OBJECTIVE -Streptozotocin-induced type 1 diabetes in experimental animals inhibits cholesterol synthesis and increases cholesterol absorption. In contrast to human type 2 diabetes, virtually no information is available on cholesterol synthesis and absorption in type 1 diabetes.RESEARCH DESIGN AND METHODS -We studied the variables of cholesterol metabolism in 27 patients with type 1 diabetes and in 10 patients with type 2 diabetes matched for body weight, using cholesterol precursor sterol ratios to cholesterol as surrogate markers of synthesis, and those of cholestanol and plant sterols of cholesterol absorption. Glucose control was good in all subjects.RESULTS -Total and HDL cholesterol and LDL triglycerides were higher in type 2 than in type 1 diabetes. Serum sterols, measured also in VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL, were transported up to Ͼ90% by LDL and HDL in type 1 diabetes. The ratios of all absorption sterols in serum and in each lipoprotein were higher, and those of the synthesis markers, especially cholestenol and lathosterol, were lower in type 1 than in type 2 diabetes.CONCLUSIONS -In contrast to type 2 diabetes, the findings in type 1 diabetes could be related to low expression of ABC G/5 G/8 genes, resulting in high absorption of cholesterol and sterols in general and low synthesis of cholesterol.
Diabetes Care 27:53-58, 2004D yslipidemia characterizes patients with type 2 diabetes, showing normal or modestly increased cholesterol, small dense LDL, reduced HDL cholesterol, and modestly increased serum triglycerides with altered metabolism of triglyceride-rich lipoproteins (1). Cholesterol absorption efficiency and serum plant sterols, reflecting cholesterol absorption (2), are low in type 2 diabetes (3,4), and synthesis of cholesterol and its biliary and fecal elimination are increased (3,5,6). Type 1 diabetes has less advanced dyslipidemia (7), yet obliterating arterial disease, both microvascular and macrovascular, develops frequently, and myocardial infarction is also an important cause of death in these patients. The relatively normal lipid pattern is apparently a reason that scientific interest has been less frequently focused to metabolism of serum lipids in patients with type 1 than type 2 diabetes. For instance, there is virtually no information on cholesterol absorption or synthesis in patients with type 1 diabetes. However, serum plant sterols were increased in a group of poorly controlled patients with type 1 diabetes but no more at intensified insulin treatment (8). That lack of insulin might actually improve cholesterol absorption and downregulate hepatic cholesterol synthesis is indicated by streptozotocin-induced diabetes in experimental animals (9). To this end, our intention was to study cholesterol metabolism in type 1 diabetes, and in the present study we investigated surrogate markers of cholesterol absorption and synthesis by measuring serum noncholesterol sterols in patients with type 1 diabetes and compared the results with those in type 2 diabetes....