Blood Sugar: History and Origins

"Blood sugar management" is not a remedy with a single inventor. It is the practical end of a two-thousand-year scientific story — the slow, often-contested discovery of what sugar in the blood is, where the body keeps it steady, what goes wrong in diabetes, and how a person can actually measure and influence their own glucose. This article tells that history honestly: the ancient physicians who tasted sweet urine; Claude Bernard's discovery that the liver itself makes sugar; the 1889 dog experiment that pinned diabetes on the pancreas; the 1921–22 isolation of insulin in Toronto that turned a death sentence into a manageable disease; the arrival of metformin from a medieval herb; and the modern toolkit — the HbA1c blood test, the glycemic index, the "insulin resistance" framework, and the continuous glucose monitor — that made everyday blood-sugar self-management possible for the first time in history. Where the record is firm we say so; where something is folklore, interpretation, or still debated, we name it as such, and we close with an honest account of what the evidence does and does not support.

Table of Contents

  1. Sweet Urine: The Ancient World
  2. Claude Bernard and the Sugar-Making Liver (1850s)
  3. The Pancreas Pinned Down (1889)
  4. Insulin: The Toronto Breakthrough (1921–1922)
  5. From French Lilac to Metformin (1920s–1957)
  6. Measuring the Average: HbA1c (1968)
  7. Ranking the Foods: The Glycemic Index (1981)
  8. Insulin Resistance and "Syndrome X" (1988)
  9. Proving Control Matters: DCCT and UKPDS (1993–1998)
  10. The Measurement Revolution: Continuous Glucose Monitoring
  11. Evidence & Reception: What Is Actually Established
  12. Research Papers and References
  13. Connections
  14. Featured Videos

Sweet Urine: The Ancient World

Long before anyone could measure a milligram of glucose, physicians recognized the disease we now tie to blood sugar by a single unforgettable clue: urine that was abnormally copious and abnormally sweet. The word diabetes — from a Greek root meaning "to pass through," the sense being that fluids ran straight through the body like a siphon — is usually credited to the Greek physician Aretaeus of Cappadocia, who in roughly the second century CE left a vivid clinical description of the wasting, unquenchable thirst, and relentless urination of the condition. Ancient Indian physicians in the Ayurvedic tradition independently described a disease they called madhumeha ("honey urine"), noting that the urine of affected people attracted ants and flies — a shrewd, low-tech sugar test centuries before chemistry existed.

The Latin epithet mellitus ("honey-sweet") was added much later, and the most-repeated account credits the eighteenth-century English physician Thomas Willis with re-emphasizing the sweet taste of diabetic urine in the 1670s — the era when European doctors literally diagnosed the disease by tasting it. It is worth being precise here: these early observers correctly tied the disease to sugar leaving the body, but they had no concept of blood sugar as a regulated quantity, and several of their proposed causes were wrong. What the ancient record reliably gives us is the clinical recognition of the disease and its sweet-urine signature — the question of where the sugar came from would not be answered for another two millennia.

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Claude Bernard and the Sugar-Making Liver (1850s)

The modern science of blood sugar begins with one of the towering figures of nineteenth-century physiology, the French experimentalist Claude Bernard (1813–1878). Trained in Paris and a pioneer of controlled animal experimentation, Bernard overturned a deeply held assumption: that animals could only break sugar down, and that any glucose in the body must have come from food. In a series of experiments in the mid-1850s he showed the opposite — that the liver itself manufactures and releases glucose into the blood, even in an animal fed no carbohydrate at all. He called this the liver's "glycogenic" (sugar-forming) function, and in 1857 he isolated the storage carbohydrate the liver uses for the purpose, naming it glycogen — literally "sugar-former," the "animal starch" that the liver builds up when blood sugar is high and breaks back down to glucose when it falls.

This was the conceptual birth of blood-sugar regulation as we now understand it: a quantity actively held within a range, not a passive leftover of digestion. Bernard generalized the insight into one of the most important ideas in all of physiology — the milieu intérieur, the "internal environment" whose constancy the body works to maintain. That idea, later refined and renamed homeostasis by the American physiologist Walter Cannon in the twentieth century, is the intellectual frame inside which every later discovery about glucose sits. Bernard did not discover insulin or explain diabetes, and some of his specific mechanistic claims were later corrected; his enduring contribution was to establish that the body keeps blood sugar steady on purpose, and that the liver is a central player in doing so.

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The Pancreas Pinned Down (1889)

If Bernard showed that blood sugar is regulated, the next question was what organ governs it — and the answer arrived almost by accident. In 1889, at the University of Strasbourg, two researchers, Oskar Minkowski (1858–1931) and Joseph von Mering (1849–1908), were investigating the role of the pancreas in fat digestion. They surgically removed the entire pancreas from a dog. Within a short time the previously healthy animal developed the classic signs of severe diabetes: it drank and urinated enormously, and — in the detail that made history — its urine was loaded with sugar (Minkowski measured roughly 12 percent). The observation is often retold with the laboratory caretaker noticing that flies swarmed the dog's urine, prompting Minkowski to test it.

