Role of Endoplasmic Reticulum Stress in the Pathophysiology of Type 2 Diabetes

NCT02368704 | Unknown

• 1 other identifier: GLUCOSTRESS P 08 11 22
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate whether Endoplasmic Reticulum (ER) stress pathway is activated in peripheral tissues (adipose tissue) in insulin resistant diabetic patients compared to healthy subjects normoglycemic matched for age and sex an to investigate whether ER stress pathway can be activated in response to insulin. Indeed, some preliminar on rates studies shows that ER stress pathway is activated by insulin in liver and adipose tissue showing that hyperinsulinemia might help trigger stress path ER. For this, we propose a case control study of type 2 diabetic patients vs control subjects in which markers of ER stress will be evaluated from abdominal subcutaneous adipose tissue obtained before and after euglycemic hyperinsulinemic. We chose to consider adipose tissue subcutaneous rather than visceral adipose tissue for obvious reasons of lesser invasiveness.

Conditions

Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress

Keywords

Endoplasmic Reticulum

Outcome Measures

Primary Outcomes (1)

• Show an increase in markers of ER stress in fasting patients with type 2 diabetes

  Protein expression markers of ER stress pathway BiP / GRP 78, CHOP, ATF4 EDEM and XBP-1

  2 days

Secondary Outcomes (4)

• Assess whether insulin induces an increase in markers of ER stress

  2 days

• Insulin secretion in response to glucose infusion

  2 days

• Insulin secretion in response to arginine infusion

  2 days

• Lipolysis on insulin

  2 days

Study Arms (2)

control

control subjects with : * Nondiabetic subjects (blood glucose \<7.0 mmol/l without hypoglycemic treatment). * The control subjects should be matched to patients for age (± 5 years), sex, and BMI (± 2 kg/m2).

Other: No intervention

case

Diabetic patients with : * Having type 2 diabetes for at least 6 months * HbA1c ≤ 8% * Treat by lifestyle and dietary rules associated or not to a hypoglycemic therapy (metformin and / or sulfamid) and / or insulin secretors dependent glucose as inhibitors of DPP4 (dipeptidyl peptidase-4): Vildagliptin, Sitagliptin, Saxagliptin * No modification of hypoglycemic therapy and / or insulin secretors for at least 3 months

Other: No intervention

Interventions

No intervention OTHER

case; control

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes Healthy volunteers Adults

You may qualify if:

• Specific criteria for diabetic patients:
• Having type 2 diabetes for at least 6 months
• HbA1c ≤ 8%
• Treated by lifestyle and dietary rules associated or not to a hypoglycemic therapy (metformin and / or sulfamid) and / or insulin secretors dependent glucose as inhibitors of DPP4 (dipeptidyl peptidase-4): Vildagliptin, Sitagliptin, Saxagliptin
• No modification of hypoglycemic therapy and / or insulin secretors for at least 3 months
• Specific criteria for control subjects:
• Nondiabetic subjects (fasting blood glucose \<7.0 mmol / l without hypoglycemic treatment).
• The control subjects should be matched to patients for age (± 5 years), sex, and BMI (± 2 kg/m2).
• Common criteria for patients and control subjects:
• Aged 18 to 60 years
• Body Mass Index between 25 and 35 kg/m2
• Accepting the constraints of the protocol and who signed the informed consent
• Systolic blood pressure \< 160 mmHg, diastolic blood pressure \< 90 mm Hg (with or without antihypertensive treatment)
• Resting heart rate between 55 and 100 beats/min.
• Normal laboratory tests or not clinically significant abnormality for NFS platelets, PT, aPTT, fibrinogen ALT, AST, GGT, Serum electrolytes, urea, creatinine, Uric acid Triglycerides, total cholesterol, HDL cholesterol

You may not qualify if:

• Current infections or recent infections (\<10 days)
• Neoplastic disorders (with the exception of carcinoma in situ of the cervix or cutaneous epithelioma), haematological, cardiovascular, psychiatric, neurological
• Poisoning smoking (\>10 cigarettes per day, what ever the duration of intoxication)
• Treatment with insulin or glitazones Pregnancy, Breastfeeding
• Body Mass Index \> 35 kg/m2

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Saint-Louis Hospital

Paris, Paris, 75010, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood samples. These samples will be anonymized, frozen and stored in the INSERM UMR-S 872 in the Cordeliers Research Center (Madame Fabienne Foufelle) under the responsibility of Professor Jean-François Gautier for a maximum period of 15 years, beyond which they will be destroyed. These samples will be destroyed at any time at the request of the patient. This DNA storage will be used to study genes related to the secretion of insulin and to identify other genes involved in the onset of diabetes.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2015
• First Posted: February 23, 2015
• Study Start: November 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 18, 2016

Record last verified: 2016-04

Locations

FR (1)