Diabetes: A comprehensive review of the Indian landscape in contrast with global trends

Table 4 Demonstration of environmental factor interaction with gene causing diabetes

Ref.	Kleinberger et al[71], 2015; Cerf et al[72], 2013; Pervjakova et al[73], 2022; Crudele et al[74], 2023; Guidotti et al[75], 2013; Andersen et al[76], 2012; Landin-Olsson[77], 2002; Garcia-Gutierrez[78], 2024; Schulz et al[79], 2021; Kota et al[80], 2012; Pilla et al[81], 2022
Environmental factor	Type of diabetes affected	Gene(s) involved	Mechanism of interaction
Obesity/high-fat diet	T2D	TCF7 L2, FTO, PPARG	Alters gene expression involved in insulin sensitivity and metabolism through epigenetic changes
Physical inactivity	T2D	PPARG, IRS1	Reduces insulin sensitivity via modulation of glucose metabolism genes
Maternal nutrition	GDM, T2D	IGF2, H19, PDX1	Epigenetic modifications affecting pancreatic beta-cell development and fetal metabolic programming
Endocrine disruptors (e.g., BPA)	T2D	PPARG, GLUT4	Mimics or blocks hormonal action, disrupting insulin signaling and glucose transport
Chronic stress/cortisol	T2D	NR3C1, FKBP5	Alters glucocorticoid receptor expression and function, affecting glucose metabolism
Smoking	T2D, GDM	CYP1A1, GSTM1	Increases oxidative stress and induces insulin resistance
Air pollution (PM2.5, NO2)	T2D	GSTP1, NFE2 L2	Induces oxidative stress and systemic inflammation, impairing insulin signaling
Vitamin D deficiency	T1D, T2D	VDR	Modulates immune response and beta-cell function, increasing susceptibility
Viral infections	T1D	HLA-DR, INS	Triggers autoimmune destruction of pancreatic beta cells in genetically susceptible individuals
Gut microbiome dysbiosis	T1D, T2D, GDM	NOD2, TLR4	Alters immune homeostasis and promotes systemic inflammation, impacting insulin sensitivity
Chemical EXPosure (e.g., pesticides, phthalates)	T2D	PPARG, IRS1	Acts as an endocrine disruptor, interfering with insulin signaling pathways
Sleep/circadian disruption	T2D	CLOCK, BMAL1	Alters circadian regulation of metabolic gene expression, leading to impaired glucose metabolism
Socioeconomic status (SES)	All types	Multiple genes	Influences access to healthcare, nutrition, and stress levels, leading to epigenetic modifications

GDM: Gestational diabetes mellitus; T1D: Type 1 diabetes; T2D: Type 2 diabetes; TCF7 L2: Transcription factor 7 like 2; FTO: Fat mass and obesity associated; PPARG: Peroxisome proliferator activated receptor gamma; IRS1: Insulin receptor substrate 1; IGF2: Insulin like growth factor 2; H19: H19 imprinted maternally expressed transcript; PDX1: Pancreatic and duodenal homeobox 1; GLUT4: Glucose transporter type 4; NR3C1: Nuclear receptor subfamily 3 group C member 1; FKBP5: FKBP prolyl isomerase 5; CYP1A1: Cytochrome P450 family 1 subfamily A member 1; GSTM1: Glutathione S-transferase Mu 1; GSTP1: Glutathione S-transferase Pi 1; NFE2 L2: NFE2 like BZIP transcription factor 2; VDR: Vitamin D receptor; HLA-DR: Major histocompatibility complex, class II, DR beta; INS: Insulin; NOD2: Nucleotide binding oligomerization domain containing 2; TLR4: Toll like receptor 4; CLOCK: Clock circadian regulator; BMAL1: Aryl hydrocarbon receptor nuclear translocator like; SES: Socioeconomic status.