Maternal country of origin and infant birthplace: implications for birth-weight

Insulin-dependent diabetes mellitus (IDDM) is characterized by altered composition of atherogenic lipoproteins, especially a depletion in choline-containing phospholipids (PL) of apolipoprotein (apo) B lipoproteins (LpB). To determine the effects of continuous intraperitoneal (IP) insulin infusion (CIPII) on this qualitative lipoprotein abnormality, we compared lipoprotein profiles of 14 IDDM patients treated by continuous subcutaneous insulin infusion (CSII) and at 2 and 4 months after treatment with CIPII using an implantable pump. IDDM patients were in fair metabolic control and were compared with 14 healthy control subjects matched for sex, age, body mass index, and plasma lipids. The following parameters were studies: hemoglobin A1c (HbA1c), monthly blood glucose, daily insulin dose (units per kilogram per day), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, apo A-I, and apo B. Choline-containing PL were assessed in plasma and in apo B- and no-apo B-containing lipoprotein particles (LpB and Lp no B). As compared with the control group, plasma PL and LpB-PL were significantly lower in IDDM patients treated by CSII (2.95 +/- 0.26 v 3.30 +/- 0.45 mmol/L,P<.05, and 1.09 +/- 0.45 v 1.68 +/- 0.33 mmol/L,P<.01, respectively). No significant differences were observed for Lp no B lipid determinations between both groups. After initiation of CIPII, IDDM patients did not experience any significant changes in mean values for body mass index, HbA1c, and monthly blood glucose throughout the study. Daily insulin doses were identical to those observed before IP therapy. Lipid parameters remained unchanged in IDDM patients (TC, TG, HDL and LDL cholesterol, apo A-I, and apo B). A moderate but progressive elevation of plasma PL was noted, and after 4 months of CIPII, PL and LpB-PL levels were no longer significantly different between IDDM patients and controls. The increase in plasma and LpB choline-containing PL observed after 2 and 4 months of CIPII is not linked to changes in blood glucose control, body weight or daily insulin requirements. These changes may be related to the route of insulin administration, which may be accompanied by a reduction of lipoprotein lipase (LPL) activity and consequently a reduction of phospholipase activity. These results suggest that IP insulin delivery may be a more physiological route that increases the choline-containing PL content of LpB particles.     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intensive glycemic control on fibrinogen, lipids, and lipoproteins: Veterans Affairs Cooperative Study in Type II Diabetes Mellitus

BACKGROUND: The Veterans Affairs Cooperative Study in Type II Diabetes Mellitus prospectively studied insulin-treated patients with type 2 (non-insulin-dependent) diabetes mellitus, achieving 2.1% glycosylated hemoglobin separation between intensive- and standard-treatment arms (P<.001) for 2 years. OBJECTIVE: To assess the effect of intensive therapy on serum fibrinogen and lipid levels, compared with standard treatment. METHODS: One hundred fifty-three male subjects with type 2 diabetes mellitus and who required insulin treatment were recruited from 5 Veterans Affairs medical centers. The subjects were divided into intensive- and standard-treatment arms for a randomized prospective study. Dyslipidemia was managed identically in both arms (diet, drugs). Fibrinogen levels and lipid fractions were measured in the full cohort. Lipid fractions are separately reported in patients not treated with hypolipidemic agents. RESULTS: There were no baseline differences between arms. Fibrinogen levels rose in the intensive-treatment arm at 1 year (from 3.34+/-0.12 to 3.75+/-0.15 g/L; P<.001) but returned to baseline at 2 years (3.47+/-0.12 g/L). There was no change in the standard-treatment arm. Triglyceride levels decreased in the intensive-treatment arm from 2.25+/-0.27 to 1.54+/-0.14 mmol/L (199+/-24 to 136+/-12 mg/ dL) at 1 year (P = .004) and to 1.74+/-0.18 mmol/L (154+/-16 mg/dL) at 2 years (P = .03); there was no change in the standard-treatment arm. Cholesterol levels decreased in the intensive-treatment arm at 1 year from 5.4+/-0.21 to 4.99+/-0.13 mmol/L (207+/-8 to 193+/-5 mg/dL) (P = .02); there was no change in the standard-treatment arm. Levels of low- and high-density lipoprotein cholesterol decreased in the standard-treatment arm only by 2 years, from 3.44+/-0.13 to 3.16+/-0.10 mmol/L (133+/-5 to 122+/-4 mg/ dL) (P =.02) and from 1.10+/-0.03 to 1.00+/-0.03 mmol/L (42+/-1 to 38+/-1 mg/dL) (P<.001) for low-density and high-density lipoprotein cholesterol, respectively. Levels of apolipoprotein B decreased in both treatment arms (P<.001), and apolipoprotein A1 levels decreased in the standard-treatment arm (P<.01). Lipoprotein (a) levels did not change in either treatment arm. Lipid results were essentially identical whether examined in the full cohort or excluding those patients receiving hypolipidemic agents. CONCLUSIONS: Intensive insulin therapy led to a potentially beneficial reduction in serum triglyceride levels and preservation of high-density lipoprotein cholesterol and apolipoprotein A1 levels. However, it caused transient elevation in plasma fibrinogen levels, a possible thrombogenic effect.     

