bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Pitavastatin on Urinary Liver-Type Fatty Acid–Binding Protein Levels in Patients With Early Diabetic Nephropathy
Authors: Nakamura Tsukasa , Sugaya Takeshi , Kawagoe Yasuhiro , Ueda Yoshihiko , Osada Shiwori , Koide Hikaru
Published: March 2007

OBJECTIVE—Liver-type fatty acid–binding protein (l-FABP) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis. The aim of this study was to determine whether urinary l-FABP levels are altered at various stages of diabetic nephropathy and whether pitavastatin affects urinary l-FABP levels in early diabetic nephropathy.

RESEARCH DESIGN AND METHODS—Fifty-eight patients with type 2 diabetes (34 men and 24 women, median age 52 years) and 20 healthy, age-matched subjects (group E) were recruited for the study. The diabetic patients included 12 patients without nephropathy (group A), 20 patients with microalbuminuria (group B), 14 patients with macroalbuminuria and normal renal function (group C), and 12 patients with chronic renal failure but not undergoing hemodialysis (blood creatinine >1.2 mg/dl; mean 2.5 mg/dl, group D). Twenty group B patients were randomly assigned to receive 1 mg/day pitavastatin (10 patients, group B1) or placebo (10 patients, group B2). Treatment was continued for 12 months. Urinary l-FABP levels were measured by enzyme-linked immunosorbent assay. Urinary 8-hydroxydeoxyguanosine and serum free fatty acids (FFAs) were also measured in group B.

RESULTS—Urinary l-FABP levels in groups A-D were 6.2 ± 4.6 μg/g creatinine, 19.6 ± 13.5 μg/g creatinine, 26.8 ± 20.4 μg/g creatinine, and 52.4 ± 46.8 μg/g creatinine, respectively. Urinary l-FABP levels in groups B-D were significantly higher than those in healthy subjects (group E, 5.8 ± 4.0 μg/g creatinine) (group B, P < 0.05; group C, P < 0.01; group D, P < 0.01). In group B1, urinary albumin excretion (UAE) and urinary l-FABP levels were decreased after pitavastatin treatment (UAE before, 110 ± 74 μg/min; 6 months, 88 ± 60 μg/min, P < 0.05; 12 months, 58 ± 32 μg/min, P < 0.01; l-FABP before, 18.6 ± 12.5 μg/g creatinine; 6 months, 12.2 ± 8.8 μg/g creatinine, P < 0.05; 12 months, 8.8 ± 6.4 μg/g creatinine, P < 0.01). In group B2, UAE and l-FABP levels showed little change during the experimental period. In group B1, urinary 8-hydroxydeoxyguanosine was decreased 12 months after pitavastatin treatment (before 32.5 ± 19.5 ng/mg creatinine, after 18.8 ± 14.5 ng/mg creatinine, P < 0.01), but in group B2, these showed little difference during the experimental period. In both groups B1 and B2, serum FFAs showed little difference during the experimental period.

CONCLUSIONS—Urinary l-FABP levels appear to be associated with the progression of diabetic nephropathy, and pitavastatin may be effective in ameliorating tubulointerstitial damage in early diabetic nephropathy.
High Incidence of Diabetes in Men With Sleep Complaints or Short Sleep Duration
Authors: Mallon Lena , Broman Jan-Erik , Hetta Jerker
Published: March 2007

OBJECTIVE—The aim of this study was to investigate the possible relationship among sleep complaints, sleep duration, and the development of diabetes prospectively over a 12-year period in a middle-aged Swedish population.

RESEARCH DESIGN AND METHODS—A random sample of 2,663 subjects aged 45–65 years living in mid-Sweden were sent a postal questionnaire including questions about sleep complaints, sleep duration, sociodemographic characteristics, behavioral risk factors, medical conditions, and depression (response rate 70.2%). Twelve years later, a new questionnaire with almost identical questions was sent to all the survivors (n = 1,604) in 1995, and the questionnaire was answered by 1,244 subjects (77.6%).

RESULTS—Men reporting new diabetes at follow-up more often reported short sleep duration (≤5 h per night) (16.0 vs. 5.9%, P < 0.01), difficulties initiating sleep (16.0 vs. 3.1%, P < 0.001), and difficulties maintaining sleep (28.0 vs. 6.3%, P < 0.001) at baseline than men who did not develop diabetes. Women reporting new diabetes at follow-up reported long sleep duration (≥9 h per night) more often at baseline than women not developing diabetes (7.9 vs. 2.4%, P < 0.05). In multiple logistic regression models, the relative risk (95% CI) for development of diabetes was higher in men with short sleep duration (2.8 [1.1–7.3]) or difficulties maintaining sleep (4.8 [1.9–12.5]) after adjustment for age and other relevant risk factors. Short or long sleep duration or sleep complaints did not influence the risk of new diabetes in women.

CONCLUSIONS—Difficulties maintaining sleep or short sleep duration (≤5 h) are associated with an increased incidence of diabetes in men.
Type 2 Diabetes as a “Coronary Heart Disease Equivalent”
Authors: Juutilainen Auni , Lehto Seppo , Rönnemaa Tapani , Pyörälä Kalevi , Laakso Markku
Published: March 2007

OBJECTIVE—The purpose of this study was to investigate the hypothesis that coronary heart disease (CHD) mortality in diabetic subjects without prior evidence of CHD is equal to that in nondiabetic subjects with prior myocardial infarction or any prior evidence of CHD.

RESEARCH DESIGN AND METHODS—During an 18-year follow-up total, cardiovascular disease (CVD) and CHD deaths were registered in a Finnish population-based study of 1,373 nondiabetic and 1,059 diabetic subjects.

