Abnormalities in lipoprotein metabolism in Gaucher type 1 disease

We have previously described an association between Gaucher type 1 disease and reduced levels of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol. Plasma concentrations of apolipoprotein B and apolipoprotein AI were reduced in these subjects, while plasma apolipoprotein E (apoE), which can be synthesized and secreted by macrophages, was increased. To study the pathophysiologic basis for these changes in lipoprotein and apolipoprotein levels, we studied very low density lipoprotein (VLDL), LDL, and HDL metabolism in-depth in four subjects with Gaucher disease. Gel filtration of their plasma revealed that apoE was present in essentially a single population of lipoproteins in the large HDL range. In subject no. 4, studied presplenectomy and post-splenectomy, plasma apoE levels fell after surgery in association with a redistribution of apoE among the plasma lipoproteins to a pattern seen in normal subjects. Determination of the rates of secretion and catabolism of VLDL apoB and triglyceride were within normal limits. The reduced plasma levels of LDL and HDL cholesterol, and of both plasma apoB and apoAI, were associated with increased fractional catabolic rates of these apolipoproteins in LDL and HDL. These results indicate that the hypocholesterolemia present in subjects with Gaucher type 1 disease is associated with increased fractional catabolism of LDL and HDL. These findings, together with the evidence for alternations in plasma apoE metabolism in this disorder, suggest a role for the macrophage as the basis for these abnormalities.     

Regional adiposity patterns in relation to lipids, lipoprotein cholesterol, and lipoprotein subfraction mass in men

Anatomical adipose tissue distribution patterns are reported to relate to plasma lipids and risk of cardiovascular disease. Waist to hip girth ratios (WHR) and subscapular 10 triceps skinfold thickness ratios (STR) were compared with percent body fat and body mass index values as correlates of plasma lipids and lipoprotein cholesterol and serum lipoprotein subfraction mass by analytic ultracentrifugation in 81 sedentary middle-aged men in a typical range of adiposity. WHR was significantly and positively correlated with plasma concentrations of triglycerides, cholesterol, and low and very low density lipoprotein (LDL and VLDL) cholesterol and inversely correlated with high density lipoprotein (HDL) cholesterol. STR followed these trends, though less strongly, in relation to plasma triglycerides, VLDL cholesterol, and HDL cholesterol. Pronounced differences were found between regional adiposity patterns in their relationships to lipoprotein subfractions, as determined by analytic ultracentrifugation. WHR was negatively correlated with HDL2 (flotation rate F(1.2) 3.5-9), positively with small LDL (S.f 0-7), intermediate density lipoprotein (S.f 12-20), and VLDL (S.f 20-400), while STR correlated with larger LDL (S.f 7-12) and larger VLDL (S.f 60-400). Overall adiposity was not significantly associated with plasma lipoprotein levels after adjusting for regional adiposity patterns. Plasma sex hormone-binding globulin and percent free testosterone were associated with regional adiposity, but did not account for the correlations between WHR and lipoproteins. WHR and STR are measures of fat distribution that correlate with plasma lipoprotein profiles consistent with cardiovascular disease risk and have different relationships to lipoprotein mass subfractions.     

中国人血中脂类指标的随龄变化

选择513例健康人作为研究对象，根据年龄分为9组，测定其血中脂类指标．结果发现血中胆固醇（CH）、甘油三酯（TG）、低密度脂蛋白（LDL）和极低密度脂蛋白（VLDL）在出生时含量较低，以后随增龄而升高；高密度脂蛋白（HDL）在出生时较低，以后逐渐升高．到20岁之前达高峰，以后又逐渐下降，脂蛋白（a）[Lp（a）]自出生后在一生中变化不大，无明显波动；氧化型低密度脂蛋白（ox－LDL）在出生时极低，以后随增龄而升高，到70岁之前达高峰，70岁之后又有下降的趋势．相关分析也发现血CH、TG、LDL、和xo－LDL与年龄之间里明显的正相关，HDL与年纷呈负相关关系，Lp（a）与年龄之间无相关关系．以上结果提示，随着增龄，脂类代谢的变化为动脉粥样梗化的发生提供了更多的物质基础．     

