Low Synthesis and High Absorption of Cholesterol Characterize Type 1 Diabetes

Abstract

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....

Cholesterol Absorption and Synthesis in Children With Type 1 Diabetes

“…In two previous studies (2,3), plant sterol and cholestanol ratios were markedly increased in sera of adult type 1 diabetic subjects compared with control or type 2 diabetic subjects. In addition, cholesterol synthesis markers appeared to be low, most likely indicating reduced overall synthesis of cholesterol (2,3).…”

“…Recent studies (2,3) have suggested that in adults with type 1 diabetes, cholesterol synthesis is low and cholesterol absorption high compared with healthy individuals or subjects with type 2 diabetes. These clinical findings have been corroborated in the experimental model of streptozotocin-induced diabetes, in which expression of ABCG 5/8 genes in enterocytes and hepatocytes were reduced (4).…”

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

“…cholestanol, desmosterol, and lathosterol. The results obtained in this field showed that in T1D patients the markers of cholesterol absorption were increased, while the markers of cholesterol synthesis were decreased compared with control subjects, indicating that both high cholesterol absorption and low cholesterol synthesis are present in type 1 diabetic patients [2]. This mechanism has been hypothesized to be the result of an upregulation of specific genes for the synthesis of key proteins in the process of cholesterol intestinal absorption.…”

The spectrum of mild cognitive impairment in dyslipidemic non-elderly type 1 diabetics

“…This fact has been established through various studies such as that of Saydah SH et al The reason that has been suggested for a lesser degree of dyslipidemia in type 1 diabetics being physiological decreased hepatic synthesis of cholesterol. 18,19 Other possible reasons for less dyslipidemia in type 1 diabetes in this study may include younger age group and more conscious lifestyle changes in patients with type 1 diabetes Some domains of cognitive functioning were spared (p>0.05) in our study that may be due to heterogeneity of the population selected, limited sample size, and a lesser degree of dyslipidemia that was observed in a study population of this area. Hence, a need of further longitudinal study for type 1 diabetics is necessary for better generalizations of results.…”