RESULTS—Adjusted multivariate Cox hazard models indicated that diabetic subjects without prior myocardial infarction, compared with nondiabetic subjects with prior myocardial infarction, had a hazard ratio (HR) of 0.9 (95% CI 0.6–1.5) for the risk of CHD death. The corresponding HR was 0.9 (0.5–1.4) in men and 1.9 (0.6 –6.1) in women. Diabetic subjects without any prior evidence of CHD (myocardial infarction or ischemic electrocardiogram [ECG] changes or angina pectoris), compared with nondiabetic subjects with prior evidence of CHD, had an HR of 1.9 (1.4–2.6) for CHD death (men 1.5 [1.0–2.2]; women 3.5 [1.8–6.8]). The results for CVD and total mortality were quite similar to those for CHD mortality.

CONCLUSIONS—Diabetes without prior myocardial infarction and prior myocardial infarction without diabetes indicate similar risk for CHD death in men and women. However, diabetes without any prior evidence of CHD (myocardial infarction or angina pectoris or ischemic ECG changes) indicates a higher risk than prior evidence of CHD in nondiabetic subjects, especially in women.
Determinants of Diabetes-Attributable Non–Blood Glucose–Lowering Medication Costs in Type 2 Diabetes
Authors: Davis Wendy A. , Knuiman Matthew W. , Hendrie Delia , Davis Timothy M.E.
Published: March 2007

OBJECTIVE— To prospectively examine the magnitude and predictors of diabetes-attributable non–blood glucose–lowering (non-BGL) medication costs in type 2 diabetes.

RESEARCH DESIGN AND METHODS— Detailed data from 593 community-dwelling patients were available over 4.3 ± 0.4 years. Diabetes-attributable costs (in year 2000 Australian dollars [A$]) were calculated by applying a range of attributable proportions for each complication for which medication was prescribed.

RESULTS— Non-BGL medications accounted for 75% of all prescription medication costs over the study period, and one-third were attributable to diabetes. The median annual cost (in A$) of non-BGL medications per patient increased from A$220 to A$429 over 4 years (P < 0.001), whereas the diabetes-attributable contribution increased from A$31 (range 15–40) to A$159 (range 95–219) per patient (P < 0.001). Diabetes-attributable hospital costs remained stable during the study. Diabetes-attributable non-BGL costs were skewed and, therefore, square root transformed before regression analysis. Independent baseline determinants of √cost/year were coronary heart disease, systolic blood pressure, total serum cholesterol, ln(serum triglycerides), ln(albumin-to-creatinine ratio), serum creatinine, education, and, negatively, male sex and fasting plasma glucose (P ≤ 0.043; R2 = 29%). Projected to the Australian population, diabetes-attributable non-BGL medication costs for patients with type 2 diabetes totaled A$79 million/year.

CONCLUSIONS— The median annual cost of diabetes-attributable non-BGL medications increased fivefold over 4 years. This increase was predicted by vascular risk factors and complications at baseline. Better-educated patients had higher costs, probably reflecting improved health care access. Men and patients with higher fasting plasma glucose levels had lower costs, suggesting barriers to health care and/or poor self-care. The contemporaneous containment of hospital costs may be due to the beneficial effect of increased medication use.
Effects of Oral Fat Load on Insulin Output and Glucose Tolerance in Healthy Control Subjects and Obese Patients Without Diabetes
Authors: Wuesten Oliver , Balz Cristoph H. , Bretzel Reinhard G. , Kloer Hans-Ulrich , Hardt Philip D.
Published: March 2007

OBJECTIVE—Elevated plasma nonesterified fatty acid (NEFA) concentrations cause peripheral and hepatic insulin resistance and may play an important role in regulating glucose-induced insulin secretion. The aim of our study was to investigate the influence of physiologically elevated NEFA levels on glucose-stimulated insulin secretion in order to find evidence that NEFAs are a potential factor predisposing for type 2 diabetes and related metabolic disorders, which are known risk factors for cardiovascular disease.

RESEARCH DESIGN AND METHODS—We combined an orally administered fat emulsion with an intravenous glucose tolerance test and measured the time course of NEFA, insulin, and glucose. In order to find pathological conditions we applied the experiment to healthy and obese subjects.

RESULTS—The main findings are a significant increase in glucose-stimulated insulin secretion after oral fat load in both groups compared with the condition without preceding fat ingestion and a prolonged insulin secretion after fat load in obese patients compared with control subjects.

CONCLUSIONS—The results provide evidence that fat ingestion modulates β-cell function and that NEFA is a plausible mediator that acts as a link between fat and glucose metabolism by modulating glucose-stimulated insulin secretion. Under the condition of elevated plasma levels of NEFA, this mechanism may be responsible for hyperinsulinemia in obese patients and a potential target of type 2 diabetes prevention strategies.
Metabolic Syndrome, Obesity, and Mortality
Authors: Katzmarzyk Peter T. , Church Timothy S. , Janssen Ian , Ross Robert , Blair Steven N.
Published: March 2007

OBJECTIVE—To determine in normal weight, overweight, and obese men the risk of all-cause and cardiovascular disease (CVD) mortality associated with the metabolic syndrome (MetS) and the influence of cardiorespiratory fitness (CRF).

RESEARCH DESIGN AND METHODS—This observational cohort study included 19,173 men who underwent a clinical examination, including a maximal exercise test. MetS was defined according to National Cholesterol Education Program guidelines.

RESULTS—At baseline 19.5% of the men had MetS. The ORs of the metabolic syndrome at baseline were 4.7 (95% CI 4.2–5.3) in overweight and 30.6 (26.7–35.0) in obese men compared with normal weight men. A total of 477 deaths (160 CVD) occurred in 10.2 years of follow-up. The risks of all-cause mortality were 1.11 (0.75–1.17) in normal weight, 1.09 (0.82–1.47) in overweight, and 1.55 (1.14–2.11) in obese men with MetS compared with normal weight healthy men. The corresponding risks for CVD mortality were 2.06 (0.92–4.63) in normal weight, 1.80 (1.10–2.97) in overweight, and 2.83 (1.70–4.72) in obese men with the MetS compared with normal weight healthy men. After the inclusion of CRF in the model, the risks associated with obesity and MetS were no longer significant.

