James M Hempe

Research Institute for Children at Children's Hospital New Orleans, New Orleans, Louisiana, United States

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Publications (66)285.25 Total impact

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    ABSTRACT: 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. 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. Patients (n = 86, 53 white, 33 black) were recruited from diabetes clinics. Self-monitored mean blood glucose (MBG) was downloaded from patient glucose meters. Blood was collected for analysis of HbA1c and C-reactive protein (CRP). Patient addresses and census data were used to calculate a concentrated disadvantage index (CDI). High CDI reflects characteristics of disadvantaged neighborhoods. HbA1c and MBG were higher (p < 0.0001) in blacks [10.4% (90.3 mmol/mol), 255 mg/dL] than whites [8.9% (73.9 mmol/mol), 198 mg/dL). CDI was higher in blacks (p < 0.0001) and positively correlated with HbA1c (r = 0.40, p = 0.0002) and MBG (r = 0.35, p = 0.0011) unless controlled for race. CDI was positively associated with CRP by linear regression within racial groups. CRP was not different between racial groups, and was not correlated with MBG, but was positively correlated with HbA1c when controlled for race (p = 0.04). Neighborhood disadvantage was associated with inflammation and poor metabolic control in pediatric type 1 diabetes patients. Marked racial differences in potential confounding factors precluded differentiation between genetic and environmental effects. Future studies should recruit patients matched for neighborhood characteristics and treatment regimen to more comprehensively assess racial variation in HbA1c.
    No preview · Article · Jan 2016 · Pediatric Diabetes
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    Preview · Article · Oct 2015 · Diabetes Care
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    ABSTRACT: This study tested the hypothesis that intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial disproportionately produced adverse outcomes in patients with diabetes with a high hemoglobin glycation index (HGI = observed HbA1c - predicted HbA1c). ACCORD was a randomized controlled trial of 10,251 patients with type 2 diabetes assigned to standard or intensive treatment with HbA1c goals of 7.0% to 7.9% (53 to 63 mmol/mol) and less than 6% (42 mmol/mol), respectively. In this ancillary study, a linear regression equation (HbA1c = 0.009 × fasting plasma glucose [FPG] [mg/dL] + 6.8) was derived from 1,000 randomly extracted participants at baseline. Baseline FPG values were used to calculate predicted HbA1c and HGI for the remaining 9,125 participants. Kaplan-Meier and Cox regression were used to assess the effects of intensive treatment on outcomes in patients with a low, moderate, or high HGI. Intensive treatment was associated with improved primary outcomes (composite of cardiovascular events) in the low (hazard ratio [HR] 0.75 [95% CI 0.59-0.95]) and moderate (HR 0.77 [95% CI 0.61-0.97]) HGI subgroups but not in the high HGI subgroup (HR 1.14 [95% CI 0.93-1.40]). Higher total mortality in intensively treated patients was confined to the high HGI subgroup (HR 1.41 [95% CI 1.10-1.80]). A high HGI was associated with a greater risk for hypoglycemia in the standard and intensive treatment groups. HGI calculated at baseline identified subpopulations in ACCORD with harms or benefits from intensive glycemic control. HbA1c is not a one-size-fits-all indicator of blood glucose control, and taking this into account when making management decisions could improve diabetes care. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    No preview · Article · Apr 2015 · Diabetes care
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    ABSTRACT: Inflammation is associated with higher glycated hemoglobin (HbA1c) levels. Whether the relationship is independent of blood glucose concentration remains unclear. The hemoglobin glycation index (HGI) was used to test the hypothesis that inter-individual variation in HbA1c is associated with inflammation. This study used non-diabetic adults from the National Health and Nutrition Examination Survey (1999-2008). A subsample of participants was used to estimate the linear regression relationship between HbA1c and fasting plasma glucose (FPG). Predicted HbA1c were calculated for 7,323 non-diabetic participants by inserting FPG into the equation (HbA1c= 0.017× FPG (mg/dl) + 3.7). HGI was calculated as the difference between the observed and predicted HbA1c and the population was divided into low, moderate and high HGI subgroups. Polymorphonuclear leukocytes (PMNL), monocytes, and C-reactive protein (CRP) were used as biomarkers of inflammation. Mean HbA1c, CRP, monocyte and PMNL levels, but not FPG, progressively increased in the low, moderate and high HGI subgroups. There were disproportionately more blacks than whites in the high HGI subgroup. CRP (ß: 0.009, 95% CI 0.0001, 0.017), PMNL (ß: 0.036, 95% CI: 0.010, 0.062), and monocyte count (ß: 0.072, 95% CI: 0.041, 0.104) were each independent predictors of HGI after adjustment for age, gender, race, triglycerides, hemoglobin level, mean corpuscular volume, red cell distribution width, and obesity status. HGI reflects the effects of inflammation on HbA1c in a non-diabetic population of U.S. adults and may be a marker of risk associated with inflammation independent of FPG, race and obesity.
    No preview · Article · Apr 2015 · The Journal of Clinical Endocrinology and Metabolism

