bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Study of Lipoprotein(a) as a Risk Factor for Deteriorating Renal Function in Type 2 Diabetic Patients With Overt Proteinuria
Authors: Song Ki-Ho , Ko Seung Hyun , Kim Hyung-Wook , Ahn Yu-Bae , Lee Jong-Min , Son Hyun-Shik , Yoon Kun-Ho , Cha Bong-Yun , Lee Kwang-Woo , Son Ho-Young 
Published: March 2007

OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy.
RESEARCH DESIGN AND METHODS—We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels ≤30 mg/dl (n = 40) and group 2 had Lp(a) levels &gt;30 mg/dl (n = 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value.
RESULTS—At baseline and during the follow-up, there was no difference in HbA1c and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 ± 78.0 vs. 108.1 ± 34.9 μmol/l, P = 0.004) and after 2 years (216.9 ± 144.5 vs. 131.3 ± 47.3 μmol/l, P = 0.001), although baseline serum creatinine did not differ significantly between groups. In all, 13 of 14 patients with progression of diabetic nephropathy (progressors) were from group 2. Baseline Lp(a) levels were higher in the progressors than in the nonprogressors (62.9 ± 26.7 vs. 33.5 ± 27.5 mg/dl, P &lt; 0.001). Multiple logistic regression showed that baseline Lp(a) level was a significant and independent predictor of the progression of diabetic nephropathy.
CONCLUSIONS—Our study demonstrated that Lp(a) is an independent risk factor for the progression of diabetic nephropathy in type 2 diabetic patients with overt proteinuria.
β-Cell Dysfunction, Insulin Sensitivity, and Glycosuria Precede Diabetes in Hepatocyte Nuclear Factor-1α Mutation Carriers
Authors: Stride Amanda , Ellard Sian , Clark Penny , Shakespeare Lynette , Salzmann Maurice , Shepherd Maggie , Hattersley Andrew T. 
Published: March 2007

OBJECTIVE—Patients with diabetes due to hepatocyte nuclear factor (HNF)-1α mutations have β-cell deficiency, insulin sensitivity, altered proinsulin levels, and a low renal threshold for glucose. It is uncertain how many of these features precede the development of diabetes. The aim of our study was to test for these characteristics in young nondiabetic HNF-1α mutation carriers.
RESEARCH DESIGN AND METHODS—A total of 47 offspring from 19 extended families underwent genetic testing, a standard oral glucose tolerance test, and urine testing.
RESULTS—HNF-1α mutations were found in 20 offspring, 7 with diabetes and 13 without diabetes. The 13 nondiabetic mutation carriers were compared with 27 family control subjects, who were matched for age, sex, and BMI. There was marked β-cell deficiency with reduced insulinogenic index (53.5 [31.5–90.9] vs. 226.0 [126.0–407.1], SD [range], P &lt; 0.001) and area under the curve for insulin (P &lt; 0.001). Insulin sensitivity was increased in mutation carriers (homeostatic model assessment of insulin sensitivity 144.6 [82.7–252.7] vs. 100 [66.9–149.4], P = 0.025). A total of 38% of mutation carriers had glycosuria at 2 h compared with 0% of control subjects (P = 0.0034). Those with glycosuria had peak glucose values that were higher than the mutations carriers without glycosuria (range 8.1–11.8 vs. 6.2–8.4 mmol/l, P = 0.002). The seven subjects with diabetes all showed glycosuria.
CONCLUSIONS—We conclude that marked β-cell deficiency, increased insulin sensitivity, and a low renal threshold are present in young nondiabetic HNF-1α mutation carriers. The presence of glycosuria post–glucose load could be used to screen children of mutation carriers as it occurs in all mutation carriers with a peak glucose in the oral glucose tolerance test &gt;8.4 mmol/l.
Transfer of Glyburide and Glipizide Into Breast Milk
Authors: Feig Denice S. , Briggs Gerald G. , Kraemer Jennifer M. , Ambrose Peter J. , Moskovitz David N. , Nageotte Michael , Donat Diane J. , Padilla Guadalupe , Wan Stephanie , Klein Julia , Koren Gideon 
Published: March 2007

