75 Years On
How a brilliant physician's observation reshaped our understanding of diabetes
Explore the DiscoveryImagine it's 1936. The medical world is still buzzing about insulin, discovered just 15 years earlier and rightfully hailed as a miracle treatment for diabetes. Doctors administer insulin to diabetic patients, expecting near-miraculous results. But Sir Harold Himsworth, a brilliant British physician and researcher, notices something puzzling: while some patients respond dramatically to insulin, others show barely any response at all 1 8 .
This observation led him to a revolutionary idea that would fundamentally reshape our understanding of diabetes. He proposed that diabetes wasn't one disease but (at least) two distinct conditions: "insulin-sensitive" and "insulin-insensitive" diabetes 1 .
Seventy-five years later, we recognize this as the fundamental distinction between Type 1 and Type 2 diabetes, and his work laid the foundation for our modern understanding of insulin resistance—a concept now recognized as a central driver of metabolic disease worldwide 7 .
Noticed differential responses to insulin treatment
Proposed two distinct types of diabetes
Foundation for modern diabetes classification
To appreciate Himsworth's genius, we must understand the scientific landscape of his time. Before his work, diabetes was primarily viewed through the lens of pancreatic failure—the idea that the pancreas simply couldn't produce enough insulin.
The 1921 discovery of insulin by Banting and Best had been rightfully celebrated as a landmark achievement, transforming a fatal diagnosis into a manageable condition . The medical establishment became so focused on insulin deficiency as the cause of all diabetes that alternative possibilities were largely overlooked. The primary question doctors asked was: "How much insulin does this patient need?" rather than "Why does this patient need so much insulin?" 8
Himsworth dared to ask this different question. He suspected that the problem in many diabetic patients wasn't a lack of insulin, but rather that their bodies had become unresponsive to it. He called this condition "insulin insensitivity"—what we now term insulin resistance 1 .
In an era before sophisticated laboratory technology, Himsworth devised an elegantly simple yet powerful test to distinguish between different types of diabetes. His glucose-insulin tolerance test represented a masterpiece of clinical reasoning 1 .
Participants fasted before the test to establish baseline metabolic conditions.
Subjects were given a standard amount of glucose by mouth to simulate a meal and stimulate insulin production.
On one day, participants received only oral glucose. On another day, they received the same oral glucose dose plus an injection of insulin.
Blood glucose levels were measured at regular intervals over several hours.
Himsworth compared how quickly blood glucose levels normalized with and without insulin administration.
Himsworth categorized patients based on their responses to these tests. Those whose glucose levels dropped significantly with insulin administration had "insulin-sensitive" diabetes. Those whose glucose levels showed little response to insulin had "insulin-insensitive" diabetes 1 .
| Patient Category | Response to Insulin Administration | Proposed Mechanism | Modern Equivalent |
|---|---|---|---|
| Insulin-Sensitive | Significant drop in blood glucose | Lack of insulin production | Type 1 Diabetes |
| Insulin-Insensitive | Minimal change in blood glucose | Body tissues don't respond to insulin | Type 2 Diabetes |
Himsworth's analysis went further. He noticed that insulin-insensitive diabetes was strongly associated with middle age and obesity, while insulin-sensitive diabetes was more common in younger, thinner individuals 1 . This observation, made simply by observing patient responses, remarkably presaged our current understanding of risk factors for Type 2 diabetes.
| Clinical Feature | Insulin-Sensitive Diabetes | Insulin-Insensitive Diabetes |
|---|---|---|
| Age at Onset | Typically younger | Typically middle-aged or older |
| Body Weight | Often underweight | Often overweight or obese |
| Prevalence | Less common | More common |
| Response to Insulin Therapy | Excellent | Poor to moderate |
While Himsworth identified the phenomenon of insulin resistance at the whole-body level, modern science has revealed the intricate molecular mechanisms behind it. We now know that insulin resistance occurs when muscles, fat, and liver cells don't respond properly to insulin and can't easily take up glucose from the blood 4 7 .
Defects can occur at any point in this pathway, creating the cellular resistance to insulin that Himsworth first observed clinically 7 .