Minkowski repeated the experiment carefully and confirmed it: removing the pancreas reliably produced diabetes. Crucially, he then showed that if a small piece of pancreas was grafted back under the dog's skin, the diabetes was held off until that graft was removed — powerful evidence that the pancreas was releasing some internal substance into the blood that controlled sugar, rather than acting only through its digestive juices. This pointed straight at the small clusters of pancreatic cells that the German anatomy student Paul Langerhans had described in 1869 (the "islets of Langerhans") without knowing their function. The pancreas was now the prime suspect; the hunt was on for the hormone it made. That hunt would take another three decades and would end in Toronto.

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Insulin: The Toronto Breakthrough (1921–1922)

The single most consequential event in the history of blood sugar is the isolation of insulin — the pancreatic hormone that lowers blood glucose — at the University of Toronto in 1921 and its first successful use in a patient in 1922. Before insulin, a diagnosis of what we now call type 1 diabetes was effectively a death sentence; the only treatment was a brutal near-starvation diet that bought, at most, a little time. The breakthrough came from an unlikely team. Frederick Banting (1891–1941) was a young Canadian surgeon with an idea but no track record in research. Charles Best (1899–1978) was a medical student assigned as his assistant. They worked in the laboratory of the Scottish-born physiologist John Macleod (1876–1935), who provided the facilities, expertise, and direction, and the biochemist James Collip (1892–1965) developed the methods to purify the extract enough to inject safely into humans.

Over the summer of 1921 Banting and Best produced pancreatic extracts that lowered blood sugar in diabetic dogs. With Collip's purification, the extract was ready for a human trial. In January 1922, a 14-year-old boy named Leonard Thompson, dying of diabetes in Toronto General Hospital, became the first person treated with insulin. The first, less-pure dose produced an allergic reaction and little benefit; a refined batch given days later dramatically lowered his blood sugar and reversed his decline. Word spread fast, and within little more than a year insulin — manufactured at scale in partnership with Eli Lilly and Company — was saving lives around the world. The 1923 Nobel Prize in Physiology or Medicine went to Banting and Macleod; in a gesture that also reflected real bitterness over who deserved credit, Banting shared his prize money with Best and Macleod shared his with Collip. The discovery did not cure diabetes — insulin must be taken for life — but it transformed an acute killer into a chronic condition that could be managed, and it made "controlling blood sugar" a daily, lifelong, achievable task for millions.

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From French Lilac to Metformin (1920s–1957)

Insulin solved the crisis of type 1 diabetes, but the far more common type 2 — in which the body still makes insulin but responds to it poorly — needed different tools, and one of the most important has a genuinely old botanical origin. The plant Galega officinalis, known as goat's rue or French lilac, was used in European folk and herbal medicine for symptoms we would now recognize as diabetes; it was eventually found to be rich in guanidine and related compounds that lower blood glucose. Guanidine itself proved too toxic for routine use, but chemists in the early twentieth century synthesized a family of safer derivatives, the biguanides. One of them, dimethylbiguanide, is the drug we now call metformin.

Metformin's clinical career was launched by the French physician Jean Sterne (1909–1997), who in collaboration with colleagues studied the compound and published results supporting its use in diabetes in 1957; he gave it the evocative trade name Glucophage — "glucose eater." Metformin spread through Europe and was eventually approved in the United States in 1994. Today it is one of the most widely prescribed medicines on earth and the standard first-line drug for type 2 diabetes, working largely by reducing the liver's output of glucose — the very organ whose sugar-making role Claude Bernard had identified a century earlier. The lineage from a medieval herb to a modern first-line drug is a clean example of how blood-sugar treatment has repeatedly moved from folk observation to isolated compound to rigorously tested medicine.

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Measuring the Average: HbA1c (1968)

For most of the twentieth century, a blood-sugar reading was a snapshot — a single value that could be high or low depending on the last meal, the time of day, or stress. What was missing was a way to measure long-term control. That gap was closed by the Iranian-born physician and biochemist Samuel Rahbar (1929–2012). In 1968, while screening blood samples by electrophoresis, Rahbar noticed an unusual fast-moving hemoglobin fraction that appeared consistently and at elevated levels in the blood of people with diabetes. He confirmed the pattern across dozens of additional diabetic patients and recognized that this was a form of hemoglobin chemically modified by glucose — what we now call glycated hemoglobin, or HbA1c.