OBJECTIVE—To determine if glyburide and glipizide are excreted into breast milk and if breast-feeding from women taking these drugs causes infant hypoglycemia.
RESEARCH DESIGN AND METHODS—We studied eight women who had received a single oral dose of 5 or 10 mg glyburide. Drug concentrations were measured in maternal blood and milk for 8 h after the dose. In a separate study, five women were given a daily dosage (5 mg/day) of glyburide or glipizide, starting on the first postpartum day. Maternal blood and milk drug concentrations and infant blood glucose were measured 5–16 days after delivery.
RESULTS—In the single-dose glyburide study, the mean maximum theoretical infant dose (MTID) as a percent of the weight-adjusted maternal dose (WAMD) was &lt;1.5 and &lt;0.7% for the 5- and 10-mg doses, respectively. For the five women taking daily dosages, the mean MTID as a percent of the WAMD was &lt;28% for glyburide and &lt;27% for glipizide. The high estimates were due to the insensitivity of the assay. Neither glyburide nor glipizide were detected in breast milk in either study and blood glucose was normal in the three infants (one glyburide and two glipizide) who were wholly breast-fed when the drug concentrations were at steady state.
CONCLUSIONS—Neither glyburide nor glipizide were detected in breast milk, and hypoglycemia was not observed in the three nursing infants. Both agents, at the doses tested, appear to be compatible with breast-feeding.
Family History of Type 2 Diabetes Is Associated With Increased Carotid Artery Intimal-Medial Thickness in Mexican Americans
Authors: Kao W.H. Linda , Hsueh Wen-Chi , Rainwater David L. , O’Leary Daniel H. , Imumorin Ikhide G. , Stern Michael P. , Mitchell Braxton D. 
Published: March 2007

OBJECTIVE—To evaluate whether the joint risk of diabetes and atherosclerosis tracked within families, we assessed the correlation between a family history of diabetes and intimal-medial thickness (IMT) of the common carotid artery (CCA).
RESEARCH DESIGN AND METHODS—Study subjects included 620 nondiabetic individuals from 24 families enrolled in the San Antonio Family Heart Study. The thickness of the far walls of the CCA was measured by B-mode ultrasonography. Statistical analyses included familial correlations to account for the nonindependence of family data.
RESULTS—After adjusting for sex, age, and IMT reader effects, the heritability of IMT in this population was 16% (P = 0.009). Using a more comprehensive family history score that accounted for diabetes status of the individual’s parents and older siblings, we observed a significant correlation between family history score and increased CCA IMT (0.006 mm increase in CCA IMT for every point increase of diabetes family history score, P = 0.016). This association remained even after further adjustment for BMI, smoking, and fasting insulin and glucose levels. After adjusting for several cardiovascular risk factors, the mean CCA IMT in those with high family history scores for diabetes was still 0.037 mm thicker than those with low family history scores for diabetes (P = 0.040).
CONCLUSIONS—These results suggest that the genetic contribution to CCA IMT variability is modest. Also, the small increase in subclinical atherosclerosis observed even among nondiabetic Mexican Americans with a positive family history of diabetes is probably transmitted along with the risk of diabetes through shared etiologic risk factors between diabetes and cardiovascular disease.
Randomized Trial of Quality Improvement Intervention to Improve Diabetes Care in Primary Care Settings
Authors: O’Connor Patrick J. , Desai Jay , Solberg Leif I. , Reger Laurel A. , Crain A. Lauren , Asche Stephen E. , Pearson Teresa L. , Clark Cynthia K. , Rush William A. , Cherney Linda M. , Sperl-Hillen JoAnn M. , Bishop Donald B. 
Published: March 2007

