bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-Effectiveness of Early Irbesartan Treatment Versus Control (Standard Antihypertensive Medications Excluding ACE Inhibitors, Other Angiotensin-2 Receptor Antagonists, and Dihydropyridine Calcium Channel Blockers) or Late Irbesartan Treatment in Patients With Type 2 Diabetes, Hypertension, and Renal Disease
Authors: Palmer Andrew J. , Annemans Lieven , Roze Stéphane , Lamotte Mark , Lapuerta Pablo , Chen Roland , Gabriel Sylvie , Carita Paulo , Rodby Roger A. , de Zeeuw Dick , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—The aim of this study was to determine the most cost-effective time point for initiation of irbesartan treatment in hypertensive patients with type 2 diabetes and renal disease.

RESEARCH DESIGN AND METHODS—This study was a Markov model–simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease, and death in hypertensive patients with type 2 diabetes. Two irbesartan strategies were created: early irbesartan 300 mg daily (initiated with microalbuminuria) and late irbesartan (initiated with overt nephropathy). These strategies were compared with control, which consisted of antihypertensive therapy with standard medications (excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) with comparable blood pressure control, initiated at microalbuminuria. Transition probabilities were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial, and other published sources. Costs and life expectancy, discounted at 3% yearly, were projected over 25 years for 1,000 simulated patients using a third-party payer perspective in a U.S. setting.

RESULTS—Compared with control, early and late irbesartan treatment in 1,000 patients were projected to save (mean ± SD) $11.9 ± 3.3 million and $3.3 ± 2.7 million, respectively. Early use of irbesartan added 1,550 ± 270 undiscounted life-years (discounted 960 ± 180), whereas late irbesartan added 71 ± 40 life-years (discounted 48 ± 27) in 1,000 patients. Early irbesartan treatment was superior under a wide-range of plausible assumptions.

CONCLUSIONS—Early irbesartan treatment was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria. Later use of irbesartan in overt nephropathy is also superior to standard care, but irbesartan should be started earlier and continued long term.
Reduced Forearm Blood Flow in Children and Adolescents With Type 1 Diabetes (Measured by Near-Infrared Spectroscopy)
Authors: Pichler Gerhard , Urlesberger Berndt , Jirak Paul , Zotter Heinz , Reiterer Elke , Müller Wilhelm , Borkenstein Martin
Published: March 2007

OBJECTIVE—The aim of this study was to measure forearm blood flow (FBF) to detect any possible changes that might indicate vascular disorders in children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—FBF was measured by near-infrared spectroscopy (NIRS), venous occlusion at rest, and after handgrip exercise. A total of 40 children and adolescents with type 1 diabetes and 40 healthy children and adolescents (6–18 years) were matched for age and sex for comparison.

RESULTS—In the diabetic group (age 12.79 ± 2.9 years, duration of diabetes 51.5 ± 36 months), FBF at rest was significantly lower (1.39 ± 0.76 ml · 100 g muscle–1 · min–1) than in control subjects (age 12.66 ± 2.9 years, FBF at rest 1.90 ± 1.19 ml · 100 g muscle–1 · min–1). After exercise, FBF increased significantly less in the diabetic group (0.70 ± 0.82 ml · 100 g muscle–1 · min–1) compared with the control subjects (1.15 ± 1.05 ml · 100 g muscle–1 · min–1). FBF at rest decreased with increasing age in both groups. The change in FBF after exercise was independent of age in the diabetic group and increased with increasing age in control subjects. FBF is reduced with impaired hyperemic response after exercise in children and adolescents with type 1 diabetes.

CONCLUSIONS—These data suggest that vascular disorders in childhood are detectable noninvasively by NIRS.
Prevalence and Factor Analysis of Metabolic Syndrome in an Urban Korean Population
Authors: Oh Jee-Young , Hong Young Sun , Sung Yeon-Ah , Barrett-Connor Elizabeth
Published: March 2007

OBJECTIVE—The aim of this study was to explore the prevalence and pattern of the metabolic syndrome and its association with hyperinsulinemia in an urban Korean population of 269 men and 505 women.

RESEARCH DESIGN AND METHODS—The National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines were used to calculate the sex-specific prevalence of the metabolic syndrome. After excluding individuals taking medication for hypertension, diabetes, or dyslipidemia, we used factor analysis to examine the pattern of the metabolic syndrome in 206 men and 449 women.

RESULTS—The prevalence of metabolic syndrome was 16.0% in men and 10.7% in women aged 30–80 years. However, ATP III criteria for central obesity are not optimal for an Asian-Pacific population; when waist circumference is reduced from 102 to 90 cm in men and 88 to 80 cm in women, the prevalence of the metabolic syndrome increased to 29.0 and 16.8%, respectively. Sex-specific factor analysis showed four factors in men (obesity, glucose intolerance, hypertension, and dyslipidemia) and three in women (obesity-hypertension, glucose intolerance, and obesity-dyslipidemia). Insulin resistance estimated from fasting insulin levels clustered with three of the four factors in men and two of the three factors in women. By ATP III or Asian-Pacific waist circumference criteria, the prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance, which was estimated by a homeostasis model assessment.

CONCLUSIONS—The metabolic syndrome is common in an urban Korean population when using Asian-Pacific waist criteria. The prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance.
Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes
Authors: Awata Takuya , Neda Tamotsu , Iizuka Hiroyuki , Kurihara Susumu , Ohkubo Tomoko , Takata Nobuki , Osaki Masataka , Watanabe Masaki , Nakashima Youhei , Sawa Takahiro , Inukai Kouichi , Inoue Ikuo , Shibuya Masayuki , Mori Keisuke , Yoneya Shin , Katayama Shigehiro
Published: March 2007

OBJECTIVE—We examined the endothelial nitric oxide (eNOS) gene polymorphisms to assess its possible association with diabetic retinopathy and macular edema.