The insight that made HbA1c revolutionary is simple and elegant: because glucose attaches to hemoglobin slowly and irreversibly over the lifetime of a red blood cell (about three months), the percentage of hemoglobin that is glycated reflects the average blood sugar over roughly the preceding 8–12 weeks. A single HbA1c test, in other words, summarizes months of glucose exposure in one number that no single fingerstick can fake. It took years for the field to accept the finding — many assumed an enzyme must be responsible — but HbA1c eventually became the central yardstick of diabetes care, the metric used to diagnose the disease, to judge whether treatment is working, and (as later research showed) to predict the risk of long-term complications. The companion Hemoglobin A1C page covers the test in clinical detail.

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Ranking the Foods: The Glycemic Index (1981)

Blood sugar is shaped not only by hormones and drugs but by food — and for a long time nutrition advice lumped all carbohydrates together, distinguishing only crudely between "simple" sugars and "complex" starches. That framework was upended in 1981 when David J. A. Jenkins and colleagues at the University of Toronto published the glycemic index in the American Journal of Clinical Nutrition. Jenkins's team fed healthy volunteers fixed amounts of carbohydrate from 62 different foods and measured the actual rise in blood glucose each produced over two hours, expressing it as a percentage of the response to pure glucose. The results overturned conventional wisdom: some starchy "complex" foods spiked blood sugar more than table sugar did, while legumes produced surprisingly gentle rises.

The glycemic index gave clinicians and patients, for the first time, an evidence-based way to rank foods by their real-world effect on blood sugar rather than by their chemical category. It was later refined with the concept of glycemic load (which accounts for how much carbohydrate a normal serving actually contains, not just how fast it is absorbed), and it remains a practical tool wherever continuous monitoring is unavailable. The history here is honest in both directions: the glycemic index was a genuine advance and is well validated as a measurement, but its usefulness for predicting long-term health outcomes in the general population is more debated than its popularity suggests, because real meals mix foods and individual responses vary. Our Glycemic Index & Load deep-dive treats the nuances.

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Insulin Resistance and "Syndrome X" (1988)

By the late twentieth century it was clear that the most common blood-sugar problem in the developed world was not a shortage of insulin but a blunted response to it — insulin resistance. The idea that tissues could resist insulin had been raised decades earlier (the British physician Harold Himsworth distinguished "insulin-sensitive" from "insulin-insensitive" diabetes in the 1930s), but its central importance was crystallized by the Stanford endocrinologist Gerald Reaven (1928–2018). In his 1988 Banting Lecture to the American Diabetes Association, Reaven proposed that insulin resistance was not merely one feature of type 2 diabetes but the common thread linking a whole cluster of disorders — high blood sugar, high blood pressure, abnormal blood fats, and elevated cardiovascular risk. He named the cluster "Syndrome X."

The framework reshaped how medicine thinks about blood sugar. It shifted attention upstream, from glucose itself to the hormonal dysfunction driving it, and it explained why high blood sugar so often travels with heart disease, obesity, and stroke. The cluster Reaven described is now usually called the metabolic syndrome, and insulin resistance is understood to precede overt type 2 diabetes by many years — which is precisely why measuring and addressing it early has become a goal of preventive medicine. Our Insulin Resistance deep-dive and the Metabolic Syndrome page carry this thread forward.

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Proving Control Matters: DCCT and UKPDS (1993–1998)

It is one thing to say blood sugar should be controlled; it is another to prove, in a rigorous trial, that tighter control actually prevents the blindness, kidney failure, nerve damage, and amputations that diabetes causes. Two landmark studies settled the question. The Diabetes Control and Complications Trial (DCCT), published in the New England Journal of Medicine in 1993, followed 1,441 people with type 1 diabetes and compared intensive blood-sugar control against the conventional standard of the day. The result was decisive: intensive control (lower average HbA1c) cut the development and progression of diabetic eye, kidney, and nerve disease by large margins — retinopathy risk fell by roughly three-quarters. The trade-off, honestly reported, was a higher rate of dangerous low-blood-sugar episodes.

What DCCT did for type 1, the United Kingdom Prospective Diabetes Study (UKPDS) did for the far more common type 2. Published in The Lancet in 1998 after following more than 5,000 patients for a median of ten years, UKPDS showed that intensive blood-glucose control substantially reduced microvascular complications in type 2 diabetes — though, importantly, it did not significantly reduce heart attacks and strokes within the trial period, and it too increased the risk of hypoglycemia. Together these two trials are the evidentiary bedrock of modern diabetes care: they are why HbA1c targets exist, why "tight control" is recommended, and also why that recommendation is tempered by honesty about its limits and its risks. They are the moment blood-sugar management stopped being a plausible idea and became a proven one.

