A cell culture system was employed to test a large number of samples of human serum for the ability to stimulate the efflux of cell cholesterol. The extent of efflux obtained with each specimen was correlated with the serum concentrations of cholesterol, triglycerides, apoprotein (apo) B, apo A-I, apo A-II, and lipoprotein subfractions (ie, high-density lipoprotein 2 [HDL 2 ], HDL 3 , lipoprotein [Lp] A-I, and LpA-I:A-II). In addition, the subsequent esterification of the released cholesterol and the distribution of the synthesized exogenous cholesteryl esters between HDL and low-density lipoprotein/ very-low-density lipoprotein provided estimates of the lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities of each serum. The values for these activities were analyzed for correlations with cell efflux and the various serum parameters. Cell cholesterol efflux best correlated with serum total HDL cholesterol values. HDL 2 and HDL 3 correlated about equally well with efflux, whereas LpA-I demonstrated a much greater association with T he process by which cholesterol in peripheral tissues is transported back to the liver for excretion has been termed reverse cholesterol transport (RCT). While the importance of high-density lipoprotein (HDL) in RCT is now universally accepted, it is not known which specific fractions of HDL are most important. Most in vitro studies have used either native lipoproteins, particularly subclasses of HDL, or reconstituted particles containing apolipoproteins and phospholipids to study cholesterol efflux, which is the first step in RCT. The difficulties in clearly identifying the specific lipoprotein in serum or interstitial fluid that plays the primary role in cholesterol efflux are due to several facts. First, there is a wide variety of particles within the HDL class of lipoproteins, and no single class of particles appears to be uniquely responsible for cholesterol efflux. 1 -2 Second, depending on the method of separation, two subclasses of HDL have been pro- Studies with whole serum have been limited, and it is not known if the quantification of a single serum parameter, or even combinations of parameters, is sufficient to allow the prediction of how individual samples of human serum will influence cellular cholesterol efflux.Cholesterol efflux studies using whole sera are best represented by the investigations of Fielding and colleagues. 68 The initial studies using fibroblasts as the cholesterol donor cell clearly established that sera from individuals differed in their ability to produce changes in net cellular cholesterol efflux. These differences were correlated to a number of clinical conditions that are known to influence serum lipoprotein patterns, such as by guest on May 9, 2018 http://atvb.ahajournals.org/ Downloaded from

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We studied the effect of omega-3 fatty acids (omega 3FA) on glucose homeostasis and lipoprotein levels in eight type II (non-insulin-dependent)-diabetic subjects ingesting 8 g/day omega 3FA for 8 wk as marine-lipid concentrate capsules. After omega 3FA supplementation, fasting plasma glucose levels increased 22% (P = .005) and meal-stimulated glucose increased 35% (P = .036). The percentage of glucose elevation correlated with percentage ideal body weight (r = .73, P = .04). No significant changes were seen in fasting or meal-stimulated plasma insulin, glucose disposal, or insulin-to-glucagon ratios. Very-low-density lipoprotein cholesterol and triglyceride (TG) levels showed consistent reductions of 56% (P less than .001) and 42% (P less than .001), respectively, after omega 3FA supplementation. Total cholesterol levels decreased 7% (P less than .05) without alteration in low- or high-density lipoprotein cholesterol. Thus, omega 3FA supplementation at a dose of 8 g/day significantly improves plasma TG levels but increases fasting and meal-stimulated glucose concentrations in the type II diabetic patient not treated with insulin or sulfonylurea agents. Marine-lipid concentrate capsules supplying large amounts of omega 3FAs should be used cautiously in the type II diabetic patient.

Up to one-third of subjects who have had bilateral adrenalectomy for treatment of Cushing's disease will develop Nelson's syndrome. To examine the value of pre-operative ACTH assays in predicting outcome, we have studied fifteen cases of Cushing's disease treated by bilateral adrenalectomy and pituitary irradiation. Three patients developed Nelson's syndrome. There was no significant correlation between preoperative ACTH level, either 8 am 'basal' or during metyrapone testing, and ACTH concentration post-treatment. Plasma ACTH concentration in the first year after treatment, however, showed a highly significant correlation with the latest postoperative value (n = 14, r = 0.684, P less than 0.01), even more marked when subjects with duration of follow-up less than 3 years were excluded (n = 11, r = 0.836, P less than 0.002). In nine of fifteen patients, plasma ACTH showed either no change or a definite fall during subsequent follow-up. We conclude that plasma ACTH measurement in the first post-operative year is a good indicator of eventual outcome. The continued fall in plasma ACTH shown in many patients after the first year of treatment suggests an effect of irradiation on the pituitary.

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