Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling

Lee, Aejin; Jang, Han Byul; Ra, Moonjin; Choi, Youngshim; Lee, Hye-Ja; Park, Ju Yeon; Kang, Jae Heon; Park, Kyung-Hee; Park, Sang Ick; Song, Jihyun

doi:10.1016/j.orcp.2014.10.220

Cited by 49 publications

(62 citation statements)

References 23 publications

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“…This difference may be because most previous studies were undertaken in adults . In contrast, a series of relatively small studies have been reported in children, and with limited exceptions most of these were cross‐sectional. In the mainly cross‐sectional studies of obese children included in the systematic review of Zhao et al, IR was found to be positively associated with BCAA .…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72)

et al. 2019

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Background While insulin resistance (IR) is associated with specific metabolite signatures in adults, there have been few truly longitudinal studies in healthy children, either to confirm which abnormalities are present, or to determine whether they precede or result from IR. Therefore, we investigated the association of serum metabolites with IR in childhood in the Earlybird cohort. Methods The Earlybird cohort is a well‐characterized cohort of healthy children with annual measurements from age 5 to 16 years. For the first time, longitudinal association analyses between individual serum metabolites and homeostatic model assessment (HOMA) of insulin resistance (HOMA‐IR) have been performed taking into account the effects of age, growth, puberty, adiposity, and physical activity. Results IR was higher in girls than in boys and was associated with increasing body mass index (BMI). In longitudinal analysis IR was associated with reduced concentrations of branched‐chain amino acids (BCAA), 2‐ketobutyrate, citrate and 3‐hydroxybutyrate, and higher concentrations of lactate and alanine. These findings demonstrate the widespread biochemical consequences of IR for intermediary metabolism, ketogenesis, and pyruvate oxidation during normal child growth and development. Conclusions Longitudinal analysis can differentiate metabolite signatures that precede or follow the development of greater levels of IR. In healthy normal weight children, higher levels of IR are associated with reduced levels of BCAA, ketogenesis, and fuel oxidation. In contrast, elevated lactate concentrations preceded the rise in IR. These changes reveal the metabolite signature of insulin action during normal growth, and they contrast with previous findings in obese children and adults that represent the consequences of IR and obesity.

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Section: Discussionmentioning

confidence: 99%

Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72)

et al. 2019

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“…For this study, data were obtained from the Korean Children-Adolescents Study (KoCAS) conducted by the Korea National Institute of Health (KNIH) [4,21]. A total of 135 volunteers on collection of stool samples, aged 13-16 years, including those with severe obesity, were recruited from Seoul and Kyunggi Province in 2012.…”

Section: Study Participantsmentioning

confidence: 99%

Association of dietary patterns with the fecal microbiota in Korean adolescents

et al. 2017

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Background: The gut microbiota has emerged as an important environmental factor associated with obesity, type 2 diabetes, and cardiovascular disease, through its interactions with dietary factors. Therefore, we analyzed the composition of the fecal microbiota and levels of biochemical markers related to metabolic disease according to dietary pattern in Korean adolescents. Methods: We collected fecal samples from 112 student subjects aged 13-16 years with sufficient information available regarding clinical biomarkers and diet, and performed 16S rRNA targeted gene sequencing. Results: Regarding bacterial composition according to taxonomic rank, we found that traditional dietary patterns enriched in plant-based and fermented foods were associated with higher proportions of Bacteroides (Bacteroidaceae) and Bifidobacterium (Bifidobacteriaceae-Actinobacteria) and a lower proportion of Prevotella (Prevotellaceae) relative to modified Western dietary patterns (a greater proportion of animal-based foods). Specifically, the proportion of Bacteroides (Bacteroidaceae) was associated with intake of plant-based nutrients such as fiber; however, that of Prevotella (Prevotellaceae) was negatively associated with these factors. Additionally, we observed that the increase of prevotella (Prevotellaceae) and decrease of Bacteroides (Bacteroidaceae) and Ruminococcaceae had a higher risk of obesity. We also found that the traditional dietary pattern was negatively associated with general and central adiposity and levels of clinical biomarkers, including AST, ALT, total cholesterol, triglyceride, hs-CRP, insulin, and HOMA-IR, whereas the positive associations were found for a modified Western dietary pattern.

