The pathophysiological meaning of depressed Sirt1 expression in monocytes has beendemonstrated in C57Bl/6 mice with a targeted deletion of Sirt1 inmacrophages (Lys‐Cre), which showed a metabolic syndrome–like phenotype.48 In subjects at risk for diabetes, downregulation of Sirt1resulting from metabolic toxicity reduced the expression of tissue inhibitor of metalloproteinase 3(TIMP3), a protease inhibitor with antidiabetic and antiatherosclerotic functions.49–52 TIMP3exerts its functions mainly through the inhibition of ADAM‐17, also known as TNF‐alphaconverting enzyme. This evidence concerns the gene TIMP3 and diabetes mellitus.