What Is Diabetes? — The Letter That Never Comes, the Letter That Isn't Read

When a Single Line on a Health Checkup Report Stays High

A person who receives a health checkup report stops at a line in the blood test column. Told to measure it again, after several tests they hear the word diabetes. A parent or spouse may have heard those words. The explanations that come to mind at that time are usually about "eating too many sweets" or "gaining weight."

Blood sugar is the amount of sugar dissolved in the blood. Diabetes is a disease in which a state where blood sugar is higher than the normal range continues for a long time. In this article, some of the numbers representing scale are taken from national statistics surveying South Korean adults. Among South Korean adults aged 30 and older in 2020, it was estimated that one in six people had diabetes (16.7%) (PMID 35656565).

The preceding article covering blood sugar, "How Blood Sugar Stays Steady — A Letter to Store, a Letter to Release," explained how a healthy body keeps blood sugar trapped within a narrow band by comparing it to letters. When blood sugar rises, a letter saying "store it away" travels through the blood, and the liver, muscles, and fat read that letter and pull in the sugar from the blood. In diabetes, this letter breaks down. The letter does not arrive at all, or even if the letter arrives it is not read well and sending more cannot keep up.

Diabetes is divided into two major branches: "the disease where letters do not arrive" and "the disease where letters are not read well even when they arrive."

The Cells That Write Letters

Glucose is a sugar produced as carbohydrates in rice, bread, and fruit are digested, in a form that cells can immediately burn as fuel. The "sugar" in blood sugar is mostly glucose. A hormone is a substance made in one part of the body that travels through the blood to a distant place and changes what the cells there do. The letters this article talks about are hormones.

Letters about blood sugar mostly go out from one organ. The pancreas is an organ laid horizontally behind the stomach, which both makes digestive juices to send to the gut and releases hormones into the blood to handle blood sugar. Insulin is a hormone that comes out of the pancreas when blood sugar rises, telling the liver, muscle, and fat to "gather glucose from the blood and store it."

The cells that make insulin are gathered in small clusters inside the pancreas. Beta cells are the cells within those clusters that make and release insulin. The cell that writes the letter lowering blood sugar is the single beta cell, and the places that read that letter are the liver, muscle, and fat.

The breakdown of diabetes spans across multiple locations including beta cells, adipose tissue, muscles, and the liver (PMID 39059357). One branch happens when immunity destroys beta cells, and another more common branch happens when a state where the body responds less to insulin overlaps with varying degrees of beta cell functional decline (PMID 39059357). The former is a breakdown on the letter-writing side, and the latter is a breakdown of both the reading side and the writing side together.

Type 1 — The Cells That Write the Letters Disappear

Immunity is the system that finds and destroys bacteria and viruses that enter the body. Autoimmunity is when the immunity that protects the body mistakes its own cells for enemies and attacks them. Type 1 diabetes is a form of diabetes where autoimmunity destroys the beta cells of the pancreas, leaving almost no insulin to be produced. Standing at the front of the attack are T cells, a type of immune cell (PMID 40375390). Once the beta cells disappear, insulin stops coming out entirely or almost entirely (PMID 40734585). Because the cells that write the letters have vanished, the letters do not arrive.

Type 1 accounts for 5 to 10% of all diabetes (PMID 41697686). It is most commonly diagnosed at a young age, but in the United States, half of those diagnosed are 24 or older (PMID 41697686). Type 1 can develop at any age (PMID 40734585).

The attack begins quietly, before symptoms appear. Antibodies targeting beta cells are found in the blood from several weeks to as long as 20 years before the disease becomes apparent (PMID 31534209). Most people diagnosed with type 1 have at least one such antibody (PMID 41697686). Only after enough beta cells have disappeared does even fasting blood sugar rise and symptoms appear (PMID 40375390).

Type 1 develops when environmental or immune triggers are added to a genetic predisposition (PMID 40375390). Factors such as viruses that infect the gut are linked to the risk, but a connection showing that a specific pathogen causes type 1 has been hard to confirm (PMID 40375390). It is still unknown what first starts the attack (PMID 40734585). Nine out of ten people diagnosed with type 1 do not have anyone with type 1 in their family (PMID 40375390).

Type 1 is a disease in which immunity destroys the cells that write the letters, and why that attack starts is not yet known. For now, insulin must be supplied from outside the body for life (PMID 41697686).

Type 2 — Not Read Well, and Failing to Keep Up When More Are Sent

The previous article about blood sugar ended with this preview: in the most common form, tissues respond less to insulin, and beta cells fail to pump out enough extra to make up for it. That most common form is Type 2. The vast majority of diabetes is Type 2 (PMID 25568613).