Relation of angiographically defined coronary artery disease to serum lipoprotein levels

The relationship of coronary artery disease to plasma lipoproteins was examined in 43 men admitted to our unit with suspected ischemic heart disease. Coronary arteriography was performed, and a score reflecting the severity of disease was assigned to the angiogram. Plasma, obtained after a 12-h overnight fast, was assayed for triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and HDL-3 cholesterol. HDL-2 cholesterol was found by subtraction. The cholesterol contents of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) were quantitated by the Freidwald equation. Men with high coronary scores tended to be older, and subjects with moderate coronary disease had significantly higher total and LDL cholesterol values than those with minimal disease. Age was the only factor to be significantly associated with coronary score and there was no significant association between coronary score and total LDL and HDL cholesterol or its subfractions when the age factor was taken into account.     

Serum Lipoproteins in Children with Anaemia

Plasma and erythrocyte lipids were estimated in 9 children with different types of anaemia and in 9 healthy control children. The anaemic children had rather high plasma triglycerides, but low total cholesterol and phospholipids. The levels of high density lipoprotein (HDL) cholesterol were particularly low, with a mean of only 70% of the controls. A positive correlation was found for haematocrit with HDL cholesterol, but not with low density lipoprotein (LDL) cholesterol. Plasma albumin was at the same level in both groups of children, however, suggesting that the diluting effect of increase in plasma volume could only partly explain the lowering of HDL cholesterol. A striking, inverse correlation between HDL cholesterol and very low density lipoprotein (VLDL) triglycerides was present in the anaemic children. Anaemia in children adds to previously recognized pathophysiological conditions which induce inversely interrelated changes in HDL and VLDL.     

Serum lipoproteins in children with anaemia.

Plasma and erythrocyte lipids were estimated in 9 children with different types of anaemia and in 9 healthy control children. The anaemic children had rather high plasma triglcerides, but low total cholesterol and phospholipids. The levels of high density lipoprotein (HDL) cholesterol were particularly low, with a mean of only 70% of the controls. A positive correlation was found for haematocrit with HDL cholesterol, but not with low density lipoprotein (LDL) cholesterol. Plasma albumin was at the same level in both groups of children, however, suggesting that the diluting effect of increase in plasma volume could only partly explain the lowering of HDL cholesterol. A striking, inverse correlation between HDL cholesterol and very low density lipoprotein (VLDL) triglycerides was present in the anaemic children. Anaemia in children adds to previously recognized pathophysiological condditions which induce inversely interrelated changes in HDL and VLDL.     

Effects of a low-fat diet on plasma lipoprotein levels

Lowering the intake of fat to decrease serum cholesterol levels has unknown effects on the proportion of cholesterol in low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Twenty normolipidemic nonvegetarians were given dietary instruction and supervision in a low-fat, semivegetarian diet for three months. Mean consumption of total fat, saturated fat, and cholesterol decreased, whereas intake of carbohydrate increased significantly on a low-fat diet. Plasma LDL levels decreased by 18% and HDL levels by 7% from prestudy baseline levels. The LDL/HDL ratio declined by 11%. Plasma triglyceride levels and body weight were unchanged. In individual subjects, the decrements in consumption of saturated fat and the increments in ingestion of polyunsaturated fat were each significantly correlated with decreases in LDL. One year after the subjects had returned to a self-selected diet, levels of dietary saturated fat and cholesterol and the plasma LDL/HDL ratio remained significantly below prestudy levels. This study and others suggest that a low-fat, high-carbohydrate diet favorably affects the plasma LDL/HDL proportion by decreasing LDL on a percentage basis 2 1/2 to three times more than it decreases HDL.     

Relationships of low density lipoprotein subfractions to angiographically defined coronary artery disease in young survivors of myocardial infarction.