CONCLUSIONS—Obesity and MetS are associated with an increased risk of all-cause and CVD mortality; however; these risks were largely explained by CRF.
Sex Disparities in Treatment of Cardiac Risk Factors in Patients With Type 2 Diabetes
Authors: Wexler Deborah J. , Grant Richard W. , Meigs James B. , Nathan David M. , Cagliero Enrico
Published: March 2007

OBJECTIVE—Diabetes eliminates the protective effect of female sex on the risk of coronary heart disease (CHD). We assessed sex differences in the treatment of CHD risk factors among patients with diabetes.

RESEARCH DESIGN AND METHODS—A cross-sectional analysis included 3,849 patients with diabetes treated in five academic internal medicine practices from 2000 to 2003. Outcomes were stratified by the presence of CHD and included adjusted odds ratios (AORs) that women (relative to men) were treated with hypoglycemic, antihypertensive, lipid-lowering medications or aspirin (if indicated) and AORs of reaching target HbA1c, blood pressure, or lipid levels.

RESULTS—Women were less likely than men to have HbA1c <7% (without CHD: AOR 0.84 [95% CI 0.75–0.95], P = 0.005; with CHD: 0.63 [0.53–0.75], P < 0.0001). Women without CHD were less likely than men to be treated with lipid-lowering medication (0.82 [0.71–0.96], P = 0.01) or, when treated, to have LDL cholesterol levels <100 mg/dl (0.75 [0.62–0.93], P = 0.004) and were less likely than men to be prescribed aspirin (0.63 [0.55–0.72], P < 0.0001). Women with diabetes and CHD were less likely than men to be prescribed aspirin (0.70 [0.60–0.83], P < 0.0001) or, when treated for hypertension or hyperlipidemia, were less likely to have blood pressure levels <130/80 mmHg (0.75 [0.69–0.82], P < 0.0001) or LDL cholesterol levels <100 mg/dl (0.80 [0.68–0.94], P = 0.006).

CONCLUSIONS—Women with diabetes received less treatment for many modifiable CHD risk factors than diabetic men. More aggressive treatment of CHD risk factors in this population offers a specific target for improvement in diabetes care.
Impact of Early Neonatal Breast-Feeding on Psychomotor and Neuropsychological Development in Children of Diabetic Mothers
Authors: Plagemann Andreas , Harder Thomas , Kohlhoff Rainer , Fahrenkrog Sonja , Rodekamp Elke , Franke Kerstin , Dudenhausen Joachim W.
Published: March 2007

OBJECTIVE—In general, breast-feeding positively influences development of psychomotor function and cognition in children. Offspring of diabetic mothers (ODM) have delayed psychomotor and cognitive development. Recently, we observed a dose-dependent negative effect of early neonatal ingestion of breast milk from diabetic mothers (diabetic breast milk [DBM]) on the risk of overweight during early childhood. Here, we investigated the influence of early neonatal intake of DBM on neurodevelopment in ODM.

RESEARCH DESIGN AND METHODS—A total of 242 ODM were evaluated for age of achieving major developmental milestones (Denver Developmental Scale) according to the volume of DBM ingested during the first week of life, using Kruskal-Wallis and Kaplan-Meier analysis.

RESULTS—Children in the upper tertile of early neonatal ingestion of DBM achieved early psychomotor developmental milestones (“lifting head while prone,” “following with eyes”) earlier than those in lower tertiles (P = 0.002). In contrast, a delay in the onset of speaking was observed in children who had ingested larger volumes of DBM compared with those with lower DBM intake (P = 0.002). This negative impact of DBM ingestion was not confounded by birth characteristics, total milk intake, or socioeconomic/educational status.

CONCLUSIONS—Our data indicate differential effects of early neonatal DBM ingestion on psychomotor and cognitive development. Ingesting larger compared with smaller volumes of DBM may normalize early psychomotor development in ODM but delays onset of speaking as a parameter indicative of cognitive development. This effect may result from qualitative alterations in the composition of DBM. Further studies are urgently recommended on the benefits and harms of breast-feeding in ODM.
Increasing Prevalence of Gestational Diabetes Mellitus (GDM) Over Time and by Birth Cohort
Authors: Dabelea Dana , Snell-Bergeon Janet K. , Hartsfield Cynthia L. , Bischoff Kimberly J. , Hamman Richard F. , McDuffie Robert S.
Published: March 2007

OBJECTIVE—The prevalence of gestational diabetes mellitus (GDM) varies in direct proportion with the prevalence of type 2 diabetes in a given population or ethnic group. Given that the number of people with diabetes worldwide is expected to increase at record levels through 2030, we examined temporal trends in GDM among diverse ethnic groups.

RESEARCH DESIGN AND METHODS—Kaiser Permanente of Colorado (KPCO) has used a standard protocol to universally screen for GDM since 1994. This report is based on 36,403 KPCO singleton pregnancies occurring between 1994 and 2002 and examines trends in GDM prevalence among women with diverse ethnic backgrounds.

RESULTS—The prevalence of GDM among KPCO members doubled from 1994 to 2002 (2.1–4.1%, P < 0.001), with significant increases in all racial/ethnic groups. In logistic regression, year of diagnosis (odds ratio [OR] and 95% CI per 1 year = 1.12 [1.09–1.14]), mother’s age (OR per 5 years = 1.7 [1.6–1.8]) and ethnicity other than non-Hispanic white (OR = 2.1 [1.9–2.4]) were all significantly associated with GDM. Birth year remained significant (OR = 1.06, P = 0.006), even after adjusting for prior GDM history.

