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Advanced 10 min read
Beyond the Basics: Advanced Biomarkers
Once you have a solid baseline, these advanced markers — from fasting insulin to cystatin C — provide deeper insight into metabolic health, inflammation, and early disease detection.
Key Takeaways
- →Fasting insulin is one of the earliest markers of metabolic dysfunction — often elevated years before glucose.
- →Homocysteine, when elevated, is an independent cardiovascular risk factor that is often correctable with B vitamins.
- →DHEA-S and IGF-1 reflect anabolic and growth hormone status and decline predictably with age.
- →Cystatin C provides a more accurate estimate of kidney function than creatinine alone, especially in active adults.
Standard lab panels cover the basics, but they miss important signals. A normal fasting glucose does not rule out insulin resistance. A standard kidney panel may overestimate function in muscular individuals. Advanced biomarkers fill these gaps, offering earlier detection and more nuanced risk stratification.
Metabolic Deep Dive
- •Fasting insulin — While glucose stays normal until beta-cell function is significantly impaired, insulin rises much earlier to compensate. A fasting insulin above 8–10 μIU/mL in a non-diabetic individual may indicate insulin resistance. The Whitehall II study found that fasting insulin predicted type 2 diabetes development up to 18 years in advance.
- •HOMA-IR — Calculated from fasting glucose and fasting insulin, HOMA-IR quantifies insulin resistance. Values above 2.0 suggest insulin resistance; above 2.9 indicate significant resistance.
- •Uric acid — Beyond its role in gout, elevated serum uric acid is associated with hypertension, metabolic syndrome, and kidney disease. Optimal levels are typically below 6.0 mg/dL for men and 5.0 mg/dL for women.
Inflammatory & Vascular Markers
- •Homocysteine — An amino acid elevated by folate, B6, or B12 deficiency, MTHFR gene variants, or kidney dysfunction. Levels above 10 μmol/L are associated with increased cardiovascular risk. Often correctable with methylated B vitamins.
- •Fibrinogen — A clotting factor and acute phase reactant. Elevated fibrinogen increases thrombotic risk and is associated with cardiovascular events independently of cholesterol (Fibrinogen Studies Collaboration, JAMA 2005).
- •Ferritin — While low ferritin indicates iron deficiency, elevated ferritin can signal iron overload, inflammation, or liver disease. Optimal ranges are typically 40–100 ng/mL for men and 20–80 ng/mL for premenopausal women.
Hormonal & Growth Markers
- •DHEA-S — The most abundant circulating steroid hormone, produced by the adrenal glands. DHEA-S declines steadily with age and low levels have been associated with increased mortality in some observational studies. It is sometimes used as a marker of adrenal reserve and biological aging.
- •IGF-1 — Insulin-like growth factor 1 reflects growth hormone activity. Very low and very high levels are both associated with increased mortality (a U-shaped curve). Optimal levels appear to be in the mid-normal range for age.
- •Free and total testosterone — Relevant for both men and women. Low testosterone is associated with increased cardiovascular risk, reduced bone density, and decreased muscle mass. The Endocrine Society recommends testing in symptomatic individuals.
- •Cortisol — The primary stress hormone. Chronically elevated cortisol is associated with visceral fat accumulation, immune suppression, and cognitive decline.
Kidney & Organ Function
- •Cystatin C — A small protein filtered by the kidneys. Unlike creatinine, cystatin C is not significantly affected by muscle mass, making it a more accurate marker of kidney function in athletic or very lean individuals. The CKD-EPI equation using both creatinine and cystatin C is the most accurate available estimate of GFR.
- •GGT (Gamma-Glutamyl Transferase) — While often checked as a liver enzyme, GGT is also an independent predictor of cardiovascular mortality and metabolic syndrome, even at levels within the standard reference range.
Which advanced markers to add first
If you can only add a few markers beyond a standard panel, prioritize fasting insulin, ApoB (if not already included), homocysteine, and cystatin C. These four markers cover metabolic, cardiovascular, and kidney health gaps at relatively low cost.