Modern research has confirmed and expanded another of Himsworth's key insights: the compensatory hyperinsulinemia that occurs as the pancreas produces more and more insulin to overcome resistance 4 8 . This creates a vicious cycle where high insulin levels themselves may contribute to further insulin resistance 4 .
Insulin Resistance
Begins
Compensatory
Hyperinsulinemia
Beta Cell
Exhaustion
Type 2
Diabetes
This process typically unfolds over 10-15 years, providing a crucial window for intervention 4 .
Himsworth's revolutionary discoveries were made with surprisingly simple tools. His genius lay not in sophisticated technology but in asking the right questions and designing elegant experiments to answer them.
| Research Tool | Himsworth's Era (1930s-1940s) | Modern Equivalents |
|---|---|---|
| Insulin Sensitivity Measurement | Glucose-insulin tolerance test | Hyperinsulinemic-euglycemic clamp (gold standard) 6 |
| Insulin Administration | Animal-derived insulin injections | Recombinant human insulin, insulin analogs |
| Glucose Monitoring | Basic blood glucose measurements | Continuous glucose monitors, standardized assays |
| Data Analysis | Manual calculations | HOMA-IR, QUICKI indices, computational modeling 6 |
| Mechanistic Studies | Clinical observation | Molecular biology, genetic sequencing, cell signaling studies 7 |
Today's researchers have a sophisticated arsenal for studying insulin resistance. The hyperinsulinemic-euglycemic clamp developed in the 1970s remains the gold standard for directly measuring insulin sensitivity 6 . This technique involves infusing insulin at a constant rate while simultaneously administering glucose to maintain normal blood sugar levels. The amount of glucose required to maintain euglycemia indicates how sensitive the body is to insulin—more glucose means greater sensitivity 6 .
For large-scale studies where the clamp method isn't feasible, simpler surrogate markers like HOMA-IR and QUICKI use fasting insulin and glucose levels to estimate insulin resistance 6 . These methods, along with advanced imaging and molecular techniques, continue to build upon the foundation Himsworth established eight decades ago.
Seventy-five years after Himsworth's pioneering work, insulin resistance is recognized as a central feature of metabolic syndrome—a cluster of conditions that increase the risk of heart disease, stroke, and Type 2 diabetes 4 7 . Contemporary research has linked insulin resistance not just to diabetes but to a surprising range of conditions including cardiovascular disease, polycystic ovary syndrome (PCOS), and certain cancers 3 7 .
Insulin resistance is a major risk factor for heart disease and stroke
Strong association between insulin resistance and polycystic ovary syndrome
Emerging evidence links insulin resistance to certain cancer types
The global prevalence of insulin resistance has reached epidemic proportions, driven largely by rising obesity rates—exactly the pattern Himsworth first observed in his clinical practice 7 . Recent analyses of clinical trials reveal that research on insulin resistance has grown exponentially, with major contributions from the United States, Iran, China, and the United Kingdom 3 .
Current studies focus on three main areas: using lipid panels as indicators of insulin resistance, analyzing the impact of diet composition and physical activity on insulin sensitivity in obese individuals, and exploring insulin resistance in polycystic ovary syndrome 3 . These research priorities reflect how Himsworth's initial clinical insight has expanded into diverse areas of medicine.
Sir Harold Himsworth's work stands as a testament to the power of careful clinical observation and the courage to challenge medical orthodoxy. At a time when the medical world was focused exclusively on insulin deficiency, he saw a different pattern—one that wouldn't be fully appreciated for decades.
His simple yet profound distinction between insulin-sensitive and insulin-insensitive diabetes laid the groundwork for our modern understanding of Type 2 diabetes and metabolic disease. The 75th anniversary of his insights reminds us that revolutionary ideas in science don't always require advanced technology—sometimes what's needed most is a perceptive mind willing to question what "everyone knows."
As we continue to grapple with a global diabetes epidemic, Himsworth's legacy endures in every research study on insulin signaling, every public health initiative aimed at diabetes prevention, and every clinical approach that treats diabetes as the complex, multifaceted condition he recognized it to be.