Type 2 diabetes (T2D) is a heterogeneous disease with a multifactorial aetiology involving defects in the pancreatic beta cells, liver, muscles, adipose tissue, guts, brain, kidneys and heart. While genetics may only explain a minor proportion of T2D, the contribution of an adverse intrauterine environment may take centre stage in the global propagation of T2D. Impaired expandability of subcutaneous adipose tissue in persons with low birthweight may cause T2D due to lipotoxicity in non-adipose organs. Future implications include a stronger focus on individualized treatments in T2D patients and prevention of T2D in the next generations.