Plasma lipids and lipoprotein changes after biliopancreatic diversion for morbid obesity.

BACKGROUND: The reduction in plasma cholesterol with increase in large and lower dense LDL (pattern A) obtained by statins is usually associated with a prompt reduction in cardiovascular risk, but after bariatric surgery for morbid obesity a delay of some years is observed. No data regarding LDL pattern are available in obese subjects after biliopancreatic surgery. OBJECTIVE: To evaluate the modifications in LDL composition and LDL density after biliopancreatic surgery. SUBJECTS: 29 patients (17 type 2 diabetics (type 2) and 12 non-diabetics (ND)) with BMI <35, who failed previous attempts to decrease weight by diet, were studied before and 6 months after biliopancreatic diversion for morbid obesity. MEASUREMENTS: In all subjects, besides fasting circulating lipids, glucose and insulin, LDL and VLDL composition were determined and LDL density was evaluated as well. RESULTS: After surgery we observed a significant reduction of all circulating lipids, including apolipoprotein (Apo) B. The decrease was more marked for total cholesterol (-41%) than for triglycerides (-28%), without a significant difference between type 2 and ND. After surgery, LDL presented a marked decrease in the percentage of cholesterol (from 36 to 32%) with a marked increase in the percentage of triglycerides (from 13 to 18%), without appreciable modification of ApoB. After surgery, 1 patient changed from pattern B to A, while 2 patients previously pattern A became pattern B. Also a decrease in HDL and ApoAI was evident in all the subjects with an increase in the VLDL-1. CONCLUSIONS: Our data indicate that after biliopancreatic diversion, the plasma lipid profile improves along with improvement of plasma glucose and insulin sensitivity, but the LDLs become richer in triglycerides. It is possible that the greater atherogenicity of these LDLs is compensated by an improvement in the general metabolic condition.

Low-dose dexamethasone in the rat: a model to study insulin resistance.

The main aim of this study was to set up a new animal model to study insulin resistance. Wistar rats (6 or 7 per group) received the following for 4 wk in experiment 1: 1) vehicle, 2) 2 microg/day subcutaneous dexamethasone, 3) metformin (400 mg x kg(-1) x day(-1) os), and 4) dexamethasone plus metformin. In experiment 2 the rats received the following: 1) vehicle, 2) dexamethasone, 3) dexamethasone plus arginine (2%; as substrate of the nitric oxide synthase for nitric oxide production) in tap water, and 4) dexamethasone plus isosorbide dinitrate (70 mg/kg; as direct nitric oxide donor) in tap water. Insulin sensitivity was significantly reduced by dexamethasone already at week 1, before the increase in blood pressure (day 15) and without significant changes in body weight compared with vehicle. Dexamethasone-treated rats had significantly higher triglycerides, hematocrit, and insulin, whereas serum total nitrates/ nitrites were lower compared with vehicle. The concomitant treatment with metformin minimized all the described effects of dexamethasone. In experiment 2, only isosorbide dinitrate was able to prevent the observed dexamethasone-induced metabolic, hemodynamic, and insulin sensitivity changes. Chronic low-dose subcutaneous dexamethasone (2 microg/day) is a useful model to study the relationships between insulin resistance and blood pressure in the rat, and dexamethasone might decrease insulin sensitivity and increase blood pressure through an endothelium-mediated mechanism.

Additive effects of Simvastatin beyond its effects on LDL cholesterol in hypertensive type 2 diabetic patients.

BACKGROUND: Experimental evidence indicates that statins might have direct vascular effects independently from low-density lipoprotein (LDL) cholesterol reduction and we reported that the reduction in urinary albumin excretion rate during Simvastatin treatment in type 2 diabetic patients was not correlated with LDL-cholesterol decrease. However in humans there are no data regarding possible additional effects of Simvastatin on blood pressure and urinary albumin excretion beyond its capacity to lower serum cholesterol. PATIENTS AND METHODS: Twenty-six microalbuminuric hypertensive type 2 diabetic patients (diastolic blood pressure - after four months wash-out from the previous antihypertensive therapy - consistently > 90 and < 100 mmHg; plasma LDL-cholesterol > 3.9 and < 6.5 mmol L-1) were enrolled in the study. In random order, these patients received Simvastatin (20 mg day-1) or Cholestyramine (6 g three times a day) for a period of 10 months and after three months of wash-out (cross-over) the sequence was reversed for an additional 10 months. Blood pressure, lipid parameters, glycated haemoglobin and urinary albumin excretion were measured during the study. Additionally, in eight patients, urinary glycosaminoglycan excretion (GAG) was also measured during the study. RESULTS: Simvastatin and Cholestyramine were equally effective in reducing total and LDL cholesterol. Only during Simvastatin treatment a significant reduction in diastolic blood pressure and both 24 h urinary albumin and GAG excretion rates were observed, while no significant changes were seen with Cholestyramine treatment. CONCLUSIONS: Our results clearly show for the first time that the reduction of blood pressure, together with 24 h urinary albumin excretion rate - two established cardiovascular risk factors, obtained during Simvastatin therapy in hypertensive type 2 diabetic patients - is in large part independent from the reduction of LDL Cholesterol.

