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O Simell

Publications and source records attributed to O Simell.

At least 55 records · Page 3Linked to original sources

Short-term exclusive breastfeeding predisposes young children with increased genetic risk of Type I diabetes to progressive beta-cell autoimmunity.

AIMS/HYPOTHESIS: This study aimed to establish the relation between early infant nutrition and signs of beta-cell autoimmunity in young children. METHODS: We identified and observed from birth 2949 infants with increased genetic risk of Type I (insulin-dependent) diabetes mellitus (HLA DQB1*02/ *0302 or DQB1*0302/x, x = other than *02, *0301 or *0602) and monitored them for islet cell antibodies at 3 to 6 month intervals. If an infant seroconverted to islet cell antibody positivity, all of his or her samples were also analysed for autoantibodies to insulin, GAD65 (GADA) and to the protein tyrosine phosphatase related IA-2 molecule (IA-2A). Our case-control study comprises the first 65 children who seroconverted to islet cell antibody positivity before the age of 4 years and 390 control children who were islet cell antibody-negative (six control children/ case). We monitored the duration of exclusive and total breastfeeding and the age at which cows' milk was introduced. RESULTS: Infants who had been breastfed exclusively for at least 4 months had lower risk of seroconversion to positivity for IA-2A or all four autoantibodies [odds ratio (OR) 0.24; 95 % CI 0.06-0.94 and OR 0.17; 95 % CI 0.03-0.86, respectively] than those infants who had been breastfed exclusively for less than 2 months. The risk of seroconversion to positivity for IA-2A or all four autoantibodies was higher in those younger than 2 months (OR 4.37; 95 % CI 1.33-14.42 and OR 5.02; 95 % CI 1.27-19.89) or aged 2 to 3.9 months (OR 5.50; 95 % CI 1.21-25.04 and 6.19; 95% CI 1.10-34.84) when they first received cows' milk than in those aged 4 months or older. CONCLUSIONS/INTERPRETATION: These observations suggest that short-term breastfeeding and the early introduction of cows' milk-based infant formula predispose young children who are genetically susceptible to Type I diabetes to progressive signs of beta-cell autoimmunity.

Aging↗

Feasibility of genetic and immunological prediction of type I diabetes in a population-based birth cohort.

AIMS/HYPOTHESIS: Population-wide genetic screening of susceptibility to multifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified. METHODS: Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the at-risk children to frequent autoantibody follow-up were studied. Screening was offered to all families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x not equal to *02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of beta-cell autoimmunity were invited to a separate prevention trial. RESULTS: The parents of 31,526 babies born between November 1994 and April 1999 (94.4% of those eligible) agreed to genetic screening. We found that 4651 infants (14.8%) had increased genetic risk (2.5 to 15 times that of the general population) for Type I (insulin-dependent) diabetes mellitus, and 80% of them joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69, 68 and 76% of the at-risk children, respectively, attended the follow-up. A total of 17 of the 22 children (77%) who were born during the study period and have developed diabetes carry the risk genotypes we currently use for screening. CONCLUSIONS/INTERPRETATION: Population-based screening of genetic susceptibility for Type I diabetes, linked with a possibility to participate later in a prevention trial, is highly accepted in Finland and identifies about 75% of those developing diabetes at an early age. Families adhere well to the frequent measurement of signs of beta-cell autoimmunity in the children at-risk.

Alleles↗

Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children.

