The purpose of this study is to determine the effect of gastric banding or gastric bypass on hypothalamic morphology and function, gut hormones and systems biology in obese subjects with and without type 2 diabetes.

Inclusion Criteria:

• Patients aged 35-65 years;
• BMI > 40 kg/m2;
• BMI > 35 and <40 kg/m2 with co-morbidity, which is expected to improve after surgically-induced weight loss;
• A history of longstanding obesity (>5 years);
• Proven failed attempts to lose weight in a conventional way, or primarily successful weight loss with eventual weight regain;
• Intention to adhere to a postoperative follow-up programme.

Exclusion Criteria:

• BMI> 50 or body weight > 150 kg (because it is impossible to safely put people above this weight on a standard table for MRI);
• Subjects with disease related obesity, i.e. Cushing or medication related obesity;
• Use of medication known to affect glucose or lipid metabolism (i.e. prednisone)
• Monogenetic diabetes: MODY, Mitochondrial diabetes;
• LADA (adult-onset latent autoimmune diabetes); detected by c-peptide measurement on screening.
• Impaired renal function (serum creatinine > 176 μmol/L);
• Leg ulcers, gangrene.
• Any genetic or psychiatric disease (e.g. fragile X syndrome, major depression) affecting the brain
• Any significant chronic disease
• Renal or hepatic disease
• Pregnancy
• Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months)
• Aerobic exercise more that 3 times 60 minutes a week
• Alcohol consumption of more than 28 units per week at present or in the past
• Recent blood donation (within the last 2 months)
• Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
• Contra-indications to operative procedures as regular in bariatric surgery
• Contra-indications to MRI scanning

Obese (type 2 diabetic or not) population from primary care (dietary intervention) and hospital setting (bariatric surgery)