Fiber intake, serum cholesterol levels, and cardiovascular disease in European individuals with type 1 diabetes. EURODIAB IDDM Complications Study Group.

Toeller M, Buyken AE, Heitkamp G, de Pergola G, Giorgino F, Fuller JH.

Clinical Department, Heinrich-Heine-University, Dusseldorf, Germany.

OBJECTIVE: A cross-sectional analysis of dietary fiber intake was performed in European type 1 diabetic patients enrolled in the EURODIAB IDDM Complications Study to explore its potential relationship to serum cholesterol levels and the prevalence of cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Dietary intake was assessed by a standardized 3-day dietary record. For analysis of fiber intake (total, soluble, and insoluble) and its associations with CVD (past history or electrocardiogram abnormalities), complete data were available from 1,050 male and 1,012 female individuals. Relationships of fiber intakes to serum cholesterol levels (total, HDL, and LDL cholesterol) were examined in 926 men and 881 women with type 1 diabetes. RESULTS: Higher intakes of total fiber (g/day) were independently associated with significantly higher levels of HDL cholesterol in male (P = 0.01) and female individuals (P = 0.03). Fiber intakes of men with type 1 diabetes were also inversely related to ratios of total cholesterol to HDL cholesterol (P = 0.0001) and levels of LDL cholesterol (P = 0.0002). A protective effect of total fiber intake against CVD was observed for female subjects, where a significant trend was maintained after adjustment for potential confounders, including energy and saturated fat (P = 0.03 vs. P = 0.2 in men). Results were similar in separate analyses of soluble and insoluble fiber. CONCLUSIONS: The present study demonstrates that higher fiber intakes are independently related to beneficial alterations of the serum cholesterol pattern in men and to a lower risk for CVD in European insulin-dependent women. Beneficial effects can already be observed for fiber amounts within the range commonly consumed by outpatients with type 1 diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10097895&dopt=Abstract cholesterol




Diminished rate of mouse peritoneal macrophage cholesterol efflux is not related to the degree of HDL glycation in diabetes mellitus.

Passarelli M, Shimabukuro AF, Catanozi S, Nakandakare ER, Rocha JC, Carrilho AJ, Quintao EC.

Lipids Laboratory, University of Sao Paulo Medical School, Av. Dr. Arnaldo, 455 s/3317, Sao Paulo, Brazil.

The efflux of (14)C-cholesterol from mouse peritoneal macrophages mediated by in vivo and in vitro glycation of intact HDL(3) and by HDL(3) apolipoproteins was investigated. Cholesterol-laden cells were incubated a long time with HDL(3) from control subjects (C), poorly controlled diabetes mellitus patients (D) and with HDL C submitted to in vitro glycation (G), as well as with all their respectively isolated apolipoproteins. A diminished cholesterol efflux rate occurred in incubations with intact HDL(3) D but not with intact HDL(3)G or with apoHDL(3)C, G or D. The specific binding of (125)I-HDL(3)G to the cell receptor, obtained upon incubation in the absence and in the presence of excess unlabelled HDL(3), was lower than the control. The role of apoE secretion by cholesterol-laden macrophages on cholesterol efflux was analyzed by incubating apoE knockout and control mice macrophages with HDL C or HDL G: a lower cholesterol efflux was observed from apoE knockout macrophages but glycation of HDL(3) did not influence this process either. The diminished capacity to remove cholesterol by the HDL drawn from diabetic subjects must be attributed to other modifications of the lipoproteins, except for non enzymatic glycation. Thus, events that impair the cell cholesterol removal in diabetes mellitus are multifaceted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020467&dopt=Abstract cholesterol




An independent, inverse association of high-density-lipoprotein-cholesterol concentration with nonadipose body mass.

Pietrobelli A, Lee RC, Capristo E, Deckelbaum RJ, Heymsfield SB.

Department of Medicine, St Luke's-Roosevelt Hospital Center and Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, NY, USA.