OBJECTIVE—To assess the impact of a quality improvement (QI) intervention on the quality of diabetes care at primary care clinics.
RESEARCH DESIGN AND METHODS—Twelve primary care medical practices were matched by size and location and randomized to intervention or control conditions. Intervention clinic staff were trained in a seven-step QI change process to improve diabetes care. Surveys and medical record reviews of 754 patients, surveys of 329 clinic staff, interviews with clinic leaders, and analysis of training session videotapes evaluated compliance with and impact of the intervention. Mixed-model nested analyses compared differences in the quality of diabetes care before and after intervention.
RESULTS—All intervention clinics completed at least six steps of the seven-step QI change process in an 18-month period and, compared with control clinics, had broader staff participation in QI activities (P = 0.04), used patient registries more often (P = 0.03), and had better test rates for HbA1c (A1C), LDL, and blood pressure (P = 0.02). Other processes of diabetes care were unchanged. The intervention did not improve A1C (P = 0.54), LDL (P = 0.46), or blood pressure (P = 0.69) levels or a composite of these outcomes (P = 0.35).
CONCLUSIONS—This QI change process was successfully implemented but failed to improve A1C, LDL, or blood pressure levels. Data suggest that to be successful, such a QI change process should direct more attention to specific clinical actions, such as drug intensification and patient activation.
Depressive Symptoms in Mothers of Infants Identified as Genetically at Risk for Type 1 Diabetes
Authors: Hood Korey K. , Bennett Johnson Suzanne , Carmichael Stacy K. , Laffel Lori M.B. , She Jin-Xiong , Schatz Desmond A. 
Published: March 2007

OBJECTIVE—This study describes maternal depression associated with newborn genetic screening for type 1 diabetes after risk notification.
RESEARCH DESIGN AND METHODS—Mothers of at-risk infants (n = 192), identified through newborn genetic screening as part of the Prospective Assessment of Newborns for Diabetes Autoimmunity study, were administered a structured telephone interview assessing maternal depressive symptoms 1 and 3.5 months after risk notification. Statistical analyses were conducted to examine predictors and correlates of maternal depressive symptoms.
RESULTS—For the total sample, maternal depressive symptoms in response to infant risk status were not elevated at 1 and 3.5 months after risk notification. However, at the first interview, mothers from ethnic minority backgrounds (P &lt; 0.002), with limited education (P &lt; 0.001), and with postpartum depression symptomatology (P &lt; 0.001) reported significantly more depressive symptoms in response to risk notification (r2 = 0.354). At the second interview, postpartum depression symptomatology remained a powerful predictor of depressive symptoms in response to risk notification (P &lt; 0.001). In addition, certain coping styles (wishful thinking, self-blame, and seeking social support) were associated with increased depressive symptoms. A history of major depression was a correlate of both postpartum depressive symptomatology (r = 0.26) and maternal depressive response to risk notification (r = 0.21).
CONCLUSIONS—For the most part, mothers of infants genetically at risk for type 1 diabetes do not appear to evidence elevated depressive symptoms. This suggests that most mothers are resilient when notified of infant risk. However, certain maternal characteristics such as ethnic minority status, less than a high school education, postpartum depression symptomatology, a history of major depression, and certain coping strategies (wishful thinking, self-blame, and seeking social support) appear to be associated with a more difficult maternal response to the news of an infant’s increased genetic risk for type 1 diabetes.
Joint Distribution of Non-HDL and LDL Cholesterol and Coronary Heart Disease Risk Prediction Among Individuals With and Without Diabetes
Authors: Liu Jian , Sempos Christopher , Donahue Richard P. , Dorn Joan , Trevisan Maurizio , Grundy Scott M. 
Published: March 2007

OBJECTIVE—To assess coronary heart disease (CHD) risk within levels of the joint distribution of non-HDL and LDL cholesterol among individuals with and without diabetes.
RESEARCH DESIGN AND METHODS—We used four publicly available data sets for this pooled post hoc analysis and confined the eligible subjects to white individuals aged ≥30 years and free of CHD at baseline (12,660 men and 6,721 women). Diabetes status was defined as either “reported by physician-diagnosed and on medication” or having a fasting glucose level ≥126 mg/dl at the baseline examination. The primary end point was CHD death. Within diabetes categories, risk was assessed based on lipid levels (in mg/dl): non-HDL &lt;130 and LDL &lt;100 (group 1); non-HDL &lt;130 and LDL ≥100 (group 2); non-HDL ≥130 and LDL &lt;100 (group 3); and non-HDL ≥130 and LDL ≥100 (group 4). Group 1 within those without diabetes was the overall reference group.
RESULTS—Of the subjects studied, ∼6% of men and 4% of women were defined as having diabetes. A total of 773 CHD deaths occurred during the average 13 years of follow-up time. A Cox proportional hazard model was used to estimate the relative risk (RR) of CHD death. Those with diabetes had a 200% higher RR than those without diabetes. In a multivariate model, CHD risk in those with diabetes did not increase with increasing LDL, whereas it did increase with increasing non-HDL: RR (95% confidence interval) for group 1: 5.7 (2.0–16.8); group 2: 5.7 (1.6–20.7); group 3: 7.2 (2.6–19.8); and group 4: 7.1 (3.7–13.6).
CONCLUSIONS—Non-HDL is a stronger predictor of CHD death among those with diabetes than LDL and should be given more consideration in the clinical approach to risk reduction among diabetic patients.
Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes
Authors: Selvin Elizabeth , Coresh Josef , Golden Sherita H. , Boland Lori L. , Brancati Frederick L. , Steffes Michael W. 
Published: March 2007

