Short Term Intermittent Fasting and Insulin Resistance (IFAST)

The purpose of the study is to determine the effect of intermittent fasting on insulin secretion and insulin sensitivity in skeletal muscle and fat distribution.

Approximately 250.000 patients are diagnosed with type 2 diabetes (T2DM) in Denmark, and world-wide close to 350 million people suffer from diabetes. T2DM develops in genetically susceptible individuals as a result of excess energy intake and insufficient amount of daily physical activity. The pathophysiology encompasses a mismatch between the insulin secretory capacity and insulin sensitivity, predominantly manifested in skeletal muscle as insulin resistance. T2DM is associated with increased morbidity and mortality. The disease is triggered by the individual lifestyle, and thereby the potential for prevention and reversal of the disease in its early years after diagnosis is quite large. One potential way to improve glucose homeostasis is by intermittent fasting, also known as alternate day fasting. Intermittent fasting means switching between eating and fasting, and it is a variation of calorie restriction. Intermittent fasting has been studied in animals. Together with calorie restriction, intermittent fasting is the most efficient way to expand lifespan of many animal species without genetically altering them. A wide range of age related changes are delayed including beneficial effects on hypertension, degenerative brain disease, immune responses, DNA repair capacity and glucose homeostasis. Fat redistribution with fat translocating from between the organs and the liver to the subcutis. Little is known about intermittent fasting in humans. In 2005 the investigators experimentally tested this concept in young healthy males and found that 15 days of alternating days with fast and food intake increased insulin sensitivity by 16% without any changes in body weight. The explanation could be oscillations in cellular energy stores. Skeletal muscle contains approximately 80% of the stored glycogen alone by virtue of the muscle mass. The liver has a higher glycogen concentration, but it is much smaller. A single prolonged (>24 hrs) day of fasting may not decrease muscle glycogen, while the decrease in the liver is very fast. A muscle glycogen lowering effect of continued intermittent fasting would be expected, and experimentally indicated. The intermittent fasting method may appeal to some patients, who do not exercise, and the need for testing this intervention in patients with type 2 diabetes is obvious.

intermittent fasting, alternate day fasting, diabetes mellitus, non-alcoholic fatty liver disease, insulin sensitivity

Intermittent fasting conducted by a group of subjects with type 2 diabetes mellitus and an age- and BMI matched control group.

Alternate day fasting (ADF) (water permitted) for 3 weeks with double energy intake every other day. Followed by ADF for 3 weeks with ad libitum diet on eating days.

An euglycemic hyperinsulinemic clamp is performed at day 1 and repeated at day 23 after a control period with no change in the diet. Baseline insulin sensitivity is determined based on these two measurements. The euglycemic hyperinsulinemic clamp is repeated at day 46 after the intermittent fasting period (day 25-44) and two days (day 24 and 45) with a normal diet.

IVGTT performed at baseline, after intermittent fasting without weight loss and again after intermittent fasting with weight loss

Analysis of glycogen content from muscle biopsies obtained after a day of fasting and after a day of eating during the intermittent fasting period.

Change from Baseline in Fat Content in the Liver and Visceral Fat after 20 Days of Intermittent Fasting

By Western blot determine any change in proteins relevant for insulin signalling and turnover of intramyocellular lipids.

Inclusion Criteria: BMI 28-35 Type 2 diabetes or metabolically healthy Diet or orally administered treatment for type 2 diabetes Exclusion Criteria: Regular physical activity Other diseases than type 2 diabetes insulin treatment alcohol abuse