Adaptive Mechanisms In GRown up ObeSity Study (AMIGROS)

Prior treatment

• Previous pancreatitis or other disease in pancreas that needs treatment
• Drug addiction interfering with the study procedures
• Medication with potential to affect adipose tissue metabolism that can not be stopped 10 days before the study days
• Treatment with beta-blockers
• Less than three months from previous use of antibiotics

Other illness

• Type 2 diabetes according to ADA criteria
• Heart failure (NYHA II-IV) or cardiac arrhytmia that needs medical treatment
• Peripheral arterial insufficiency eg claudication
• Hypertension \>170/105 mmHg at screening or more than one class of drugs for treatment of known hypertension
• Renal failure defined as absolute estimated glomerular filtration rate (eGFRcreatinine) \< 60 ml/min/1.73 m2
• Systemic inflammatory disease e.g. rheumatoid arthritis, ulcerative cholitis or Chrons disease. Celiac disease, dyspepsia or IBS are excepted
• Chronic bronchitis or chronic obstructive pulmonary with disease symptoms
• Spinal insufficiency causing inconvenience lying in supine position during the study day
• Psychiatric insufficiency interfering with the study procedures

Lab values

• Impaired fasting glucose (IFG) (venous fasting plasma glucose 6.1-6.9 mmol/l)
• Ongoing or previous ischemic heart disease, eg angina pectoris, unstable angina or previous myocardial infarction treated with platelet inhibitors or non vitamin-K oral anticoagulants
• Previous cerebral infarction or transitory ischemic episodes (TIA) treated with platelet inhibitors or other anticoagulants
• Lipid disorder defined as fasting serum triglycerides \> 5.0 mmol/l or serum cholesterol \> 7.5 mmol/l
• Hematologic diseases such as anemia not being substituted (Hb \< 130 g/l in males and Hv \< 120 g/l in females) or disease causing bleeding disorder
• Liver disease e.g. hepatitis B, cirrhosis or conditions where AST or ALT are \> 2 times UNL
• Physical examination or laboratory results indicating that participation in the study is inappropriate

Age

• Alcohol intake \> 10 units/week or known high alcohol intake \< 10 years back in time
• Cancer disease \< 5 years since diagnosis

Other

• First-degree relative with known T2D in lean or Ob-IS subjects
• Daily use of cigarettes or daily frequent use of smokeless tobacco not enabling the participant to suspend nicotine during a visit at the research center without getting abstinent
• Regular physical activity corresponding to Saltin-Gimby level 4
• Special diet eg Atkins or 5:2 for weight reduction. Vegetarian food accepted if duration \> 1 year
• Hypothyroidism defined as TSH \> 4.0 mIE/l and symptoms
• Migraine elicited by stress
• Pregnancy or intention to be pregnant during the study
• Shift work \> 1 time per week that might interfere with the circadian rhytm
• Other reasons that causes the PI to believe that participation is inappropriate

• Men and women of age: 40.0 - 70.0 years
• BMI: 18.0 - 25.0 kg/m2 (lean subjects) and BMI 30.0 - 38.0 kg/m2 (Ob-IS and Ob-IR)
• Fasting insulin \< 9.0 mU/l (lean and Ob-IS subjects) and fasting insulin \> 9.0 mU/l (Ob-IR)
• Fasting glucose \< 6.1 mmol/l
• Body temperature \< 37.5°C
• First-degree relative with known T2D in Ob-IR
• Weight stable ± 5 kg \< 3 months before screening
• Fluent in Swedish and can follow given instructions
• Consent given to participate