Low density lipoprotein (LDL) from 36 young post-infarction patients was separated by isopycnic density gradient ultracentrifugation to determine the relationships of plasma levels and chemical composition of different LDL subfractions to the global severity and rate of progression of coronary atherosclerosis assessed by angiography. There were marked elevations of the cholesterol and triglyceride concentrations in the very low density lipoprotein (VLDL) fraction, whereas the high density lipoprotein (HDL) cholesterol level was reduced in the patients compared with 70 healthy population-based controls. Plasma total LDL cholesterol and triglyceride concentrations were similar. The distribution of apolipoprotein B along the LDL density range, viz. the LDL particle distribution, was displaced towards the dense LDL region among the patients compared with 14 healthy normolipidaemic controls. A preponderance of dense LDL particles was associated with elevated plasma VLDL triglyceride concentration. The patients had significantly higher plasma concentrations of lipid and protein in dense LDL (d greater than 1.040 kg/l), while no group differences were found in the light LDL (d less than 1.040 kg/l). However, there were no percentage compositional differences in the light or dense LDL between patients and controls. Among all constituents of lipoprotein fractions and subfractions determined, only the plasma level of triglycerides in both light and dense LDL correlated significantly with the angiographic estimates of global severity and rate of progression of coronary atherosclerosis, respectively. On a percentage composition basis, both light and dense LDL tended to be richer in triglycerides in the subjects with a more severe coronary artery disease. Neither VLDL or HDL, nor LDL cholesterol were associated with the angiographic scores, the plasma LDL triglyceride concentration or the triglyceride enrichment of LDL. Although there is ample experimental evidence that triglyceride-enriched LDL predisposes to atherosclerosis, the LDL associations with coronary lesion severity and progression observed in the present study might not reflect a causal mechanism, but merely mirror the atherogenicity of disturbances affecting the metabolism of triglyceride-rich lipoproteins. Prospective studies of larger groups of unselected patients are needed to corroborate these findings.     

Influence of plasma triglycerides on lipoprotein patterns in normal subjects and in patients with coronary artery disease

This study examined the correlation of plasma triglyceride levels with concentrations of intermediate, low and high density lipoproteins (IDL, LDL, and HDL, respectively) and to particle sizes of LDL in 93 normal men and 106 men with coronary artery disease. Plasma triglyceride concentrations were in the normal range for all persons in both groups. Analysis of lipoproteins of density less than 1.063 g/ml was carried out by analytical ultracentrifugation. The analytical pattern gave the peak Sf for LDL as well as an indication of heterogeneity of particle sizes in the density range of LDL. In both normal subjects and patients with coronary artery disease, a positive correlation was found between peak Sf for LDL and concentrations of plasma triglycerides. Plasma triglyceride levels also were correlated positively with concentrations of Sf 20 to 60 lipoproteins and total IDL mass, and inversely with HDL cholesterol levels. Furthermore, the value for peak Sf for LDL correlated inversely with the IDL mass concentration and IDL/LDL mass ratio, and positively with the HDL cholesterol levels. The results indicate that the lipoprotein pattern, including lipoprotein concentrations and particle sizes, is sensitive to concentrations of plasma triglycerides even when the latter are within the normal range.     

Effects of long-term negative energy balance with exercise on plasma lipid and lipoprotein levels in identical twins

Plasma lipid and lipoprotein concentrations were measured before and after a 58,000kcal (244MJ) negative energy balance protocol induced entirely by supervised endurance exercise over a 93-day period in seven pairs of young sedentary and healthy male monozygotic twins. The negative energy balance induced significant changes in all measures of body weight and composition except fat free mass. The mean weight loss was 5.0+/-0.6kg, and it was entirely accounted for by the loss of body fat. In response to the program, improvement in the plasma lipid profile was seen including decreases in plasma total (P=0.028) and low density lipoprotein (LDL) (P=0.004) cholesterol; total cholesterol/high density lipoprotein (HDL) cholesterol ratio (P=0.002); and HDL apolipoprotein A-I concentration (P=0.062). Statistically significant within-pair resemblance was found for the changes in total and very low density lipoprotein (VLDL) cholesterol; total, VLDL and LDL triglycerides, and total, VLDL and LDL apolipoprotein B. The findings suggest that favorable changes in the lipid profile can be obtained through chronic negative energy balance achieved by clamping daily energy intake and adding daily moderate intensity exercise even in persons with relatively normal lipid levels at baseline. Furthermore, within-pair resemblance among twin brothers strongly suggests that genetic differences partially account for the variation in the response of lipids and lipoproteins to the negative energy balance protocol.     

