bluuebunny/crossref_metadata_2025 huggingface dataset:
Fasting Blood Sample-Based Assessment of Insulin Sensitivity in Kidney-Pancreas-Transplanted Patients
Authors: Perseghin Gianluca , Caumo Andrea , Sereni Lucia Piceni , Battezzati Alberto , Luzi Livio
Published: March 2007

OBJECTIVE—To ascertain whether simple indexes of insulin sensitivity based on a fasting blood sample may be reliable measures of insulin sensitivity in combined kidney-pancreas- transplanted patients.

RESEARCH DESIGN AND METHODS—Estimates of insulin sensitivity based on fasting plasma glucose, insulin (homeostasis model assessment of insulin sensitivity [HOMA-IS], Quantitative Insulin Sensitivity Check Index [QUICKI]), and free fatty acid (revised QUICKI) concentrations were compared with insulin sensitivity as assessed with the gold standard technique (euglycemic-hyperinsulinemic clamp) in 22 patients who had undergone kidney-pancreas transplantation (KP-Tx) and 18 matched healthy subjects (NOR).

RESULTS—In KP-Tx patients, indexes based on the glucose-insulin product, HOMA-IS (r = 0.47, P = 0.03) and QUICKI (r = 0.47, P = 0.03), were shown to be reliable measures of insulin sensitivity. The introduction of fasting plasma free fatty acid concentration in the revised QUICKI (r = 0.76, P < 0.0001) considerably improved the power of prediction of the clamp-based measure of insulin sensitivity as observed in the healthy control subjects (r = 0.83, P < 0.0001).

CONCLUSIONS—This study shows that in KP-Tx patients, HOMA-IS and QUICKI are reliable measures of insulin sensitivity; the additional incorporation of fasting plasma free fatty acid concentration into the glucose-insulin product (revised QUICKI) resulted in a considerably more powerful index.
Variation in Diabetes Care Among States
Authors: Arday David R. , Fleming Barbara B. , Keller Dana K. , Pendergrass Peter W. , Vaughn Robert J. , Turpin James M. , Nicewander David A.
Published: March 2007

OBJECTIVE—To examine state variability in diabetes care for Medicare beneficiaries and the impact of certain beneficiary characteristics on those variations.

RESEARCH DESIGN AND METHODS—Medicare beneficiaries with diabetes, aged 18–75 years, were identified from 1997 to 1999 claims data. Claims data were used to construct rates for three quality of care measures (HbA1c tests, eye examinations, and lipid profiles). Person-level variables (e.g., age, sex, race, and socioeconomic status) were used to adjust state rates using logistic regression.

RESULTS—A third of 2 million beneficiaries with diabetes aged 18–75 years did not have annual HbA1c tests, biennial eye examinations, or biennial lipid profiles. There was wide variability in the measures among states (e.g., receipt of HbA1c tests ranged from 52 to 83%). Adjustment using person-level variables reduced the variance in HbA1c tests, eye examinations, and lipid profiles by 30, 23, and 27%, respectively, but considerable variability remained. The impact of the adjustment variables was also inconsistent across measures.

CONCLUSIONS—Opportunities remain for improvement in diabetes care. Large variations in care among states were reduced significantly by adjustment for characteristics of state residents. However, much variability remained unexplained. Variability of measures within states and variable impact of the adjustment variables argues against systems effects operating with uniformity on the three measures. These findings suggest that a single approach to quality improvement is unlikely to be effective. Further understanding variability will be important to improving quality.
Insulin-Induced Decreases in Aortic Wave Reflection and Central Systolic Pressure Are Impaired in Type 2 Diabetes
Authors: Tamminen Marjo , Westerbacka Jukka , Vehkavaara Satu , Yki-Järvinen Hannele
Published: March 2007

OBJECTIVE—To determine whether large arteries are resistant to insulin.

RESEARCH DESIGN AND METHODS—Insulin normally acutely decreases central systolic pressure by decreasing wave reflection in vivo. This effect occurs before any changes in peripheral vascular resistance or heart rate under normoglycemic conditions. We determined whether the ability of insulin to decrease central aortic pressure is altered in uncomplicated type 2 diabetes. The study subjects consisted of 16 type 2 diabetic patients (age 54 ± 2 years, BMI 29 ± 1 kg/m2) and 19 matched nondiabetic individuals (51 ± 2 years, 29 ± 1 kg/m2) studied under normoglycemic-hyperinsulinemic conditions. Central aortic pressure waveforms were synthesized from those recorded in the periphery using applanation tonometry and a validated reverse transfer function to construct the central aortic pressure waveform every 30 min. This method allowed determination of aortic augmentation (the pressure difference between the first and second central systolic pressure waves) and the augmentation index (augmentation divided by pulse pressure).

RESULTS—Whole-body insulin sensitivity was 31% lower (P < 0.05) in the type 2 diabetic patients than in the normal subjects. Basally, before the insulin infusion, augmentation averaged 8.9 ± 1.3 and 11.1 ± 1.2 mmHg (NS) and the augmentation index averaged 23.1 ± 2.1 and 27.5 ± 2.1% (NS) in the normal subjects and diabetic patients, respectively. After 30 min of hyperinsulinemia, augmentation decreased significantly to 6.1 ± 1.1 mmHg (P < 0.001) in the normal subjects but remained unchanged at 9.1 ± 1.1 mmHg (NS) in type 2 diabetic patients. At 30 min, the augmentation index had decreased significantly (30 ± 7% decrease) to 17.9 ± 2.6% in the normal subjects but remained at 24.4 ± 2.4% in the diabetic patients (13 ± 4% decrease, P < 0.05 for change vs. normal subjects). Central systolic pressure decreased significantly by 30 min in the normal subjects but only after 120 min in the type 2 diabetic patients. There were no significant changes in heart rate, pulse pressure, or forearm blood flow during the first 120 min of the insulin infusion.

