Type 1 diabetes is associated with an increase in cholesterol absorption markers but a decrease in cholesterol synthesis markers in a young adult population
Open accessAbstract
Background To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes.Objective The objective of the study was to compare plasma levels of campesterol and β-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes.Methods Serum samples were obtained from adolescent subjects with type 1 diabetes (n = 175, mean age 15.2 years, mean duration of diabetes 8.2 years) and without diabetes (n = 74, mean age 15.4 years). Campesterol, β-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, compared between groups, and correlated with the available cardiometabolic variables.Results Campesterol and β-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure.Conclusion Plasma markers suggest that cholesterol absorption is increased, whereas cholesterol synthesis is decreased in adolescent subjects with type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Young adults with type 1 diabetes have increased cholesterol absorption, as shown in a recent study, suggesting greater efficacy of ezetimibe in this population, which remains to be assessed with dedicated randomized controlled trials.
“Young adults with T1DM have increased cholesterol absorption, as shown in a recent study, suggesting greater efficacy of ezetimibe in this population, which remains to be assessed with dedicated RCTs.261”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [261]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
(2005) · New England Journal of Medicine · doi:10.1056/nejmoa052187 · Cited by 5,138 · see citing works
Collaborators, C. T. T. (. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60104-x · Cited by 2,081 · see citing works
Glycemic Control and Excess Mortality in Type 1 Diabetes
Lind, M., Svensson, A.-M., Kosiborod, M., Gudbjörnsdottir, S., Pivodic, A., Wedel, H., Dahlqvist, S., Clements, M., & Rosengren, A. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408214 · Cited by 964 · see citing works
MIETTINEN, T. A., TILVIS, R. S., & KESÄNIEMI, Y. A. (1990) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a115479 · Cited by 646 · see citing works
Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010
Livingstone, S. J., Levin, D., Looker, H. C., Lindsay, R. S., Wild, S. H., Joss, N., Leese, G., Leslie, P., McCrimmon, R. J., Metcalfe, W., et al. (2015) · JAMA · doi:10.1001/jama.2014.16425 · Cited by 621 · see citing works
Biddinger, S. B., Hernandez-Ono, A., Rask-Madsen, C., Haas, J. T., Alemán, J. O., Suzuki, R., Scapa, E. F., Agarwal, C., Carey, M. C., Stephanopoulos, G., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.013 · Cited by 469 · see citing works
Self-citationSerum plant sterols and their relation to cholesterol absorption
Tilvis, R. S., & Miettinen, T. A. (1986) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/43.1.92 · Cited by 328 · see citing works
Schwab, K. O., Doerfer, J., Hecker, W., Grulich‐Henn, J., Wiemann, D., Kordonouri, O., Beyer, P., Holl, R. W., & on behalf of the DPV Initiative of the German Working Group for Pediatric Diabetology (2006) · Diabetes Care · doi:10.2337/diacare.29.02.06.dc05-0724 · Cited by 259 · see citing works
Lipid and Lipoprotein Profiles in Youth With and Without Type 1 Diabetes
Guy, J., Ogden, L. G., Wadwa, R. P., Hamman, R. F., Mayer‐Davis, E. J., Liese, A. D., D'Agostino, R., Marcovina, S. M., & Dabelea, D. (2008) · Diabetes Care · doi:10.2337/dc08-1775 · Cited by 235 · see citing works
Self-citationSerum cholestanol and plant sterol levels in relation to cholesterol metabolism in middle-aged men
Miettinen, T. A., Tilvis, R. S., & Kesäniemi, Y. A. (1989) · Metabolism · doi:10.1016/0026-0495(89)90252-7 · Cited by 218 · see citing works
Pihlajamäki, J., Gylling, H. K., Miettinen, T. A., & Laakso, M. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m300368-jlr200 · Cited by 201 · see citing works
Hyperglycemia and Plasma Lipid Levels
Sosenko, J. M., Breslow, J. L., Miettinen, O. S., & Gabbay, K. H. (1980) · New England Journal of Medicine · doi:10.1056/nejm198003203021202 · Cited by 195 · see citing works
Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia
Avis, H. J., Hutten, B. A., Gagné, C., Langslet, G., McCrindle, B. W., Wiegman, A., Hsia, J. A., Kastelein, J. J. P., & Stein, E. A. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.10.042 · Cited by 166 · see citing works
Highly sensitive analysis of sterol profiles in human serum by LC-ESI-MS/MS
