A genome-wide association study identifies genetic determinants of hemoglobin glycation index with implications across sex and ethnicity.

Introduction: We investigated the genetic determinants of variation in the hemoglobin glycation index (HGI), an emerging biomarker for the risk of diabetes complications.

Methods: We conducted a genome-wide association study (GWAS) for HGI in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial ( = 7,913) using linear regression and additive genotype encoding on variants with minor allele frequency greater than 3%. We conducted replication analyses of top findings in the Atherosclerosis Risk in Communities (ARIC) study with inverse variance-weighted meta-analysis.

The glucosylamine oxidation pathway of vitamin C recycling.

The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP is presented from the perspective of the hemoglobin glycation index, a clinically practical biomarker of risk for chronic vascular disease that we propose is mechanistically explained by person-to-person variation in GOP activity.

Effect of biological variation in HbA1c and blood glucose on the diagnosis of prediabetes.

Introduction: People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI.

Methods: Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self-reported diabetes.

Variation in the hemoglobin glycation index.

A high hemoglobin glycation index (HGI) has been repeatedly associated with greater risk for hypoglycemia in people with diabetes and greater risk for chronic vascular disease in people with or without diabetes. This review explores how different sources of analytical and biological variation in HbA1c and blood glucose individually and collectively affect the clinical information value of HGI. We conclude that HGI is a complex quantitative trait that is a clinically practical biomarker of risk for both hypoglycemia and chronic vascular disease.

Standardizing the haemoglobin glycation index.

Aims: A high haemoglobin glycation index (HGI) is associated with greater risk for hypoglycaemia and chronic vascular disease. Standardizing how the HGI is calculated would normalize results between research studies and hospital laboratories and facilitate the clinical use of HGI for assessing risk.

Methods: The HGI is the difference between an observed HbA1c and a predicted HbA1c obtained by inserting fasting plasma glucose (FPG) into a regression equation describing the linear relationship between FPG and HbA1c in a reference population.

The relationship of glycemic control, insulin dose, and race with hypoglycemia in youth with type 1 diabetes.

Introduction: Black youth with T1D have been reported to experience more episodes of hypoglycemia than white patients, despite blacks having higher levels of HbA1c. We hypothesized that black patients may be prescribed higher daily doses of insulin putting them at greater higher risk for hypoglycemia.

Methods: We performed a retrospective analysis of data from a study of social and environmental factors influencing HbA1c in a biracial pediatric population with T1DM.

Implications of the Hemoglobin Glycation Index on the Diagnosis of Prediabetes and Diabetes.

Objective: Fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) from a 75-g oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) can lead to different results when diagnosing prediabetes and diabetes. The Hemoglobin Glycation Index (HGI) quantifies the interindividual variation in glycation resulting in discrepancies between FPG and HbA1c. We used data from the Vitamin D and Type 2 Diabetes (D2d) study to calculate HGI, to identify HGI-associated variables, and to determine how HGI affects prediabetes and diabetes diagnosis.

Associations Between Depressive Symptoms, Fear of Hypoglycemia, Adherence to Management Behaviors and Metabolic Control in Children and Adolescents with Type 1 Diabetes.

We examined the relationship between two malleable risk factors, depressive symptoms and fear of hypoglycemia, in children and adolescents with Type 1 diabetes and their relationship to two important outcomes, adherence behaviors and metabolic control. To assess this relationship, we used a multidimensional measure of adherence, assessing frequency of both blood glucose monitoring and healthy behaviors including diet and exercise. We predicted that higher levels of depressive symptoms and higher levels of fear of hypoglycemia would be associated with worse metabolic control as mediated by poor adherence.

Hemoglobin A1c, frequency of glucose testing and social disadvantage: Metrics of racial health disparity in youth with type 1 diabetes.

Introduction: Black youth with type 1 diabetes (T1D) have higher HbA1c than whites. To understand HbA1c differences, we examined the relationship of psycho-social factors and glucose testing with HbA1c.

Methods: Glucose tests per day (BGs/d) and mean blood glucose (MBG) were calculated from meter data of youth self-identified as black (n = 33) or white (n = 53) with T1D.

Bordetella pseudohinzii targets cilia and impairs tracheal cilia-driven transport in naturally acquired infection in mice.

Several species of the Gram-negative genus Bordetella are the cause of respiratory infections in mammals and birds, including whooping cough (pertussis) in humans. Very recently, a novel atypical species, Bordetella pseudohinzii, was isolated from laboratory mice. These mice presented no obvious clinical symptoms but elevated numbers of neutrophils in bronchoalveolar lavage fluid and inflammatory signs in histopathology.