RESEARCH DESIGN AND METHODS—A total of 226 patients with type 2 diabetes and 186 healthy subjects were studied. Type 2 diabetic patients consisted of 110 patients without retinopathy, 46 patients with nonproliferative diabetic retinopathy, and 71 patients with proliferative diabetic retinopathy. Diabetic macular edema was present in 48 patients. Three polymorphisms of the eNOS gene were determined: T-786C in the promoter region, 27-bp repeat in intron 4, and Glu298Asp in exon 7.

RESULTS—Close linkage disequilibrium was observed between the T-786C polymorphism and the 27-bp repeat, as has been previously reported, but Glu298Asp was not in linkage disequilibrium with the other two polymorphisms. The eNOS gene polymorphisms were not significantly associated with the presence of retinopathy or with retinopathy severity or type 2 diabetes itself. However, by both association study and multiple logistic regression analysis, the T-786C and 27-bp repeat polymorphisms were significantly associated with a risk of developing macular edema with the −786C allele and the “a” allele increasing the risk.

CONCLUSIONS—The present study suggests that the eNOS gene is a novel genetic risk factor for diabetic macular edema. The eNOS gene polymorphisms may contribute to the development of macular edema by impairing basal eNOS expression and resulting in the breakdown of the blood-retina barrier.
Who Has Diabetes? Best Estimates of Diabetes Prevalence in the Department of Veterans Affairs Based on Computerized Patient Data
Authors: Miller Donald R. , Safford Monika M. , Pogach Leonard M.
Published: March 2007

OBJECTIVE—To optimize methods for identifying patients with diabetes based on computerized records and to obtain best estimates of diabetes prevalence in Department of Veterans Affairs (VA) patients.

RESEARCH DESIGN AND METHODS—The VA Diabetes Epidemiology Cohort (DEpiC) is a linked national database of all VA patients since 1998 with data from VA medical visits, Medicare claims, pharmacy and laboratory records, and patient surveys. Using DEpiC, we examined concordance of diabetes indicators, including ICD-9-CM codes (250.xx), prescription drug treatment, HbA1c tests, and patient self-report. We determined the optimal criterion for identifying diabetes and used it in estimating diabetes prevalence in the VA.

RESULTS—The best criterion was a prescription for a diabetes medication in the current year and/or 2+ diabetes codes from inpatient and/or outpatient visits (VA and Medicare) over a 24-month period. This definition had high sensitivity (93%) and specificity (98%) against patient self-report, and reasonable rates of HbA1c testing (75%). HbA1c testing alone added few additional cases, and a single diagnostic code added many patients, but without confirmation (reduced specificity). However, including codes from Medicare was critical. Applying this definition for 1998–2000, we identified an average of 500,000 VA patients with diabetes per year. We also estimated high and increasing diabetes prevalence rates of 16.7% in FY1998, 18.6% in FY1999, and 19.6% in FY2000 and an incidence estimated to be ∼2% per year.

CONCLUSIONS—Development and evaluation of methodology for analyzing computerized patient data can improve the identification of patients with diabetes. The increasing high prevalence of diabetes in VA patients will present challenges for clinicians and health system management.
Cardiovascular Risk Factor Control Among Veterans With Diabetes
Authors: Smith Nicholas L. , Chen Leway , Au David H. , McDonell Mary , Fihn Stephan D.
Published: March 2007

OBJECTIVE—To describe the extent to which hyperglycemia, hypertension, and dyslipidemia are currently detected, treated, and controlled in U.S. veterans with diabetes with and without ischemic heart disease (IHD).

RESEARCH DESIGN AND METHODS—A cohort of 3,769 veterans who self-reported diabetes and who received all health care from the Veterans Administration (VA) medical centers were selected from subjects enrolled in the Ambulatory Care Quality Improvement Project, a randomized health services intervention at seven VA primary care clinics. IHD was defined by a self-reported history of myocardial ischemia, infarction, or revascularization. Mean values of HbA1c, blood pressure, and cholesterol subfractions were collected from computerized laboratory databases. Medication data were collected from computerized pharmacy databases.

RESULTS—Mean HbA1c and optimal control (HbA1c <7%) did not differ for those without and with IHD: 8.1 vs. 8.0%, and 26 vs. 24%, respectively. Veterans with IHD were more likely to have hypertension (73 vs. 64%), to be treated (88 vs. 78%), and to have optimal blood pressure control (19 vs. 10%) compared with veterans without IHD (all P values <0.01). Veterans with IHD were more likely to have dyslipidemia (81 vs. 53%), were equally likely to be treated (54 vs. 50%), and were more likely to have optimal LDL levels (30 vs. 16%) compared with veterans without IHD, all P values <0.01.

CONCLUSIONS—Optimal cardiovascular risk factor control was the exception in this cohort of diabetic veterans attending primary care clinics. More aggressive management of cardiovascular risk factors in veterans with diabetes may be warranted, especially among those without prevalent IHD.
Family History of Type 2 Diabetes Is Associated With Decreased Insulin Sensitivity and an Impaired Balance Between Insulin Sensitivity and Insulin Secretion in White Youth
Authors: Arslanian Silva A. , Bacha Fida , Saad Rola , Gungor Neslihan
Published: March 2007

OBJECTIVE—Family history of type 2 diabetes is a major risk factor for type 2 diabetes in youth, which is increasing. This investigation aimed to evaluate the impact of family history of type 2 diabetes on insulin secretion relative to insulin sensitivity in healthy children. β-Cell compensation for insulin sensitivity was calculated as the product of insulin sensitivity × first-phase insulin secretion, termed glucose disposition index (GDI).

