bluuebunny/crossref_metadata_2025_split huggingface dataset:
African-American Women Have Higher Initial HbAlc Levels in Diabetic Pregnancy
Authors: Holcomb William L. , Mostello Dorothea J. , Leguizamon Gustavo F. 
Published: March 2007

OBJECTIVE— African-American women with diabetes are at greater risk for poor glycemic control outside of pregnancy. We evaluated the effect of race on glycemic control in a racially mixed population of women with diabetes entering prenatal care.
RESEARCH DESIGN AND METHODS— HbAlc levels along with demographic data were collected at the first prenatal visit from a group of 234 women with preexisting diabetes. We applied logistic multivariate analysis to identify factors associated with HbAlc levels above the median for the group.
RESULTS— The median HbAlc level for the group was 8%. HbAlc levels were 8.7 ± 2.0% in African-Americans and 7.7 ± 1.5% in Caucasians (P &lt; 0.001). African-American racial designation was significantly and independently associated with high HbAlc when controlled for maternal age, parity, White classification, diabetes type, education, marital status, obesity, insurance type, and first trimester entry into care. The effect of race was confined to the nonobese patients, for whom the adjusted odds ratio for African-American race as a predictor of high HbAlc was 8.15 with a 95% CI of 2.41-27.58 (P = 0.001).
CONCLUSIONS— We found a clear racial disparity in glycemic control among women entering prenatal care with preexisting diabetes. This study demonstrates that there generally is need for better glycemic control among reproductive-age women with diabetes, but especially among those who are African-American.
Macrophage Activation in Type 1 Diabetic Patients With Catheter Obstruction During Peritoneal Insulin Delivery With an Implantable Pump
Authors: Kessler Laurence , Tritschler Sylviane , Bohbot Alain , Sigrist Severine , Karsten Veronique , Boivin Sophie , Dufour Patrick , Belcourt Alain , Pinget Michel 
Published: March 2007

OBJECTIVE— The purpose of this study was to evaluate the activation of macrophages in type 1 diabetic patients during peritoneal insulin delivery with an implantable pump against two types of insulin: that which was collected from the pump reservoir and that which came straight from the bottle (i.e., vial insulin). Macrophage activation was studied in patients with and without catheter obstruction and compared with activation in healthy subjects.
RESEARCH DESIGN AND METHODS— Human insulin (21PH, 400 U/ml;Hoescht) was collected from the pump reservoir (Minimed) of diabetic patients with (n = 3) or without (n = 7) catheter obstruction, as assessed by histological examination of the catheter tip. Monocytes were obtained from venous blood samples from both kinds of diabetic patients and from healthy subjects (n = 5) and were differentiated into monocyte-derived macrophages in culture. Their chemotaxis and tumor necrosis factor-α (TNF-α) release were studied with respect to both types of insulin, as previously stated. Formyl-methionyl-leucyl-phenylalanine (fMLP)and lipopolysaccharide (LPS) were used as controls.
RESULTS— Neither insulin recovered from the pump reservoir nor vial insulin proved chemotactic to macrophages from either healthy subjects or those diabetic patients with and without catheter obstruction. The migration toward fMLP of macrophages from patients presenting a catheter obstruction was significantly higher than that observed with macrophages from either diabetic patients without obstruction or healthy subjects; the chemotactic index (mean± SD) was 3.81 ± 0.36 vs. 2.30 ± 0.89 and 2.60 ±0.80, respectively (P &lt; 0.05). LPS significantly stimulated the TNF-α secretion of macrophages from diabetic subjects with a catheter obstruction, whereas both native and reservoir-recovered insulin had no effect on this release (144.83 ± 67.25 vs. 5.15 ± 2.93 and 5.27± 2.43 pg/ml, P &lt; 0.001).
CONCLUSIONS— The human insulin used in implantable pumps,regardless of how long it had remained in the pump reservoir, did not induce macrophage activation in diabetic patients treated through intraperitoneal insulin delivery. In some of these diabetic patients, catheter obstruction could be explained by their high capacity of macrophage chemotaxis.
Plasma Levels of Cellular Fibronectin in Diabetes
Authors: Kanters Suzan D.J.M. , Banga Jan-Dirk , Algra Ale , Frijns Rini C.J.M. , Beutler Jaap J. , Fijnheer Rob 
Published: March 2007

