Intermittent Fasting and Insulin Sensitivity
Lean Healthy Male Subjects.
|- candidate number||5949|
|- NTR Number||NTR1841|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||15-jun-2009|
|- Secondary IDs||06-170 MEC AMC|
|- Public Title||Intermittent Fasting and Insulin Sensitivity
Lean Healthy Male Subjects.
|- Scientific Title||Intermittent Fasting and Insulin Sensitivity
Lean Healthy Male Subjects.
|- hypothesis||We hypothesize that peripheral insulin sensitivity increases after a period of intermittent fasting because of an increased turnover of IMCL and/or subsequent changes in the composition of intramyocellular lipids (glyco(shpingo)lipids and acylcarnitineprofiles) and by that a more favourable intramyocellular milieu with less oxidized lipids, preserved mitochondrial function and insulin signalling. |
|- Healt Condition(s) or Problem(s) studied||Insulin resistance, Fasting|
|- Inclusion criteria||1. Lean healthy male volunteers;|
2. Age 18 - 35 years;
3. BMI 20-25 kg/m2;
4. Stable weight three months prior to study inclusion;
5. Normal oral glucose tolerance test (OGTT) using the ADA-criteria.
|- Exclusion criteria||1. Any medication;|
2. DM II in first degree family members;
3. Hypertriglyceridemia or any other lipid metabolism disorder;
4. Intensive sports (> three times weekly);
5. Any medical disorder of significant relevance;
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2007|
|- planned closingdate||31-dec-2007|
|- Target number of participants||8|
|- Interventions||After the first study day, volunteers are randomly assigned to: |
1. Two weeks standard diet;
2. Two weeks of intermittent fasting.
After these two weeks, a study day as previously described will follow where after volunteers change diet (standard vs IF, or IF vs standard).
|- Primary outcome||Insulin sensitivity of glucose metabolism.|
|- Secondary outcome||Insulin sensitivity of lipid and protein metabolism.|
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||MD. M.R. Soeters|
|- CONTACT for SCIENTIFIC QUERIES||MD. M.R. Soeters|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Department of Endocrinology and Metabolism|
(Source(s) of Monetary or Material Support)
|Academic Medical Center (AMC), Department of Endocrinology and Metabolism|
Soeters MR, Serlie MJ.
Ned Tijdschr Geneeskd. 2009 Apr 18;153(16):742. Dutch.
2:Effects of Insulin on Ketogenesis Following Fasting in Lean and Obese Men.
Soeters MR, Sauerwein HP, Faas L, Smeenge M, Duran M, Wanders RJ, Ruiter AF, Ackermans MT, Fliers E, Houten SM, Serlie MJ.
Obesity (Silver Spring). 2009 Feb 19. [Epub ahead of print]
Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting.
Heemstra KA, Soeters MR, Fliers E, Serlie MJ, Burggraaf J, van Doorn MB, van der Klaauw AA, Romijn JA, Smit JW, Corssmit EP, Visser TJ.
J Clin Endocrinol Metab. 2009 Jun;94(6):2144-50. Epub 2009 Mar 17.
Muscle acylcarnitines during short-term fasting in lean healthy men.
Soeters MR, Sauerwein HP, Duran M, Wanders RJ, Ackermans MT, Fliers E, Houten SM, Serlie MJ.
Clin Sci (Lond). 2009 Apr;116(7):585-92.
Muscle adaptation to short-term fasting in healthy lean humans.
Soeters MR, Sauerwein HP, Dubbelhuis PF, Groener JE, Ackermans MT, Fliers E, Aerts JM, Serlie MJ.
J Clin Endocrinol Metab. 2008 Jul;93(7):2900-3. Epub 2008 Apr 8.
Gender-related differences in the metabolic response to fasting.
Soeters MR, Sauerwein HP, Groener JE, Aerts JM, Ackermans MT, Glatz JF, Fliers E, Serlie MJ.
J Clin Endocrinol Metab. 2007 Sep;92(9):3646-52. Epub 2007 Jun 12.
Recombinant human C1-inhibitor in the treatment of acute angioedema attacks.
Choi G, Soeters MR, Farkas H, Varga L, Obtulowicz K, Bilo B, Porebski G, Hack CE, Verdonk R, Nuijens J, Levi M.
Transfusion. 2007 Jun;47(6):1028-32.
|- Brief summary||An important adaptation during fasting is a change in fuel utilization. In skeletal muscle, fatty acids and ketone bodies will be used for ATP production and glucose uptake and subsequent glucose oxidation will be minimized. The supply of fatty acids is derived from lipolysis and partly by oxidation of stored intramyocellular triglycerides and diacylglycerol.
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 with implications for metabolism (“cycles of feast and famine”). In the last few hundred years, but most notably very recently, a tremendous change has occurred in feeding and exercise behaviour leading to the troublesome obesity and diabetic epidemic. Some postulate that 10.000 years ago our genome was made, build for the cycles of feast and famine, but not made for the continuous oversupply of food and lack of exercise in our modern era. This hypothesis is outlined underneath.
A recent study found that intermittent fasting (IF) for two weeks, mimicking cycles of feast and famine, improves insulin sensitivity. In this study total IMCL and the expression of glucose transporter GLUT 4 did not change. This could indicate that IMCL composition and lipid turnover may be responsible for the difference found in insulin sensitivity. In the same study, during the hyperinsulinemic euglycemic clamp, IMCL decreased very rapidly, indicating that even under hyperinsulinemic conditions, fatty acid oxidation is the main energy providing flux and by definition glucose is preferentially stored as glycogen. Lipolysis is almost completely suppressed by high levels of insulin, meaning that the substrates for fatty acid oxidation come from stored intramyocellular lipids instead of from fatty acid uptake from the plasma compartment. Depletion of IMCL can then be followed by replenishment, indicating turnover. This could be physiological during cycles of feast and famine.
We hypothesize that peripheral insulin sensitivity increases after a period of intermittent fasting because of an increased turnover of IMCL and/or subsequent changes in the composition of intramyocellular lipids (glyco(shpingo)lipids and acylcarnitineprofiles) and by that a more favourable intramyocellular milieu with less oxidized lipids, preserved mitochondrial function and insulin signalling.
|- Main changes (audit trail)|
|- RECORD||15-jun-2009 - 18-jan-2010|
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