Linda A Barbour

University of Colorado, Denver, Colorado, United States

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Publications (29)127.39 Total impact

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    ABSTRACT: Conventional diet therapy in women with gestational diabetes (GDM) has focused on restriction of carbohydrate (CHO), which typically results in greater fat intake. Diets higher in fat are known to promote insulin resistance and thus may increase fetal adiposity.
    09/2015; 11(3):92-92. DOI:10.1007/s12467-013-0045-3
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    ABSTRACT: Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher-complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity. At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks. After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P < 0.01). Infant adiposity trended lower with CHOICE (10.1 ± 1.4 vs. 12.6 ± 2%, respectively). A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet. © 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.
    Diabetes care 07/2015; DOI:10.2337/dc15-0515 · 8.57 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S172. DOI:10.1016/j.ajog.2014.10.365 · 3.97 Impact Factor
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    ABSTRACT: The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (-60-75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.
    PLoS ONE 09/2014; 9(9):e106872. DOI:10.1371/journal.pone.0106872 · 3.53 Impact Factor
  • Linda A Barbour
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    ABSTRACT: Climbing obesity rates in women have propelled the increasing prevalence of type 2 diabetes mellitus (T2DM) in pregnancy, and an increasing number of women with type 1 diabetes mellitus (T1DM) are also affected by obesity. Increasing recognition that an intrauterine environment characterized by obesity, insulin resistance, nutrient excess, and diabetes may be fueling the obesity epidemic in children has created enormous pressure to re-examine the conventional wisdom of our current approaches.
  • Linda A Barbour
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    ABSTRACT: Gestational diabetes mellitus (GDM) is a major public health concern because of rising rates and offspring consequences; yet, expert panels are in complete disagreement on how to diagnose and optimally treat GDM. This review underscores why there remains no diagnostic standard, no agreement on whether excess dietary carbohydrate or fat should be reduced, and whether oral hypoglycemic therapy is safe given the unknown offspring effects on hepatic, pancreatic, or fat development.
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    ABSTRACT: OBJECTIVE The conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids.RESEARCH DESIGN AND METHODS Using a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m(2)) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal.RESULTSThere were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (∼6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ≤ 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P < 0.05), TG AUC was no different, but the FFA AUC was significantly lower (∼19%; P ≤ 0.01) on the CHOICE diet.CONCLUSION This highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia.
    Diabetes care 03/2014; 37(5). DOI:10.2337/dc13-2411 · 8.57 Impact Factor
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    ABSTRACT: Elucidating the optimal macronutrient composition for dietary management of gestational diabetes mellitus has enormous potential to improve perinatal outcomes. Diet therapy may result in significant cost savings if effective in deterring the need for expensive medical management within this growing population. In only 6 randomized controlled trials in 250 women, data suggest that a diet higher in complex carbohydrate and fiber, low in simple sugar, and lower in saturated fat may be effective in blunting postprandial hyperglycemia, preventing worsened insulin resistance and excess fetal growth. The use of diet in gestational diabetes mellitus remains an area in grave need for high-quality randomized controlled trials.
    Clinical obstetrics and gynecology 09/2013; 56(4). DOI:10.1097/GRF.0b013e3182a8e0e5 · 1.53 Impact Factor
  • 60th Annual Scientific Meeting of the; 03/2013
  • 60th Annual Scientific Meeting of the; 03/2013
  • Teri L Hernandez, Linda A Barbour
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    ABSTRACT: Abstract The power of continuous glucose monitoring system (CGMS) technology to profile glycemic patterns throughout a 24-h period has benefited the care of individuals with diabetes mellitus for over 10 years. Recently, this technology has been utilized to better understand glucose patterns in pregnancy, especially as they relate to abnormal fetal growth given that adiposity at birth is associated with increased risks for childhood obesity and metabolic syndrome. However, the lack of a standardized approach to defining glucose measures associated with maternal outcomes and fetal growth has greatly limited comparison and pooling of CGMS data among pregnancy trials, hindering our ability to take advantage of the enormous amount of data available to explore these relationships. The purpose of this article is to offer a methodical approach to the identification and