Honda, A., Yamashita, K., Miyazaki, H., Shirai, M., Ikegami, T., Xu, G., Numazawa, M., Hara, T., & Matsuzaki, Y. (2008) · Journal of Lipid Research · doi:10.1194/jlr.d800017-jlr200 · Cited by 164 · see citing works
Huo, L., Harding, J. L., Peeters, A., Shaw, J. E., & Magliano, D. J. (2016) · Diabetologia · doi:10.1007/s00125-015-3857-4 · Cited by 154 · see citing works
Serum Lipids and Glucose Control
Petitti, D. B. (2007) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.161.2.159 · Cited by 127 · see citing works
Miller, R. G., Mahajan, H., Costacou, T., Sekikawa, A. M., Anderson, S., & Orchard, T. J. (2016) · Diabetes Care · doi:10.2337/dc16-1162 · Cited by 125 · see citing works
Low Synthesis and High Absorption of Cholesterol Characterize Type 1 Diabetes
Miettinen, T. A., Gylling, H. K., Tuominen, J. A., Simonen, P. P., & Koivisto, V. A. (2004) · Diabetes Care · doi:10.2337/diacare.27.1.53 · Cited by 99 · see citing works
The DCCT Research Group (1992) · Diabetes Care · doi:10.2337/diacare.15.7.886 · Cited by 95 · see citing works
Simonen, P. P., Gylling, H. K., & Miettinen, T. A. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.08.003 · Cited by 87 · see citing works
Bebu, I., Braffett, B. H., Pop‐Busui, R., Orchard, T. J., Nathan, D. M., & Lachin, J. M. (2017) · Diabetologia · doi:10.1007/s00125-017-4374-4 · Cited by 87 · see citing works
Indices of Cholesterol Metabolism and Relative Responsiveness to Ezetimibe and Simvastatin
Gilchrist, S. C., Xu, F., Vega, G. L., Grundy, S. M., Chandalia, M., Lam, C., Lowe, R. S., Stepanavage, M. E., Musliner, T. A., Cohen, J. C., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1952 · Cited by 74 · see citing works
Cholesterol gallstones in alloxan-diabetic mice.
Akiyoshi, T., Uchida, K., Takase, H., Nomura, Y., & Takeuchi, N. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38774-5 · Cited by 71 · see citing works
Longitudinal Lipid Screening and Use of Lipid-Lowering Medications in Pediatric Type 1 Diabetes
Maahs, D. M., Wadwa, R. P., McFann, K., Nadeau, K. J., Williams, M. R., Eckel, R. H., & KLINGENSMITH, G. J. (2007) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2006.10.054 · Cited by 68 · see citing works
Self-citationEzetimibe Treatment of Pediatric Patients with Hypercholesterolemia
Clauss, S. B., Wai, K., Kavey, R.-E. W., & KUEHL, K. S. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2008.12.044 · Cited by 66 · see citing works
Altered Bile Acid Metabolism in Nonobese, Spontaneously Diabetic (NOD) Mice
Uchida, K., Makino, S., & Akiyoshi, T. (1985) · Diabetes · doi:10.2337/diab.34.1.79 · Cited by 59 · see citing works
Mashnafi, S., Plat, J., Mensink, R. P., & Baumgartner, S. (2019) · Nutrients · doi:10.3390/nu11010124 · Cited by 53 · see citing works
Ezetimibe as Monotherapy in the Treatment of Hypercholesterolemia in Children and Adolescents
Yeste, D., Chacón, P. M., Clemente, M., Albisu, M., Gussinyé, M., & Carrascosa, A. (2009) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2009.22.6.487 · Cited by 47 · see citing works
Hallikainen, M., Kurl, S., Laakso, M., Miettinen, T. A., & Gylling, H. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.03.041 · Cited by 46 · see citing works
ALTERED BILE ACID METABOLISM IN ALLOXAN DIABETIC RATS
Uchida, K., Takase, H., KADOWAKI, M., et al. (1979) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.29.553 · Cited by 44 · see citing works
Winkler, K., Jacob, S., Schewe, T., Hoffmann, M. M., & Konrad, T. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.10.043 · Cited by 39 · see citing works
Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins
Miao, J., Haas, J. T., Manthena, P. V., Wang, Y., Zhao, E., Vaitheesvaran, B., Kurland, I. J., & Biddinger, S. B. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m043711 · Cited by 39 · see citing works
Self-citationKallien, G., Lange, K., Stange, E. F., et al. (1999) · Hepatology · doi:10.1002/hep.510300119 · Cited by 36 · see citing works
Spark, T. L., Maahs, D. M., Bishop, F. K., Snell‐Bergeon, J. K., & Wadwa, R. P. (2016) · International Journal of Pediatric Endocrinology · doi:10.1186/s13633-016-0026-6 · Cited by 33 · see citing works
Self-citationCholesterol Absorption and Synthesis in Children With Type 1 Diabetes
Järvisalo, M. J., Raitakari, O. T., Gylling, H. K., et al. (2006) · Diabetes Care · doi:10.2337/dc05-2235 · Cited by 31 · see citing works
Markers of absorption and synthesis of cholesterol in men with type 1 diabetes
Gylling, H. K., Laaksonen, D. E., Atalay, M., Hallikainen, M., NISKANEN, L. K., & Miettinen, T. A. (2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.697 · Cited by 31 · see citing works
