NOTICE: We are experiencing technical issues with Academy members trying to log into the JAND site using Academy member login credentials. We are working to resolve the issue as soon as possible. Alternatively, if you are an Academy member, you can access the JAND site by registering for an Elsevier account and claiming access using the links at the top of the JAND site. Email us at [email protected] for assistance. Thanks for your patience!

Hyperglycemia and Carotenoid Intake Are Associated with Serum Carotenoids in Youth with Type 1 Diabetes



      Serum carotenoids are commonly used as biomarkers of fruit and vegetable (F/V) intake in the general population. Although hyperglycemia induces oxidative stress, it is unknown whether this pathway is associated with lower serum carotenoid concentrations in individuals with type 1 diabetes. Consequently, the utility of serum carotenoids as markers of F/V intake in individuals with type 1 diabetes is unclear.


      The study objectives were: 1) to investigate the relationship of glycemic control, oxidative stress, dietary carotenoid and F/V intake with serum carotenoid concentrations in youth with type 1 diabetes and 2) to determine whether glycemic control or oxidative stress moderates the association of carotenoid and F/V intake with serum carotenoids.


      The study was a secondary analysis of baseline data from youth with type 1 diabetes. Blood samples were drawn from youth with type 1 diabetes to assess carotenoids and markers of glycemic control (glycated hemoglobin and 1,5-anhydroglucitol); urine samples were used to assess oxidative stress (8-iso-prostaglandin F); and 3-day diet records completed by families were used to determine F/V and carotenoid intake.


      The study participants were youth with type 1 diabetes (n=136; age range: 8 to 16.9 years; diabetes duration ≥1 year; glycated hemoglobin: 5.8% to 11.9%) enrolled in a nutrition intervention trial from 2010 to 2013 at a tertiary diabetes center in Boston, MA.

      Main outcome measures

      Serum carotenoids (total carotenoids and α-carotene, β-carotene, lycopene, β-cryptoxanthin, and lutein+zeaxanthin).

      Statistical analysis

      Regression analyses were used to estimate the association of glycemic control, oxidative stress, F/V and carotenoid intake with serum carotenoids, as well as the role of glycemic control and oxidative stress in moderating diet-serum carotenoid associations.


      Greater F/V intake (β=0.35, P<0.001) and carotenoid intake (β=0.28, P<0.01) were associated with higher total serum carotenoids, and no moderation by glycemic control or oxidative stress was observed. Greater hyperglycemia, as indicated by lower 1,5-anhydroglucitol (β=0.27, P<0.01), was related to lower serum carotenoids; however, glycated hemoglobin was not associated with serum carotenoids. 8-Iso-prostaglandin F2α was not associated with glycemic control or serum carotenoids.


