Diabetes Mellitus, Type 2, Endoplasmic Reticulum Stress
Conditions
Keywords
Endoplasmic Reticulum
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.
Interventions
OTHERNo intervention
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* 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 * HCG negative blood (for female subjects) * Affiliated to the Social Security.
Exclusion criteria
* 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 * Any drug taken for less than 8 days without the inclusion of minor analgesics (aspirin, paracetamol), anti-hypertensive medications, oral hypoglycemic (metformin and sulphonylureas) and insulin secretors dependent glucose as inhibitors of DPP4 (dipeptidyl peptidase-4) and oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Show an increase in markers of ER stress in fasting patients with type 2 diabetes | 2 days | Protein expression markers of ER stress pathway BiP / GRP 78, CHOP, ATF4 EDEM and XBP-1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess whether insulin induces an increase in markers of ER stress | 2 days | Insulin sensitivity |
| Insulin secretion in response to glucose infusion | 2 days | — |
| Insulin secretion in response to arginine infusion | 2 days | — |
| Lipolysis on insulin | 2 days | — |
Countries
France
Outcome results
None listed