Type 2 Diabetes
Conditions
Keywords
Resveratrol, SIRT1, AMPK
Brief summary
Animal studies indicate that resveratrol, a phytoalexin enriched in the skin of red grapes and a constituent of red wine, is associated with longevity likely through the increased production of a protein, SIRT1. The trial is a proof-of-concept study primarily designed to examine for the first time in humans, the effect of 12 weeks of oral resveratrol on skeletal muscle SIRT1 expression in 10 patients with T2DM in a randomized, placebo-controlled, double-blind fashion. Secondary outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure, physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels and insulin sensitivity.
Detailed description
Eligible criteria include Chinese males, aged between 40 and 69 years old, with T2DM with a HbA1c of 7.1 to 12% and who have been on a stable oral hypoglycemic regimen for the past 3 months. Subjects who were insulin-dependent, with renal or liver impairment or who were terminally ill were excluded.
Interventions
Starting dose of 500 mg daily of either resveratrol to be administered on Day 1 and increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia.
DRUGPlacebo
Sponsors
National Medical Research Council (NMRC), Singapore
Khoo Teck Puat Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to give informed consent 2. Chinese Male 3. Age 40 to 69 yrs old 4. For subjects with type 2 diabetes mellitus * Diagnosis of type 2 diabetes mellitus based on MOH criteria and, * HbA1c \>6.5 during screening
Exclusion criteria
Willing to abstain from ingesting large quantities of resveratrol-containing foods (eg. red wine, nuts) Cancer diagnosis that is currently under treatment, is clinically detectable, or that has been treated within the past 5 years Terminal disease or on palliative care Current excessive alcohol intake (\>21 units per week for men; 14 units per week for women) On maximal doses of 3 or \> oral hypoglycaemic agents On insulin therapy or known type 1 diabetes mellitus Past history of documented or suspected hypoglycemia within last 3 months Past history of recurrent hypoglycemia Past history of serious hypoglycemia as defined by documented hypoglycemia requiring hospital admission Past history of hyperglycemic emergencies within last 6 months Past or current history of hemorrhagic strokes On anti-platelet agents, non-steroidal anti-inflammatory drugs (NSAIDs), anti-coagulation therapy or omega-3 fatty acids History of unexplained bleeding disorders History of any grape allergy History of allergy to local anaesthetic History of surgery with surgery with clips, staples or stents Presence of cardiac pacemaker or metallic foreign body in any part of the body On alternative or traditional medications Treated with another investigational drug within last 6 months Poorly controlled hypertension (SBP \>/= 160 or DBP \>/= 100) within last one month ALT and/or AST \> 1.5 times above upper limit of normal within last 6 months GFR \< 50 ml/min/1.73m2 (MDRD equation) within last 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Skeletal muscle sirtuin 1 (SIRT1) expression | 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Skeletal muscle phosphorylated-AMPK-Thr172 (p-AMPK) expression | 3 months | — |
| Skeletal muscle glucose transporter type 4 (GLUT 4) expression | 3 months | — |
| Glycated hemoglobin (HbA1c) | 3 months | — |
| Body weight | 3 months | — |
| Insulin sensitivity | 3 months | — |
| Lipid profile | 3 months | — |
| Skeletal muscle 5'-AMP-activated protein kinase (AMPK) expression | 3 months | — |
| Physical activity level | 3 months | — |
| Abdominal adipose tissue distribution | 3 months | — |
| Skeletal muscle fibre type composition | 3 months | — |
| Renal function | 3 months | Serum creatinine |
| Liver function | 3 months | Transaminases |
| Energy expenditure | 3 months | — |
Countries
Singapore
Outcome results
None listed