  • No preview · Conference Paper · Feb 2015
  • S. Liu · J. M. Hempe · R. J. McCarter · S. Li · V. A. Fonseca
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    ABSTRACT: 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 inter-individual variation in HbA1c is associated with inflammation. PARTICIPANTS: This study used non-diabetic adults from the National Health and Nutrition Examination Survey (1999-2008). MAIN OUTCOME MEASURES: A subsample of participants was used to estimate the linear regression relationship between HbA1c and fasting plasma glucose (FPG). Predicted HbA1c were calculated for 7,323 non-diabetic participants by inserting FPG into the equation (HbA1c= 0.017x FPG (mg/dl) + 3.7). HGI was calculated as the difference between the observed and predicted HbA1c and the population was divided into low, moderate and high HGI subgroups. Polymorphonuclear leukocytes (PMNL), monocytes, and C-reactive protein (CRP) were used as biomarkers of inflammation. RESULTS: Mean HbA1c, CRP, monocyte and PMNL levels, but not FPG, progressively increased in the low, moderate and high HGI subgroups. There were disproportionately more blacks than whites in the high HGI subgroup. CRP (ss: 0.009, 95% CI 0.0001, 0.017), PMNL (ss: 0.036, 95% CI: 0.010, 0.062), and monocyte count (ss: 0.072, 95% CI: 0.041, 0.104) were each independent predictors of HGI after adjustment for age, gender, race, triglycerides, hemoglobin level, mean corpuscular volume, red cell distribution width, and obesity status. CONCLUSIONS: HGI reflects the effects of inflammation on HbA1c in a non-diabetic population of U.S. adults and may be a marker of risk associated with inflammation independent of FPG, race and obesity.
    No preview · Article · Jan 2015
  • James M Hempe · Jeannine Ory-Ascani
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    ABSTRACT: This report describes modifications to a capillary zone electrophoresis method developed by Serru et al. (Clinical Chemistry 47:1321, 2001) 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 8.4 to 7.8 markedly improved GSH peak area reproducibility and allowed multiple samples to be analyzed without changing run buffers due to ion depletion. Sample preparation using red blood cells (RBC) instead of whole blood, combined with glutathione extraction at a lower concentration of metaphosphoric acid (5%), increased assay sensitivity and decreased interference. CZE assay results for clinical samples containing 1000 to 3200 μmol GSH/l RBC and 100 to 400 μmol GSSG/l RBC were highly correlated (r(2) ≥0.95) with results obtained using a commercial dithionitrobenze-based glutathione assay. The modified CZE assay has proven useful for the analysis of glutathione in both mouse and human RBC. This article is protected by copyright. All rights reserved.
    No preview · Article · Apr 2014 · Electrophoresis
  • Stuart A Chalew · Robert J McCarter · James M Hempe

