Type 4 Diabetes: Causes, Signs, and Management

Type 4 diabetes — it’s not a typo. In 2015, researchers at the Salk Institute for Biological Studies published research suggesting that many cases of diabetes may not be associated with obesity as commonly thought. Rather, this form of diabetes — which they termed type 4 — is determined by older age.

What is type 4 diabetes?

Like other forms of diabetes, type 4 diabetes (T4D) is characterized by insulin resistance leading to high blood sugar. However, the underlying cause of insulin resistance is different in T4D compared to other diabetes types. Understanding the cause is important in developing effective preventative and treatment strategies for this disease, which are currently under exploration.

The distinguishing feature of T4D is that insulin resistance occurs due to advancing age in people who have normal weight. The typical profile of someone with T4D is a thin, elderly individual.

Although the exact cause of T4D is still under investigation, genetic changes do not appear to play a role. Among people over the age of 65 newly diagnosed with diabetes in the United States, 20% (2 million) may have T4D.

What are the other types of diabetes?

T4D differs from the traditional classifications of diabetes:

  • Type 1 diabetes (T1D) is an autoimmune condition in which the immune cells of the body attack the pancreas, impairing its ability to produce insulin. The incidence of T1D peaks between the ages of 4–6 and 10–14. People who have T1D depend on treatment with insulin.
  • Type 2 diabetes (T2D) is the most common form of the disease, affecting 6% of the world’s population. It is characterized initially by insulin resistance, and decreased insulin production can occur in later stages of the disease. T2D risk is increased in people who suffer from overweight or obesity, have a family history of diabetes, or have lifestyle factors such as smoking and lack of exercise.
  • Gestational diabetes occurs during pregnancy. The placenta produces a hormone called human placental lactogen that benefits the fetus but decreases the mother’s insulin sensitivity. The risk of gestational diabetes is higher among women who carry excess weight, have prediabetes, or have a family history of diabetes.

Other diabetes types also exist, although — like T4D — they have not been formally classified:

  • Maturity onset diabetes of the young (MODY) runs strongly in families and occurs in people under 25 due to a genetic mutation.
  • Neonatal diabetes is a rare genetic disease that occurs in babies younger than 6 months. It can be temporary or permanent.
  • Latent autoimmune diabetes in adults (LADA) is an autoimmune disease like T1D, but unlike T1D, it develops slowly, usually affects people over 30, and does not immediately require insulin treatment.
  • Type 3c diabetes describes diabetes that occurs when the pancreas is damaged from other diseases such as pancreatitis, cystic fibrosis, or pancreatic cancer.
  • Type 3 diabetes (T3D) refers to insulin resistance occurring in brain cells that has been linked to Alzheimer’s disease.

What are the causes of type 4 diabetes?

What we know about the cause of T4D — insulin resistance due to older age — comes from a landmark 2015 study published in the journal Nature.

Researchers compared the adipose (fat) tissue of older, lean mice to that of younger mice with obesity. They found that the adipose tissue of older, lean mice contained high levels of immune cells called T regulatory cells (Tregs), while obese mice had low levels of these cells.

When the researchers removed Tregs from the older mice, they found that the mice did not develop insulin resistance — in contrast to older mice with the presence of Tregs. Similarly, when the researchers disrupted the function of Tregs using an antibody treatment in the older mice, insulin sensitivity increased.

They concluded that Tregs play a critical role in the development of insulin resistance among older mice, and by inhibiting the activity of Tregs, insulin sensitivity could be restored.

Notably, blocking Tregs in obese mice did not prevent insulin resistance. This suggested that the mechanisms underlying insulin resistance differ in older mice compared to obese mice. While human studies have not verified these results, this experiment laid the groundwork for describing why elderly individuals commonly develop diabetes without being overweight or obese.

According to the study authors, "We suggest Type IV diabetes as a designation for non-obese dependent Treg driven metabolic disease of the elderly."

Beyond this study in mice, however, little is known about T4D. Although lifestyle factors can lead to T2D in older adults, it is unclear whether they contribute to the development of T4D. Unlike T3D, it is also not known whether T4D is associated with brain health and Alzheimer’s disease.

Symptoms of type 4 diabetes

Older adults with T4D who do not have overweight or obesity may experience similar symptoms as younger, overweight, or obese individuals with T2D. Prolonged high blood sugar levels occurring in T4D may be associated with:

  • Excessive thirst or urination
  • Feeling hungry even after eating
  • Unexplained weight loss
  • Tingling or numbness
  • Vision changes
  • Wounds that heal slowly
  • Recurrent infections

These symptoms are not exclusive to diabetes. But, if you are older and experience any of these symptoms, even if you are otherwise healthy and in shape, it is important to be evaluated for T4D or other type of diabetes.

Treatment and management for type 4 diabetes

One of the mainstays of T2D treatment is weight loss, but this is not applicable to patients with T4D who already have normal weight.

Instead, current management of T4D focuses on maintaining optimal blood sugar control with the use of medications and a healthy lifestyle, including a diabetes-friendly diet and regular exercise. Actionable steps include:

  • Consuming a diet rich in vegetables and fiber
  • Limiting sweets, fried foods, sugary beverages, refined carbohydrates, and alcohol
  • Aiming for 150 minutes of moderate-intensity exercise per week
  • Getting enough sleep

It is also important to see your doctor for regular check-ups of your blood sugar. Your doctor may obtain your hemoglobin A1C levels to determine how high your blood sugar levels have been on average over the past 3 months. This is a good marker for how well your diabetes is being controlled.

T4D is a recently described entity that may be characterized by insulin resistance due to high levels of Tregs in the adipose tissue of lean, older adults. Traditional diabetes risk factors such as overweight or obesity are not seen in T4D. More research is needed to understand how T4D develops in older adults and whether medical interventions can be useful beyond the traditional drug therapies used to treat T2D. In the meantime, awareness of T4D can help you be better prepared to live a healthy lifestyle as you get older.

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