Intima-media thickness at different arterial segments in pediatric type 1 diabetes patients and its relationship with advanced glycation end products.

Background: Patients with type 1 diabetes mellitus (T1DM) are at risk for premature atherosclerosis (AS), which has its origin in childhood. Carotid intima-media thickness (IMT) is an established surrogate marker for subclinical AS in adults. The first macroscopically detectable AS changes, however, begin in the abdominal aorta.

Differences in Red Blood Cell Indices Do Not Explain Racial Disparity in Hemoglobin A1c in Children with Type 1 Diabetes.

We assessed the association of erythrocyte indices on mean blood glucose-independent racial disparity in hemoglobin A1c (HbA1c) in youth with type 1 diabetes. Blacks still had higher HbA1c after adjustment for mean blood glucose, red blood cell indices, age, and sex. Such differences need to be taken into account when interpreting HbA1c in Black patients.

Racial differences in neighborhood disadvantage, inflammation and metabolic control in black and white pediatric type 1 diabetes patients.

Background: Racial variation in the relationship between blood glucose and hemoglobin A1c (HbA1c) complicates diabetes diagnosis and management in racially mixed populations. Understanding why HbA1c is persistently higher in blacks than whites could help reduce racial disparity in diabetes outcomes.

Objective: Test the hypothesis that neighborhood disadvantage is associated with inflammation and poor metabolic control in a racially mixed population of pediatric type 1 diabetes patients.

Association between Inflammation and Biological Variation in Hemoglobin A1c in U.S. Nondiabetic Adults.

Context: Inflammation is associated with higher glycated hemoglobin (HbA1c) levels. Whether the relationship is independent of blood glucose concentration remains unclear.

Objective: The hemoglobin glycation index (HGI) was used to test the hypothesis that interindividual variation in HbA1c is associated with inflammation.

Simultaneous analysis of reduced glutathione and glutathione disulfide by capillary zone electrophoresis.

This report describes modifications to a CZE method developed by Serru et al. (Clinical Chemistry 2001, 47, 1321-1324) for the simultaneous analysis of reduced glutathione (GSH) and glutathione disulfide (GSSG). Lowering the pH of the run buffer (75 mmol/L boric acid, 25 mmol/L bis-Tris) from pH 8.

Advanced glycation endproducts in children with diabetes.

Objectives: To estimate skin content of advanced glycation endproducts (AGEs) by measurements of skin intrinsic fluorescence (SIF) from youth with diabetes in comparison with a population of youth and adults without diabetes.

Study Design: Using a specialized instrument, skin AGEs were estimated from skin auto-fluorescence induced at 420 nm and corrected for skin pigmentation (SIF420[kx0.5, km0.

Two-dimensional analysis of glycated hemoglobin heterogeneity in pediatric type 1 diabetes patients.

Interindividual and ethnic variation in glycated hemoglobin levels, unrelated to blood glucose variation, complicates the clinical use of glycated hemoglobin assays for the diagnosis and management of diabetes. Assessing the types and amounts of glycated hemoglobins present in erythrocytes could provide insight into the mechanism. Blood samples and self-monitored mean blood glucose (MBG) levels were obtained from 85 pediatric type 1 diabetes patients.

Characterization of unstable hemoglobin A1c complexes by dynamic capillary isoelectric focusing.

Glucose spontaneously reacts with hemoglobin amino groups to produce unstable Schiff base complexes that can dissociate or rearrange to form stable Amadori products. We used dynamic capillary isoelectric focusing and boronate affinity chromatography to assess the formation and dissociation of unstable hemoglobin complexes in vitro. Formation was studied by incubating erythrocytes at 37°C for up to 24h in phosphate-buffered saline (PBS) supplemented with 0 to 55.

Economic burden of hypoglycemia in patients with Type 2 diabetes.

Hypoglycemia is an acute complication of diabetes that increases morbidity, mortality and economic costs of diabetes. It presents major clinical problems for the management of Type 2 diabetes as this disease represents the great majority of all diabetes cases. Hypoglycemia makes it difficult for some individuals to achieve good glycemic control, reduces quality of life and increases the burden of diabetes to healthcare systems.

Appropriateness of the Zucker Diabetic Fatty rat as a model for diabetic microvascular late complications.

Male obese Zucker Diabetic Fatty (ZDF) rats develop type 2 diabetes around eight weeks of age, and are widely used as a model for human diabetes and its complications. The objective of the study was to test whether the complications manifested in the kidney and nerves of ZDF rats really correspond to human diabetic complications in their being related to the hyperglycaemic state. Four groups of ZDF rats were used.