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The doctrine of the multiple strike theory, based on the second strike theory, is currently widely accepted, and includes lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, adipose tissue dysfunction, inflammatory cytokines, and enteric endotoxin multiple strike factors
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Notably, it has been used in Germany as an approved treatment for diabetic neuropathy for decades
In a recent EWAS study, 792 genes were hypermethylated and 2341 were hypomethylated in children with overweight/obesity as compared to those with normal weight, with the genes PCDHGA4, BRD2 and PTPRN2 involved in regulating dysglycemia and the hypothalamic appetite network, obesity and type 1 diabetes having the highest number of differentially methylated sites [158,159,160] Another study comparing obese vs
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