Adaptive Mechanisms In GRown up ObeSity Study (AMIGROS)

The investigator recently showed that the glycan-binding adipokine galectin-1 increased during overfeeding and that galectin-1 independently could predict type 2 diabetes. Further, the molecules that induce insulin release in the fasting state when blood glucose is normal remain elusive. It is possible that galectin-1 is involved in adaptive mechanisms in adipose tissue in obese subjects.

The investigator will define adaptive mechanisms in adipose tissue associated with galectin-1 in obese insulin-sensitive (Ob-IS) subjects compared with obese insulin-resistant (Ob-IR) subjects and lean healthy controls. Further, the investigator will study molecules secreted from adipose tissue that might trigger insulin secretion when blood glucose is normal.

The investigator hypothesizes that Ob-IS subjects keep fatty acid levels normal through an adaptive response in adipose tissue that involves up-regulation of galectin-1 for dampening of immune cell activity and stimulation of lipolysis.

Eligibility Criteria:
Inclusion Criteria:

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

   Exclusion Criteria:
10. First-degree relative with known T2D in lean or Ob-IS subjects
11. Alcohol intake \> 10 units/week or known high alcohol intake \< 10 years back in time
12. 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
13. Regular physical activity corresponding to Saltin-Gimby level 4
14. Special diet eg Atkins or 5:2 for weight reduction. Vegetarian food accepted if duration \> 1 year
15. Impaired fasting glucose (IFG) (venous fasting plasma glucose 6.1-6.9 mmol/l)
16. Type 2 diabetes according to ADA criteria
17. 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
18. Heart failure (NYHA II-IV) or cardiac arrhytmia that needs medical treatment
19. Previous cerebral infarction or transitory ischemic episodes (TIA) treated with platelet inhibitors or other anticoagulants
20. Peripheral arterial insufficiency eg claudication
21. Hypertension \>170/105 mmHg at screening or more than one class of drugs for treatment of known hypertension
22. Lipid disorder defined as fasting serum triglycerides \> 5.0 mmol/l or serum cholesterol \> 7.5 mmol/l
23. 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
24. Renal failure defined as absolute estimated glomerular filtration rate (eGFRcreatinine) \< 60 ml/min/1.73 m2
25. Hypothyroidism defined as TSH \> 4.0 mIE/l and symptoms
26. Liver disease e.g. hepatitis B, cirrhosis or conditions where AST or ALT are \> 2 times UNL
27. Systemic inflammatory disease e.g. rheumatoid arthritis, ulcerative cholitis or Chrons disease. Celiac disease, dyspepsia or IBS are excepted
28. Chronic bronchitis or chronic obstructive pulmonary with disease symptoms
29. Previous pancreatitis or other disease in pancreas that needs treatment
30. Migraine elicited by stress
31. Spinal insufficiency causing inconvenience lying in supine position during the study day
32. Drug addiction interfering with the study procedures
33. Psychiatric insufficiency interfering with the study procedures
34. Medication with potential to affect adipose tissue metabolism that can not be stopped 10 days before the study days
35. Treatment with beta-blockers
36. Less than three months from previous use of antibiotics
37. Cancer disease \< 5 years since diagnosis
38. Physical examination or laboratory results indicating that participation in the study is inappropriate
39. Pregnancy or intention to be pregnant during the study
40. Shift work \> 1 time per week that might interfere with the circadian rhytm
41. Other reasons that causes the PI to believe that participation is inappropriate