BACKGROUND: Increasing body mass index (BMI) is associated with progressively lower serum HDL-cholesterol concentrations, although the underlying body-composition compartment accounting for this unfavorable lipid change remains uncertain. OBJECTIVE: Because growing evidence favors a role of lean tissue in HDL homeostasis, the hypothesis was tested that non-adipose tissue components of body mass explain the inverse association of HDL cholesterol and BMI. DESIGN: Fasting serum lipid concentrations and body composition [total, subcutaneous, and visceral adipose tissue; adipose tissue-free mass (ATFM); and skeletal muscle by whole-body magnetic resonance imaging and body cell mass by 40K counting) were evaluated in healthy adults. Body-composition compartments were expressed as height2-normalized indexes. RESULTS: An inverse correlation was observed between serum HDL cholesterol and BMI in women (n = 68; R2 = 0.08, P = 0.023) and men (n = 61; R2 = 0.07, P = 0.046). Significant inverse correlations (P = 0.005-0.02) were also observed between HDL cholesterol and nonadipose components (ie, ATFM, skeletal muscle, and body cell mass) but not between HDL cholesterol and any adipose tissue component. The association between HDL cholesterol and ATFM remained significant after serum triacylglycerol was controlled for. When BMI was entered into the HDL cholesterol-ATFM regression model, BMI was not a significant independent variable. The strongest correlate of serum triacylglycerol was visceral adipose tissue (P = 0.002 for both women and men). CONCLUSIONS: Lean tissues and body cell mass appear to account in part for the long-observed inverse association of HDL cholesterol and BMI. These observations suggest a link between nonadipose tissue compartments and the greater cardiovascular risk associated with high BMI.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10197562&dopt=Abstract cholesterol




Apolipoprotein B-containing lipoproteins in renal failure: the relation to mode of dialysis.

Attman PO, Samuelsson OG, Moberly J, Johansson AC, Ljungman S, Weiss LG, Knight-Gibson C, Alaupovic P.

Department of Nephrology, Sahlgrenska University Hospital, Goteborg, Sweden. per-ola.attman sahlgrenska.se

BACKGROUND: The aim of this study was to establish whether there is a differential effect of mode of dialysis, hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) on the dyslipidemia of renal failure. METHODS: The lipoprotein profile was determined in 61 non-diabetic patients on chronic HD (N = 30) and CAPD treatment (N = 31), and in a control group of 27 healthy subjects. The analysis included the measurement of individual apolipoprotein (apo) A- and apo B-containing lipoproteins (LPs) separated by sequential immunoaffinity chromatography. Apo A-containing lipoproteins include lipoprotein A-I with apo A-I and lipoprotein A-I:A-II with apo A-I and apo A-II as the main protein constituents, whereas apo B-containing lipoproteins comprise simple cholesterol-rich lipoprotein B (LP-B), with apo B as the only protein moiety and complex triglyceride (TG)-rich lipoprotein B complex (LP-Bc) particles with apo B, apo A-II, apo C, and/or apo E as the protein constituents. RESULTS: CAPD patients had significantly higher concentrations of total cholesterol (6.8 vs. 5.1 mmol/liter), low-density lipoprotein (LDL) cholesterol (4.6 vs. 3.2 mmol/liter), TG (2.3 vs. 1.5 mmol/liter), apo B (155.3 vs. 105.7 mg/dl), LP-B (136.0 vs. 91.9 mg/dl), and LP-Bc (19.3 vs. 13.8 mg/dl) than HD patients. Both HD and CAPD patients had significantly higher TG, VLDL cholesterol, apo C-III, and apo E and significantly lower high-density lipoprotein cholesterol, apo A-II, and lipoprotein A-I:A-II levels than control subjects. The distribution of apo C-III in high-density lipoprotein and VLDL-LDL was altered in CAPD patients in comparison with control subjects. This suggests that the removal of TG-rich lipoproteins is less efficient in patients on CAPD. Normotriglyceridemic (NTG; TG < or = 1.7 mmol/liter, 150 mg/dl) CAPD patients had significantly higher levels of TC, LDL cholesterol, apo B, and LP-B than NTG-HD patients. There was little difference in the LP-Bc levels between NTG-CAPD, NTG-HD, and controls. Similarly, hypertriglyceridemic (HTG) CAPD patients had significantly higher TC, LDL cholesterol, apo B, and LP-B levels than HTG-HD patients. The LP-Bc levels were significantly increased in HTG-HD and HTG-CAPD patients compared with controls, but the slightly higher levels in the CAPD patients did not differ significantly from the HD group. CONCLUSION: CAPD and HD patients have a lipoprotein profile characteristic of renal failure. Patients on long-term CAPD have higher levels of cholesterol-rich apo B-containing lipoproteins unrelated to TG levels. Many patients on CAPD also have a substantial elevation of the plasma concentrations of TG-rich LPs. The clinical significance of increased levels of potentially atherogenic LP-B during CAPD remains to be investigated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10201020&dopt=Abstract cholesterol




