Diabetes has several distinct forms, and each one has a different cause. Type 2 diabetes, which accounts for roughly 90% of all cases, is driven by a combination of insulin resistance and declining insulin production, both heavily influenced by excess body fat and genetics. Type 1 diabetes is an autoimmune condition where the body’s own immune system destroys the cells that make insulin. Other forms, including gestational diabetes and rare genetic types, have their own separate triggers. As of 2024, about 589 million adults worldwide live with diabetes, and that number is projected to reach 853 million by 2050.
How Type 2 Diabetes Develops
Type 2 diabetes doesn’t appear overnight. It builds over years as two problems compound each other: your cells become less responsive to insulin (insulin resistance), and the insulin-producing cells in your pancreas gradually wear out trying to compensate.
The liver plays a central role in this process. Research from the American Diabetes Association has shown that the high blood sugar seen in established type 2 diabetes is primarily linked to insulin resistance in the liver, not in muscle tissue. When the liver stops responding properly to insulin, it keeps releasing stored sugar into the bloodstream even when levels are already high. Studies of moderate calorie restriction in people with type 2 diabetes found that reducing liver fat normalized the liver’s response to insulin and brought fasting blood sugar back to healthy levels, while muscle insulin resistance remained unchanged. This is one reason why even modest weight loss can have an outsized effect on blood sugar control.
In muscle cells, the problem traces back to a reduction in mitochondria, the tiny structures inside cells that burn fuel for energy. When muscles have fewer mitochondria, they burn less fat and sugar, contributing to the buildup of glucose in the blood.
The Role of Body Fat and Inflammation
Excess body fat, particularly around the midsection, doesn’t just sit there storing energy. Fat tissue in people with obesity becomes a source of chronic, low-grade inflammation that actively interferes with insulin signaling throughout the body.
Immune cells called macrophages accumulate in fat tissue as it expands. These macrophages release inflammatory molecules, most notably TNF-alpha, IL-1 beta, and IL-6, that disrupt the way insulin communicates with cells. Normally, insulin binds to a receptor on the surface of a cell and triggers a chain of signals that lets glucose in. These inflammatory molecules interrupt that chain at multiple points. They can block the insulin receptor itself, degrade the relay proteins inside the cell, or activate pathways that essentially turn off the cell’s ability to hear insulin’s signal. The result is that your pancreas has to produce more and more insulin to get the same effect, until eventually it can’t keep up.
Genetics and Type 2 Diabetes Risk
Genes play a substantial role in type 2 diabetes. Twin studies consistently show this: when one identical twin develops type 2 diabetes, the other twin’s risk is remarkably high. In a large UK study that followed identical twin pairs over 15 years, 76% of co-twins eventually developed diabetes as well. When the definition was expanded to include any blood sugar abnormality, concordance reached 96%. By contrast, non-identical twins showed much lower rates, around 12% to 19%.
These numbers make clear that type 2 diabetes has a powerful hereditary component, but they also reveal that genes alone don’t seal your fate. The fact that not every identical twin develops the condition points to the critical influence of diet, physical activity, and body weight.
What Causes Type 1 Diabetes
Type 1 diabetes is fundamentally different from type 2. It’s an autoimmune disease in which the body’s immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Without these cells, the body produces little to no insulin, and blood sugar rises uncontrollably.
The attack begins quietly, often years before any symptoms appear. The immune system generates antibodies against proteins found on beta cells, and these autoantibodies can be detected in the blood months or even years before blood sugar levels become abnormal. Interestingly, the destruction is surprisingly subtle. Fewer than 10% of the insulin-producing cell clusters in the pancreas typically show signs of immune cell infiltration, and the number of immune cells involved is modest, roughly double what’s found in a healthy pancreas. Yet this is enough to progressively erode insulin production until the body can no longer maintain normal blood sugar.
The process occurs in people who are genetically predisposed, but environmental triggers appear to play a role in setting it off. Viral infections, particularly from a family of viruses called enteroviruses, have been a major area of focus. One specific type, Coxsackievirus B, has been shown in lab studies to directly damage beta cells. The leading theory is that a viral infection may cause initial beta cell death, which then triggers the immune system to mistakenly recognize beta cell proteins as threats and mount a sustained attack.
Gestational Diabetes
Gestational diabetes develops during pregnancy, typically in the second or third trimester, and usually resolves after delivery. It occurs because the placenta produces hormones, particularly progesterone, cortisol, and placental growth hormone, that make the mother’s fat and muscle tissue increasingly resistant to insulin as pregnancy progresses. This resistance is actually a normal part of pregnancy; it helps ensure enough glucose reaches the growing baby. But in some women, the pancreas can’t ramp up insulin production enough to overcome this resistance, and blood sugar rises to unhealthy levels.
Women who develop gestational diabetes are at significantly higher risk for type 2 diabetes later in life. Research has found that women who had gestational diabetes show reduced diversity in their gut bacteria and lower levels of bacteria that produce short-chain fatty acids, metabolites created when gut bacteria ferment dietary fiber. These fatty acids have anti-obesity and anti-diabetic effects, and their depletion may contribute to the progression from gestational diabetes to type 2 diabetes in the years after pregnancy.
Rarer Genetic Forms
A small percentage of diabetes cases are caused by single gene mutations rather than the complex mix of genes and lifestyle factors behind type 2. The most well-known is MODY (maturity onset diabetes of the young), which typically appears before age 25 and runs strongly in families with an autosomal dominant pattern, meaning a child has a 50% chance of inheriting it from an affected parent.
The two most common forms account for the vast majority of MODY cases. The first involves a mutation in the glucokinase gene, which acts as the body’s glucose sensor. People with this mutation have mildly elevated fasting blood sugar that’s stable over time and generally doesn’t require treatment. The second involves mutations in genes that regulate beta cell function, leading to progressive decline in insulin production and earlier onset of significant diabetes. MODY is frequently misdiagnosed as type 1 or type 2, which matters because treatment differs. Many people with certain forms of MODY respond well to a specific class of oral medications and don’t need insulin.
Medications That Raise Blood Sugar
Certain medications can cause or worsen diabetes, with corticosteroids (such as prednisone) being the most common culprit. These drugs trigger insulin resistance throughout the body, increase fat storage around the organs, and impair the function of insulin-producing beta cells. They also promote the breakdown of muscle and fat tissue in ways that flood the bloodstream with fatty acids and glucose. People on long-term corticosteroid therapy frequently develop elevated blood sugar, and those who already have prediabetes or risk factors for type 2 diabetes are especially vulnerable.
Some antipsychotic medications and certain drugs used after organ transplants can also push blood sugar into the diabetic range through similar mechanisms involving weight gain and insulin resistance.
Gut Bacteria and Diabetes Risk
An emerging piece of the puzzle involves the trillions of bacteria living in your gut. People with type 2 diabetes and prediabetes consistently show lower diversity in their gut bacteria compared to people with normal blood sugar. One bacterium that stands out is Faecalibacterium, a species that produces butyrate, a short-chain fatty acid that helps maintain the intestinal lining and appears to improve insulin sensitivity. This bacterium is depleted in people with obesity and type 2 diabetes.
When the gut lining becomes more permeable, bacterial products can leak into the bloodstream and trigger the kind of low-grade inflammation that worsens insulin resistance. A healthy, fiber-rich diet feeds the bacteria that produce protective short-chain fatty acids, which is one biological mechanism behind the well-established link between dietary fiber and lower diabetes risk.