CONCLUSIONS—Insulin resistance in type 2 diabetes involves a delay in the ability of insulin to decrease central aortic pressure. This defect could predispose these patients to develop systolic hypertension.
Circulating and Urinary Transforming Growth Factor β1, Amadori Albumin, and Complications of Type 1 Diabetes
Authors: Chaturvedi Nish , Schalkwijk Casper G. , Abrahamian Heidemarie , Fuller John H. , Stehouwer Coen D.A.
Published: March 2007

OBJECTIVE—Transforming growth factor (TGF)-β1 is overexpressed in diabetes as a consequence of hyperglycemia and the creation of early glycated end products and may be responsible for the characteristic structural renal changes associated with diabetes. We sought to examine the role of both urinary and circulating TGF-β1 and its promoter Amadori albumin in the vascular complications of type 1 diabetes.

RESEARCH DESIGN AND METHODS—The present article reports on a nested case-control study from the EURODIAB Prospective Complications Study of Europeans with type 1 diabetes. Case subjects (n = 356) were all individuals with one or more complications of diabetes; control subjects (n = 185) were all individuals with no evidence of complications.

RESULTS—Urinary TGF-β1 and Amadori albumin were elevated in patients with micro- or macroalbuminuria. Standardized regression effects (SREs) for macroalbuminuria versus normoalbuminuria were 2.45 (95% CI 1.88–3.18, P = 0.0001 for urinary TGF-β1) and 1.67 (1.34–2.07, P = 0.001 for Amadori albumin). The SRE for urinary TGF-β1 remained statistically significant when adjusted for HbA1c, Amadori albumin, and blood pressure. Circulating TGF-β1 was elevated in individuals with proliferative retinopathy compared with individuals without retinopathy (SRE 1.29 [1.07–1.550], P = 0.007). This result was attenuated to 1.16 (0.95–1.43, P = 0.2) in the multivariate model, largely because of HbA1c.

CONCLUSIONS—Elevated levels of urinary TGF-β1 in macroalbuminuria were associated with elevations in Amadori albumin and HbA1c and also in blood pressure. In contrast, only circulating TGF-β1 was related to proliferative retinopathy, and HbA1c largely accounted for this. These findings may indicate novel pathways for understanding mechanisms and therapeutic interventions.
Assessment of Group Versus Individual Diabetes Education
Authors: Rickheim Patti. L. , Weaver Todd W. , Flader Jill. L. , Kendall David. M.
Published: March 2007

OBJECTIVES— The current study was conducted to compare the effectiveness of delivering diabetes education in either a group or individual setting using a consistent, evidence-based curriculum.

RESEARCH DESIGN AND METHODS— A total of 170 subjects with type 2 diabetes were randomly assigned to either group (n = 87) or individual (n = 83) educational settings. Subjects received education in four sequential sessions delivered at consistent time intervals over a 6-month period. Outcomes included changes in knowledge, self-management behaviors, weight, BMI, HbA1c, health-related quality of life, patient attitudes, and medication regimen. Changes were assessed at baseline and after the 2-week, 3-month, and 6-month education sessions.

RESULTS— Both educational settings had similar improvements in knowledge, BMI, health-related quality of life, attitudes, and all other measured indicators. HbA1c decreased from 8.5 ± 1.8% at baseline to 6.5 ± 0.8% at 6 months (P < 0.01) in the study population as a whole. Subjects assigned to the individual setting had a 1.7 ± 1.9% reduction in HbA1c (P < 0.01), whereas subjects assigned to the group setting had a 2.5 ± 1.8% reduction in HbA1c (P < 0.01). The difference in HbA1c improvement was marginally greater in subjects assigned to group education versus individualized education (P = 0.05).

CONCLUSIONS— This study demonstrates that diabetes education delivered in a group setting, when compared with an individual setting, was equally effective at providing equivalent or slightly greater improvements in glycemic control. Group diabetes education was similarly effective in delivering key educational components and may allow for more efficient and cost-effective methods in the delivery of diabetes education programs.
Defining the Relationship Between Plasma Glucose and HbA1c
Authors: Rohlfing Curt L. , Wiedmeyer Hsiao-Mei , Little Randie R. , England Jack D. , Tennill Alethea , Goldstein David E.
Published: March 2007

OBJECTIVE— To define the relationship between HbA1c and plasma glucose (PG) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial (DCCT).

RESEARCH DESIGN AND METHODS— The DCCT was a multicenter, randomized clinical trial designed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes. Quarterly HbA1c and corresponding seven-point capillary blood glucose profiles (premeal, postmeal, and bedtime) obtained in the DCCT were analyzed to define the relationship between HbA1c and PG. Only data from complete profiles with corresponding HbA1c were used (n = 26,056). Of the 1,441 subjects who participated in the study, 2 were excluded due to missing data. Mean plasma glucose (MPG) was estimated by multiplying capillary blood glucose by 1.11. Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA1c.

RESULTS— Linear regression analysis, using MPG and HbA1c summarized by patient (n = 1,439), produced a relationship of MPG (mmol/l) = (1.98 ○1 HbA1c) - 4.29 or MPG (mg/dl) = (35.6 ○1 HbA1c) - 77.3, r = 0.82). Among individual time points, afternoon and evening PG (postlunch, predinner, postdinner, and bedtime) showed higher correlations with HbA1c than the morning time points (prebreakfast, postbreakfast, and prelunch).