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“…Similarly, amino acid metabolites are positively related to cardiometabolic risk markers (CRM) in children, adolescents, and young adults, albeit with a few exceptions. The positive associations include branched-chain amino acids (BCAAs) with insulin resistance (IR) 15,21,22 , triglycerides 23 , and triglycerides to high-density lipoprotein-cholesterol (HDL-C) ratio 24 ; valine, leucine, and isoleucine 10 , phenylalanine and tyrosine 21 , and kynurenine and KTR 25 with IR; cysteine with fasting plasma glucose (FPG), leptin, and IR; 12 indole-3 propionic acid with HDL-C 16 ; arginine, histidine, and serine with insulin sensitivity 5 ; KTR with C-reactive protein (CRP), interferon-gamma, interleukin (IL)−6, IL-10, and alpha-1-acid glycoprotein 26 ; and isoleucine and valine with IR 27 . The few reported negative associations include BCCAs with FPG 23 and adiponectin 24 ; tryptophan with CRP, interferon-gamma, IL-6, IL-10, and alpha-1-acid glycoprotein 26 ; and numerous amino acids with CRP and IL-6 28 .…”

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confidence: 99%

“…The few reported negative associations include BCCAs with FPG 23 and adiponectin 24 ; tryptophan with CRP, interferon-gamma, IL-6, IL-10, and alpha-1-acid glycoprotein 26 ; and numerous amino acids with CRP and IL-6 28 . The relation of BCCA with BCCAs with FPG 23 and adiponectin 24 , and that of isoleucine and valine with IR 27 are restricted to males, while the relation of BCAA with triglycerides 23 , and triglycerides to HDL-C ratio 24 are restricted to females. The mechanistic involvement of BCCAs in the development of IR includes persistent activation of mTOR signaling pathway and accumulation of toxic BCAA metabolites that trigger mitochondrial dysfunction 29 , and the involvement of tryptophan and KTR in inflammation is through the immunoregulatory role of indoleamine 2,3-dioxygenase 1 30 .…”

mentioning

confidence: 99%

Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

Oluwagbemigun

Anesi

Ulaszewska

et al. 2020

Sci Rep

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Amino acid metabolites in biofluids are associated with high body mass index (BMI) and cardiometabolic abnormalities. However, prospective investigations regarding these associations are few, particularly among young individuals. Moreover, little is presently known about the impact of long-term high BMI. Using data from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study (111 males and 107 females), we prospectively investigated relations between repeatedly measured urinary levels of 33 metabolites and (1) previously identified long-term BMI trajectory groups from childhood into late adolescence and (2) cardiometabolic risk markers in late adolescence-young adulthood, in sex-specific linear mixed regression models. Males with long-term overweight had lower indole-3-acetic acid when compared to others. Further, methionine, isoleucine, tryptophan, xanthurenic acid, and indole-3-carboxaldehyde were negatively associated with C-reactive protein (CRP), but 5-hydroxyindole-3-acetic acid was positively associated with CRP. No associations were observed in females. Long-term overweight from childhood into late adolescence is associated with decreased urinary levels of gut bacteria-derived indole-3-acetic acid, and several urinary amino acids, including gut bacteria-derived indole-3-carboxaldehyde are associated with elevated CRP later on in life. taken together, our data suggest that indole metabolites, and their gut bacteria producers play potentially important roles in overweight-related inflammation. High body mass index (BMI) during childhood and adolescence is still a major public health concern 1,2. The condition contributes to the development of cardiometabolic abnormalities such as inflammation over the life course 3. Dysregulated metabolism is one of the biological mechanisms through which high BMI contributes to the development of these cardiometabolic abnormalities 4,5. Scientific efforts have focused on carbohydrate and lipid metabolic perturbations as one of these mechanisms, interest in the impact of unfavorable alterations in protein/amino acid metabolism is now emerging 6,7. Therefore, it would be necessary to explore the link of high BMI, amino acid metabolites, and cardiometabolic abnormalities.

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Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling

Cited by 49 publications

References 23 publications

Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72)

Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72)

Association of dietary patterns with the fecal microbiota in Korean adolescents

Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

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