Protective role of the free glucocorticoid pool in development of autoimmune hemolytic anemia

OBJECTIVE: Patients with type II diabetes mellitus have an increased risk of coronary he disease. We investigated the efficacy and safety of pravastatin in the treatment of patients with diabetic nephropathy and hypercholesterolemia. METHOD: In this 6-months study, 12 patients (4 men, 8 women, mean age 60.5 +/- 10.8 years), with diabetic nephropathy and hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol levels -LDL-C- > 130 mg/dl) received pravastatin 10 mg/day. The dose could be doubled after 4 weeks. Seven patients have chronic renal failure. RESULTS: Significant reductions in LDL-C (-19.1%, p < 0.05), total cholesterol (-16%, p < 0.01), very-low-density lipoprotein cholesterol (-29.2%, p < 0.05), apolipoprotein B (-21.5%, p < 0.05), and triglycerides (-26.0%, p < 0.01) were noted. No changes were found either in high-density-cholesterol or its fractions (HDL2 and HDL3) or in apolipoprotein A plasmatic levels. Pravastatin was well tolerated and no one side effect was detected. No clinically significant changes on the control of diabetes, renal function, as assessed by plasmatic creatinin and creatinin clearance, and proteinuria were seen during the follow-up time. CONCLUSIONS: The results of the study demonstrate that pravastatin is well tolerated and effective in lowering total cholesterol and LDL-C in patients with diabetic nephropathy and hypercholesterolemia.     

Psychological and socio-medical aspects of HIV/AIDS: a reflection on publications in AIDS care (1989-1995)

Cardiovascular disease is the leading cause of death in non-insulin dependent diabetes mellitus and first degree relatives of such patients are at increased risk of developing diabetes and cardiovascular disease. The aim of the present study was to determine whether lipid abnormalities occur in normoglycaemic relatives of non-insulin dependent diabetic patients. Cholesterol, triglycerides, apolipoprotein A-I and apolipoprotein B concentrations were measured in serum; the lipoprotein fractions very low density, intermediate density, low density and high density lipoprotein were prepared by sequential flotation ultracentrifugation and their composition investigated. The groups were matched for age, sex and blood glucose concentrations although the relatives (n = 126) were more insulin resistant as determined using the homeostasis model assessment method [1.9 (0.8-9.0) vs 1.6 (0.4-4.9) mmol/mU per l (mean [95% confidence intervals]); p < 0.001] and had greater body mass indices [26.6 (4.1) vs 24.8 (3.9) (mean [S.D.]); p = 0.001] than control subjects (n = 126). Relatives had higher serum apolipoprotein B concentrations than control subjects [0.9 (0.3) vs 0.8 (0.3) g/l, p = 0.02) and lower serum apolipoprotein A-I concentrations (1.4 (0.3) vs 1.5 (0.3), p = 0.02). In multivariate linear regression analysis of all subjects log insulin resistance (p = 0.0001), age (p = 0.002) and waist:hip ratio (p = 0.01) were independent predicators of apolipoprotein B concentrations while waist:hip ratio (p < 0.001) and smoking status (p = 0.002) were independent predictors of apolipoprotein A-I concentrations. Lipoprotein composition (measured in a subgroup of 76 control subjects and 88 relatives), serum cholesterol and serum triglyceride concentrations did not differ between the groups. We conclude that atherogenic apolipoprotein abnormalities occur in normoglycaemic relatives of non-insulin dependent diabetic patients.     

Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.     

Intra-individual variations in triglyceride and total cholesterol levels in serum in mixed hyperlipidemia

Swings in serum concentrations of total cholesterol and triglycerides were assessed retrospectively in 12 of 60 patients with mixed hyperlipidaemia (ten men, two women; mean age 44 [38-55] years). A second disease as a cause of the hyperlipidaemia had been excluded. Despite clinical stability and unchanged drug therapy the fasting values of triglycerides, measured enzymatically, in a minimum of four different samples (over several months) differed by more than 5 mmol/l, a mean of 16.6 (5-41.9) mmol/l. The lowest values were 2.7 (1.3-7.5) mmol/l, the highest 17.9 (6.4-44.6) mmol/l. Total cholesterol concentrations varied around 5.5 (1.6-31.7) mmol/l, minimal values 5.7 (4.2-8.9) mmol/l, maximal ones 12.0 (6.9-37.4) mmol/l. Six of the twelve patients consumed more than 60 g alcohol daily. The cause of the marked variations between individual samples is uncertain. Marked swings in triglyceride and total cholesterol concentrations are likely in mixed hyperlipidaemia. It is, therefore, essential to measure these concentrations repeatedly to assess correctly the diagnosis and treatment.     

Lack of association of the apolipoprotein A-I-C-III-A-IV gene XmnI and SstI polymorphisms and of the lipoprotein lipase gene mutations in familial combined hyperlipoproteinemia in French Canadian subjects

Familial combined hyperlipoproteinemia (FCH) is a common familial lipoprotein disorder characterized by elevated plasma cholesterol and triglyceride levels with segregation in first-degree relatives. Most affected subjects with FCH have elevated plasma levels of apolipoprotein (apo) B. The disorder results from oversecretion of hepatic apoB-containing lipoprotein particles. The genetic defect(s) are unknown. Previous work has suggested that genetic polymorphisms of the apoA-I gene and functional abnormalities of the lipoprotein lipase (LPL) gene are associated with FCH. We investigated the XmnI and SstI restriction fragment length polymorphisms (RFLP) of the apoA-I gene in FCH subjects of French Canadian descent. We also investigated three common functional mutations of the lipoprotein lipase (LPL) gene (LPLGly188Glu, LPLPro207Leu, and LPLAsp250Asn) in French Canadians that account for approximately 97% of cases of complete LPL deficiency in the province of Québec, Canada. We identified and characterized 54 FCH probands in lipid clinics and examined at least one first-degree relative. There were 37 men and 17 women (mean age 48 +/- 9 and 58 +/- 8 years, respectively). None of the probands had diabetes mellitus; mean plasma glucose was 5.5 mmol/L. High blood pressure was diagnosed in 32% of men and 29% of women. The body mass index (weight (kg)/height(m2)) was elevated in probands (27 +/- 4 for men and 26 +/- 4 for women). Mean plasma levels of cholesterol (C) was 7.6 +/- 1.5 mmol/L, triglycerides 3.5 +/- 1.6 mmol/L, LDL-C 4.9 +/- 1.2 mmol/L, HDL-C 1.0 +/- 0.3 mmol/L, and apoB 1.83 +/- 0.67 g/L in the probands. Allele frequency of the rare alleles of the XmnI and SstI RFLP was not significantly different from a healthy reference group. In several families studied, the XmnI and SstI RFLP did not unequivocally segregate with the FCH phenotype. There was no significant effect of the presence or absence of the XmnI or SstI RFLP's on plasma lipids, lipoprotein cholesterol or apoB levels. Only one FCH proband was found to have a mutation of the LPL gene (Gly188Glu), and this did not segregate with the FCH phenotype in the family. We conclude that in our highly selected group of FCH subjects of French Canadian descent, the XmnI and SstI RFLPs of the apoA-I gene and common functional mutations of the LPL gene resulting in complete LPL deficiency are not associated with FCH.     

The treatment of chronic ischemic heart disease: the potentials for hypolipidemic correction using current drugs

The data obtained by the authors suggest that lipanor may correct those lipid metabolic disturbances that are most pronounced in each individual case. Moreover, the above drug is capable of lowering substantially the level of total blood cholesterol and atherogenic fractions of lipoproteins as early as at day 14 after its intake. Being associated with minimum adverse effects, and intended to be taken on a once-daily schedule, the drug will, we believe, come in wide use.     