CONCLUSIONS— We have defined the relationship between HbA1c and PG as assessed in the DCCT. Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA1c goals.
Regional Variation in Cardiovascular Disease Risk Factors Among American Indians and Alaska Natives With Diabetes
Authors: Rith-Najarian Stephen J. , Gohdes Dorothy M. , Shields Raymond , Skipper Betty , Moore Kelly R. , Tolbert Bernadine , Raymer Terry , Acton Kelly J.
Published: March 2007

OBJECTIVE—To compare by region risk factors for cardiovascular disease among American Indian populations with diabetes.

RESEARCH DESIGN AND METHODS—Trained providers from 185 federal, urban, and tribally operated facilities reviewed the records from systematic random samples of the patients included in the local diabetes registries in the 1998 Indian Health Service (IHS) Diabetes Care and Outcomes Audit. Selected measures of cardiovascular risk were aggregated by region and adjusted to calculate regional rates for patients <45 years of age (n = 2,595) and those aged ≥45 years (n = 8,294).

RESULTS—Among the younger group of patients with diabetes, the rates of elevated HbA1c (≥9%) and tobacco use varied significantly among regions. High rates of obesity (78%) and elevated HbA1c (56%) were found in the Southwest. High rates of tobacco use (55%) but the lowest rates of elevated HbA1c (27%) were found in Alaska. Among patients aged ≥45 years, all measures including rates of proteinuria, cholesterol ≥200 mg/dl, and mean blood pressure ≥130/85 varied significantly among all regions. Tobacco use was highest in the Great Lakes (44%) and Great Plains (42%) regions and lowest in the Southwest (14%) and Colorado Plateau (8%) regions. Proteinuria was found most frequently in the Southwest (35%), Colorado Plateau (30%), and Pacific regions (35%). Older individuals with diabetes were more likely than younger individuals to have proteinuria and blood pressure ≥130/85.

CONCLUSIONS—American Indians and Alaska Natives with diabetes carry a large burden of potentially modifiable cardiovascular risk factors, but there is significant regional variation.
Increased Fructose Concentrations in Blood and Urine in Patients With Diabetes
Authors: Kawasaki Takahiro , Akanuma Hiroshi , Yamanouchi Toshikazu
Published: March 2007

OBJECTIVE—To investigate fructose metabolic changes in patients with diabetes.

RESEARCH DESIGN AND METHODS—Serum and urinary fructose concentrations were determined in healthy subjects (n = 23) and in nondiabetic (n = 23) and diabetic patients (n = 26). Fructose was measured using our newly developed method, and 13C6-fructose was used as the internal standard. After adding sample to a fixed amount of internal standard, ion-exchange resins and high-performance liquid chromatography pretreatments were performed. Then, the amount of fructose in the sample was measured by gas chromatography-mass spectrometry.

RESULTS—Serum fructose concentrations in patients with diabetes (12.0 ± 3.8 μmol/l) were significantly higher than those in healthy subjects (8.1 ± 1.0 μmol/l, P < 0.001) and nondiabetic patients (7.7 ± 1.6 μmol/l, P < 0.001), and daily urinary fructose excretion was significantly greater in patients with diabetes (127.8 ± 106.7 μmol/day) than in nondiabetic patients (37.7 ± 23.0 μmol/day, P < 0.001). In patients with diabetes (n = 20), serum fructose concentrations (8.6 ± 1.8 μmol/l, P < 0.001) and daily urinary fructose excretion (63.4 ± 63.8 μmol/day, P < 0.01) significantly decreased by week 2 after admission.

CONCLUSIONS—The present results differed from those of previous studies in that we found that the serum and urinary fructose concentrations decreased rapidly, concomitant with an improvement in glycemia. Therefore, hyperglycemia was associated with increased serum and urinary fructose concentrations in patients with diabetes.
Effects of an Energy-Restrictive Diet With or Without Exercise on Abdominal Fat, Intermuscular Fat, and Metabolic Risk Factors in Obese Women
Authors: Janssen Ian , Fortier Anne , Hudson Robert , Ross Robert
Published: March 2007

OBJECTIVE—The primary objective was to examine whether the combination of diet and aerobic exercise (DA) or diet and resistance exercise (DR) is associated with greater improvements in metabolic risk factors by comparison to diet only (DO) in obese women. A second objective considered whether reductions in metabolic risk factors are related to concurrent changes in abdominal and/or intermuscular fat distribution.

RESEARCH DESIGN AND METHODS—A total of 38 premenopausal obese women were randomly assigned to one of three 16-week treatments: DO (n=13), DA (n=11), or DR (n=14). Plasma glucose, insulin, and lipid levels were measured in a fasting state and after a 75-g oral glucose challenge (oral glucose tolerance test [OGTT]). Total, abdominal subcutaneous, visceral, and intermuscular fat were measured by magnetic resonance imaging.

RESULTS—Significant reductions (P < 0.02) in body weight (∼10 kg or 10%) and in total, abdominal subcutaneous, visceral, and intermuscular fat were observed within each group. Fasting and OGTT insulin, total cholesterol, LDL cholesterol, and apolipoprotein B also decreased within each group (P ≤ 0.02). The changes in the body fat and metabolic variables were not different across treatment (P > 0.05). Visceral fat alone was related to the metabolic risk factors both before and after the treatment.

CONCLUSIONS—Weight loss was associated with reductions in metabolic risk factors in obese women. The improvement in the metabolic profile was not enhanced by the addition of aerobic or resistance exercise. The findings reinforce the importance of diminished visceral fat in the treatment of insulin resistance.
A Comparison of Rates, Risk Factors, and Outcomes of Gestational Diabetes Between Aboriginal and Non-Aboriginal Women in the Saskatoon Health District
Authors: Dyck Roland , Klomp Helena , Tan Leonard K. , Turnell Roger W. , Boctor Makram A.
Published: March 2007

OBJECTIVE—To determine possible differences in gestational diabetes mellitus (GDM) between aboriginal and non-aboriginal people in the Saskatoon Health District.

