Showing papers by "Scott M. Grundy published in 1992"
TL;DR: The effect of dietary supplementation with alpha-tocopherol on the time course of copper-catalyzed oxidation of LDL was tested in a randomized placebo-controlled single-blind study and did not result in any side effects or exert an adverse effect on the plasma lipid and lipoprotein profile.
297 citations
TL;DR: Lauric acid raises total and LDL cholesterol concentrations compared with oleic acid, but is not as potent for increasing cholesterol concentrations as is palmitic acid.
248 citations
TL;DR: In patients with mild NIDDM, high-carbohydrate diets do not improve glycemic control nor insulin sensitivity, and they raise plasma triglyceride and VLDL-ch cholesterol concentrations and reduce HDL-cholesterol levels, which may not be desirable.
Abstract: Previous studies indicate that diets rich in digestible carbohydrates improve glucose tolerance in nondiabetic individuals, but may worsen glycemic control in NIDDM patients with moderately severe hyperglycemia. The effects of such high-carbohydrate diets on glucose metabolism in patients with mild NIDDM have not been studied adequately. This study compares responses to an isocaloric high-carbohydrate diet (60% of total energy from carbohydrates) and a low-carbohydrate diet (35% of total energy from carbohydrates) in 8 men with mild NIDDM. Both diets were low in saturated fatty acids, whereas the low-carbohydrate diet was rich in monounsaturated fatty acids. The two diets were matched for dietary fiber content (25 g/day). All patients were randomly assigned to receive first one and then the other diet, each for a period of 21 days, in a metabolic ward. Compared with the low-carbohydrate diet, the high-carbohydrate diet caused a 27.5% increase in plasma triglycerides and a similar increase in VLDL-cholesterol levels; it also reduced levels of HDL cholesterol by 11%. Plasma glucose and insulin responses to identical standard breakfast meals were studied on days 4 and 21 of each period, and these did not differ significantly between the two diets. At the end of each period, a euglycemic hyperinsulinemic glucose clamp study with simultaneous infusion of [3- 3 H]glucose revealed no significant changes in hepatic insulin sensitivity; and peripheral insulin-mediated glucose disposal remained unchanged (14.7 ± 1.4 vs. 16.5 ± 2.3 μM · kg −1 · min −1 on the high-carbohydrate and low-carbohydrate diets, respectively). We conclude that in patients with mild NIDDM, high-carbohydrate diets do not improve glycemic control nor insulin sensitivity, and they raise plasma triglyceride and VLDL-cholesterol concentrations and reduce HDL-cholesterol levels, which may not be desirable.
230 citations
TL;DR: The discovery of the mechanism of the connection between triglycerides and coronary heart disease is crucial for developing a rational therapy.
Abstract: Hypertriglyceridemia is commonly found in patients with coronary heart disease. The reason for this connection, however, is not well understood, and two different views have been put forth to explain the link. First, triglyceriderich lipoproteins, particularly very-low-density lipoproteins, may be directly atherogenic. Or second, the metabolic consequences of hypertriglyceridemia may account for the triglyceride-coronary heart disease relationship. These consequences include an increase in postprandial lipoproteins, large very-low-density lipoprotein particles, small, dense low-density lipoprotein particles, low levels of high-density lipoprotein cholesterol, and possibly a procoagulant state. The appropriate treatment of hypertriglyceridemia depends on which of these views is nearer the truth. If triglyceride-rich lipoproteins are directly atherogenic, then the preferred therapy would be hepatic hydroxymethylglutaryl coenzyme A reductase inhibitors, which lower both very-low-density lipoprotein and low-density lipoprotein levels. On the other hand, if the link to atherogenesis is through the metabolic consequences of hypertriglyceridemia, the appropriate therapy would be to directly lower serum triglyceride levels, as with niacin or a fibric acid. Thus, discovery of the mechanism of the connection between triglycerides and coronary heart disease is crucial for developing a rational therapy. ( Arch Intern Med. 1992;152:28-34)
143 citations
TL;DR: Patients with CGL provided a unique opportunity to identify the various sites of localization of "mechanical" adipose tissue in the human body, and this study suggests that the genetic defect in CGL results in poor growth and development of metabolically active adiposed tissue, whereas mechanical adipose tissues is well preserved.
