Pre-diabetes, a condition characterized by hyperglycaemia, is associated with increased
cardiovascular risk and reduced life expectancy, as compared to the general population.
AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy
homeostasis and metabolism, and recently it has been demonstrated that AMPK regulates aging
pathways, as well. AMPK is susceptible to modulation through pharmacologic (e.g. metformin)
and non-pharmacologic (e.g. physical exercise) interventions. This clinical trial aims to
describe the effects of the AMPK pathway on longevity genes and inflammation in the setting
of pre-diabetes in vivo and in vitro. To this end, the investigators will compare treatment
with metformin (500 mg t.i.d) for 2 months, versus placebo in pre-diabetic subjects. The
investigators will assess expression of longevity genes SIRT1, p66Shc, p53 and mTOR in
peripheral blood mononuclear cells (PBMCs) ex vivo. The investigators will evaluate monocyte
polarization by flow cytometry, according to the expression of surface antigens (CD68, CCR2,
CD163, CD206, CX3CR1) to determine the prevalence of pro- or anti-inflammatory cells.
Inflammatory cytokines (TNF-alpha, MCP-1, IL-1, IL-6, IL-10, CCL12) will also be determined.
In the in vitro study the investigators will evaluate the effects of AMPK activation or
inhibition on longevity gene and protein expression.