Implication of Metabolic and Genomic Modifications in Elderly Subjects

NCT ID: NCT00951392

Last Updated: 2019-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2009-11-30

Brief Summary

An increase of longevity and of the number of men and women older than 60 years old is observed in most industrialized countries. Aging is a complex, multifactorial and continuous process involving physical and biological modifications such as a notably decrease in glucose tolerance and type 2 diabetes risk. Insulin sensitivity follow-up during aging is difficult mainly because of many confounding factors (environment, lifestyle).

In 2006, SUVIMAX 2 study began, based on the monitoring of volunteers who participated in former SUVIMAX study (1994-2003). This study was a randomised trial which was designed to study the link between a low antioxidant intake and risk of cancer or ischemic heart disease. The subjects recently had a health check-up including complete information about their diet, physical and neurosensory status. Based on these data, a score was established to classify subjects according to their quality of aging ("successful aging versus "problematic aging") These volunteers, who undertook a 13-year follow-up (dietary and medical status), constitute the reference population to determine the mechanisms involved in the insulin resistance development in aging.

The purpose of our research work is to determine whether the quality of aging could influence insulin sensitivity, by studying metabolic profile and change in gene expression (genes involved in glucose metabolism and metabolic senescence in muscle tissue) during aging.

Conditions

Insulin Sensitivity; Aging

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Problematic aging

Group Type: EXPERIMENTAL

euglycemic hyperinsulinemic clamp

Intervention Type: DRUG

Insulin perfusion at 1 mU.kg-1.min-1

Glucose perfusion to maintain euglycemia at 5,0 ± 0,5 mmol/l

Blood tests

muscle biopsy

Intervention Type: PROCEDURE

Gene expression in muscle tissue will be studied with two approaches :

• Candidate gene approach by quantitative RT-PCR : genes involved in the carbohydrates and lipids metabolism including lipid oxidation in muscle (lipid carriers, PPARs), expression of 7 sirtuins isoforms as well as some of their target genes (NFkB, PGC1a)
• Global transcriptome analysis by DNA Chip

indirect calorimetry

Intervention Type: DEVICE

energy expenditure measurement

successful aging

Group Type: EXPERIMENTAL

euglycemic hyperinsulinemic clamp

Intervention Type: DRUG

Insulin perfusion at 1 mU.kg-1.min-1

Glucose perfusion to maintain euglycemia at 5,0 ± 0,5 mmol/l

Blood tests

muscle biopsy

Intervention Type: PROCEDURE

Gene expression in muscle tissue will be studied with two approaches :

• Candidate gene approach by quantitative RT-PCR : genes involved in the carbohydrates and lipids metabolism including lipid oxidation in muscle (lipid carriers, PPARs), expression of 7 sirtuins isoforms as well as some of their target genes (NFkB, PGC1a)
• Global transcriptome analysis by DNA Chip

indirect calorimetry

Intervention Type: DEVICE

energy expenditure measurement

Interventions

euglycemic hyperinsulinemic clamp

Insulin perfusion at 1 mU.kg-1.min-1

Glucose perfusion to maintain euglycemia at 5,0 ± 0,5 mmol/l

Blood tests

Intervention Type: DRUG

muscle biopsy

Gene expression in muscle tissue will be studied with two approaches :

• Candidate gene approach by quantitative RT-PCR : genes involved in the carbohydrates and lipids metabolism including lipid oxidation in muscle (lipid carriers, PPARs), expression of 7 sirtuins isoforms as well as some of their target genes (NFkB, PGC1a)
• Global transcriptome analysis by DNA Chip

Intervention Type: PROCEDURE

indirect calorimetry

energy expenditure measurement

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Volunteers from the cohort aging SUVIMAX 2
• Men and Women
• over 60 years
• BMI between 18 and 35 kg/m2 (including terminals)
• Normal medical check up
• Blood pressure < 140/90 mmHg
• Normal glycemia, lipid profile
• sedentary or moderate physical activity (maximum 4 hours per week)

Exclusion Criteria

• Biological results or anormal chek-up
• medical or surgical history not compatible with study
• severe digestive, cardiovascular, renal, liver or tumor disorders history in the 5 last years
• infectious or inflammatory disease within 2 months
• surgical history within 3 months
• bood donation within 2 months
• coagulation disease, anticoagulant or antiplatelet agents (aspirin ...) treatment
• xylocaïn allergy
• claustrophobia
• Drug that could affect insulin sensitivity (beta blockers, lipid lowering, oral antidiabetics, insulin, , steroids)

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Hospices Civils de Lyon

Principal Investigators

Martine LAVILLE, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre de Recherche en Nutrition Humaine Rhône-Alpes

Locations

Centre de recherche en nutrition humaine Rhône-Alpes

Pierre-Bénite, , France

Countries

France

References

Betry C, Meugnier E, Pflieger M, Grenet G, Hercberg S, Galan P, Kesse-Guyot E, Vidal H, Laville M. High expression of CPT1b in skeletal muscle in metabolically healthy older subjects. Diabetes Metab. 2019 Apr;45(2):152-159. doi: 10.1016/j.diabet.2018.01.018. Epub 2018 Feb 12.

Reference Type: RESULT

PMID: 29657112 (View on PubMed)

Other Identifiers

2008.547

Identifier Type: -

Identifier Source: org_study_id