RESEARCH DESIGN AND METHODS—A total of 28 healthy white children (12 boys and 16 girls; 12.1 ± 0.5 years of age) with a positive family history of type 2 diabetes and 26 healthy white children (13 boys and 13 girls; 11.5 ± 0.4 years of age) with a negative family history of type 2 diabetes underwent a 3-h 40 mU · m−2 · min−1 hyperinsulinemic-euglycemic clamp to assess insulin sensitivity and clearance and a 2-h hyperglycemic clamp to assess insulin secretion. Body composition and visceral adiposity were evaluated with dual-energy X-ray absorptiometry and computed tomography at the L4-L5 intervertebral space.

RESULTS—Insulin sensitivity was lower in children with a family history of type 2 diabetes versus children without a family history (8.8 ± 0.9 vs. 12.2 ± 1.1 μmol · kg−1 · min−1 per pmol/l, P = 0.02). Similarly, insulin clearance was lower. First- and second-phase insulin levels were not different between groups with and without a positive family history. The GDI was lower in youth with versus youth without a positive family history (4.1 ± 0.3 vs. 5.2 ± 0.5 mmol · kg−1 · min−1, P = 0.039). IGF binding protein-1 (IGFBP-1) was 60% lower in youth with versus youth without the positive family history.

CONCLUSIONS—These results demonstrate that family history of type 2 diabetes in white children is associated with decreased insulin sensitivity and clearance, decreased IGFBP-1, and an impaired relationship between insulin action and β-cell compensation. Detection of these alterations in hormonal and metabolic parameters in children with a positive family history suggests that at least some of the determinants of GDI are genetic/heritable.
α-Glucosidase Inhibitors for Patients With Type 2 Diabetes
Authors: van de Laar Floris A. , Lucassen Peter L. , Akkermans Reinier P. , van de Lisdonk Eloy H. , Rutten Guy E. , van Weel Chris
Published: March 2007

OBJECTIVE—To review the effects of monotherapy with α-glucosidase inhibitors (AGIs) for patients with type 2 diabetes, with respect to mortality, morbidity, glycemic control, insulin levels, plasma lipids, body weight, and side effects.

RESEARCH DESIGN AND METHODS—We systematically searched the Cochrane Central register of Controlled Trials, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, and reference lists, and we contacted experts and manufacturers. Inclusion criteria were randomized controlled trials of at least 12 weeks’ duration, AGI monotherapy compared with any intervention, and one of the following outcome measures: mortality, morbidity, GHb, blood glucose, lipids, insulin levels, body weight, or side effects. Two independent reviewers assessed all abstracts, extracted all data, and assessed quality. We contacted all authors for data clarification. Continuous data were expressed as weighted mean differences and analyzed with a random-effects model. Possible influences of study characteristics and quality were assessed in sensitivity and meta-regression analyses.

RESULTS—Forty-one studies were included in the review (30 acarbose, 7 miglitol, 1 voglibose, and 3 combined), and heterogeneity was limited. We found no evidence for an effect on mortality or morbidity. Compared with placebo, AGIs had a beneficial effect on GHb (acarbose −0.77%; miglitol −0.68%), fasting and postload blood glucose and postload insulin. With acarbose dosages higher than 50 mg t.i.d., the effect on GHb was the same, but the occurrence of side effects increased. Acarbose decreased the BMI by 0.17 kg/m2 (95% CI 0.08–0.26). None of the AGIs had an effect on plasma lipids. Compared with sulfonylurea, AGIs seemed inferior with respect to glycemic control, but they reduced fasting and postload insulin levels. For comparisons with other agents, little data were available.

CONCLUSIONS—We found no evidence for an effect on mortality or morbidity. AGIs have clear beneficial effects on glycemic control and postload insulin levels but not on plasma lipids. There is no need for dosages higher than 50 mg acarbose t.i.d.
Relationships Between Hyperglycemia and Cognitive Performance Among Adults With Type 1 and Type 2 Diabetes
Authors: Cox Daniel J. , Kovatchev Boris P. , Gonder-Frederick Linda A. , Summers Kent H. , McCall Anthony , Grimm Kevin J. , Clarke William L.
Published: March 2007

OBJECTIVE—Hyperglycemia is a common event among patients with type 1 and type 2 diabetes. While the cognitive-motor slowing associated with hypoglycemia is well documented, the acute effects of hyperglycemia have not been studied extensively, despite patients’ reports of negative effects. This study prospectively and objectively assessed the effects of hyperglycemia on cognitive-motor functioning in subjects’ natural environment.

RESEARCH DESIGN AND METHODS—Study 1 investigated 105 adults with type 1 diabetes (mean age 37 years and mean duration of diabetes 20 years), study 2 investigated 36 adults with type 2 diabetes (mean age 50 years and mean duration of diabetes 10 years), and study 3 investigated 91 adults with type 1 diabetes (mean age 39 years and mean duration of diabetes 20 years). Subjects used a hand-held computer for 70 trials over 4 weeks, which required them to complete various cognitive-motor tasks and then measure and enter their current blood glucose reading.

RESULTS—Hyperglycemia (blood glucose >15 mmol/l) was associated with slowing of all cognitive performance tests (P < 0.02) and an increased number of mental subtraction errors for both type 1 and type 2 diabetic subjects. The effects of hyperglycemia were highly individualized, impacting ∼50% of the subjects.

