Otherindependent cross-checkabstract checked★ key study I-FAST-102 in-depth review
Insulin after a 36-hour fast
Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males.
Overview
Jørgensen SW et al.. Am J Physiol Endocrinol Metab 2021 · PMID 33284087 · DOI 10.1152/ajpendo.00433.2020
In 13 healthy men, a 36-hour fast only slightly reduced early insulin release; the body became more insulin resistant for a while.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Understand how insulin release and action change with a longer fast.
- How was the study done?
Compared 36-h and 12-h fasts with glucose tolerance testing and tracers.
- How many people, animals or samples were studied?
13 healthy young men in Denmark.
- What was actually found?
Insulin secretion persisted with a minor reduction; whole-body insulin resistance increased.
- How large was the observed effect?
Not available (abstract only).
- What do the results mean in everyday life?
Healthy bodies keep making some insulin even after a day and a half without food.
- What are the study's limitations?
Tiny sample, men only, short fast.
- What does it say about Elawady's specific claim?
Insulin does not go to zero; physiological insulin resistance during fasting is real but different from diabetes.
- Do the results apply to Germany and Europe?
Applies; same physiology.
- What can explicitly not be concluded from this study?
Effects of fasts longer than 36 h; women; people with diabetes.
Scientific in-depth review
1. Full reference
- Authors
- Jørgensen SW et al.
- Journal
- Am J Physiol Endocrinol Metab
- Year
- 2021
- Identifier
- PMID 33284087 DOI 10.1152/ajpendo.00433.2020
- Verification
- verified – PubMed efetch 2026-10-26; Crossref update-to/updated-by check
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Two authors hold shares in Novo Nordisk / AstraZeneca (stated in record).
2. Research question
Does reduced insulin secretion during prolonged fasting reflect failure to compensate for insulin resistance or a normal adaptation?
3. Study design and population
- Study design
- Other – Within-subject experimental comparison of 36-h vs 12-h fasting with stable isotopes, IVGTT and minimal modelling
- Population
Healthy young men
- Country
Denmark
- Period
not stated in abstract
- Sample size
13
- Inclusion and exclusion criteria
not stated in abstract
4. Methods and endpoints
- Exposure / intervention
36-h fast
- Comparator
12-h overnight fast
- Endpoints
First-phase insulin secretion, hepatic glucose production, hepatic and whole-body insulin action, refeeding meal response
- Statistical methods
Paired comparisons; minimal model indices
5. Actual results
- Results
36-h fasting caused 'a minor reduction of first-phase insulin secretion' with improved hepatic insulin action and increased whole-body insulin resistance; serum insulin during the refeeding meal test was higher after the 36-h fast.
- Absolute risks
not reported
- Authors' conclusion
Reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action.
6. Strengths
- Gold-standard isotope and IVGTT methods
- Healthy participants, within-subject design
7. Weaknesses
- Very small sample, men only
- Full text not open; numbers not available
8. Risk of bias
- Orienting tool
- none applicable
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Small physiological crossover-type study; randomisation of order not stated in abstract.
9. Assessment of the statistical interpretation
Insulin secretion persists after 36 h; only first-phase secretion is slightly reduced. Whole-body insulin resistance rises (physiological 'starvation insulin resistance').
10. Relevance to the specific claim
Shows insulin secretion continues after 36 h of fasting (against 'insulin equals zero') and that prolonged fasting produces a physiological, reversible insulin resistance (relevant to C-FAST-03).
11. Independent contrary findings
12. Transferability to Germany and Europe
Universal biology; applies in Europe and Egypt.
13. Overall methodological judgement
Direct physiological evidence that fasting lowers but does not abolish insulin secretion.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
15. Linked fact checks
- Fasting brings gut hormones, above all insulin, to zero ('your fasting insulin equals zero'). – Studies contradicting or limiting the claim
- Rising blood glucose and acetone (ketones) during fasting are evidence that the liver is working properly, not a danger; high glucose plus acetone is not insulin deficiency. – Studies with mixed or unclear results