 Type-2 Diabetes (T2D) is a multi-factorial disease attributed to complex

interplay of genetic, epigenetic, and environmental factors.

 Adiposopathy or sick fat has been considered a root cause of some of the
most common metabolic diseases observed in clinical practice, including
Type 2 diabetes mellitus, hypertension and dyslipidemia.
 As Asian Indians have been considered genetically predisposed to
adiposopathy; it is therefore of significant clinical interest to undertake
transcriptomics of different depots of adipose tissues to ascertain various
aspects of cellular physiology in clinically-characterized T2D.
 Functional genomics of Type 2 Diabetes is quite challenging as
prioritized genes do not clearly converge on functional categories
consistent with the known aspects of T2D pathophysiology
 Epidemiological evidences suggest that genetically programmed
pancreatic β-cell dysfunction interacts with environmentally
triggered insulin resistance to cause T2D
 Functional genomics of Type 2 Diabetes is quite challenging as
prioritized genes do not clearly converge on functional categories
consistent with the known aspects of T2D pathophysiology
 Epidemiological evidences suggest that genetically programmed
pancreatic β-cell dysfunction interacts with environmentally
triggered insulin resistance to cause T2D
 To address these challenges, we analyzed T2D-transcritome using two
approaches:

 System integration of transcriptomic-data with different omics-level

data: GWAS, Toxicogenomics, Protein-protein interactions, gene-

disease etc. to reconstruct Phenome-Intractome network, and
Genome-Phenome correlations.

 Assessment of disease related intermediate phenotypic traits: HOMA-R,

HOMA-β, HbA1c, NEFA, TNF-α, Leptin, Adipnectin etc. and their

correlation with adipose tissue transcriptome profiles using Weighted
Gene Correlation Network Analysis (WGCNA)
1. Genes obtained from T2D GWAS at p value
thresholds up to 10-5:T2D Genome
2. Physical and genetic interactions of T2D
Genome from BioGRID:T2D Intractome
3. Genes in T2D Intractome, also interacting
with antidiabetic drugs from The Comparative
Toxicogenomic Database (CTD): T2D
Toxicogenome
4. Microarray expression profiles of skeletal
muscle, visceral adipose and subcutaneous
adipose from Asian Indians: T2D
Transcriptome
Genome to phenome pathway of TGF-beta signaling. T2D genome, T2D interactome, T2D
transcriptome and antidiabetic drug interacting genes are mapped on to KEGG pathway for TGF-beta
signaling. Red: genome, interactome and transcriptome; brown: interactome, transcriptome and
antidiabetic drug interacting genes; green: interactome and transcriptome; yellow: interactome; grey:
antidiabetic drug interacting genes.
 Extra Mural Research (EMR) Project:
“Clinical, Biochemical and Cellular Correlates of
Transcriptome of Adipose Tissue among Type-2
Diabetics”

Objectives of the study –

 Generation and analysis of genome –wide gene expression profile of Adipocytes
and infiltration macrophages obtained from different depots of adipose tissue
among type-2 diabetics.
 To find relation between these molecular alteration with clinical, biochemical
and cellular phenotypes.
Salient features of study:
 Largest number of samples collected (130 individuals) in an Indian Microarray
study
 Recording of large numbers of parameters per subject :
 Anthropometric measurements (Body Weight, Height, Waist to Hip (W: H) ratio, BMI,
Supine Blood Pressure)
 Biochemical Parameters (Serum Glucose, Lipid Profile, Triglycerides, Cholesterol (LDL,
HDL, and VLDL), Serum Insulin, HbA1c, Homeostasis Model Assessment (HOMA-R),
OMA-B, NEFA, Leptin, Adiponectin, HsCRP)
 Radiological Investigation for Body Fat Content & Distribution using Dual Energy X-Ray
Absorptiometry (DEXA), and Medical Resonance Imaging
Thanks