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Biomedical subjects

Helena Gylling

Publications and source records attributed to Helena Gylling.

At least 37 records · Page 2Linked to original sources
PubMed2005

Plant sterols in serum and in atherosclerotic plaques of patients undergoing carotid endarterectomy.

OBJECTIVES: The purpose of this research was to determine whether serum plant sterol levels are associated with those in atheromatous plaque. BACKGROUND: Cholesterol of low-density lipoprotein (LDL) particles contributes to atheromatous plaque formation; LDL also contains most serum non-cholesterol sterols, including plant sterols. The role of plant sterols in atheromatous plaque formation is open. METHODS: Free, ester, and total cholesterol and the respective non-cholesterol sterols were measured by gas-liquid chromatography in serum and arterial tissue of 25 consecutive patients undergoing carotid endarterectomy. The population was ranked to triads according to tissue cholesterol concentration. RESULTS: Cholesterol concentration increased markedly in tissues but not in serum with triads. The ester percentage was lower in the third than in the first triad (47% vs. 56%; p < 0.01) and lower than in serum triads (70%; p < 0.001). Ratios to cholesterol of non-cholesterol sterols decreased in increasing tissue triads, but were unchanged in serum. A major new observation was that the higher the ratio to cholesterol of the surrogate absorption sterols (cholestanol, campesterol, sitosterol, and avenasterol) in serum, the higher was their ratio also in the carotid artery wall (e.g., r = 0.683 for campesterol). Despite undetectable differences in serum and tissue cholesterol concentrations off and on statins, an additional important novel finding was that statin treatment was associated with increased ratios of the absorption sterols in serum and also in the arterial plaque. CONCLUSIONS: The higher the absorption of cholesterol, the higher are the plant sterol contents in serum resulting also in their higher contents in atherosclerotic plaque. However, the role of dietary plant sterols in the development of atherosclerotic plaque is not known.

Absorption↗
PubMed2005

Cholesterol absorption: influence of body weight and the role of plant sterols.

Cholesterol absorption and synthesis are inter-regulated, so if one changes then the other changes in the opposite direction. The regulation and detailed mechanism of cholesterol absorption have been intensely investigated. Inhibition of cholesterol absorption has become an additional factor for cholesterol lowering. Agents inhibiting cholesterol absorption, mainly plant stanols and sterols or ezetimibe, usually lower low-density lipoprotein cholesterol in monotherapy by less than 20%, indicating that these inhibitors can normalize cholesterol levels only in patients with a modest baseline hypercholesterolemia. Body weight, especially obesity with and without diabetes, and dietary plant sterols alter cholesterol absorption differently. This article briefly reviews some special questions of cholesterol absorption under these conditions.

Absorption↗
PubMed2005

Non-cholesterol sterols in serum, lipoproteins, and red cells in statin-treated FH subjects off and on plant stanol and sterol ester spreads.

BACKGROUND: Serum plant sterol levels are increased by consumption of statins and dietary plant sterols, and decreased by dietary plant stanols, but little is known about combination therapy of statin and plant sterols. METHODS: We measured plant sterols in serum, lipoproteins, and red cells in subjects with familial hypercholesterolemia (FH) (n=18) treated with variable doses of statins off and on plant stanol (STA) and sterol ester (STE) spreads. RESULTS: STA and STE spreads lowered LDL cholesterol approximately 15%. Plant sterols were decreased in serum, lipoproteins, and red cells by approximately 25% with STA and increased from 37% to 80% with STE, especially with high statin doses. The changes in serum were related to those in red cells. The baseline levels of serum plant sterols were negatively (r-range -0.639 to -0.935) and positively (r-range 0.526 to 0.598) correlated with the respective changes evoked by the STA and STE spreads. CONCLUSIONS: STE reduces LDL cholesterol, but increases serum, lipoprotein, and red cell plant sterol levels in statin-treated FH subjects, while all the respective values are decreased with STA. Recent predictions that elevated serum plant sterols pose an increased coronary risk suggest that increases of serum plant sterol levels should be avoided, especially in atherosclerosis-prone individuals, such as subjects with FH.