CONCLUSIONS—This study shows that the prevalence of GDM is increasing in a universally screened multiethnic population. The increasing GDM prevalence suggests that the vicious cycle of diabetes in pregnancy initially described among Pima Indians may also be occurring among other U.S. ethnic groups.
Effects of Pramlintide on Postprandial Glucose Excursions and Measures of Oxidative Stress in Patients With Type 1 Diabetes
Authors: Ceriello Antonio , Piconi Ludovica , Quagliaro Lisa , Wang Yan , Schnabel Catherine A. , Ruggles James A. , Gloster Maurice A. , Maggs David G. , Weyer Christian
Published: March 2007

OBJECTIVE—Oxidative stress has been shown to be increased in the postprandial period in patients with diabetes and has been implicated in the pathogenesis of micro- and macrovascular complications. The aim of this post hoc analysis was to assess the effects of pramlintide, an amylin analog shown to reduce postprandial glucose excursions in patients with diabetes, on markers of oxidative stress in the postprandial period.

RESEARCH DESIGN AND METHODS—In a randomized, single-blind, placebo-controlled, crossover study, 18 evaluable subjects with type 1 diabetes underwent two standardized breakfast meal tests and received pramlintide or placebo in addition to their preprandial insulin. The plasma concentrations of glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL], and total radical-trapping antioxidant parameter [TRAP]) were measured at baseline and during the 4-h postprandial period.

RESULTS—Compared with placebo, pramlintide treatment significantly reduced postprandial excursions of glucose, nitrotyrosine, and ox-LDL and prevented a decline in TRAP (P < 0.03 for all comparisons). Correlation analyses adjusted for treatment revealed a significant association between postprandial mean incremental area under the curve from 0 to 4 h (AUC0–4 h) for glucose and postprandial mean incremental AUC0–4 h for each measure of oxidative stress (r = 0.75, 0.54, and −0.63 for nitrotyrosine, ox-LDL, and TRAP, respectively; P < 0.001 for all correlations).

CONCLUSIONS—These findings indicate that the postprandial glucose-lowering effect of pramlintide in type 1 diabetes is associated with a significant reduction in postprandial oxidative stress.
Diabetes, Glucose, Insulin, and Heart Rate Variability
Authors: Schroeder Emily B. , Chambless Lloyd E. , Liao Duanping , Prineas Ronald J. , Evans Gregory W. , Rosamond Wayne D. , Heiss Gerardo
Published: March 2007

OBJECTIVE—To describe the progression of autonomic impairment among individuals with diabetes and pre-diabetic metabolic impairments.

RESEARCH DESIGN AND METHODS—We investigated the consequence of diabetes and pre-diabetic metabolic impairments on the 9-year change in heart rate variability (HRV) in a population-based cohort of 6,245 individuals aged 45–64 years at baseline and cross-sectional associations among 9,940 individuals.

RESULTS—Diabetic subjects had a more rapid temporal decrease in HRV conditional on baseline HRV than nondiabetic subjects. Adjusted mean annual changes (95% CI) (ms/year) in the SD of all normal-to-normal R-R intervals were −0.65 (−0.69 to −0.61) for those with normal fasting glucose vs. −0.95 (−1.09 to −0.81) for diabetic subjects, in root mean square of successive differences in normal-to-normal R-R intervals −0.35 (−0.39 to −0.30) vs. −0.66 (−0.82 to −0.51), and in R-R interval 6.70 (6.37–7.04) vs. 3.89 (2.72–5.05). While we found cross-sectional associations between decreased HRV and diabetes and nondiabetic hyperinsulinemia and a weak inverse association with fasting glucose, neither impaired fasting glucose nor nondiabetic hyperinsulimenia was associated with a measurably more rapid decline in HRV than normal.

CONCLUSIONS—Cardiac autonomic impairment appears to be present at early stages of diabetic metabolic impairment, and progressive worsening of autonomic cardiac function over 9 years was observed in diabetic subjects. The degree to which pre-diabetic metabolic impairments in insulin and glucose metabolism contribute to decreases in cardiac autonomic function remains to be determined.
Presence of the Metabolic Syndrome Does Not Impair Coronary Collateral Vessel Formation in Patients With Documented Coronary Artery Disease
Authors: Olijhoek Jobien K. , Koerselman Jeroen , de Jaegere Peter P.Th. , Verhaar Marianne C. , Grobbee Diederick E. , van der Graaf Yolanda , Visseren Frank L.J. ,   for the SMART Study Group
Published: March 2007

OBJECTIVE—The metabolic syndrome confers an increased risk for cardiovascular morbidity and mortality. The presence of coronary collaterals may have beneficial effects during myocardial ischemia and may improve cardiovascular outcome in patients with coronary artery disease. Impaired collateral formation could be one of the reasons for the increased cardiovascular risk in patients with the metabolic syndrome. The aim of the present study was to determine the influence of the metabolic syndrome and insulin resistance on the presence of coronary collaterals.

RESEARCH DESIGNS AND METHODS—We conducted a cross-sectional study in 227 patients referred for elective percutaneous transluminal coronary angioplasty to the University Medical Centre Utrecht. The metabolic syndrome was diagnosed according to Adult Treatment Panel III, and homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were used to quantify insulin resistance. Coronary collaterals were graded with Rentrop’s classification. Rentrop grade ≥1 indicated the presence of collaterals. Results were adjusted for age, sex, and severity of coronary artery disease.

RESULTS—A total of 103 patients (45%) were diagnosed with the metabolic syndrome. There was no association between the metabolic syndrome and the presence of coronary collateral formation (odds ratio [OR] 1.2 [95% CI 0.7–2.0]). Also, the degree of insulin resistance was not related to the presence of coronary collaterals. The OR for HOMA-IR (highest versus lowest tertile) was 0.7 (0.3–1.5) and for QUICKI (lowest versus highest tertile) 0.8 (0.4–1.6).

