IFIS-study: Intermittent Fasting and Insulin Sensitivity In Lean Healthy Male Subjects.

An important feature of fasting is a change in fuel utilization. Glucose
oxidation will decrease and lipid and ketone body oxidation take over. Besides
the fact that a substantial part of oxidized lipids have a hepatic origin, a
substantial part of FFA lies waiting in peripheral tissues (skeletal muscle,
IMLC) to be oxidized. Our early ancestors (50.000 * 10.000 B.C.) had no
unlimited access to food as most people in Western countries have these days.
Furthermore they had to hunt/gather to obtain food and periods of fasting and
exercise were followed by periods of feeding and rest. In the last few hundred
years, but most notably very recently, a tremendous change had occurred in
feeding and exercise behaviour leading to the troublesome obesity and diabetic
epidemic. Skeletal muscle of diabetic and obese subjects contains more lipid
than their healthy, lean counterparts. This is correlated to insulin
resistance. Surprisingly the IMLC content of well trained endurance athletes is
equivalent with the diabetic and obese subjects although these subjects are
very insulin sensitive. A possible explanation for this finding could be that
the high turnover of lipid (and it*s metabolites) in athletes. Intermittent
fasting (IF) for two weeks also improves insulin sensitivity although IMCL and
expression of glucose transporter 4 do not change. This possibly indicates that
very subtle changes are responsible for differences in insulin sensitivity. We
hypothesize that insulin sensitivity increases after a period of intermittent
fasting because of an increased turnover/change in IMLC: subtle changes in
glycolipids and acylcarnitin profiles could be responsible. If proven
effective, IF could be a very simple and cheap measure to prevent obesity or
insulin resistance.

Investigate effect of IF on insulin resistance and possible role acylcarinitin
profiles and glycolipids

Volunteers will be included and undergo two hyperinsulinemic euglycemic clamps
separated with two weeks in which volunteers will be fasting intermittent.
During the clamps insulin sensitivity will be measured as well as other
parameters of glucose metabolism in plasma and muscle.

Intermittent Fasting for two weeks.

Stable isotopes are harmless. Muscle biopsies can cause hematoma: a minimal
invasive biopsy and pressure bandage are used in order to minimalize this risk.
Volunteers can however experience a bruising feeling.