In endocrinology, we often depend on numbers. HbA1c, fasting sugars, post-prandial values—these guide most of our decisions. But with time and experience, every clinician realizes one thing very clearly: numbers don’t always reflect reality.
Recent developments in endocrinology, especially in diabetes care, have helped us understand why this mismatch happens and how we can deal with it better in daily practice.
HbA1c: Useful, But Not Always Reliable
HbA1c is still the most commonly used marker for long-term glucose control. The gold standard method to measure it is HPLC. It is accurate, no doubt about that. But it is expensive, requires batch processing, and is not practical in many OPD settings.
Most clinics and hospitals therefore use other methods—immunoturbidimetry, nephelometry, or point-of-care testing. These methods are quicker and more accessible. To maintain accuracy, labs usually follow external quality control, where samples are cross-checked with reference centres using HPLC.
So yes, HbA1c is important—but it is not flawless.
Same HbA1c, Completely Different Patients
This is something we see all the time.
A type 1 diabetic patient on insulin comes with an HbA1c of 6%. His glucose levels swing wildly—severe highs followed by sudden lows.
Another patient, prediabetic, also has an HbA1c of 6%. His sugars are mostly stable with occasional mild elevations.
On paper, both look “well controlled”. Clinically, they are not even close.
This difference is explained by something called the glycation gap.
What Is the Glycation Gap?
The glycation gap is the difference between:
- The HbA1c you measure in the lab
- The HbA1c you should expect based on actual glucose exposure
This difference is also known as the Hemoglobin Glycation Index.
It tells us whether HbA1c is under-representing or over-representing the patient’s real glucose burden.
Why is the Glycation Gap Important?
When the Gap Is Low?
HbA1c looks normal, but glucose levels are actually high.
What happens then?
We feel reassured. We don’t increase insulin. Hyperglycemia continues silently. Over time, the patient walks straight into microvascular and macrovascular complications.
When the Gap Is High?
HbA1c looks high, but actual glucose exposure is not that bad.
Now the opposite happens.
We increase insulin aggressively. The patient starts having frequent hypoglycemia.
Both situations are dangerous—and both happen when we trust HbA1c blindly.
CGMS: Seeing What HbA1c Cannot
Continuous glucose monitoring has changed how we understand diabetes. Instead of a single average, CGMS shows:
- Daily glucose patterns
- Time spent in hyperglycemia and hypoglycemia
- Median glucose values
- Estimated HbA1c based on real data
Many patients who look “controlled” on HbA1c spend a large part of their day in hyperglycemia. CGMS makes this visible.
If CGMS Is Not Affordable
This is a common concern, especially in smaller towns and rural practice.
In such cases, serum fructosamine is extremely useful. It reflects glucose control over the previous 2–3 weeks and is much more affordable. Comparing fructosamine-derived HbA1c with measured HbA1c helps identify a glycation gap even without CGMS.
Why HbA1c Can Be Misleading?
HbA1c formation is not purely glucose-dependent. It is influenced by:
- GLUT1 transporter activity
- Red cell lifespan
- Intracellular pH
- Hemoglobin variants
- Non-enzymatic glycation differences
So two patients with similar glucose levels can still show very different HbA1c values.
Smart Insulin: Where We Are Headed
Smart insulin, also called glucose-responsive insulin, is designed to work only when needed. It increases action when glucose rises and reduces or stops action when glucose falls.
Several types—algorithm-based, polymer-based, and molecule-based—are already in advanced trials. This is no longer science fiction.
Insulin Pumps and Closed-Loop Systems
Insulin pumps have evolved far beyond simple delivery devices. When combined with glucose sensors and predictive algorithms, they can:
- Adjust basal insulin automatically
- Predict glucose trends
- Reduce both hypoglycemia and hyperglycemia
We now have hybrid closed-loop systems, and we are moving towards fully automated systems that mimic pancreatic function. Some even include glucagon delivery, bringing us closer to a true bionic pancreas.
Practical Take-Home Points
- HbA1c should never be interpreted alone
- Always think about glucose variability
- Use CGMS or fructosamine when HbA1c doesn’t match the clinical picture
- Technology is helping us treat patients, not just numbers
- Individualized diabetes care is the future
Final Thought
Good diabetes management is not about chasing perfect HbA1c values. It’s about understanding the patient’s real glucose behavior and adjusting treatment wisely. When we combine clinical judgment with the right use of technology, outcomes improve—and so does patient safety.