Insulin resistance is a state where the liver, muscle, and fat do not respond to insulin as well as they used to. Type 2 diabetes is a condition where insulin resistance is compounded by a drop in beta cell function, raising blood sugar because the body fails to release as much insulin as it needs. Insulin resistance and impaired insulin secretion are the two core defects in Type 2 (PMID 27189025).

When a letter is not read well, less work gets done. A liver with insulin resistance still fails to stop making glucose even after receiving insulin, and muscles take in less glucose after a meal (PMID 40409800).

Even so, the body holds out for a while. Even with insulin resistance, blood sugar stays normal as long as beta cells pump out more insulin, and blood sugar only rises when beta cells can no longer keep up by sending that extra insulin (PMID 24315620). Blood sugar does not rise simply because the letters are not read well; Type 2 diabetes happens when even the extra letters sent can no longer keep up.

The strength of beta cells begins to decline long before diagnosis. It is thought that a significant portion of the capacity to release insulin has already vanished before diagnosis (PMID 32543261). A progressive drop in beta cell function is a hallmark of Type 2 (PMID 27189025). However, because reports show that some of this functional decline can be reversed, it is hard to conclude that beta cells are inevitably ruined all the way to the end (PMID 32543261).

Type 2 arises from a combination of multiple factors. Environmental factors like obesity, unhealthy diets, and a sedentary lifestyle work together with genetic factors (PMID 27189025). Having Type 2 in the family raises the risk 1.5- to 3-fold (PMID 40409800). Genetic variants directly or indirectly contribute to insulin resistance in the liver, muscle, and fat (PMID 40409800). Social conditions, such as whether one can obtain nutritious food, also alter the risk of developing diabetes (PMID 39059357).

Body weight is a major factor. In data from the Korea National Health and Nutrition Examination Survey, the prevalence of diabetes in adults with obesity was nearly double that in adults without obesity. Yet even among adults without obesity, about one in ten had diabetes (PMID 41813264). Conversely, among Korean adults aged 19 and older with diabetes, just over half were classified as obese by body mass index, while nearly the other half were not. However, looking at waist circumference, abdominal obesity affected about six in ten (PMID 41813263).

Gestational diabetes is diabetes that did not exist before pregnancy and appears for the first time during pregnancy. In Korean health insurance data, women who experienced gestational diabetes had a significantly higher risk of developing Type 2 diabetes after childbirth compared to women who did not (PMID 41813263).

Type 2 diabetes is a disease that arises from overlapping genetics, weight, and living conditions, and cannot be explained by a single cause.

What "Your Fault" Leaves Behind

Four out of five adults with diabetes experience stigma on average because of diabetes, and one out of five experiences discrimination (PMID 38128969). Stigma is negative social judgment, stereotypes, and prejudice, while discrimination is unfair treatment in healthcare, education, and employment (PMID 38128969).

An international consensus statement created by 51 experts from 18 countries identified "blaming," viewing someone as a burden or a patient, the fact that the disease is not visible, and fear or disgust as the primary forces driving diabetes stigma (PMID 38128969). The same consensus statement concluded that diabetes stigma and discrimination are harmful, unacceptable, unethical, and actually counterproductive (PMID 38128969).

Stigma also appears alongside physical outcomes. In both adults with type 1 and type 2, diabetes stigma is associated with reduced self-care behaviors, higher values reflecting long-term average blood sugar, and more frequent long-term damage (PMID 39105174). This association alone cannot confirm that stigma causes these outcomes. In an online study of 1,212 adults with type 2 in the United States, many respondents reported frequently experiencing blaming and judgmental looks, and many were turning that stigma inward upon themselves (PMID 32799378).

Language that attributes type 2 diabetes to a person's "fault" omits the evidence that multiple factors overlap. The position of the international consensus is that such stigma is harmful in its own right.

One Rotation a Day, in a Body with Type 2 Diabetes

The previous article followed the day of a healthy body from breakfast to the following morning. We walk that same day again, this time in a body with type 2 diabetes.

At 7:30 AM, you eat breakfast with rice and side dishes. Digested glucose enters the blood, blood sugar rises, and beta cells release insulin. The letters arrive. But in a body with insulin resistance, the liver does not stop making glucose enough, and muscles take in less of the glucose after eating (PMID 40409800).