      Findings support the validity of serum carotenoids as markers of F/V and carotenoid intake in youth with type 1 diabetes.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Academy of Nutrition and Dietetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ermakov I.V.
        • Sharifzadeh M.
        • Ermakova M.
        • Gellermann W.
        Resonance Raman detection of carotenoid antioxidants in living human tissue.
        J Biomed Opt. 2005; 10: 064028
        • Voutilainen S.
        • Nurmi T.
        • Mursu J.
        • Rissanen T.H.
        Carotenoids and cardiovascular health.
        Am J Clin Nutr. 2006; 83: 1265-1271
        • Chang S.
        • Erdman Jr., J.W.
        • Clinton S.K.
        • et al.
        Relationship between plasma carotenoids and prostate cancer.
        Nutr Cancer. 2005; 53: 127-134
        • Eliassen A.H.
        • Liao X.
        • Rosner B.
        • Tamimi R.M.
        • Tworoger S.S.
        • Hankinson S.E.
        Plasma carotenoids and risk of breast cancer over 20 y of follow-up.
        Am J Clin Nutr. 2015; 101: 1197-1205
        • Gey K.F.
        • Stahelin H.B.
        • Eichholzer M.
        Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study.
        Clin Invest. 1993; 71: 3-6
        • Morris D.L.
        • Kritchevsky S.B.
        • Davis C.E.
        Serum carotenoids and coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study.
        JAMA. 1994; 272: 1439-1441
        • Buijsse B.
        • Feskens E.J.
        • Schlettwein-Gsell D.
        • et al.
        Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: The Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA).
        Am J Clin Nutr. 2005; 82: 879-886
        • Sesso H.D.
        • Buring J.E.
        • Norkus E.P.
        • Gaziano J.M.
        Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women.
        Am J Clin Nutr. 2004; 79: 47-53
        • Secrest A.M.
        • Becker D.J.
        • Kelsey S.F.
        • Laporte R.E.
        • Orchard T.J.
        Cause-specific mortality trends in a large population-based cohort with long-standing childhood-onset type 1 diabetes.
        Diabetes. 2010; 59: 3216-3222
        • Block G.
        • Norkus E.
        • Hudes M.
        • Mandel S.
        • Helzlsouer K.
        Which plasma antioxidants are most related to fruit and vegetable consumption?.
        Am J Epidemiol. 2001; 154: 1113-1118
        • Burrows T.L.
        • Williams R.
        • Rollo M.
        • Wood L.
        • Garg M.L.
        • Jensen M.
        • Collins C.E.
        Plasma carotenoid levels as biomarkers of dietary carotenoid consumption: A systematic review of the validation studies.
        J Nutr Intermed Metab. 2015; 2: 15-64
        • Alberg A.
        The influence of cigarette smoking on circulating concentrations of antioxidant micronutrients.
        Toxicology. 2002; 180: 121-137
        • Bolton-Smith C.
        • Casey C.E.
        • Gey K.F.
        • Smith W.C.
        • Tunstall-Pedoe H.
        Antioxidant vitamin intakes assessed using a food-frequency questionnaire: Correlation with biochemical status in smokers and non-smokers.
        Br J Nutr. 1991; 65: 337-346
        • Stryker W.S.
        • Kaplan L.A.
        • Stein E.A.
        • Stampfer M.J.
        • Sober A.
        • Willett W.C.
        The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels.
        Am J Epidemiol. 1988; 127: 283-296
        • Rains J.L.
        • Jain S.K.
        Oxidative stress, insulin signaling, and diabetes.
        Free Radic Biol Med. 2011; 50: 567-575
        • Schulze P.C.
        • Yoshioka J.
        • Takahashi T.
        • He Z.
        • King G.L.
        • Lee R.T.
        Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein.
        J Biol Chem. 2004; 279: 30369-30374
        • Fiorentino T.V.
        • Prioletta A.
        • Zuo P.
        • Folli F.
        Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.
        Curr Pharm Des. 2013; 19: 5695-5703
        • Wolff S.P.
        Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications.
