Effects of jejuno-ileal bypass on serum lipoproteins and glucose tolerance in severely obese patients

Plasma insulin and blood glucose during oral glucose tolerance tests (OGTT) and serial determinations of serum lipoprotein fractions before and after jejuno-ileostomy in twenty severely obese (mean weight 137 kg) patients with a mean age of 29 years revealed statistically significant postoperative decreases in all parameters concomitant with a mean weight loss of 42 kg. Before the operation the patients were hyperinsulinaemic and had elevated blood glucose levels during OGTT though no patient had overt diabetes. Serum triglyceride and total cholesterol levels were normal but HDL cholesterol was significantly lower than in controls. During follow-up at least until body weight had levelled off a mean 19 months post-operative, there were statistically significant reductions in blood glucose and plasma insulin as well as serum total cholesterol and lipoprotein fractions. There was no change in serum triglycerides. The low preoperative HDL levels decreased. In a subgroup of these patients we have earlier shown postoperative increases in arterial tissue cholesterol coincident with the present significant decreases in HDL as well as in LDL cholesterol. Correlations between total cholesterol and lipoprotein cholesterol values in serum and blood glucose and plasma insulin at fast and during OGTT and changes in these parameters demonstrate interrelationships between lipid and carbohydrate metabolism. The bypass procedure most likely reduces the intestinal synthesis of HDL which in turn may increase hepatic cholesterol synthesis. Evidently there is a multifactorial aetiology for the low HDL levels in the severely obese both before and after jejuno-ileostomy.     

血脂、腰臀比异常对糖尿病血管并发症的影响及护理干预

目的对544例2型糖尿病(T2DM)患者及278例健康人进行空腹血糖(FBG)、总胆固醇(TC)、甘油三酯TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、LDL/HDL及腰臀比(WHR)、体重指数(BMⅠ)的测定,探讨其T2DM血管并发症与血脂代谢及WHR的关系。方法将T2DM组(A、B组)的FBG、TC、TG、HDL、LDL、LDL/HDL及WHR、BMI与正常对照组及组间进行比较分析。结果T2DM组(A、B组)与正常对照组相比FBG、TC、TG、LDL、LDL/HDL及WHR有显著增高,HDL明显降低。特别是有血管病变组与无血管病变组相比TC、LDL、LDL/HDL增高差异有显著意义(P<0.001),HDL也降低,差异有显著意义(P<0.001),同时WHR及BMI增高差异有显著意义。结论血脂代谢紊乱是DM患者导致血管病变的主要原因,而WHR及BMI增高是发生T2DM的重要危险因素,同时,WHR及BMI可作为自我了解健康状况的重要指标之一。     

Metabolic Control of the Circulation: EFFECTS OF ACETATE AND PYRUVATE

Chloralose-anesthetized dogs were infused intravenously with either Tris-acetate or Tris-pyruvate at 0.0375, 0.075, and 0.15 mmol/kg per min successively, each for 20 min. Acetate infusion increased cardiac output, left ventricular dP/dt and dP/dt/P, and coronary blood flow, while pyruvate infusion did not. Infusions of either substance increased arterial blood and skeletal muscle concentrations of citrate and malate, but only acetate infusion increased the tissue AMP content and decreased the ATP:AMP ratio. The increase in cardiac output produced by acetate was accompanied by an increase in total body oxygen consumption and a decrease in the difference between arterial and mixed venous blood oxygen.Myocardial oxygen consumption increased during acetate infusion, but the decrease in myocardial oxygen extraction and the increase in coronary sinus blood oxygen saturation suggest that an active coronary vasodilation which was not a result of the increased cardiac work, occurred. The concentration of hypoxanthine in the coronary sinus and the content of myocardial adenosine increased, which suggests that the increase in coronary blood flow was caused by the vasodilator action of adenosine released from the myocardium, and that adenosine production is not necessarily tied to PO(2).These systemic and coronary hemodynamic changes also occurred when acetate (0.075 mmol/kg per min) was infused into conscious dogs. Acetate infusion also increased blood flow to the gastrointestinal tract, kidneys, intercostal muscle, and diaphragm. These changes were not affected by propranolol pretreatment, but were abolished by pretreatment with fluoroacetate which reduced acetate oxidation.These results suggest that the circulatory stimulation produced by acetate was not caused by increases in tricarboxylic acid cycle intermediates. Instead, it was probably related to the increased cleavage of ATP to AMP that accompanies activation of acetate to acetyl CoA, and was not mediated via beta-adrenergic receptors. It is speculated that hemodynamic changes may occur in patients who undergo hemodialysis with acetate-containing dialysate. Hemodynamic changes of ethanol may also be brought about by acetate, which is one of the intermediates that accumulates during ethanol metabolism.     