    No preview · Article · Sep 2013 · Pediatric Diabetes
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    ABSTRACT: 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. Using a specialized instrument, skin AGEs were estimated from skin auto-fluorescence induced at 420 nm and corrected for skin pigmentation (SIF420[kx0.5, km0.5]) in children with types 1 and 2 diabetes, as well as children and adults without diabetes. The effect of age, sex, ethnicity, and diabetes status on SIF420[kx0.5, km0.5] was analyzed. SIF420[kx0.5, km0.5] increased with chronologic age and was higher in children with diabetes compared with children without diabetes (P = .0001). SIF420[kx0.5, km0.5] from 43% of children with type 1 diabetes and 55% with type 2 diabetes overlapped the range of adults without diabetes. SIF420[kx0.5, km0.5] was higher in girls than boys in patients with diabetes patients. However, there was no effect of sex or race on SIF420[kx0.5, km0.5] in subjects without diabetes. After 4-6 years' exposure to diabetes, many children will have precociously high estimates of skin AGEs, comparable with levels that would naturally accumulate only after ∼25 years of chronologic aging. Potentially, this technology identifies children who are at increased risk for complications.
    No preview · Article · Aug 2013 · The Journal of pediatrics
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    James M Hempe · Amanda M McGehee · Stuart A Chalew
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    ABSTRACT: Inter-individual 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. Glycated hemoglobin levels were measured using three primary assays (boronate affinity chromatography, capillary isoelectric focusing (CIEF), and standardized DCA2000+ immunoassay), and a two-dimensional (2D) analytical system consisting of boronate affinity chromatography followed by CIEF. The 2D system separated hemoglobin into five subfractions, four of which contained glycated hemoglobins. Glycated hemoglobin measurements were compared in patients with low, moderate or high hemoglobin glycation index (HGI), a measure of glycated hemoglobin controlled for blood glucose variation. MBG was not significantly different between HGI groups. Glycated hemoglobin levels measured by all three primary assays and in all four glycated 2D subfractions were significantly different between HGI groups and highest in high HGI patients. These results show that inter-individual variation in glycated hemoglobin levels was evident in diabetes patients with similar blood glucose levels regardless of which glycated hemoglobins were measured.
    Full-text · Article · Jul 2013 · Analytical Biochemistry
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    Full-text · Article · Mar 2013 · Diabetes Care
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    ABSTRACT: 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 55.6 mmol/L glucose. Dissociation was studied by incubating glucose-loaded erythrocytes in PBS without glucose. Dynamic capillary isoelectric focusing separated hemoglobin A1c into two subfractions identified as A1c1 and A1c2. The A1c1 subfraction contained both stable and unstable hemoglobin complexes. The A1c2 subfraction contained only unstable hemoglobin complexes. Both subfractions quantitatively increased in the presence of glucose and decreased in its absence. Rates of increase and decrease were faster and time to equilibrium was shorter for A1c2 (~4 h) compared with A1c1 (~20 h). Unstable hemoglobin complexes did not bind to boronate affinity columns but instead eluted intact in A1c1 and A1c2 subfractions from nonglycated affinity fractions. Cyanoborohydride reduction confirmed the presence of Schiff base complexes. Evidence of multiple unstable hemoglobin complexes with different rates of glycation suggests that new models are needed to describe nonenzymatic hemoglobin glycation.
    Full-text · Article · Feb 2012 · Analytical Biochemistry
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    ABSTRACT: 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. Understanding hypoglycemia risk factors can help patients with Type 2 diabetes to correct and avoid hypoglycemia. Recently, an increased risk of hypoglycemia with intensive glycemic control has been identified as an important problem in optimally controlling blood glucose levels in patients with Type 2 diabetes.
    Full-text · Article · Feb 2012 · Expert Review of Pharmacoeconomics & Outcomes Research
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    James M Hempe · Robert J McCarter · Stuart A Chalew

    Full-text · Article · Nov 2011 · Diabetes care
  • Stuart Chalew · James Hempe · Robert McCarter