Cloning and functional expression of a human liver organic cation transporter

OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.     

In Process Citation

Diabetes mellitus type 2 (DM type 2) is a common disease that is associated with high mortality and morbidity due to macrovascular and microvascular complications. CHD mortality and morbidity is 2-3 times higher in diabetic than in non-diabetic patients. There are many potentially atherogenic factors in diabetes these may underlie this problems. Except major risk factors (high serum cholesterol concentration, hypertension, cigarette smoking), insulin resistance is common in DM type 2 patients. The dyslipidemic component of insulin resistance is "atherogenic lipoprotein phenotype", its components include small LDL particles (pattern B) with higher atherogenic risk. Several recent studies have demonstrated the preponderance of small, dense LDL in patients with DM type 2 and IR. The question of whether small, dense LDL can be explained by triglyceride levels alone or whether it is directly related to DM type 2 and insulin resistance is still the subject of debate. If serum triglycerides exceed 1.3 mmol/l, small, dense LDL increases. The practical implication is that serum triglyceride levels should be maintained as low as possible to prevent the deleterious effects of triglycerides on LDL subclass distribution and size. There are several potential mechanisms to explain the increased atherogenicity of dense LDL (small dense LDL is more susceptible to lipid peroxidation and oxidation leading to its increased uptake by macrophages and subsequent removal by scavenger pathway, also has a lower binding affinity to LDL receptors). Theoretical grounds postulate that the treating of diabetic dyslipoproteinemias would reduce atherosclerosis disease. However, to date, there have been no intervention studies specifically designed to test this postulate in the diabetic population. Such studies the Diabetes Atherosclerosis Intervention Study (DAIS), Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), Collaborative Atorvastatin in Diabetes Study and Lipid in Diabetes Study are currently in progress. (Tab. 4, Fig. 2, Ref. 81.)     

A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease

Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9,214 men and women from a general population sample and 948 patients with ischemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/liter), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/liter and delta = 0.11 mmol/liter, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischemic heart disease in both genders. On univariate analysis, odds ratios for ischemic heart disease in probands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0.62-1.31), and on multivariate analysis were 1.98 in women (95% CI: 1.11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides not predisposed to ischemic heart disease.     

Plasma endothelin-1 levels in non-insulin dependent diabetes mellitus patients with macrovascular disease

BACKGROUND: Endothelin-1 (ET-1) with its well-known vasoconstrictive and mitogenic action and through its interaction with insulin, blood glucose, and lipids might play an important role in the accelerated atherogenic process in diabetes mellitus. OBJECTIVE: To determine whether ET-1 levels are indicative of macrovascular disease in diabetes mellitus. METHODS: In the present cross-sectional study, plasma ET-1 concentrations were measured in members of three groups. The first group consisted of 20 patients (15 men and five women; aged 56.3 +/- 12.5 years) with non-insulin-dependent diabetes mellitus and coronary artery disease, the second group of 20 patients (16 men and four women, aged 56.9 +/- 11.2 years) with coronary artery disease only, and the third group of 10 healthy subjects who served as controls. ET-1 levels were determined by a radioimmunoassay. RESULTS: The mean plasma ET-1 levels for the three groups were 3.59 +/- 1.88, 4.31 +/- 1.32, and 4.42 +/- 1.01 pmol/l respectively, and there was no statistically significant difference among the groups (P = 0.23). There was also no correlation between the plasma ET-1 concentration and age, sex, body mass index, triglyceride, total cholesterol, high-, low- and very-low density lipoprotein levels, for all groups, and, for the first group, hemoglobin A1c (HbA1c), the duration of diabetes mellitus. CONCLUSION: The plasma ET-1 concentration is not elevated in non-insulin-dependent diabetes mellitus patients with macrovascular disease, which might reflect the fact that its action occurs in a paracrine or an autocrine rather than an endocrine fashion and suggests that ET-1 levels are not necessarily indicative of macrovascular disease in diabetes mellitus.     

Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes

The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.     

Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia

We have investigated the effects of two fibric acid derivatives, bezafibrate mono (400 mg daily) and gemfibrozil (600 mg b.d.), in 29 patients with type IIb hyperlipoproteinaemia. All patients received placebo and each drug for 8 weeks in randomised order in a double-blind, cross-over study designed to evaluate any different effects of the drugs on serum lipoproteins, cholesteryl ester transfer protein (CETP), cholesteryl ester transfer activity (CETA), plasma fibrinogen, plasminogen activator inhibitor-I (PAI-1) or paraoxonase. Serum cholesterol decreased (P < 0.05) with gemfibrozil, but the effect of bezafibrate on serum cholesterol did not achieve statistical significance (placebo 8.34 +/- 1.05 (mean +/- S.D.), gemfibrozil 7.70 +/- 1.23 and bezafibrate 7.8 +/- 1.37 mmol/l). Both drugs decreased the serum triglyceride concentration (both P < 0.001) (placebo 4.39 (3.13-5.75) (median (interquartile range)), bezafibrate 2.26 (1.89-3.89) and gemfibrozil 2.00 (1.30-3.30) mmol/l) and very low density lipoprotein (VLDL) cholesterol (both P < 0.001) (placebo 1.18 (0.74-2.30), bezafibrate 0.59 (0.34-0.85) and gemfibrozil 0.48 (0.34-0.68) mmol/l). Discontinuous gradient ultracentrifugation (DGU) revealed that Sf 60-400 (large VLDL) decreased by more than 50% and Sf 20-60 (small VLDL) by more than 30% with each of the drugs (both P < 0.001), neither of which affected the composition of these lipoproteins. Gemfibrozil decreased the concentration of Sf 12-20 lipoprotein (intermediate density lipoprotein; IDL) by 23% (P < 0.01), whereas the effect of bezafibrate on this lipoprotein did not achieve statistical significance. Neither drug altered the concentration of apolipoprotein B or of total Sf 0-12 lipoproteins (low density lipoprotein, (LDL)). Both, however, significantly increased the quantity of free cholesterol in Sf 0-12 lipoproteins (P < 0.05). Overall the concentration of triglycerides decreased significantly in all lipoproteins isolated by DGU (Sf 0-12, Sf 12-20, Sf 20-60, Sf 60-400) on gemfibrozil treatment, but only in Sf 20-60 and Sf 60-400 on bezafibrate (all P < 0.05). Both drugs also increased serum high density lipoprotein (HDL) cholesterol (placebo 1.15 +/- 0.29, bezafibrate 1.27 +/- 0.38 (P < 0.01) and gemfibrozil 1.26 +/- 0.49 (P < 0.05) mmol/l) and HDL3 cholesterol concentration (placebo 0.59 +/- 0.12, bezafibrate 0.72 +/- 0.23 (P < 0.001) and gemfibrozil 0.70 +/- 0.24 (P < 0.01) mmol/l). Serum apolipoprotein A1 (apo A1) was increased (P < 0.05) by bezafibrate compared to gemfibrozil (placebo 103 +/- 26, bezafibrate 111 +/- 28 and gemfibrozil 102 +/- 25 mg/dl) and CETA from HDL to VLDL and LDL was decreased (P < 0.05) by bezafibrate compared to placebo, but the apparent decrease with gemfibrozil did not achieve statistical significance (placebo 39.6 +/- 17.7, bezafibrate 32.3 +/- 14.7 and gemfibrozil 33.8 +/- 15.0 nmol/ml/h). Neither drug affected the circulating concentration of CETP. Plasma fibrinogen was increased (P < 0.05) by gemfibrozil (placebo 4.16 (3.38-4.71) and gemfibrozil 4.65 (4.05-5.77) g/l) and was significantly lower (P < 0.001) on bezafibrate (3.60 (3.18-4.54) g/l) than on gemfibrozil treatment. There was a significant (P < 0.05) increase in PAI-1 activity with bezafibrate and a similar trend with gemfibrozil (placebo 41.2 (25.6-64.5), bezafibrate 50.5 (35.1-73.9) and gemfibrozil 48.5 (31.5-5.4 U/l). Neither fibrate influenced plasma concentrations of PAI-1 nor were the activities of lecithin:cholesterol acyl transferase or paraoxonase affected. The major difference in the action of the two drugs on lipoprotein metabolism was the greater effect of gemfibrozil in decreasing the overall serum concentration of Sf 12-20 lipoproteins and the triglycerides in Sf 12-20 and 0-12 lipoproteins. Bezafibrate, however, increased serum apo A1 concentration and significantly decreased CETA. The two drugs also had different effects on the plasma fibrinogen levels, which increased with gemfibrozil and tended to decrea     

