Fats in Foods: Current Evidence for Dietary Advice.

Current discussion of the importance of food fats in the risk of coronary heart disease (CHD) often suffers from preconceptions, misunderstandings, insufficient knowledge, and selective reasoning. As a result, the sustained controversy about dietary fat recommendations can be contradictory and confusing. To clarify some of these issues, the International Expert Movement to Improve Dietary Fat Quality in cooperation with the International Union of Nutritional Sciences (IUNS) organized a symposium at the 21st meeting of the IUNS, October 17, 2017, Buenos Aires, Argentina, to summarize the key scientific evidence underlying the controversy on the relationship between the saturated and unsaturated fat consumption and CHD risk. Presenters also discussed, using examples, the rationale for and implications of the partial replacement of foods rich in saturated fats by those rich in unsaturated fats. Presentations included strategies to fit healthier fats into meals. This report summarizes the symposium presentations.

Saturated Fat Consumption and Risk of Coronary Heart Disease and Ischemic Stroke: A Science Update.

At a workshop to update the science linking saturated fatty acid (SAFA) consumption with the risk of coronary heart disease (CHD) and ischemic stroke, invited participants presented data on the consumption and bioavailability of SAFA and their functions in the body and food technology. Epidemiological methods and outcomes were related to the association between SAFA consumption and disease events and mortality. Participants reviewed the effects of SAFA on CHD, causal risk factors, and surrogate risk markers. Higher intakes of SAFA were not associated with higher risks of CHD or stroke apparently, but studies did not take macronutrient replacement into account. Replacing SAFA by cis-polyunsaturated fatty acids was associated with significant CHD risk reduction, which was confirmed by randomized controlled trials. SAFA reduction had little direct effect on stroke risk. Cohort studies suggest that the food matrix and source of SAFA have important health effects.

Progressing Insights into the Role of Dietary Fats in the Prevention of Cardiovascular Disease.

Dietary fats have important effects on the risk of cardiovascular disease (CVD). Abundant evidence shows that partial replacement of saturated fatty acids (SAFA) with unsaturated fatty acids improves the blood lipid and lipoprotein profile and reduces the risk of coronary heart disease (CHD). Low-fat diets high in refined carbohydrates and sugar are not effective. Very long-chain polyunsaturated n-3 or omega-3 fatty acids (n-3 VLCPUFA) present in fish have multiple beneficial metabolic effects, and regular intake of fatty fish is associated with lower risks of fatal CHD and stroke. Food-based guidelines on dietary fats recommend limiting the consumption of animal fats high in SAFA, using vegetable oils high in monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and eating fatty fish. These recommendations are part of a healthy eating pattern that also includes ample intake of plant-based foods rich in fiber and limited sugar and salt.

Potential programming of selected cardiometabolic risk factors at childhood by maternal polyunsaturated fatty acid availability in the MEFAB cohort.

BACKGROUND: Increasing evidence suggests that long-chain polyunsaturated fatty acid (LCPUFA) availability in utero could program later health. OBJECTIVE: The objective of the study was to explore whether prenatal LCPUFA availability could be involved in programming cardiometabolic disease risk at childhood. METHODS: Data of 242 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort were used. Multi-variable linear regression analysis was applied to identify associations between maternal LCPUFA concentrations around weeks 11, 22 and 32 of pregnancy and at time of delivery and cardiometabolic risk factors of their children (glucose metabolism, blood lipids, and blood pressure) at age 7. RESULTS: Maternal eicosapentaenoic acid (20:5n-3) at week 11 of pregnancy was negatively associated with children׳s glucose (B=-0.34mmol/L; 95% CI: -0.56, -0.12). Positive associations were found between maternal linoleic acid (18:2n-6) at time of delivery and children׳s proinsulin (B=0.25pmol/L; 95% CI: 0.08, 0.41); maternal 3-docosapentaenoic acid (22:5n-3) at week 11 and children׳s total cholesterol (B=1.23mmol/L; 95% CI: 0.45, 2.01) and low-density-lipoprotein cholesterol (B=1.12mmol/L; 95% CI: 0.42, 1.82); and maternal osbond acid (22:5n-6) at week 22 and tetracosadienoic acid (24:2n-6) at week 32 and children׳s diastolic blood pressure (B=16.86mmHg; 95% CI: 7.63, 26.08 and B=17.75mmHg; 95% CI: 6.37, 29.94, respectively). CONCLUSION: Our findings suggest that maternal omega-6 (n-6) fatty acids may be of particular importance in relation to children׳s glucose metabolism and blood pressure, whereas omega-3 (n-3) fatty acids seem particularly related to blood lipids at childhood. In general, the strength of the associations appeared stronger with fatty acid concentrations in early pregnancy compared to late pregnancy.

