The Four-Tier Metabolic Framework
The Valens MD tier system is built on five biomarkers: fasting insulin, HOMA-IR, TG:HDL ratio, HbA1c, and TyG Index. Each has been independently validated in large population studies as a predictor of metabolic dysfunction, cardiovascular risk, and Type 2 diabetes progression. Together, they provide a multi-dimensional picture significantly more sensitive than any single marker alone.
The tier thresholds are derived from a synthesis of NHANES population data, ADA clinical standards, and published research on insulin resistance staging. They reflect optimal targets — not simply the absence of disease — which is why they are more stringent than standard laboratory reference ranges.
The Five Biomarkers
Biomarker 01
Fasting Insulin
The primary direct measure of pancreatic output and insulin sensitivity. Elevated fasting insulin precedes abnormal glucose by 10–15 years. Optimal: below 6 µIU/mL. Reference: Kraft JR (2008); Crofts et al., JABFM (2015).
Biomarker 02
HOMA-IR
Calculated from fasting insulin and fasting glucose. The most widely validated non-invasive measure of insulin resistance in clinical research. Optimal: below 1.0. Reference: Matthews et al., Diabetologia (1985).
Biomarker 03
TG:HDL Ratio
The triglyceride-to-HDL ratio is the most accessible proxy for insulin resistance on a standard lipid panel. A ratio above 2.0 has strong predictive value for both insulin resistance and cardiovascular risk. Reference: McLaughlin et al., JCEM (2005).
Biomarker 04
TyG Index
The Triglyceride-Glucose Index provides a complementary pathway for assessing insulin resistance, with particular utility in predicting cardiovascular outcomes. Reference: Simental-Mendía et al., Cardiovasc Diabetol (2016).
Biomarker 05
HbA1c
Glycated hemoglobin reflects average blood glucose over approximately 90 days. Used as a longitudinal marker of glycemic control and to identify transition between tiers. Interpreted alongside fasting insulin for full context.
The Evidence on Early Insulin Resistance Detection
The clinical case for measuring fasting insulin rests on a body of evidence accumulated over four decades. Joseph Kraft's analysis of more than 14,000 glucose-insulin tolerance tests — conducted at the University of Chicago — demonstrated that the majority of patients with abnormal insulin patterns had entirely normal fasting glucose and HbA1c. His concept of "diabetes in situ" described the compensated insulin-resistant state that standard labs miss entirely.
More recent work from Crofts and colleagues formalized threshold criteria for early insulin resistance detection using fasting insulin and HOMA-IR, providing the evidence base for the tier 2 classification used at Valens MD.
Why Our Thresholds Differ from Standard Reference Ranges
Standard laboratory reference ranges for fasting insulin vary widely — some laboratories list "normal" as up to 25 µIU/mL. These ranges are derived from population distributions, not from outcomes data. A fasting insulin of 18 µIU/mL falls within some labs' normal range and is consistent with Tier 4 dysfunction in our framework. We use optimal targets derived from outcomes literature, not distribution-based normal ranges.
Exercise Science Foundation
The exercise prescription methodology at Valens MD is grounded in the work of exercise physiologists whose research on metabolic adaptations to training intensity informs our lactate-based approach. Zone 2 training for mitochondrial development and fat oxidation improvement is among the most replicated findings in exercise science, with direct metabolic health applications validated in both athletic and clinical populations.
Lactate threshold testing as the basis for individual zone prescription — rather than formula-based heart rate estimates — reflects the standard approach in elite endurance sport and is increasingly adopted in precision medicine contexts for its accuracy and individual specificity.
Advisors
Dr. Benjamin Bikman, PhD
Founding Metabolic Advisor
Professor of Cell Biology and Physiology at Brigham Young University. Author of Why We Get Sick (2020). His research focuses on the role of insulin and metabolic dysfunction in chronic disease. Dr. Bikman's work on insulin resistance staging and threshold classification forms the scientific foundation of the Valens MD tier framework.
Key References
Kraft JR. Diabetes Epidemic & You. (2008)
Foundational evidence for insulin pattern analysis and early detection of insulin resistance prior to glucose abnormality.
Matthews DR et al. Homeostasis model assessment. Diabetologia (1985)
Original HOMA-IR derivation and validation paper. The foundational reference for this widely used clinical measure.
Crofts CAP et al. Hyperinsulinemia: Best Management Practice. JABFM (2015)
Clinical framework for identifying and managing hyperinsulinemia. Basis for Tier 2 identification criteria.
McLaughlin T et al. Use of metabolic markers to identify overweight individuals who are insulin resistant. JCEM (2005)
Validation of TG:HDL ratio as a clinical proxy for insulin resistance in outpatient practice.
Simental-Mendía LE et al. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance. Cardiovasc Diabetol (2016)
TyG Index validation across multiple large cohorts for insulin resistance and cardiovascular risk prediction.
Estrada-Luna D et al. Zone 2 training and mitochondrial adaptations. Sports Medicine (2022)
Evidence base for low-intensity aerobic training as the primary driver of mitochondrial biogenesis and fat oxidation capacity.
See the methodology in practice.
Your evaluation applies this framework to your specific biology — not a population average.