Visceral fat positively correlates with cholesterol synthesis in dyslipidaemic patients
Lupattelli, G., Pirro, M., Mannarino, M. R., Siepi, D., Roscini, A. R., Schillaci, G., & Mannarino, E. (2011) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2011.02572.x · Cited by 27 · see citing works
Guyton, J. R., Betteridge, D. J., Farnier, M., Leiter, L. A., Lin, J., Shah, A. K., Johnson‐Levonas, A. O., & Brudi, P. (2011) · Diabetes and Vascular Disease Research · doi:10.1177/1479164111406457 · Cited by 22 · see citing works
Self-citationMilliat, F., Gripois, D., Blouquit, M.-F., et al. (2000) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2000-8401 · Cited by 21 · see citing works
Ciriacks, K., Coly, G., Krishnaswami, S., Patel, S. B., & Kidambi, S. (2015) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2014.0114 · Cited by 18 · see citing works
Farnier, M., Guyton, J. R., Jensen, E. H., Polis, A. B., Johnson‐Levonas, A. O., & Brudi, P. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.05.010 · Cited by 17 · see citing works
Inoue, T., Taguchi, I., Abe, S., et al. (2010) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.2010.01161.x · Cited by 16 · see citing works
Kojima, H., Hidaka, H., Matsumura, K., et al. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(99)00070-2 · Cited by 15 · see citing works
Sittiwet, C., Gylling, H. K., Hallikainen, M., Pihlajamäki, J., Moilanen, L., Laaksonen, D. E., NISKANEN, L. K., Ågren, J. J., Laakso, M., & Miettinen, T. A. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.08.044 · Cited by 12 · see citing works
Involvement of angiotensin II in intestinal cholesterol absorption
Nakamura, K., Matsui, T., Adachi, H., et al. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.12.002 · Cited by 10 · see citing works
Body mass index and glycemic control influence lipoproteins in children with type 1 diabetes
Vaid, S., Hanks, L. J., Griffin, R. L., & Ashraf, A. P. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.07.010 · Cited by 10 · see citing works
Lessons learned from a lipid lowering trial in adolescents with type 1 diabetes
Bishop, F. K., Wadwa, R. P., Ellis, S., et al. (2012) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2012-24 · Cited by 5 · see citing works
Self-citationJohn, C. C., Regier, M., Lilly, C. L., & Aly, S. (2015) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.11.012 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad192 · Cited by 1,642 · see citing works
Lipid management for cardiovascular risk reduction in type 1 diabetes
Tell, S., Nadeau, K. J., & Eckel, R. H. (2020) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000551 · Cited by 30 · see citing works
- Authors
- Semova, I., Levenson, A. E., Krawczyk, J., Bullock, K., Williams, K. A., Wadwa, R. P., Shah, A. S., Khoury, P. R., Kimball, T. R., Urbina, E. M., de Ferranti, S. D., Bishop, F. K., Maahs, D. M., Dolan, L. M., Clish, C. B., & Biddinger, S. B.
- Affiliations
- Boston Children's Hospital (US)
- Broad Institute (US)
- University of Colorado Anschutz (US)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Biddinger, Sudha B.
- ORCID
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 13
- Issue
- 6
- Pages
- 940-946
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- PMC
- PMC6980756
- OpenAlex
- W2976022438
- Cited by
- 33
- References
- 48
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 1
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of clinical lipidology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- Broad Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (DK075360, P30 DK116074)
- American Diabetes Association (P30 DK116074, K23 DK075360, T32 DK007260, 9-18-CVD1-003)
- Juvenile Diabetes Research Foundation United Kingdom
- National Center for Research Resources
- National Heart, Lung, and Blood Institute (R01-HL-109650)
- Juvenile Diabetes Research Foundation United States of America (11-2007-694)
- National Institutes of Health (T32 DK007260)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 1 diabetes, cholesterol absorption, cholesterol biosynthesis, campesterol, β-sitosterol, lathosterol, plasma sterols, adolescents, cardiovascular risk, HbA1c, triglycerides, body mass index, systolic blood pressure
- MeSH terms
- Adolescent, Adult, Anthropometry, Cardiovascular Diseases, Child, Cholesterol, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Male, Risk Factors, Mass Spectrometry, Biomarkers, Dyslipidemias, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