AIMS/HYPOTHESIS: We evaluated the role of enterovirus infections in the pathogenesis of Type I (insulin-dependent) diabetes mellitus by monitoring enterovirus antibody levels in prediabetic children who turned positive for diabetes-associated autoantibodies in a prospective birth cohort study. METHODS: Serial serum samples taken during prospective observation starting at birth were analysed for IgG and IgA class antibodies against enterovirus antigens including purified coxsackievirus B4, echovirus 11, poliovirus 1 and a synthetic enterovirus peptide antigen using enzyme immunoassay. Maternal samples taken at the end of the third month of pregnancy were also studied. Analyses were done from 21 childen who developed autoantibodies and from 104 autoantibody-negative control children who were matched for the time of birth, gender and HLA susceptibility alleles. For comparison, adenovirus antibodies were also analysed from all samples collected. RESULTS: IgG class enterovirus antibody levels were high in maternal samples and in cord blood in both case and control children. After birth the IgG levels decreased reaching a nadir at the age of 6 months. No IgA class antibodies were detected at birth but started to emerge postnatally. Antibody levels did not differ between the autoantibody positive and the control children during the first 6 months of life. From 6 months to 24 months of age, the autoantibody positive children had higher IgG and IgA levels against coxsackievirus B4, echovirus 11 and the synthetic enterovirus peptide antigens than control children but poliovirus 1 and adenovirus antibodies were closely similar in the two groups. The difference between children with autoantibodies and control children was predominantly seen among boys and among those with the HLA-DQB1*0302/x genotype. CONCLUSIONS/INTERPRETATION: Our data show that children who seroconverted for diabetes-associated auto-antibodies develop stronger humoral immune responses to coxsackievirus B4, echovirus 11 and a synthetic enterovirus peptide antigen than children who remained negative for autoantibodies. Poliovirus antibodies induced by uniform vaccinations did not differ between the prediabetic and control children suggesting that the regulation of antibody responses to enteroviruses is not disturbed. Accordingly, the results imply a stronger enterovirus exposure in prediabetic children supporting the role of enteroviruses in the pathogenesis of Type I diabetes.

Antibodies, Viral↗

Ophthalmologic heterogeneity in subjects with gyrate atrophy of choroid and retina harboring the L402P mutation of ornithine aminotransferase.

OBJECTIVE/PURPOSE: To investigate clinical variation in a genetically homogenous group of subjects with gyrate atrophy of choroid and retina with hyperornithinemia (GA). The group was made up of homozygotes and compound heterozygotes for mutation L402P in the ornithine aminotransferase (OAT) gene. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty-five Finnish subjects (18 men) with GA with a mean age of 33 years (range, 5-74 years) carrying the Finnish founder mutation L402P. METHODS: All subjects were examined between 1993 and 1995. The analysis was composed of, in addition to careful clinical evaluation, studies of visual fields with Goldmann perimeter, photographing of the eye fundi, and corneal electroretinography (ERG) recordings. MAIN OUTCOME MEASURES: The changes in eye fundi, visual acuity, cataract changes in the lens, visual field constriction, and ERG responses were determined. RESULTS: Myopia, early cataracts, and highly abnormal ERG were typical for the GA subjects. The changes progressed rather uniformly with age. However, visual acuity, funduscopic findings, and visual fields showed great phenotypic variation. Despite the great interindividual variation, both eyes of each subject were always similarly affected. CONCLUSIONS: This study of 35 subjects with GA carrying a single mutation shows that the ophthalmologic symptoms and findings vary widely. The data also reveal that GA subjects are already affected by severe visual impairment in young adulthood. However, the diagnosis is often made very late.

Adolescent↗

A prospective study on sucrose consumption, visible plaque and caries in children from 3 to 6 years of age.