RESEARCH DESIGN AND METHODS—This was a prospective survey of all women admitted for childbirth to the Saskatoon Royal University Hospital between January and July 1998. We compared prevalence rates, risk factors, and outcomes of GDM between aboriginal and non-aboriginal women.

RESULTS—Information was obtained from 2,006 women, of whom 252 aboriginal and 1,360 non-aboriginal subjects had been tested for GDM. The overall rates of GDM were 3.5% for women in the general population and 11.5% for aboriginal women. For those living within the Saskatoon Health District, GDM rates were 3.7 and 6.4%, respectively. Multivariate analysis demonstrated that aboriginal ethnicity, most notably when combined with obesity, was an independent predictor for GDM. Pregravid BMI ≥27 kg/m2 and maternal age ≥33 years were the most important risk factors for GDM in aboriginal women, whereas previous GDM, family history of diabetes, and maternal age ≥38 years were the strongest predictors for GDM in non-aboriginal women.

CONCLUSIONS—There may be fundamental differences in GDM between aboriginal and non-aboriginal people. Because GDM contributes to an increased risk for type 2 diabetes in aboriginal women and their offspring, the impact of prevention and optimal treatment of GDM on the type 2 diabetes epidemic in susceptible populations are important areas for further investigation.
Differential Effects of Metformin and Troglitazone on Cardiovascular Risk Factors in Patients With Type 2 Diabetes
Authors: Chu Neelima V. , Kong Alice P. S. , Kim Dennis D. , Armstrong Debra , Baxi Sunita , Deutsch Reena , Caulfield Michael , Mudaliar Sunder R. , Reitz Richard , Henry Robert R. , Reaven Peter D.
Published: March 2007

OBJECTIVE—Traditional cardiovascular risk factors (CVRF) only partly explain the excessive risk of cardiovascular disease in patients with type 2 diabetes. There is now an increasing appreciation for many novel CVRF that occur largely as a result of insulin resistance and hyperinsulinemia. Therefore, we investigated whether diabetes medications that vary in their mechanism of action and ability to reduce insulin resistance may differ in their effects on both traditional and novel CVRF.

RESEARCH DESIGN AND METHODS—We compared the addition of metformin or troglitazone therapy on CVRF in 22 subjects with type 2 diabetes who remained in poor glycemic control (with HbA1c >8.5%) while taking glyburide 10 mg twice daily. Subjects were initially randomized to either metformin 850 mg once daily or troglitazone 200 mg once daily. Both medications were then titrated upward as needed to achieve fasting plasma glucose <120 mg/dl. Measures of glucose control, insulin resistance, and CVRF (blood pressure, lipids, plasminogen activator inhibitor-1, C-reactive protein, fibrinogen, and small dense LDL) were assessed both before and after therapy.

RESULTS—After 4 months of treatment, both metformin and troglitazone led to similar decreases in fasting plasma glucose and HbA1c. The reduction in insulin resistance determined by hyperinsulinemic-euglycemic clamp was nearly twofold greater with troglitazone than metformin. Metformin did not induce significant changes in blood pressure, LDL cholesterol, LDL size, HDL cholesterol, triglycerides, or plasminogen activator inhibitor-1. However, C-reactive protein did decrease by 33% (6± 1 to 4± 1 ng/l; P < 0.01). Troglitazone therapy was associated with increases in LDL size (26.21± 0.22 to 26.56 ±0.25 nm; P=0.04) and HDL cholesterol (33 ±3 to 36± 3 mg/dl; P=0.05) and decreases in triglycerides (197± 19 to 155± 23 mg/dl; P=0.07) and C-reactive protein by 60% (8± 3 to 3± 1 ng/l, P < 0.01).

CONCLUSIONS—For patients with type 2 diabetes in whom maximal sulfonylurea therapy failed, the addition of the insulin sensitizer troglitazone seemed to have greater benefits on several traditional and novel CVRF than metformin therapy. These differences were not related to glycemic improvement but reflected, in part, the greater reduction in insulin resistance obtained with addition of troglitazone. These data suggest that medications that more effectively address this underlying metabolic defect may be more beneficial in reducing cardiovascular risk in type 2 diabetes.
A Low-Sodium Diet Potentiates the Effects of Losartan in Type 2 Diabetes
Authors: Houlihan Christine A. , Allen Terri J. , Baxter Amynta L. , Panangiotopoulos Sianna , Casley David J. , Cooper Mark E. , Jerums George
Published: March 2007

OBJECTIVE—Diabetic subjects have a high prevalence of hypertension, increased total body exchangeable sodium levels, and an impaired ability to excrete a sodium load. This study assessed the effect of dietary sodium restriction on the efficacy of losartan in hypertensive subjects with type 2 diabetes and albumin excretion rates of 10–200 μg/min.

RESEARCH DESIGN AND METHODS—In this study, 20 subjects were randomized to losartan 50 mg/day (n = 10) or placebo (n = 10). Drug therapy was given in two 4-week phases separated by a washout period. In the last 2 weeks of each phase, patients were assigned to low- or regular-sodium diets, in random order. In each phase, 24-h ambulatory blood pressure, urinary albumin-to-creatinine ratio (ACR), and renal hemodynamics were measured.