        Br Med Bull. 1993; 49: 642-652
        • Marra G.
        • Cotroneo P.
        • Pitocco D.
        • et al.
        Early increase of oxidative stress and reduced antioxidant defenses in patients with uncomplicated type 1 diabetes: A case for gender difference.
        Diabetes Care. 2002; 25: 370-375
        • Dominguez C.
        • Ruiz E.
        • Gussinye M.
        • Carrascosa A.
        Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents.
        Diabetes Care. 1998; 21: 1736-1742
        • Dierckx N.
        • Horvath G.
        • van Gils C.
        • et al.
        Oxidative stress status in patients with diabetes mellitus: Relationship to diet.
        Eur J Clin Nutr. 2003; 57: 999-1008
        • Erciyas F.
        • Taneli F.
        • Arslan B.
        • Uslu Y.
        Glycemic control, oxidative stress, and lipid profile in children with type 1 diabetes mellitus.
        Arch Med Res. 2004; 35: 134-140
        • Ramakrishna V.
        • Jailkhani R.
        Evaluation of oxidative stress in insulin dependent diabetes mellitus (IDDM) patients.
        Diagn Pathol. 2007; 2: 22
        • Quilliot D.
        • Walters E.
        • Bonte J.P.
        • Fruchart J.C.
        • Duriez P.
        • Ziegler O.
        Diabetes mellitus worsens antioxidant status in patients with chronic pancreatitis.
        Am J Clin Nutr. 2005; 81: 1117-1125
        • Ford E.S.
        • Will J.C.
        • Bowman B.A.
        • Narayan K.M.
        Diabetes mellitus and serum carotenoids: Findings from the Third National Health and Nutrition Examination Survey.
        Am J Epidemiol. 1999; 149: 168-176
        • Coyne T.
        • Ibiebele T.I.
        • Baade P.D.
        • et al.
        Diabetes mellitus and serum carotenoids: Findings of a population-based study in Queensland, Australia.
        Am J Clin Nutr. 2005; 82: 685-693
        • Ylonen K.
        • Alfthan G.
        • Groop L.
        • Saloranta C.
        • Aro A.
        • Virtanen S.M.
        Dietary intakes and plasma concentrations of carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk of type 2 diabetes: The Botnia Dietary Study.
        Am J Clin Nutr. 2003; 77: 1434-1441
        • Suzuki K.
        • Ito Y.
        • Nakamura S.
        • Ochiai J.
        • Aoki K.
        Relationship between serum carotenoids and hyperglycemia: A population-based cross-sectional study.
        J Epidemiol. 2002; 12: 357-366
        • Granado-Lorencio F.
        • Olmedilla-Alonso B.
        • Blanco-Navarro I.
        • Botella-Romero F.
        • Simal-Anton A.
        Assessment of carotenoid status and the relation to glycaemic control in type I diabetics: A follow-up study.
        Eur J Clin Nutr. 2006; 60: 1000-1008
        • Nansel T.R.
        • Laffel L.M.
        • Haynie D.L.
        • et al.
        Improving dietary quality in youth with type 1 diabetes: Randomized clinical trial of a family-based behavioral intervention.
        Int J Behav Nutr Phys Act. 2015; 12: 58
        • Natarajan L.
        • Pu M.
        • Fan J.
        • et al.
        Measurement error of dietary self-report in intervention trials.
        Am J Epidemiol. 2010; 172: 819-827
        • Gamboa-Pinto A.J.
        • Rock C.L.
        • Ferruzzi M.G.
        • Schowinsky A.B.
        • Schwartz S.J.
        Cervical tissue and plasma concentrations of alpha-carotene and beta-carotene in women are correlated.
        J Nutr. 1998; 128: 1933-1936
        • Burtis C.A.
        • Ashwood E.R.
        • Bruns D.E.
        TIETZ Textbook of Clinical Chemistry and Molecular Diagnostics.
        5th ed. 2006;
        • Lawler P.R.
        • Mora S.
        Moving beyond mean glycemia: 1,5-Anhydroglucitol and microvascular complications of diabetes.
        Clin Chem. 2014; 60: 1359-1361
      1. Nutrition Data System for Research (NDSR). University of Minnesota, [computer program]. Minneapolis, MN2012
        • Kuczmarski R.J.
        • Ogden C.L.
        • Guo S.S.
        • et al.
        2000 CDC Growth charts for the United States: Methods and development.
        Vital Health Stat. 2002; 11: 1-190