OBJECTIVES: As data on the association of sugar consumption and dental caries in the industrialized countries give mixed results, we prospectively studied this association in 135 healthy Finnish children (71 boys, 64 girls). METHODS: The dental health and oral hygiene of the children was first examined at the mean age (+/-SD) of 37.4 (+/-2.1) months and again at 73.7 (+/-2.6) months. On both occasions the parents were interviewed about the child's sweet intake and toothbrushing habits, and sucrose consumption was analyzed using 4-day food diaries. RESULTS: The proportion of children with caries experience, enamel and dentin lesions combined, increased from 16% to 40%. Daily sucrose intake of children who developed caries by 6 years of age, whether expressed as absolute (g) or as relative (E%) amounts, was already higher at 3 years of age than that of children who stayed caries-free (P<0.05 and P<0.03, respectively). Furthermore, children who used sweets more than once a week at 3 years of age, consumed more sucrose 3 years later (P<0.01) than those who used sweets once a week or less. The proportion of children with a combination of a sweet intake more than once a week and visible plaque, increased (P<0.05) during the follow-up. The risk ratio of children with the combined risk habit at 3 years of age to develop carious lesions by 6 years of age was 1.7 compared to the rest of the children (95% confidence interval 0.9-3.0). CONCLUSIONS: We conclude that the manifestation of dental caries at 6 years of age seemed to be associated with a higher daily sucrose intake that had started already at 3 years of age. Moreover, a combination of sweet intake more than once a week and visible plaque at 3 years of age may be predictive of dental health 3 years later.

Candy↗

Nutrition knowledge and food intake of seven-year-old children in an atherosclerosis prevention project with onset in infancy: the impact of child-targeted nutrition counselling given to the parents.

OBJECTIVE: To compare nutrition knowledge and food intake in 7-y-old intervention and control children in an atherosclerosis risk factor intervention trial after 6.5 y of nutrition counselling given to the parents. DESIGN, SUBJECTS AND METHODS: Intervention families in the Special Turku Coronary Risk Factor Intervention Project received child-oriented nutritional counselling one to three times a year since child's age of 7 months, aimed at reduced saturated fat and cholesterol intake. Children's nutrition knowledge was analysed in a time-restricted cohort of 70 seven-y-old (34 boys) intervention children and 70 control children (40 boys) with a picture identification test. For comparison, children's food intake was evaluated using scores developed for the project that reflected quality and quantity of fat and quantity of salt in children's two or three 4-day food diaries recorded between 5.5 and 7 y of age. RESULTS: Child-targeted nutrition counselling of the intervention families only slightly increased intervention children's knowledge of heart-healthy foods (42.6% vs 34.9% correct answers by the intervention and control children, P = 0.057). Only < or = 20% of the children were able to adequately justify their answers in the test. The food diaries of the intervention children comprised more foods low in saturated fat and high in unsaturated fat than those of the control children (57.1% vs 41.7% of the maximum score for low fat foods, P = 0.0001; 48.9% vs 37.7% for high unsaturated fat foods, P = 0.0009, respectively), but the intervention and control children consumed similar amounts of low-salt foods (P = 0.23). Nutrition knowledge and food use scores correlated poorly (r = -0.20-0.35). CONCLUSIONS: Child-targeted nutrition counselling repeatedly given to the parents during and after child's infancy strongly influenced food choice scores of the 5.5-7-y-old children but failed to influence children's salt intake or scores in a nutrition knowledge picture test.

Arteriosclerosis↗

Cytokine expression in unstimulated PBMC of children with type 1 diabetes and subjects positive for diabetes-associated autoantibodies.

The aim of this study was to evaluate possible changes in the circulating levels of interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor (TGF)-beta in association with the autoimmune process leading to type 1 diabetes. Expression levels of mRNAs specific for each cytokine were determined in peripheral blood mononuclear cells (PBMC) by a multiplex reverse transcription-polymerase chain reaction (RT-PCR) followed by hybridization reactions with lanthanide-labelled probes and detection by time-resolved fluorometry. Newly diagnosed diabetic children had lower levels of IFN-gamma, IL-4 and TGF-beta 1 signals compared to their age- and sex-matched controls (P < 0.02, P < 0.005 and P < 0.005, respectively) and also the autoantibody-positive subjects had significantly lower levels of IL-4 and TGF-beta 1 in comparison with their matched controls (P = 0.0013 and P = 0.012). No significant differences were observed when comparing matched pairs of diabetic children and autoantibody-positive subjects. Our results suggest a systemic bias towards reduced production of T-helper cell type 2 cytokines (IL-4 and TGF-beta 1) during the autoimmune process, but there was also a reduced level of IFN-gamma expression in the periphery at the onset of clinical diabetes.