Before the disease began, beta cells would have released more insulin here to pull blood sugar back to normal (PMID 24315620). In a body with type 2 diabetes, beta cells cannot release that much, so blood sugar rises (PMID 24315620). The same thing repeats at lunch and dinner.

You fall asleep at 11:00 PM. Fasting blood sugar is the blood sugar measured before breakfast after not eating anything all night. We saw in the previous article that in a healthy body, this value is balanced between the glucose the liver released through the night and the glucose the body used. The view that traces the main cause of type 2 to fat accumulated in the liver and pancreas explains that fat excessively accumulated in the liver lowers the liver's insulin response and increases the liver's glucose production (PMID 31097391). In diabetes, the reason blood sugar is high even after fasting all night is mainly because the liver newly makes and excessively releases glucose (PMID 8379904). The liver spends the night unable to read the "stop" letter well and without even receiving enough of those letters, and the next morning's fasting blood sugar comes out high.

As this day repeats year after year, there is a path where things become more difficult. High blood sugar and blood fat abnormalities further drive insulin resistance and beta cell function decline through common pathways like inflammation (PMID 39353925). In a body where letters are not read well, even the beta cells that used to send more grow exhausted—that is how the days of type 2 diabetes accumulate.

What Long-Term High Blood Sugar Leaves Behind

If you peer into the back of the eye of a person with diabetes, blood vessel damage is visible in roughly one out of five. In an analysis pooling population-based studies from several countries, the proportion of people with diabetes who had diabetic retinopathy was around that level, and this condition is one of the leading causes of preventable vision loss in working-age adults (PMID 33940045).

A complication is a disease that follows somewhere else in the body because of an existing condition. The vascular complications of diabetes are divided into small blood vessel and large blood vessel categories (PMID 9315387). Microvascular complications are those that occur when long-term high blood sugar damages the very fine blood vessels in the eyes, kidneys, and nerves. When exposed to high blood sugar for a long time, these delicate vessels are affected, eventually leading to diseases of the kidneys, eyes, and nerves (PMID 31057114).

The names of the three conditions follow where they are located. Diabetic retinopathy is a disease in which the fine blood vessels of the retina—the light-sensing membrane at the back of the inside of the eye—are damaged. Diabetic kidney disease is a condition where the kidneys, which filter blood to make urine, are damaged.

Diabetic neuropathy is a condition where the nerves stretching throughout the body are damaged. In people with type 2 diabetes, kidney disease and retinopathy each occur at a rate of about one in four, while neuropathy appears in nearly one in two people with diabetes (PMID 31057114). Blood sugar is not the only factor that raises this risk. The duration of having diabetes, along with the degree of management of blood sugar, blood pressure, and fats in the blood, are common risk factors (PMID 31057114).

Macrovascular complications are those that occur when the thick arteries leading to the heart, brain, and legs narrow or become blocked. In diabetes, the process of the inner arterial walls narrowing progresses rapidly, and as a result, diseases of a lack of blood flow to the heart muscle, cerebrovascular diseases, and diseases of the leg vessels occur (PMID 9315387). In type 2, these complications stem from other metabolic abnormalities that accompany insulin resistance alongside high blood sugar (PMID 27189025).

In a literature review pooling studies from various countries around the world, about one in three people with type 2 diabetes in their mid-60s on average who had lived with diabetes for a little over 10 years had cardiovascular disease, and roughly half of the deaths recorded during the study periods were due to cardiovascular disease. Among those, coronary heart disease and stroke accounted for a large share (PMID 29884191). However, not everyone with diabetes carries the same magnitude of cardiovascular risk, and the size of the risk varies greatly from person to person (PMID 30828746). The heart side of the story continues in "What Coronary Artery Disease Is — The Road That Feeds the Heart, Narrowed and Blocked", and the brain side continues in "What a Stroke Actually Is — Blocked, Burst, and the Clock".

Does Lowering Blood Sugar Reduce It?

There is a trial that divided people with type 1 diabetes into two groups. One side aimed to bring blood sugar close to normal using insulin injections three or more times a day or an insulin pump, while the other side continued the conventional approach of injecting once or twice a day. After an average of 6.5 years, the risk of developing retinopathy among people who initially had no retinopathy was 76% lower in the intensive management group. Looking at all participants combined, neuropathy was also reduced by more than half (PMID 8366922). The authors concluded that intensive management delays the onset of retinopathy, nephropathy, and neuropathy and slows their progression (PMID 8366922).