OBJECTIVE—Glycemic control (HbA1c [A1C]) is strongly associated with microvascular disease in individuals with diabetes, but its relation to macrovascular disease and atherosclerosis is less clear. This study examines the relationship between A1C, carotid intima-media thickness (IMT), and traditional cardiovascular risk factors in individuals with diabetes.
RESEARCH DESIGN AND METHODS—A cross-sectional study of 2,060 people with diagnosed and undiagnosed (unrecognized) diabetes in the Atherosclerosis Risk in Communities study was performed.
RESULTS—LDL and HDL cholesterol, plasma triglycerides, and waist-to-hip ratio were significantly associated with A1C after multivariable adjustment. African Americans with undiagnosed and diagnosed diabetes had significantly elevated A1C values compared with whites, even after adjustment for potentially confounding factors. There was a graded association between A1C and carotid IMT. In a fully adjusted model in individuals with undiagnosed diabetes, the odds ratio (OR) of being in the highest quartile of IMT versus the lowest was 2.46 (95% CI 1.16–5.03, comparing the highest quartile of A1C to the lowest). In people with diagnosed diabetes, the comparable OR was 2.62 (1.36–5.06).
CONCLUSIONS—This study identified several important associations between A1C and known risk factors for cardiovascular disease and suggested that A1C is independently related to carotid IMT. Chronically elevated glucose levels may contribute to the development of atherosclerosis in people with diabetes, independent of other risk factors.
Discordant Trends in Microvascular Complications in Adolescents With Type 1 Diabetes From 1990 to 2002
Authors: Mohsin Fauzia , Craig Maria E , Cusumano Janine , Chan Albert K.F. , Hing Stephen , Lee Jennifer W. , Silink Martin , Howard Neville J. , Donaghue Kim C. 
Published: March 2007

OBJECTIVE—Since the Diabetes Control and Complications Trial, diabetes management goals have changed. The aims of the present study were to assess complication rates, including nerve abnormalities, in adolescents from 1990 to 2002 and to investigate associated risk factors.
RESEARCH DESIGN AND METHODS—Cross-sectional analysis of complications was assessed in three study periods (1990–1994 [T1], 1995–1998 [T2], and 1999–2002 [T3]) in adolescents matched for age and diabetes duration (n = 878, median age 14.6 years, median duration 7.5 years). Retinopathy was assessed by seven-field stereoscopic fundal photography, albumin excretion rate (AER) from three consecutive timed overnight urine collections, peripheral nerve function by thermal and vibration thresholds, and autonomic nerve function by cardiovascular reflexes.
RESULTS—Retinopathy declined significantly (T1, 49%; T2, 31%; and T3, 24%; P &lt; 0.0001), early elevation of AER (≥7.5 μg/min) declined (38, 30, and 25%, respectively, P = 0.022), and microalbuminuria (AER ≥20 μg/min) declined (7, 3, and 3%, respectively; P = 0.017, T1 vs. T2 and T3). Autonomic nerve abnormalities were unchanged (18, 21, and 18%, respectively; P = 0.60), but peripheral nerve abnormalities increased (12, 19, and 24%, respectively; P = 0.0017). More patients were treated with three or more injections per day (12, 46, and 67%, respectively; P &lt; 0.0001) and insulin dose increased (1.08, 1.17, and 1.22 units · kg−1 · day−1, respectively; P &lt; 0.0001), but median HbA1c (A1C) was unchanged (8.5, 8.5, and 8.4%, respectively). BMI and height SD score increased: BMI 0.46, 0.67, and 0.79, respectively (P &lt; 0.0001), and height −0.09, 0.05, and 0.27, respectively (P &lt; 0.0001).
CONCLUSIONS—Retinopathy and microalbuminuria declined over time in this cohort, but the increased rate of peripheral nerve abnormalities is of concern. Despite intensified management (higher insulin dose and more injections), A1C has not changed and remains well above the recommended targets for adolescents.
Relationship Between HbA1c Level and Peripheral Arterial Disease
Authors: Muntner Paul , Wildman Rachel P. , Reynolds Kristi , DeSalvo Karen B. , Chen Jing , Fonseca Vivian 
Published: March 2007

