Around two decades, Hales and Barker along with their co-workers proposed the 'thrifty phenotype hypothesis' claiming that fetal programming could represent an important player in the origin of type 2 diabetes, the metabolic syndrome and cardiovascular disease (CVD). The hypothesis was initially met with great skepticism, but nevertheless their observations have subsequently been confirmed and expanded in many epidemiological and animal experimental studies. To this end, human integrative physiological studies have provided insights into some of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the more than 50 type 2 diabetes susceptibility genes have been associated with low birth weight. This support results from twin studies of the association between low birth weight on one side, and type 2 diabetes on the other, being mainly of non-genetic origin. DNA functions may be permanently or transiently altered by epigenetic modifications including alterations in the degree of methylation of DNA at specific (CpG) sites in the promotor region of the gene, changes in the expression of short (20 bases) long miRNA sequences influencing gene or protein expression functions, or by changes in the chromatin structure or acetylation(s) of the DNA. Examples of how the fetal environment associated with low birth weight may influence epigenetic regulations in human muscle and fat samples, and thereby the risk of developing type 2 diabetes, will be presented in the lecture. For instance, young men born with low birth weight shows impaired flexibility of DNA methylations in skeletal muscle biopsies when exposed to a 5-days high fat overfeeding challenge. Nevertheless, being born with low birth weight may represent a much too simplistic marker of people at increased risk of type 2 diabetes due to adverse exposures in utero. The extent to which other more distinct exposures in fetal life such as gestational diabetes may play a role in fetal programming of type 2 diabetes will be addressed. Finally, recent data indicating that immature adipose tissue stem cell functions may be involved in developmental programming of type 2 diabetes will be presented.