CONCLUSIONS—The metabolic syndrome and insulin resistance are not related to the presence of coronary collaterals in patients with documented coronary artery disease.
Endothelial-Dependent Vasodilation and Incidence of Type 2 Diabetes in a Population of Healthy Postmenopausal Women
Authors: Rossi Rosario , Cioni Elena , Nuzzo Annachiara , Origliani Giorgia , Modena Maria Grazia
Published: March 2007

OBJECTIVE—Both postmenopausal state and diabetes are associated with endothelial dysfunction and are well-known risk factors for atherosclerosis. However, the relationship of endothelium-dependent vasodilation and diabetes has never been prospectively evaluated. This study provided the opportunity to assess the association between endothelial vasodilation function and the incidence of diabetes in a cohort of apparently healthy postmenopausal women.

RESEARCH DESIGN AND METHODS—We conducted a prospective cohort study that began in 1997 with 840 apparently healthy, nonobese, postmenopausal women, aged 53 ± 6 years, initially with normal glucose tolerance at the oral glucose tolerance test. All participants were followed up for a mean period of 3.9 ± 0.7 years (range 0.5–6.9). Endothelial function was measured as flow-mediated dilation (FMD) of the brachial artery, using high-resolution ultrasound.

RESULTS—There were no significant differences in demographic, blood pressure, and biochemical profiles among each tertile group at baseline or at follow-up review. During follow-up, 102 women developed type 2 diabetes. The adjusted relative risk (RR) for women with FMD ≤4.3 (lowest tertile) was 5.87 (95% CI 4.34–8.10) versus women with FMD ≥5.6 (highest tertile reference). Each 1-unit decrease of FMD was associated with a significant 32% (22–48%) increase in the multiple-adjusted RR of incident diabetes.

CONCLUSIONS—These prospective data indicate a significant increase in the RR of diabetes with each unit decrease of FMD. This could suggest that an impaired endothelial function may play a fundamental role in diabetogenesis in postmenopausal women.
Effect of a Pharmaceutical Care Program on Vascular Risk Factors in Type 2 Diabetes
Authors: Clifford Rhonda M. , Davis Wendy A. , Batty Kevin T. , Davis Timothy M.E.
Published: March 2007

OBJECTIVE—To examine the effect of a 12-month pharmaceutical care (PC) program on vascular risk in type 2 diabetes.

RESEARCH DESIGN AND METHODS—We recruited 198 community-based patients randomized to PC or usual care. PC patients had face-to-face goal-directed medication and lifestyle counseling at baseline and at 6 and 12 months plus 6-weekly telephone assessments and provision of other educational material. Clinical, biochemical, and medication-related data were sent regularly to each patient’s physician(s). The main outcome measure was change in HbA1c. A diabetes-specific risk engine was used to estimate changes in 10-year coronary heart disease (CHD) and stroke risk in patients without a history of cardiovascular disease.

RESULTS—At total of 180 patients (91%) completed the study. Mean (95% CI) reductions were greater in PC case subjects (n = 92) than control subjects (n = 88) for HbA1c (−0.5% [95% CI −0.7 to −0.3] vs. 0 [−0.2 to 0.2]) and systolic (−14 mmHg [−19 to −9] vs. −7 [−11 to −2]) and diastolic (−5 mmHg [−8 to −3] vs. −2 [−4 to 1]) blood pressure (P ≤ 0.043). The improvement in HbA1c persisted after adjustment for baseline value and demographic and treatment-specific variables. The median (interquartile range) 10-year estimated risk of a first CHD event decreased in the PC case subjects (25.1% [15.6–36.2] to 20.3 [14.6–30.2]; n = 42, P = 0.002) but not in the control subjects (26.1% [17.2–39.4] vs. 26.4 [16.7–38.0]; n = 52, P = 0.17).

CONCLUSIONS—A 12-month PC program in type 2 diabetes reduced glycemia and blood pressure. Pharmacist involvement contributed to improvement in HbA1c independently of pharmacotherapeutic changes. PC could prove a valuable component of community-based multidisciplinary diabetes care.
Physical Activity, Cardiovascular Risk Factors, and Mortality Among Finnish Adults With Diabetes
Authors: Hu Gang , Jousilahti Pekka , Barengo Noël C. , Qiao Qing , Lakka Timo A. , Tuomilehto Jaakko
Published: March 2007

OBJECTIVE—The aim of this study was to examine both single and joint associations of physical activity and conventional cardiovascular risk factors with total and cardiovascular mortality among patients with diabetes.

RESEARCH DESIGN AND METHODS—We prospectively followed 3,708 Finnish patients with type 2 diabetes aged 25–74 years. Physical activity, smoking status, blood pressure, height, weight, and serum cholesterol level were determined at baseline. Cox proportional hazard models were used to estimate single and joint effects of physical activity and other cardiovascular risk factors on the risk of mortality.

RESULTS—During a mean follow-up of 18.7 years, 1,423 deaths were recorded, 906 of which were due to cardiovascular disease. Moderate or high levels of physical activity were associated with decreased total and cardiovascular mortality, whereas higher levels of BMI and blood pressure and current smoking were associated with increased total and cardiovascular mortality. High serum cholesterol levels also increased cardiovascular mortality. The protective effect of physical activity was consistent in diabetic patients with any levels of BMI, blood pressure, total cholesterol, and smoking.