Adult↗
PubMed2005

The effect of plant stanol- and sterol-enriched foods on lipid metabolism, serum lipids and coronary heart disease.

Phytosterols are plant sterols, mainly campesterol and sitosterol, and their respective stanols (5alpha-saturated derivatives), which chemically resemble cholesterol. They are present in a normal diet and are absorbed proportionally to cholesterol, but to a much lesser extent, such that less than 0.1% of serum sterols are plant sterols. Phytosterols inhibit intestinal cholesterol absorption, and fat-soluble plant stanol esters were introduced as a functional food for lowering serum cholesterol in the early 1990s; plant sterol esters entered the market at the end of the 1990s. Inhibition of the intestinal absorption of cholesterol stimulates cholesterol synthesis, a factor which limits serum cholesterol lowering to about 10% with phytosterols. Enrichment of the diet with plant stanol esters reduces absorption and serum concentrations of both cholesterol and plant sterols, whereas enrichment of the diet with plant sterol esters, especially in combination with statins, lowers serum cholesterol but increases serum plant sterol levels. Recent studies have suggested that high-serum plant sterol levels may be associated with increased coincidence of coronary heart disease. Estimates of coronary heart disease reduction by 20--25% with plant sterols/stanols is based mainly on short-term studies. Long-term cholesterol lowering, needed for the prevention of coronary heart disease, may be successful with plant stanol esters, which lower serum cholesterol in both genders over at least a year.

Coronary Artery Disease↗
PubMed2004

Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity.

The roles of polymorphisms of the sitosterolemia genes ABCG5 and ABCG8 in the regulation of cholesterol metabolism and insulin sensitivity were studied in mildly hypercholesterolemic noncoronary subjects (n = 263, 144 men and 119 women) divided into tertiles by baseline serum cholestanol-to-cholesterol ratio (< or = 118.3 and > or = 147.7 10(2) x mmol/mol cholesterol), a surrogate marker of cholesterol absorption efficiency. The lowest cholestanol tertile was associated with high body mass index (BMI), plasma glucose, serum insulin and triglycerides, and cholesterol synthesis markers (cholestenol, desmosterol, lathosterol) and low HDL cholesterol and cholesterol absorption markers (campesterol, sitosterol) (P < 0.01 for all). The 19H allele of the ABCG8 gene accumulated in the lowest cholestanol tertile (P < 0.001) and was associated with low total and LDL cholesterol and absorption markers and with high synthesis markers (P < 0.05 for all). The 604E allele of the ABCG5 gene in men was associated with high BMI, plasma insulin, low serum sitosterol, and high serum cholestenol levels (P < 0.05 for all). In a subgroup of 71 men, the 604E allele was associated with insulin resistance measured with the hyperinsulinemic euglycemic clamp. In conclusion, low cholesterol absorption efficiency was associated with characteristics of the metabolic syndrome. Low serum cholesterol and cholesterol absorption were linked to the D19H polymorphism of the ABCG8 gene, and characteristics of the insulin resistance syndrome in men were linked with the Q604E polymorphism of the ABCG5 gene.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2004

Removal of intravenous Intralipid in patients with familial hypercholesterolemia during inhibition of cholesterol absorption and synthesis.

BACKGROUND: While plant stanols are known to upregulate low density lipoprotein (LDL) receptors, we studied the effects of plant stanol (STA) and sterol (STE) ester spreads on triglyceride-rich lipoprotein (TRL) removal in statin-treated patients with familial hypercholesterolemia (FH) using intravenous Intralipid-squalene fat tolerance test. METHODS: Five patients consumed STA and STE in a randomized, crossover study for 4 weeks. TRL removal was studied at baseline and at the end of both periods. Serum, chylomicron (CM), and very low density lipoprotein lipids, squalene, and plant sterols were measured. RESULTS: LDL cholesterol was decreased by both spreads (15-16%, p<0.05). Plant sterol concentrations were doubled in serum and CM by STE vs. STA. After the injection of Intralipid, CM squalene and sitosterol, but not triglycerides (TG), reached higher peak levels (and area under the incremental curve (AUIC) of squalene) by both spreads than at baseline. Despite different plant sterol concentrations by STE vs. STA, the incremental curves for plant sterols were similar by the spreads. CONCLUSIONS: Despite the retarded removal of TRL lipids by STA and STE in the statin-treated subjects with FH, improvement of the fasting lipid profile was suggested important in consideration of combination of cholesterol absorption inhibitor with statins even in FH.

