Beyond Blood Sugar: Why Insulin Matters Long Before Diabetes

For decades, metabolic health has been judged largely by blood sugar. If glucose is “normal,” we reassure. If it rises, we intervene.

But a growing body of evidence suggests this approach is too late.

A recent perspective in Diabetes Care titled “Beyond Glucose—Rethinking Prediabetes for Precision Prevention” makes this problem explicit. The authors argue that what we call prediabetes is not a single condition, but a collection of distinct metabolic states, each with different risks for disease and complications. Importantly, they show that organ damage can accumulate for many years before diabetes is ever diagnosed.

In other words, blood sugar is often the last signal, not the first.

What the study proposes

Using advanced research tools—oral glucose tolerance tests (OGTTs), MRI-based fat imaging, and genetic data—the researchers identified several prediabetes subtypes. Some progress rapidly to diabetes. Others progress slowly, yet develop kidney disease, cardiovascular disease, and higher mortality, even while glucose levels remain only mildly abnormal.

One group stands out: individuals with long-standing hyperinsulinemia and insulin resistance. These people may live for a decade or more with only modest elevations in glucose, yet their bodies are already paying a metabolic price.

The study’s key message is clear:

Waiting for glucose to rise means missing the period when metabolic damage is actively accumulating.

The limitation the authors openly acknowledge

While the concept is powerful, the authors also recognize a major obstacle: their subtyping approach relies on specialized tests that are expensive, time-consuming, and not realistic for routine clinical use.

• OGTTs with insulin measurements

• MRI scans to quantify liver and visceral fat

• Genetic risk scores

These tools are excellent for research—but not scalable for everyday prevention.

This is where a crucial opportunity emerges.

Why we need to shift the focus to insulin

When we step back, the study’s findings support a broader, simpler truth:

Hyperinsulinemia and insulin resistance are often present for years—sometimes decades—before blood sugar crosses a diagnostic threshold.

During this long window, chronic insulin excess quietly contributes to a wide range of conditions that are often treated as separate problems:

• Hypertension (via renal sodium retention and sympathetic activation)

• Fatty liver (driven by insulin-stimulated lipogenesis)

• Dyslipidemia (high triglycerides, low HDL)

• PCOS and infertility (through ovarian insulin signaling and androgen excess)

• Weight gain resistant to calorie restriction

These are not unrelated diseases. They are downstream consequences of chronic insulin signaling in a resistant system.

Blood sugar rises only when the system can no longer compensate.

The good news: we already have practical tools

Unlike MRI scanners or genetic panels, many insulin-centric markers are already available, affordable, and familiar to clinicians:

• Fasting insulin

• HOMA-IR / HOMA2 (insulin resistance and β-cell strain)

• Triglyceride-to-HDL ratio (hepatic insulin resistance proxy)

• Waist-to-height ratio (visceral adiposity burden)

• Patterns of stress hyperglycemia

• Fasting triglycerides and liver enzymes (ALT/AST)

Individually, these markers are imperfect.

Together, they tell a coherent story about insulin load, metabolic congestion, and risk—often long before glucose becomes abnormal.

A call for a more practical, earlier prevention model

The Diabetes Care paper stops short of redefining prediabetes—and rightly so. But it opens the door to a more effective approach:

• Shift attention upstream, from glucose to insulin

• Recognize metabolic disease as a process, not a threshold

• Use readily available biomarkers to identify risk earlier

• Intervene before years of silent damage accumulate

This is not about labeling more people as “sick.”It is about recognizing stress on the system early enough to reverse it.

The takeaway

If we continue to wait for blood sugar to rise, we will keep missing the real disease phase.

Insulin resistance and hyperinsulinemia are not merely precursors to diabetes—they are active drivers of metabolic dysfunction across the body, affecting the liver, kidneys, blood vessels, hormones, and reproductive health.

The science is already pointing us in this direction.

The tools are already in our hands.

What’s needed now is the willingness to look beyond glucose—and act sooner.

Wagner, R., Selvin, E., Sehgal, R., Prystupa, K., Misra, S., Fritsche, A., & Heni, M. (2025). Beyond glucose—Rethinking prediabetes for precision prevention. Diabetes Care, 48(1), 1–10. https://doi.org/10.2337/dci25-0054