    No preview · Article · Jun 2011 · JAMA The Journal of the American Medical Association
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    ABSTRACT: To evaluate the relationship between skin advanced glycation end products (sAGEs) with mean blood glucose (MBG), hemoglobin A(1c) (HbA(1c)), and MBG-independent, between-patient differences in HbA(1c) among children with type 1 diabetes. Children aged 5 to 20 years with type 1 diabetes of at least 1 year duration participated. At a clinic visit, sAGE was estimated noninvasively by measurement of skin intrinsic fluorescence (SIF). SIF data were adjusted to correct for variation in skin pigmentation. MBG-independent, between-patient differences in HbA(1c) were examined by statistically controlling HbA(1c) for MBG or alternatively by use of a hemoglobin glycation index (HGI). Results were similar whether HbA(1c), MBG, and HGI were analyzed as single values from the time of the SIF examination visit or as the mean values from all available visits of the patient. HbA(1c) was correlated with MBG (r = 0.5; P < 0.001; n = 110). HbA(1c) and HGI, but not MBG, were statistically associated with SIF after adjustment for age, duration of diabetes, race, sex, and BMI z-score. SIF increased with age and duration of diabetes and was higher in girls than boys. sAGE levels estimated by SIF increase with age, duration of diabetes, and female sex. sAGE is correlated with MBG-independent biological variation in HbA(1c), but not with MBG itself. These results suggest that factors besides MBG that influence HbA(1c) levels also contribute to accumulation of sAGE.
    Full-text · Article · Jun 2011 · Diabetes care
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    ABSTRACT: The hemoglobin glycation index (HGI) assesses biological variation in A1c after accounting for the effect of mean blood glucose (MBG). Previous studies minimized analytical variation that could mask biological variation and showed that HGI was consistent within individuals over time and positively associated with risk for microvascular complications. We tested the hypothesis that biological variation in A1c can be assessed by HGI calculated using routine MBG and A1c data obtained from a typical diabetes clinic. Self-monitored MBG and A1c were collected from charts of 202 pediatric type 1 diabetes patients attending 1612 clinic visits over 6 yr. Predicted A1c was calculated from the linear regression equation of A1c on MBG in the study population. HGI was calculated by subtracting predicted A1c from observed A1c. Patients were divided into low, moderate, and high HGI tertile groups. Patients used 12 models of glucose meters. Download protocols varied with clinical practice over time. A1c was measured by multiple assays and laboratories. Despite this analytical heterogeneity, HGI was significantly different between individuals and correlated within individuals. MBG (mean ± SD, mg/dL) was similar in the low (186 ± 31), moderate (195 ± 28), and high (199 ± 42) HGI groups. A1c (%) was significantly different (p < 0.0001) in the low (7.6 ± 0.7), moderate (8.4 ± 0.7), and high (9.6 ± 1.1) HGI groups. Biological variation in A1c is a robust quantitative trait that can be assessed using HGI calculated from routine clinic data. This suggests that HGI could be used clinically for more personalized assessment of complications risk.
    No preview · Article · Nov 2010 · Pediatric Diabetes
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    James M Hempe · Arlette A Soros · Stuart A Chalew
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    ABSTRACT: The A1C-Derived Average Glucose study recommended reporting A1C in estimated average glucose (eAG) equivalents. We compared eAG with self-monitored mean blood glucose (MBG) to determine whether eAG is systematically biased due to biological variation in the relationship between MBG and A1C. MBG and A1C were recorded from charts of 202 pediatric type 1 diabetic patients at 1,612 clinic visits. Patients were divided into groups with low, moderate, or high A1C bias based on a hemoglobin glycation index (HGI). The mean +/- SD values for MBG versus eAG were as follows: total population, 194 +/- 34 vs. 196 +/- 36 mg/dl; low-HGI group, 186 +/- 31 vs. 163 +/- 20 mg/dl; moderate-HGI group, 195 +/- 28 vs. 193 +/- 19 mg/dl; and high-HGI group, 199 +/- 42 vs. 230 +/- 31 mg/dl. eAG underestimated MBG in low HGI patients and overestimated MBG in high HGI patients. Disagreement between eAG and MBG downloaded from patient glucose meters will cause confusion if eAG is implemented for clinical use.
    Preview · Article · Mar 2010 · Diabetes care
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    Jodi L Kamps · James M Hempe · Stuart A Chalew
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    ABSTRACT: Mean blood glucose (MBG) and MBG-independent factors both influence A1C levels. Race was related to A1C independent of MBG in adults. The goal of this study was to determine if racial disparity exists in A1C independent of MBG in children with diabetes. Participants included 276 children with type 1 diabetes. A1C and MBG were obtained from multiple clinic visits, and a hemoglobin glycation index (HGI) (an assessment of A1C levels independent of MBG) was calculated. A1C and HGI were analyzed controlling for age, diabetes duration, and MBG. RESULTS African Americans had statistically significantly higher A1C (9.1 +/- 0.1) and HGI (0.64 +/- 0.11) than Caucasians (A1C 8.3 +/- 0.1, HGI -0.15 +/- 0.07) independent of covariates. Because of racial disparity in A1C, which is independent of MBG, we recommend that A1C and MBG be used together to make therapeutic decisions for children with diabetes.
    Preview · Article · Feb 2010 · Diabetes care
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    ABSTRACT: We hypothesized that labile A1C (LA1C) is directly correlated with stable A1C (SA1C) and between-patient differences in SA1C, which are independent of mean blood glucose (MBG). We measured SA1C, LA1C, MBG, and a single clinic capillary glucose (CCG) from 152 pediatric patients with type 1 diabetes. Patients were grouped as high, moderate, or low glycators by hemoglobin glycation index (HGI). LA1C and SA1C were correlated with CCG and MBG. LA1C was not correlated with SA1C (r = 0.06, P = 0.453). LA1C level was significantly associated with glycator group status (P < 0.0019) and CCG (P < 0.0001). Adjusted LA1C levels were highest in the low-HGI patients and lowest in the high-HGI group. A conventional model of SA1C being directly correlated with LA1C concentration was not confirmed. Between-patient differences in SA1C at the same MBG may be due to complex intracellular factors influencing formation of SA1C from LA1C.
    Full-text · Article · Nov 2009 · Diabetes care

Publication Stats

1k Citations
285.25 Total Impact Points

Institutions

  • 2006-2015
    • Research Institute for Children at Children's Hospital New Orleans
      New Orleans, Louisiana, United States
  • 1997-2015
    • Children's Hospital New Orleans
      New Orleans, Louisiana, United States
  • 1995-2013
    • Louisiana State University Health Sciences Center New Orleans
      • • Department of Pediatrics
      • • Section of Pediatric Endocrinology
      • • Research Institute For Children
      • • Section of Gastroenterology
      New Orleans, Louisiana, United States
  • 2004
    • George Washington University
      • Department of Pediatrics
      Washington, Washington, D.C., United States
  • 1989-1992
    • University of Florida
      • Department of Nutritional Sciences
      Gainesville, Florida, United States