Metformin and Core Temperature in Obese and Lean Males

Obesity and diabetes mellitus type 2 (DM2) are health problems with a tremendous impact. Many attempts have been made to combat obesity and DM2, however, a breakthrough therapy is still lacking.

Obesity is the result of an imbalance between energy intake and energy expenditure. 18F-fluorodeoxy-d-glucose (18F-FDG) positron emission tomography computed tomography (PET-CT) pinpoint areas with high glucose turnover. Physiological 18F-FDG accumulation is frequently observed in the colon. Therefore, the colon might play an important role in increasing energy expenditure by consuming calories. However, the possibility of the colon as an energy dissipating tissue has not yet been explored. The colon could become an interesting new target of research to find a method to combat obesity.

Metformin is one of the few drugs in the treatment of DM2 that is associated with moderate weight loss. Interestingly, patients using metformin show an increased 18F-FDG-uptake in the colon. Whether this higher uptake of glucose also cause an increase in core temperature and/or an increase in energy expenditure is not known. The cause for this increase in glucose uptake in the colon by metformin use is unknown. Also, it is unknown whether this increase in glucose uptake results in an increased energy expenditure and/or an increase in core body temperature.

Objective: In this study the researchers aim to investigate the influence of metformin (500 mg 1/day) on temperature in the colon, glucose uptake in the colon and energy expenditure in healthy lean (BMI < 24kg/m2) or obese subjects (BMI>28kg/m2). The investigators will measure 18F-FDG uptake in the colon, temperature in the colon, insulin sensitivity and energy expenditure before after using metformin.

Inclusion criteria

• Male
• Caucasian origin
• Subjects should be able and willing to give informed consent
• > 50 years old
• BMI< 24 kg/m2 or > 28 kg/m2

Exclusion criteria

• Renal failure (GFR< 60ml/min)
• Liver insufficiency (AST or alanine aminotransferase 3 times upper value)
• Chronic use of drugs or medication
• Diabetes mellitus
• Lactate acidosis or precoma diabeticum in medical history
• Acute or chronic diseases such as: dehydration, severe infection, shock, heartfailure, pulmonary insufficiency, recent heart attack
• Alcoholism