The price was also clear. Hypoglycemia is a state where blood sugar has fallen below the normal range. Severe hypoglycemia is hypoglycemia where blood sugar drops so significantly that a person cannot manage it on their own and needs the help of another person. In the intensive management group, severe hypoglycemia increased 2 to 3 times (PMID 8366922). Among the type 1 participants in this trial, the increased hypoglycemia was not associated with a decline in cognitive function or quality of life over a long period (PMID 24356592). This does not mean that every single episode of hypoglycemia is harmless. In follow-up observations tracking the same people after the trial ended, the effects of the initial management lasted a long time even after the blood sugar difference between the two groups disappeared, and the reduction in early complications led to a decrease in severe complications and cardiovascular disease (PMID 24356592).

Similar results exist in type 2 as well. A UK trial that divided people newly diagnosed with type 2 into conventional treatment with diet control alone and intensive treatment to lower blood sugar further with medication or insulin was followed for 10 years after the trial ended. Even though the blood sugar difference between the two groups disappeared after the first year, the risk of microvascular complications remained continuously lower in the group that lowered blood sugar with a class of oral medications or insulin, and risk reductions for myocardial infarction and all-cause mortality newly appeared over time (PMID 18784090). Benefits also continued in the group that used a different oral medication for overweight people (PMID 18784090).

In a pooled analysis of four large trials involving adults with type 2, kidney and eye events were reduced in the group that lowered blood sugar further for about 5 years, but nerve events were not reduced (PMID 28365411). The authors concluded that lowering blood sugar remains important for preventing long-lasting microvascular complications in adults with type 2 (PMID 28365411).

Conditions are attached to the benefits. When blood sugar is managed intensively, the burden of microvascular complications decreases, but hypoglycemia caused by treatment is a major barrier blocking that path (PMID 27432075). In type 2, some studies suggest that aiming for very low blood sugar targets may increase the risk of death (PMID 24526393).

A systematic review pooling trials in type 1 also concluded that strict blood sugar management reduces the risk of developing microvascular complications. However, that evidence came mainly from young patients in the early stages of the disease, and trial evidence is lacking in older patients. The effect appears to weaken after complications have already developed, and the benefits must be weighed against risks such as severe hypoglycemia (PMID 24526393). Large vessel events such as stroke and myocardial infarction happen rarely, so this review did not establish clear evidence for them (PMID 24526393). The authors noted that there is no definitive evidence supporting specific blood sugar targets, and treatment targets should be individualized by considering age, disease progression, large vessel risk, and lifestyle and self-management capacity (PMID 24526393).

Trial evidence shows that managing blood sugar reduces small vessel complications like those in the eyes and kidneys, but since lowering it too much brings opposing risks like hypoglycemia, targets are set differently for each person.

An Emergency Where Time Changes the Outcome

For people taking insulin and certain oral medications that increase insulin secretion, hypoglycemia has long been a known and dangerous side effect (PMID 30926258). When blood sugar drops significantly, brain function becomes disrupted (PMID 30926258), and in severe cases, it can lead to seizures or loss of consciousness (PMID 11699552).

Early in the disease, hormones that work in the opposite direction to raise blood sugar are secreted in abundance, and warning symptoms sent by the body prompt a person to eat, making severe hypoglycemia rare. As the duration of living with diabetes lengthens, this defense gradually weakens, and the more often hypoglycemia is experienced, the weaker the defense becomes, increasing the risk of severe hypoglycemia (PMID 27432075). For someone taking blood-sugar-lowering medication, losing consciousness or having a seizure is an emergency. Hypoglycemia is a serious complication that must be quickly recognized, diagnosed, and treated (PMID 26893262).

On the other side is the emergency of skyrocketing blood sugar. Diabetic ketoacidosis is an emergency state where a severe lack of insulin causes blood sugar to skyrocket and acidic substances called ketones to build up in the blood, tipping the blood toward acidity. It is characterized by the concurrent appearance of high blood sugar, ketones, and acidosis (PMID 35577617), and it is the most common hyperglycemia emergency in people with diabetes (PMID 32409703). Type 1 diabetes is not infrequently diagnosed at the very moment of ketoacidosis, with up to 44% of children and up to 23% of adults presenting with ketoacidosis at the time of a Type 1 diagnosis (PMID 41697686). Ketoacidosis can also occur in people with Type 2 diabetes (PMID 35577617).

Another soaring blood sugar emergency is hyperosmolar hyperglycemic state. It is an emergency where blood sugar becomes extremely high and a massive amount of water is lost from the body; whereas ketoacidosis is more common in young people with Type 1, this state is more common in adults and older adults with Type 2 diabetes (PMID 28372715). The two conditions are distinguished by the degree of dehydration and the degree of acidosis, and the mortality rate of hyperosmolar hyperglycemic state is roughly ten times that of ketoacidosis (PMID 26893262).