Abstract: Congenital generalized lipodystrophy (CGL) is a rare genetic disease with extreme paucity of fat from birth which is believed to be generalized, involving the whole body. Affected patients are characterized by severe insulin resistance. Sites of adipose tissue distribution in patients with CGL have not been studied systematically. Therefore, the fat distribution in three women (17-20 yr old) with CGL was investigated. Determination of body composition by underwater volume displacement suggested the complete absence of body fat (range, -3 to -7%; normal, 15-25%). Whole body magnetic resonance imaging, however, detected fat in particular anatomical sites, namely in orbits, palms and soles, and periarticular and epidural regions. Some fat was also localized in the tongue, breasts, vulva, and buccal area. Fat in other subcutaneous areas, intraabdominal and intrathoracic regions, and bone marrow was essentially absent. Thus, patients with CGL do not have a complete absence of body fat; of interest, fat is present in those sites where adipose tissue may be serving mainly a mechanical function. Patients with CGL, therefore, provided a unique opportunity to identify the various sites of localization of "mechanical" adipose tissue in the human body. Our study suggests that the genetic defect in CGL results in poor growth and development of metabolically active adipose tissue, whereas mechanical adipose tissue is well preserved.
112 citations
TL;DR: High-carbohydrate diets may cause accentuation of hyperglycemia and a rise in plasma glucagon levels in NIDDM patients and also adversely affect lipoproteins and therefore may not be desirable in all NID DM patients.
Abstract: OBJECTIVE To study effects of high carbohydrate intake on hyperglycemia, islet functions, and plasma lipoproteins in patients with NIDDM. RESEARCH DESIGN AND METHODS An attempt was made to induce hyperglycemia in 10 men with NIDDM by feeding them an isocaloric high-carbohydrate diet (65% of energy as simple carbohydrates [31% as glucose] and 20% as fat) for 28 days in a metabolic ward. Response to the high-carbohydrate diet was compared with that of feeding a diet rich in monounsaturated fat (45% of energy as fat [31% as monounsaturated fat] and 38% as carbohydrates) for 28 days in a cross-over manner. Islet functions were assessed by evaluating plasma glucose, insulin, C-peptide and glucagon responses to standard meal tolerance tests on days 0, 14, 21, and 28 of each dietary period. Fasting plasma lipoproteins were determined during the last week of each dietary period. RESULTS The high-carbohydrate diet caused significant but modest accentuation of hyperglycemia, particularly in patients with moderately severe diabetes mellitus, whereas no change was observed with the high-monounsaturated fatty-acid diet. Accentuation of hyperglycemia was accompanied by an increase in plasma glucagon levels, but no significant change in insulin and C-peptide responses. In 1 patient, feeding the high-carbohydrate diet for 68 days produced marked hyperglycemia and caused definite suppression of insulin and C-peptide responses along with an increase in glucagon levels. Compared with the high-monounsaturated fat diet, the high-carbohydrate diet also raised plasma triglyceride and VLDL cholesterol concentrations. CONCLUSIONS High-carbohydrate diets may cause accentuation of hyperglycemia and a rise in plasma glucagon levels in NIDDM patients. High-carbohydrate diets also adversely affect lipoproteins and therefore may not be desirable in all NIDDM patients.
84 citations
TL;DR: Evidence continues to accumulate supporting the hypothesis that the oxidative modification of LDL is a key step in the genesis of the atherosclerotic lesion and dietary micronutrients with antioxidant properties could prove a safe approach in inhibiting LDL oxidation and consequently preventing atherosclerosis progression.
