What are the optimal ranges for blood testing biomarkers in a generally healthy adult with no significant past medical history, associated with the top 20% healthiest phenotype?

Optimal Blood Biomarker Ranges for Top 20% Healthiest Phenotype

For generally healthy adults without significant comorbidities, target HbA1c should be maintained between 5.0-5.7% (31-39 mmol/mol), fasting glucose 80-100 mg/dL (4.4-5.6 mmol/L), and 2-hour post-meal glucose <140 mg/dL (7.8 mmol/L), as these ranges define normal glucose metabolism and predict lowest cardiovascular and mortality risk. 1

Glucose Metabolism Markers

HbA1c (Hemoglobin A1c)

• Optimal range: 5.0-5.7% (31-39 mmol/mol) 1
• Values <5.0% may paradoxically associate with increased cardiovascular disease and mortality risk when sustained chronically 2
• The prediabetes threshold begins at 5.7%, indicating this represents the upper boundary of optimal metabolic health 1
• Critical caveat: Single low measurements (<5.0%) are less concerning than chronically sustained low values, which may indicate underlying pathology 2

Fasting Plasma Glucose (FPG)

• Optimal range: 80-100 mg/dL (4.4-5.6 mmol/L) 1
• Values <80 mg/dL, when chronically sustained, associate with 2-fold increased cardiovascular disease risk (OR 2.04) and mortality (OR 1.93) 2
• The American Diabetes Association defines impaired fasting glucose starting at 100 mg/dL, establishing this as the upper limit of normal 1
• Avoid: Chronic fasting glucose <80 mg/dL is not healthier and may indicate increased glycemic variability or underlying metabolic dysfunction 2

2-Hour Post-Meal Glucose

• Optimal range: <140 mg/dL (7.8 mmol/L) 1
• This threshold distinguishes normal glucose tolerance from impaired glucose tolerance across all major guidelines 1
• Post-meal glucose contributes 70% to overall glycemic control in individuals with HbA1c <7.3%, making it the dominant determinant of optimal metabolic health 3
• For predicting HbA1c <7%, the 2 PM glucose threshold is 160 mg/dL, but for top 20% phenotype, maintain <140 mg/dL 3, 4

Lipid Panel

HDL Cholesterol

• Optimal range: ≥35 mg/dL (0.90 mmol/L) minimum; higher is better 1
• Values <35 mg/dL represent a diabetes risk factor and indicate suboptimal cardiovascular health 1
• The American Diabetes Association uses this threshold to identify high-risk individuals requiring screening 1

Triglycerides

• Optimal range: <250 mg/dL (2.82 mmol/L) maximum; lower is better 1
• Elevated triglycerides >250 mg/dL associate with insulin resistance and increased diabetes risk 1
• For top 20% phenotype, aim for the lower end of normal range, though specific optimal targets require individualized cardiovascular risk assessment 5

Blood Pressure

• Optimal range: <130/80 mmHg 1
• The European Society of Cardiology defines hypertension as ≥140/90 mmHg, but cardiovascular risk increases progressively above 130/80 mmHg 1
• Annual screening recommended for all adults, with more frequent monitoring if values approach 130/80 mmHg 5

Liver Fibrosis Markers (For Context, Not Routine Screening)

APRI (AST to Platelet Ratio Index)

• Optimal: <0.5 1
• Values ≥0.5 indicate possible significant fibrosis (F2-4) with moderate sensitivity (78%) and specificity (65%) in NAFLD populations 1
• This is not a routine screening test for healthy adults but provides context for liver health assessment 1

FIB-4 Index

• Optimal: <1.3 1
• Values 1.3-1.45 suggest possible fibrosis; ≥1.45 indicates higher risk 1
• The lower cutoff of 1.3 has 82% sensitivity for detecting advanced fibrosis (F3-4) in NAFLD 1

Kidney Function Markers

Urinary Albumin

• Optimal: Routine assessment for microalbuminuria to identify early renal dysfunction risk 1
• The European Society of Cardiology recommends routine microalbuminuria screening as it predicts both renal and cardiovascular disease risk 1
• Normal values indicate absence of early diabetic nephropathy and optimal kidney function 1

Age-Specific Considerations

Adults Under 40 Without Comorbidities

• Target HbA1c 6.0-7.0% if diabetes is present, but for optimal health without diabetes, maintain 5.0-5.7% 6
• Life expectancy >10-15 years justifies more aggressive metabolic optimization to prevent microvascular complications 6
• Do not over-treat: If HbA1c falls <6.5% on medication, reduce therapy as no benefit exists below this threshold and mortality risk increases 6

Adults 35-65 Years

• Screen for diabetes starting at age 35 regardless of risk factors 1, 5
• Repeat screening every 3 years if normal, more frequently if overweight/obese or other risk factors present 1, 5
• Maintain HbA1c 5.0-5.7% for optimal metabolic health 1, 5

Adults Over 65 Years

• For healthy older adults with good functional status, target HbA1c 7.5-8.0% if diabetic 7
• Critical safety point: Older adults ≥80 years have 5-fold higher hospitalization risk for insulin-related hypoglycemia 7
• For optimal health without diabetes, maintain HbA1c 5.0-5.7%, but avoid aggressive treatment if values drift slightly higher 7

Common Pitfalls to Avoid

• Do not assume lower is always better: Chronically low glucose (FPG <80 mg/dL) and HbA1c (<5.0%) associate with increased cardiovascular disease and mortality 2
• Do not ignore post-meal glucose: In individuals with optimal HbA1c, postprandial glucose contributes 70% to overall glycemic control and is the primary target for optimization 3, 4
• Do not apply diabetic targets to healthy individuals: The HbA1c targets of 6.5-7.0% apply to diabetes management, not optimal health in non-diabetics 1
• Do not screen with HbA1c alone: Oral glucose tolerance testing detects 33% with impaired glucose tolerance and 6% with diabetes among those with normal HbA1c (<6.0%) 4

Monitoring Frequency

• Diabetes screening: Every 3 years starting at age 35 if normal; annually if prediabetes (HbA1c 5.7-6.4%) 1, 5
• Blood pressure: Every visit, minimum annually 5
• Lipid profile: Every 2 years if low-risk values; annually if high-risk 5
• HbA1c (if diabetic): Every 6 months if stable and meeting targets; every 3 months if therapy changed or not meeting goals 5