Absorption↗
PubMed2004

Effects of plant stanol and sterol esters on serum phytosterols in a family with familial hypercholesterolemia including a homozygous subject.

We studied the concentrations and ratios to cholesterol of noncholesterol sterols reflecting absorption (eg, campesterol) or synthesis (eg, lathosterol) of cholesterol off and on plant sterol and stanol ester spreads in serum and in different lipoproteins of a family with familial hypercholesterolemia, including heterozygous parents receiving no treatment and their homozygous offspring undergoing long-term treatment with statins and apheresis. Serum cholesterol levels were similar in the homozygous and heterozygous individuals, but the concentrations of sterols reflecting cholesterol absorption were as much as 10 times greater in the homozygous child than in the heterozygous parents, whereas the respective markers of cholesterol synthesis only tended to be higher. About 70% of squalene in the homozygous individual (60% in the heterozygous family members) and 85% to 90% of noncholesterol sterols (60%-80% in the heterozygous subjects) were transported by low-density lipoprotein. The ratios of absorption sterols to cholesterol were higher in high-density lipoprotein (HDL) than in very low-density lipoprotein (VLDL), whereas those of synthesis markers and plant stanols were highest in VLDL. The ratios of absorption sterols in serum were mostly lower than those in HDL but higher than in VLDL, whereas the ratios of synthesis sterols in serum were lower than they were in VLDL. Both spreads reduced serum total cholesterol by about 14% in the heterozygous family members and 9% in the homozygous individual. The sterol ester spread increased serum plant sterol concentrations (eg, campesterol in the homozygous family member increased from 5 to 9 mg/dL) and the ratios to cholesterol, but the stanol ester spread decreased them. Plant sterol esters seemed to similarly decrease serum cholesterol in this family with familial hypercholesterolemia, but the clinical role of increased plant sterol concentrations, almost doubled in the LDL of homozygous individuals, is not known.

Adult↗
PubMed2004

Ileal pouch-anal anastomosis, conventional ileostomy and ileorectal anastomosis modify cholesterol metabolism.

Proctocolectomy modifies the enterohepatic circulation and activity of bacterial enzymes depending on the structure of the stoma and function of the terminal ileum. We evaluated in our comparative study effects of different colectomy constructions on cholesterol metabolism. Levels of lipoprotein cholesterol and triglycerides, noncholesterol sterols, and squalene in serum, fecal fat, and bile acids, cholesterol absorption efficiency, and cholesterol metabolism by sterol balance technique were analyzed in human subjects with ileal pouch-anal anastomosis (n = 34), conventional ileostomy (n = 8), ileorectostomy (n = 6), and controls (n = 29). Malabsorption of bile acids, but not of fat, and low serum levels of total and low-density lipoprotein cholesterol, but high levels of high-density lipoprotein cholesterol and increased cholesterol synthesis were evident in the colectomy groups. In contrast to the ileorectostomy group, expressing high absorption and biliary secretion of cholesterol, a low cholesterol absorption percentage accompanied by elevated serum proportions of cholesterol precursor sterols and phytosterols characterized the ileal pouch-anal anastomosis and conventional ileostomy groups. After colectomy, fecal excretion of secondary bile acids was low, whereas relative proportions of identifiable bile acids remained the same in each study group. Low serum levels of total and low-density lipoprotein cholesterol of colectomized subjects may decrease the risk of premature atherosclerosis. The favorable serum lipid profile was due to enhanced fecal loss of cholesterol as bile acids despite abnormally high cholesterol synthesis. Ileal dysfunction probably diminished cholesterol absorption in subjects with ileal pouch-anal anastomosis and conventional ileostomy, with no explanation for those with ileorectostomy with no clinical gastrointestinal dysfunction. Relative synthesis of identifiable primary bile acids remained unchanged postoperatively, but formation of secondary bile acids was weak due to scarce bacterial flora.

