Cohort studyindependent cross-checkabstract only checked★ key study I-INTB-02 in-depth review
Insulin resistance appears years before type 2 diabetes
Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents.
Overview
Warram JH et al.. Ann Intern Med 1990 · PMID 2240915 · DOI 10.7326/0003-4819-113-12-909
In high-risk offspring, slow glucose clearance with high insulin levels predicted diabetes one to two decades later.
Does the study support the specific claim? No · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Find the first defect in type 2 diabetes
- How was the study done?
Prospective cohort with glucose tolerance tests
- How many people, animals or samples were studied?
155 offspring of diabetic parents, 186 controls
- What was actually found?
Slow glucose clearance and high insulin preceded diabetes
- How large was the observed effect?
Kg 1.7 vs 2.2 %/min; second-phase insulin 329 vs 117 pM
- What do the results mean in everyday life?
The body's reduced response to insulin can be measured long before diabetes appears.
- What are the study's limitations?
High-risk selected group; indirect measure
- What does it say about Elawady's specific claim?
Contradicts the claim that insulin resistance does not exist.
- Do the results apply to Germany and Europe?
Moderate
- What can explicitly not be concluded from this study?
Does not prove insulin resistance is the only cause of diabetes.
Scientific in-depth review
1. Full reference
- Authors
- Warram JH et al.
- Journal
- Ann Intern Med
- Year
- 1990
- Identifier
- PMID 2240915 DOI 10.7326/0003-4819-113-12-909
- Verification
- verified – PubMed efetch 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Research Support, U.S. Gov't, P.H.S. and Non-U.S. Gov't (publication types); no COI statement in record
2. Research question
Is insulin resistance or insulin deficiency primary in the pathogenesis of type 2 diabetes?
3. Study design and population
- Study design
- Cohort study – Prospective cohort with baseline intravenous glucose tolerance test, average follow-up 13 years
- Population
155 normoglycaemic offspring of two parents with type 2 diabetes and 186 controls without family history, aged 16-60
- Country
not stated in abstract
- Period
average 13 years of follow-up
- Sample size
341
- Inclusion and exclusion criteria
Normal glucose tolerance at baseline
4. Methods and endpoints
- Exposure / intervention
Glucose removal rate (Kg) and insulin levels in IVGTT
- Comparator
Offspring who did not develop diabetes; control subjects
- Endpoints
Incident type 2 diabetes
- Statistical methods
Multivariate analysis
5. Actual results
- Results
Offspring had slower glucose removal (P<0.01) and higher insulin levels (P<0.0001) than controls, even after adjustment for obesity. 16% of offspring developed type 2 diabetes. Baseline Kg 1.7%/min in offspring who developed diabetes vs 2.2%/min in those who did not and 2.3%/min in controls; second-phase insulin 329 vs 117 vs 87 pM. Low Kg and high insulin independently increased diabetes risk.
- Absolute risks
16% of offspring developed type 2 diabetes over about 13 years
- Authors' conclusion
One to two decades before type 2 diabetes is diagnosed, reduced glucose clearance with compensatory hyperinsulinaemia is present, suggesting a primary defect in peripheral tissue response to insulin.
6. Strengths
- Long prospective follow-up
- Direct metabolic measurement at baseline
- High-risk cohort allows observation of disease onset
7. Weaknesses
- Selected high-risk population (both parents diabetic)
- IVGTT is an indirect index of insulin sensitivity
- Older study; abstract only read
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Observational; residual confounding possible but obesity adjusted.
9. Assessment of the statistical interpretation
Associations are strong and prospective; they show that insulin resistance precedes diabetes, not that it is the only cause.
10. Relevance to the specific claim
Shows insulin resistance is measurable and predicts type 2 diabetes years in advance; contradicts C-SRC-37.
11. Independent contrary findings
Insulin secretion defects also contribute in other populations.
12. Transferability to Germany and Europe
Physiology transferable; population was US.
13. Overall methodological judgement
Classic prospective evidence that insulin resistance with compensatory hyperinsulinaemia precedes type 2 diabetes.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | moderate |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Relative contribution of beta-cell failure in different ethnic groups.
15. Linked fact checks
- 'Insulin resistance' is a wrong term; there is no such thing as insulin resistance. – Studies contradicting or limiting the claim