Most people know that diabetes is the result of prolonged high levels of glucose (sugar) in the blood. This happens when the pancreas can’t or doesn’t make enough insulin (the chief hormone that controls blood glucose and metabolism), or the body cannot effectively use the insulin that is produced. And most people have heard of the two types of diabetes…
Type 1 diabetes, a chronic condition in which the body’s immune system mistakenly destroys insulin-producing cells in the pancreas. Type 1 diabetes can occur at any age, but about half of the cases occur by age 20. People with type 1 diabetes need insulin therapy for life.
Type 2 diabetes, which develops over time and is far more common. At its root is insulin resistance—when cells in the body don’t respond to insulin properly. The body needs insulin to transfer glucose from your blood into your cells for energy. When this fails to happen, the level of sugar in the blood rises, setting the stage for diabetes. Gestational diabetes (during pregnancy) can be a precursor to type 2 diabetes.
What Is Type 3 Diabetes?
In recent years, a third term has emerged—type 3 diabetes—to identify how insulin resistance impacts the brain and risk for Alzheimer’s disease. The metabolic processes that go wrong in diabetes don’t just affect the liver and the heart. They also can affect mental and cognitive health. What’s more, having type 2 diabetes can promote or hasten the progression of Alzheimer’s disease.
Bottom Line Personal asked C. Ronald Kahn, MD, an expert in diabetes and obesity research and chief academic officer at Harvard-affiliated Joslin Diabetes Center, to explain how diabetes can affect your brain…
Insulin Sensitivity and Insulin Resistance
Insulin sensitivity is your body’s ability to appropriately respond to insulin. If you become insulin-resistant, when your blood glucose level is measured first thing in the morning after having consumed nothing but water for eight to 12 hours, your blood sugar is above the normal fasting blood glucose level of 70 mg/dL to 99 mg/dL (prediabetes is 100 mg/dL to 125 mg/dL…and type 2 diabetes is 126 mg/dL and above). Many doctors screen using HbA1C, a blood test that measures the average blood sugar (glucose) levels over the past two to three months. A result of 5.7% to 6.4% is prediabetes…6.5% or higher is diabetes.
While insulin resistance is associated with diabetes, many people have some degree of insulin resistance without having diabetes. And almost everyone with type 2 diabetes is insulin resistant, especially those who are overweight or obese, which comprises 90% of people with type 2 diabetes. Insulin resistance can stem from other conditions, including obesity, metabolic syndrome (high cholesterol and triglycerides), fatty liver disease and even hypertension.
In fact, nearly 10% of the adult population has type 2 diabetes, but between 40% and 50% have insulin resistance, and many of those people can have glucose levels in the normal range on a blood test. Important: Even if your body makes enough insulin to have a normal blood glucose reading, you still can be at high risk for cognitive consequences because of insulin resistance.
How Insulin Resistance Affects the Brain
Your brain uses a lot of glucose, and it needs insulin to activate receptors on the three types of brain cells most responsible for brain function…
Neurons, the wiring that connects every tissue in the body to the brain and connects parts of the brain to one another. (Your brain also needs insulin to regulate the metabolism of lipids, which are important for making protective sheaths around neurons.)
Astrocytes and microglial cells—two types of glial cells that support and protect neurons in the nervous system.
When the cells in your brain are not insulin-resistant and are working normally, the brain’s functions are appropriately fine-tuned.
If you have insulin resistance in other tissues, you likely also have insulin resistance in your brain. When that happens, many functions lose some of their flexibility. Example: According to recent studies from University of Birmingham, UK, Johns Hopkins University School of Medicine and Public Health, and Indiana University School of Medicine, people with type 2 diabetes are twice as likely to have depression and more likely to suffer anxiety and schizophrenia than people without insulin resistance.
We also know that people who have insulin resistance and type 2 diabetes are at higher risk for Alzheimer’s disease…and when they do develop Alzheimer’s, it tends to progress more rapidly.
While insulin resistance creates abnormalities in all three brain cell types mentioned above, the astrocytes and the microglial cells, in particular, are part of the process that goes wrong in Alzheimer’s. Under normal circumstances, astrocytes contribute to making the waxy substance amyloid and microglial cells eat up that amyloid—both those functions are partly regulated by insulin. When you have insulin resistance, the amount of amyloid your body produces doesn’t change, but it does alter how much amyloid accumulates. The accumulation of amyloid in the brain forms plaques that disrupt brain function and are a hallmark of Alzheimer’s.
Type 3 Diabetes Symptoms
Unlike type 2 diabetes, often characterized by excessive thirst and urination, there are no specific symptoms for type 3 diabetes. Depressive behavior can be one manifestation, but that occurs in a lot of people for a lot of reasons so it’s not an exact indicator. There also are no direct tests, outside of a research setting, to determine if you have insulin resistance, though it’s possible to measure insulin levels with a blood test—if you have a normal-to-high glucose level, you can assume that you have insulin resistance as well.
Can Type 3 Diabetes Be Reversed?
Exercise is a natural way to combat insulin resistance. When you exercise, your cells take up glucose without the need for insulin, so exercise helps lower blood sugar while improving insulin resistance. What’s more, exercise is the single most important thing you can do in terms of lifestyle changes to reduce risk for Alzheimer’s. Even modest activity, such as walking for 30 minutes a day, makes a difference in how effectively your brain clears amyloid plaques and can reduce Alzheimer’s risk by more than 50%.
Losing weight also improves insulin resistance. Most people can’t burn off enough calories with exercise to lose significant weight. Calorie restriction also is needed to drop more pounds and treat the diabetes component of insulin resistance as well as the non-diabetes components, such as the predisposition to fatty liver disease and Alzheimer’s risk.
Are There Medications for Type 3 Diabetes?
Widely used GPL-1 receptor agonist drugs, such as Ozempic, Wegovy, Mounjaro and Zepbound, don’t directly improve insulin sensitivity, but because they create an aversion to food, they lead to weight loss that help you become more insulin sensitive. (That, in turn, also helps all your metabolic functions, both for improving glucose and lipid metabolism and lowering risks for fatty liver disease and atherosclerosis.) Small clinical trials are currently looking at whether these drugs also have effects on the turnover of amyloid in the brain.
The oldest diabetes drug, metformin, not only improves blood glucose but also has metabolic benefits beyond that, including some improvement in insulin sensitivity and potential benefits on longevity, though it’s not known if it has any effect on preventing Alzheimer’s.