Inverse relationship in Jamaica between plasma high-density lipoprotein cholesterol concentration and coronary-disease risk as predicted by multiple risk-factor status.

1. The relation between plasma high-density lipoprotein (HDL) cholesterol concentration and multiple coronary-risk factor status has been assessed in fifty-two middle-aged clinically healthy men from urban and rural Jamaica. 2. Rural hill-farmers had a superior exercise performance (assessed by the responses to submaximal test exercise), less body fat, and lower fasting levels for plasma total cholesterol, low-density liproprotein (LDL) cholesterol, total triglyceride and blood glucose than urban businessmen. Mean plasma HDL cholesterol was considerably higher in farmers then businessmen. 3. Multilinear regression analysis showed HDL cholesterol concentration to be independently and inversely correlated with plasma triglyceride, LDL cholesterol and diastolic blood pressure and that these relationships applied across the urban and rural sub-groups. There was also some evidence that HDL cholesterol concentration increased with stature. When these factors were taken into account, age, ethnic group, adiposity, weight, exercise performance, smoking history and blood glucose made no further significant contribution to the prediction of HDL cholesterol concentration. 4. Thus plasma HDL cholesterol concentration was highest in those subjects with the lowest coronary-risk as predicted by their multiple risk-factor status, an observation which supported other evidence that coronary-risk is inversely related to plasma HDL concentration. 5. The results raise the possibility that coronary-risk can be more simply estimated from the plasma HDL cholesterol concentration than from a consideration of other major lipid risk factors and blood pressure.     

Lipid profile, glucose homeostasis, blood pressure, and obesity-anthropometric markers in macrosomic offspring of nondiabetic mothers

OBJECTIVE: The study was to determine whether being the macrosomic offspring of a mother without detected glucose intolerance during pregnancy has an impact on lipid profile, glucose homeostasis, and blood pressure during childhood. RESEARCH DESIGN AND METHODS: Plasma total, HDL, and LDL cholesterol; triglycerides; apolipoprotein (Apo) A-1, -B, and -E; lipoprotein (a); fasting glucose and insulin; homeostasis model assessment of insulin resistance (HOMA-IR) index; blood pressure; BMI; and detailed anthropometry were evaluated in 85 children aged 3-10 years old, born appropriate for gestational age (AGA; n = 48) and large for gestational age (LGA; n = 37) of healthy mothers. RESULTS: At the time of the assessment, body weight, height, skinfold thickness, BMI, waist circumference, and blood pressure did not differ between the LGA and AGA groups with the exception of head circumference (P < 0.01). There were no significant differences in plasma total or LDL cholesterol; triglycerides; Apo A-1, -B, or -E; lipoprotein (a); Apo B-to-Apo A-1 ratio; or glucose levels between the groups. The LGA group had significantly higher HDL cholesterol levels (P < 0.01), fasting insulin levels (P < 0.01), and HOMA-IR index (P < 0.01) but lower values of the glucose-to-insulin ratio (P < 0.01) as compared with the AGA group. CONCLUSIONS: Children born LGA of mothers without confirmed impaired glucose tolerance during pregnancy show higher insulin concentrations than AGAs.     

Bile acids and plasma high density lipoproteins: biliary lipid metabolism in fish eye disease

Cholesterol in plasma high density lipoproteins (HDL) has been proposed to serve as preferential precursor for bile acid biosynthesis in the liver. Furthermore, a negative relationship between plasma levels of HDL cholesterol and biliary saturation with cholesterol has been reported in healthy females. We have performed metabolic studies on a female patient with fish eye disease, a familial condition where plasma HDL levels are reduced by 90% and the concentration of plasma triglycerides is moderately increased. Both the total production of bile acids and the net steroid 'balance' (reflecting total body cholesterol synthesis) were within the range seen in normolipidaemic as well as in hypertriglyceridaemic females. Also the biliary lipid composition and cholesterol saturation of bile were normal. A qualitative abnormality in the bile acid pattern was observed, however, in that the ratio between the synthesis of cholic acid and chenodeoxycholic acid was reduced. It is concluded that a low HDL cholesterol level is not necessarily associated with quantitative abnormalities of biliary lipid metabolism. The abnormal bile acid synthesis ratio may reflect changes in the hepatic precursor pools of cholesterol as the consequence of HDL deficiency, however.     

Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with prior gestational diabetes mellitus

OBJECTIVE: Women with prior gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes and associated vasculopathy. Because increased fat mass and inflammatory processes are angiopathic risk factors, the relationship between insulin sensitivity, parameters of subclinical inflammation, and plasma concentrations of adipocytokines was investigated in pGDM both at 3 months and 12 months after delivery. RESEARCH DESIGN AND METHODS: Insulin sensitivity (through a frequently sampled intravenous glucose tolerance test) and plasma concentrations of ultrasensitive C-reactive protein (CRP), adiponectin, plasminogen activator inhibitor (PAI)-1, tumor necrosis factor-alpha, leptin, and interleukin-6 were measured in 89 pGDM (BMI 26.9 +/- 0.5 kg/m(2), age 32 +/- 0.5 years) and in 19 women with normal glucose tolerance during pregnancy (NGT) (23.7 +/- 0.9 kg/m(2), 31 +/- 1.3 years). RESULTS: pGDM showed lower (P < 0.0001) plasma adiponectin (6.7 +/- 0.2 microg/ml) than NGT (9.8 +/- 0.6 microg/ml) and a decreased (P < 0.003) insulin sensitivity index (S(i)) and disposition index (P < 0.03), but increased plasma leptin (P < 0.003), PAI-1 (P < 0.002), and CRP (P < 0.03). After adjustment for body fat mass, plasma adiponectin remained lower in pGDM (P < 0.004) and correlated positively with S(i) (P < 0.003) and HDL cholesterol (P < 0.0001) but negatively with plasma glucose (2-h oral glucose tolerance test [OGTT]) (P < 0.0001), leptin (P < 0.01), CRP (P < 0.007), and PAI-1 (P < 0.0001). On regression analysis, only HDL cholesterol, postload (2-h OGTT) plasma glucose, and S(i) remained significant predictors of plasma adiponectin, explaining 42% of its variability. Of note, adiponectin further decreased (P < 0.05) only in insulin-resistant pGDM despite unchanged body fat content and distribution after a 1-year follow-up. CONCLUSIONS: Lower plasma adiponectin concentrations characterize women with previous GDM independently of the prevailing insulin sensitivity or the degree of obesity and are associated with subclinical inflammation and atherogenic parameters.     

Lipoproteins and apolipoproteins in young nonobese Arab women with NIDDM treated with insulin

The effects of insulin on the lipid values of nonobese non-insulin-dependent diabetic (NIDDM) Arab women requiring insulin was investigated to find whether these patients have the same coronary artery risk factor related to lipid levels. In this study, 55 NIDDM women on insulin therapy (mean age 28 +/- 8.1 yr and duration of disease 5 +/- 1.2 yr) and 70 control subjects (matched for sex, age, and body mass index) were studied for their plasma levels of lipids, lipoproteins, and apolipoproteins. Concentrations of total cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride (TG), LDL TG, high-density lipoprotein triglyceride (HDL TG), phospholipid, glucose, glycosylated hemoglobin (HbAtc), apolipoprotein B (apoB), LDL-apoB, and apoB/apoAl were significantly elevated in diabetic women compared with control subjects. There was no significant change in the levels of apoAll in plasma and lipoprotein fractions. Concentrations of HDL cholesterol (chol), HDL2-chol, HDL3-chol, plasma apoAl, HDL2-apoAl, HDL3-apoAl, and HDL-apoAl were significantly lower in diabetic women than in control subjects. There was no significant correlation between glucose or HbAtc and most of the lipids, lipoprotein lipids, and apolipoproteins measured. Despite normal body weight and insulin therapy, abnormalities in lipids, lipoprotein lipids, and apoB persisted in NIDDM patients compared with control subjects. Our data may favor an enhanced affinity toward atherosclerosis in these patients.     

Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes

BACKGROUND: Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. MATERIALS AND METHODS: The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides <2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h. RESULTS: No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (Rs = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (Rs = -0.48, P < 0.05) and the HDL triglyceride content was positively (Rs = 0.64, P < 0.01) correlated with CET. CONCLUSION: Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus.     

缺血性脑血管病病人血浆LCAT 活性与脂蛋白和红细胞膜脂质成分的相关性研究

目的:探讨缺血性脑血管病（ischemic cerebrovascular disorders,ICVD）病人血浆卵磷脂-胆固醇酰基转移酶（LCAT）活性与脂蛋白和红细胞膜脂质成分含量的相互关系。方法:采用改良的Nagaski酶学方法-外加底物法测定103例ICVD病人和60例健康者血浆LCAT活性,并检测血浆高密度脂蛋白胆固醇（HDL-C）及其亚组分（HDL2-C、HDL3-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A1和B（apoA1,apoB）、红细胞膜胆固醇（RBCM-C）和红细胞膜磷脂（RBCM-PL）的含量变化。结果:ICVD病人血浆LCAT活性、HDL-C、HDL2-C及apoA1含量明显降低,血浆LDL-C、apoB、RBCM-C及RBCM-C/RBCM-PL比值显著增高,与对照组相比差异有显著性（P<0.05）,血浆LCAT活性分别与HDL-C、HDL2-C及apoA1水平呈正相关（P<0.05、P<0.05、P<0.05）,而与LDL-C（和RBCM-C呈负相关（P<0.05）。结论:ICVD病人脂质代谢异常与血浆LCAT活性降低有关。     

Induction of net mass lipid transfer reactions in plasma by wine consumption with dinner

Abstract. Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Alcohol may exert protection through its effects on the metabolism of plasma lipoproteins. In the present study we investigated the effects of moderate wine consumption with an evening dinner on lipoprotein composition and parameters of reverse cholesterol transport (plasma lipid transfer reactions and cholesterol esterification) in eight healthy middle-aged men. Wine consumption, if compared with mineral water, resulted in increased postprandial plasma levels of triglyceride-(TG)-rich lipoproteins ( P < 0.005 or <0.002 at two different time points) and in increased net mass transfer of cholesterylesters (CE) from high-density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins during in vitro incubation of plasma ( P < 0.001). Net mass transfer of TG (in the opposite direction) was also significantly increased by wine ( P = 0.014). The concentrations of total plasma cholesterol, HDL-cholesterol and apolipoproteins A-I, A-II and B did not change postprandially and were not affected significantly by wine, but the CE TG^-1 in HDL was affected postprandially and decreased by wine consumption. It is concluded that moderate wine consumption with evening dinner induces transfer reactions of CE and TG between HDL and TG-rich lipoproteins. Due to the fact that wine raises plasma TG, it also causes changes in plasma cholesterol metabolism and lipoprotein composition, without major effects on total plasma cholesterol concentration.     

Metabolic and antihypertensive effects of nebivolol and atenolol in normometabolic patients with mild-to-moderate hypertension.