Both conditions are the most serious and life-threatening hyperglycemia emergencies in diabetes, and they are treated promptly with intravenous fluids and insulin (PMID 28372715). The diagnosis of ketoacidosis is confirmed by tests that check for ketones in the blood or urine and for acidity in the blood (PMID 32409703). If not treated in a timely manner, the condition deepens and can result in loss of life, but a substantial portion of that can be prevented (PMID 32409703).

In all of these emergencies, the time from recognition and diagnosis to treatment changes the outcome. It is common to all these emergencies that recognizing, diagnosing, and treating them early is paramount (PMID 28372715, PMID 26893262). Which condition is present cannot be sorted out by symptoms alone, definitive diagnosis can only be made through tests, and all are emergency states that require immediate treatment at a hospital.

What Is Done

For someone with type 1 diabetes, insulin must currently be supplied from outside the body for life, delivered through subcutaneous injections or an insulin pump (PMID 41697686). As for treatments that target the immune system's attack, the first drug to delay that onset at a stage before type 1 fully manifests has been approved (PMID 38308004, PMID 40033931), and other methods are being investigated (PMID 40033931).

The treatment of type 2 diabetes is grounded in methods that do not use drugs. Moving the body more, diet control, and cognitive behavioral therapy are important for maintaining normal blood sugar, and multiple classes of drugs are added on top of that (PMID 39940862). Because type 2 involves multiple overlapping breakdowns, keeping blood sugar in check often requires using several drugs together (PMID 27189025). Among them, GLP-1 receptor agonist drugs are covered separately in the articles on obesity and GLP-1.

Even in type 2, a time frequently comes when insulin becomes necessary (PMID 38559691). Barriers that prevent starting insulin include fear of hypoglycemia, the stigma attached to injections, weight gain, feeling that starting insulin is a treatment failure, and a lack of experience among some medical staff along with guidelines pushing insulin further down the line (PMID 38559691).

The goal of treatment does not stay at blood sugar alone. An article summarizing the American Diabetes Association's 2026 standards of care notes that diabetes management must be personalized care, and that the focus should be on reducing adverse outcomes themselves beyond just blood sugar management (PMID 41692340). Managing both blood sugar and blood pressure together is central to preventing complications in small and large blood vessels (PMID 37947481). Deciding what blood sugar target to aim for is something determined individually based on guidelines, and how to read those numbers is taken up by the article dealing with blood test numbers.

Can It Be Reversed — Remission

Remission is a state where blood sugar drops below the diabetes range and stays there, even without medications that lower blood sugar. There is as of yet no cure that makes type 2 diabetes go away completely, but remission can be reached with lifestyle interventions or the help of some medications (PMID 39353925). Remission is different from a cure.

The evidence has mainly come from weight loss. A review looking at the causes of type 2 in the fat of the liver and pancreas, as seen in "How Blood Sugar Stays Steady — A Letter to Store, a Letter to Release", notes that losing a large amount of weight can return the liver's response to insulin to normal, and that for many people within the first few years after diagnosis, this is linked to the recovery of insulin secretion by beta cells (PMID 31097391). In a trial conducted in primary care settings, 46% of type 2 diabetes participants who received a weight-loss program were in remission at 12 months, and 36% at 24 months, with the effect following weight loss (PMID 31097391). Fewer people were in remission at two years than at one year.

In an analysis combining randomized trials of adults with type 2 who were overweight or obese, the rate of reaching remission one year after the intervention varied greatly depending on how much weight was lost. Remission by the strictest criteria was almost nonexistent in the group that lost less than 10% of their body weight, and was about half in the group that lost 20% to 29% (PMID 40023186). In this analysis, no clear link was seen between age or duration of having diabetes and remission (PMID 40023186). On the other hand, a review notes that what primarily determines the likelihood of reaching remission after a 15% weight loss is the duration of having diabetes (PMID 33289165). How important the duration of the disease is remains debated across the evidence.

Maintaining that state is difficult. It is not easy to sustain reduced weight for a long time (PMID 32690918), and most studies where remission was seen through diet observed participants for one year or less, so the effects over longer periods are not yet fully confirmed (PMID 34796367).

Remission is a state that appears when large amounts of weight are lost in type 2, the evidence on how important the disease duration is remains mixed, and it may not be maintained over time. The studies looked at here all focused on type 2.

