Diabetes

• 1. Introduction

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  In 1500 BCE, an Egyptian manuscript described a strange affliction as "too great emptying of the urine." The complaint would echo across thousands of years and dozens of cultures. The disease is diabetes mellitus, a group of endocrine conditions defined by sustained high blood sugar. Indian physicians once called it madhumeha, or honey urine, because the urine would attract ants. Greek doctors named it after the idea of a siphon, something passing through. Today the numbers are staggering. The count of people diagnosed worldwide rose from 200 million in 1990 to 828 million in 2024. It affects one in seven adults. More than half of those affected do not know they have it. How does a single hormone hold so much sway over the body? Why do its types behave so differently? And how did a condition known to the ancient world become one of the defining health challenges of our age?

• 2. The Insulin Switch

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  Insulin is the principal hormone that regulates how glucose moves from the blood into the body's cells, especially in the liver, fat tissue, and muscle. Beta cells in the islets of Langerhans, found in the pancreas, release it in response to rising blood glucose after eating. About two-thirds of the body's cells rely on insulin to absorb glucose for fuel, conversion, or storage. The hormone glucagon works in the opposite manner, prompting the breakdown of stored glycogen back into glucose when levels fall.

  The body draws glucose from three sources. It absorbs glucose from food in the intestine. It breaks down glycogen stored in the liver. And it manufactures glucose from non-carbohydrate substrates through gluconeogenesis. Insulin can inhibit both glycogen breakdown and gluconeogenesis, while pushing glucose into fat and muscle cells for storage.

  When insulin runs short, or cells respond poorly to it, or the insulin itself is defective, this balance collapses. Glucose is not absorbed properly and is not stored in the liver and muscles. The result is persistently high blood glucose, poor protein synthesis, and in complete insulin deficiency, metabolic acidosis. When too much glucose lingers, the kidneys reach a reabsorption threshold and pass the surplus into urine, a condition called glycosuria. That sugary urine pulls water along with it, driving heavy urination and fluid loss. The lost volume is replaced from water inside the body's cells, causing dehydration and intense thirst, while glucose-starved cells stimulate the appetite.

• 3. One Name, Many Diseases

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  The World Health Organization sorts diabetes into six categories: type 1, type 2, hybrid forms, hyperglycemia first detected during pregnancy, other specific types, and unclassified diabetes. Type 1 and type 2 are the major forms, and individuals may even carry a combination of forms.

  Type 1 diabetes accounts for 5 to 10% of cases and is the most common type diagnosed in patients under 20. The older label "juvenile-onset diabetes" has been dropped because onset in adulthood is possible. It is an autoimmune condition in which a T cell-mediated attack destroys the insulin-producing beta cells, leaving severe insulin deficiency. Certain HLA genotypes influence the risk, and twin studies show only about a 50% concordance rate, pointing to inherited risk that is real but not total. When type 1 develops in adults it is called latent autoimmune diabetes of adults, or LADA, with a slower onset than in children. Some use the unofficial term "type 1.5 diabetes," and adults with LADA are frequently misdiagnosed as having type 2 based on age rather than cause.

  Type 2 diabetes is marked by insulin resistance, sometimes combined with reduced insulin secretion, and it accounts for more than 95% of cases. The defective responsiveness is believed to involve the insulin receptor, though the specific defects are not known. It stems primarily from lifestyle factors and genetics. Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 60 to 80% in those of European and African descent, and 100% of Pima Indians and Pacific Islanders. Sugar-sweetened drinks raise the risk, saturated and trans fats increase it, and adverse childhood experiences such as abuse and neglect raise the likelihood by 32%, with neglect having the strongest effect.

  Gestational diabetes occurs in about 2 to 10% of all pregnancies and may improve or disappear after delivery. Maturity-onset diabetes of the young, or MODY, is a rare autosomal dominant form making up 1 to 2% of cases, with at least 14 subtypes. Malnutrition-related diabetes, also called type 5, involves decreased insulin production but unlike type 1 does not produce ketonuria or ketosis. Beyond these, researchers have floated unofficial labels: "type 3 diabetes" for the insulin resistance Alzheimer's disease causes in the brain, and "type 4 diabetes" for age-related insulin resistance seen in lean mice.

• 4. The Three Ps And Beyond

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  Polydipsia, polyuria, and polyphagia are the three Ps, the classic signs of diabetes meaning excessive thirst, excessive urination, and excessive hunger. They arrive alongside weight loss and blurred vision. Other non-specific signs include fatigue, sweet-smelling urine, and genital itchiness from Candida infection. About half of affected individuals may be asymptomatic. Type 1 presents abruptly after a pre-clinical phase, while type 2 has an insidious onset, and patients may stay symptom-free for years.

  Diabetic ketoacidosis is a medical emergency, most common in type 1, where excessive production of ketone bodies brings nausea, vomiting, abdominal pain, the smell of acetone on the breath, and the deep breathing known as Kussmaul breathing. In severe cases it lowers the level of consciousness. Hyperosmolar hyperglycemic state is another emergency, marked by dehydration from severe hyperglycemia and an altered mental state that can reach coma. Hypoglycemia, a complication of insulin treatment, ranges from sweating, trembling, and palpitations to confusion, seizures, coma, and rarely death.