CONCLUSIONS—Acute hyperglycemia is not a benign event for many individuals with diabetes, but it is associated with mild cognitive dysfunction.
Mothers’ Experiences of Serious Life Events Increase the Risk of Diabetes-Related Autoimmunity in Their Children
Authors: Sepa Anneli , Frodi Ann , Ludvigsson Johnny
Published: March 2007

OBJECTIVE—Stressful life events have been shown to constitute a risk factor for type 1 diabetes during childhood. Our aim was to investigate in the general child population (i.e., irrespective of genetic risk for type 1 diabetes) whether mothers’ experiences of serious life events, such as divorce and violence, were associated with diabetes-related autoimmunity in their children at age 2.5 years.

RESEARCH DESIGN AND METHODS—The study cohort was comprised of the first 5,986 consecutive children and their families from the prospective population-based All Babies in Southeast Sweden project for whom 2.5-year study data were available. Data were drawn from parental questionnaires that included questions about experiences of serious life events and the blood samples taken from the children when the children were age 2.5 years. The blood samples were analyzed for diabetes-related autoantibodies against tyrosine phosphatase and GAD.

RESULTS—Mothers’ experiences of divorce (odds ratio 3.6, 95% CI 1.4–9.6, P < 0.05) and violence (2.9, 1.0–7.8, P < 0.05) were associated with diabetes-related autoimmunity in the children, independent of a family history of type 1 diabetes.

CONCLUSIONS—The results support the β-cell stress hypothesis and suggest that maternal experiences of serious life events such as divorce and violence seem to be involved in the induction or progression of diabetes-related autoimmunity in children at age 2.5 years, independent of family history of type 1 diabetes.
Glycemic Status and Development of Kidney Disease
Authors: Fox Caroline S. , Larson Martin G. , Leip Eric P. , Meigs James B. , Wilson Peter W.F. , Levy Daniel
Published: March 2007

OBJECTIVE—Diabetes is a major risk factor for the development of kidney disease and is the leading cause of end-stage renal disease in the U.S. Whether pre-diabetes is associated with the development of kidney disease is unclear.

RESEARCH DESIGN AND METHODS—Subjects free of chronic kidney disease (CKD) were drawn from the Framingham Heart Study offspring cohort (1991–1995), given an oral glucose tolerance test, and followed for an average of 7 years for development of CKD (glomerular filtration rate [GFR] of <59 ml/min per 1.73 m2 in women and <64 ml/min per 1.73 m2 in men). Multivariable logistic regression models, adjusted for cardiovascular disease risk factors including age, sex, hypertension, smoking, BMI, total and HDL cholesterol levels, and prevalent myocardial infarction or congestive heart failure, were used to estimate the odds of patients developing kidney disease among glycemic categories.

RESULTS—Of 2,398 subjects (53% women; mean age 54 years), 63% were normoglycemic, 29% had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), 3.4% were newly diabetic, and 4.6% had known diabetes. By glycemic category, mean GFR at follow-up was 87, 85, 82, and 78 ml/min per 1.73 m2, respectively. The fully adjusted odds of developing CKD were 0.98 (95% CI 0.67–1.45), 1.71 (95% CI 0.83–3.55), and 1.93 (95% CI 1.06–3.49) among those with IFG or IGT, newly diagnosed diabetes, or known diabetes, respectively, compared with those who were normoglycemic at baseline. Among participants without diabetes, metabolic syndrome was not associated with kidney disease at follow-up (odds ratio 1.46, P = 0.06).

CONCLUSIONS—Cardiovascular disease risk factors explain much of the relationship between prediabetes and the development of chronic kidney disease. Clinical trials are warranted to determine whether vascular risk factor modification can slow the decline of kidney function among those with pre-diabetes.
Incidence of Type 1 and Type 2 Diabetes in Adults Aged 30–49 Years
Authors: Bruno Graziella , Runzo Cristina , Cavallo-Perin Paolo , Merletti Franco , Rivetti Marina , Pinach Silvia , Novelli Giulia , Trovati Mariella , Cerutti Franco , Pagano Gianfranco ,   for the Piedmont Study Group for Diabetes Epidemiology
Published: March 2007

OBJECTIVE—Incidence of type 1 diabetes is considered to be low in adults, but no study has been performed in Mediterranean countries.

RESEARCH DESIGN AND METHODS—We extended the study base of the registry of the province of Turin, Italy, to subjects aged 30–49 years in the period 1999–2001 to estimate the incidences of type 1 and type 2 diabetes. Diagnosis of type 1 diabetes was based on permanent insulin treatment or a fasting C-peptide level ≤0.20 nmol/l or islet cell (ICA) or GAD (GADA) antibody positivities.

RESULTS—We identified 1,135 case subjects with high completeness of ascertainment (99%), giving an incidence rate of 58.0 per 100,000 person-years (95% CI 54.7–61.5). The incidence of type 1 diabetes was 7.3 per 100,000 person-years (6.2–8.6), comparable with the rates in subjects aged 0–14 and 15–29 years (10.3 [9.5–11.2] and 6.8 [6.3–7.4]). Male subjects had a higher risk than female subjects for both type 1 (rate ratio [RR] 1.70 [95% CI 1.21–2.38]) and type 2 (2.10 [1.84–2.40]) diabetes. ICA and/or GADA positivities were found in 16% of the cohort. In logistic regression, variables independently associated with autoimmune diabetes were age 30–39 years (odds ratio [OR] 2.39 [95% CI 1.40–4.07]), fasting C-peptide <0.60 nmol/l (3.09 [1.74–5.5]), and BMI <26 kg/m2 (2.17 [1.22–3.85]).