Where to Look Next

This article departed from the normal operation drawn in "How Blood Sugar Stays Steady — A Letter to Store, a Letter to Release". The detailed stories of large blood vessel complications are handled by "What Coronary Artery Disease Is — The Road That Feeds the Heart, Narrowed and Blocked" and "What a Stroke Actually Is — Blocked, Burst, and the Clock". The blood sugar numbers and diagnostic criteria on health checkup sheets will be taken over by an article dealing with blood sugar test numbers, and body weight and the GLP-1 class of drugs by an article dealing with obesity and GLP-1. Neither of those two articles has been released yet.

Questions that have not yet been settled also remain. There are both those who argue that the cause of type 2 can be explained down a single branch of excessive nutrition (PMID 39038473) and those who view it as a disease where multiple branches are mixed (PMID 39059357).

Source Papers

• "Diabetes Fact Sheet in Korea 2021." (2022) — PMID 35656565 — Korea National Health and Nutrition Examination Survey, 2020 diabetes prevalence in Korean adults aged 30 and older was 16.7%, and 9.7% achieved all three management targets.
• "Diabetes mellitus-Progress and opportunities in the evolving epidemic." (2024) — PMID 39059357 — Diabetes is characterized by hyperglycemia, functional abnormalities in beta cells, fat, muscle, and liver; type 1 involves immune-mediated beta-cell destruction, while the more common type 2 involves insulin resistance and varying degrees of beta-cell dysfunction, with risk driven by the interaction between genetics and the environment (social determinants such as access to nutritious food).
• "Type 1 Diabetes: A Guide to Autoimmune Mechanisms for Clinicians." (2025) — PMID 40375390 — Autoreactive T cells destroy beta cells, driven by genetic predisposition plus environmental and immune triggers, with enteroviruses implicated though causality is difficult to establish; fasting blood sugar rises at stage 3 when beta cells are sufficiently destroyed, and 90% of those diagnosed have no family history.
• "The pathophysiology, presentation and classification of Type 1 diabetes." (2025) — PMID 40734585 — Autoimmune beta-cell destruction leads to absolute or near-absolute insulin deficiency, can develop at any age, and has an unknown trigger.
• "Type 1 Diabetes: A Review." (2026) — PMID 41697686 — Accounts for 5 to 10% of diabetes, 90 to 95% have autoantibodies at diagnosis, most common at ages 10 to 14 but median diagnosis age in the U.S. is 24, up to 44% of children and 23% of adults present with ketoacidosis, and requires lifelong insulin (injections or pump).
• "The heterogeneous pathogenesis of type 1 diabetes mellitus." (2019) — PMID 31534209 — Islet autoantibodies circulate from weeks up to 20 years before disease onset.
• "Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications." (2025) — PMID 39940862 — Affects over 400 million people worldwide, driven by genetics and environment, with treatment based on non-pharmacological therapy (physical activity, diet, cognitive behavioral therapy) supplemented by medication.
• "Type 2 diabetes mellitus." (2015) — PMID 27189025 — Caused by obesity, unhealthy diet, physical inactivity, and genetics, with core defects of insulin resistance and impaired secretion, micro- and macrovascular complications driven by hyperglycemia and insulin resistance syndrome components, characterized by progressive beta-cell failure and the need for multi-drug combinations.
• "Genetic underpinnnings of type 2 diabetes." (2025) — PMID 40409800 — Family history increases risk 1.5 to 3 times, with genetic variants contributing to liver, muscle, and fat insulin resistance where the liver fails to efficiently suppress glucose production and muscle shows reduced postprandial uptake.
• "Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future." (2014) — PMID 24315620 — Insulin resistance prompts beta cells to increase secretion to maintain normal glucose tolerance, and blood sugar rises only when beta cells fail to pump out enough.
• "Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications." (2020) — PMID 32543261 — A significant portion of beta-cell secretory capacity is lost before diagnosis, and dysfunction may be partially reversible.
• "Diabetes Fact Sheet 2025: Comparative Epidemiology and Clinical Features of Obese and Non-Obese Diabetes in Korea." (2026) — PMID 41813264 — Korea National Health and Nutrition Examination Survey 2012–2023, diabetes prevalence 17.6% in obese adults vs. 9.5% in non-obese adults.
• "Diabetes Fact Sheet 2025: Special Edition on Diabetes with Obesity and in Pregnancy." (2026) — PMID 41813263 — 52.4% of Korean adults aged 19 and older with diabetes are obese, and a history of gestational diabetes yields a postpartum type 2 diabetes hazard ratio of 6.07.
