Cholesterol metabolism in type 2 diabetes

This thesis is based on the following original articles, which are referred to in the text by their Roman numerals. metabolism in non-insulin dependent type 2 diabetics. cholesterol metabolism in obese type 2 diabetes. a new component of the metabolic syndrome: low cholesterol absorption. ABBREVIATIONS ABC adenosine triphosphate-binding cassette transporter ACAT acyl-CoA cholesterol acyltransferase ANOVA analysis of variance Apo apolipoprotein BMI body mass index BSEP bile salt export pump CETP cholesteryl ester transfer protein Cr 2 O 3 chromic oxide CYP7A1 cholesterol 7α-hydroxylase d density ∆ 8 – cholestenol cholestenol ∆ 7 – lathosterol lathosterol DM diabetes group FCR fractional catabolic rate FXR farnesoid X receptor HbA1c glycosylated hemoglobin A1c GLC gas-liquid chromatography HDL high density lipoprotein HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme A HOMA homeostasis model assessment I-BABP ileal bile-acid binding protein IDL intermediate density lipoprotein LCAT lecithin:cholesterol acyltransferase LDL low density lipoprotein LED low energy diet LRP LDL receptor-related protein LXR liver X receptor MTP microsomal triglyceride transfer protein PLTP plasma phospholipid transfer protein RXR retinoid X receptor SHBG sex hormone binding globulin SR-BI scavenger receptor BI SREBP sterol regulatory element binding protein TR transport rate TRL triglyceride rich lipoproteins VLDL very low density lipoprotein VLED very low energy diet 9 ABSTRACT Type 2 diabetes is associated with many metabolic disturbances including hyperinsulinemia, insulin resistance, hyperglycemia, dyslipidemia and obesity. The alterations occurring in lipoprotein metabolism in diabetes have been described in detail, but the metabolism of cholesterol and bile acids has been less well characterized, and the results from the few previous studies are controversial. Obesity, in addition to predisposing to the development of diabetes, is associated with abnormal cholesterol metabolism. Accordingly, cholesterol metabolism was studied in obesity with and without type 2 diabetes, and in type 2 diabetes with and without overweight. In addition, the effects of weight reduction were studied on cholesterol and sterol metabolism in a non-stable state during fasting and also in subsequent steady state after a prolonged follow-up. Cholesterol absorption and cholesterol and bile acid synthesis were studied in 16 obese (BMI > 30 kg/m 2) type 2 diabetic patients and compared to 16 similarly obese controls to reveal the role of diabetes on cholesterol metabolism. The effects of body weight on cholesterol metabolism were investigated with 20 normal-weight (BMI ≤ 26.0 kg/m 2) and 44 overweight (BMI > 26.1 kg/m 2) type 2 diabetic patients. Cholesterol absorption was evaluated with the peroral dual isotope technique and …