Systemic Cross-talk Between Brain, Gut, and Peripheral Tissues in Glucose Homeostasis: Effects of Exercise Training (CROSSYS)

Systemic Cross-talk Between Brain, Gut, and Peripheral Tissues in Glucose Homeostasis: Effects of Exercise Training

Modelling Systemic Cross-talk Between Brain, Gut, and Peripheral Tissues in Glucose Homeostasis: Exercise Training and Public Health

University of Helsinki, University of Eastern Finland, Turku University Hospital, Academy of Finland, Finnish Cultural Foundation, Diabetes Research Foundation, Finland, Juho Vainio Foundation

Obesity and insulin resistance are worldwide epidemic and taking a major public health toll. Obesity also increases the risk for cognitive impairment which is also an increasing medical, societal, and economic challenge. The ultimate goal of this proposal is to develop a statistical model to assess systemic cross-talk between brain, peripheral tissues, gut microbiota and glucose metabolism. Integrated with exercise training intervention the results will be utilized to provide disease risk profiling and personalized predictions of exercise training as a drug free treatment for insulin resistance and type 2 diabetes.

Subjects are required to exercise four times a week during six months. Exercise training consists of endurance training, resistance training and high-intensity interval training adjusted to subject's fitness level.

Brain glucose uptake (micromol/100g/min) is measured with positron emission tomography (PET) with [18F]-labelled fluoro-deoxy-glucose (FDG) tracer.

Brain inflammation (dimensionless; standistibution volume ratio) is measured with positron emission tomography (PET) with PK11195 tracer

Liver glucose uptake (micromol/100g/min) is measured with positron emission tomography (PET) with [18F]-labelled fluoro-deoxy-glucose (FDG) tracer

Adipose tissue glucose uptake (micromol/100g/min) is measured with positron emission tomography (PET) with [18F]-labelled fluoro-deoxy-glucose (FDG) tracer

Whole-body insulin sensitivity (M-value; micromol/100g/min) during the hyperinsulinemic euglycemic clamp

Inclusion Criteria: monozygotic twins body mass index (BMI) difference ≥ 2 kg/m2 and/or type 2 diabetes At least one co-twin is overweight (BMI > 25 kg/m2) Exclusion Criteria: BMI > 60 kg/m2 body weight > 170 kg waist circumference > 150 cm mental disorder or poor compliance eating disorder or excessive use of alcohol active ulcus disease diabetes requiring insulin treatment or fasting glucose > 10 mmol/l pregnancy past dose of radiation claustrophobia presence of ferromagnetic objects that would make MRI contraindicated

IPD of the main outcome measures will be opened if possible to such as extent that individuals cannot be identified.

Heiskanen MA, Honkala SM, Hentila J, Ojala R, Lautamaki R, Koskensalo K, Lietzen MS, Saunavaara V, Saunavaara J, Helmio M, Loyttyniemi E, Nummenmaa L, Collado MC, Malm T, Lahti L, Pietilainen KH, Kaprio J, Rinne JO, Hannukainen JC. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS). Exercise training intervention in monozygotic twins discordant for body weight. BMC Sports Sci Med Rehabil. 2021 Feb 24;13(1):16. doi: 10.1186/s13102-021-00241-z.