RESULTS—Achieved urinary sodium on a low-sodium diet was 85 ± 14 and 80 ± 22 mmol/day in the losartan and placebo groups, respectively. In the losartan group, the additional blood pressure-lowering effects of a low-sodium diet compared with a regular-sodium diet for 24-h systolic, diastolic, and mean arterial blood pressures were 9.7 mmHg (95% confidence interval [CI], 2.2−17.2; P = 0.002), 5.5 mmHg (2.6−8.4; P = 0.002), and 7.3 mmHg (3.3− 11.3; P = 0.003), respectively. In the losartan group, the ACR decreased significantly on a low-sodium diet versus on a regular-sodium diet (−29% [CI −50.0 to −8.5%] vs. + 14% [−19.4 to 47.9%], respectively; P = 0.02). There was a strong correlation between fall in blood pressure and percent reduction in the ACR (r = 0.7, P = 0.02). In the placebo group, there were no significant changes in blood pressure or ACR between regular- and low-sodium diets. There were no significant changes in renal hemodynamics in either group.

CONCLUSIONS—These data demonstrated that a low-sodium diet potentiates the antihypertensive and antiproteinuric effects of losartan in type 2 diabetes. The blood pressure reduction resulting from the addition of a low-sodium diet to losartan was of similar magnitude to that predicted from the addition of a second antihypertensive agent.
Association of Parity With Risk of Type 2 Diabetes and Related Metabolic Disorders
Authors: Hanley Anthony J.G. , McKeown-Eyssen Gail , Harris Stewart B. , Hegele Robert A. , Wolever Thomas M.S. , Kwan Jeremy , Zinman Bernard
Published: March 2007

OBJECTIVE—The relationship between parity and risk of diabetes is controversial, and little information is available regarding associations between parity and measures of insulin resistance and β-cell function. The objective of this study was to investigate the association between parity and risk of glucose intolerance and related metabolic disorders using data from a population-based study in a Native Canadian community.

RESEARCH DESIGN AND METHODS—Female participants (n = 383, aged 12–79 years) provided fasting blood samples for the determination of glucose, insulin, C-peptide, and proinsulin concentrations. A 75-g oral glucose tolerance test was administered, and diabetes and impaired glucose tolerance were diagnosed according to World Health Organization criteria. Waist circumference and percent body fat were determined. Information regarding occurrence of live births and previously diagnosed diabetes was obtained from interviewer-administered questionnaires.

RESULTS—Parity was associated with a significantly reduced risk of diabetes (nulliparous vs. ≥1 birth, odds ratio 0.43, 95% CI 0.19– 0.94, P < 0.05) after adjustment for age and waist circumference. In addition, nondiabetic nulliparous women had significantly elevated concentrations of fasting insulin and proinsulin relative to nondiabetic parous women (all P < 0.05) in analyses adjusted for age and waist circumference.

CONCLUSIONS—Our results are consistent with those from other populations experiencing high rates of diabetes and suggest the presence of a diabetes-prone phenotype within the nulliparous subcohort of this population, which may contribute to infertility.
Hostility, Race, and Glucose Metabolism in Nondiabetic Individuals
Authors: Surwit Richard S. , Williams Redford B. , Siegler Ilene C. , Lane James D. , Helms Michael , Applegate Katherine L. , Zucker Nancy , Feinglos Mark N. , McCaskill Cynthia M. , Barefoot John C.
Published: March 2007

OBJECTIVE—The present study was designed to determine whether hostility is differentially related to measures of glucose metabolism in African-Americans and Caucasians.

RESEARCH DESIGN AND METHODS—The relationship of hostility, as measured by a subset of the Cook-Medley hostility scale (CMHOST) inventory items, to various parameters of glucose metabolism were examined in a young, healthy sample of male and female African-American and Caucasian volunteers. Fasting blood samples were collected during an inpatient admission, at which time the CMHOST was also administered.

RESULTS—In the entire sample, the CMHOST was found to be significantly correlated with fasting glucose and insulin sensitivity, as measured by the homeostatic model assessment (HOMA). However, the relationship of hostility to these parameters of glucose metabolism was different in African-American and Caucasian subjects. Hostility was significantly related to fasting glucose in African-Americans and to insulin sensitivity and fasting insulin in Caucasian subjects. The relationship of hostility to insulin sensitivity and fasting insulin was partially dependent on BMI in Caucasians, but the relationship of hostility to fasting glucose was unrelated to BMI in African-Americans.

CONCLUSIONS—Our data suggest that the relationship of hostility to measures of glucose metabolism is mediated differently in these two ethnic groups. Therefore, hostility seems to be part of a constellation of risk-related behaviors related to BMI in Caucasians but independently related to fasting glucose in African-Americans.
Gestational Diabetes Mellitus in Women of Single Gravidity in Tianjin City, China
Authors: Yang Xilin , Hsu-Hage Bridget , Zhang Hong , Yu Lichun , Dong Ling , Li Jingchun , Shao Ping , Zhang Changjun
Published: March 2007

OBJECTIVE—The aim of this study was to investigate the prevalence of gestational diabetes mellitus (GDM) and risk factors for the development of GDM in pregnant women in Tianjin, China, where the prevalence of GDM is still unknown.

STUDY DESIGN AND METHODS—A total of 9,471 pregnant women living in the six urban districts of Tianjin, China, took part in the initial screening between December 1998 and December 1999. The screening test consisted of a 50-g 1-h glucose test. Women with a reading ≥7.8 mmol/l at the initial screening were invited to undergo a 75-g 2-h oral glucose tolerance test (OGTT). GDM was confirmed using the World Health Organization’s diagnostic criteria.

RESULTS—At the initial screening test, 888 women had a glucose reading of ≥7.8 mmol/l. A total of 701 (79%) women took a subsequent OGTT. Of these, 174 women were confirmed to have GDM (154 with impaired glucose tolerance [IGT] and 20 with diabetes). The prevalence of GDM was 2.31% (2.03% for IGT and 0.28% for diabetes), adjusting for serum glucose levels at the initial screening test. Independent predictors for GDM were maternal age, stature, prepregnancy BMI, weight gain in pregnancy before screening, diabetes in first-degree relatives, and habitual cigarette smoking during pregnancy. Women who smoked or had a short stature are more likely to develop GDM than their counterparts.