Plasma testosterone,high density lipoprotein cholesterol and other lipoprotein fractions

High density lipoprotein (HDL) cholesterol levels are strongly related to risk of heart attack. Identification of determinants of high density lipoprotein cholesterol may provide important information concerning the cause of heart disease. The relation between one possible determinant, testosterone, and high density lipoprotein cholesterol and other lipoprotein fractions was evaluated in 247 middle-aged men. The results indicate that testosterone levels (both free and total) were positively correlated with high density lipoprotein cholesterol (r = +0.24, p < 0.01) and negatively correlated with triglycerides and very low density lipoprotein cholesterol. The association between testosterone and high density lipoprotein cholesterol could not be explained by intake of alcohol, obesity, age, smoking or physical activity. Furthermore, the relation of testosterone to HDL cholesterol was independent of the relation of testosterone to very low density lipoprotein (VLDL) cholesterol or triglycerides.     

Importance of HDL cholesterol levels and the total/ HDL cholesterol ratio as a risk factor for coronary heart disease in molecularly defined heterozygous familial hypercholesterolaemia.

AIMS: To assess the relationship of the lipid profile to coronary heart disease in a group of heterozygous familial hypercholesterolaemic subjects with similar age, sex, body mass index, prevalence of angiotensin converting enzyme DD genotype and type of low density lipoprotein receptor mutation. METHODS AND RESULTS: A total of 66 molecularly defined heterozygous familial hypercholesterolaemic subjects, 33 of whom had coronary heart disease, were studied. Clinical features, cardiovascular risk factors and lipid parameters were compared in both groups. Familial hypercholesterolaemic patients with coronary heart disease showed significantly lower values of mean plasma HDL cholesterol and a higher total/HDL cholesterol ratio as compared with familial hypercholesterolaemic subjects free of coronary heart disease. Total and LDL cholesterol concentrations were higher in patients with coronary heart disease, without reaching statistical significance. No differences in plasma lipoprotein(a) levels on absolute and log-transformed values were observed between the two groups. In the whole familial hypercholesterolaemia group, plasma HDL cholesterol levels were related to plasma triglyceride values and to LDL receptor gene 'null mutations'. CONCLUSIONS: In familial hypercholesterolaemic subjects of similar age, gender, body mass index, systolic and diastolic blood pressure, and genetic factors that could influence coronary heart disease risk, plasma HDL cholesterol values and total/HDL cholesterol ratios are two important coronary risk factors. Hence, treatment of familial hypercholesterolaemia should focus not only on lowering total and LDL cholesterol levels, but also on increasing HDL cholesterol values for coronary heart disease prevention. More prospective and intervention trials should be conducted to establish the relationship of HDL cholesterol levels and coronary heart disease in familial hypercholesterolaemia.     

内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白对血凝及纤维蛋白溶解的影响

研究内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白是否发生了氧化修饰及其对凝血及纤维蛋白溶解活性的影响。对 2 1例内源性高甘油三酯血症患者与 2 1例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白。测定这 3种脂蛋白的 2 34nm吸光度、相对电泳迁移率和硫代巴比妥酸反应物质含量。分别将这 3种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中 ,按试剂盒分别测定凝血酶原时间、活化部分凝血酶原时间、组织型纤溶酶原激活物活性及纤溶酶原激活物抑制剂 1活性。内源性高甘油三酯血症患者血浆甘油三酯含量平均升高 2 .73倍 ,高密度脂蛋白胆固醇下降 1.71倍 ,同时硫代巴比妥酸反应物质含量升高 1.2 2倍 ;内源性高甘油三酯血症组极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白的 2 34nm吸光度、相对电泳迁移率和硫代巴比妥酸反应物质含量均较对照组显著增加 (P <0 .0 1) ,表明内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白均发生了氧化修饰 ,生成了氧化极低密度脂蛋白、氧化低密度脂蛋白及氧化高密度脂蛋白。凝血酶原时间及活化部分凝血酶原时间在分别加入内     