Anal Canal↗
PubMed2004

Plant stanol and sterol esters in prevention of cardiovascular diseases.

Statin trials have indicated that effective reduction of serum cholesterol should last up to one year before reduced risk of cardiovascular diseases can be detected. This observation can be applied most probably also to the use of plant stanol/sterol ester spreads for the treatment of hypercholesterolemia. However, despite the fact that the two spreads lower serum cholesterol similarly in short term studies, a comparison of one year results reveals an inconsistent effect of plant sterol spread as compared with that of plant stanol spread on cholesterol concentration in both men and women. This favors the use of plant stanol ester spread for long-term lowering of serum cholesterol. Doses of about 2 g/day of plant stanols as fatty acid ester spread enhances fecal elimination of cholesterol, but not of bile acids, through inhibition of cholesterol absorption by about 40%. This lowers serum total and low density lipoprotein (LDL) cholesterol despite enhanced compensatory increase in cholesterol synthesis by about 10% and 15% as compared with control spread, respectively, and by up to 20% as compared with the baseline diet. About one-third of mildly hypercholesterolemic subjects reach an accepted cholesterol level. A small dose of statin should be added to treatment in individuals resistant to monotherapy with plant stanol ester spread. A life-long consumption of plant stanol ester spread has been predicted to lower coronary events by about 20%.

Animals↗
PubMed2004

Effect of 12-month statin therapy on antioxidant potential of LDL and serum antioxidant vitamin concentrations.

BACKGROUND: Statins are known to cause short-term reduction in serum lipid-soluble antioxidant concentrations, but their long-term effects are not known. AIM: We randomised 104 subjects with CHD and hypercholesterolaemia to receive either atorvastatin or simvastatin treatment for 52 weeks and measured the antioxidant potential of LDL and serum antioxidant vitamin concentrations. METHOD: Initial daily dose for both statins was 20 mg. RESULTS: LDL antioxidant capacity and serum alpha-tocopherol, gamma-tocopherol and beta-carotene concentrations decreased by 22%-35% with both statins during the first 12 weeks' therapy (P < 0.01 for all). After 52 weeks' therapy, the concentrations of serum gamma-tocopherol in the simvastatin group and serum beta-carotene in both treatment groups returned to baseline levels, while the concentrations of serum gamma-tocopherol in the atorvastatin group and LDL anti-oxidant capacity and serum alpha-tocopherol in both treatment groups remained reduced (P < 0.001 for all). The LDL antioxidant capacity:LDL-cholesterol and the serum alpha-tocopherol:LDL-cholesterol ratios were significantly elevated with both statins after 12 and 52 weeks (P < 0.001 for all). Statistically significant increases were also observed for corresponding ratios of the less abundant vitamins gamma-tocopherol and beta-carotene. CONCLUSIONS: Some of the decreases in serum lipid soluble antioxidant vitamins reported in short-term statin interventions may become attenuated when therapy continues longer. The relative antioxidant capacity of LDL particles increased during the 52-week treatment, suggesting that the oxidation resistance of LDL particles did not become impaired and that their atherogenicity did not increase.

Atorvastatin↗
PubMed2004

Long-term results, late complications and quality of life in a series of adjustable gastric banding.