First-degree kinship with young coronary artery disease patients markedly increases lipid-level disorders in asymptomatic hypertensives.

Giannini SD, Diament J, Forti N, Issa JS, Dal Bo C, Fukushima J, Barretto AC.

Heart Institute of the University of Sao Paulo Medical School, SP, Brazil.

BACKGROUND: Association of hypertension and serum lipid disorders has been demonstrated in previous studies. However, there are no investigations about the behaviour of serum lipids in asymptomatic hypertensive individuals who are first degree relatives of young coronary patients. OBJECTIVE: To determine the degree of lipid disorders in Brazilian hypertensive individuals who are first degree relatives of young coronary patients. METHODS: There were four study groups, 2 in each arm of the study: a) 846 subjects without any evidence of heart disease or diabetes who were first degree relatives of patients who underwent coronary artery bypass grafting (CABG) surgery before 55 years-of-age. Of these subjects, 226 individuals were hypertensive (group Hyp F), and 620 were normotensive (group Normo F): b) 910 hospital employees without evidence of cardiovascular disease and family history of coronary artery disease of whom 152 were hypertensive (group Hyp NF), and 758 were normotensive (group Normo NF). Hypertension was defined as blood pressure greater than 140/90 mmHg. The following serum lipid measurements were performed: total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprtein cholesterol (LDLC), and triglycerides. Lipid disorders were defined according to the 2nd Report of the National Cholesterol Education Program (NCEP) (total cholesterol>240 mg/dl; LDLC>160 mg/dl; triglycerides>200 mg/dl). The frequency of lipid disorders in each group was calculated. Subjects were classified according to their body mass index (BMI) as normal, overweight, or obese. The following statistical analyses were performed as indicated: ANOVA (with Tukey's corrections for multiple comparisons), chi-square (x2), and odds ratio (OR). RESULTS: Hyp F subjects had significantly higher total cholesterol, LDLC and triglyceride levels, and significantly lower levels of HDLC than all other groups. There was a higher frequency of lipid disorders in Hyp F subjects than in Hyp NF individuals, with a significant OR of 1.71 (CI 1.26-2.32) and 2.09 (CI 1.48-2.72) for total cholesterol and LDLC respectively. When compared to Normo F subjects, Hyp F individuals had significantly higher risk of having lipid disorders: total cholesterol (OR=8), LDLC (OR=6), and triglycerides (OR=5). There was a higher frequency of obesity among Hyp F patients than in all other groups. The frequency of subjects who were overweight or obese was higher in Hyp F than in Hyp NF subjects. CONCLUSION: Hypertensive patients who were first degree relatives of patients revascularized at a young age had a higher prevalence of lipid disorders, particularly higher total cholesterol and LDLC, than hypertensive individuals without this family history. These individuals may have a greater genetic propensity to develop lipid disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10201549&dopt=Abstract cholesterol




Blocking cholesterol synthesis impairs acquisition of the classically conditioned eyeblink response.

O'Brien WT, Xu G, Tint GS, Salen G, Servatius RJ.

Department of Neurosciences, New Jersey Medical School, Newark, USA.

