Insulin resistance is the stage in which the pancreas has to make more and more insulin to keep blood sugar normal. That excess insulin, called hyperinsulinemia, is itself inflammatory. It shuts down fat burning and drives fat into storage, including in the liver. That fatty liver makes still more metabolic inflammation.
Most of what goes wrong in type 2 diabetes happens years before blood sugar turns abnormal. The driver is insulin itself. It stays high for years, it quietly feeds inflammation, and it is mostly invisible on the tests most people get.
What does insulin actually do?
Insulin is widely described as the hormone that pushes glucose into cells by opening a channel. That description leaves out so much that it misleads. Insulin is mainly a fat-storage hormone. It shifts the body away from burning fat for energy and toward storing it.
Without insulin, the default state is lipolysis: fat comes out of storage and turns into usable energy. When insulin is present, lipolysis stops and lipogenesis begins. Lipogenesis turns the glucose in your blood into stored fat. The more insulin present, the more fat builds up.
At the enzyme level, insulin turns on hexokinase. Hexokinase tags glucose with a phosphate and traps it inside the cell. Insulin also blocks glucose-6-phosphatase, which would otherwise let the glucose back out. It turns on phosphofructokinase and glycogen synthase too, which drives glycogen building. With plenty of glucose coming in, the liver fills its glycogen stores fast. Then it turns the extra into fat.
Insulin is the disease; glucose is the symptom
For type 2 diabetes to appear, two things must exist together. One is insulin resistance. The other is insulin output that has fallen short of what that resistance demands. Overweight people commonly have insulin resistance without diabetes, because the pancreas makes up for it by making more insulin. Diabetes only appears when that makeup effort fails.
Here is why that matters in the clinic. The makeup period, hyperinsulinemia before insulin production collapses, is not a safe waiting room. It is highly inflammatory. Significant tissue damage builds up all through it, while fasting glucose still reads normal.
Does when you eat affect insulin resistance?
Most people eat from waking until bedtime: three meals, several snacks, and often sweet drinks in between. That pattern keeps insulin output high all day and wears out the insulin receptors. Insulin is a storage hormone. So keeping it high also drives fat buildup in the liver, which makes still more metabolic inflammation.
So giving the body a stretch of time when insulin is truly low is not a fad. It is how stored energy becomes usable again.
How are insulin resistance and inflammation linked?
Hyperinsulinemia is the common link between inflamed fat tissue and metabolic syndrome. The metabolic pattern associated with obesity raises pro-inflammatory cells, M1 macrophages and NK cells. It also holds down anti-inflammatory M2 macrophages, eosinophils and regulatory T cells. Notably, lowering blood insulin partway eases the fat tissue inflammation that excess calories cause. It also improves insulin sensitivity. That points at insulin, not fat mass, as the real driver. (Mol Cell Endocrinol. 2018 Dec 5;477:15-28.)
In diabetes, blood sugar stays high for a long time. That raises reactive oxygen species, which are harmful oxygen molecules. They harm how the beta cells that make insulin work. They also make insulin resistance even worse. The same process adds to the atherosclerosis (clogged, hard arteries) so often seen with diabetes.
Insulin resistance, not LDL, is the cardiovascular signal
Total and LDL cholesterol are poor markers of heart health. High triglycerides with low HDL predict heart risk considerably better. That pattern is also a reliable marker of insulin resistance. The QRISK calculator estimates ten-year heart and blood vessel risk. It does not use LDL at all. It uses the ratio of total cholesterol to HDL.
Preventing insulin resistance in young men would prevent an estimated 42% of myocardial infarctions (heart attacks). That is a bigger drop than correcting high blood pressure, at 36%.
An unrecognized cause of chronic pain
Metabolic inflammation from obesity and hyperinsulinemia is an overlooked driver of pain. Musculoskeletal pain (pain in muscles, bones and joints) affects an estimated 13.5% to 47% of the general population. Roughly 75% of those people report two or more painful areas. Pain in many joints, and its spread, is linked on its own to the inflammatory cascade, not just to mechanical load. That includes joints that bear no weight.
That independence is the point. A joint that bears no weight does not hurt because of body mass. It hurts because it sits in an inflammatory environment. A pain physician who never addresses insulin resistance is treating half the problem.
How do you reverse insulin resistance?
Weight loss and carbohydrate restriction each help reverse diabetes on their own, and combining them works better than either alone. Weight loss helps by easing the crowding in the liver and pancreas, improving blood flow and cutting hormone signals from fat cells. Carbohydrate restriction helps by lowering the insulin signal that drives storage in the first place.
The size of the problem justifies the effort. As obesity has worsened worldwide, type 2 diabetes has followed. One in every two Americans born today is predicted to develop it.
Frequently asked questions
What are the symptoms of being insulin resistant?
Often nothing you notice. Insulin resistance does its damage quietly for years while fasting blood sugar still reads normal. That is because the pancreas keeps pouring out extra insulin to hold it there. That excess insulin is inflammatory and drives fat into storage, including in the liver. One sign worth taking seriously is pain in several joints, even ones that bear no weight. That pain tracks metabolic inflammation, not body mass.
How can I know if I am insulin resistant?
Do not rely on fasting glucose. It stays normal through the damaging years, and the tests most people get miss the problem. Look at your triglycerides and HDL instead. High triglycerides with low HDL is a reliable marker of insulin resistance. That pattern predicts heart risk considerably better than total or LDL cholesterol. Ask your physician to read the pattern, not just your sugar.
What foods increase insulin?
Carbohydrates drive the insulin signal that pushes fuel into storage. That is why cutting them is one of the two independent factors that reverse diabetes. When you eat matters as much as what you eat. Three meals, several snacks and sweet drinks from waking to bedtime keep insulin high all the time and wear out the insulin receptors. A daily stretch of truly low insulin makes stored energy usable again.
Related reading
- What Is Cotton-Mouth and Why Does It Happen?
- Reactive Oxygen Species and Type 2 Diabetes
- GGT blood test: the oracle of death
- What Is Metabolic Inflammation?
Sources
- Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017. PMID 28179656
- Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. Journal of Clinical Investigation. 2006. PMID 16823477
Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed August 25, 2026
