Magdalena Bossowska, Filip Bossowski, Edyta Adamska-Patruno, Katarzyna Maliszewska, Adam Krętowski
Journal: Nutrients 2026;18(5):
PMID: 41829986
Obesity and prediabetes are growing global health concerns and increase the risk of developing type 2 diabetes and cardiovascular disease. While healthy dietary patterns such as the Mediterranean and DASH diets are generally recommended, not everyone responds the same way to these diets. One possible reason is genetic variation. Understanding whether a person’s genes influence the way they respond to specific dietary changes could help improve personalised nutrition strategies. This systematic review aimed to evaluate whether genetic differences (genotypes) modify the effects of dietary interventions in adults with obesity or prediabetes. The authors reviewed available clinical and observational studies examining interactions between diet and specific gene variants. Particular attention was given to genes linked to metabolism and obesity risk, including variants such as TCF7L2 and APOA2.
The review found that general dietary improvements, such as reducing saturated fat intake and improving carbohydrate quality, were beneficial across most individuals. However, some studies suggested that individuals with a higher genetic risk for obesity or diabetes may experience greater improvements in body weight, fat distribution, or glycaemic markers when following structured healthy dietary patterns. Certain gene–diet interactions appeared to influence how macronutrients affected metabolic outcomes. However, the evidence was not always consistent, and study quality varied.
In conclusion, genetics may influence how individuals with obesity or prediabetes respond to dietary interventions, but current evidence does not yet fully support gene-based dietary interventions. Healthcare professionals can use this information to understand the emerging role of nutrigenetics while continuing to prioritise evidence-based dietary recommendations that benefit most individuals.
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• Genetic based nutrition should not replace standard dietary advice, but it may help refine dietary approaches in selected high-risk individuals.
• Individuals with higher genetic risk for diabetes may benefit most from targeted dietary changes, but ongoing monitoring may be essential due to varying individual responses.
Introduction –
Obesity and prediabetes are global epidemics with increasing public health implications. Whilst dieting may help, there is a heterogenous response to healthy diets, which may be due to genetics. Nutrigenetics investigates this relationship. This systematic review study aimed to evaluate the findings of human gene-diet interaction studies in adults with obesity, prediabetes, or at an increased cardiometabolic risk focusing on the Mediterranean and Dietary Approaches to Stop Hypertension diets and those which focus on carbohydrate, protein, fat, and energy restriction.
Methods –
• This was a systematic review of PubMed
• Eligible studies enrolled adults and addressed genotype-diet interactions for type 2 diabetes (T2D) and prediabetes.
• Less than 200 studies were identified for inclusion and analysis (precise figure not given).
Results –
• Regardless of genotype, restricting saturated fat and consuming good quality carbohydrates were important for individuals with T2D, prediabetes and obesity.
• Individuals who were at a higher polygenic risk and more likely to develop T2D had a much greater benefit from a healthy diet (OR~0.53), with little to no benefit in those at low risk.
• Individuals with the rs7903146 T allele variant, higher saturated fat intake was associated with worse insulin sensitivity and substituting with unsaturated fat was linked to improved insulin sensitivity.
• Amongst those with the APOA2-265T>C CC homozygote genotype, higher dietary antioxidant capacity was linked to higher inflammatory and lipid peroxidation markers, whereas the expected anti-inflammatory effect was seen in those who were T-allele carriers.
Conclusion –
Anti-inflammatory diets improve biomarkers in those with T2D, prediabetes, or obesity regardless of genetics. Tailoring nutrition based on an individual's genetics may lead to the greatest health benefits in those at higher genetic risk. However, the current evidence is limited by underpowered studies.
• Improving diet quality should be a primary intervention in those at high-risk of T2D/insulin resistance.
• Individuals with a higher polygenic risk for T2D/prediabetes may derive greater metabolic benefit from dietary change.
• Genetics could be used as a tool to stratify prevention urgency.
• There should be an emphasis on fat quality and unsaturated fats in those with poor insulin sensitivity.
• All individuals should be monitored when placed on a healthy eating programme as not all responses will be heterogenous.
• Future research should aim at determining if genotype meaningfully alters dietary response with large, genotype stratified, randomised controlled trials.
BACKGROUND/OBJECTIVES
Obesity and prediabetes are overlapping global epidemics. This systematic review synthesises evidence on gene-diet interactions in adults with obesity, prediabetes, or related cardiometabolic risks. It evaluates Mediterranean and DASH dietary patterns, macronutrient quality, and energy restriction across both single-variant and polygenic score approaches.
METHODS
PubMed was searched for English language papers published in the last 5 years (last run: 31 October 2025). Fewer than 200 studies were retained after excluding those lacking explicit statistical testing for gene-diet interactions or relevant endpoints.
RESULTS
Evidence supports restricting saturated fat and preserving carbohydrate quality as general baseline targets, with associations heterogeneous by genotype. Effect modification was observed: healthy dietary patterns were associated with lower risk in high polygenic-risk strata (OR~0.53) but little or no benefit in low-risk groups. TCF7L2 variants were associated with macronutrient thresholds (e.g., protein > 18%, carbohydrate < 48%) affecting visceral adiposity, while APOA2 variants showed genotype-dependent inflammation, including paradoxical increases in markers with higher dietary antioxidant capacity. Interpretation was limited by underpowered interaction tests, multiplicity, and uneven ancestry representation (e.g., unique SLC16A11 and CREBRF signals).
CONCLUSIONS
While anti-inflammatory dietary substitutions improve biomarkers irrespective of some variants (e.g., TCF7L2), genotype-informed nutrition appears to yield the largest absolute risk reduction in high-risk populations. Clinical implementation should therefore combine baseline diet-quality guidance with targeted strategies for genotype-specific response patterns (e.g., APOA2 antioxidant heterogeneity and TCF7L2 carbohydrate thresholds), rather than rely on uniform recommendations alone. Future progress requires preregistered, genotype-stratified trials and locally trained polygenic scores to address ancestry-specific genetic architecture.
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