Increase in plasma high-density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma

There is evidence that endogenous estrogens have a positive effect on plasma high density lipoprotein (HDL) concentration, whereas the relation between HDL and male sex hormones is unclear, since both positive and negative effects have been reported. This study examined the effects of LHRH agonist in combination with an antiandrogen on plasma lipids and lipoproteins in 17 elderly men with prostatic carcinoma. Subjects were examined prior to and after therapy at 4-week intervals up to 16 weeks. Prior to therapy, their lipid and lipoprotein profiles were not significantly different from a control group composed of individuals of similar age and living in the same community area. Following therapy plasma levels of testosterone and dihydrotestosterone were markedly decreased (above 90%) and their residual activity neutralized through effective use of an antiandrogen. Plasma estradiol decreased between 65% and 85% and the concentration of cortisol was unaffected. The very low density lipoprotein (VLDL) apo-B decreased and low density lipoprotein (LDL) apo-B increased; thus, no change was observed in the total plasma apo-B levels. Total plasma cholesterol increased by 6% (baseline v peak values, mg/dL, mean +/- SEM; 219 +/- 9 v 233 +/- 9, P less than 0.05) due to a significant rise in HDL cholesterol concentration (45.5 +/- 2.8 v 56.5 +/- 3.6, P less than 0.01). Both VLDL and LDL cholesterol levels remained unchanged. The mean elevation of 21% in HDL cholesterol was accompanied by a significant rise in HDL apo-A concentration (161 +/- 6 v 193 +/- 10, P less than 0.01), thus suggesting an increase in HDL mass and/or particle number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma lipoprotein cholesterol in India in healthy persons and those with coronary heart disease

The plasma total cholesterol and lipoprotein cholesterol levels are presented for 186 healthy Indian subjects and 213 patients with coronary heart disease (CHD). Plasma lipid and lipoprotein concentrations vary with age. Higher total cholesterol and LDL cholesterol were noted in men compared with women. HDL cholesterol is highest in women in the age group 20-49 years. HDL cholesterol levels (negatively associated with CHD) are significantly higher in India compared with western countries. It is suggested that the high level of HDL cholesterol may be responsible for the relatively low incidence of CHD in India.     

Accelerated turnover of very low density lipoprotein triglycerides in chronic alcohol users. A possible mechanism for the up-regulation of high density lipoprotein by ethanol

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.     

Hyperlipemia and arteriosclerotic cardiovascular disease in the Polynesian population of Rarotonga

Total cholesterol, total triglyceride and high density lipoprotein (HDL) cholesterol and their relation to arteriosclerotic cardiovascular disease (ASCVD) were investigated in a population of Polynesian Maoris in Rarotonga who are becoming increasingly westernized. 8.5% of the population had plasma triglyceride elevations (triglyceride greater than or equal to 200 mg/dl), and the occurrence of hypertriglyceridemia was significantly higher in males than females. 5.8% of the population had elevations of total cholesterol (cholesterol greater than or equal to 250 mg/dl), and the proportion with elevation of total cholesterol was similar for males and females. 3.2% of the population had elevations of both triglyceride and cholesterol. HDL cholesterol concentrations were relatively low, and no sex differences were observed at any age. Analysis of lipoprotein cholesterol and triglyceride in a subset of those who had hyperlipemia indicated that the elevations of total cholesterol and triglyceride were mainly due to elevations of low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) triglyceride, respectively; furthermore, elevations of VLDL triglyceride and LDL cholesterol were significantly correlated with increase in VLDL apolipoprotein B (apo B) and LDL apo B, respectively. Although an appreciable prevalence of diabetes was observed in this population (male: 6.7%, female: 8.4%), the diabetes could not account for the hyperlipemia. Among 693 subjects between the ages of 30 and 59 years, approx. 3% of males and 1% of females had Q-wave changes, and 16% of females and 4% of males had ST-T changes. Among males with Q-wave abnormalities, hyperlipemia was more frequent. There was also increased frequency of hypertension in those with elevated lipids. The data indicate the occurrence of some hyperlipemia in this population which could be of the familial-combined type; the elevated plasma lipids may contribute to the increased frequency of coronary heart disease.     

