Metformin and Longevity Genes in Prediabetes

University of Padova

Status and phase

Completed

Phase 4

Conditions

Aging

Prediabetes

Inflammation

Insulin Resistance

Treatments

Drug: placebo

Drug: Metformin

Study type

Interventional

Funder types

Other

Identifiers

NCT01765946

MetAge

Details and patient eligibility

About

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.

Enrollment

38 patients

Sex

All

Ages

40 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Pre-diabetes, defined as IFG (fasting glucose between 100 and 125 mg/dl) or IGT (2h post-oral glucose load (75g) between 140 and 199 mg/dl);
Age 40-75 years;
Both genders.

Exclusion criteria

Type 1 or 2 diabetes mellitus;
Pregnancy, lactation;
Acute, chronic or inflammatory diseases;
Neoplasms;
Immunological diseases, organ transplantation, steroid therapy;
Uncontrolled arterial hypertension (systolic pressure > 180 mmHg or diastolic > 120 mmHg);
Recent(within 3 months) surgical intervention or cardiovascular accidents;
Known allergy to metformin.