CONCLUSIONS—A moderate or high level of physical activity was associated with a reduced risk of total and cardiovascular mortality among patients with type 2 diabetes. The favorable association of physical activity with longevity was observed regardless of the levels of BMI, blood pressure, total cholesterol, and smoking.
Estimation of Glomerular Filtration Rate in Diabetic Subjects
Authors: Rigalleau Vincent , Lasseur Catherine , Perlemoine Caroline , Barthe Nicole , Raffaitin C. , Liu Chung , Chauveau Phillipe , Baillet-Blanco Laurence , Beauvieux Marie-Christine , Combe C. , Gin Henri
Published: March 2007

OBJECTIVE—The Cockcroft-Gault formula is recommended for the evaluation of renal function in diabetic patients. The more recent Modification of Diet in Renal Disease (MDRD) study equation seems more accurate, but it has not been validated in diabetic patients. This study compares the two methods.

RESEARCH DESIGN AND METHODS—In 160 diabetic patients, we compared the Cockcroft-Gault formula and MDRD equation estimations to glomerular filtration rates (GFRs) measured by an isotopic method (51Cr-EDTA) by correlation studies and a Bland-Altman procedure. Their accuracy for the diagnosis of moderately (GFR <60 ml · min−1 · 1.73 m−2) or severely (GFR <30 ml · min−1 · 1.73 m−2) impaired renal function were compared with receiver operating characteristic (ROC) curves.

RESULTS—Both the Cockcroft-Gault formula (r = 0.74; P < 0.0001) and MDRD equation (r = 0.81; P < 0.0001) were well correlated with isotopic GFR. The Bland-Altman procedure revealed a bias for the MDRD equation, which was not the case for the Cockcroft-Gault formula. Analysis of ROC curves showed that the MDRD equation had a better maximal accuracy for the diagnosis of moderate (areas under the curve [AUCs] 0.868 for the Cockcroft-Gault formula and 0.927 for the MDRD equation; P = 0.012) and severe renal failure (AUC 0.883 for the Cockcroft-Gault formula and 0.962 for the MDRD equation; P = 0.0001). In the 87 patients with renal insufficiency, the MDRD equation estimation was better correlated with isotopic GFR (Cockcroft-Gault formula r = 0.57; the MDRD equation r = 0.78; P < 0.01), and it was not biased as evaluated by the Bland-Altman procedure.

CONCLUSIONS—Although both equations have imperfections, the MDRD equation is more accurate for the diagnosis and stratification of renal failure in diabetic patients.
Autoantibody “Subspecificity” in Type 1 Diabetes
Authors: Barker Jennifer M. , Yu Jeesuk , Yu Liping , Wang Jian , Miao Dongmei , Bao Fei , Hoffenberg Edward , Nelson Jerald C. , Gottlieb Peter A. , Rewers Marian , Eisenbarth George S.
Published: March 2007

OBJECTIVE—Autoimmune thyroid disease (AIT), celiac disease, and Addison’s disease are characterized by the presence of autoantibodies: thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in AIT, tissue transglutaminase antibody (TTGAb) in celiac disease, and 21-hydroxylase antibody (21-OHAb) in Addison’s disease. The objective of this study was to define the prevalence of these autoantibodies and clinical disease in a population with type 1 diabetes.

RESEARCH DESIGN AND METHODS—We screened 814 individuals with type 1 diabetes for TPOAb, TGAb, TTGAb, and 21-OHAb. Clinical disease was defined by chart review. Factors related to the presence of autoimmunity and clinical disease including age at onset of type 1 diabetes, duration of diabetes, age at screening, sex, and the presence of autoantibodies were reviewed.

RESULTS—The most common autoantibodies expressed were TPOAb and/or TGAb (29%), followed by TTGAb (10.1%) and 21-OHAb (1.6%). Specific HLA DR/DQ genotypes were associated with the highest risk for expression of 21-OHAb (DRB1*0404-DQ8, DR3-DQ2) and TTGAb (DR3-DQ2- DR3-DQ2). The expression of thyroid autoantibodies was related to 21-OHAb but not to TTGAb. The presence of autoantibodies was associated with and predictive of disease.

CONCLUSIONS—In this large cohort of individuals with type 1 diabetes, the expression of organ-specific autoantibodies was very high. The grouping of autoantibody expression suggests common factors contributing to the clustering.
Effect of Maternal Use of Antiretroviral Agents on Serum Insulin Levels of the Newborn Infant
Authors: El Beitune Patrícia , Duarte Geraldo , Foss Milton C. , Montenegro Renan M. , Quintana Silvana M. , Figueiró-Filho Ernesto A. , Nogueira Antonio A.
Published: March 2007

OBJECTIVE—The aim of this study was to investigate the effect of antiretroviral drugs on neonatal serum insulin levels.

RESEARCH DESIGN AND METHODS—A prospective study was conducted on 57 pregnant women divided into three groups: the zidovudine (ZDV) group, HIV-infected women taking ZDV (n = 20); the triple treatment group, HIV-infected women taking triple antiretroviral agents ZDV + lamivudine + nelfinavir (n = 25); and the control group, pregnant women considered normal from a clinical and laboratory standpoint (n = 12). Blood was collected from the umbilical cord of newborn infants upon delivery for measurement of insulin level. The insulin measurements were performed in duplicate by radioimmunoassay.

RESULTS—Demographic and anthropometric data were homogeneous, and pregnant women with a personal and family history of diabetes were excluded. There was no difference between groups regarding glycemia in the newborn. Median newborn insulin doses were 2.9, 4.8, and 6.5 μU/ml for the triple treatment, ZDV, and control groups, respectively (P < 0.05).

CONCLUSIONS—Use of triple therapy during pregnancy induced a significant decrease in serum levels of neonatal insulin compared with the control group. Active surveillance of short- and long-term adverse events is imperative to issue a definitive statement regarding the impact that use of protease inhibitors during pregnancy will have on infant metabolism.
Metabolic Syndrome and Risk of Restenosis in Patients Undergoing Percutaneous Coronary Intervention
Authors: Rana Jamal S. , Monraats Pascalle S. , Zwinderman Aeilko H. , de Maat Moniek P.M. , Kastelein John J.P. , Doevendans Pieter A.F. , de Winter Robbert J. , Tio René A. , Frants Rune R. , van der Laarse Arnoud , van der Wall Ernst E. , Jukema J. Wouter
Published: March 2007

OBJECTIVE—Patients with metabolic syndrome have increased risk of cardiovascular events. The number of patients with metabolic syndrome is rapidly increasing, and these patients often need revascularization. However, only limited data are available on the effect of metabolic syndrome on restenosis in patients undergoing percutaneous coronary intervention (PCI).