CONCLUSIONS—Risk of type 1 diabetes between age 30 and 49 years is similar to that found in the same area between age 15 and 29 years. Further studies are required to allow geographical comparisons of risks of both childhood and adulthood autoimmune diabetes, the latter being probably higher than previously believed.
Use of the Patient Assessment of Chronic Illness Care (PACIC) With Diabetic Patients
Authors: Glasgow Russell E. , Whitesides Holly , Nelson Candace C. , King Diane K.
Published: March 2007

OBJECTIVE—There is a dearth of information on the extent to which diabetic patients receive care congruent with the chronic care model (CCM) and evidence-based behavioral counseling. This study evaluates a new instrument to fill this gap.

RESEARCH DESIGN AND METHODS—A heterogeneous sample of 363 type 2 diabetic patients completed the original Patient Assessment of Chronic Illness Care (PACIC), along with additional items that allowed it to be scored according to the “5As” (ask, advise, agree, assist, and arrange) model of behavioral counseling. We evaluated relationships between survey scores and patient characteristics, quality of diabetes care, and self-management.

RESULTS—Findings replicated those of the initial PACIC validation study but with a much larger sample of diabetic patients and more Latinos. Areas of CCM activities reported least often were goal setting/intervention tailoring and follow-up/coordination. The 5As scoring revealed that patients were least likely to receive assistance with problem solving and arrangement of follow-up support. Few demographic or medical characteristics were related to PACIC or 5As scores, but survey scores were significantly related to quality of diabetes care received and level of physical activity.

CONCLUSIONS—The PACIC and the new 5As scoring method appear useful for diabetic patients. Its use is encouraged in future research and quality improvement studies.
Elevated Homocysteine as a Risk Factor for the Development of Diabetes in Women With a Previous History of Gestational Diabetes Mellitus
Authors: Cho Nam H. , Lim Soo , Jang Hak C. , Park Hae K. , Metzger Boyd E.
Published: March 2007

OBJECTIVE—To investigate the potential use of the plasma homocysteine level as a predictor of diabetes in women with a previous history of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS—At 6 weeks’ postpartum, baseline examination was performed in 177 GAD-negative subjects. Of these subjects, 7 who were diagnosed with diabetes at baseline were excluded from further evaluation, and 170 with normal or impaired glucose tolerance (IGT) at baseline were followed annually over 4 years. The follow-up examinations included 2-h 75-g oral glucose tolerance tests (OGTTs), lipid profiles, homocysteine levels, anthropometric measurements, history taking, diet, and lifestyle. During the OGTTs, insulin and glucose levels were assayed every 30 min. Plasma homocysteine levels were determined by ion-exchange chromatography.

RESULTS—Of the 170 women, 18 (10.6%) converted to diabetes during the 4-year follow-up period. Mean age, BMI, fasting insulin, and total cholesterol at baseline (6 weeks’ postpartum test) were similar in the three study groups (i.e., normal, IGT, and diabetes). Fasting glucose levels, insulin-to-glucose ratios, and homocysteine levels were significantly higher in the diabetic group (P < 0.05). Higher glucose at the time of the diagnosis of GDM and higher homocysteine levels at baseline were independently associated with the onset of postpartum diabetes. These relationships were independent of age, BMI, and family history of diabetes.

CONCLUSIONS—This prospective study identified homocysteine level as a significant risk factor for development of diabetes in women with previous GDM.
Adherence to Statin Therapy and LDL Cholesterol Goal Attainment by Patients With Diabetes and Dyslipidemia
Authors: Parris Elizabeth S. , Lawrence David B. , Mohn Lisa A. , Long Laura B.
Published: March 2007

OBJECTIVE—The purpose of this study was to assess the relationship between adherence to statin therapy and LDL cholesterol goal achievement in patients with diabetes and dyslipidemia.

RESEARCH DESIGN AND METHODS—The records of patients being medically treated for dyslipidemia in a managed care diabetes program from January 2001 to December 2002 were used to assess LDL cholesterol goal attainment (<100 mg/dl) and to compute a 9-month medication possession ratio (percentage of days when medication was available [MPR], beginning with the first prescription in the database).

RESULTS—A total of 653 patient records was analyzed. The average MPR was significantly higher for men than for women (0.75 vs. 0.66, P < 0.05). Overall, 44% (n = 290) of the patients achieved an LDL cholesterol level <100 mg/dl (52% of men and 37% of women, P < 0.05). A significant correlation emerged between MPR and plasma LDL cholesterol (P < 0.001), and MPR was significantly higher in patients who achieved the LDL cholesterol target than in those who did not (0.82 vs. 0.61, P < 0.05).

CONCLUSIONS— Although statins are highly effective for decreasing LDL cholesterol levels in patients with dyslipidemia, including those with diabetes, failure to reach LDL cholesterol targets remains common. Adherence to statin therapy, as reflected by MPR, is closely related to LDL cholesterol goal attainment in patients with diabetes and dyslipidemia. The probability of goal achievement appears to increase substantially when the MPR is >0.80. Pharmacy records can be used to identify patients who are poorly compliant with statin therapy and at high risk for failure to attain LDL cholesterol goals. Because outcomes are directly related to patients’ medication-taking behavior, when clinical goals (such as serum cholesterol levels) are not being reached, adherence should be the first item assessed by the clinician.
The Association Between Glucose Abnormalities and Heart Failure in the Population-Based Reykjavík Study
Authors: Thrainsdottir Inga S. , Aspelund Thor , Thorgeirsson Gudmundur , Gudnason Vilmundur , Hardarson Thordur , Malmberg Klas , Sigurdsson Gunnar , Rydén Lars
Published: March 2007

OBJECTIVE—Diabetes is an independent risk factor for heart failure, whereas the relation between heart failure and abnormal glucose regulation (AGR) needs further evaluation. We studied this combination in the Reykjavík Study.