BACKGROUND: Adjustable gastric banding is currently the most common bariatric operation. This study is a retrospective analysis of the Finnish experience with this procedure over the last 10 years. METHODS: Between March 1993 and June 1999, 123 patients underwent either open (36) or laparoscopic (87) surgery for morbid obesity by the application of an adjustable gastric band. Data on preoperative clinical characteristics and postoperative outcome and weight-loss patterns up to 9 years (mean 55 months) are presented and also evaluated by the Bariatric Analysis and Reporting Outcome System (BAROS). Sex ratio was 31% males / 69% females, mean age 44 years and mean +/- SD preoperative BMI 49 +/- 8 kg/m(2) (range 33.6-85.1). RESULTS: During the evaluation period (March 1993 December 2002), 54% of patients experienced postoperative complications requiring hospital treatment >or= 7 days, and 52% underwent a reoperation. 33% of bands were removed. The most important late complications were esophagitis (30%), obstruction due to slippage / pouch dilatation (21%), incisional hernia (9%) and band erosion (9%). Mean excess weight loss at 1 and 2 year follow-up was 36% and 38%, which later stabilized to 30%. During the evaluation period, there were 10 deaths, 2 of which were 30-day deaths, and the remainder were not associated with the band. According to BAROS, the outcome was regarded as "very good" in 3%, "good" in 7%, "fair" in 40% and "failure" in 50%. CONCLUSION: Our long-term data found that weight reduction is acceptable,but the incidence of late complications and reoperations was high.

Adult↗
PubMed2004

Hypolipidemic treatment of heterozygous familial hypercholesterolemia: a lifelong challenge.

In familial hypercholesterolemia, a defect in low-density lipoprotein receptors causes lifelong two- to threefold elevations in serum low-density lipoprotein-cholesterol levels. This leads to early atherosclerotic changes in infancy. Lifelong hypolipidemic treatment that can be started at a young age is thus greatly needed. Early diagnosis of familial hypercholesterolemia is important, and improved DNA tests for low-density lipoprotein receptor mutations have made it possible to carry out diagnosis at birth. A low saturated-fat, low cholesterol diet can be safely started at 7 months of age. This can be accompanied by dietary stanol esters from 2 years of age. At the age of 10, statin treatment can be safely started. In adults, more aggressive hypolipidemic treatment is required in order to reach the treatment goal for serum low-density lipoprotein-cholesterol levels less than 2.5 mmol/l. This can be achieved by using high doses of statin, or preferably by combining a statin with resin or ezetimibe (Zeita), Merck and Shering-Plough Pharmaceuticals). Once started, treatment of familial hypercholesterolemia is lifelong.

Heterozygote↗
PubMed2004

Cholesterol metabolism in type 1 diabetes.

Little information is available on cholesterol absorption and synthesis in human type 1 diabetes. We studied these variables using serum cholesterol precursor sterol ratios to cholesterol as surrogate markers of cholesterol synthesis and those of cholestanol and plant sterols to reflect cholesterol absorption in seven type 1 diabetic subjects and in five age- and body weight-matched control subjects. Total and lipoprotein cholesterol levels were similar, but triglycerides in intermediate-density lipoprotein (IDL) and LDL were higher in type 1 diabetic than in control subjects. Most of the marker sterols were transported by LDL and HDL in both groups. The percentage of esterified cholesterol was lower in triglyceride-rich lipoproteins in diabetic patients than in control subjects. The ratios of the absorption marker sterols in serum were higher, and those of the synthesis markers were lower in type 1 diabetic than in control subjects. The increased cholestanol ratios were seen in all lipoproteins, and those of free and total plant sterols were mainly in LDL, whereas the decreased free and total synthesis markers were mainly in all lipoproteins. In conclusion, high absorption and low synthesis marker sterols seem to characterize human type 1 diabetes. These findings could be related to low expression of ABC G/5 G/8 genes, resulting in high absorption of cholesterol and sterols in general and low synthesis of cholesterol compared with type 2 diabetes.

Adult↗
PubMed2004

Low synthesis and high absorption of cholesterol characterize type 1 diabetes.