OBJECTIVE— Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Elevated plasma levels of cellular fibronectin therefore reflect loss of endothelial cell polarization or injury to blood vessels. Consequently, elevated plasma levels of circulating cellular fibronectin have been described in clinical syndromes with vascular damage, although not in diabetes or atherosclerosis.
RESEARCH DESIGN AND METHODS— We determined fibronectin levels in 52 patients with type 1 diabetes, 50 patients with type 2 diabetes, 54 patients with a history of ischemic stroke, 23 patients with renal artery stenosis, and 64 healthy subjects.
RESULTS— Circulating cellular fibronectin was significantly elevated in patients with diabetes (4.3 ± 2.8 μg/ml) compared with patients with ischemic stroke (2.0 ± 0.9 μg/ml), patients with renovascular hypertension (1.7 ± 1.1 μg/ml), and healthy subjects(1.4 ± 0.6 μg/ml). Patients with diabetes and at least one cardiovascular risk factor had an almost 2.5-fold increase in cellular fibronectin compared with diabetic subjects without such a risk factor. In multivariate regression analysis, higher triglycerides, current or past cigarette smoking, and higher urinary albumin excretion were independently associated with an increase in circulating cellular fibronectin in diabetes.
CONCLUSIONS— These results suggest that circulating cellular fibronectin may be a marker protein for endothelial cell activation,especially in diabetes. Prospective studies are needed to explore this possibility.
Plasma Levels of Tumor Necrosis Factor-α, Angiotensin II, Growth Hormone, and IGF-I Are Not Elevated in Insulin-Resistant Obese Individuals With Impaired Glucose Tolerance
Authors: Blüher Matthias , Kratzsch Juergen , Paschke Ralf 
Published: March 2007

OBJECTIVE— To investigate the relationship between insulin resistance and plasma concentrations of free fatty acids (FFAs), leptin, and potential agonists of the insulin receptor substrate (IRS) system, including tumor necrosis factor-α (TNF-α), IGF-I, growth hormone (GH), and angiotensin II in individuals with impaired glucose tolerance (IGT).
RESEARCH DESIGN AND METHODS— Because glucose toxicity per se leads to insulin resistance, the determination of the primary metabolic alterations leading to insulin resistance is best accomplished in individuals who are at an increased risk to develop type 2 diabetes. Therefore, 48 subjects with IGT and insulin resistance (IR), characterized by hyperinsulinemic-euglycemic clamps, were compared with 52 healthy insulin-sensitive (IS) control subjects with respect to the relationship between the plasma levels of TNF-α, IGF-I, GH, angiotensin II, FFA,leptin, and insulin resistance.
RESULTS— Between the IR and the IS groups, there were no significant differences in the plasma concentrations of TNF-α, GH,angiotensin II, IGF-I, and leptin. However, plasma FFA levels were significantly elevated in the IR group compared with the IS group after matching for BMI.
CONCLUSIONS— The plasma concentrations of FFA, but not TNF-α, IGF-I, GH, and angiotensin II, are elevated in patients at an early stage of insulin resistance, suggesting that FFAs, but not the other modulators of the IRS system, may be a primary metabolic abnormality leading to insulin resistance.
Increased Prevalence of Significant Coronary Artery Calcification in Patients With Diabetes
Authors: Schurgin Sunita , Rich Stuart , Mazzone Theodore 
Published: March 2007

OBJECTIVE— Coronary artery disease is the major cause of morbidity and mortality in patients with diabetes. Detection of coronary artery disease before the first myocardial infarction and before anginal symptoms will allow for strategies designed to reduce the cardiovascular event rate in this group of patients. Electron beam—computed tomography (EBCT)is a noninvasive technology for evaluating the extent of coronary artery atherosclerosis that relies on the detection of coronary artery calcium (CAC). We used EBCT to detect significant coronary artery atherosclerosis in diabetic patients without symptoms of heart disease.
RESEARCH DESIGN AND METHODS— We used EBCT to evaluate calcium in the coronary arteries of 139 consecutive diabetic patients scanned over a 20-month period. The CAC scores in this group were compared with a randomly selected nondiabetic control group and a control group that was selected to match a number of established cardiovascular risk factors.
RESULTS— Patients with diabetes had a significant increase in the prevalence of CAC scores ≥400 (25.9%) compared with the randomly selected (7.2%) and matched (14.4%) nondiabetic control groups. Scores in this range have been reported to be highly predictive for abnormal stress myocardial perfusion tomography and subsequent coronary events.
CONCLUSIONS— Our results, therefore, indicate a substantial prevalence of significant coronary artery disease in an asymptomatic diabetic patient population compared with non-diabetic control subjects. They also suggest that EBCT may be a useful approach for selecting a group of diabetic subjects who would benefit most from additional evaluation for subclinical coronary artery disease.
Subclinical States of Glucose Intolerance and Risk of Death in the U.S.
Authors: Saydah Sharon H. , Loria Catherine M. , Eberhardt Mark S. , Brancati Frederick L. 
Published: March 2007

