PDF Ebook Cholesterol metabolism in type 2 diabetes
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 by quantitating serum ratios of phytosterols and cholestanol to cholesterol, cholesterol synthesis with sterol balance as well as serum ratios of squalene and precursor sterols (cholestenol, desmosterol, lathosterol) to cholesterol.
In order to clarify the role of weight reduction in modulating cholesterol metabolism in type 2 diabetes, parameters associated with cholesterol and sterol metabolism were determined during weight reduction, and during a 2-year follow-up after weight reduction. Ten obese type 2 diabetic patients consumed a very low energy diet virtually free of cholesterol, cholestanol and plant sterols for 3 months, and serum squalene and non-cholesterol sterol levels were determined before and after the weight reduction program in a non-steady state situation. Sixteen obese type 2 diabetic patients consumed a very low energy or low-energy diet for 3 months, after which they consumed a weight-maintaining diet for up to 2 years. The changes in cholesterol metabolism were determined by assaying cholesterol absorption efficiency, sterol balance, and serum sterols after a 2-year follow-up, at a stable, reduced weight level.
The efficiency of cholesterol absorption and the amounts of absorbed total, dietary and biliary cholesterol were lower in the obese type 2 diabetic patients than obese controls or in normal-weight type 2 diabetic patients. Cholesterol absorption was similar in both diabetics with normal body weight and obese controls. Fecal elimination of cholesterol, mainly as neutral sterols and less as bile acids, was increased, and this enhanced cholesterol synthesis more in obese patients with type 2 diabetes than in obese controls or normal-weight diabetic patients. In addition, fecal bile acids, the total intestinal cholesterol pool, biliary cholesterol secretion and cholesterol turnover were significantly higher in obese diabetic patients than normal-weight diabetic patients, when expressed as mg/d. Moreover, BMI was positively associated with variables of cholesterol synthesis and negatively with cholesterol absorption. Cholesterol absorption and synthesis were inversely related in the diabetic population suggesting that the homeostatic regulation between cholesterol absorption and synthesis was not distrupted by diabetes.
Serum plant sterols and cholestanol ratios correlated with the cholesterol absorption efficiency, and those of cholesterol precursor sterols correlated with variables of cholesterol synthesis and excretion, suggesting that they reflect cholesterol metabolism similarly as in the non-diabetic population. Indeed, lower cholesterol absorption and higher synthesis in obese type 2 diabetes was also seen as lower ratios of serum plant sterols and cholestanol and higher ratios of cholesterol precursor sterols as compared with normal weight diabetes.
Serum levels of SHBG were lower and serum insulin higher in obese than in normal-weight diabetic patients, suggesting that insulin resistance increased with weight. With high levels of serum insulin and low levels of SHBG, cholesterol absorption was low and cholesterol synthesis was enhanced in obese diabetes. Serum SHBG was positively associated with variables of cholesterol absorption and negatively with cholesterol synthesis. Thus, insulin resistance is related to cholesterol metabolism so that with increasing insulin resistance, cholesterol absorption is lowered and synthesis enhanced.
During effective weight reduction, the ratio of cholestanol increased and those of cholesterol precursor sterols decreased, suggesting that cholesterol absorption was increased and synthesis decreased in a non-steady state situation. Weight reduction to a steady state caloric balance after the 2-year follow-up increased the efficiency of lowered baseline cholesterol absorption capacity and the ratios of serum plant sterols markedly. In addition, the SHBG level increased and serum insulin level decreased, and SHBG was related to plant sterols and cholestanol after weight reduction. Thus, with weight reduction, variables related to glucose metabolism improved and cholesterol absorption increased, and the improvement of insulin resistance possibly contributed to the enhanced absorption of cholesterol.
In conclusion, type 2 diabetes is associated with low cholesterol absorption and enhanced cholesterol synthesis, and these alterations in cholesterol metabolism are not explained by obesity. In addition, body weight, over its entire range, regulates cholesterol metabolism in type 2 diabetes, so that increasing body weight further lowers cholesterol absorption. Cholesterol and glucose metabolism are closely linked, and the regulation of cholesterol metabolism is related to variables reflecting insulin resistance; the magnitude of the abnormalities in cholesterol absorption and synthesis possibly indicating the severity of the insulin resistance. The abnormalities in cholesterol metabolism are not irreversibile, weight reduction is an efficient way to improve cholesterol metabolism. In addition, the beneficial effects of weight loss on cholesterol metabolism can be seen rather quickly, even in a non-steady state situation.
These studies have increased our knowledge of cholesterol metabolism in type 2 diabetes, and also provided new insights into the beneficial effects of weight reduction as the primary treatment for obese type 2 diabetes.
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PDF Ebook Cholesterol metabolism in type 2 diabetes
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