Metformin and Longevity Genes in Prediabetes

Phase 4

Completed

• Conditions: Insulin Resistance; Prediabetes; Aging; Inflammation
• Interventions: Drug: placebo; Drug: Metformin

• Registration Number: NCT01765946
• Lead Sponsor: University of Padova

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2013-01-08
• Study First Submitted QC: 2013-01-10
• Study First Posted: 2013-01-11
• Status Verified: 2013-03
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Last Update Submitted: 2013-03-12
• Last Update Posted: 2013-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo tables tid for 2 months
Metformin	Metformin	Metformin tablets 500 mg tid for 2 months

Primary Outcome Measures

Name	Time	Method
Longevity gene expression	2 month after treatment	Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC)

Secondary Outcome Measures

Name	Time	Method
Insulin sensitivity	2 months after treatment	A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT
Monocyte polarization status	2 months after treatment	Polarization of circulating monocytes in M1 (CD68+CCR2+) and M2 (CX3CR1+CD163+/CD206+)

Trial Locations

Locations (1)

University Hospital Diabetes Outpatient Clinic; 🇮🇹 Padova, Italy