        • Al-Delaimy W.K.
        • van Kappel A.L.
        • Ferrari P.
        • et al.
        Plasma levels of six carotenoids in nine European countries: Report from the European Prospective Investigation into Cancer and Nutrition (EPIC).
        Public Health Nutr. 2004; 7: 713-722
        • Vogel S.
        • Contois J.H.
        • Tucker K.L.
        • Wilson P.W.
        • Schaefer E.J.
        • Lammi-Keefe C.J.
        Plasma retinol and plasma and lipoprotein tocopherol and carotenoid concentrations in healthy elderly participants of the Framingham Heart Study.
        Am J Clin Nutr. 1997; 66: 950-958
      2. Statistical Package for the Social Sciences [computer program]. Version 22. IBM Corporation, Armonk, NY2013
        • Toft U.
        • Kristoffersen L.
        • Ladelund S.
        • et al.
        Relative validity of a food frequency questionnaire used in the Inter99 study.
        Eur J Clin Nutr. 2008; 62: 1038-1046
        • Eliassen A.H.
        • Colditz G.A.
        • Peterson K.E.
        • et al.
        Biomarker validation of dietary intervention in two multiethnic populations.
        Prev Chronic Dis. 2006; 3: A44
        • Bogers R.P.
        • Van Assema P.
        • Kester A.D.
        • Westerterp K.R.
        • Dagnelie P.C.
        Reproducibility, validity, and responsiveness to change of a short questionnaire for measuring fruit and vegetable intake.
        Am J Epidemiol. 2004; 159: 900-909
        • Rawlings A.M.
        • Sharrett A.R.
        • Mosley T.H.
        • Ballew S.H.
        • Deal J.A.
        • Selvin E.
        Glucose peaks and the risk of dementia and 20-year cognitive decline.
        Diabetes Care. 2017; 40: 879-886
        • Nguyen T.M.
        • Rodriguez L.M.
        • Mason K.J.
        • Heptulla R.A.
        Serum 1,5-anhydroglucitol (Glycomark) levels in children with and without type 1 diabetes mellitus.
        Pediatr Diabetes. 2007; 8: 214-219
        • Tang G.
        Bioconversion of dietary provitamin A carotenoids to vitamin A in humans.
        Am J Clin Nutr. 2010; 91: 1468S-1473S
        • Yeum K.J.
        • Booth S.L.
        • Sadowski J.A.
        • et al.
        Human plasma carotenoid response to the ingestion of controlled diets high in fruits and vegetables.
        Am J Clin Nutr. 1996; 64: 594-602
        • McGill J.B.
        • Cole T.G.
        • Nowatzke W.
        • et al.
        Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia: A U.S. trial of the GlycoMark assay.
        Diabetes Care. 2004; 27: 1859-1865
        • Seok H.
        • Huh J.H.
        • Kim H.M.
        • et al.
        1,5-Anhydroglucitol as a useful marker for assessing short-term glycemic excursions in type 1 diabetes.
        Diabetes Metab J. 2015; 39: 164-170
        • Thomson C.A.
        • Stendell-Hollis N.R.
        • Rock C.L.
        • Cussler E.C.
        • Flatt S.W.
        • Pierce J.P.
        Plasma and dietary carotenoids are associated with reduced oxidative stress in women previously treated for breast cancer.
        Cancer Epidemiol Biomarkers Prev. 2007; 16: 2008-2015
        • Dorjgochoo T.
        • Gao Y.T.
        • Chow W.H.
        • et al.
        Major metabolite of F2-isoprostane in urine may be a more sensitive biomarker of oxidative stress than isoprostane itself.
        Am J Clin Nutr. 2012; 96: 405-414
        • MacGregor I.L.
        • Deveney C.
        • Way L.W.
        • Meyer J.H.
        The effect of acute hyperglycemia on meal-stimulated gastric, biliary, and pancreatic secretion, and serum gastrin.
        Gastroenterology. 1976; 70: 197-202
        • Balderas C.
        • Ruperez F.J.
        • Ibanez E.
        • et al.
        Plasma and urine metabolic fingerprinting of type 1 diabetic children.
        Electrophoresis. 2013; 34: 2882-2890
        • Dutta T.
        • Kudva Y.C.
        • Persson X.M.
        • et al.
        Impact of long-term poor and good glycemic control on metabolomics alterations in type 1 diabetic people.
        J Clin Endocrinol Metab. 2016; 101: 1023-1033
        • Yonekura L.
        • Nagao A.
