Effect of Dietary Counseling on a Comprehensive Metabolic Profile from Childhood to Adulthood

Lehtovirta, Miia; Pahkala, Katja; Niinikoski, Harri; Kangas, Antti J.; Soininen, Pasi; Lagström, Hanna; Viikari, Jorma; Rönnemaa, Tapani; Jula, Antti; Ala‐Korpela, Mika; Würtz, Peter; Raitakari, Olli T.

doi:10.1016/j.jpeds.2017.11.057

Cited by 25 publications

(27 citation statements)

References 39 publications

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“…These fatty acids are likely reflective of both dietary composition and endogenous metabolism (31). Dietary counseling aiming to replace saturated fat with unsaturated fat in the diet, in accordance with Nordic dietary recommendations, has been shown to decrease circulating MUFA and increase circulating omega-3 and omega-6 levels (32). If these fatty acids play a causal role in the development of type 2 diabetes, then our results suggest that interventions modifying dietary fatty acid composition could be effective in prevention.…”

Section: Discussionmentioning

confidence: 67%

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Ahola‐Olli

Mustelin

Kettunen

et al. 2019

Preprint

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Objective: Advances in metabolomics now allow high-throughput biomarker profiling of large population studies. We aimed to identify circulating metabolic biomarkers predictive of type 2 diabetes in young adults.Methods: Nuclear magnetic resonance metabolomics was used to quantify 229 metabolic measures in 11,896 individuals from four Finnish cohorts (mean age 33 years, range 24-45). Associations between baseline metabolites and risk of type 2 diabetes onset during 8-15 years of follow-up (392 incident cases) were assessed by logistic regression adjusted for sex, age, body mass index, and fasting glucose.Results: Out of 229 metabolic measures, 113 were associated with incident diabetes in metaanalysis of the four cohorts (P<0.0009; odds ratios per 1-SD: 0.59-1.50). Among the strongest predictors of diabetes risk were branched-chained and aromatic amino acids (odds ratios 1.31-1.33), triglyceride fractions within the largest very-low-density lipoprotein particles (VLDL; odds ratios 1.33-1.50)), as well as linoleic omega-6 fatty acids (odds ratio 0.75) and free cholesterol in large high-density lipoprotein particles (HDL; odds ratio 0.59). A biomarker score comprised of phenylalanine, free cholesterol in large HDL, and the ratio of cholesteryl esters to total lipids in large VLDL was predictive of the risk for future diabetes in an independent validation cohort (odds ratio 10.1 [95% confidence intervals 4.2-24.1] comparing individuals in upper vs lower fifth of biomarker score). Adjustment for routine lipids and insulin attenuated the odds ratio to 5.8 [2.2-15.1]. Conclusions:Metabolic aberrations across multiple molecular pathways are predictive of the longterm risk of type 2 diabetes in young adults. Comprehensive metabolic profiling may potentially help targeting preventive interventions for young asymptomatic individuals at increased risk for type 2 diabetes.

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Section: Discussionmentioning

confidence: 67%

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Ahola‐Olli

Mustelin

Kettunen

et al. 2019

Preprint

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“…The circulating fatty acid biomarkers are reflective of both dietary composition and endogenous metabolism [32]. Dietary counselling aiming to replace saturated fat with unsaturated fat in the diet, in accordance with Nordic dietary recommendations, has been shown to decrease circulating MUFA and increase circulating n -3 and n -6 levels [33]. If these fatty acids play a causal role in the development of type 2 diabetes, then our results suggest that interventions modifying the circulating fatty acid composition could be effective in prevention.…”

Section: Discussionmentioning

confidence: 99%

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Ahola‐Olli

Mustelin

Kalimeri³

et al. 2019

Diabetologia

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137

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Aims/hypothesisMetabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults.MethodsNMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up.ResultsOut of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31–1.33) and triacylglycerol within VLDL particles (OR 1.33–1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years).Conclusions/interpretationMetabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.Electronic supplementary materialThe online version of this article (10.1007/s00125-019-05001-w) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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“…The favorable metabolic associations were, however, often evident even when just one dietary target was attained. Furthermore, when compared to the STRIP intervention effect [20], having a diet concordant to the intervention targets was associated with a more beneficial cardio-metabolic health profile.…”

Section: Discussionmentioning

confidence: 93%

“…We recently showed that the dietary intervention given in STRIP from infancy to early adulthood resulted in significant differences in the fatty acid intakes between the intervention group and the control group [20]. These differences were favorably reflected in the metabolic profiles of the intervention children.…”

Section: Discussionmentioning

confidence: 99%

“…A prior study about the STRIP intervention effect on a comprehensive metabolic profile showed that the intervention led to favorable changes in circulating fatty acids and lipoprotein subclass lipids [20]. We also recently examined the effects of achieving the STRIP intervention dietary targets, regardless of study group allocation, on insulin sensitivity and serum lipids [21].…”

Section: Introductionmentioning

confidence: 99%

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Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention—Association with Metabolic Profile from Childhood to Adulthood

et al. 2021

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The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9–19 years (n = 549–338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) < 1:2, (2) intake of SAFA < 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.

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Effect of Dietary Counseling on a Comprehensive Metabolic Profile from Childhood to Adulthood

Cited by 25 publications

References 39 publications

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention—Association with Metabolic Profile from Childhood to Adulthood

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