CONCLUSIONS—The prevalence of GDM in pregnant women in the city of Tianjin, China, was 2.31%. Short stature and smoking in pregnancy were additional risk factors for GDM.
Association of Acanthosis Nigricans With Hyperinsulinemia Compared With Other Selected Risk Factors for Type 2 Diabetes in Cherokee Indians
Authors: Stoddart Martha L. , Blevins Kathleen S. , Lee Elisa T. , Wang Wenyu , Blackett Piers R.
Published: March 2007

OBJECTIVE—To report prevalence rates of acanthosis nigricans (AN) and hyperinsulinemia and the association of AN with hyperinsulinemia compared with other known or suspected risk factors for type 2 diabetes in young American Indians.

RESEARCH DESIGN AND METHODS—A random sample of Cherokee Nation members aged 5–40 years was invited to participate in the Cherokee Diabetes Study, a cross-sectional study of type 2 diabetes and its risk factors in a young American Indian population. Data were collected by personal interview, medical history, physical examination (including anthropometric and blood pressure measurements and examination of the neck for AN), and laboratory analyses of blood specimens. Levels of insulin, lipids, and glucose were measured on fasting blood specimens. Diabetes status was determined according to the American Diabetes Association criteria.

RESULTS—A total of 2,205 participants were examined. Overall prevalence rates for AN and hyperinsulinemia were 34.2 and 47.2%, respectively. In general, the rates for both increased with age and degree of Indian heritage and were higher in female subjects, overweight/obese individuals, those with type 2 diabetes, and those with a parental history of type 2 diabetes. In addition, both had significantly higher age- and sex-adjusted means for selected known or suspected risk factors for type 2 diabetes. AN remained significantly associated with hyperinsulinemia (P = 0.0001) in multivariate analysis.

CONCLUSIONS—AN is independently associated with hyperinsulinemia and therefore may be useful as an early indicator of high risk for diabetes.
Urinary Transforming Growth Factor-β Excretion in Patients With Hypertension, Type 2 Diabetes, and Elevated Albumin Excretion Rate
Authors: Houlihan Christine A. , Akdeniz Aysel , Tsalamandris Con , Cooper Mark E. , Jerums George , Gilbert Richard E.
Published: March 2007

OBJECTIVE—Transforming growth factor-β (TGF-β) is a prosclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. In addition to high glucose, other factors implicated in renal fibrosis and increased TGF-β synthesis include angiotensin II and high dietary sodium intake. The aim of this study was to examine the effect of angiotensin receptor blockade (ARB) and dietary sodium restriction on the plasma concentration and urinary excretion of TGF-β in hypertensive patients with type 2 diabetes and elevated albumin excretion rate (AER).

RESEARCH DESIGN AND METHODS—Twenty-one subjects with hypertension and AER between 10 and 200 μg/min were randomized to receive either 50 mg losartan daily (n = 11) or placebo (n = 10). Drug therapy was given in two 4-week phases, separated by a 4-week washout period. In the last 2 weeks of each phase, patients were assigned to regular- or low-sodium diets in random order. Parameters measured at week 0 and 4 of each phase included plasma TGF-β concentration, TGF-β urinary excretion, AER, clinic mean arterial blood pressure, and urinary sodium excretion.

RESULTS—Plasma TGF-β was unaffected by losartan treatment or sodium intake. In the losartan group, urinary TGF-β excretion decreased by 23.2% (−39.2 and 13.6) [median (interquartile range)] and 38.5% (−46.8 and −6.1) in the regular- and low-sodium phases, respectively (P < 0.05 for drug effect). In the placebo group, median changes of 0.0% (−12.1 and 44.4) and 0.0% (−29.2 and 110.7) occurred in the regular- and low-sodium phases, respectively. Sodium restriction did not affect urinary TGF-β excretion in either losartan- or placebo-treated patients (P = 0.54 for overall dietary effect), and there was no evidence of interaction between drug and diet (P = 0.29).

CONCLUSIONS—In hypertensive type 2 diabetic patients with elevated AER, the ARB losartan, but not sodium restriction, reduced urinary TGF-β excretion. These data suggest that the renoprotective effects of losartan in patients with type 2 diabetes and nephropathy may include a reduction in renal TGF-β production.
Glucose Monitoring at the Arm
Authors: Jungheim Karsten , Koschinsky Theodor
Published: March 2007

OBJECTIVE—We have examined whether rapid changes in blood glucose (BG) result in clinically relevant differences between capillary BG values measured at the forearm and the fingertip and whether local rubbing of the skin before blood sampling can diminish such differences.

RESEARCH DESIGN AND METHODS—Capillary BG samples were collected every 15 min for 3–5 h from the fingertip and the forearm of 17 insulin-treated diabetic patients and analyzed with different glucose monitors (FreeStyle, One Touch Ultra, and Soft-Sense). In a subgroup of patients (n = 8), local rubbing of the forearm skin was performed before blood sampling. A rapid increase in BG was induced by oral administration of glucose, and subsequently, a rapid decrease in glucose was induced by intravenous administration of insulin.

RESULTS—In the fasting state, the BG values at the fingertip and at the forearm were similar (7.8 ± 2.4 vs. 7.2 ± 2.3 mmol/l, P = 0.06). However, during rapid increase in glucose, BG values at the fingertip were consistently higher than at the forearm (maximal difference 4.6 ± 1.2 mmol/l, P < 0.001). During rapid decrease in glucose, lower BG values were recorded at the fingertip (maximal difference to forearm 5.0 ± 1.0 mmol/l, P < 0.001). At the forearm, BG was delayed by a median of 35 min (P < 0.01) in relation to the fingertip. Rubbing of forearm skin decreased the observed differences but with a large intraindividual and interindividual variability. There were no obvious device-specific differences.