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The Measurement Revolution: Continuous Glucose Monitoring

For most of this history, a person could only know their blood sugar by drawing blood. The home glucose meter, which let patients test a fingertip drop themselves, spread in the 1970s and 1980s and was itself a revolution in self-management. But a fingerstick is still a single snapshot, and it tells you nothing about what happens between tests — the overnight lows, the post-meal spikes, the slow drift before breakfast. The technology that closed that gap traces back to the American chemist Leland Clark, whose work on enzyme-based electrochemical glucose sensing in the 1960s underlies essentially every modern sensor: an enzyme (glucose oxidase) reacts with glucose and generates a tiny electrical signal proportional to its concentration.

Decades of engineering turned that principle into a wearable. The first commercial continuous glucose monitor (CGM) — a small sensor worn under the skin that reads glucose in the interstitial fluid every few minutes — was approved by the U.S. Food and Drug Administration in 1999 (the MiniMed system), initially as a professional tool that stored data for a clinician to review later. From there the devices improved relentlessly: real-time displays, longer wear time, factory calibration, and direct streaming to a phone. Modern systems — brands such as the Dexcom and FreeStyle Libre families — let a person watch their own glucose curve in real time and learn, meal by meal, exactly how their body responds. This is the development that finally made the abstract goal of "blood-sugar management" into something an ordinary person can see, measure, and act on day to day; our Continuous Glucose Monitoring deep-dive covers the current devices and their limits.

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Evidence & Reception: What Is Actually Established

Because "blood sugar management" spans everything from life-saving medicine to popular wellness advice, honesty requires separating what is firmly established from what is promising or merely marketed. The following are well established by strong evidence: that blood glucose is actively regulated, with the liver and the pancreatic hormone insulin at the center; that insulin replacement is essential and life-saving in type 1 diabetes; that metformin is a safe, effective first-line drug for type 2 diabetes; that HbA1c reliably reflects long-term glucose exposure; and that, as the DCCT and UKPDS trials proved, sustained control of blood sugar reduces the microvascular complications of diabetes (eye, kidney, and nerve damage). These are not in serious scientific dispute.

Other widely promoted ideas are genuine but more limited or more debated than popular sources imply. Intensive glucose lowering has a clearer benefit for small-vessel complications than for heart attacks and strokes, and pushing blood sugar too low carries real danger from hypoglycemia — the benefit-versus-risk balance is individual, not one-size-fits-all. The glycemic index is a valid measurement but an imperfect guide to whole-diet health. And the fast-growing practice of using continuous glucose monitors in people without diabetes — now heavily marketed for "metabolic optimization" — is an area where enthusiasm currently outruns the evidence: it is plausible and increasingly studied, but the long-term health benefit of CGM-guided eating in healthy adults is not yet established by large outcome trials. Finally, the many herbs, foods, and supplements promoted for blood sugar (cinnamon, berberine, chromium, bitter melon, and others) range from modestly supported to weak; some show real but small effects in trials, and none is a substitute for proven care.

The honest bottom line is that blood-sugar management is one of the best-validated areas in all of medicine at its core — insulin, metformin, HbA1c, and the case for control are bedrock — while its newer, consumer-facing fringes (non-diabetic CGM, supplement claims, and aggressive "optimization") are exactly the parts that demand the most skepticism. Anyone with diabetes or pre-diabetes should make decisions about medication, targets, and monitoring with a clinician, because the right level of blood-sugar control is a balance that depends on the individual.

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Research Papers and References

The list below combines key primary and historical papers in the science of blood-sugar regulation with curated PubMed topic-search links. Foundational nineteenth-century work (Claude Bernard's isolation of glycogen; the 1889 Minkowski–von Mering pancreatectomy) is described in the article as historical milestones. Author names, titles, and journals are given as plain text; only the stable DOI, PMID, or archive link is hyperlinked, and each opens in a new tab.

  1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine. 1993;329(14):977-986. — doi:10.1056/NEJM199309303291401 · PMID: 8366922
  2. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The Lancet. 1998;352(9131):837-853. — PMID: 9742976
  3. Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-1607. — doi:10.2337/diab.37.12.1595 · PMID: 3056758
  4. Jenkins DJ, Wolever TM, Taylor RH, et al. Glycemic index of foods: a physiological basis for carbohydrate exchange. American Journal of Clinical Nutrition. 1981;34(3):362-366. — PMID: 6259925
  5. Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. New England Journal of Medicine. 2010;362(9):800-811. — doi:10.1056/NEJMoa0908359 · PMID: 20200384
  6. Azizi MH, Bahadori M, Azizi F. Breakthrough discovery of HbA1c by Professor Samuel Rahbar in 1968. Archives of Iranian Medicine. 2013;16(12):743-745. — PMID: 24329151
  7. History of blood glucose regulation, insulin discovery, and diabetes — PubMed: history of insulin and blood-glucose regulation
  8. Continuous glucose monitoring — history and clinical use — PubMed: continuous glucose monitoring

External Authoritative Resources

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Connections

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