NCT01765946

Metformin and Longevity Genes in Prediabetes

Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 38 (actual)
• Sponsor: University of Padova · Academic / Other
• Sex: All
• Age: 40 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Insulin Resistance
• Prediabetes
• Aging
• Inflammation

Interventions

Type	Name	Description
DRUG	Metformin	Metformin tablets 500 mg tris in die (tid)
DRUG	placebo

Timeline

• Start date: 2010-06-01
• Primary completion: 2013-03-01
• Completion: 2013-03-01
• First posted: 2013-01-11
• Last updated: 2013-03-13

Locations

1 site across 1 country: Italy