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Originally published In Press as doi:10.1194/jlr.M300368-JLR200 on December 1, 2003

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Journal of Lipid Research, Vol. 45, 507-512, March 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men

Jussi Pihlajamäki1,*, Helena Gylling{dagger}, Tatu A. Miettinen§ and Markku Laakso*

* Department of Medicine, University of Kuopio, Kuopio, Finland
{dagger} Clinical Nutrition, University of Kuopio, Kuopio, Finland
§ Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland

1 To whom correspondence should be addressed. e-mail: pihlajam{at}uku.fi

Type 2 diabetes has been associated with high synthesis and low absorption of cholesterol independent of weight, indicating that insulin resistance may be a link between glucose and cholesterol metabolism. Therefore, we investigated the relationship of serum cholesterol precursors, reflecting cholesterol synthesis, and serum plant sterols and cholestanol, reflecting cholesterol absorption efficiency, with insulin sensitivity measured with the hyperinsulinemic euglycemic clamp in 72 healthy normoglycemic men. Men in the most insulin-resistant tertile had higher serum cholesterol precursor ratios (P < 0.05), whereas no significant differences in serum absorption sterols were observed. In bivariate analysis, cholesterol synthesis markers correlated with fasting insulin (r = 0.36–0.46, P < 0.01) and the rates of insulin-stimulated whole-body glucose uptake (WBGU; r = -0.37–0.40, P < 0.01). Also, cholesterol absorption markers correlated with fasting insulin and WBGU (P < 0.05). Fasting insulin correlated with desmosterol (r = 0.286, P = 0.015) and lathosterol (r = 0.248, P = 0.037) even when the rates of WBGU and body mass index (BMI) were controlled for.

We conclude that insulin resistance is linked to high cholesterol synthesis and decreased cholesterol absorption. Because fasting insulin correlated with cholesterol synthesis independent of the rates of BMI and WBGU, it is possible that regulation of cholesterol synthesis by hyperinsulinemia may be a link between insulin resistance and cholesterol metabolism.

Abbreviations: BMI, body mass index; LXR, liver X receptor; T2DM, type 2 diabetes; WBGU, whole-body glucose uptake

Supplementary key words insulin sensitivity • hyperinsulinemic euglycemic clamp • cholestanol • campesterol • sitosterol • cholestenol • desmosterol • lathosterol • squalene


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