Abstract
Lifestyle intervention may be effective in reducing type 2 diabetes mellitus incidence and cardiometabolic risk. A more personalised nutritional approach based on an individual or subgroup-based metabolic profile may optimise intervention outcome. Whole body insulin resistance (IR) reflects defective insulin action in tissues such as muscle, liver, adipose tissue, gut and brain, which may precede the development of cardiometabolic diseases. IR may develop in different organs but the severity may vary between organs. Individuals with more pronounced hepatic IR have a distinct plasma metabolome and lipidome profile as compared with individuals with more pronounced muscle IR. Additionally, genes related to extracellular modelling were upregulated in abdominal subcutaneous adipose tissue in individuals with more pronounced hepatic IR, whilst genes related to inflammation as well as systemic low-grade inflammation were upregulated in individuals with primarily muscle IR. There are indications that these distinct IR phenotypes may also respond differentially to dietary macronutrient composition. Besides metabolic phenotype, microbial phenotype may be of importance in personalising the response to diet. In particular fibres or fibre mixtures, leading to a high distal acetate and SCFA production may have more pronounced effects on metabolic health. Notably, individuals with prediabetes may have a reduced response to diet-induced microbiota modulation with respect to host insulin sensitivity and metabolic health outcomes. Overall, we need more research to relate metabolic subphenotypes to intervention outcomes to define more optimal diets for individuals with or predisposed to chronic metabolic diseases.
Highlights
Worldwide, the prevalence of obesity, insulin resistance (IR) and type 2 diabetes mellitus has grown dramatically since the 1980s
Whole body IR reflects defective insulin action in tissues such as muscle, liver, adipose tissue, gut and brain, which may precede the development of cardiometabolic diseases[11]
In the different prediabetic phenotypes the state of impaired glucose tolerance may be characterised by more pronounced peripheral or muscle IR, whilst the state of impaired fasting glucose by more pronounced hepatic IR[12]
Summary
Lifestyle intervention may be effective in reducing type 2 diabetes mellitus incidence and cardiometabolic risk. A first question that has to be addressed is whether these phenotypes are really distinct We addressed this question by characterising the plasma metabolome[15] and lipidome[16] and adipose tissue transcriptome profiles[17] in individuals with either more pronounced hepatic IR or more pronounced muscle IR in the European multicentre DIOGenes trial in overweight and obese individuals[18]; and used the Cohort on Diabetes and Atherosclerosis Maastricht[19] and the Maastricht study, a large population-based cohort in the Maastricht area[20] as validation cohorts. We investigated whether in individuals with overweight or obesity but without diabetes, hepatic IR and muscle insulin sensitivity were characterised by distinct metabolic profiles. Personalisation based on microbial composition and phenotype has received increased attention, and in the following paragraphs this will be addressed targeting the microbial functionality with emphasis on the production of SCFA
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