extraction of CGMS-derived glucose variables for the characterization of glycemic profiles in pregnant women, particularly focusing on women with gestational diabetes or obesity who are at risk for abnormal fetal growth. A review of the properties of CGMS data and examples of how CGMS data in pregnancy have been reported to date are included. We further define several pregnancy-relevant, CGMS-derived glucose variables and directly apply them to unpublished data to illustrate how these measures might be utilized. This approach offers one possible standardized method to define and analyze these time-sensitive glucose measures to facilitate comparisons among studies and to increase our understanding of how glycemic profiles contribute to excess infant adiposity in pregnant women with and without diabetes.
    Diabetes Technology &amp Therapeutics 12/2012; 15(2). DOI:10.1089/dia.2012.0223 · 2.29 Impact Factor
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    ABSTRACT: OBJECTIVES: To assess precision magnetic resonance imaging in the neonate and determine whether there is an early maternal influence on the pattern of neonatal fat deposition in the offspring of mothers with gestational diabetes mellitus (GDM) and obesity compared with the offspring of normal-weight women. STUDY DESIGN: A total of 25 neonates born to normal weight mothers (n = 13) and to obese mothers with GDM (n = 12) underwent magnetic resonance imaging for the measurement of subcutaneous and intra-abdominal fat and magnetic resonance spectroscopy for the measurement of intrahepatocellular lipid (IHCL) fat at 1-3 weeks of age. RESULTS: Infants born to obese/GDM mothers had a mean 68% increase in IHCL compared with infants born to normal-weight mothers. For all infants, IHCL correlated with maternal prepregnancy body mass index but not with subcutaneous adiposity. CONCLUSION: Deposition of liver fat in the neonate correlates highly with maternal body mass index. This finding may have implications for understanding the developmental origins of childhood nonalcoholic fatty liver disease.
    The Journal of pediatrics 12/2012; 162(5). DOI:10.1016/j.jpeds.2012.11.017 · 3.74 Impact Factor
  • Journal of Obstetric Gynecologic & Neonatal Nursing 06/2012; 41(s1):S124-S124. DOI:10.1111/j.1552-6909.2012.01362_8.x · 1.20 Impact Factor
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    Diabetes care 03/2012; 35(3):e28; author reply e30. DOI:10.2337/dc11-2107 · 8.57 Impact Factor
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    ABSTRACT: Higher rates of macrosomia and large for gestational age are observed among newborns of obese nondiabetic mothers with presumably normal glucose tolerance (NGT). These adverse neonatal outcomes are similar to those observed in women with gestational diabetes. There is continuing debate over what constitutes NGT in pregnancy and whether obese and normal-weight women would have similar glycemic patterns if their respective diets were controlled. The aim of this prospective study was to determine whether (1) glycemic profiles differ between obese and normal-weight women who have NGT; and (2) glycemic profiles in obese women both early and late in gestation are influenced by a controlled diet. Continuous glucose monitoring was used to define 24-hour glycemia among 22 normal-weight and 16 obese pregnant women on an ad libitum and controlled diet. Measurements of glycemia occurred in early (15.7 ± 0.3 weeks) and late (27.7 ± 0.3 weeks) gestation. Fasting blood glucose, nonesterified fatty acids (FFAs), and insulin were also measured both in early and late gestation; however, triglycerides were measured only in early gestation. The 24-hour glucose area under the curve was significantly higher in obese women than in normal-weight women, despite controlled diets both in early (P < 0.05) and late (P < 0.01) pregnancy. Compared with normal-weight women, nearly all fasting and postprandial glycemic parameters, as well as insulin, triglycerides, and FFAs were higher in the obese women late in pregnancy. The percentage body fat was significantly higher in infants born to obese mothers than in those born to normal-weight mothers (9.2% ± 0.5% vs. 7.3% ± 0.4%, P < 0.01). Early maternal body mass index (r, 0.54, P = 0.01), as well as late mean daytime glucose (r, 0.48; P < 0.05), and late fasting insulin (r, 0.49; P < 0.05) correlated with infant percentage body fat in glucose tolerant women. The strongest correlates with infant adiposity were early fasting triglycerides (r, 0.67, P < 0.001) and late fasting FFAs (r, 0.54, P < 0.01). These findings demonstrate that the glycemic profiles of obese pregnant women without diabetes are higher than those of normal-weight women when diet is tightly controlled. Late fasting FFAs, insulin, and mean daytime glucose are highly correlated with infant adiposity, independent of maternal body mass index, but the strongest predictor is early triglycerides. The data suggest the need for study of new management strategies in obese pregnant women with NGT.
    Obstetrical and Gynecological Survey 01/2012; 67(2):75-77. DOI:10.1097/OGX.0b013e318247c535 · 2.36 Impact Factor
  • Diabetes care 11/2011; 34(11):e175. DOI:10.2337/dc11-1542 · 8.57 Impact Factor
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    ABSTRACT: We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates. This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.