OBJECTIVE: Streptozotocin-induced type 1 diabetes in experimental animals inhibits cholesterol synthesis and increases cholesterol absorption. In contrast to human type 2 diabetes, virtually no information is available on cholesterol synthesis and absorption in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied the variables of cholesterol metabolism in 27 patients with type 1 diabetes and in 10 patients with type 2 diabetes matched for body weight, using cholesterol precursor sterol ratios to cholesterol as surrogate markers of synthesis, and those of cholestanol and plant sterols of cholesterol absorption. Glucose control was good in all subjects. RESULTS: Total and HDL cholesterol and LDL triglycerides were higher in type 2 than in type 1 diabetes. Serum sterols, measured also in VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL, were transported up to >90% by LDL and HDL in type 1 diabetes. The ratios of all absorption sterols in serum and in each lipoprotein were higher, and those of the synthesis markers, especially cholestenol and lathosterol, were lower in type 1 than in type 2 diabetes. CONCLUSIONS: In contrast to type 2 diabetes, the findings in type 1 diabetes could be related to low expression of ABC G/5 G/8 genes, resulting in high absorption of cholesterol and sterols in general and low synthesis of cholesterol.

Adolescent↗
PubMed2003

Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men.

Type 2 diabetes has been associated with high synthesis and low absorption of cholesterol independent of weight, indicating that insulin resistance may be a link between glucose and cholesterol metabolism. Therefore, we investigated the relationship of serum cholesterol precursors, reflecting cholesterol synthesis, and serum plant sterols and cholestanol, reflecting cholesterol absorption efficiency, with insulin sensitivity measured with the hyperinsulinemic euglycemic clamp in 72 healthy normoglycemic men. Men in the most insulin-resistant tertile had higher serum cholesterol precursor ratios (P < 0.05), whereas no significant differences in serum absorption sterols were observed. In bivariate analysis, cholesterol synthesis markers correlated with fasting insulin (r = 0.36-0.46, P < 0.01) and the rates of insulin-stimulated whole-body glucose uptake (WBGU; r = -0.37-0.40, P < 0.01). Also, cholesterol absorption markers correlated with fasting insulin and WBGU (P < 0.05). Fasting insulin correlated with desmosterol (r = 0.286, P = 0.015) and lathosterol (r = 0.248, P = 0.037) even when the rates of WBGU and body mass index (BMI) were controlled for. We conclude that insulin resistance is linked to high cholesterol synthesis and decreased cholesterol absorption. Because fasting insulin correlated with cholesterol synthesis independent of the rates of BMI and WBGU, it is possible that regulation of cholesterol synthesis by hyperinsulinemia may be a link between insulin resistance and cholesterol metabolism.

Biomarkers↗
PubMed2003

Squalene and noncholesterol sterols in serum and lipoproteins of children with and without familial hypercholesterolemia.

Squalene and noncholesterol sterols, e.g. lathosterol and plant sterols, the respective markers of cholesterol synthesis and absorption, are transported with cholesterol in serum lipoproteins. Their concentrations and ratios to cholesterol in serum and lipoproteins have not been carefully compared, especially in children and in marked hypercholesterolemia. Thus, we measured these variables with gas-liquid chromatography in 18 children with and 29 without familial hypercholesterolemia, all aged 5-17 y. Concentrations of most noncholesterol sterols were higher in serum, LDL, and intermediate density lipoprotein in the children with than those without familial hypercholesterolemia. Despite accumulation of noncholesterol sterols mainly in LDL (75% in familial hypercholesterolemia and 55% in non-familial hypercholesterolemia, p < 0.001), their ratios were mostly similar in serum and lipoproteins of the two groups. The ratios of squalene and lathosterol were higher in VLDL and intermediate density lipoprotein, whereas in LDL that of lathosterol was lower than the respective serum values in both groups. Absorption marker sterol ratios were highest in HDL in both groups. Thus, even though the ratios of noncholesterol sterols to cholesterol in serum reflect, in general, synthesis and absorption of cholesterol, their ratios in different lipoproteins could give additional information of cholesterol metabolism.

Adolescent↗