Cohort studyindependent cross-checkabstract checked★ key study I-SRC-112 in-depth review

Insulin resistance measured directly predicts diabetes

Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.

Overview

Lillioja S et al.. N Engl J Med 1993 · PMID 8247074 · DOI 10.1056/NEJM199312303292703

People whose bodies responded poorly to insulin in a clamp test were much more likely to develop diabetes.

Does the study support the specific claim? No · Methodological quality: moderate

Study explained simply

What did the researchers want to find out?: Find predictors of type 2 diabetes
How was the study done?: Prospective cohort with clamp test
How many people, animals or samples were studied?: 200 Pima Indians
What was actually found?: Insulin resistance predicted diabetes
How large was the observed effect?: 6-y incidence 0% vs 27-39%
What do the results mean in everyday life?: Insulin resistance is real and measurable
What are the study's limitations?: One high-risk population
What does it say about Elawady's specific claim?: Contradicts 'no such thing'
Do the results apply to Germany and Europe?: Moderate

Authors: Lillioja S et al.
Journal: N Engl J Med
Year: 1993
Identifier: PMID 8247074 DOI 10.1056/NEJM199312303292703
Verification: verified – PubMed efetch 2026-10-26; Crossref works record checked
Retracted: no
Corrections: none
Extent checked: abstract only
Conflicts of interest and funding: Not stated.

Do insulin resistance and insulin secretory dysfunction predict type 2 diabetes?

Study design: Cohort study – Prospective cohort with hyperinsulinaemic-euglycaemic clamp at baseline
Population: Non-diabetic Pima Indians (mean age 26 years)
Country: USA
Period: Mean follow-up 5.3 years
Sample size: 200; 38 incident diabetes cases
Inclusion and exclusion criteria: Non-diabetic at baseline

Exposure / intervention: Insulin action (clamp), acute insulin response, obesity
Comparator: Values above vs below median
Endpoints: Incident type 2 diabetes
Statistical methods: Cumulative incidence; multivariable prediction

Results: Obesity, insulin resistance (independent of obesity) and low acute insulin response predicted diabetes. Six-year cumulative incidence 39% with both insulin action and insulin response below median, 27% with low action/high response, 13% with high action/low response, 0% with both above median.
Absolute risks: Six-year cumulative incidence 0% to 39% across groups (reported).
Authors' conclusion: Insulin resistance is a major risk factor for type 2 diabetes; a low acute insulin response is an additional but weaker risk factor.

Orienting tool: ROBINS-E
Type of assessment: simplified assessment (abstract only)
Full formal assessment: no
Overall risk of bias: some concerns
Rationale: Small cohort; confounding limited by direct physiological measurement.

Risk difference of about 26-27 percentage points between low and high insulin action (stats/C-SRC-37_lillioja.py).

Insulin resistance was measured directly and predicted diabetes; this directly contradicts the statement that insulin resistance does not exist.

I-SRC-127 (hyperinsulinaemia can cause insulin resistance) - addresses cause, not existence.

Physiology transferable; absolute risks population-specific.

Classic direct evidence.

Multidimensional assessment
Multidimensional assessment
Authenticity of the source	verified
Methodological quality	moderate
Risk of bias	some concerns
Precision of results	low
Directness	direct
Reproducibility	replicated
Consistency with the overall evidence	consistent
Regional transferability	moderate
Adequacy of the interpretation (by the archive)	not applicable