Autoantibodies↗

Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations in young children (the STRIP Study). Special Turku Coronary Risk Factor Intervention Project.

Plant sterol supplementation reduces serum cholesterol concentration but may increase serum plant sterol concentrations, especially in children. We determined whether natural dietary plant sterols derived mainly from vegetable oil or margarine in early childhood affect serum concentrations of plant sterols (campesterol and sitosterol) and cholesterol precursor sterols (Delta-8 cholestenol, desmosterol, and lathosterol), reflecting endogenous cholesterol synthesis. We measured the serum sterol concentrations using gas liquid chromatography in 20 healthy 13-mo-old intervention children in a randomized, prospective study designed to decrease exposure of the children to known environmental atherosclerosis risk factors and in 20 control children. The diet of the intervention children was rich in plant sterols due to replacement of milk fat with vegetable fat, whereas the diet of the control children contained only small amounts of plant sterols. The intervention children consumed twice as much plant sterols as the control children (P < 0.001). Their serum concentrations of campesterol and sitosterol were 75% and 44% higher, respectively, than those in the control children (P < 0.001 for both), but serum cholesterol precursor sterol concentrations did not differ between the two groups. We conclude that doubling dietary plant sterol intake almost doubles serum plant sterol concentrations in 13-mo-old children, but has no effect on endogenous cholesterol synthesis. Relative intestinal absorption of natural plant sterols from the diet in early childhood is similar to that in adults.

Arteriosclerosis↗

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children.

Enterovirus infections are a potential environmental trigger of the autoimmune process leading to clinical type 1 diabetes. It has been suggested that the risk of virus-induced beta-cell damage might be connected with a defect in humoral immune responsiveness to enteroviruses. In the present study we assessed whether such a defect in IgG responsiveness to coxsackievirus B4 antigen existed in young children who developed diabetes-associated autoantibodies during prospective observation from birth until the age of 18 months. IgG levels and maturation of antibody avidity were analysed in 21 children with autoantibodies and 41 control children who had experienced an equal number of enterovirus infections and were additionally matched for age, sex and HLA-DQB1 risk alleles for type 1 diabetes but had not produced diabetes-associated autoantibodies. IgG levels to coxsackievirus B4 were high in cord serum reflecting the presence of maternal antibodies. Mean IgG levels gradually decreased but began to increase after the age of 6 months, showing no significant difference between autoantibody positive and control children. The avidity of antibodies was strong in cord serum and decreased gradually during the first year of life when maternal antibodies disappeared. The avidity indices, which varied considerably from child to child, did not differ between the autoantibody-positive and -negative subjects. In conclusion, our data suggest that children affected by a beta-cell damaging autoimmune process show normal responses to coxsackievirus B4 antigens.

Antibodies, Viral↗

Apolipoprotein E phenotype regulates cholesterol absorption in healthy 13-month-old children--The STRIP Study.

High serum cholesterol concentration is one of the key risk factors in development of atherosclerosis, which may begin early in life and later progress to symptomatic coronary heart disease. In adults, apoE polymorphism strongly influences cholesterol metabolism, as subjects with apoE 3/4 or 4/4 (collectively called apoE4) phenotype absorb cholesterol effectively and thus also have higher cholesterol absorption-reflecting plant sterol concentrations in serum than subjects with other apoE phenotypes. Because of the inverse correlation of absorption and synthesis of cholesterol, concentrations of cholesterol synthesis-reflecting serum cholesterol precursor sterols are lower in subjects with apoE4 than in subjects with other phenotypes. To analyze whether apoE phenotype affects cholesterol absorption and synthesis in early childhood, we measured serum plant sterol (campesterol and sitosterol) and cholesterol precursor sterol (desmosterol and lathosterol) concentrations in healthy 13-month old children using gas-liquid chromatography. The 36 study children were participants in a randomized prospective trial (the Special Turku Coronary Risk Factor Intervention Project) aimed at decreasing exposure of the children to environmental atherosclerosis risk factors. The 16 apoE4 children had 30% to 50% higher cholesterol-adjusted campesterol and sitosterol concentrations in serum than the 20 apoE 3/3 children (p = 0.002 and p = 0.02, respectively). The concentrations of cholesterol precursor sterols in serum did not differ between the two groups of children. We conclude that the young apoE4 children may absorb cholesterol and plant sterols more effectively than the children with apoE 3/3 phenotype without compensatory reduction in endogenous synthesis of cholesterol.