Lipoprotein metabolism during normal pregnancy.

OBJECTIVE: We sought to investigate the changes in circulating serum lipids and lipoproteins, including lipoprotein (a), and low-density lipoprotein size in women during normal pregnancy. STUDY DESIGN: Twenty-two women (mean age, 31 +/- 5 years; 13 primiparous subjects) were studied during uncomplicated pregnancy with normal outcome. Twenty-four nulliparous women of similar age (31 +/- 4 years) were studied as control subjects. RESULTS: Serum triglycerides and total and low-density lipoprotein cholesterol increased significantly during pregnancy in all women. Women with changes in low-density lipoprotein during the second and third trimesters showed a more marked increase in serum triglycerides, and this effect was slightly more evident in the multiparous subjects. No other differences were evident between primiparous and multiparous women apart from high-density lipoprotein cholesterol levels, which were slightly decreased in the latter subjects. CONCLUSIONS: Our results show that during normal pregnancy, the increase in plasma triglycerides may lead to the appearance of the atherogenic dense low-density lipoproteins in a subgroup of women. We suggest that the observed changes in low-density lipoprotein patterns during pregnancy might be used to identify those women who later in life will have these atherogenic small and dense low-density lipoproteins.

Serum apolipoprotein(a) concentrations and Apo(a) phenotypes in patients with liver cirrhosis.

OBJECTIVE: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline. METHODS: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function. RESULTS: Apo(a) serum levels were significantly lower (p < 0.01) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations (p = 0.0313). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration. CONCLUSION: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apolipoprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.

Reduction of albumin excretion rate in normotensive microalbuminuric type 2 diabetic patients during long-term simvastatin treatment.

OBJECTIVE: To study the long-term effects of simvastatin on urinary albumin excretion rate (AER) in normotensive microalbuminuric type 2 diabetic patients with hypercholesterolemia. RESEARCH DESIGN AND METHODS: A total of 19 normotensive microalbuminuric hypercholesterolemic type 2 diabetic patients entered a double-blind crossover study for 2 years, receiving either simvastatin (20 mg/day) or placebo (each treatment for 1 year). RESULTS: Simvastatin significantly decreased plasma cholesterol (total and LDL) after 52 weeks of treatment. A concomitant significant decrease of AER (25% from basal) with no significant changes in creatinine clearance was observed during the same period. CONCLUSIONS: Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients.

Plasma lipoprotein composition, apolipoprotein(a) concentration and isoforms in beta-thalassemia.

Patients with homozygous beta-thalassemia show an abnormal lipoprotein profile. In asymptomatic heterozygotes the lipid pattern is less markedly affected but interestingly related to a diminished cardiovascular risk. The extent and significance of these findings are still a matter of debate and no data are available on lipoprotein(a) plasma levels. Seventy patients with homozygous beta-thalassemia (HT-P), 70 beta-thalassemia trait carriers (TT-C) and 70 sex and age-matched controls were investigated and their plasma lipoprotein profile and apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12 TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous beta-thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration than TT-C (-7, -11, -8, -8, -13 and +11%, respectively) or controls (-39, -50, -46, -32, -30 and + 35%, respectively). All lipoprotein subclasses were triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein-depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B plasma levels but only minor lipoprotein abnormalities with respect to the controls. BMT-P lipoprotein composition was intermediate between HT-P and normal subjects. Apo(a) plasma levels did not differ among the groups. A higher prevalence of 'small' apo(a) isoforms was present in HT-P. Within the same 'isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT-C or controls. Since liver cirrhosis is almost always present in HT-P, it is conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to diminished apolipoprotein glycation may be involved. In TT-C a partially improved cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and apo B), thus justifying the claim for a low prevalence of ischemic heart disease, but no Lp(a) plasma level modification could be detected.

