Background: Genetic predisposition and metabolic needs are important in determining the optimal diet for development and prevention of metabolic syndrome. There is the need for the new tools to identify the genotype-phenotype interactions leading to insulin resistance

The aim of this study was to find the relation between risk originating from gene variations and diet-dependent development of insulin resistance.

Methods: The insulin output as an area under curve for insulin after standard glucose tolerance (AUCIns OGTT) and lipid tolerance tests (AUCIns OLTT) were measured in 167 overweight/obese patients. Estimation of the polymorphisms of 18 common “obesity risk-genes” and standard phenotyping was performed.

Results: Insulin output during oral glucose tolerance test (AUCIns OGTT) correlated strongly with insulin output after standard high fat meal (AUCIns OLTT) in the whole group. However, within the genotype sub-groups the correlation was lower or did not exist. The nutrient-induced insulin output ratio (NIOR), calculated as AUCIns OLTT/AUCIns OGTT, values ranged from 0,42 to 5,83, and correlated significantly with body mass index (BMI) and leptin but not with age, gender, waist/hip ratio (WHR) and insulin resistance index (HOMA) or plasma adiponectin. High NIOR was found in a subgroup of carriers of rare allelic variants of genes characteristic for the worse tolerance to lipids in the diet. Low NIOR values were found within a sub-group with rare genetic variants regulating carbohydrate metabolism.

Thus, the new insulin index NIOR may distinguish the gene variant carriers into groups, which are glucose- or lipid-content in diet sensitive phenotypes.

Conclusion: We suggest that the OLTT/OGTT insulin output ratio (NIOR) measured on the basis od functional postprandial tests for glucose and lipids may be predictive for identifying individuals (genotypes) who are phenotypically predisposed to insulin resistance in response to high fat or carbohydrate content in their habitual diet.

Granted by Polish MNiI: Nr 3PO5D08424 and Nr 501/NKL/49/L and NuGO, a Network of Excellence funded by the European Union (CT-2004–505944)

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