August 6, 2026Circulation
Inflammation in the Prediabetic State Is Related to Increased Insulin Resistance Rather Than Decreased Insulin Secretion
Key result
Insulin resistance in prediabetes is linked to ~58% higher PAI-1 levels alongside elevated CRP.
- P=0.003
- n=906
Population
906 nondiabetic individuals from the Insulin Resistance Atherosclerosis Study, of whom 148 developed diabetes
Design
Cohort
Follow-up
mean 5.2 years
Authors
Discussion
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Implication
An increased proinflammatory state in prediabetes is associated with insulin resistance rather than a primary defect in beta-cell function, suggesting cardiovascular risk in prediabetes is concentrated in insulin-resistant subjects.
Key Points
- To examine whether elevated circulating inflammatory markers in prediabetic individuals are associated with impaired insulin sensitivity or impaired first-phase insulin secretion.
- Analyzed baseline inflammatory markers (CRP, PAI-1, and fibrinogen) in 906 nondiabetic participants from the Insulin Resistance Atherosclerosis Study (IRAS) followed for a mean of 5.2 years.
- Assessed insulin sensitivity and first-phase acute insulin response using a frequently sampled intravenous glucose tolerance test to characterize 148 individuals who progressed to diabetes.
- Insulin-resistant prediabetic individuals exhibited significantly higher levels of PAI-1 (mean [95% CI], 25.83 ng/mL [22.42 to 29.77] vs. 16.31 ng/mL [12.56 to 21.18]; P=0.003) and CRP (mean [95% CI], 2.88 mg/L [2.33 to 3.56] vs. 1.68 mg/L [1.13 to 2.49]; P=0.018) compared with insulin-sensitive individuals.
- Prediabetic individuals with predominant defects in first-phase insulin secretion showed inflammatory marker levels indistinguishable from nonconverters, whereas those with predominant insulin resistance had elevated inflammatory markers compared to both secretor-defect subjects and nonconverters.
Study Design
Type
Cohort (n=906)
Structured PICO
P
Population
906 nondiabetic individuals from the Insulin Resistance Atherosclerosis Study, followed for a mean of 5.2 years to evaluate the relationship between inflammatory proteins and insulin resistance.
O
Outcome
Relation of C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-1, and fibrinogen to defects in insulin sensitivity and first-phase insulin secretionsurrogate
Main Result
Absolute Event Rate: 25.83% vs 16.31%
p-value: p=0.003
An increased proinflammatory state in prediabetes is associated with insulin resistance rather than a primary defect in beta-cell function, suggesting cardiovascular risk in prediabetes is concentrated in insulin-resistant subjects.
Cite This Study
Festa et al. (2003) conducted a cohort in Prediabetes (n=906). Insulin resistance vs. Insulin sensitivity was evaluated on Plasminogen activator inhibitor (PAI)-1 levels (p=0.003). Prediabetic individuals who were insulin resistant had higher levels of PAI-1 (25.83 vs 16.31 ng/mL, P=0.003) and CRP (2.88 vs 1.68 mg/L, P=0.018) compared to insulin-sensitive individuals.