly higher than in others (−2.96 ± 0.62 vs. −1.63 ± 0.15 ml/min per 1.73 m2/year, P = 0.02). The estimated frequency of this risk T-G haplotype was significantly higher in the progressors who showed transition to advanced nephropathy stages (12%) than in the nonprogressors (5%) (odds ratio 2.3 [95% CI 1.0–5.2]), and it was also higher in those with accelerated decline of the Δ eGFR (≥3 ml/min per 1.73 m2/year) than in those without (2.1 [1.1–3.9]).

CONCLUSIONS—Our study indicates that PRKCB1 is a predictor for worsening of kidney disease in Japanese subjects with type 2 diabetes.
The Association Among Autonomic Nervous System Function, Incident Diabetes, and Intervention Arm in the Diabetes Prevention Program
Authors: Carnethon Mercedes R. , Prineas Ronald J. , Temprosa Marinella , Zhang Zhu-Ming , Uwaifo Gabriel , Molitch Mark E. ,   for the Diabetes Prevention Program Research Group
Published: May 2006

OBJECTIVE—Autonomic nervous system dysfunction, a correlate of obesity and poor cardiorespiratory fitness, is associated with the development of diabetes. We tested whether estimates of autonomic nervous system function improved in the intensive lifestyle versus metformin or placebo arms of the Diabetes Prevention Program (DPP) and whether baseline or a change in autonomic nervous system function was associated with the development of diabetes over 3.2 years.

RESEARCH DESIGN AND METHODS—In 2,980 DPP participants, 12-lead electrocardiograms were measured at baseline and annually. Heart rate, heart rate variability (HRV), and QT duration were used to estimate fitness and autonomic nervous system function.

RESULTS—In the lifestyle arm, heart rate and QT indexes decreased, and HRV increased over time. The magnitude of decline in heart rate and QT duration was substantially smaller in the other arms, whereas HRV did not increase. Baseline heart rate was the only index significantly (P < 0.05) associated with incident diabetes after adjustment for demographics and weight change (hazard ratio for lifestyle and metformin arms = 1.19 and 1.17 per 10.6 beats/min, respectively). Decreases in heart rate and QT indexes and increases in HRV over time were associated with a lower risk of developing diabetes. The protective association between decreased heart rate and incident diabetes in the lifestyle arm remained significant after accounting for change in weight and physical activity.

CONCLUSIONS—Indexes that reflect autonomic function and fitness improved (i.e., heart rate decreased and HRV increased) in the lifestyle modification arm of the DPP. Improvements in these indexes are inversely associated with the development of diabetes independent of weight change.
Depression and Glycemic Control in Elderly Ethnically Diverse Patients With Diabetes
Authors: Trief Paula M. , Morin Philip C. , Izquierdo Roberto , Teresi Jeanne A. , Eimicke Joseph P. , Goland Robin , Starren Justin , Shea Steven , Weinstock Ruth S.
Published: May 2006

OBJECTIVE—The purpose of the study was to investigate the effect of comorbid depression on glycemic control and on response to a telemedicine case management intervention for elderly, ethnically diverse diabetic patients.

RESEARCH DESIGN AND METHODS—Medicare beneficiaries in underserved areas were participants (n = 1,665) in the Informatics for Diabetes Education and Telemedicine (IDEATel) project and randomized to a telemedicine case management intervention or usual care. The data analyzed include baseline demographics (age, sex, race/ethnicity, marital status, insulin use, years of education, years of diabetes, and pack-years smoked) and measures of glycemic control (HbA1c [A1C]), comorbidity, diabetes symptom severity, functional disability and depression, and 1-year (n = 1,578) A1C. The association between depression and glycemic control was analyzed cross-sectionally and prospectively.

RESULTS—At baseline, there was a significant correlation between depression and A1C and a trend for depression to predict A1C when other factors were controlled. However, in prospective analyses, depression did not predict change in A1C, either in the control or intervention group.