Apolipoproteins E↗

The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study.

Little is known about the timing of the etiological events and the preclinical process of type 1 diabetes during the first years of life in the general population. In this population-based prospective birth cohort study, the appearance of diabetes-associated autoantibodies as a sign of beta-cell autoimmunity and the development of type 1 diabetes were monitored from birth. Of 25,983 newborn infants, 2,448 genetically susceptible children were monitored for islet cell antibodies (ICA) at 3- to 6-month intervals. If an infant seroconverted to ICA positivity, all his/her samples were also analyzed for insulin autoantibodies (IAA), antibodies to the 65-kDa isoform of glutamic acid decarboxylase, and antibodies to the protein tyrosine phosphatase-related IA-2 molecule. Fifteen children of those who carried the high-risk genotype (2.7%) and 23 of those who carried the moderate-risk genotype (1.2%; P = 0.019) tested positive for ICA at least once. Among those who showed positivity for at least 2 antibodies during the observation period (25 of 38), IAA appeared as the first or among the first antibodies in 22 children (88%) and emerged earlier than the other antibodies (P < 0.019 or less). The first autoantibodies appeared in the majority of the children in the fall and winter (30 of 38 vs. 8 of 38 in the spring and summer, P < 0.001). These observations suggest that young children in the general population with a strong human-leukocyte-antigen-DQ-defined genetic risk of type 1 diabetes show signs of beta-cell autoimmunity proportionally more often than those with a moderate genetic risk. IAA emerge as the first detectable antibody more commonly than any other antibody specificity, implying that insulin may be the primary antigen in most cases of human type 1 diabetes associated with the DR4-DQB1*0302 haplotype. The seasonal variation in the emergence of the first signs of beta-cell autoimmunity suggests that infectious agents may play a role in the induction of such autoimmunity.

Autoantibodies↗

Induction of interferon-gamma and IL-4 production by mitogen and specific antigens in peripheral blood lymphocytes of Type 1 diabetes patients.

A functional imbalance in cytokine production resulting in dominance of Th1 over Th2 type response has been suggested to play a critical role in the pathogenesis of type 1 diabetes. In this study the cellular responses to pokeweed mitogen and a panel of specific antigens were analysed by measuring the production of IFN-gamma and IL-4 cytokines at the levels of mRNA expression (expression index=antigen/medium) and protein secretion in culture supernatants. Two enterovirus preparates were included due to the suggested significance of these viruses in the aetiology of type 1 diabetes. The study included 22 children with newly-diagnosed type 1 diabetes, 15 children with longer duration of disease and 20 healthy children. Comparisons were made between age- and sex-matched groups. Newly diagnosed diabetic patients had significantly higher IFN-gamma mRNA expression index (p<0.02) but also higher IL-4 mRNA expression index (p<0.05) in tetanus toxoid stimulated peripheral blood mononuclear cells compared to healthy controls. Also the diabetic patients studied 3-72 months after the diagnosis of type 1 diabetes showed a tendency to higher IFN-gamma mRNA expression index compared to controls (0.05<p<0.1). Enhanced mitogen-stimulated IFN-gamma mRNA expression index was observed in children with newly-diagnosed type 1 diabetes when compared to subjects with longer duration of diabetes (p<0.05). No significant differences were observed in IFN-gamma produced into the culture supernatants. In conclusion, imbalance in both IFN-gamma and IL-4 mRNA levels was demonstrated between diabetic patients and healthy subjects.

