Randomised controlled trialindependent cross-checkabstract checked I-SRC-127 standard review
High insulin levels can make the body resistant to insulin
Effect of sustained physiologic hyperinsulinaemia and hyperglycaemia on insulin secretion and insulin sensitivity in man.
Overview
Del Prato S et al.. Diabetologia 1994 · PMID 7851681 · DOI 10.1007/BF00400466
Four days of raised insulin reduced the body's response to insulin by 20-40% in healthy volunteers.
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?
Test whether high insulin causes insulin resistance
- How was the study done?
Infusion experiment with clamp tests
- How many people, animals or samples were studied?
15 healthy adults
- What was actually found?
Insulin resistance developed
- How large was the observed effect?
Glucose disposal -20 to -40%
- What do the results mean in everyday life?
Too much insulin can feed the problem
- What are the study's limitations?
Small, short
- What does it say about Elawady's specific claim?
Supports the causal debate, not the denial of insulin resistance
- Do the results apply to Germany and Europe?
High
- What can explicitly not be concluded from this study?
Long-term relevance
Scientific in-depth review
1. Full reference
- Authors
- Del Prato S et al.
- Journal
- Diabetologia
- Year
- 1994
- Identifier
- PMID 7851681 DOI 10.1007/BF00400466
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works record checked
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
NIH grants; no COI statement.
2. Research question
Does sustained physiological hyperinsulinaemia cause insulin resistance in healthy humans?
3. Study design and population
- Study design
- Randomised controlled trial – Experimental infusion study (randomised protocols) with glucose clamps
- Population
Healthy young adults
- Country
USA
- Period
Published 1994
- Sample size
15
- Inclusion and exclusion criteria
Healthy volunteers
4. Methods and endpoints
- Exposure / intervention
72-96 h euglycaemic hyperinsulinaemia (+72 pmol/l) or hyperglycaemic hyperinsulinaemia
- Comparator
Pre-infusion clamp
- Endpoints
Whole-body glucose disposal, insulin secretion
- Statistical methods
Before-after comparison
5. Actual results
- Results
After 4 days of sustained euglycaemic hyperinsulinaemia, whole-body glucose disposal decreased by 20-40%, due to impaired non-oxidative glucose disposal; insulin secretion response to hyperglycaemia was diminished.
- Absolute risks
not applicable
- Authors' conclusion
Chronic physiological hyperinsulinaemia leads to insulin resistance; hyperinsulinaemia is not only a compensatory response but also a self-perpetuating cause of the defect in insulin action.
6. Strengths
- Direct experimental manipulation in humans
7. Weaknesses
- Very small
- Short duration
- Healthy volunteers
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Small mechanistic study.
9. Assessment of the statistical interpretation
Effect large in relative terms (20-40%) but in 15 people over 4 days.
10. Relevance to the specific claim
Strongest supporting-side evidence for his underlying idea that high insulin is a driver. But it measures insulin resistance and thereby confirms that the phenomenon exists.
11. Independent contrary findings
I-SRC-112, I-SRC-128 (insulin resistance predicts diabetes).
12. Transferability to Germany and Europe
Physiology universal.
13. Overall methodological judgement
Supports 'hyperinsulinaemia causes insulin resistance', not 'insulin resistance does not exist'.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | indirect |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Relevance of short infusions for long-term disease.
15. Linked fact checks
- 'Insulin resistance' is a wrong term; there is no such thing as insulin resistance. – Studies with mixed or unclear results