This was a double-blind, randomized, two-center, active-controlled, prospective, parallel study designed to evaluate the effects of nebivolol at daily doses of 5 mg on lipid and carbohydrate metabolism and on blood pressure in comparison with atenolol at daily doses of 50 mg. Normometabolic subjects with mild-to-moderate essential hypertension were recruited for this study, which included a 4-week, single-blind placebo washout phase and a 12-week double-blind treatment phase. After 12 weeks of treatment, both drugs demonstrated a significant decrease from baseline in high-density lipoprotein (HDL) apolipoprotein A-I (HDL-apoA-I) (nebivolol, P <.02; atenolol, P <.05). A significant reduction in HDL cholesterol (HDL-C) from baseline was also observed with nebivolol (P <.05). There were no significant differences between the drugs for these parameters, and the ratio low-density lipoprotein cholesterol (LDL-C)-to-HDL-C did not change significantly after 12 weeks of active treatment with nebivolol or atenolol. There were no significant changes in total cholesterol, HDL (2) -C, HDL (3) -C, LDL-C, very-low-density lipoprotein cholesterol (VLDL-C), total triglycerides, HDL-triglycerides (TG), LDL-TG, VLDL-TG, total apoB, LDL-B, VLDL-B (including the ratio LDL-C-to-LDL-apoB), or Lp(a) during treatment with both drugs. No significant differences in plasma apoA-I and apoC-III as well as in apoA-I-, C-III-containing lipoprotein particles (including the apoC-III ratio) were observed between the drugs, neither before nor after each active treatment. There were no significant differences between the drugs or within each treatment group in plasma glucose, insulin, or C-peptide concentrations after a 2-hour oral glucose tolerance test. Mean clinic trough sitting systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 150/98 mm Hg at baseline to 141/90 mm Hg at termination for nebivolol and from 160/99 mm Hg at baseline to 145/88 mm Hg at termination for atenolol. No significant between-treatment differences were observed for the mean clinic trough sitting SBP/DBP. Both drugs significantly increased the atrial natriuretic factor (ANF) N-terminal plasma levels, whereas no changes were observed in ANF C-terminal plasma concentrations. A significant decrease (P <. 05) in the plasma adrenocorticotropic hormone levels was observed after administration of both drugs. A significant decrease (P <.05) in plasma cortisol levels was observed only after atenolol treatment. The incidence of adverse events reported during nebivolol treatment was comparable to that observed during atenolol treatment. Heart rate was significantly reduced by both drugs. There were no significant changes in hematology, biochemistry, or urinalysis studies. Neither nebivolol nor atenolol adversely affected lipid or carbohydrate metabolism in normometabolic hypertensive patients. Both treatments demonstrated adequate and similar antihypertensive effects and were well tolerated.     

Sex hormone-binding globulin levels in middle-aged premenopausal women. Associations with visceral obesity and metabolic profile.

OBJECTIVE: Low sex hormone-binding globulin (SHBG) levels in women are associated not only with hyperinsulinemia, increased risk for cardiovascular disease, and type 2 diabetes but also with excess body fatness and abdominal obesity. We tested the hypothesis that an elevated total or intra-abdominal adipose tissue accumulation mediates the relationship between low SHBG levels and an altered metabolic profile. RESEARCH DESIGN AND METHODS: We measured body composition (dual-energy X-ray absorptiometry [DEXA]) and body fat distribution (computed tomography) in 52 middle-aged (46.7 +/- 0.4, mean +/- SEM) premenopausal women. Insulin and glucose responses to a 75-g oral glucose load and plasma lipid-lipoprotein levels were also measured. RESULTS: Low plasma SHBG concentrations were associated with increased total body fat mass (r = -0.41, P < 0.005) and subcutaneous abdominal (r = -0.39, P < 0.005) and intra-abdominal (r = -0.37, P < 0.008) adipose tissue area. Low SHBG was also associated with a greater insulin response to oral glucose (r = -0.40, P < 0.005), higher triglyceride levels (r = -0.29, P < 0.05), higher cholesterol/HDL cholesterol ratio (r = -0.51, P < 0.005), but lower HDL cholesterol concentrations (r = 0.65, P < 0.005). When matched for intra-abdominal fat or total fat mass, subjects with either low or high SHBG showed no difference in the insulin response to an oral glucose challenge. Statistical adjustment for differences in intra-abdominal adipose tissue accumulation or total body fat mass also eliminated the associations between SHBG levels and metabolic variables, with the exception of the association between SHBG and HDL cholesterol levels (r = 0.52, P < 0.005). CONCLUSIONS: Our results suggest that the previously reported relationship between low SHBG levels and increased metabolic disease risk in women is mediated, to a large extent, by concomitant variation in body fatness and intra-abdominal adipose tissue accumulation.     

Fibrates

Fibrates regulates not only plasma lipid metabolism but vascular biology by activating nuclear receptor peroxisome proliferating activated alpha (PPAR alpha). Major effects on plasma lipid levels are lowering plasma triglyceride level and elevating plasma HDL cholesterol level, whereas its effect on plasma cholesterol level is moderate compared to HMG-CoA reductase inhibitor. As a mechanism for its effects on plasma lipid levels and atherosclerosis, recent studies reported that fibrates activates various genes involved in metabolism of remnants and HDL such as lipoprotein lipase, apo AI, apo AII, and apo CIII genes through the interaction with PPAR alpha, lowering atherogenic lipoproteins and elevating anti-atherogenic lipoproteins. Furthermore, fibrates may influence the process of atherosclerosis by modifying inflammatory process in vascular wall. Recent clinical studies demonstrated that fibrates significantly reduce cardiovascular events in patients with either hypertriglyceridemia or low HDL cholesterol level.     

Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study.

OBJECTIVE: To identify risk factors for incident coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: A total of 175 Japanese-American men without CHD were followed for up to 10 years. Baseline variables were blood pressure, weight, BMI, fat areas by computed tomography, skinfold thicknesses, abdominal circumference, plasma insulin, C-peptide, cholesterol, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, and HDL3 cholesterol, triglycerides, apoproteins A1 and B, and diagnosis of diabetes and hypertension. CHD was diagnosed by electrocardiogram and clinical events. Logistic regression was used to estimate odds ratio. RESULTS: There were 50 incident cases of CHD. Using univariate logistic regression analysis, significant risk factors were intra-abdominal fat (P = 0.0090), fasting glucose (P = 0.0002), 2-h glucose (P = 0.0008), fasting HDL cholesterol (P = 0.0086), fasting HDL2 cholesterol (P = 0.030), fasting HDL3 cholesterol (P = 0.018), fasting triglycerides (P = 0.013), systolic (P = 0.0007) and diastolic blood pressure (P = 0.0002), and presence of diabetes (P = 0.0023). Multiple logistic regression models adjusted for BMI and age showed that intra-abdominal fat accounted for the effects of HDL cholesterol or triglycerides. In a multiple logistic regression model that included intra-abdominal fat, all systolic blood pressure and fasting glucose were significant. Substituting diastolic blood pressure for systolic blood pressure and 2-h glucose or diabetes status for fasting glucose produced similar results. CONCLUSIONS: Visceral adiposity, blood pressure, and plasma glucose are important independent risk factors for incident CHD in this population of diabetic and nondiabetic Japanese-American men.     

Cholesterol ester metabolism in plasma during estrogen and antiandrogen treatment in men with carcinoma of the prostate

The male predominance in atherosclerotic disease has been ascribed to differences in lipid and lipoprotein metabolism between men and women. The influences of estrogen and antiandrogen treatment on the cholesterol ester metabolism and lipoproteins in plasma in men were therefore studied. Forty-six men with carcinoma of the prostate were studied before and after 2 and 8 weeks' treatment with either polyestradiol phosphate and ethinyl estradiol or orchidectomy or the testosterone receptor-blocking gestagenic drug cyproterone acetate. The estrogen treatment increased the HDL-TC and the level of TGs in HDL and LDL and reduced the TC and LDL-TC simultaneously with elevations of the fractional and molar cholesterol esterification rates. Orchidectomy caused only slight elevations of the TC level and the molar cholesterol esterification rate. Cyproterone acetate reduced the TC, LDL-TC, and HDL-TC concentrations simultaneously with an increase in the fractional cholesterol esterification rate. The alterations of TC and LDL-TC were positively correlated to the changes in the molar cholesterol esterification rate and negatively correlated to the alteration in the fractional cholesterol esterification rate. High doses of estrogen appeared to raise the TG level and the production of CE in plasma. Both estrogen and cyproterone acetate therapy lowered the LDL-TC level simultaneously with a raised fractional elimination of unesterified cholesterol as CEs from plasma. Although the testosterone production was practically eliminated by all three forms of treatment, there was no change of plasma lipoproteins common to all three groups. Therefore the lower estrogen level rather than the higher testosterone level might cause the lower HDL levels in men compared to women.     