Adolescent↗

Connections between parental eating attitudes and children's meagre eating: questionnaire findings.

UNLABELLED: This study investigated whether young children's problematic, meagre eating is associated with the eating habits and attitudes of the parents. The subjects, 397 children, their mothers (n = 397) and fathers (n = 375) participated in a prospective atherosclerosis risk-factor intervention trial. The parents evaluated their own eating behaviour in questionnaires when their child was 13 mo old. The children's eating problems were recorded by the mothers when the child was 13 mo old, and by both parents when the child was 5 y old. At both ages, the weight and height of the children were measured. Problematic or maladaptive eating habits of the children were found to be connected to those of their parents. The mother's poor ability to enjoy eating, high tendency to snack and low tendency to eat only when hungry, as well as the father's difficulty in maintaining ideal weight significantly predicted persistent problems of meagre eating in their children. CONCLUSION: The study suggests that the eating habits and attitudes of parents may be reflected in the eating behaviour of young children.

Adult↗

Prospective, randomized, infancy-onset trial of the effects of a low-saturated-fat, low-cholesterol diet on serum lipids and lipoproteins before school age: The Special Turku Coronary Risk Factor Intervention Project (STRIP).

BACKGROUND: We showed previously that repeated dietary counseling during the first 3 years of life reduces the concentration of serum nonfasting cholesterol. We have now extended the study to children 5 years of age and analyzed fasting blood samples, enabling LDL cholesterol calculations for the first time. METHODS AND RESULTS: Families of 7-month-old infants (n=1062) were randomized to a control group (n=522) or an intervention group (n=540) that received individualized dietary counseling with the aims of a fat intake of 30% to 35% of daily energy, a saturated/monounsaturated/polyunsaturated fatty acid ratio of 1:1:1, and a cholesterol intake of <200 mg/d. Nutrient intakes were studied biannually, nonfasting serum lipid values were studied annually, and fasting values were studied at 5 years of age. The intervention children always had lower intakes of saturated fat and cholesterol than the control children. The intervention boys had 0.39 mmol/L (P:<0.0001) lower mean serum cholesterol values than the control boys between 13 and 60 months of age, but among girls, the difference was of marginal significance (0.15 mmol/L, P:=0.052). Five-year-old intervention boys had 9% lower mean serum LDL cholesterol concentrations than the control boys (P:=0.0002; 95% CI, -0.39 to -0.12 mmol/L), whereas no difference was observed in girls. In both sexes, serum triglyceride concentrations were similar in the 2 groups. CONCLUSIONS: The restriction of saturated fat and cholesterol intake by repeated, individualized dietary counseling since infancy resulted in lower serum total and LDL cholesterol concentrations at 5 years of age. However, the effect was significant only in boys.

Age of Onset↗

Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI).

Lysinuric protein intolerance (LPI; MIM 222700) is an autosomal recessive disorder characterized by defective transport of the cationic amino acids lysine, arginine and ornithine at the basolateral membrane of the polar epithelial cells in the intestine and renal tubules, and by hyperammonemia after high-protein meals. LPI is caused by mutations in the SLC7A7 (solute carrier family 7, member 7) gene encoding y(+)LAT-1 (y(+)L amino acid transporter-1), which co-induces together with 4F2 heavy chain (4F2hc) system y(+)L in Xenopus oocytes. All Finnish LPI patients share the same founder mutation 1181-2A-->T (LPI(Fin)) not found in LPI patients elsewhere. Mutation screening of 20 non-Finnish LPI patients revealed 10 novel mutations: four deletions, two missense mutations, two nonsense mutations, a splice site mutation and a tandem duplication. Five LPI mutations (L334R, G54V, 1291delCTTT, 1548delC and LPI(Fin)) were studied functionally. All mutant proteins failed to co-induce amino acid transport activity when expressed with 4F2hc in Xenopus oocytes. Immunostaining experiments revealed that frameshift mutants 1291delCTTT, 1548delC and LPI(Fin)remained intracellular on expression with 4F2hc. In contrast, the missense mutants L334R and G54V reached the oocyte plasma membrane when co-expressed with 4F2hc, demonstrating that they are transport-inactivating mutations. This finding, together with the strong degree of conservation among all members of this family of amino acid transporters, indicates that residues L334 and G54 play a crucial role in the function of the y(+)LAT-1 transporter.

