Clinical trial NCT01765946: Metformin and Longevity Genes in Prediabetes
Official title: Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Insulin Resistance
Prediabetes
Aging
Inflammation
Keywords: Insulin resistance
Prediabetes
Longevity genes
Inflammation
Metformin
Lead sponsor: University of Padova
Sponsor class: OTHER
First posted: 2013-01-11
Enrollment: 38
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Longevity gene expression
timeFrame: 2 month after treatment
Secondary outcomes:
measure: Insulin sensitivity
timeFrame: 2 months after treatment
measure: Monocyte polarization status
timeFrame: 2 months after treatment
Other outcomes:
Locations:
city: Padova
country: Italy
facility: University Hospital Diabetes Outpatient Clinic
Study officials:
affiliation: University of Padova
name: Angelo Avogaro, M.D. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Kreutzenberg SV, Ceolotto G, Cattelan A, Pagnin E, Mazzucato M, Garagnani P, Borelli V, Bacalini MG, Franceschi C, Fadini GP, Avogaro A. Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2015 Jul;25(7):686-93. doi: 10.1016/j.numecd.2015.03.007. Epub 2015 Mar 24.