  Diagnosis rests on measuring blood glucose. A fasting plasma glucose at or above 7.0 mmol/L, which is 126 mg/dL, qualifies, as does a reading at or above 11.1 mmol/L, or 200 mg/dL, two hours after a 75 gram oral glucose load. A glycated hemoglobin, or HbA1C, at or above 48 mmol/mol, which is 6.5 percent, also meets the bar. Between these states lies prediabetes, and as of 2020-38% of all US adults had it.

• 5. The Slow Damage

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  Diabetes doubles the risk of cardiovascular disease, and about 75% of deaths in people with diabetes come from coronary artery disease. The major long-term complications trace back to damage to blood vessels at both the large and small scale. Stroke and peripheral artery disease sit among the larger-vessel harms.

  Diabetic retinopathy, damage to the retina, is the most common cause of blindness in people of working age. The eyes can also develop cataract and glaucoma, which is why people with diabetes are advised to see an optometrist or ophthalmologist once a year. Diabetic nephropathy is a major cause of chronic kidney disease, accounting for over 50% of patients on dialysis in the United States.

  Diabetic neuropathy, nerve damage, shows up as sensory loss, neuropathic pain, and autonomic dysfunction such as postural hypotension and erectile dysfunction. Loss of pain sensation invites injury, leading to diabetic foot problems like ulceration, the most common cause of non-traumatic lower-limb amputation. Hearing loss is another long-term complication. A causal link appears to exist between type 2 diabetes and gallstones, and diabetes increases the risk of dementia, with the risk climbing the earlier one is diagnosed.

• 6. Holding The Line

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  An HbA1C level below 7% is the goal of treatment, the threshold at which complications grow far less common and less severe. Diabetes management keeps blood sugar close to normal without tipping into low blood sugar, achieved through dietary changes, exercise, weight loss, and appropriate medications. Attention also goes to smoking, high blood pressure, metabolic syndrome, and obesity, all of which can accelerate the disease's harm.

  Type 1 diabetes requires insulin, ideally a basal bolus regimen using long-acting insulin for the basal rate and short-acting insulin with meals. Metformin is the recommended first-line treatment for type 2, working by decreasing the liver's glucose production and increasing glucose stored in peripheral tissue, with good evidence that it lowers mortality. Other drug classes follow: sulfonylureas to increase insulin release, acarbose to slow sugar absorption in the intestines, DPP-4 inhibitors such as sitagliptin, thiazolidinediones to improve insulin sensitivity, and SGLT2 inhibitors to push glucose out in the urine.

  Weight loss surgery in people with obesity and type 2 diabetes is often effective, with many maintaining normal blood sugar afterward and decreased long-term mortality, against a short-term surgical mortality risk of less than 1%. A pancreas transplant is occasionally considered for type 1 patients with severe complications, including end-stage kidney disease. For type 2 diabetes that accounts for 85 to 90% of all cases, prevention is possible: more than 90 minutes of physical activity per day reduces the risk by 28%.

• 7. An Ancient Diagnosis

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  In 230 BCE, the Greek Apollonius of Memphis first used the term diabetes, meaning to pass through. The disease was considered rare during the Roman Empire, and the physician Galen said he had seen only two cases in his career, naming it diarrhea of the urine. The earliest surviving detailed account belongs to Aretaeus of Cappadocia, from the 2nd or early 3rd century CE, who attributed the disease to moisture and coldness in keeping with the Pneumatic School of medicine. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.

  The Indian physicians Sushruta and Charaka, in 400 to 500 CE, were the first to identify two types of diabetes as separate conditions, one tied to youth and another to being overweight. The word mellitus arrived much later. Thomas Willis added it in 1675 after noticing that the urine of a person with diabetes tasted sweet, a sweetness the ancient Greeks, Chinese, Egyptians, and Indians had all observed.

  Effective treatment did not arrive until the early 20th century. The Canadians Frederick Banting and Charles Best isolated and purified insulin in 1921 and 1922, and the long-acting insulin NPH followed in the 1940s. The St. Vincent Declaration of 1989 marked international efforts to improve care for those with the disease.

• 8. A Shared Burden

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  In 2010, diabetes-related emergency room visit rates in the United States reached 526 per 10,000 people in the lowest-income communities, against 236 per 10,000 in the highest-income communities. The disease does not fall evenly. Racial and ethnic minorities carry higher prevalence: US adults overall face a 40% chance of developing type 2 diabetes, while the chance for Hispanic and Latino adults is more than 50%. Among Asian Americans, 1 in 3 cases go undiagnosed, compared with 1 in 5 nationally.

  Diabetes stigma describes the negative judgment and prejudice aimed at people with the disease, often rooted in the idea that type 2 diabetes results from poor lifestyle choices rather than genetics and social determinants of health. Stigma reaches into marriage proposals, employment, and social standing, and it turns inward as self-stigma tied to higher distress and depression. Women fare worse than men: they face more mental health issues such as eating disorders, are three times more likely to be housebound, and seek more medical help while receiving less than men of the same race and economic class.

  The disease is not confined to humans. It is most common in dogs and cats, with female dogs twice as likely to be affected as males, and small breeds such as Miniature Poodles particularly prone. Feline diabetes is strikingly similar to human type 2 diabetes, with the Burmese, Russian Blue, Abyssinian, and Norwegian Forest breeds at higher risk. Birds, by contrast, do not develop diabetes at all, owing to their unusually high tolerance for elevated blood glucose.