Smith-Lemli-Opitz (SLO) syndrome is a congenital disorder characterized by severe mental retardation. Patients with SLO lack 7-dehydrocholesterol (7 dH) reductase, which catalyzes the last step of cholesterol synthesis. Administration of an agent that blocks 7 dH cholesterol reductase, BM 15.766 (BM), leads to a biochemical profile which resembles that of SLO patients, i.e., lower plasma, liver, and brain cholesterol levels accompanied by the appearance of the precursors 7 dH and 8 dH cholesterol. In this article we address the functional consequences of chronic BM treatment on new motor learning by assessing acquisition of the classically conditioned eyeblink response. Just-weaned rats were fed BM by gavage for four months, with half of these rats given exogenous cholesterol during the last two months of BM treatment. Acquisition of the eyeblink response was impaired in BM-treated rats. Impaired acquisition of the eyeblink response was not accompanied by alterations in responsiveness to either the conditioned or unconditioned stimulus. Exogenous cholesterol, a clinically relevant countertreatment, failed to correct for the learning impairment produced by BM treatment. Chronic treatment with a cholesterol synthesis-blocking agent impaired associative learning in just-weaned rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11021337&dopt=Abstract cholesterol




Influence of apolipoprotein E polymorphism on serum lipids and lipoprotein changes from childhood to adulthood: the Bogalusa Heart Study.

Srinivasan SR, Ehnholm C, Elkasabany A, Berenson G.

The Tulane Center for Cardiovascular Health, Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112-2824, USA.

The influence of apolipoprotein (apo) E polymorphism on serum lipoproteins from childhood to adulthood was examined in 1520 individuals, aged 5-14 years at baseline, followed over a 16-year period. At both times, the e2 allele associated with lower LDL cholesterol (P < 0.001) and higher HDL cholesterol (P < 0.05-0.01), the e4 allele with higher LDL cholesterol (P < 0.001). The e2 allele lowered the adulthood LDL cholesterol level to a greater extent than the childhood level (P < 0.05). With respect to tracking, at the lowest quartile of LDL cholesterol distribution, the persistence in ranks over time was higher in the apoE2 group with E2/3 and E2/2 phenotypes compared with the apoE3 group with E3/3 phenotype and the apoE4 group with E3/4 and E4/4 phenotypes (P = 0.001). Longitudinal increases in the ponderal index (weight/height3) lowered the adulthood HDL cholesterol to a larger extent in e2 carriers (P = 0.017). The interindividual variability in LDL cholesterol due to childhood and adulthood ponderal index was 1.8- to 2.3-fold greater in the apoE2 group versus the apoE3 group. Likewise, cigarette smoking, alcohol use and oral contraceptive use in adulthood explained greater variability in triglycerides (5.3-fold), VLDL cholesterol (7.8-fold) and HDL cholesterol (2.9-fold) in the apoE2 group versus the apoE3 group. Thus, the apoE locus influences not only the levels and tracking of certain lipoproteins from childhood to adulthood but also modulates the association between lifestyle-related factors and lipoproteins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10217374&dopt=Abstract cholesterol




Comparative cholesterol lowering properties of vegetable oils: beyond fatty acids.

Wilson TA, Ausman LM, Lawton CW, Hegsted DM, Nicolosi RJ.

Department of Health and Clinical Science, Center for Chronic Disease Control and Prevention, University of Massachusetts, Lowell 01854-5125, USA.

OBJECTIVE: Our laboratory has previously reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Although RBO has up to three times more serum cholesterol-raising saturated fatty acids (SATS) than some unsaturated vegetable oils, we hypothesized that its greater content of the unsaponifiables would compensate for its high SATS and yield comparable cholesterol-lowering properties to other vegetable oils with less SATS. METHODS: To study the comparative effects of different unsaturated vegetable oils on serum lipoprotein levels, nine cynomologus monkeys (Macaca fascicularis) were fed diets, for four weeks, in a Latin square design, containing rice bran, canola or corn oils (as 20% of energy) in a basal mixture of other fats to yield a final dietary fat concentration of 30% of energy. All animals were fed a baseline diet containing 36% of energy as fat with 15% SATS, 15% monounsaturated fatty acids (MONOS) and 6% polyunsaturated fatty acids (POLYS). RESULTS: Despite the lower SATS and higher MONOS content of canola oil and the higher POLYS content of corn oil, RBO produced similar reductions in serum total cholesterol (TC) (-25%) and low density lipoprotein cholesterol (LDL-C) (-30%). In addition, as compared to the baseline diet, the reduction in serum TC and LDL-C cholesterol with RBO was not accompanied by reductions in high density lipoprotein cholesterol (HDL-C) which occurred with the other two dietary oils. Using predictive equations developed from data gathered from several studies with non-human primates, we noted that the observed serum TC and LDL-C lowering capabilities of the RBO diet were in excess of those predicted based on the fatty acid composition of RBO. CONCLUSIONS: These studies suggest that non-fatty acid components (unsaponifiables) of RBO can contribute significantly to its cholesterol-lowering capability.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11022873&dopt=Abstract cholesterol




