Glucose & insulin
Glycated hemoglobinHbA1c
Integrated glycemia over the prior 8–12 weeks; the diagnostic and monitoring workhorse.
Sample
EDTA whole blood
Fasting
Not required
Clinical reference range
— to 5.6 %
Normal
Conv: —–5.6 %Func: 4.6–5.3 %
Biology
What it measures
Non-enzymatic glycation of valine on the β-chain of hemoglobin. Concentration reflects mean glucose weighted toward the most recent month (50% from last 30 d).
Clinical use
Why we order it
Diagnose diabetes (≥6.5%), set treatment targets, and monitor therapy. Avoids fasting and within-day variation.
Lens · Clinical
Interpretation by lens
Clinical interpretation
ADA target <7% for most adults; <6.5% if achievable without hypoglycemia; <8% in frail elderly or limited life expectancy.
Functional interpretation
Functional 'optimal' 4.6–5.3% is a long-term metabolic target; values 5.4–5.7 already correlate with insulin resistance in many cohorts.
Research note
HbA1c–glucose discordance (high glycation index) is independently associated with microvascular complications.
Differential
Causes of abnormal values
Causes of HIGH
- ↑Hyperglycemia
- ↑Iron deficiency anemia (falsely raises A1c)
- ↑Splenectomy / decreased RBC turnover
- ↑Uremia (carbamylation interferes with some assays)
Causes of LOW
- ↓Hemolysis
- ↓Recent transfusion
- ↓Pregnancy (lower turnover)
- ↓Hemoglobinopathies (HbS, HbC) — verify with A1c assay validation
Pitfalls
Pre-analytic & interpretation traps
- !HbA1c is unreliable in any condition that alters RBC lifespan — use fructosamine or CGM-derived measures instead.
- !African ancestry HbS or HbC trait can interfere with some assays — request electrophoresis if A1c discordant with glucose.
Follow-up orders
Logical next-step labs
Evidence-graded claims
What the data says
A
HbA1c ≥6.5% diagnoses diabetes when assay is standardized
ADA, IDF, WHO.
A
Tight glycemic control (<7%) reduces microvascular complications in type 2
UKPDS.
D
Aggressive A1c targets (<6.5%) reduce macrovascular risk
ACCORD found increased mortality with aggressive glycemic targets.
References
Primary literature
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