Association between polyunsaturated fatty acid concentrations in maternal plasma phospholipids during pregnancy and offspring adiposity at age 7: the MEFAB cohort.

Prenatal polyunsaturated fatty acid (PUFA) concentrations may be involved in the prenatal programming of adiposity. In this study we therefore explored the association between maternal PUFA concentrations, measured up to four times during pregnancy, and offspring adiposity at age 7 in 234 mother-child pairs of the Maastricht Essential Fatty Acid Birth cohort. Only dihomo-gamma-linolenic acid (DGLA, an n-6 fatty acid) concentration was associated with adiposity: per standard deviation increase in relative DGLA concentration, BMI increased by 0.44kg/m(2) (CI95: 0.16, 0.72), sum of skinfolds increased by 3.41mm (CI95: 1.88, 4.95), waist circumference increased by 1.09cm (CI95: 0.40, 1.78), and plasma leptin concentration increased by 0.66µg/l (CI95: 0.20, 1.11). In conclusion, maternal DGLA throughout gestation was associated with increased BMI and some additional measures of adiposity at age 7. This suggests that maternal DGLA might play a role in or reflect the prenatal programming of adiposity.

The association between interpregnancy interval and birth weight: what is the role of maternal polyunsaturated fatty acid status?

BACKGROUND: The objective of this study was to evaluate the mediating role of maternal early pregnancy plasma levels of long chain polyunsaturated fatty acids (LCPUFAs) in the association of interpregnancy interval (IPI) with birth weight and smallness for gestational age (SGA) at birth. METHODS: We analysed a subsample of the Amsterdam Born Children and their Development (ABCD) cohort, comprising 1,659 parous pregnant women recruited between January 2003 and March 2004. We used linear and logistic regression to evaluate the associations between fatty acid status, interpregnancy interval and pregnancy outcome. RESULTS: Low plasma phospholipids concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DGLA), and high concentrations of arachidonic acid (AA) during early pregnancy were associated with reduced birth weight and/or an increased risk of SGA. Short IPIs (< 6 months, with 18-23 months as a reference) were associated with a mean decrease of 207.6 g (SE: ± 73.1) in birth weight (p = 0.005) and a twofold increased risk of SGA (OR: 2.05; CI: 0.93-4.51; p = 0.074). Adjustment for maternal fatty acid concentrations did not affect these results to any meaningful extent. CONCLUSIONS: Despite the observed association of maternal early pregnancy LCPUFA status with birth weight and SGA, our study provides no evidence for the existence of an important role of maternal EPA, DHA, DGLA or AA in the association of short interpregnancy intervals with birth weight and SGA.

Body mass index and cognitive ability of young children.

OBJECTIVE: This study prospectively assessed the association between body mass index (BMI) and cognitive ability of young children, while accounting for confounding factors. METHODS: The study included 236 children born between 1990 and 1994 participating in a Dutch birth cohort study. Anthropometric data of the children at birth, 4, and 7 years of age were collected from growth records or measured at the Academic Hospital of Maastricht. The Kaufman Assessment Battery for Children (K-ABC) was used to assess cognitive ability at 7 years of age. The association between BMI and cognitive ability was investigated using univariate and multivariate linear regression analyses, including various covariates. RESULTS: Although the results suggest that cognitive ability at 7 years of age decreased with increasing BMI at 4 years and 7 years of age, this association was not significant in any performed analysis. Multivariate analyses showed that maternal intelligence was strongly associated with all scales of the K-ABC as a significant covariate. Adjusting analyses for physical fitness of the child, maternal education, maternal pre-pregnancy BMI, maternal smoking during pregnancy, and birth weight did not change the results. CONCLUSION: This study found no evidence for an association between BMI and cognitive ability of school-aged children.

ISSFAL 2010 dinner debate: healthy fats for healthy hearts - annotated report of a scientific discussion.