RESEARCH DESIGN AND METHODS—The Reykjavík Study, a population-based cohort study during 1967–1997, recruited 19,381 participants aged 33–84 years who were followed until 2002. Oral glucose tolerance tests and chest X-rays were obtained from all participants. Cases were defined in accordance with World Health Organization criteria for type 2 diabetes or AGR (impaired glucose tolerance or impaired fasting glucose) and European Society of Cardiology guidelines for heart failure.

RESULTS—The overall prevalence of type 2 diabetes and heart failure was 0.5% in men and 0.4% in women, while AGR and heart failure were found in 0.7% of men and 0.6% of women. Among participants with normal glucose regulation, heart failure was diagnosed in 3.2% compared with 6.0 and 11.8% among those with AGR and type 2 diabetes, respectively. The prevalence of type 2 diabetes in the age-group 45–65 years increased in both sexes during the period (P for trend = 0.007). The odds ratio was 2.8 (95% CI 2.2–3.6) for the association between type 2 diabetes and heart failure and 1.7 (1.4–2.1) between AGR and heart failure.

CONCLUSIONS—There is a strong association between any form of glucometabolic perturbation and heart failure. Future studies in this field should focus on all types of glucose abnormalities rather than previously diagnosed diabetes only.
Assessing Psychosocial Distress in Diabetes
Authors: Polonsky William H. , Fisher Lawrence , Earles Jay , Dudl R. James , Lees Joel , Mullan Joseph , Jackson Richard A.
Published: March 2007

OBJECTIVE—The purpose of this study was to describe the development of the Diabetes Distress Scale (DDS), a new instrument for the assessment of diabetes-related emotional distress, based on four independent patient samples.

RESEARCH DESIGN AND METHODS—In consultation with patients and professionals from multiple disciplines, a preliminary scale of 28 items was developed, based a priori on four distress-related domains: emotional burden subscale, physician-related distress subscale, regimen-related distress subscale, and diabetes-related interpersonal distress. The new instrument was included in a larger battery of questionnaires used in diabetes studies at four diverse sites: waiting room at a primary care clinic (n = 200), waiting room at a diabetes specialty clinic (n = 179), a diabetes management study program (n = 167), and an ongoing diabetes management program (n = 158).

RESULTS—Exploratory factor analyses revealed four factors consistent across sites (involving 17 of the 28 items) that matched the critical content domains identified earlier. The correlation between the 28-item and 17-item scales was very high (r = 0.99). The mean correlation between the 17-item total score (DDS) and the four subscales was high (r = 0.82), but the pattern of interscale correlations suggested that the subscales, although not totally independent, tapped into relatively different areas of diabetes-related distress. Internal reliability of the DDS and the four subscales was adequate (α > 0.87), and validity coefficients yielded significant linkages with the Center for Epidemiological Studies Depression Scale, meal planning, exercise, and total cholesterol. Insulin users evidenced the highest mean DDS total scores, whereas diet-controlled subjects displayed the lowest scores (P < 0.001).

CONCLUSIONS—The DDS has a consistent, generalizable factor structure and good internal reliability and validity across four different clinical sites. The new instrument may serve as a valuable measure of diabetes-related emotional distress for use in research and clinical practice.
Youth Type 2 Diabetes
Authors: Gungor Neslihan , Bacha Fida , Saad Rola , Janosky Janine , Arslanian Silva
Published: March 2007

OBJECTIVE—This study evaluates insulin sensitivity, pancreatic β-cell function (BCF), and the balance between the two in youth with type 2 diabetes and assesses the relationship of diabetes duration and HbA1c to insulin sensitivity and BCF.

RESEARCH DESIGN AND METHODS—The subjects were 14 adolescents with type 2 diabetes and 20 obese control subjects of comparable age, BMI, body composition, and puberty. Insulin sensitivity was evaluated with a 3-h hyperinsulinemic (80 mU · m–2 · min–1) euglycemic clamp. First-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS) were evaluated with a 2-h hyperglycemic (12.5 mmol/l) clamp. Fasting glucose rate of appearance was determined with the use of [6,6-2H2]glucose.

RESULTS—Fasting glucose rate of appearance was higher in type 2 diabetic patients than in obese control subjects (16.5 ± 1.1 vs. 12.3 ± 0.5 μmol · kg–1 · min–1; P = 0.002). Insulin sensitivity was lower in type 2 diabetic patients than in obese control subjects (1.0 ± 0.1 vs. 2.0 ± 0.2 μmol · kg–1 · min–1 per pmol/l; P = 0.001). Fasting insulin was higher in type 2 diabetic patients than in obese control subjects (289.8 ± 24.6 vs. 220.2 ± 18.0 pmol/l; P = 0.007), and FPIS and SPIS were lower (FPIS: 357.6 ± 42.0 vs. 1,365.0 ± 111.0 pmol/l; SPIS: 652.2 ± 88.8 vs. 1,376.4 ± 88.8 pmol/l; P < 0.001 for both). The glucose disposition index (GDI = insulin sensitivity × FPIS) was ∼86% lower in type 2 diabetic patients than in obese control subjects. HbA1c correlated with FPIS (r = −0.61, P = 0.025) with no relationship to insulin sensitivity.