Abstract: Evidence continues to accumulate supporting the hypothesis that the oxidative modification of LDL is a key step in the genesis of the atherosclerotic lesion. Dietary micronutrients with antioxidant properties, such as ascorbate, alphatocopherol, and beta-carotene, levels of which can be favorably manipulated by dietary measures without generally resulting in side effects, could prove a safe approach in inhibiting LDL oxidation and consequently preventing atherosclerosis progression. Hence this review will focus on the role of antioxidant vitamins on LDL oxidation and atherosclerosis. First the role of oxidized LDL (Ox-LDL) in atherosclerosis will be discussed. Then the relationship between antioxidant vitamins and atherosclerosis will be reviewed. Finally the studies focusing on the effect of antioxidant vitamins on LDL oxidation will be presented.
68 citations
TL;DR: For individuals with normal levels of plasma lipids, both residence times and input rates for apoA-I appeared to be important determinants of apo A-I levels, whereas input rates were highly variable among individuals.
68 citations
TL;DR: The fatty acid patterns of triglycerides and phospholipids extracted from adipose tissue, liver, heart, kidney, spleen, and lung of 3 groups of C57BL/6 mice were determined after feeding diets rich in palmitic acid and oleic acid for 9 months.
55 citations
TL;DR: A low dose of probucol (250 mg/day) given daily seems to afford protection against the oxidative modification of LDL, and does not appear to exert any substantial effect on the plasma lipoprotein profile.
40 citations
TL;DR: The data suggest that defects in chylomicron-triglyceride clearance that give rise to excess postprandial lipemia are not a common occurrence in normolipidemic men with low HDL cholesterol concentrations.
Abstract: To examine the relation between postprandial lipemia and high density lipoprotein (HDL) concentrations, we measured the plasma triglyceride and retinyl palmitate responses to 50-g fat meals of 1) 25 men with low HDL cholesterol concentrations (less than 36 mg.dl-1) and normal fasting triglyceride concentrations, 2) 25 men with normal HDL cholesterol (greater than 40 mg.dl-1) and normal fasting triglyceride concentrations, and 3) 20 men with mild to moderate fasting hypertriglyceridemia (250-347 mg.dl-1). The average magnitude of postprandial lipemia induced by the fat meals was markedly higher in the hypertriglyceridemic men (593 +/- 311 mg.dl-1.8 hr) than in either of the normolipidemic groups. In normotriglyceridemic men with low HDL cholesterol, mean postprandial lipemia (303 +/- 158 mg.dl-1.8 hr) was similar to the corresponding value of men with normal HDL (283 +/- 130 mg.dl-1.8 hr). Postprandial plasma retinyl palmitate concentrations, which reflect chylomicron remnant metabolism, also were similar in normal-HDL and low-HDL groups. These data suggest that defects in chylomicron-triglyceride clearance that give rise to excess postprandial lipemia are not a common occurrence in normolipidemic men with low HDL cholesterol concentrations. Accordingly, the low HDL cholesterol concentrations measured in the normotriglyceridemic men in this study must be attributable to factors other than an exaggerated postprandial lipemia.
TL;DR: The appropriate use and benefits of bile acid sequestrants, nicotinic acid, fibric acids, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and probucol are individually discussed, whereas nonpharmacologic approaches used in conjunction with the drugs are recommended emphatically.
Abstract: A detailed overview of the various forms of hyperlipidemia/dyslipidemia that constitute a major risk factor for coronary heart disease and a detailed discussion of the various types of cholesterol-lowering drugs are presented. The importance of identifying the type of dyslipidemia with respect to the choice of treatment is emphasized, as is the use of nonpharmacologic intervention, i.e., diet, exercise, and weight loss. The appropriate use and benefits of bile acid sequestrants, nicotinic acid, fibric acids, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and probucol are individually discussed, whereas nonpharmacologic approaches used in conjunction with the drugs are recommended emphatically.
TL;DR: To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range, and measurements were made of plasma lipid, lipop protein, and apolipoprotein levels and the kinetics.