OBJECTIVE—Homeostatic glucose control may play an important role in the development of peripheral arterial disease among individuals without diabetes. We sought to evaluate the association of HbA1c (A1C) with peripheral arterial disease in a representative sample of the U.S. population with and without diabetes.
RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted among 4,526 National Health and Nutrition Examination Survey 1999–2002 participants ≥40 years of age. Peripheral arterial disease was defined as an ankle-brachial index &lt;0.9 (n = 327).
RESULTS—Among nondiabetic subjects, the age-standardized prevalence of peripheral arterial disease was 3.1, 4.8, 4.7, and 6.4% for participants with an A1C &lt;5.3, 5.3–5.4, 5.5–5.6, and 5.7–6.0%, respectively (P trend &lt;0.001). The prevalence of peripheral arterial disease was 7.5 and 8.8% for diabetic participants with A1C &lt;7 and ≥7%, respectively. After multivariable adjustment and compared with nondiabetic participants with A1C &lt;5.3%, the odds ratio (95% CI) of peripheral arterial disease for nondiabetic participants with an A1C of 5.3–5.4, 5.5–5.6, and 5.7–6.0% was 1.41 (0.85–2.32), 1.39 (0.70–2.75), and 1.57 (1.02–2.47), respectively, and it was 2.33 (1.15–4.70) and 2.74 (1.25–6.02) for diabetic participants with A1C &lt;7 and ≥7%, respectively.
CONCLUSIONS—An association exists between higher levels of A1C and peripheral arterial disease, even among patients without diabetes. Individuals with A1C levels ≥5.3% should be targeted for aggressive risk factor reduction, which may reduce the burden of subclinical cardiovascular disease even among those without diabetes.
C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance
Authors: Cardellini Marina , Perego Lucia , D’Adamo Monica , Marini Maria Adelaide , Procopio Cristina , Hribal Marta Letizia , Andreozzi Francesco , Frontoni Simona , Giacomelli Maurizio , Paganelli Michele , Pontiroli Antonio E. , Lauro Renato , Folli Franco , Sesti Giorgio 
Published: March 2007

OBJECTIVE—The C-174G promoter polymorphism of the interleukin (IL)-6 gene was found to influence transcriptional activity and plasma IL-6 levels in humans. We addressed the question of whether the C-174G IL-6 polymorphism contributes to variation of insulin sensitivity.
RESEARCH DESIGN AND METHODS—Two cohorts of subjects were genotyped. Cohort 1 includes 275 nondiabetic subjects who underwent a euglycemic-hyperinsulinemic clamp. Cohort 2 includes 77 patients with morbid obesity who underwent laparoscopic adjustable gastric banding (LAGB).
RESULTS—The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In cohort 1, insulin sensitivity was reduced in carriers of the −174G/G genotype as compared with subjects carrying the C allele (P = 0.004). Carriers of −174G/G displayed significantly higher plasma IL-6 levels in comparison with carriers of the C allele. In a stepwise linear regression analysis, the C-174G polymorphism was independently associated with insulin sensitivity; however, after inclusion of plasma IL-6 concentrations, the polymorphism was excluded from the model explaining insulin sensitivity variability, thus suggesting that the polymorphism was affecting insulin sensitivity by regulating IL-6 plasma levels. IL-6 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from obese patients of cohort 2 during LAGB. Carriers of −174G/G showed increased IL-6 expression compared with subjects carrying the C allele (P = 0.04). There was a significant correlation between adipose IL-6 mRNA expression and insulin resistance assessed by homeostasis model assessment (ρ = 0.28, P = 0.014).
CONCLUSIONS—These results indicate that the −174G/G genotype of the IL-6 gene may contribute to variations in insulin sensitivity.