Alcohol-Induced Changes in Lipids and Lipoproteins

Fasting plasma samples from 42 voluntary subjects of moderate to high socioeconomic status families and living in Delhi, taking 5-20 oz/week of alcohol regularly, and 42 normal subjects from comparable socioeconomic status with no history of intake of alcohol and no evidence of any known metabolic or coronary problems were analyzed for cholesterol and triglycerides and their levels in lipoprotein fractions, i.e., very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). Free fatty acids, urea, uric acid, and glucose levels were also determined and dietary intake was calculated in the two groups. Cholesterol and triglycerides in plasma, and VLDL and LDL fractions were found to be increased in the alcohol-taking group even though their intake of alcohol was moderate. VLDL fraction formed 65 and 32% of total triglycerides and cholesterol, respectively. Sugar, uric acid, and free fatty acids (FFA) increased significantly in the alcohol-taking group. Total energy intake was significantly higher in the alcohol-taking group mainly from significant high intake of proteins and fats. Calculated on the basis of intake/day/kg of body weight, the difference in intake of protein, fat, and carbohydrates was insignificant. Regular intake of even small quantity of alcohol along with food rich in proteins and fats may induce elevation of high cholesterol-containing lipoproteins, i.e., LDL and VLDL with increased hypertriglyceridemia, and these increased levels may constitute important coronary risk factors.     

Abnormal low and high density lipoproteins in homozygous beta-thalassaemia

The levels, structure and composition of plasma lipoproteins were determined in 67 patients with homozygous beta-thalassaemia and compared to healthy or heterozygous members of the same families and to patients with either sickle cell or iron deficiency anaemia. Plasma total and LDL and HDL cholesterol levels were low in patients with homozygous beta-thalassaemia and with sickle cell anaemia. Plasma triglycerides did not differ between subjects. The low plasma and lipoprotein cholesterol was independent of age, transfusion requirements and splenectomy. Abnormal structure and composition of lipoproteins was found in homozygous beta-thalassaemia. The LDL was of higher density and was triglyceride-rich and cholesterol ester-poor. HDL separated to three populations. HDL2 was prominent (in spite of low plasma HDL cholesterol). HDL3 was of normal density and an intermediate HDL population, not found in normal subjects, was identified and designated HDL2-3. All three HDL populations were enriched with triglycerides and poor in cholesterol ester content. The modified LDL and HDL particles may then be possibly cleared rapidly from the plasma by activated monocytes and macrophages.     

Lipoprotein subfraction composition in non-insulin-dependent diabetes treated by diet, sulphonylurea, and insulin

Lipoprotein abnormalities may predispose to an increased risk of coronary heart disease in type II (non-insulin-dependent) diabetes mellitus. To investigate the effects of different treatment modalities, the composition and concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of patients with type II diabetes at diagnosis, treated by diet alone, treated by diet + glibenclamide (2.5 to 15 mg/d for 6 to 48 months), and treated by diet + insulin (25 to 65 U/d for 8 to 144 months). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, type II patients at diagnosis showed increased concentrations of nonesterified and esterified cholesterol, triglyceride, phospholipid, and protein in the very low density lipoprotein (VLDL) fraction. However, the only alteration in VLDL composition was a small decrease in the relative proportion of phospholipid. Apolipoprotein-B and low density lipoprotein (LDL) cholesterol concentrations were also raised in type II patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) nonesterified and esterified cholesterol, phospholipid, and apo-AI were lower in type II patients at diagnosis. This was largely accounted for by reduced concentrations of these components in the HDL2 subfraction, which retained a normal composition. Type II patients treated by diet alone and diet + glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations, which are associated with premature coronary disease, to the type II patients at diagnosis. However, in type II patients treated with insulin, plasma lipoprotein concentrations and composition were normal, except LDL cholesterol, which was lower than normal in insulin-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)