        Intestinal absorption of dietary carotenoids.
        Mol Nutr Food Res. 2007; 51: 107-115
        • Al-Delaimy W.K.
        • Ferrari P.
        • Slimani N.
        • et al.
        Plasma carotenoids as biomarkers of intake of fruits and vegetables: Individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).
        Eur J Clin Nutr. 2005; 59: 1387-1396
        • Tucker K.L.
        • Chen H.
        • Vogel S.
        • Wilson P.W.
        • Schaefer E.J.
        • Lammi-Keefe C.J.
        Carotenoid intakes, assessed by dietary questionnaire, are associated with plasma carotenoid concentrations in an elderly population.
        J Nutr. 1999; 129: 438-445
        • Neuhouser M.L.
        • Thompson B.
        • Coronado G.
        • Martinez T.
        • Qu P.
        A household food inventory is not a good measure of fruit and vegetable intake among ethnically diverse rural women.
        J Am Diet Assoc. 2007; 107: 672-677
        • Slater B.
        • Enes C.C.
        • Lopez R.V.
        • Damasceno N.R.
        • Voci S.M.
        Validation of a food frequency questionnaire to assess the consumption of carotenoids, fruits and vegetables among adolescents: The method of triads.
        Cad Saude Publica. 2010; 26: 2090-2100
        • Vioque J.
        • Weinbrenner T.
        • Asensio L.
        • Castello A.
        • Young I.S.
        • Fletcher A.
        Plasma concentrations of carotenoids and vitamin C are better correlated with dietary intake in normal weight than overweight and obese elderly subjects.
        Br J Nutr. 2007; 97: 977-986
        • Vioque J.
        • Navarrete-Munoz E.M.
        • Gimenez-Monzo D.
        • et al.
        Reproducibility and validity of a food frequency questionnaire among pregnant women in a Mediterranean area.
        Nutr J. 2013; 12: 26
        • Galan P.
        • Viteri F.E.
        • Bertrais S.
        • et al.
        Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population.
        Eur J Clin Nutr. 2005; 59: 1181-1190
        • Freisling H.
        • Elmadfa I.
        • Schuh W.
        • Wagner K.H.
        Development and validation of a food frequency index using nutritional biomarkers in a sample of middle-aged and older adults.
        J Hum Nutr Diet. 2009; 22: 29-39
        • Polsinelli M.L.
        • Rock C.L.
        • Henderson S.A.
        • Drewnowski A.
        Plasma carotenoids as biomarkers of fruit and vegetable servings in women.
        J Am Diet Assoc. 1998; 98: 194-196
        • Talegawkar S.A.
        • Johnson E.J.
        • Carithers T.C.
        • Taylor H.A.
        • Bogle M.L.
        • Tucker K.L.
        Carotenoid intakes, assessed by food-frequency questionnaires (FFQs), are associated with serum carotenoid concentrations in the Jackson Heart Study: Validation of the Jackson Heart Study Delta NIRI Adult FFQs.
        Public Health Nutr. 2008; 11: 989-997
        • Burrows T.L.
        • Warren J.M.
        • Colyvas K.
        • Garg M.L.
        • Collins C.E.
        Validation of overweight children's fruit and vegetable intake using plasma carotenoids.
        Obesity (Silver Spring). 2009; 17: 162-168
        • Ortega R.M.
        • Perez-Rodrigo C.
        • Lopez-Sobaler A.M.
        Dietary assessment methods: Dietary records.
        Nutr Hosp. 2015; 31: 38-45
        • Ford E.S.
        Variations in serum carotenoid concentrations among United States adults by ethnicity and sex.
        Ethn Dis. 2000; 10: 208-217
        • Schleicher R.L.
        • Sternberg M.R.
        • Pfeiffer C.M.
        Race-ethnicity is a strong correlate of circulating fat-soluble nutrient concentrations in a representative sample of the U.S. population.
        J Nutr. 2013; 143: 966S-976S


      N. Sanjeevi is a postdoctoral fellow, Social and Behavioral Sciences Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.


      L. M. Lipsky is a staff scientist, Social and Behavioral Sciences Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.


      T. R. Nansel is a senior investigator, Social and Behavioral Sciences Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.