Decades of Scientific Discovery.One Unified Diagnostic Platform.
Kihealth's InterceptIQ™ platform integrates decades of published scientific discoveries demonstrating that pancreatic β-cell stress, dysfunction, and apoptosis begin years before conventional metabolic markers become abnormal. Our research builds upon foundational work in β-cell biology, molecular diagnostics, liquid biopsy, epigenetics, immunology, and diabetes pathogenesis.
30+ years · peer-reviewed17 · landmark publications6 · research domains
Islet · β-cell · cfDNAInterceptIQ™
Research Domains
Six domains of evidence behind one platform.
Before β-cells die, they suffer. Chronic demand triggers the unfolded protein response; the ER becomes overloaded with proinsulin; oxidative and mitochondrial stress accumulate; cytokine signaling tips the balance toward apoptosis. Each of these stress states leaves a measurable molecular fingerprint in the circulation — proinsulin spillover, altered C-peptide kinetics, and rising unmethylated INS cfDNA — long before HbA1c or fasting glucose breach diagnostic thresholds.
Key topics
ER Stress
Unfolded Protein Response
Oxidative stress
Glucotoxicity
Lipotoxicity
Mitochondrial dysfunction
Inflammatory cytokines
Cellular senescence
Loss of insulin processing
Proinsulin accumulation
Disease Continuum
From a healthy β-cell to clinical diabetes.
Hover any stage to see the molecular signal that becomes detectable in circulation.
Stage 1
Healthy β-cell
Normoglycemia, full functional reserve
Stage 2
Cellular stress
ER overload, UPR activation
Stage 3
Functional decline
Proinsulin:C-peptide ratio rises
Stage 4
Apoptosis
Unmethylated INS cfDNA detectable
Stage 5
Loss of β-cell mass
Reserve falls below compensation threshold
Stage 6
Prediabetes / Dysglycemia
HbA1c begins to rise
Stage 7
Clinical diabetes
T1D (autoimmune) or T2D (metabolic)
The same continuum bifurcates at the end: Type 1 Diabetes via autoimmune destruction, or Type 2 Diabetes via metabolic exhaustion. InterceptIQ™ resolves both trajectories molecularly.
Biomarkers of β-Cell Injury
A multi-analyte panel reads the islet in real time.
Unmethylated INS cfDNA
Measures
DNA fragments released specifically from dying β-cells.
Clinical significance
Direct, real-time signal of active β-cell death.
Role in β-cell health
Quantifies the rate of islet attrition.
Complements
Adds a death-rate dimension absent from glucose and antibody panels.
Proinsulin : C-peptide Ratio
Measures
Relative spillover of unprocessed proinsulin vs mature C-peptide.
Clinical significance
Reports ER stress and impaired proinsulin processing.
Role in β-cell health
Detects functional stress before mass is lost.
Complements
Pairs with cfDNA to separate 'stressed but alive' from 'dying' β-cells.
C-Peptide
Measures
Endogenous insulin secretion (1:1 stoichiometry with insulin).
Clinical significance
Gold standard for residual β-cell function.
Role in β-cell health
Tracks functional reserve longitudinally.
Complements
Denominator for PI:C ratio; orthogonal to cfDNA.
HbA1c
Measures
Average glycemia over ~3 months.
Clinical significance
Diagnostic and monitoring standard for established diabetes.
Role in β-cell health
Late, lagging marker of net glycemic burden.
Complements
Late-stage anchor; molecular biomarkers fill the earlier window.
Fasting Insulin
Measures
Circulating insulin in the fasted state.
Clinical significance
Surrogate for insulin resistance and basal β-cell output.
Role in β-cell health
Contextualizes β-cell workload.
Complements
Disambiguates resistance-driven vs failure-driven dysglycemia.
Autoantibodies
Measures
GAD65, IA-2, ZnT8, insulin autoantibodies.
Clinical significance
Define autoimmune risk and T1D staging.
Role in β-cell health
Stratifies who is on the T1D trajectory.
Complements
Risk classifier; cfDNA/PI:C quantify how fast that risk is realizing.
Glucose
Measures
Point-in-time glycemia.
Clinical significance
Universal but non-specific; reflects failure, not cause.
Role in β-cell health
Reference signal for downstream clinical action.
Complements
Where molecular biomarkers point — glucose eventually confirms.
Epigenetics & Liquid Biopsy
Every dying β-cell releases molecular information into circulation.
The insulin gene promoter is unmethylated in β-cells and methylated almost everywhere else. When a β-cell dies, it sheds DNA fragments that retain this tissue-specific methylation signature. Detecting unmethylated INS cfDNA in plasma is a direct, non-invasive measurement of β-cell death.
Clinical Translation Timeline
Three decades, converging on a platform.
1980s
Understanding insulin secretion
β-cell glucose sensing, KATP channels, and C-peptide kinetics defined.
1990s
β-cell dysfunction recognized
Functional reserve, proinsulin processing, and insulin resistance frameworks emerge.
2000s
ER stress and apoptosis
Unfolded protein response identified as a driver of β-cell failure in T1D and T2D.
2010s
Cell-free DNA biomarkers
Tissue-specific methylation enables direct measurement of β-cell death from plasma.
2020s
Precision molecular diagnostics
Multi-analyte panels integrate stress, death, and function into clinical decisions.
Kihealth
InterceptIQ™ platform
Clinical translation of three decades of β-cell science into a unified diagnostic.
Today
Landmark Publications
The peer-reviewed canon behind InterceptIQ™.
17 of 17 publications
Diabetes Care2023
High Proinsulin:C-Peptide Ratio Identifies Individuals with Stage 2 Type 1 Diabetes
Sims EK, et al. · Indiana University; TrialNet
Key finding
PI:C ratio identifies dysglycemic stage 2 T1D individuals at highest near-term risk.
Why it matters
Validates the staging utility of PI:C for therapeutic intervention windows.
