Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI

Inclusion Criteria

Subjects will be men and women between the ages of 18 and 65. The following table list inclusion criteria for each group (lean diabetic and obese diabetic). Subjects must meet either HbA1c or fasting plasma glucose (FPG) criteria.

Lean diabetic:

BMI: 18-25 kg/m2 HbA1c: 27 kg/m2 HbA1c: 8.9%, or FPG>250 mg/dL)

• Women who are breastfeeding, pregnant, or wanting to become pregnant.
• Women using IUD
• Any change in the dosage of hormonal contraceptive medications (birth control pills, implanon). Subjects should remain on same medication/ same dose during the time of the entire study.
• Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min) and end-stage renal disease
• Moderate, or severe hepatic impairment
• Hypersensitivity to the active substance or any of the excipients in liraglutide
• History of diabetic ketoacidosis
• Congestive heart failure
• Inflammatory conditions like inflammatory bowel disease, Rheumatoid arthritis etc
• Gastroparesis
• Pancreatitis
• Gallstones- as they may cause increased risk of pancreatitis
• Alcohol consumption- the maximum quantity for men is 140g-210g per week. For women, the range is 84g-140g per week or drinking as consuming no more than two drinks a day for men and one for women. Alcohol can cause increased risk of pancreatitis and hypoglycemia.
• Untreated thyroid disease like hypothyroidism or hyperthyroidism
• Subjects taking the following medications: warfarin, steroids (inhaled or systemic due to reduced hypoglycemic effect), and subjects on other hormones (LHRH analogs etc).
• Subjects on any oral anti-diabetic agent except metformin
• Personal or family history of MEN II or medullary thyroid cancer
• Subjects with any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neuron or biostimulators, electronic infusion pumps, etc.)
• Subjects with any type of metallic implant that could potentially be displaced or damaged during MRI, such as aneurysm clips, metallic skull plates, surgical implants etc. or metal containing tattoos
• Anxiety and/or claustrophobia
• Uncontrolled cardiac impairment, circulatory impairment, or inability to perspire (poor thermoregulatory function)
• Significant sensory or motor impairment
• Epilepsy, particularly photo-sensitive epilepsy, which may place the individual at a higher risk for adverse events during fMRI scanning with visual stimulation
• Subjects with neurological problems which may interfere with or complicate testing (e.g. presence of titubation)
• Body weight above the limitation of the MRI scanning table (330lbs/150 Kg) or body dimensions that could difficult the performance of the scan.
• Subjects who cannot adhere to the experimental protocol for any reason
• Anemia with Hgb less than 10
• Uncontrolled infectious diseases (e.g. HIV, hepatitis, chronic infections etc)
• Any uncontrolled endocrine condition, e.g Cushing's, Acromegaly, etc
• Any cancers or lymphoma
• Eating disorders like anorexia, bulimia
• Severe hypertriglyceridemia (triglycerides >500 mg/dl)
• Weight loss surgery or gastrectomy
• Any changes in medications that affect brain function, e.g. anti-depressants, anti-psychotics, anti-anxiety, anti-seizure medications, antihypertensives etc (subjects should remain on same medication/ same dose during the time of the entire study).
• Irregular periods, defined as cycle length less than 22 days or more than 40 days.
• Any change in smoking status.
• Vegetarians- as food images presented will include numerous non-vegetarian items and thus will not be appealing as high calorie food items.