RESEARCH DESIGN AND METHODS—To assess the role of metabolic syndrome in the development of restenosis, we performed an analysis in a population of patients from the GENetic DEterminants of Restenosis (GENDER) study. The GENDER project, a multicenter prospective study, included consecutive patients after successful PCI and was designed to study the predictive value of various genetic and other risk factors for subsequent clinical restenosis, defined as target vessel revascularization (TVR) or combined end point of death, myocardial infarction, and TVR. This subpopulation of GENDER consisted of 901 patients, 448 of whom (49.7%) had metabolic syndrome.

RESULTS—On multivariable Cox regression analysis, controlling for age, sex, previous myocardial infarction, stent length, current smoking, and statin therapy, there was no association between increased risk of TVR (hazard ratio 1.03 [95% CI 0.68–1.57]) or the combined end point (1.05 [0.71–1.55]) and the presence of metabolic syndrome.

CONCLUSIONS—This study demonstrates that metabolic syndrome is not associated with TVR or the combined end point after PCI. Furthermore, accumulating characteristics of metabolic syndrome were neither associated with increased risk of TVR nor with the combined end point. Therefore, PCI has equal beneficial results in patients with or without metabolic syndrome. This is important information in light of the pandemic proportion of metabolic syndrome that the medical community will face.
Reduced Hypoglycemia Risk With Insulin Glargine
Authors: Rosenstock Julio , Dailey George , Massi-Benedetti Massimo , Fritsche Andreas , Lin Zhengning , Salzman Alan
Published: March 2007

OBJECTIVE—Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent “treat-to-target” study has shown that more patients on insulin glargine reached HbA1c levels ≤7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes.

RESEARCH DESIGN AND METHODS—All studies were 24–28 weeks long, except one 52-week study, for which interim 20-week data were used.

RESULTS—Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA1c (≤7.0%) was similar between insulin glargine–and NPH insulin–treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively.

CONCLUSIONS—These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA1c target of ≤7.0% in patients with type 2 diabetes.
Amputation Prevention Initiative in South India
Authors: Viswanathan Vijay , Madhavan Sivagami , Rajasekar Seena , Chamukuttan Snehalatha , Ambady Ramachandran
Published: March 2007

OBJECTIVE—To determine whether intensive treatment and education strategies for type 2 diabetic patients with high-risk diabetic foot disease helps in preventing foot amputations.

RESEARCH DESIGN AND METHODS—Participants included 4,872 consecutive type 2 diabetic patients (male-to-female ratio 3,422:1,450, mean (±SD) age 60.5 ± 8.8 years, mean duration of diabetes 13.7 ± 7.6 years) with high-risk diabetic foot disease. The patients were categorized as high-risk subjects according to the International Consensus on the Diabetic Foot. The three study groups were subjects with diabetes and neuropathy (group 1; n = 2,871), diabetic neuropathy with deformity (group 2; n = 235), and diabetic neuropathy with deformity and foot ulceration or peripheral vascular disease (group 3; n = 1,766). Neuropathy was diagnosed by biothesiometry. Peripheral vascular disease was diagnosed as an ankle brachial index <0.8. All the subjects were educated regarding diabetic foot disease and its complications and prevention. They were also instructed to visit the center if any sign of new lesions appeared.

RESULTS—Among the 1,259 group 3 subjects who came for follow-up, 718 (57%) strictly followed the advice given and 541 (43%) did not. Ulcers present during the recruitment had healed in 585 (82%) subjects who followed the advice, but in only 269 (50%) subjects who did not. A significantly larger proportion of subjects who did not follow the advice developed new problems (26%) and required surgical procedures (14%) compared with those who followed the advice (5 and 3%, respectively).

CONCLUSIONS—Strategies such as intensive management and foot care education are helpful in preventing newer problems and surgery in diabetic foot disease.
Dietary Glycemic Index, Glycemic Load, Cereal Fiber, and Plasma Adiponectin Concentration in Diabetic Men
Authors: Qi Lu , Rimm Eric , Liu Simin , Rifai Nader , Hu Frank B.
Published: March 2007

OBJECTIVE—Adiponectin may improve insulin sensitivity, reduce inflammation, and ameliorate glycemic control. However, few studies have evaluated dietary predictors of plasma adiponectin levels, especially among subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—To examine the associations of dietary glycemic load, glycemic index, and fibers with plasma adiponectin levels, we conducted a cross-sectional analysis in 780 diabetic men from the Health Professionals’ Follow-up Study. Dietary information was obtained in 1986, 1990, and 1994 using semiquantitative food-frequency questionnaires.

RESULTS—After adjustment for age, BMI, smoking, alcohol consumption, physical activity, aspirin use, HbA1c, history of hypertension or hypercholesterolemia, and fiber intake, dietary glycemic index and glycemic load were inversely associated with plasma adiponectin in a dose-dependent fashion (P for trend = 0.005 for glycemic index and 0.004 for glycemic load). Adiponectin levels were 13% lower in the highest quintile of dietary glycemic index than in the lowest quintile. For dietary glycemic load, adiponectin levels were 18% lower in the highest quintile than in the lowest. In contrast, high intake of cereal fiber was associated with increased plasma adiponectin levels, adjusting for lifestyle factors and dietary glycemic load (P for trend = 0.003). Adiponectin levels were 19% higher in the highest quintile than in the lowest quintile. Higher magnesium intake was also associated with increased plasma adiponectin.