CONCLUSIONS—Despite the impairment in both insulin sensitivity and BCF in youth with type 2 diabetes, the magnitude of the derangement is greater in BCF than insulin sensitivity when compared with that in obese control subjects. The inverse relationship between BCF and HbA1c may either reflect the impact of deteriorating BCF on glycemic control or be a manifestation of a glucotoxic phenomenon on BCF. Future studies in youth type 2 diabetes should target the natural course of β-cell failure and means of retarding and/or preventing it.
Autoantibodies Against Oxidized LDLs and Atherosclerosis in Type 2 Diabetes
Authors: Piarulli Francesco , Lapolla Annunziata , Sartore Giovanni , Rossetti Ciro , Bax Giuseppe , Noale Marianna , Minicuci Nadia , Fiore Cristina , Marchioro Lucio , Manzato Enzo , Fedele Domenico
Published: March 2007

OBJECTIVE—The aim of our study was to examine, in type 2 diabetic patients, the relationship between autoantibodies against oxidatively modified LDL (oxLDL Ab) and two indexes of atherosclerosis, intimal-medial thickness of the common carotid artery (CCA-IMT), which reflects early atherosclerosis, and the ankle-brachial index (ABI), which reflects advanced atherosclerosis.

RESEARCH DESIGN AND METHODS—Thirty newly diagnosed type 2 diabetic patients, 30 type 2 diabetic patients with long duration of disease, and 56 control subjects were studied. To detect oxLDL Ab, the ImmunoLisa Anti-oxLDL Antibody ELISA was used. ABI was estimated at rest by strain-gauge plethysmography. Carotid B-mode imaging was performed on a high-resolution imaging system (ATL HDI 5000).

RESULTS—In patients with long duration of disease, IgG oxLDL Ab were significantly higher and ABI significantly lower compared with the other two groups. We found a correlation between IgG oxLDL Ab and CCA-IMT in all diabetic patients. A significant inverse correlation between IgG oxLDL Ab and ABI only in patients with long duration of disease was seen, demonstrating a close relationship between these autoantibodies and advanced atherosclerosis.

CONCLUSIONS—IgG OxLDL Ab may be markers of the advanced phase of the atherosclerotic process and the response of the immunological system to the oxLDL, which are present within atherosclerotic lesions.
Leisure Time Physical Activity Is Associated With Poor Glycemic Control in Type 1 Diabetic Women
Authors: Wadén Johan , Tikkanen Heikki , Forsblom Carol , Fagerudd Johan , Pettersson-Fernholm Kim , Lakka Timo , Riska Mikael , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: March 2007

OBJECTIVE—We studied the association between leisure time physical activity (LTPA) and glycemic control, insulin dose, and estimated glucose disposal rate (eGDR) in type 1 diabetes.

RESEARCH DESIGN AND METHODS—This is a cross-sectional study of 1,030 type 1 diabetic patients participating in the Finnish Diabetic Nephropathy Study, a nationwide multicenter study. LTPA was assessed by a validated 12-month questionnaire and expressed in metabolic equivalent (MET) units. Patients were grouped as sedentary (LTPA <10 MET h/week, n = 247), moderately active (LTPA 10–40 MET h/week, n = 568), and active (LTPA >40 MET h/week, n = 215). Outcome measures were HbA1c, insulin dose, and eGDR (estimate of insulin sensitivity based on waist-to-hip ratio, hypertension, and HbA1c).

RESULTS—LTPA correlated with HbA1c in women (r = −0.12, P = 0.007) but not in men (r = −0.03, P = 0.592). Sedentary women had higher HbA1c than moderately active and active women: 8.8 ± 1.4% vs. 8.3 ± 1.4% vs. 8.3 ± 1.4% (P = 0.004), whereas HbA1c in men was 8.4 ± 1.3% vs. 8.2 ± 1.4% vs. 8.2 ± 1.3% (P = 0.774), respectively. In men, insulin doses were 0.74 ± 0.21 vs. 0.71 ± 0.20 vs. 0.68 ± 0.23 IU · kg–1 · 24 h–1 (P = 0.003). In both sexes, sedentary patients had lower eGDRs than active patients [median (interquartile range) 5.5 (4.0–8.2) vs. 6.8 (4.7–8.8) vs. 6.7 (4.6–8.6) mg · kg–1 · min–1; P < 0.01 for sedentary vs. others]. Age, obesity, smoking, insulin dose, social class, diabetic nephropathy, or cardiovascular disease did not explain the results.

CONCLUSIONS—Low levels of LTPA were associated with poor glycemic control in type 1 diabetic women. Men seem to use less insulin when physically active. Increased LTPA levels were associated with increased estimated insulin sensitivity. Longitudinal studies are needed to further clarify the effects of LTPA on type 1 diabetes.
Use of HLA Typing in Diagnosing Celiac Disease in Patients With Type 1 Diabetes
Authors: Doolan Alessandra , Donaghue Kim , Fairchild Jan , Wong Melanie , Williams Andrew J.
Published: March 2007

OBJECTIVE—This study examines the use of HLA typing for the diagnosis of celiac disease in a group of Australians with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Subjects included 131 sequential patients with type 1 diabetes (mean age 17 years [range 10–37]), 77 patients with biopsy-proven celiac disease (mean age 52 years [range 12–84]), and 162 healthy control subjects (mean age 17 years [range 2 months to 56 years]). Subjects were prospectively screened for celiac disease using endomysial antibodies (EMAs), tissue transglutaminase antibodies (TTGAs), and celiac disease–specific HLA typing.

RESULTS—Celiac disease was diagnosed in 11 subjects after an intestinal biopsy (prevalence 8.4%). There was 95% agreement between TTGA and EMA for positive results and 100% for negative results. There was no significant difference for HLA DQ2 and DR4 among patients with type 1 diabetes with or without celiac disease.

