T2DM also known as non-insulin dependent diabetes or adult-onset diabetes is a non-autoimmune polygenic disorder in which the body fails to produce enough insulin. T2DM accounts for 90% of diabetes cases. It is an outcome of a complex environment and gene interaction. Intragenic and gene-environment interaction in T2DM is poorly understood. Environmental characteristics influence risk factors of T2DM by intensifying or restraining behavioural, psychosocial, and physical stressors. It is also reported that the physical and social environment can influence choices and behaviour. For example, nutritional choices can be heavily governed by the physical and social environment, which is an important factor for controlling diabetes.  Researchers found that the pathogenesis of T2D (type 2 diabetes) during adult life is influenced by the nutritional environment during pre- and postnatal life. Before the advent of insulin, a heavily restricted dietary intervention was used to treat diabetes and diet, or exercise intervention supposed to delay the onset of diabetes onset by 4 years.  In close association with the environment, nutrition is a crucial factor which is significantly modifying the gene expression. Nutrition is considered as the most influential environmental stimuli.

In this era, nutrigenomics and nutrigenetics are the emerging fields in nutrition science and technology. This is the study of gene-diet interaction which includes genetics and epidemiological methods to find statistical associations among genes, foods, and biological pathway, like intermediate-risk factors. For about 15 years, nutritional genomics researchers have been trying to combine genetics and epidemiology to examine how nutrition is affecting one or more risk factors. They found that nutrition has a variable impact on the genetic makeup of the individual. Gene alone not necessarily produces phenotypic traits. Phenotype is influenced by nutrition and this influence may differ among individuals. The effect of dietary response and interventions on genotype and phenotype can show significant interpersonal differences. Likewise, genotypes differ for each individual and one effective dietary pattern might not be effective for other so, determining specific diet for the specific gene or set of the genes for certain diseased condition can be an effective and natural method to treat diseases. It could be useful in both the prevention and treatment of chronic diseases by adjusting dietary intervention to subject’s unique genetic makeup. Interaction of certain nutrients with genetically determined biochemical, differences in nutritional requirement and various metabolic factors suggest specific requirements for individuals. For example, low physical activity and high adherence to Western diet amplify T2DM and this pattern is evident for PPARG, TCF7L2 and FTO gene variants. Human body metabolism process food in the form of chemicals and chemical can alter the genomic expression directly or indirectly. Further, activation of nutrient receptors guides nutrients in influencing a wide variety of specific genes.

Diabetes risk is strongly influenced by hereditary factors. There is a 40% lifetime risk for development of type 2 diabetes if one parent has T2DM and 70% if both parents have T2DM. Genome-wide scanning and Candidate gene-based approach have played a significant role in identifying potential genes causing disease. An Indian study reported 388 significant SNPs (single nucleotide polymorphism) from 58 GWAS (genome wide association studies) study. Another Indian association analysis study has confirmed 31 GWAS SNPs from 24 genes with T2DM and four intermediate traits of fasting glucose; fasting insulin; HOMA-insulin resistance (HOMA-IR); and HOMA-β. Studies also show that 45 genetic regions are associated with the putative intermediary mechanism in diabetes. A genetic method called QTL (quantitative trait locus) analysis is used to identifies different locus contributing to a complex trait. 7 QTLs are identified in response to T2DM which have logs of odds greater than 3.6. These QTLs are present on chromosome 1, 2, 3, 10, 12 and 18. TCF7L2 (Chr. 10) and PPARG (Chr. 3) genes are mostly studied among T2DM patients. These two genes confer SNPs which shows worldwide association with T2DM patients. The genetic factors determining T2DM are not uniform among ethnic groups, this complicates the genetic studies of T2DM. Prior validation of genetic factors in different ethnic groups is required to conduct a multidimensional study of T2DM.

Each gene has a different recipe for a distinct protein or combinations of protein that either modulate biological activities or participate in building structural blocks for tissues. SNPs in the gene can alter these expressions which can further lead to fluctuation in protein synthesis. After the advent of the Human Genome Project, the millions of SNPs are found to have a relation with nutrition. In the case of T2DM, PPARG and TCF7L2 SNPs is also known to be associated with nutrition. It is found that SNPs (single nucleotide polymorphism) in the human genome can alter the dietary metabolic responses and are associated with the risk factor for disease onset. SNPs analysis is an important tool for estimating the role of nutrition in diseases and risk at the molecular stage. As many polymorphisms detected to increase disease susceptibility, a better understanding of the mechanisms helps us to target for more appropriate dietary advice to the relevant population sub-groups. It can be considered in metabolic and epidemiological studies to define optimal dietary requirements.

There are several diabetes control programmes in India, but grassroot level implementation is required before it became a pandemic from endemic. India currently spending a huge part of the economy in treating diabetes and lifelong prolongation making it more difficult. According to the Association of Physician of India urban poor spend as much as 34% and their rural counterpart spend 27% of their incomes on diabetes treatment. Also, various pharmacological treatment schemes lead to improper management of diabetes in India. Side effects of drug-based approach in diabetes can be easily observed among patients. Furthermore, diabetes treatment requires a lifelong consumption of drug which can`t be affordable for every people. A robust and multidisciplinary approach is required to study the various casual factors of T2DM. Targeting gene by nutrition can be a more efficient approach to treat diabetes. This minimizes the chances of side-effects and doesn’t require extra expenditure for treatment. In addition, this approach can help in diminishing and delaying the onset of other diseases. Nutrigenetic and nutrigenomics-based intervention approach must be considered for a better outcome.

Therefore, the present study will supplement a step towards determining the nutritional influence on the two genes (TCF7L2 & PPARG) in the prevention and control of type 2 diabetes mellitus. This study initially proposes to detect the polymorphisms and provide nutritional intervention package based on wild type and risk alleles. Then the final impact of nutrition on genotype and phenotype of diabetic patients will be assessed via FPG (fasting plasma glucose) levels.

·   Null Hypothesis: - The gene-based nutritional intervention will not prevent and control type 2 diabetes.

·   Alternative Hypothesis: - The gene-based nutritional intervention will prevent and control type 2 diabetes.