BACKGROUND/AIMS: The importance of reducing saturated fatty acid intake to prevent cardiovascular disease and recommended intakes for omega-6 polyunsaturated fatty acids (PUFAs) are controversial. Therefore, experts debated these topics at the biennial meeting of the International Society for the Study of Fatty Acids and Lipids (ISSFAL), in May 2010. METHODS: Debate transcripts, debaters' and discussants' reviews and literature citations were the basis of this report. RESULTS: Participants agreed that saturates per se are not 'bad', but that dietary recommendations should emphasize the substitution of unsaturates for part of the saturates. Evidence supporting omega-6 PUFA intakes of 5 to 10% is mixed; some interpret the overall data from diverse studies as consistent with a reduction in the risk of cardiovascular mortality and events. Others assert that randomized controlled trial data suggest that higher intakes of omega-6 PUFAs are not associated with lower risk of heart disease, or may even increase it. CONCLUSIONS: All agreed that a 5-year randomized controlled trial comparing the effects of historically low (2%) with currently high (7.5%) linoleic acid intakes on cardiac endpoints would address the knowledge gap about the effects of different omega-6 PUFA intakes on the risk of heart disease.

Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in children - a workshop report.

There is controversy whether children should have a dietary supply of preformed long-chain polyunsaturated n-3 fatty acids EPA and DHA. The aims of the workshop were to review evidence for a possible benefit of a preformed EPA and/or DHA supply, of data required to set desirable intakes for children aged 2-12 years, and of research priorities. The authors concluded that EPA and DHA intakes per kg body weight may often be low in 2- to 12-year-old children, relative to intakes per kg body weight of breast-fed infants and adult intakes, but reliable data are scarce. Little information is available that increasing dietary intakes of EPA or DHA in children has benefits to physical or mental function or other health endpoints. Studies addressing EPA and DHA intakes and tissue status among groups of children with different dietary habits, and measures of relevant development and health endpoints, are needed for developing potential advice on desirable intakes of EPA and/or DHA in children. At this time it appears prudent to advise that dietary intakes in childhood are consistent with future eating patterns supporting adult health, such as prevention of metabolic disorders and CVD, supporting immune function, and reproductive health. In conclusion, the available information relating dietary EPA and DHA intakes in children aged 2-12 years to growth, development and health is insufficient to derive dietary intake recommendations for EPA and DHA. Adequately designed studies addressing dietary intakes, measures of status and relevant functional or health effects across this age group are needed.

Aspects of fetal learning and memory.

Ninety-three pregnant women were recruited to assess fetal learning and memory, based on habituation to repeated vibroacoustic stimulation of fetuses of 30-38 weeks gestational age (GA). Each habituation test was repeated 10 min later to estimate the fetal short-term memory. For Groups 30-36, both measurements were replicated in a second session at 38 weeks GA for the assessment of fetal long-term memory. Within the time frame considered, fetal learning appeared GA independent. Furthermore, fetuses were observed to have a short-term (10-min) memory from at least 30 weeks GA onward, which also appeared independent of fetal age. In addition, results indicated that 34-week-old fetuses are able to store information and retrieve it 4 weeks later.

Age dependence of plasma phospholipid fatty acid levels: potential role of linoleic acid in the age-associated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations.

Limited information is available with respect to the association between age and the plasma phospholipid fatty acid profile. Therefore we investigated the association between plasma phospholipid fatty acid status and age after correction for sex, smoking, alcohol use, BMI and fish intake. Plasma phospholipid fatty acid composition was measured and information on fish intake and other potential covariates was collected in 234 participants of the Maastricht Aging Study. The participants were healthy individuals of both sexes with an age range between 36 and 88 years. Hierarchical linear regression analyses were applied to study the relationship between age and fatty acid concentrations. After correction for fish consumption and other relevant covariates, a significant positive relationship was observed between age of the subjects and their plasma phospholipid concentrations of DHA (22 : 6n-3, P = 0.006) and EPA (20 : 5n-3; P = 0.001). Age contributed 2.3 and 3.9 % to the amount of explained variance, respectively. The higher n-3 long-chain PUFA status at advanced age was confirmed by lower concentrations of their putative 'shortage marker' Osbond acid (ObA, 22 : 5n-6; P = 0.022 for the relationship with age after correction for covariates and fish intake, R2 0.022). Concentrations of linoleic acid (LA; 18 : 2n-6) were negatively associated with age (P < 0.001; R2 0.061). In conclusion, DHA and EPA concentrations appeared to be higher in older age groups, partly because of a higher fish intake and partly because of another age-associated mechanism, possibly involving the well-known competition with LA.