Venous surgery of the lower limb: value of nerve blocks

BACKGROUND: Reduction in intake of dairy products has long been recommended to reduce blood lipids. The value of monounsaturated fatty acids is increasingly recognized. METHODS: We evaluated the effects of a monounsaturate-rich butter and cheese (B) produced by modifying the bovine diet on blood lipid levels of patients with type IIa hyperlipidaemia. We compared their effects with those of normal butter and cheese (A) and polyunsaturate-rich spread and cheese (C). Using a double cross-over design, we studied 30 patients of mean age 56.4 years (23 men, one woman excluded) over 6-week periods. RESULTS: Approximately 35.5 g/day butter/cheese were consumed; no changes in serum total cholesterol, triglycerides, low-density lipoprotein, lipoprotein (a) or cholesterol: high-density lipoprotein (HDL) ratio were observed. HDL levels were higher in B(1.31 mmol/l) than in C (1.22 mmol/l; P < 0.05) and similar to those in A (1.28 mmol/l). HDL2 levels were higher in patients fed diet A(0.23 mmol/l) than they were in those fed diet C (0.19 mmol/l; P < 0.05) and similar to those in patients fed diet B (0.20 mmol/l). Serum HDL3 was significantly higher in patients fed diet B (1.11 mmol/l) than in those fed diet C (1.03 mmol/l; P < 0.05) but similar to that in patients fed diet A (1.06 mmol/l). CONCLUSIONS: Moderate intake of modified dairy products may be of value and deserves further evaluation.     

Perinatal mortality and its relationship to the reporting of low-birthweight infants

OBJECTIVE: To determine whether diabetes defined by isolated postchallenge hyperglycemia (IPH) (2-h postchallenge plasma glucose > or = 11.1 mmol/l with fasting plasma glucose [FPG] < 7.0 mmol/l) increases the risk of fatal cardiovascular disease (CVD) in older women and men. RESEARCH DESIGN AND METHODS: In a prospective study, we followed 769 men and 1,089 women, aged 50-89 years, who had no history of diabetes or myocardial infarction and demonstrated no fasting hyperglycemia (i.e., FPG < 7.0 mmol/l) when they underwent oral glucose tolerance testing at baseline in 1984-1987. RESULTS: At baseline, 70% of 125 women and 48% of 133 men with previously undiagnosed diabetes had IPH. Over the next 7 years, women with IPH had a significantly increased risk of fatal CVD and heart disease compared with nondiabetic women. This increased risk was not observed in men with IPH. This association was independent of age, hypertension, central obesity, cigarette smoking, HDL cholesterol, and triglycerides (multiply adjusted hazard ratio and 95% CI: 2.6 and 1.4-4.7 for CVD; 2.9 and 1.3-6.4 for heart disease). CONCLUSIONS: Diabetes defined by IPH alone is common in older adults and more than doubles the risk of fatal CVD and heart disease in older women. Because the prevalence of IPH increases with age, the use of fasting glucose alone for diabetes screening or diagnosis may fail to identify most older adults at high risk for CVD and should be reevaluated.     

Reproducibility of fasting serum cholesterol and triglycerides in ambulatory patients with mixed hyperlipidemia

Intraindividual variability of serum lipid concentrations in normal volunteers and in patients with hyperlipidemia is substantial. The aim of this study was to investigate prospectively the reproducibility of fasting serum triglyceride and total cholesterol concentrations in primary health care patients with combined hyperlipidemia, i.e. under conditions of daily medical practice. Secondary forms of hyperlipidemia were excluded. 19 general medical outpatients with primary combined hyperlipidemia were studied. Serum total cholesterol and triglyceride concentrations were measured after an overnight fast at 08.00 h 4 times at weekly intervals. To study the influence of alcohol intake on serum lipid concentrations, total cholesterol and triglycerides were measured without alcohol influence and 12 hours after consumption of a mean of 100 g alcohol in the evening. In 19 patients (10 males, 9 females, mean age 55 years, body mass index 27.9 +/- 4.4 kg/m2), mean +/- SD of serum triglycerides was 3.97 +/- 1.8 mmol/l and of total cholesterol 7.9 +/- 1.8 mmol/l. The combined intraindividual and interassay coefficient of variation was 18.7 +/- 8.2% for triglycerides and 5.1 +/- 2.5% for total cholesterol. Fasting serum triglycerides (3.5 +/- 1.1 vs. 3.7 +/- 1.4 mmol/l) and total cholesterol (7.6 +/- 1.4 vs. 7.8 +/- 1.0 mmol/l) did not significantly change 12 hours after acute alcohol consumption. Patients with primary combined hyperlipidemia in a primary health care setting show small intraindividual variations of overnight fasted serum triglyceride and total cholesterol concentrations. Moderate alcohol consumption 12 hours before blood sampling does not significantly affect triglyceride and cholesterol values.     