    Diabetes care 07/2011; 34(10):2198-204. DOI:10.2337/dc11-0723 · 8.57 Impact Factor
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    Diabetes care 07/2011; 34(7):1660-8. DOI:10.2337/dc11-0241 · 8.57 Impact Factor
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    ABSTRACT: The rapidly increasing prevalence of gestational diabetes mellitus (GDM) globally places a growing population at risk for developing type 2 diabetes mellitus (T2DM), particularly those with persistent impaired glucose tolerance (IGT) postpartum. We sought to 1) identify dynamic insulin signaling abnormalities in vivo in a prospective, longitudinal study of GDM women compared to weight-matched pregnant controls both antepartum and postpartum; and 2) determine abnormalities that might distinguish GDM women who normalize their glucose tolerance postpartum from those with persistent IGT. Skeletal muscle biopsies were obtained before and after a 75-g glucose load in nine overweight to obese GDM women and 10 weight-matched pregnant controls antepartum and postpartum. Postpartum biopsies were collected in five weight-matched GDM women with IGT (GDM/IGT). GDM women had decreased skeletal muscle insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine activation and reduced IRS1, concomitant with increased basal IRS1 serine phosphorylation and basal p70 S6-kinase (S6K1) activation, which resolved postpartum. However, GDM/IGT subjects had a persistent impairment in IRS1 activation and increased S6K1 phosphorylation compared to GDM subjects with normal glucose tolerance. This study reveals that women with GDM demonstrate impaired IRS1 signaling associated with increased S6K1 activation in skeletal muscle in vivo. This defect is maintained postpartum in GDM/IGT subjects, despite similar body weights and cytokine levels. Given that GDM women with persistent IGT are at a high risk of developing T2DM, understanding how the nutrient-sensitive mammalian target of rapamycin/S6K1 pathway is chronically activated in GDM may lead to important therapies that could prevent the progression to T2DM.
    The Journal of Clinical Endocrinology and Metabolism 02/2011; 96(5):1431-41. DOI:10.1210/jc.2010-2116 · 6.31 Impact Factor
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    ABSTRACT: The incidence of obesity and overweight has reached epidemic levels in the United States and developed countries worldwide. Even more alarming is the increasing prevalence of metabolic diseases in younger children and adolescents. Infants born to obese, overweight, and diabetic mothers (even when normal weight) have increased adiposity and are at increased risk of later metabolic disease. In addition to maternal glucose, hyperlipidemia and inflammation may contribute to the childhood obesity epidemic through fetal metabolic programming, the mechanisms of which are not well understood. Pregravid obesity, when combined with normal changes in maternal metabolism, may magnify increases in inflammation and blood lipids, which can have profound effects on the developing embryo and the fetus in utero. Fetal exposure to excess blood lipids, particularly saturated fatty acids, can activate proinflammatory pathways, which could impact substrate metabolism and mitochondrial function, as well as stem cell fate, all of which affect organ development and the response to the postnatal environment. Fetal and neonatal life are characterized by tremendous plasticity and the ability to respond to environmental factors (nutrients, oxygen, hormones) by altering gene expression levels via epigenetic modifications. Given that lipids act as both transcriptional activators and signaling molecules, excess fetal lipid exposure may regulate genes involved in lipid sensing and metabolism through epigenetic mechanisms. Epigenetic regulation of gene expression is characterized by covalent modifications to DNA and chromatin that alter gene expression independent of gene sequence. Epigenetic modifications can be maintained through positive and negative feedback loops, thereby creating stable changes in the expression of metabolic genes and their main transcriptional regulators. The purpose of this article is to review current literature on maternal-fetal lipid metabolism and maternal obesity outcomes and to suggest some potential mechanisms for fetal metabolic programming in key organ systems that regulate postnatal energy balance, with an emphasis on epigenetics and the intrauterine environment.
    AJP Regulatory Integrative and Comparative Physiology 09/2010; 299(3):R711-22. DOI:10.1152/ajpregu.00310.2010 · 3.53 Impact Factor

Publication Stats

748 Citations
127.39 Total Impact Points

Institutions

  • 2004–2015
    • University of Colorado
      • • Division of Endocrinology, Metabolism and Diabetes
      • • Department of Medicine
      • • Department of Obstetrics and Gynecology
      • • Department of Pediatrics
      Denver, Colorado, United States
  • 2003–2014
    • Society for Maternal-Fetal Medicine
      Aurora, Colorado, United States
  • 2012
    • Denver Health and Hospital Authority
      Denver, Colorado, United States
  • 2007
    • Case Western Reserve University
      Cleveland, Ohio, United States
  • 2002
    • University of Illinois at Chicago
      Chicago, Illinois, United States