The prevalence of hyperlipidemia in women and its association with use of oral contraceptives, sex hormone replacement therapy and nonlipid coronary artery disease risk factors. Canadian Heart Health Surveys Research Group.

Connelly PW, Stachenko S, MacLean DR, Petrasovits A, Little JA.

St Michael's Hospital and University of Toronto, Toronto, Canada. p.connelly utoronto.ca

OBJECTIVE: To report the prevalence of lipid and nonlipid coronary artery disease risk factors in women classified by use of oral contraceptives or sex hormone replacement therapy. DESIGN, SETTING AND PARTICIPANTS: A population-based cross-sectional survey in nine Canadian provinces (not including Nova Scotia) between 1988 and 1992 invited 13,506 women aged 18 to 74 years to participate. During a clinic visit after a home interview, a blood sample was obtained following a fast of 8 h or more from 8637 women. OUTCOME MEASURES: Fasting plasma total cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, blood pressure, smoking status, self-reported diabetes, and self-reported use of oral contraceptive or sex hormone replacement therapy pills. MAIN RESULTS: The prevalence of oral contraceptive use was 41% for women 18 to 24 years old and 20% for women 25 to 34 years old. The prevalence of sex hormone replacement therapy was 4% for women 35 to 44 years old, 20% for women 45 to 64 years old and 11% for women 65 to 74 years old. Users of sex hormone replacement therapy aged 35 to 44 years had slightly higher mean LDL cholesterol than nonusers (3.04 versus 2.89 mmol/L). Users and nonusers aged 45 to 54 years had similar LDL cholesterol levels, and users aged 55 to 64 and 65 to 74 years had lower LDL cholesterol and higher HDL cholesterol levels, respectively, than nonusers. Triglyceride levels were higher in oral contraceptive users and in younger women on sex hormone replacement therapy than in nonusers. In the general population of Canada the use of oral contraceptives in women less than age 35 years had only a marginal effect on the prevalence of lipid and nonlipid risk factors. Women aged 18 to 24 years using oral contraceptives had a higher mean LDL cholesterol level of 2.73 versus 2.35 mmol/L for nonusers. The prevalence of lipid and nonlipid risk factors in women using sex hormone replacement therapy increased slightly for those aged 35 to 54 years and decreased in women aged 55 to 74 years. A lower percentage of women using sex hormone replacement therapy, aged 55 to 74 years, had high risk LDL cholesterol levels (21% versus 36% for nonusers). A larger percentage of women using sex hormone replacement therapy had low risk HDL cholesterol levels (54% versus 29% for nonusers). The nonlipid risk factor profile for women aged 35 to 54 years on sex hormone replacement therapy was less favourable than for nonusers: obesity was more common (36% versus 28%, respectively), hypertension was higher (22% versus 12%, respectively), and the proportion of women with one or more nonlipid risk factors was higher. The nonlipid risk factor profile for women 55 to 74 years of age who were using sex hormone replacement therapy was more favourable than for nonusers: obesity was lower (31% versus 47%, respectively), smoking was lower (7% versus 16%, respectively), sedentary behaviour was lower (28% versus 37%, respectively), and fewer women had two or more of these risk factors (31% versus 52%, respectively). CONCLUSION: The findings suggest that women at higher risk for coronary artery disease tend to have a lower prevalence of use of sex hormone replacement therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10322251&dopt=Abstract cholesterol