CONCLUSIONS—Diets low in glycemic load and high in fiber may increase plasma adiponectin concentrations in diabetic patients.
Time Trends and Geographic Disparities in Acute Complications of Diabetes in Ontario, Canada
Authors: Booth Gillian L. , Hux Janet E. , Fang Jiming , Chan Benjamin T.B.
Published: March 2007

OBJECTIVE—This study examines whether acute diabetes complication rates have fallen in recent years and whether geographic factors influence these trends.

RESEARCH DESIGN AND METHODS—A population-based time-trend analysis of acute complications of diabetes was conducted using linked administrative and census data from Ontario, Canada. The study population included all adults identified through a province-wide electronic diabetes registry between 1994 and 1999 (n = 577,659). The primary outcome was hospitalizations for hyper- and hypoglycemia and emergency department visits for diabetes.

RESULTS—Between 1994 and 1999, rates of hospitalization for hyper- and hypoglycemic emergencies decreased by 32.5 and 76.9%, respectively; emergency department visits for diabetes fell by 23.9%. On multivariate analysis, fiscal year was an independent predictor of acute diabetes complications, with individuals in our cohort experiencing a decline in risk of ∼6% per year for either being hospitalized with hyper- or hypoglycemia or requiring an emergency department visit for diabetes. After accounting for variation in physician service use, diabetic individuals living in rural areas or Aboriginal communities were nearly twice as likely to have an acute complication, whereas those residing in remote areas of the province were nearly three times as likely to experience an event.

CONCLUSIONS—Although our findings suggest an overall improvement in diabetes care in Ontario, certain subgroups of the population continue to experience higher rates of complications that are potentially preventable through good ambulatory care. Measures to improve access to timely and effective outpatient care may further reduce rates of acute complications among the diabetic population.
Awareness and Treatment of Dyslipidemia in Young Adults With Type 1 Diabetes
Authors: Wadwa R. Paul , Kinney Gregory L. , Maahs David M. , Snell-Bergeon Janet , Hokanson John E. , Garg Satish K. , Eckel Robert H. , Rewers Marian
Published: March 2007

OBJECTIVE—Dyslipidemia is a preventable major risk factor for coronary heart disease (CHD). Despite an increased risk of CHD in type 1 diabetes, little is known concerning awareness and adequacy of dyslipidemia treatment in this population. In this report, we describe the prevalence of dyslipidemia and adequacy of pharmacological treatment in patients with type 1 diabetes and comparable nondiabetic subjects.

RESEARCH DESIGN AND METHODS—From 2000 to 2002, the Coronary Artery Calcification in Type 1 Diabetes study obtained fasting lipid profiles in 1,416 individuals aged 19–56 years with no history of CHD: 652 type 1 diabetic patients (46% men, mean age 37 ± 9 years) and 764 nondiabetic control subjects (50% men, mean age 39 ± 9 years). These data combined with patient questionnaire results were used to determine prevalence of dyslipidemia and adequacy of pharmacological treatment. For all subjects, dyslipidemia was defined using National Cholesterol Education Program Adult Treatment Panel III criteria.

RESULTS—Type 1 diabetic subjects had significantly less dyslipidemia than nondiabetic control subjects (47 vs. 58%, P < 0.001), and a higher percentage of those with abnormal lipids were aware of (52 vs. 34%, P < 0.0001), on medication for (36 vs. 9%, P < 0.0001), and in control of their lipid levels (15 vs. 1.4%, P < 0.001). Of those on treatment, control was achieved in 41% of type 1 diabetic subjects and 15% of nondiabetic participants (P < 0.01).

CONCLUSIONS—Dyslipidemia, a major risk factor for CHD, remains largely undiagnosed and undertreated in high-risk populations, such as patients with type 1 diabetes.
Physical Activity Energy Expenditure Predicts Progression Toward the Metabolic Syndrome Independently of Aerobic Fitness in Middle-Aged Healthy Caucasians
Authors: Ekelund Ulf , Brage Søren , Franks Paul W. , Hennings Susie , Emms Sue , Wareham Nicholas J.
Published: March 2007

OBJECTIVE—To examine over a period of 5.6 years the prospective associations between physical activity energy expenditure (PAEE), aerobic fitness (Vo2max), obesity, and the progression toward the metabolic syndrome in a population-based cohort of middle-aged men and women (n = 605) who were free of the metabolic syndrome at baseline.

RESEARCH DESIGN AND METHODS—PAEE was measured objectively by individually calibrated heart rate against energy expenditure. Vo2max was predicted from a submaximal exercise stress test. Fat mass and fat-free mass were assessed by bio-impedance. A metabolic syndrome score was computed by summing the standardized values for obesity, hypertension, hyperglycemia, insulin resistance, hypertriglyceridemia, and the inverse level of HDL cholesterol and expressed as a continuously distributed outcome. Generalized linear models were used to examine the independent prospective associations between PAEE and Vo2max and the metabolic syndrome score after adjusting for sex, baseline age, smoking, socioeconomic status, follow-up time, and baseline phenotypes.

RESULTS—PAEE predicted progression toward the metabolic syndrome, independent of baseline metabolic syndrome, body fat, Vo2max, and other confounding factors (standardized β = −0.00085, P = 0.046). This association was stronger when excluding the adiposity component from the metabolic syndrome (standardized β = −0.0011, P = 0.035). Vo2max was not an independent predictor of the metabolic syndrome after adjusting for physical activity (standardized β = 0.00011, P = 0.93).

CONCLUSIONS—PAEE predicts progression toward the metabolic syndrome independent of aerobic fitness, obesity, and other confounding factors. This finding underscores the importance of physical activity for metabolic disease prevention even when an improvement in aerobic fitness is absent.