title: Cholesterol metabolism and non-cholesterol sterol distribution in lipoproteins of type 1 diabetes: the effect of improved glycemic control.
abstract: In type 1 diabetes, the ratios to cholesterol of serum absorption markers, e.g., cholestanol, are elevated and those of synthesis markers, e.g., lathosterol, are reduced suggesting perturbed cholesterol metabolism. We studied 17 subjects with type 1 diabetes in poor glycemic control at baseline to assess whether improvement of glycemic control affects lathosterol and cholestanol ratios to cholesterol and their distribution in lipoproteins. Cholesterol and the non-cholesterol sterols were assayed directly from serum, and free and ester fractions after thin-layer chromatographic separation of lipoprotein sterols with gas-liquid chromatography. After the 2-6 months follow-up, the mean value of HbA1(c) decreased from 10.8% to 8.6% (p=0.001). Even though the concentrations of serum and lipoprotein cholesterol remained unchanged, the serum lathosterol to cholesterol ratio increased by 28% (p<0.05) and the lathosterol/cholestanol proportion by 23% (p<0.05). The ratios of total and esterified lathosterol to cholesterol in serum, chylomicrons and LDL, and free lathosterol to cholesterol in serum and IDL, were negatively associated with HbA1(c) at baseline and after follow-up, suggesting that the better glycemic control, the higher was cholesterol synthesis. The absorption markers were less consistently associated with HbA1(c). About half of the serum lathosterol and cholestanol was carried in LDL and one-fourth to one-fifth in HDL, but the lathosterol ratios were roughly similar in all lipoproteins. In contrast, cholestanol accumulated in chylomicrons and HDL. Glycemic control did not affect the distributions of lathosterol and cholestanol. In conclusion, improvement in glycemic control increased cholesterol synthesis, but had no effect on cholesterol absorption as measured by the serum or lipoprotein cholestanol to cholesterol ratio. From a clinical point of view, the better the glycemic control, the more antiatherogenic cholesterol metabolism may be in type 1 diabetes.
authors.affiliation: Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Chaiyasit
authors.initials: C
authors.lastname: Sittiwet
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.forename: Maarit
authors.initials: M
authors.lastname: Hallikainen
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Leena
authors.initials: L
authors.lastname: Moilanen
authors.forename: David E
authors.initials: DE
authors.lastname: Laaksonen
authors.forename: Leo
authors.initials: L
authors.lastname: Niskanen
authors.forename: Jyrki J
authors.initials: JJ
authors.lastname: Agren
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Tatu A
authors.initials: TA
authors.lastname: Miettinen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology*; D004083:Cholestanol / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008297:Male
chemical_list: D001786:Blood Glucose; D004083:Cholestanol; D002784:Cholesterol; D006442:Glycated Hemoglobin; D008074:Lipoproteins; C001521:lathosterol