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Health relevance of lowering postprandial glycaemia in the paediatric population through diet': results from a multistakeholder workshop.

ABSTRACT: To summarize current knowledge and gaps regarding the role of postprandial glycaemic response in the paediatric population, a workshop was organized in June 2021 by the European branch of the International Life Science Institute (ILSI). This virtual event comprised of talks given by experts followed by in-depth discussions in breakout sessions with workshop participants. The main pre-specified topics addressed by the workshop organizing committee to the invited speakers and the workshop participants were: (1) the role of glycaemic responses for paediatric health, based on mechanistic insights from animal and human data, and long-term evidence from observational and intervention studies in paediatric populations, and (2) changes in metabolism and changes in dietary needs from infancy to adolescence. Each talk as well as the discussions were summarised, including the main identified research gaps. The workshop led to the consensus on the crucial role on health of postprandial glycaemic response in paediatric population. However, a lack of scientific data has been identified regarding detailed glucose and insulin profiles in response to foods commonly consumed by paediatric populations, as well as a lack of long-term evidence including the need for suitable predictors during childhood and adolescence to anticipate health effects during adulthood.

SUBMITTER: Vinoy S

PROVIDER: S-EPMC10030539 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Health relevance of lowering postprandial glycaemia in the paediatric population through diet': results from a multistakeholder workshop.

Vinoy Sophie S Goletzke Janina J Rakhshandehroo Maryam M Schweitzer Lisa L Flourakis Matthieu M Körner Antje A Alexy Ute U van Schothorst Evert M EM Ceriello Antonio A Zakrzewski-Fruer Julia K JK Buyken Anette A

European journal of nutrition 20221219 3

To summarize current knowledge and gaps regarding the role of postprandial glycaemic response in the paediatric population, a workshop was organized in June 2021 by the European branch of the International Life Science Institute (ILSI). This virtual event comprised of talks given by experts followed by in-depth discussions in breakout sessions with workshop participants. The main pre-specified topics addressed by the workshop organizing committee to the invited speakers and the workshop particip ...[more]

PMID: 36534178

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Project description:Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10-8/132 = 4 × 10-10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p < 8.0 × 10-7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10-3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal.

Project description:Aims/hypothesisImbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven.MethodsWe dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet.ResultsIn individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10-7) and C-peptide release responses (rs2300757, p=6.86x10-5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states.Conclusions/interpretationThese results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes.

Project description:BackgroundPatient engagement has become increasingly important in drug development, yet structured guidance to engage children (2-11 years old), adolescents (12-17 years old), and young adults (18-24 years old) is lacking. This study aims to create a matrix tool to foster paediatric patient engagement in drug development by hosting a multistakeholder workshop.MethodsA matrix tool was co-developed by the study team and the expert group to provide a framework for paediatric patient engagement across drug development stages. The matrix tool's concept was evaluated using a Delphi-based approach. A pre-workshop questionnaire was sent to 55 experts, followed by an online multistakeholder workshop with 38 participants. A post-workshop questionnaire was redistributed to the initial participants refine the matrix tool further.ResultsThe pre-workshop questionnaire (34 respondents) confirmed the need for a co-developed matrix tool, with all statements reaching consensus (cut-off 70% consensus). The workshop (38 participants) revealed strong agreement (92%) on the necessity of such a matrix tool. Participants emphasized the importance of including both chronic and acute diseases, considering patient trial experience, involving families and patient organizations, and aligning age group categories with regulations. The post-workshop questionnaire (18 respondents) showed 89% agreement on involving children, adolescents, and young adults in the matrix tool's co-development. However, opinions varied on the appropriate minimum age for engagement, ranging from 2 to 17 years.ConclusionsThis study presents the initial steps towards developing a matrix tool to enhance paediatric patient engagement in drug development. The multistakeholder approach provided valuable insights into the matrix tool's structure and content. While further validation and refinement are needed, particularly regarding practical implementation and global applicability, this initiative lays the groundwork for more effective and inclusive paediatric drug development processes. Future research should focus on validating the matrix tool across different age groups and disease contexts, incorporating real life experiences, and addressing cultural and linguistic considerations.

Dataset Information

Health relevance of lowering postprandial glycaemia in the paediatric population through diet': results from a multistakeholder workshop.

Publications

Health relevance of lowering postprandial glycaemia in the paediatric population through diet': results from a multistakeholder workshop.

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