OBJECTIVE—Although clinically evident type 2 diabetes is a well-established cause of mortality, less is known about subclinical states of glucose intolerance.
RESEARCH DESIGN AND METHODS—Data from the Second National Health and Nutrition Examination Survey Mortality Study, a prospective study of adults, were analyzed. This analysis focused on a nationally representative sample of 3,174 adults aged 30–75 years who underwent an oral glucose tolerance test at baseline (1976–1980) and who were followed up for death through 1992.
RESULTS—Using 1985 World Health Organization criteria, adults were classified as having previously diagnosed diabetes (n = 248), undiagnosed diabetes (n = 183), impaired glucose tolerance (IGT) (n = 480), or normal glucose tolerance (n = 2,263). For these groups, cumulative all-cause mortality through age 70 was 41, 34, 27, and 20%, respectively (P &lt; 0.001). Compared with those with normal glucose tolerance, the multivariate adjusted RR of all-cause mortality was greatest for adults with diagnosed diabetes (RR 2.11, 95% CI 1.56–2.84), followed by those with undiagnosed diabetes (1.77, 1.13–2.75) and those with IGT (1.42, 1.08–1.87; P &lt; 0.001). A similar pattern of risk was observed for cardiovascular disease mortality.
CONCLUSIONS—In the U.S., there was a gradient of mortality associated with abnormal glucose tolerance ranging from a 40% greater risk in adults with IGT to a 110% greater risk in adults with clinically evident diabetes. These associations were independent of established cardiovascular disease risk factors.
Blood Pressure Does Not Rise Before the Onset of Microalbuminuria in Children Followed From Diagnosis of Type 1 Diabetes
Authors: Schultz Carl J. , Neil H. Andrew W. , Dalton R. Neil , Bahu Teresa Konopelska , Dunger David B. ,   on behalf of the Oxford Regional Prospective Study Group
Published: March 2007

OBJECTIVE—To examine whether a rise in blood pressure could be detected before the onset of microalbuminuria (MA) in a cohort of children followed from diagnosis of type 1 diabetes.
RESEARCH DESIGN AND METHODS—The Oxford Regional Prospective Study is an incident cohort study of children with type 1 diabetes aged (mean ± SD) 9.8 ± 3.7 years at diagnosis. Subjects were assessed annually from diagnosis, with measurement of HbA1c, arterial blood pressure (random zero), and three urine samples for estimation of the albumin/creatinine ratio. During follow-up, 63 of 494 children developed MA at one or more annual assessments and were designated as cases for a nested case-control study. Each case was matched for sex and age at diagnosis with two normoalbuminuric control subjects. Blood pressure (BP) data were compared at corresponding years of diabetes duration.
RESULTS—Cases with MA were similar to normoalbuminuric control subjects with respect to age and BMI, but they had higher mean HbA1c levels (mean difference 1.1%, P &lt; 0.001). In the years before the onset of MA, the diastolic BP standard deviation score (SDS) was significantly higher than zero in cases (mean 0.49, P &lt; 0.001) and in control subjects (0.50, P &lt; 0.001). No difference could be detected between cases and control subjects before the onset of MA in either systolic or diastolic BP (mean difference systolic −1.2 mmHg [95% CI −4.7 to 2.7], mean difference diastolic 0.1 mmHg [−2.4 to 2.6]). However, within the cases, the onset of MA was associated with elevations in systolic and diastolic BP SDSs (F = 16.1, P &lt; 0.001; and F = 18.0, P &lt; 0.001). BMI, but not HbA1c, was associated with systolic and diastolic BP SDSs in the subjects with MA (F = 0.6, P = 0.4; and F = 12.3, P = 0.001). However, the association of BP with MA remained significant for systolic BP (P = 0.001) and for diastolic BP (P &lt; 0.001) after adjusting for BMI.
CONCLUSIONS—A rise in systemic BP cannot be detected before the first appearance of MA in children with type 1 diabetes. BP rises concurrently with the onset of MA and is also closely related to BMI.
Recent Advances in Our Understanding of Insulin Action and Insulin Resistance
Authors: Le Roith Derek , Zick Yehiel 
Published: March 2007