Abstract: Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: A significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation, suggesting that two forms of LDL might be separable by ultracentrifugation.
Abstract: Recent studies have shown that one cause of primary moderate hypercholesterolaemia is familial defective apolipoprotein B-100 (FDB), a condition in which a mutation in apolipoprotein B-100 (apo B-100) causes low-density lipoproteins (LDL) to bind poorly to LDL receptors. One specific mutation, a glutamine-for-arginine transformation at position 3500 of apo B-100, has been reported to produce FDB. However, other mutations in apo B-100 might also cause FDB. The present study was designed to determine whether some patients with hypercholesterolaemia, who do not have the 3500 defect, may have a slowly cleared subfraction of LDL compatible with other forms of FDB. It was postulated that slowly removed LDL should accumulate excess cholesterol ester and hence be less dense than normal LDL. If so, in patients who are heterozygous for FDB, two forms of LDL might be separable by ultracentrifugation. To test this hypothesis, less-dense (d = 1.030 g ml-1) and more-dense (d = 1.040 g ml-1) subfractions of LDL were isolated from a patient with proven FDB (3500 mutation); the two forms of LDL were labelled with different isotopes of radioiodine and re-injected into the patient. The less-dense form was removed much more slowly (0.285 pools day-1) than more-dense LDL (0.570 pools day-1). This finding appeared to confirm the validity of the approach. The same procedure was then applied to 18 other patients having elevated LDL cholesterol but not the 3500 mutation. In 13 patients, the two forms of LDL were removed at essentially identical rates, suggesting that they did not have an abnormal form of LDL. In the other five, less-dense LDL were removed at a significantly slower rate than more-dense LDL; this finding suggests that a significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation.
TL;DR: The authors express the view that lack of response to a cholesterol-lowering diet may be due to a physiological nonresponsiveness, inadequate knowledge, and inability to change dietary habits.
Abstract: The investigation reported in this issue of theArchivesby Henkin et al 1 points out that long-term adherence to dietary therapy for high serum cholesterol levels remains a problem and presents a challenge to the health care team. This study revealed that many patients who initially responded to cholesterollowering diets later reverted to higher cholesterol levels. The authors express the view that lack of response to a cholesterol-lowering diet may be due to a physiological nonresponsiveness, inadequate knowledge, and inability to change dietary habits. Certainly, all of these factors are known to hamper successful long-term therapy for high serum cholesterol levels. Finally, the authors raise the question of whether continuing supervision and better nutritional labeling will improve dietary compliance in patients with elevated serum cholesterol levels. Although it is well to point out that long-term success with any dietary program presents a challenge, it can be questioned whether the
TL;DR: This trial provided the critical proof for the cholesterol-CHD hypothesis and, thereby, made possible the initiation of the National Cholesterol Education Program.
Abstract: The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) 1,2 was a landmark clinical trial that showed that lowering of the serum cholesterol level by cholestyramine therapy significantly decreased the risk for coronary heart disease (CHD). This trial provided the critical proof for the cholesterol-CHD hypothesis and, thereby, made possible the initiation of the National Cholesterol Education Program. A reduction in CHD rates by cholestyramine therapy was not accompanied by demonstrable serious side effects during the 7-year study period. However, in spite of a reduction in both new-onset CHD and deaths from CHD by cholestyramine treatment, there was not a statistically significant decrease in total mortality; this was because an apparent increase in trauma mortality offset the decrease in CHD deaths. The apparent increase in trauma mortality, it must be noted, was not statistically significant. Cholestyramine therapy in this trial also did not significantly predispose to tumor formation. Although total
Journal Article•
TL;DR: Triglyceride levels rise with increased carbohydrate intake, according to a long-term study of normal children from several countries and raises blood glucose levels and insulin requirements.
Abstract: Triglyceride levels rise with increased carbohydrate intake, according to a long-term study of normal children from several countries. Moreover, carbohydrate raises blood glucose levels and insulin requirements.