CONCLUSIONS—In this large sample of elderly diabetic patients, a weak relationship between depression and A1C was found, but depression did not prospectively predict change in glycemic control. Thus, there is no evidence that depression should be used to exclude patients from interventions. Also, we should evaluate the impact of depression on outcomes other than glycemic control.
Translating the Chronic Care Model Into the Community
Authors: Piatt Gretchen A. , Orchard Trevor J. , Emerson Sharlene , Simmons David , Songer Thomas J. , Brooks Maria M. , Korytkowski Mary , Siminerio Linda M. , Ahmad Usman , Zgibor Janice C.
Published: May 2006

OBJECTIVE—To determine whether using the chronic care model (CCM) in an underserved community leads to improved clinical and behavioral outcomes for people with diabetes.

RESEARCH DESIGN AND METHODS—This multilevel, cluster-design, randomized controlled trial examined the effectiveness of a CCM-based intervention in an underserved urban community. Eleven primary care practices, along with their patients, were randomized to three groups: CCM intervention (n = 30 patients), provider education only (PROV group) (n = 38), and usual care (UC group) (n = 51).

RESULTS—A marked decline in HbA1c was observed in the CCM group (−0.6%, P = 0.008) but not in the other groups. The magnitude of the association remained strong after adjustment for clustering (P = 0.01). The same pattern was observed for a decline in non-HDL cholesterol and for the proportion of participants who self-monitor blood glucose in the CCM group (non-HDL cholesterol: −10.4 mg/dl, P = 0.24; self-monitor blood glucose: +22.2%, P < 0.0001), with statistically significant between-group differences in improvement (non-HDL cholesterol: P = 0.05; self-monitor blood glucose: P = 0.03) after adjustment. The CCM group also showed improvement in HDL cholesterol (+5.5 mg/dl, P = 0.0004), diabetes knowledge test scores (+6.7%, P = 0.07), and empowerment scores (+2, P = 0.02).

CONCLUSIONS—These results suggest that implementing the CCM in the community is effective in improving clinical and behavioral outcomes in patients with diabetes.
Tissue Gene Expression of Renin-Angiotensin System in Human Type 2 Diabetic Nephropathy
Authors: Konoshita Tadashi , Wakahara Shigeyuki , Mizuno Shinichi , Motomura Makoto , Aoyama Chikako , Makino Yasukazu , Kawai Yasuyuki , Kato Norihiro , Koni Ichiro , Miyamori Isamu , Mabuchi Hiroshi
Published: May 2006

OBJECTIVE—Recent studies have proved that blockade of the renin-angiotensin system (RAS) retards the progression of diabetic nephropathy, whereas hyporeninemia is known as a typical state in diabetic subjects. The purpose of this study is to determine whether expression levels of RAS differ between nondiabetic and diabetic renal tissues with accurate quantitative method.

RESEARCH DESIGN AND METHODS—Subjects were 66 nondiabetic and 8 diabetic patients with biopsy-proven renal diseases. The eight diabetic subjects suffered from type 2 diabetes with overt proteinuria. Renal histology revealed typical diffuse or nodular lesions with linear IgG deposit on immunofluorescent staining and thickened basement membrane on electronic microscopy. Total RNA from a small part of the renal cortical biopsy specimens was reverse-transcribed, and the resultant cDNA was amplified for new major components of RAS (i.e., renin, renin receptor, angiotensinogen, ACE, ACE2, angiotensin II type 1 receptor, and angiotensin II type 2 receptor) and measured.

RESULTS—Among these components, a significant upregulation was observed in the ACE gene in diabetic renal tissue.