Insulin signaling at the target tissue results in a large array of biological outcomes. These events are essential for normal growth and development and for normal homeostasis of glucose, fat, and protein metabolism. Elucidating the intracellular events after activation of the IR has been the primary focus of a large number of investigators for decades, and for excellent reasons. Understanding the signaling pathways involved in insulin action could lead to a better understanding of the pathophysiology of insulin resistance associated with obesity and type 2 diabetes, and identifying key molecules and processes could lead to newer and more effective therapeutic agents for treating these common disorders.
This review summarizes our previous understanding of how insulin acts and outlines some recent developments in our understanding of insulin action and insulin resistance at the cellular level, beginning with a discussion on the discovery of evolutionarily conserved molecules of the insulin signaling pathways. This article will also provide a summary of a few in vitro and cellular models of insulin resistance and a description of some new paradigms in the cellular mechanisms of insulin action.
This review will not attempt to be all-inclusive; for a more comprehensive understanding, readers are referred to more complete reviews on insulin action (1–5).
Interactions Between Variants in the β3-Adrenergic Receptor and Peroxisome Proliferator–Activated Receptor-γ2 Genes and Obesity
Authors: Hsueh Wen-Chi , Cole Shelley A. , Shuldiner Alan R. , Beamer Brock A. , Blangero John , Hixson James E. , MacCluer Jean W. , Mitchell Braxton D. 
Published: March 2007

OBJECTIVE—Previous studies have reported modest associations between measures of obesity and the Trp64Arg variant of the β3-adrenergic receptor (ADRβ3) and the Pro12Ala variant of the peroxisome proliferator–activated receptor (PPAR)-γ2. We hypothesized that these single gene variants may mark mutations that act through convergent pathways to produce synergistic effects on obesity.
RESEARCH DESIGN AND METHODS—The sample included 453 subjects from 10 large Mexican-American families participating in the population-based San Antonio Family Heart Study. The effects of each gene variant singly and jointly were estimated as fixed effects using the measured genotype approach framework. Analyses were conditioned on the pedigree structures to account for the correlations among family members. Statistical significance was evaluated by the likelihood ratio test with adjustment for age, sex, and diabetes status.
RESULTS—The allele frequencies for the ADRβ3 Trp64Arg and PPARγ2 Pro12Ala variants were 18 and 12%, respectively. The ADRβ3 variant was not significantly associated with any of the obesity-related traits, but subjects with the PPARγ2 variant (n = 98) had significantly higher levels of fasting insulin (P = 0.03), leptin (P = 0.009), and waist circumference (P = 0.03) than those without. Subjects with both gene variants (n = 32) had significantly higher BMI, insulin, and leptin levels than those with only the PPARγ2 variant (n = 66) (P for interaction: 0.04, 0.02, and 0.01 for BMI, fasting insulin, and leptin, respectively).
CONCLUSIONS—Our results suggest that epistatic models with genes that have modest individual effects may be useful in understanding the genetic underpinnings of typical obesity in humans.
Cardiovascular Morbidity and Mortality Associated With the Metabolic Syndrome
Authors: Isomaa Bo , Almgren Peter , Tuomi Tiinamaija , Forsén Björn , Lahti Kaj , Nissén Michael , Taskinen Marja-Riitta , Groop Leif 
Published: March 2007

OBJECTIVE—To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization (WHO).
RESEARCH DESIGN AND METHODS—A total of 4,483 subjects aged 35–70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome. In subjects who had type 2 diabetes (n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798), or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years.
RESULTS—In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes. The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome (P &lt; 0.001). Cardiovascular mortality was markedly increased in subjects with the metabolic syndrome (12.0 vs. 2.2%, P &lt; 0.001). Of the individual components of the metabolic syndrome, microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P = 0.002).
CONCLUSIONS—The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from different studies.
α-Dicarbonyls Increase in the Postprandial Period and Reflect the Degree of Hyperglycemia
Authors: Beisswenger Paul J. , Howell Scott K. , O’Dell Rita M. , Wood Mary E. , Touchette Allison D. , Szwergold Benjamin S. 
Published: March 2007

