Ivana Semova1, Amy E Levenson1, Joanna Krawczyk1, Kevin Bullock2, Kathryn A Williams3, R Paul Wadwa4, Amy S Shah5, Philip R Khoury5, Thomas R Kimball6, Elaine M Urbina6, Sarah D de Ferranti7, Franziska K Bishop4, David M Maahs4, Lawrence M Dolan5, Clary B Clish2, Sudha B Biddinger8. 1. Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 2. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 3. Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Biostatistics and Research Design Center, Boston Children's Hospital, Boston, MA, USA. 4. Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. 5. Division of Endocrinology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA. 6. Division of Cardiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA. 7. Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 8. Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: sudha.biddinger@childrens.harvard.edu.
Abstract
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.
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.
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