Associations between term birth dimensions and prenatal exposure to essential and trans fatty acids.

BACKGROUND: Certain essential long-chain polyunsaturated fatty acids (LCPUFAs) are considered important for fetal growth and brain development, whereas industrial trans fatty acids (mainly 18:1trans) have been associated with negative effects. The aim of this study was to investigate associations between term birth dimensions and prenatal exposure to some of these fatty acids, reflected by neonatal fatty acid concentrations at birth. METHODS: Data of up to 700 infant-mother pairs from the Maastricht Essential Fatty Acid Birth Cohort were used for the present study. Unadjusted and multivariable-adjusted linear regression analyses were performed to investigate associations between birth weight, birth length or head circumference and relative concentrations of docosahexaenoic acid (DHA), arachidonic acid (AA), dihomo-gamma-linolenic acid (DGLA) and trans-octadecenoic acids (18:1t) measured in phospholipids of the walls of umbilical arteries and veins, and in umbilical cord plasma and erythrocytes. RESULTS: After optimal adjustment, a significant negative association was observed between birth weight and umbilical plasma DHA concentrations. Negative associations were also found for AA concentrations measured in umbilical plasma and in arterial and venous vessel walls. Birth length was negatively related to arterial vessel wall AA concentrations only. A significant negative association was observed for the relationship between 18:1t in cord erythrocytes and birth weight. For DGLA no significant associations were observed. CONCLUSIONS: Results seem to preclude a role of DHA and AA as growth factors per se. Their negative relationships with birth dimensions may result from a limited maternal-fetal LCPUFA transfer capacity. Potential effects of 18:1t and DGLA on birth dimensions are probably small or non-existing.

Prenatal arachidonic acid exposure and selected immune-related variables in childhood.

Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childhood. In 280 children aged 7 years, atopy, lung function and plasma inflammation markers were measured and their relationships with early AA exposure were studied by linear and logistic regression analyses. AA exposure was deduced from AA concentrations in plasma phospholipids of the mothers collected at several time points during pregnancy and at delivery, and in umbilical cord plasma and arterial and venous wall phospholipids. In unadjusted regression analyses, significant positive associations were observed between maternal AA concentrations at 16 and 32 weeks of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline after maximal physical exercise and plasma fibrinogen concentrations of their children, respectively. However, after correction for relevant covariables, only trends remained. A significant negative relationship was observed between AA concentrations in cord plasma (reflecting prenatal AA exposure) and the average daily amplitude of peak expiratory flow at rest, which lost significance after appropriate adjustment. Because of these few, weak and inconsistent relationships, a major impact of early-life exposure to AA on atopy, lung function and selected plasma inflammation markers of children at 7 years of age seems unlikely.

Associations between neonatal birth dimensions and maternal essential and trans fatty acid contents during pregnancy and at delivery.

Since birth dimensions have prognostic potential for later development and health, possible associations between neonatal birth dimensions and selected maternal plasma fatty acid contents were investigated, using data from 782 mother-infant pairs of the Maastricht Essential Fatty Acid Birth cohort. Unadjusted and multivariable-adjusted regression analyses were applied to study the associations between birth weight, birth length or head circumference and the relative contents of DHA, arachidonic acid (AA), dihomo-gamma-linolenic acid (DGLA) and 18 : 1trans (18 : 1t) in maternal plasma phospholipids sampled during early, middle and late pregnancies, and at delivery. Where appropriate, corrections were made for relevant covariables. Significant 'positive' associations were observed between maternal DHA contents (especially early in pregnancy) and birth weight (B = 52.10 g, 95 % CI 20.40, 83.80) and head circumference (B = 0.223 cm, 95 % CI 0.074, 0.372). AA contents at late pregnancy were 'negatively' associated with birth weight (B = - 44.25 g, 95 % CI - 68.33, - 20.16) and birth length (B = - 0.200 cm, 95 % CI - 0.335, - 0.065). Significant 'negative' associations were also observed for AA contents at delivery and birth weight (B = - 27.08 g, 95 % CI - 47.11, - 7.056) and birth length (B = - 0.207 cm, 95 % CI - 0.330, - 0.084). Maternal DGLA contents at delivery were also significantly 'negatively' associated with neonatal birth weight (B = - 85.76 g, 95 % CI - 130.9, - 40.61) and birth length (B = - 0.413 cm, 95 % CI - 0.680, - 0.146). No significant associations were observed for maternal 18 : 1t contents. We conclude that during early pregnancy, maternal DHA content may programme fetal growth in a positive way. Maternal AA and DGLA in late pregnancy might be involved in fetal growth limitation.