CONCLUSIONS—To avoid risky delays of hyperglycemia and hypoglycemia detection, BG monitoring at the arm should be limited to situations in which ongoing rapid changes in BG can be excluded.
Aspirin Use and Counseling About Aspirin Among Patients With Diabetes
Authors: Krein Sarah L. , Vijan Sandeep , Pogach Leonard M. , Hogan Mary M. , Kerr Eve A.
Published: March 2007

OBJECTIVE—Despite being a safe, effective therapy for lowering cardiovascular risk, only 20% of diabetic patients were using aspirin in the early 1990s. This study examines current physician practices and the use of aspirin therapy by individuals with diabetes.

RESEARCH DESIGN AND METHODS—A random sample of diabetic patients receiving care in the Department of Veterans Affairs health care system were surveyed during January-March 2000. The association between aspirin counseling, aspirin use, and reported coronary vascular disease (CVD) and classical CVD risk factors were examined using logistic regression. The effect of increasing aspirin use on risk of myocardial infarction (MI) and cardiovascular mortality was demonstrated by simulation.

RESULTS—Seventy-one percent of respondents reported being counseled about aspirin use, and 66% were taking daily aspirin. Individuals with known CVD were more likely to be counseled (odds ratio [OR] 4.9, 95% CI 2.9–8.1) and to use aspirin (2.1, 1.2–3.7). The factor most strongly associated with aspirin use was having been counseled about aspirin therapy by a doctor. We estimate that for this population, increasing daily aspirin use to 90% could prevent an additional 11,000 MIs and potentially save >8,000 lives.

CONCLUSIONS—Compared with previous reports, a substantial proportion of these diabetic patients have been counseled about and use aspirin. Most clinicians recognize aspirin as an important treatment for patients with preexisting coronary disease. However, since diabetes is now considered a CVD equivalent, it is imperative that clinicians include counseling about aspirin therapy as a care priority for all their diabetic patients, as this simple intervention may prevent many cardiovascular events and deaths.
The Performance of a Risk Score in Predicting Undiagnosed Hyperglycemia
Authors: Park P.J. , Griffin S.J. , Sargeant L. , Wareham N. J.
Published: March 2007

OBJECTIVE—Type 2 diabetes is a serious disease that is commonly undetected and for which screening is sometimes advocated. A number of risk factors are associated with prevalent undiagnosed diabetes. The use of routinely available information on these factors has been proposed as a simple and effective way of identifying individuals at high risk for having the disease. The objective of this study was to assess the effectiveness of the Cambridge risk score in a large and representative population.

RESEARCH DESIGN AND METHODS—A risk score derived from data in a previous study was tested for its ability to detect prevalent undiagnosed hyperglycemia as measured by a GHb ≥6.0, 6.5, or 7% in 6,567 subjects aged 39–78 years in the European Prospective Investigation of Cancer−Norfolk cohort.

RESULTS—For a specificity of 78%, the risk score predicted a GHb of ≥7.0% in subjects aged 39–78 years, with a sensitivity of 51% (95% CI 40–62). The areas under the receiver-operating characteristic (ROC) curve for GHb ≥6.0, 6.5, and 7% were 65.7% (63.8–67.6), 71.2% (68.4–75.2), and 74.2% (69.5–79.0), respectively. The area under the ROC curve was not significantly reduced if data on family and smoking history were unavailable for any of the cut-offs for GHb.

CONCLUSIONS—The risk score performed as well as other previously reported models in all age groups. We concluded that a simple risk score using data routinely available in primary care can identify people with an elevated GHb with reasonable sensitivity and specificity, and it could therefore form part of a strategy for early detection of type 2 diabetes.
Clinical, Autoimmune, and Genetic Characteristics of Adult-Onset Diabetic Patients With GAD Autoantibodies in Japan (Ehime Study)
Authors: Takeda Haruyo , Kawasaki Eiji , Shimizu Ikki , Konoue Etsushi , Fujiyama Masao , Murao Satoshi , Tanaka Kiyonobu , Mori Kennichi , Tarumi Yoshinao , Seto Isamu , Fujii Yasuhisa , Kato Kenichi , Kondo Shiori , Takada Yasuharu , Kitsuki Nobuaki , Kaino Yukikazu , Kida Kaichi , Hashimoto Naotake , Yamane Yukio , Yamawaki Takashi , Onuma Hiroshi , Nishimiya Tatsuya , Osawa Haruhiko , Saito Yasushi , Makino Hideichi
Published: March 2007

OBJECTIVE—To characterize the clinical, autoimmune, and genetic features in Japanese adult-onset diabetic patients with GAD autoantibodies.

RESEARCH DESIGN AND METHODS—GAD autoantibodies (GADab) were screened in 4,980 diabetic patients with age of onset >20 years in the hospital-based Ehime Study, and the GADab-positive (GADab+) patients were then divided into two groups according to their insulin secretion and compared with nondiabetic subjects. The insulin-deficient state was defined as <0.33 nmol/l serum C-peptide (CPR) at 2 h postprandial or 6 min after a 1-mg glucagon load.