Therapy and prevention of coronary heart diseases through lowering of the serum cholesterol levels; third consensus 'Cholesterol'. Consensus Working Group, CBO

For the second time the consensus text for lipid lowering therapy is revised. In angiographic studies it was shown that a decrease in the total cholesterol as well as the low-density lipoprotein cholesterol level results in a reduction of the progression of vascular disease. Furthermore, intervention trials demonstrated that therapy with cholesterol synthesis inhibitors reduces not only both the cardiovascular and total mortality, but also other manifestations of coronary heart disease (CHD). Hypercholesterolaemia is treated with a low-fat diet and normalisation of the weight. For individuals, this might result in a reduction of the risk for myocardial infarction or death and for the population in a decrease of the mean serum cholesterol concentration and the incidence of CHD. The indication for drug therapy is founded on the expected effectiveness to reduce the incidence of (new manifestations of) CHD, which is related to the level of the absolute risk of vascular disease. In persons without known vascular diseases this risk is calculated from the total and high-density lipoprotein cholesterol ratio, age, sex, blood pressure, diabetes mellitus, and smoking. Treatment with cholesterol synthesis inhibitors must be considered in (a) patients with familial hypercholesterolaemia, (b) all patients with a history of myocardial infarction or other symptomatic vascular disease with a total cholesterol concentration above 5.0 mmol/l and a life expectancy of at least five years; (c) persons with a combination of diabetes mellitus, hypertension, hypercholesterolaemia and high risk for development of CHD, rising from 25% per 10 years at the age of 40 years to 35-40% per 10 years at the age of 70 years, with a life expectancy of at least five years. If these guidelines are followed, the upper limit of the calculated cost-effectiveness is about Dfl. 40,000 per life year gained. The working group judges this reasonable in comparison with other therapeutic interventions in the Netherlands.     

Italian style brewed coffee: effect on serum cholesterol in young men

BACKGROUND: Increases in blood lipids have been observed in humans when coffee is brewed by the boiling method. The purpose of this study was to evaluate if giving up Italian coffee might reduce blood cholesterol levels. METHODS: Eighty-four normolipidaemic young adult males, after a 3-week baseline (BL), were randomly assigned to three different regimens of coffee consumption: espresso (E), mocha (M), and no coffee, but tea (T). The average coffee consumption during intervention (I) was 3.1 +/- 1.2 and 2.8 +/- 1.1 cups per day for espresso and mocha group respectively (espresso: 25-35 ml/cup; mocha: 40-50 ml/cup). Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were measured eight times during the study. Dietary pattern, alcohol consumption, smoking habits, drug use, and anthropometric data were also recorded. RESULTS: The changes observed in serum cholesterol concentration between baseline and intervention were not statistically different in all groups. The changes were 0.0 mmol/l (T), +0.01 mmol/l (E) and +0.05 mmol/l (M) for total serum cholesterol; 0 mmol/l (T), -0.02 mmol/l (E) and -0. 03 mmol/l (M) for HDL-C; -0.13 mmol/l (T), +0.02 mmol/l (E) and -0. 05 mmol/l (M) for LDL-C. Serum triglycerides showed a significant increase during intervention (P < 0.01 by ANOVA) in all groups with a change of 0.18 mmol/l, 0.18 mmol/l and 0.22 mmol/l, for tea, espresso and mocha group respectively. CONCLUSIONS: The results indicate that coffee brewed in the Italian way does not alter blood levels of total cholesterol, HDL-cholesterol and LDL-cholesterol, since no significant differences were observed in these blood parameters after a 6-week break from coffee consumption.