Amino-acid-based continuous ambulatory peritoneal dialysis (CAPD) fluid over twelve weeks: effects on carbohydrate and lipid metabolism

Aspects of lipid and carbohydrate metabolism were studied in 8 patients established on continuous ambulatory peritoneal dialysis (CAPD) with plasma albumin less than 35 g/L, before, during, and after substitution of 1 of the daily glucose exchanges by a commercial 1% amino acid dialysis fluid for 12 weeks. The amount of glucose absorbed from the dialysis fluid was consequently reduced by about 25%, hence total energy intake decreased by about 100 Kcal/day, but peritoneal glucose transfer kinetics were unaffected. Glucose was lost into amino acid dialysate as expected (2 g/day). Excluding 1 patient with a large rise in calorie intake, total and LDL cholesterol fell at 8 and 12 weeks (LDL cholesterol week 0, 5.26 +/- 1.13; week 8, 4.32 +/- 0.74; week 12, 4.30 +/- 1.22; mean +/- SD, p less than 0.01 for both), but returned to baseline 2 weeks after the restoration of glucose fluid (LDL 4.91 +/- 1.22, p less than 0.05 vs. week 12). Apolipoprotein B concentration also fell at 12 weeks (p less than 0.01). No changes were seen in body weight, body fat, arm muscle circumference, fasting plasma glucose, insulin, growth hormone, triglyceride, nonesterified fatty acids, or HDL cholesterol. The response of these biochemical indices to single 8-h glucose and amino acid morning exchanges at 0 and 12 weeks were studied. After 12 week's use of amino acid dialysis fluid, plasma cholesterol and apolipoprotein B were significantly lower throughout the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)     

A COMPARISON OF THE METABOLIC EFFECTS OF FLOSEQUINAN AND PROPRANOLOL IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES MELLITUS

The effects of steady-state flosequinan, a new peripheral vasodilator, and propranolol on glucose tolerance and plasma lipids in 22 non-insulin-dependent diabetics were investigated in a randomized double-blind placebo-controlled, three-way crossover trial. Flosequinan produced no impairment of glucose tolerance compared with placebo. Propranolol produced significant increases in fasting plasma glucose (P less than 0.01) and increases in the area under the glucose tolerance curve (P less than 0.05) compared to placebo. No significant effects on cholesterol levels were seen on either treatment but triglyceride levels were significantly elevated on propranolol compared with placebo (P less than 0.01). These data suggest that flosequinan, used in therapeutic dosage, has no adverse metabolic effects on the non-insulin-dependent diabetic and this may be an advantage for a drug used in the treatment of hypertension or congestive heart failure.     

老年脑梗死患者高胰岛素血症的临床研究

目的：探讨高胰岛素血症（ＨＩＳ），胰岛素抵抗（ＩＲ）与老年脑梗死发病的关系。方法：３４例６０岁以上老年脑梗死患者和２０例正常人的葡萄糖耐量试验（ＯＧＴＴ）后血糖，胰岛素及其曲线下面积（ＡＵＣ）和胰岛素／血糖，血脂变化。结果；脑梗死组糖负荷后血糖，胰岛素，胰岛素／血糖，ＡＵＣ以及总胆固醇明显高于对照组，胰岛素敏感性指数及ＨＤＬ－Ｃ明显低于对照组，糖负荷后１小时，２小时胰岛素及其ＡＵＣ与舒张压呈正相关     

Ursodeoxycholic acid treatment in humans: effects on plasma and biliary lipid metabolism with special reference to very low density lipoprotein triglyceride and bile acid kinetics

Ursodeoxycholic acid reduces biliary saturation with cholesterol and may induce dissolution of cholesterol gallstones in man. In order to characterize the effects of this potentially useful bile acid on plasma lipid metabolism, we determined lipoprotein levels and very low density lipoprotein (VLDL) triglyceride kinetics in six hypertriglyceridaemic and three normolipidaemic subjects before and after 4-6 weeks of ursodeoxycholic acid treatment at a daily dose of 15 mg kg-1 body weight. The plasma levels of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were not significantly affected by therapy. Nor were the plasma level and apparent formation of VLDL triglycerides changed. In five subjects, the effects of a low dose (7.5 mg kg-1 body weight day-1 for 4-6 weeks) of ursodeoxycholic acid on biliary lipid composition and kinetics of cholic acid and chenodeoxycholic acid were determined. The relative concentration of cholesterol in bile was reduced to the same level as during treatment with a high dose of ursodeoxycholic acid. The synthesis rates of bile acids were not suppressed with ursodeoxycholic acid. It is concluded that, unlike chenodeoxycholic acid, ursodeoxycholic acid does not suppress endogenous bile acid production. The efficiency at lower doses, and the lack of effects on plasma lipid metabolism, may make ursodeoxycholic acid a more attractive alternative for clinical attempts of gallstone dissolution.