Amino Acid Metabolism, Inborn Errors↗

Apolipoprotein E4 phenotype increases non-fasting serum triglyceride concentration in infants - the STRIP study.

As genetically determined apolipoprotein E (apo E) phenotypes influence serum cholesterol concentration, we analysed whether serum triglyceride values are also affected by the apo E phenotypes in infants. Non-fasting serum triglyceride values were measured in 7- and 13-month-old participants in the STRIP project, a randomised, prospective trial aimed at reducing children's exposure to known atherosclerosis risk factors (n=1062). The mean+/-S.D. non-fasting serum triglyceride concentrations in 7-month-old infants with apo E4/4 (n=36), E3/4 (n=209), E3/3 (n=412), and E2/3 (n=66) were 2. 05+/-1.24, 1.81+/-0.90, 1.63+/-0.90, and 1.71+/-0.83 mmol/l, respectively. Triglyceride concentrations were higher in infants with apo E4/4 or 3/4 than in those with apo E3/3 (P-value for difference 0.01 and 0.009, respectively). The apo E phenotype similarly influenced non-fasting serum triglyceride concentrations at the age of 13 months. The differences in serum triglyceride values in apo E4(+) infants (apo E3/4 and 4/4 infants combined) and apo E4(-) infants (apo E2/3 and 3/3 infants combined) occurred independently of the relative weight of the infant, milk type used at 7 months of age (breast milk or formula), and time elapsed from the previous meal. To conclude, apo E phenotypes regulate non-fasting serum triglyceride values in healthy infants. Apo E3/4 and apo E4/4 predispose infants to higher values than apo E3/3 phenotype, suggesting that the varepsilon4 allele may increase atherosclerosis risk also via it's effect on postprandial triglyceride metabolism.

Apolipoprotein E4↗

Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project.

OBJECTIVE: To investigate cholesterol-lowering efficacy and safety of plant stanol ester margarine in healthy 6-year-old children already consuming a low-saturated-fat, low-cholesterol diet. STUDY DESIGN: Eighty-one intervention children from the STRIP project, a randomized prospective trial aimed at reducing exposure of young children to the known environmental atherosclerosis risk factors, were recruited to this double-blind crossover study at 6 years of age. In randomized order the families were advised to replace daily 20 g of the child's dietary fat intake with plant stanol ester margarine or control margarine for 3 months. The washout period lasted 6 weeks. Statistical analysis was performed according to intention-to-treat principle with analysis of variance for crossover design. RESULTS: The mean daily plant stanol ester margarine consumption was 18.2 g (1.5 g plant stanol). The well-tolerated plant stanol ester margarine reduced serum total and low-density lipoprotein cholesterol concentrations by 5.4% and 7.5%, respectively (P =.0001 for both). The serum high-density lipoprotein cholesterol and triglyceride concentrations and alpha-tocopherol to low-density lipoprotein cholesterol ratio remained unchanged. The serum beta-carotene to low-density lipoprotein cholesterol ratio decreased by 19% (P =.003). CONCLUSION: Plant stanol ester margarine significantly diminishes serum total and low-density lipoprotein cholesterol concentration without adverse clinical effects in healthy children who already consume a low-saturated-fat, low-cholesterol diet but decreases the serum beta-carotene to low-density lipoprotein cholesterol ratio.

Child↗