Ethnic differences in early pregnancy maternal n-3 and n-6 fatty acid concentrations: an explorative analysis.

Ethnicity-related differences in maternal n-3 and n-6 fatty acid status may be relevant to ethnic disparities in birth outcomes observed worldwide. The present study explored differences in early pregnancy n-3 and n-6 fatty acid composition of maternal plasma phospholipids between Dutch and ethnic minority pregnant women in Amsterdam, the Netherlands, with a focus on the major functional fatty acids EPA (20 : 5n-3), DHA (22 : 6n-3), dihomo-gamma-linolenic acid (DGLA; 20 : 3n-6) and arachidonic acid (AA; 20 : 4n-6). Data were derived from the Amsterdam Born Children and their Development (ABCD) cohort (inclusion January 2003 to March 2004). Compared with Dutch women (n 2443), Surinamese (n 286), Antillean (n 63), Turkish (n 167) and Moroccan (n 241) women had generally lower proportions of n-3 fatty acids (expressed as percentage of total fatty acids) but higher proportions of n-6 fatty acids (general linear model; P < 0.001). Ghanaian women (n 54) had higher proportions of EPA and DHA, but generally lower proportions of n-6 fatty acids (P < 0.001). Differences were most pronounced in Turkish and Ghanaian women, who, by means of a simple questionnaire, reported the lowest and highest fish consumption respectively. Adjustment for fish intake, however, hardly attenuated the differences in relative EPA, DHA, DGLA and AA concentrations between the various ethnic groups. Given the limitations of this observational study, further research into the ethnicity-related differences in maternal n-3 and n-6 fatty acid patterns is warranted, particularly to elucidate the explanatory role of fatty acid intake v. metabolic differences.

Dietary arachidonic acid dose-dependently increases the arachidonic acid concentration in human milk.

Lactation hampers normalization of the maternal arachidonic acid (AA) status, which is reduced after pregnancy and can further decline by the presently recommended increased consumption of (n-3) long-chain PUFA [(n-3) LCPUFA]. This may be unfavorable for breast-fed infants, because they also require an optimum supply of (n-6) LCPUFA. We therefore investigated the LCPUFA responses in nursing mothers upon increased consumption of AA and (n-3) LCPUFA. In a parallel, double-blind, controlled trial, lactating women received for 8 wk no extra LCPUFA (control group, n = 8), 200 (low AA group, n = 9), or 400 (high AA group, n = 8) mg/d AA in combination with (n-3) LCPUFA [320 mg/d docosahexaenoic acid (DHA), 80 mg/d eicosapentaenoic acid, and 80 mg/d other (n-3) fatty acids], or this dose of (n-3) LCPUFA alone [DHA + eicosapentaenoic acid group, n = 8]. Relative concentrations of AA, DHA, and sums of (n-6) and (n-3) LCPUFA were measured in milk total lipids (TL) and erythrocyte phospholipids (PL) after 2 and 8 wk and changes were compared by ANCOVA. The combined consumption of AA and (n-3) LCPUFA caused dose-dependent elevations of AA and total (n-6) LCPUFA concentrations in milk TL and did not significantly affect the DHA and total (n-3) LCPUFA increases caused by (n-3) LCPUFA supplementation only. This latter treatment did not significantly affect breast milk AA and total (n-6) LCPUFA concentrations. AA and DHA concentrations in milk TL and their changes were strongly and positively correlated with their corresponding values in erythrocyte PL (r(2) = 0.27-0.50; P

Maternal n-3, n-6, and trans fatty acid profile early in pregnancy and term birth weight: a prospective cohort study.