OBJECTIVE—Chronic hyperglycemia is known to increase tissue glycation and diabetic complications, but controversy exists regarding the independent role of increased postprandial glucose excursions. To address this question, we have studied the effect of postprandial glycemic excursions (PPGEs) on levels of methylglyoxal (MG) and 3-deoxyglucosone (3-DG), two highly reactive precursors of advanced glycation end products (AGEs).
RESEARCH DESIGN AND METHODS—We performed 4-month crossover studies on 21 subjects with type 1 diabetes and compared the effect of premeal insulin lispro or regular insulin on PPGEs and MG/3-DG excursions. PPGE was determined after standard test meal (STMs) and by frequent postprandial glucose monitoring. HbA1c and postprandial MG and d-lactate were measured by HPLC, whereas 3-DG was determined by gas chromatography/mass spectroscopy.
RESULTS—Treatment with insulin lispro resulted in a highly significant reduction in PPGEs relative to the regular insulin–treated group (P = 0.0005). However, HbA1c levels were similar in the two groups, and no relationship was observed between HbA1c and PPGE (P = 0.93). Significant postprandial increases in MG, 3-DG, and d-lactate occurred after the STM. Excursions of MG and 3-DG were highly correlated with levels of PPGE (R = 0.55, P = 0.0002 and R = 0.61, P = 0.0004; respectively), whereas a significant inverse relationship was seen between PPGE and d-lactate excursions (R = 0.40, P = 0.01). Conversely, no correlation was observed between HbA1c and postprandial MG, 3-DG, or d-lactate levels.
CONCLUSIONS—Increased production of MG and 3-DG occur with greater PPGE, whereas HbA1c does not reflect these differences. Reduced PPGE also leads to increased production of d-lactate, indicating a role for increased detoxification in reducing MG levels. The higher postprandial levels of MG and 3-DG observed with greater PPGE may provide a partial explanation for the adverse effects of glycemic lability and support the value of agents that reduce glucose excursions.
Midpregnancy Serum C-Peptide Concentration and Subsequent Pregnancy-Induced Hypertension
Authors: Yasuhi Ichiro , Hogan Joseph W. , Canick Jacob , Sosa Maryellen B. , Carpenter Marshall W. 
Published: March 2007

OBJECTIVE—To test the hypothesis that elevated midpregnancy serum insulin (IRI) and C-peptide (CP) concentrations are associated with later development of pregnancy-induced hypertension (PIH), independent of prepregnancy obesity and midpregnancy blood pressure.
RESEARCH DESIGN AND METHODS—In this prospective study, a cohort of normotensive women, ages ≥18 years, performed a 50-g glucose challenge test at 24–30 weeks’ gestational age. Blood samples were collected after an overnight fast and 1 h after glucose ingestion. Serum IRI and CP concentrations were measured in each sample. Maternal height, blood pressure, and proteinuria were measured at the time of glucose challenge testing and after 36 weeks’ gestational age.
RESULTS—Of 320 subjects enrolled, 44 women (13.8%) had subsequent PIH. Crude odds ratios (ORs) for development of PIH associated with each 1 U rise in log fasting IRI, log fasting CP, and glucose-induced increase in CP (expressed as log [postprandial CP/fasting CP]) were 2.0 (95% CI 1.3–3.3), 1.8 (CI 1.2–2.7), and 2.3 (CI 1.1–4.9), respectively. After controlling for prepregnancy BMI, gestational age, and midpregnancy mean arterial pressure, adjusted ORs corresponding to log fasting IRI and CP for the development of PIH were 1.3 (95% CI 0.7–2.3) and 1.7 (CI 1.1–2.7), respectively, and, after adjustment for fasting CP, the adjusted OR of the glucose-induced rise in log CP was 3.7 (CI 1.5–9.3).
CONCLUSIONS—Mid-pregnancy fasting and postoral glucose CP levels are associated with subsequent development of PIH, independent of maternal obesity and midpregnancy baseline blood pressure. These findings may reflect an amplified β-cell response to glycemic stimulus, similar to that found in states of insulin resistance, that appears to be independently associated with PIH.