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The high prevalence of childhood obesity is contributing to an epidemic of type 2 diabetes mellitus in the adult population ([@B1]). To address this problem, we need to understand the complex link between the early nutritional environment and the epigenome in the developing pancreas and to understand how the phenotype is perpetuated into adulthood. We are currently investigating the interactions between the gut microbiome and the epigenome at the single-cell level.
In this issue of *Diabetes*, Yamada et al. ([@B2]) demonstrate that DNA methylation within a specific promoter is associated with metabolic outcomes in humans. This study used methylation-specific PCR to show that the levels of *IGFBP1* promoter methylation are inversely correlated with fasting insulin, glucose, and triglyceride levels. This is the first study to link genetic and epigenetic alterations in the genome to complex metabolic changes in humans. Further, this study supports the concept that the early nutritional environment plays an important role in the programming of metabolic diseases, including obesity and diabetes.
Nutrition-induced epigenetic modifications have been studied in different tissues, including the intestine, liver, muscle, and fat. DNA methylation occurs at both cytosine and adenosine residues and is a reversible epigenetic modification, catalyzed by DNA methyltransferases and demethylases, respectively ([@B3]). The levels of methylation of cytosine residues are called global or genome-wide levels, whereas the levels of methylation of adenosine residues are called gene-specific levels. Some of the DNA methylation marks are linked to the transcriptional repression of particular genes, while other marks are associated with activation. The genes that are repressed by methylation are either silenced or are not expressed, whereas genes that are activated by methylation are not repressed ([@B3]).
Genomic DNA methylation is dynamic and is altered by a variety of factors, including dietary compounds and the microbiome. The gut microbiome is an important factor in the regulation of the gut environment, and changes in the microbiome may affect the entire organism ([
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