Cholesterol metabolism and non-cholesterol sterol distribution in lipoproteins of type 1 diabetes: The effect of improved glycemic control

Sittiwet, Chaiyasit; Gylling, Helena; Hallikainen, Maarit; Pihlajamäki, Jussi; Moilanen, Leena; Laaksonen, David E.; Niskanen, Leo; Ågren, Jyrki J.; Laakso, Markku; Miettinen, Tatu A.

doi:10.1016/j.atherosclerosis.2006.08.044

« Previous Next »Atherosclerosis
Volume 194, Issue 2 , Pages 465-472, October 2007

Cholesterol metabolism and non-cholesterol sterol distribution in lipoproteins of type 1 diabetes: The effect of improved glycemic control

Chaiyasit Sittiwet
- Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland
- Department of Chemistry, Faculty of Sciences, Mahasarakham University, Mahasarakham, Thailand
- Current address: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Helena Gylling
- Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
Maarit Hallikainen
- Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
Jussi Pihlajamäki
- Department of Medicine, University of Kuopio, Kuopio, Finland
Leena Moilanen
- Department of Medicine, University of Kuopio, Kuopio, Finland
David E. Laaksonen
- Department of Medicine, University of Kuopio, Kuopio, Finland
- Department of Physiology, University of Kuopio, Kuopio, Finland
Leo Niskanen
- Department of Medicine, University of Kuopio, Kuopio, Finland
Jyrki J. Ågren
- Department of Physiology, University of Kuopio, Kuopio, Finland
Markku Laakso
- Department of Medicine, University of Kuopio, Kuopio, Finland
Tatu A. Miettinen
- Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland
- Corresponding author at: Biomedicum Helsinki C 4 22, P.O. Box 700, FIN-00029 HUS, Finland. Tel.: +358 9 4717 1852; fax: +358 9 47171851.

Received 9 June 2006; received in revised form 15 August 2006; accepted 23 August 2006. published online 25 September 2006.

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.

Keywords: Type 1 diabetes, Cholesterol synthesis, Cholesterol absorption, Cholestanol, Lathosterol, Lipoproteins, Chylomicrons