• "Bringing an end to diabetes stigma and discrimination: an international consensus statement on evidence and recommendations." (2024) — PMID 38128969 — Delphi consensus of 51 experts across 18 countries, finding main drivers of stigma are blame, burden/sick identity, invisibility, and fear/revulsion, with roughly four in five experiencing stigma and one facing discrimination, which is harmful, unacceptable, unethical, and counterproductive.
• "Diabetes Stigma and Clinical Outcomes: An International Review." (2024) — PMID 39105174 — In adults with type 1 and type 2 diabetes, stigma is linked to lower psychosocial functioning, reduced self-care, higher HbA1c, and frequent complications.
• "At multiple fronts: Diabetes stigma and weight stigma in adults with type 2 diabetes." (2021) — PMID 32799378 — Online survey of 1,212 U.S. adults with type 2 diabetes showing frequent experiences of diabetes stigma such as blame and judgment, with many internalizing it.
• "Understanding the mechanisms of reversal of type 2 diabetes." (2019) — PMID 31097391 — Liver fat impairs insulin response and increases glucose production, and substantial weight loss restores beta-cell secretion in many people early in the disease, with DiRECT trial showing 46% remission at 12 months and 36% at 24 months (mediated by weight loss).
• "Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy." (2024) — PMID 39353925 — Hyperglycemia and dyslipidemia trigger insulin resistance and beta-cell dysfunction through common pathways including inflammation, with no cure but prevention and remission possible via lifestyle interventions and/or medication.
• "Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis." (2021) — PMID 33940045 — Across 59 population-based studies, diabetic retinopathy prevalence among diabetes patients is 22.27%, making it a leading cause of preventable blindness in working-age adults.
• "Epidemiology of diabetes." (2014) — PMID 25568613 — Type 2 makes up the vast majority of diabetes prevalence (>85%), with both types sharing micro- and macrovascular complications (treating age as a separate risk factor).
• "Control of glycaemia." (1993) — PMID 8379904 — Fasting hyperglycemia in diabetes stems mainly from excessive glucose release by the liver due to increased gluconeogenesis, while postprandial hyperglycemia involves impaired suppression of liver release and impaired muscle uptake, typically combining impaired insulin secretion and tissue resistance.
• "Diabetic vascular complications." (1997) — PMID 9315387 — Divided into microvascular (kidneys, retina, nerves) and macrovascular (accelerated atherosclerosis: ischemic heart disease, cerebrovascular disease, peripheral vascular disease).
• "Microvascular Complications of Type 2 Diabetes Mellitus." (2020) — PMID 31057114 — Chronic hyperglycemia exposure targets microvessels, causing kidney disease, retinopathy, and neuropathy, affecting about 25% with kidney disease and retinopathy and about 50% with neuropathy in type 2, with disease duration, blood sugar, blood pressure, and lipid management as shared risk factors.
• "Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017." (2018) — PMID 29884191 — Across 57 studies covering 4,549,481 type 2 patients, cardiovascular disease prevalence is 32.2%, about half (50.3%) of deaths are due to cardiovascular disease, with coronary artery disease and stroke as major contributors.
• "Epidemiology of Diabetes Mellitus and Cardiovascular Disease." (2019) — PMID 30828746 — Type 2 carries a higher risk of cardiovascular death than non-diabetes but is not a coronary heart disease risk equivalent, showing substantial heterogeneity in risk.
• "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus." (1993) — PMID 8366922 — DCCT study of 1,441 patients over a mean of 6.5 years showed primary prevention cohort had a 76% reduction in retinopathy and a 60% reduction in clinical neuropathy, with severe hypoglycemia increasing 2 to 3 times as the main side effect, and intensive treatment delayed the onset and slowed the progression of retinopathy, kidney disease, and neuropathy.
• "The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview." (2014) — PMID 24356592 — EDIC follow-up showing benefits persist even after blood sugar differences disappear (metabolic memory), early complication reductions translate into reduced severe complications and cardiovascular disease, and increased hypoglycemia risk is unrelated to cognitive function or quality of life.
• "10-year follow-up of intensive glucose control in type 2 diabetes." (2008) — PMID 18784090 — UKPDS trial in newly diagnosed type 2 patients showed sustained microvascular reductions of 24% in the sulfonylurea-insulin group despite loss of HbA1c differences after 1 year, alongside newly emerged reductions of 15% in myocardial infarction and 13% in all-cause mortality, with benefits also persisting in the overweight metformin group.