Cyclical variation of plasma lipids, apolipoproteins, and lipoprotein(a) during menstrual cycle of normal women.

We report herein the effects of cyclical variations of endogenous sex steroids during the menstrual cycle on plasma lipids and apolipoproteins (apo) in normal women. We examined 16 normal women (age range 25-36 yr) with normal menstrual cycles of 28-31 days. The study covered the period from the 1st day of a menstrual phase (basal) until the 1st day of the following menstrual phase. During the study all women maintained a normolipidic diet (30% fat). Plasma total cholesterol and low-density-lipoprotein cholesterol were significantly higher than basal in the preovulatory phase until progesterone started to increase in the postovulatory phase [day +8 from luteinizing hormone (LH) surge]. High-density-lipoprotein cholesterol was significantly higher than basal from day -1 to the day after LH surge, whereas plasma apoAI levels were significantly higher from day -8 to day +8 (from LH surge). Plasma apo(a) increased significantly during the luteal phase in four women characterized by a single S4 band and lower basal plasma levels of apo(a). Our results indicate that endogenous female sex steroids have significant effects on the circulating levels of plasma lipids and apolipoproteins, including apo(a). More work needs to be done to elucidate the significance of the observed apo(a) changes, and the different phases of the menstrual cycle must be taken into account when evaluating the lipidic risk profile in premenopausal women.

Effects of water temperature on surfactant-induced skin irritation.

Surfactant-induced irritant reactions may be elicited by several endogenous and exogenous factors. Among these, surfactant concentration, and duration and frequency of exposure play important rôles. The study focuses on the influence of water temperature in determining damage of the skin barrier. 10 subjects of both sexes entered the study. 4 areas (4 x 4 cm2) were randomly selected on the volar forearm and were treated with a daily open application of 5% sodium lauryl sulphate for 4 days. The solutions were at 3 temperatures: 4 degrees, 20 degrees and 40 degrees C. One site served as untreated control. On the 5th day, skin irritation was evaluated using transepidermal water loss (TEWL) measurements, erythema (a* value), skin reflectance (L* value), hydration (capacitance) and desquamation (stripping). The results show a significant effect of the solution's temperature in determining skin irritation (P < 0.001). Skin damage was higher in sites treated with warmer temperatures and a highly significant correlation (P < 0.001) between irritation and temperature was found. In conclusion, the study shows that water temperature during washing has an important effect on the onset of irritant contact dermatitis.

Raised serum apolipoprotein (a) in active diabetic retinopathy.

Progressive capillary occlusion often leads to severe retinopathy within 15-20 years of the onset of Type 1 (insulin-dependent) diabetes mellitus. Lipoprotein(a), a complex formed by apolipoprotein(a), apo B-100 and lipids, is considered an independent, genetically determined, predictor of cardiovascular disease. It may have antifibrinolytic properties in view of its similarity to plasminogen. To test the hypothesis that circulating lipoprotein(a) is associated with the process that leads to clinically active diabetic retinopathy, we measured the circulating levels of apolipoprotein(a) (which are strictly correlated with those of lipoprotein(a)) in two groups of patients with Type 1 diabetes of at least 15 years duration: 25 with active retinopathy and 27 without clinically detectable retinal lesions. Thirty-eight healthy subjects of the same age and sex served as controls. Serum apolipoprotein(a) was higher in the patients with active retinopathy (36(2-193) U/dl, geometric mean and range) than in those without clinically detectable retinal lesion (17(1-160)) and the control subjects (14(0-115)), p < 0.01 in both cases. The distribution of apolipoprotein(a) levels was skewed to the left, as expected, in the patients without clinically evident retinal lesions and the control groups, but there was a bimodal trend of distribution among those with active retinopathy. The levels of glycated haemoglobin were similar in the two groups of diabetic patients, and no significant differences were found for total and HDL cholesterol, triglycerides or apolipoproteins A1 and B between them and the control subjects. These preliminary results suggest that serum apolipoprotein(a) is elevated in patients with active retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)