BACKGROUND: Maternal n-3, n-6, and trans fatty acids are claimed to affect fetal growth, yet evidence is limited. OBJECTIVE: We investigated the association between maternal n-3, n-6, and trans fatty acids measured early in pregnancy and fetal growth. DESIGN: Amsterdam pregnant women (n = 12 373) were invited to complete a questionnaire (response 67%) and donate blood around the 12th pregnancy week for nutrient analysis. For 4336 women, fatty acid concentrations were measured in plasma phospholipids (gas-liquid chromatography). Associations of these concentrations with birth weight and small-for-gestational-age (SGA) risk were analyzed (liveborn singleton term deliveries, n = 3704). RESULTS: Low concentrations of individual n-3 fatty acids and 20:3n-6, the precursor of arachidonic acid (20:4n-6), but high concentrations of the other n-6 fatty acids and the main dietary trans fatty acid (18:1n-9t) were associated with lower birth weight (estimated difference in univariate analysis -52 to -172 g for extreme quintile compared with middle quintile). In general, SGA risk increased accordingly. After adjustment for physiologic, lifestyle-related and sociodemographic factors, low concentrations of most n-3 fatty acids and 20:3n-6 and high concentrations of 20:4n-6 remained associated with lower birth weight (-52 to -57 g), higher SGA risk, or both (odds ratios: 1.38-1.50). Infants of the 7% of women with the most adverse fatty acid profile were on average 125 g lighter and twice as likely to be small for gestational age. CONCLUSION: An adverse maternal fatty acid profile early in pregnancy is associated with reduced fetal growth, which, if confirmed, gives perspective for the dietary prevention of lower birth weight.

Co-supplementation of healthy women with fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations.

Fish oil supplementation during pregnancy not only improves maternal and neonatal DHA status, but often reduces gamma-linolenic acid (GLA), dihomo-GLA (DGLA), and arachidonic acid (ARA) levels also, which may compromise foetal and infant development. The present study investigated the effects of a fish oil/evening primrose oil (FSO/EPO) blend (456 mg DHA/d and 353 mg GLA/d) compared to a placebo (mixture of habitual dietary fatty acids) on the plasma fatty acid (FA) composition in two groups of twenty non-pregnant women using a randomised, double-blind, placebo-controlled parallel design. FA were quantified in plasma total lipids, phospholipids, cholesterol esters, and TAG at weeks 0, 4, 6 and 8. After 8 weeks of intervention, percentage changes from baseline values of plasma total lipid FA were significantly different between FSO/EPO and placebo for GLA (+49.9 % v. +2.1 %, means), DGLA (+13.8 % v. +0.7 %) and DHA (+59.6 % v. +5.5 %), while there was no significant difference for ARA ( - 2.2 % v. - 5.9 %). FA changes were largely comparable between plasma lipid fractions. In both groups three subjects reported mild adverse effects. As compared with placebo, FSO/EPO supplementation did not result in any physiologically relevant changes of safety parameters (blood cell count, liver enzymes). In women of childbearing age the tested FSO/EPO blend was well tolerated and appears safe. It increases plasma GLA, DGLA, and DHA levels without impairing ARA status. These data provide a basis for testing this FSO/EPO blend in pregnant women for its effects on maternal and neonatal FA status and infant development.

Insulin resistance, physical fitness, body composition and leptin concentration in 7-8 year-old children.

The aim of this study was to investigate the association between insulin resistance and physical fitness, leptin concentration, body composition and family history for diabetes in non-selected young children. Physical fitness, fasting plasma glucose, insulin and leptin concentrations, anthropometric characteristics and medical history were available in two hundred and fifty-seven 7-year-old Dutch children. Correlations with the homeostasis model assessment (HOMA) index for insulin resistance were studied. A multiple regression model was calculated for HOMA. The differences between children with or without a family history for diabetes were not significant. Boys scored higher on glucose concentration and aerobic fitness and lower on sum of skin folds and leptin concentration (p<.05). After adjustment for sum of skin folds, HOMA was significantly associated with leptin in both genders (boys r=.184 p=.031; girls r=.430 p=.000). The association between physical fitness and HOMA was mediated by sum of skin folds. The associations were stronger in girls than in boys. In the regression model (R(2)=.205) the leptin concentration was the only significant predictor for HOMA. The influence of family history for diabetes on insulin resistance is shown as a trend at this age. Our findings suggest that plasma leptin concentration is independently associated with the development of insulin resistance in a non-selected prepubertal population. The association of physical fitness with insulin resistance seems to be mediated by the sum of skin folds.