• "Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials." (2017) — PMID 28365411 — Across 4 trials involving 27,049 patients followed for a median of 5 years, kidney events decreased by 20% and eye events by 13% with no decrease in nerve events, confirming blood glucose lowering remains vital for preventing long-term microvascular complications.
• "Managing hypoglycaemia." (2016) — PMID 27432075 — Intensive blood sugar control reduces microvascular burden, but iatrogenic hypoglycemia is a major hurdle; early defenses are strong making severe hypoglycemia rare, but longer disease duration impairs glucagon release and repeated hypoglycemia weakens these defenses.
• "Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus." (2014) — PMID 24526393 — Meta-analysis of 12 type 1 RCTs involving 2,230 patients showing strict control reduces microvascular complication risk, though evidence stems mostly from young early-stage patients with weaker effects after complications appear, requiring weighing against severe hypoglycemia, with no definitive evidence for a single target making targets personalized.
• "Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management." (2019) — PMID 30926258 — Hypoglycemia is a hazardous side effect of insulin and insulin secretagogue treatment that disrupts brain function, with links to cardiovascular events and death partly driven by confounding.
• "Hypoglycemic neuropathy." (2001) — PMID 11699552 — Central nervous system effects of hypoglycemia include irritability, poor concentration, cognitive impairment, seizures, and loss of consciousness.
• "Diabetic emergencies - ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia." (2016) — PMID 26893262 — Ketoacidosis, hyperosmolar state, and hypoglycemia are severe complications requiring prompt recognition, diagnosis, and treatment.
• "Diabetic ketoacidosis." (2023) — PMID 35577617 — Characterized by three features: hyperglycemia, ketosis, and anion gap metabolic acidosis.
• "Diabetic ketoacidosis." (2020) — PMID 32409703 — The most common acute hyperglycemic emergency diagnosed using three criteria (blood sugar or family history, ketone bodies, acidosis), where early diagnosis and treatment dictate outcomes to prevent substantial yet largely preventable morbidity and mortality without optimal care.
• "Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State." (2017) — PMID 28372715 — Ketoacidosis and hyperosmolar state are the most severe hyperglycemic emergencies driven by insulin deficiency and severe hyperglycemia, making early diagnosis and treatment paramount.
• "Immunotherapies for prevention and treatment of type 1 diabetes." (2025) — PMID 40033931 — Anti-CD3 antibodies approved to delay type 1 onset, with other immune modulators under investigation.
• "Current barriers to initiating insulin therapy in individuals with type 2 diabetes." (2024) — PMID 38559691 — Insulin is frequently needed in type 2, but initiation barriers include fear of hypoglycemia, injection stigma, weight gain, and feelings of treatment failure.
• "The American Diabetes Association's Standards of Care in Diabetes - 2026: key aspects for the internist's clinical practice." (2026) — PMID 41692340 — Personalized care and strategies that extend beyond blood sugar control to reduce adverse outcomes.
• "The vascular complications of diabetes: a review of their management, pathogenesis, and prevention." (2024) — PMID 37947481 — Blood sugar and blood pressure control remain central to managing micro- and macrovascular complications.
• "Impact of bodyweight loss on type 2 diabetes remission: a systematic review and meta-regression analysis of randomised controlled trials." (2025) — PMID 40023186 — RCTs in overweight and obese type 2 patients showing 1-year full remission rates of 0.7% for <10% weight loss, 49.6% for 20–29%, and 79.1% for ≥30%, demonstrating a dose-response relationship with no significant association with age or disease duration.
• "Type 2 diabetes and remission: practical management guided by pathophysiology." (2021) — PMID 33289165 — Likelihood of remission following 15% weight loss is governed mainly by disease duration, and remission is independent of body mass index (personal fat threshold concept).
• "Diet and exercise in the prevention and treatment of type 2 diabetes mellitus." (2020) — PMID 32690918 — Weight loss drives remission in a dose-dependent manner, though long-term weight maintenance is difficult.
• "Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission." (2022) — PMID 34796367 — RCTs including total diet replacement showed a median 1-year remission rate of 54%, with most evidence limited to 1 year or less.
• "The immunology of type 1 diabetes." (2024) — PMID 38308004 — Regulatory approval granted for the first T-cell-targeted immunotherapy to slow beta-cell autoimmune destruction.
• "Understanding the cause of type 2 diabetes." (2024) — PMID 39038473 — Authors argue that type 2 arises from the homogeneous cause of overnutrition across genetically diverse individuals.