CONCLUSIONS—The prevalence of celiac disease among patients with type 1 diabetes is higher than previously estimated in Australia. TTGA is a valuable diagnostic tool that can be used for screening celiac disease in patients with type 1 diabetes. HLA typing should not be used in the diagnosis of celiac disease in patients with type 1 diabetes because of the similarities of HLA types between patients with type 1 diabetes and those with celiac disease.
Rosiglitazone Improves Postprandial Triglyceride and Free Fatty Acid Metabolism in Type 2 Diabetes
Authors: van Wijk Jeroen P.H. , de Koning Eelco J.P. , Castro Cabezas Manuel , Rabelink Ton J.
Published: March 2007

OBJECTIVE—Increased postprandial lipemia is part of diabetic dyslipidemia and is associated with accelerated atherosclerosis. We investigated the effects of the peroxisome proliferator–activated receptor-γ agonist rosiglitazone on postprandial lipemia in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A randomized, 8-week, crossover, placebo-controlled, double-blind trial was performed in which rosiglitazone at 4 mg was administrated twice daily in 19 patients with type 2 diabetes. Standardized 6-h oral fat-loading tests were performed after each treatment period. Postprandial curves were calculated as the total area under the curve (AUC) and the incremental area under the curve (dAUC).

RESULTS—Rosiglitazone did not change fasting plasma triglycerides compared with placebo (1.97 ± 0.22 vs. 1.88 ± 0.20 mmol/l, respectively) but decreased postprandial triglyceride levels, leading to significantly lower triglyceride dAUC (−37%, P < 0.05), without changing total triglyceride AUC. Significant postprandial triglyceride reductions in the chylomicron fraction (Svedberg flotation rate [Sf] >400) were achieved with rosiglitazone, which resulted in a significant lower triglyceride AUC (−22%) in this fraction. The postprandial triglyceride increase in VLDL1 (Sf 60–400) was also lower after rosiglitazone (−27%), but this did not result in a significant lower triglyceride AUC. In VLDL2 (Sf 20–60), there were no significant differences in triglyceride AUC and triglyceride dAUC between rosiglitazone and placebo. Rosiglitazone decreased free fatty acid (FFA) AUC (−12%) and FFA dAUC (−18%) compared with placebo.

CONCLUSIONS—Rosiglitazone improves the metabolism of large triglyceride-rich lipoproteins and decreases postprandial FFA concentrations in type 2 diabetes. This may have clinical implications, as these effects may contribute to cardiovascular risk reduction.
Proinsulin Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality
Authors: Alssema Marjan , Dekker Jacqueline M. , Nijpels Giel , Stehouwer Coen D.A. , Bouter Lex M. , Heine Robert J.
Published: March 2007

OBJECTIVE—High proinsulin concentration may be a better predictor for cardiovascular disease (CVD) mortality than insulin concentration. Previous observations may have been confounded by glucose tolerance status or lack of precision because of high intraindividual variability. We investigated the longitudinal relation of means of duplicate measurements of insulin and proinsulin with all-cause and CVD mortality in a population-based cohort taking glucose tolerance status into account.

RESEARCH DESIGN AND METHODS—Fasting and post–75-g glucose-load (2-h) glucose, insulin, and proinsulin values were determined in duplicate on separate days in 277 participants with normal glucose metabolism, 208 participants with impaired glucose metabolism, and 119 newly detected patients with type 2 diabetes of the Hoorn Study. Insulin resistance and β-cell function were estimated by homeostasis model assessment (HOMA-IR and HOMA-B, respectively), and the fasting proinsulin-to-insulin ratio was calculated. Subjects were followed with respect to mortality until January 2003.

RESULTS—Fasting proinsulin levels were significantly associated with all-cause and CVD mortality. The hazard ratios (HRs) per increase in interquartile range adjusted for age and sex were 1.21 (95% CI 1.04–1.42) for all-cause mortality and 1.33 (1.06–1.66) for CVD mortality. Adjustment for glucose tolerance status and HOMA-IR did not substantially change the associations.

CONCLUSIONS—Fasting proinsulin was associated with all-cause and CVD mortality, independent of glucose tolerance status and insulin resistance and largely independent of other CVD risk factors. Proinsulin might play a role in the relationship between insulin resistance and CVD.
Maternal Efforts to Prevent Type 1 Diabetes in At-Risk Children
Authors: Baughcum Amy E. , Johnson Suzanne Bennett , Carmichael Stacy K. , Lewin Adam B. , She Jin-Xiong , Schatz Desmond A.
Published: March 2007

OBJECTIVE—The aim of this study was to assess maternal diabetes prevention efforts aimed at children identified as at risk through newborn genetic screening.

RESEARCH DESIGN AND METHODS—A total of 192 mothers of children identified as at risk for type 1 diabetes through newborn genetic screening were administered a structured interview 3.6 ± 0.8 years after risk notification. The interview assessed possible diabetes prevention behaviors across six domains: health surveillance, diet, physical activity, illness prevention, medications, and stress reduction. A mother’s cognitive (diabetes risk perception and perceived control), affective (anxiety), and coping responses to the child’s at-risk status were assessed.

RESULTS—A total of 67% of mothers reported one or more diabetes prevention behaviors. Monitoring behaviors (e.g., watching for signs of diabetes and checking blood glucose) were the most common, reported in 59%, followed by modifications in the child’s diet in 34% and physical activity in 14%. Potentially harmful prevention behaviors (e.g., limiting contact with other children, delaying immunizations, and giving medications including insulin) were rare. Mothers who engaged in diabetes prevention behaviors reported higher diabetes risk perception, greater anxiety, and more use of certain coping styles. Infants of these mothers were more likely to have a first-degree relative with diabetes.

CONCLUSIONS—In the absence of known methods of preventing type 1 diabetes, most mothers of at-risk children report diabetes prevention behaviors. Such behaviors must be more carefully assessed to ensure accurate interpretation of data obtained from natural history studies and prevention trials.