RESULTS—GADab was detected in 188 (3.8%) of the 4,980 diabetic patients tested. Of these patients, 72 (38.3%) were classified as insulin deficient, 97 (51.6%) were classified as non–insulin deficient, and 19 (10.1%) were unclassified. The GADab+ insulin-deficient patients were characterized by young age at onset of diabetes, low BMI, low maximum BMI, and high levels of HbA1c. The prevalence of IA-2 autoantibodies and thyrogastric autoantibodies in the GADab+ insulin-deficient patients were significantly higher than those in the GADab+ non–insulin-deficient patients (P < 0.05). GADab+ patients with insulin deficiency had increased frequencies of HLA DRB1*0405-DQB1*0401, *0802-*0302, and *0901-*0303 haplotypes, whereas the frequency of only HLA DRB1*0405-DQB1*0401 was increased in the case of GADab+ non–insulin-deficient patients. Of note is the fact that the GADab+ non–insulin-deficient group did not differ from healthy control subjects with respect to type 1 diabetes protective haplotype HLA DRB1*1502-DQB1*0601. A total of 13% of the GADab+ patients with diabetes had genotypes comprising the DRB1*1501-DQB1*0602 or *1502-*0601 and were characterized by old age at onset of diabetes, high BMI, resistance to the insulin-deficient state, low titer of GADab, and low frequency of other organ-specific autoantibodies.

CONCLUSIONS—We conclude that GADab+ non–insulin-deficient patients differ from GADab+ patients with insulin deficiency with respect to clinical characteristics, humoral autoimmunity to other organ-specific autoantibodies, as well as HLA class II genes.
Effect of Orlistat in Overweight and Obese Patients With Type 2 Diabetes Treated With Metformin
Authors: Miles John M. , Leiter Lawrence , Hollander Priscilla , Wadden Thomas , Anderson James W. , Doyle Michael , Foreyt John , Aronne Louis , Klein Samuel
Published: March 2007

OBJECTIVE—The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A 1-year multicenter, randomized, double-blind, placebo-controlled trial of 120 mg orlistat t.i.d. (n = 249) or placebo (n = 254) combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes.

RESULTS—After 1 year of treatment, mean (±SE) weight loss was greater in the orlistat than in the placebo group (−4.6 ± 0.3% vs. −1.7 ± 0.3% of baseline wt, P < 0.001). Orlistat treatment caused a greater improvement in glycemic control than placebo, as evidenced by a greater reduction in serum HbA1c, adjusted for changes in metformin and sulfonylurea therapy (−0.90 ± 0.08 vs. −0.61 ± 0.08, P = 0.014); a greater proportion of patients achieving decreases in HbA1c of ≥0.5 and ≥1.0% (both P < 0.01); and a greater reduction in fasting serum glucose (−2.0 ± 0.2 vs. −0.7 ± 0.2 mmol/l, P = 0.001). Compared with the placebo group, patients treated with orlistat also had greater decreases in total cholesterol, LDL cholesterol, and systolic blood pressure (all P < 0.05). Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo (83 vs. 62%, P < 0.05), more subjects in the placebo group withdrew prematurely from the study than in the orlistat group (44 vs. 35%, P < 0.05).

CONCLUSIONS—Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control, serum lipid levels, and blood pressure in obese patients with type 2 diabetes who are being treated with metformin.
Development of a Prediction Equation for Insulin Sensitivity From Anthropometry and Fasting Insulin in Prepubertal and Early Pubertal Children
Authors: Huang Terry T.-K. , Johnson Maria S. , Goran Michael I.
Published: March 2007

OBJECTIVE—To test the utility of homeostasis model assessment (HOMA) in predicting insulin sensitivity [×10− 4 min−1/(μIU/ml)] in children and to develop and compare two new prediction equations for insulin sensitivity in children using demographic and anthropometric measures in the presence or absence of fasting insulin.

RESEARCH DESIGN AND METHODS—We studied 156 white and African-American children with complete data (mean age 9.7 ± 1.8 years, 87.8% Tanner Stage 1 or 2). For development of new equations, two-thirds of the children were randomly assigned to a development group, whereas the remaining children were assigned to a cross-validation group.

RESULTS—A modified HOMA equation accurately predicted insulin sensitivity, but its utility is similar to fasting insulin alone. Demographic and anthropometric measures alone did not predict insulin sensitivity accurately, even when precise measures of body composition were included in the prediction model. Ethnicity, calf skinfold, and fasting insulin together explained 73% of the variance in insulin sensitivity and accurately predicted insulin sensitivity. The regression of measured versus predicted insulin sensitivity in the cross-validation group was not significantly different from the line of identity (P > 0.05). Mean difference between measured and predicted insulin sensitivity was also not significant (P > 0.05). Some bias was apparent, particularly in white boys.

CONCLUSIONS—Ethnicity, calf skinfold, and fasting insulin can accurately predict insulin sensitivity with greater precision than HOMA or fasting insulin alone (R2 = 0.73). Future studies, however, are needed to examine whether a universal equation is possible. A cross-validated prediction equation may be useful in population-based studies when complex measures of insulin sensitivity are not available.
Aggressive Lipid Lowering Does Not Improve Endothelial Function in Type 2 Diabetes
Authors: van Venrooij Francine V. , van de Ree Marcel A. , Bots Michiel L. , Stolk Ronald P. , Huisman Menno V. , Banga J. D. ,   on behalf of the DALI Study Group
Published: March 2007

OBJECTIVE—Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might be an effective method to improve endothelial function in these patients.

RESEARCH DESIGN AND METHODS—A randomized, double-blind, placebo-controlled trial was completed to study the effect of 30 weeks’ administration of atorvastatin 10 mg and 80 mg on endothelial function, as assessed by B-mode ultrasound of the brachial artery, in 133 patients with type 2 diabetes without a history of cardiovascular disease.

RESULTS—Patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction; mean flow-mediated vasodilation (SD) was 3.16% (3.56), and mean response on sublingual nitroglycerin was 6.58% (6.04). Despite substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent vasodilatation was found (P > 0.8).

CONCLUSIONS—We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease. Aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction.