The validity of serum squalene and non-cholesterol sterols as surrogate markers of cholesterol synthesis and absorption in type 2 diabetes

Objective Serum non-cholesterol sterol ratios to cholesterol reflect cholesterol metabolism in non-diabetes populations. In type 2 diabetes (T2D) cholesterol metabolism is perturbed, and the role of squalene and non-cholesterol sterols has not been related to absolute cholesterol metabolism in detail. Aim and methods We analyzed absolute cholesterol synthesis, absorption % of dietary cholesterol, and serum squalene and non-cholesterol sterol ratios (measured with gas–liquid chromatography) in 64 T2D subjects (age 41–74 years, BMI 21–40 kg/m2). Results Serum precursors of cholesterol were related to cholesterol synthesis (e.g. serum squalene to cholesterol ratio vs absolute synthesis r = 0.493, p < 0.001), and serum cholestanol and plant sterol ratios were related to absorption % (e.g. cholestanol vs absorption %, r = 0.455, p < 0.001). Furthermore, the proportions of serum synthesis/absorption markers were correlated with variables of absolute cholesterol metabolism (e.g. squalene/sitosterol vs absolute synthesis/absorption %, r = 0.569, p < 0.001). Serum synthesis and absorption markers (lathosterol vs cholestanol, r = −0.545, r < 0.001) and absolute synthesis and absorption (r = −0.540, p < 0.001) were interrelated suggesting intact regulation of cholesterol metabolism in the whole study population. Absolute synthesis/absorption ratio indicated that a change of dietary cholesterol absorption by 1% changed the mean cholesterol synthesis by 27 mg/d to the opposite direction. Conclusions In T2D including varying body weight and altered cholesterol metabolism, serum non-cholesterol sterols and squalene reveal reliable information of cholesterol synthesis and absorption without complicated clinical and laboratory methods.