CONCLUSIONS—The results suggest that renal tissue RAS might be activated in the respect that ACE gene expression is upregulated in spite of a tendency to low renin expression in type 2 diabetic nephropathy.
α2-Heremans-Schmid Glycoprotein/ Fetuin-A Is Associated With Insulin Resistance and Fat Accumulation in the Liver in Humans
Authors: Stefan Norbert , Hennige Anita M. , Staiger Harald , Machann Jürgen , Schick Fritz , Kröber Stefan M. , Machicao Fausto , Fritsche Andreas , Häring Hans-Ulrich
Published: May 2006

OBJECTIVE—The α2-Heremans-Schmid glycoprotein (AHSG; fetuin-A in animals) impairs insulin signaling in vitro and in rodents. Whether AHSG is associated with insulin resistance in humans is under investigation. In an animal model of diet-induced obesity that is commonly associated with hepatic steatosis, an increase in Ahsg mRNA expression was observed in the liver. Therefore, we hypothesized that the AHSG plasma protein, which is exclusively secreted by the liver in humans, may not only be associated with insulin resistance but also with fat accumulation in the liver.

RESEARCH DESIGN AND METHODS—Data from 106 healthy Caucasians without type 2 diabetes were included in cross-sectional analyses. A subgroup of 47 individuals had data from a longitudinal study. Insulin sensitivity was measured by a euglycemic-hyperinsulinemic clamp, and liver fat was determined by 1H magnetic resonance spectroscopy.

RESULTS—AHSG plasma levels, adjusted for age, sex, and percentage of body fat, were higher in subjects with impaired glucose tolerance compared with subjects with normal glucose tolerance (P = 0.006). AHSG plasma levels were negatively associated with insulin sensitivity (r = −0.22, P = 0.03) in cross-sectional analyses. Moreover, they were positively associated with liver fat (r = 0.27, P = 0.01). In longitudinal analyses, under weight loss, a decrease in liver fat was accompanied by a decrease in AHSG plasma concentrations. Furthermore, high AHSG levels at baseline predicted less increase in insulin sensitivity (P = 0.02).

CONCLUSIONS—We found that high AHSG plasma levels are associated with insulin resistance in humans. Moreover, AHSG plasma levels are elevated in subjects with fat accumulation in the liver. This is consistent with a potential role of AHSG as a link between fatty liver and insulin resistance.
Adult Treatment Panel III 2001 but Not International Diabetes Federation 2005 Criteria of the Metabolic Syndrome Predict Clinical Cardiovascular Events in Subjects Who Underwent Coronary Angiography
Authors: Saely Christoph H. , Koch Lorena , Schmid Fabian , Marte Thomas , Aczel Stefan , Langer Peter , Hoefle Guenter , Drexel Heinz
Published: May 2006

OBJECTIVE—The International Diabetes Federation (IDF) has recently established a worldwide consensus definition of the metabolic syndrome. No prospective data are available on the cardiovascular risk associated with this new metabolic syndrome definition.

RESEARCH DESIGN AND METHODS—In a prospective study of 750 coronary patients, we recorded vascular events over 4 years.

RESULTS—From our patients, 37.3% (n = 280) had the metabolic syndrome according to the Adult Treatment Panel III (ATPIII) definition and 45.5% (n = 341) according to the IDF definition. The metabolic syndrome as defined by the ATPIII criteria significantly predicted vascular events (adjusted hazard ratio 1.745 [95% CI 1.255–2.427]; P = 0.001), but the metabolic syndrome as defined by IDF criteria did not (1.189 [0.859–1.646]; P = 0.297). Accordingly, event-free survival was significantly lower among patients who fulfilled the ATPIII but not the IDF criteria than among those who met the IDF but not the ATPIII criteria (P = 0.012). The metabolic syndrome as defined by ATPIII criteria remained significantly predictive of vascular events after adjustment for type 2 diabetes but not after additional adjustment for the metabolic syndrome components high triglycerides and low HDL cholesterol. These lipid traits in turn proved significantly predictive of vascular events even after adjustment for the metabolic syndrome.

CONCLUSIONS—The ATPIII definition of the metabolic syndrome confers a significantly higher risk of vascular events than the IDF definition. However, among angiographied coronary patients, even the ATPIII definition of the metabolic syndrome does not provide prognostic information beyond its dyslipidemic features.