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Type 4, and 5, diabetes in adults, children often misdiagnosed

A study to find solutions for treating two new variations of diabetes, type 4 and type 5, is underway in US research institutions as the overall disease population is expected to reach 783 million people by 2045.

HQ Team

May 22, 2023: A study to find solutions for treating two new variations of diabetes, type 4 and type 5, is underway in US research institutions as the overall disease population is expected to reach 783 million people by 2045.

About 537 million adults or one in ten were living with diabetes in 2021. This number is expected to rise to 643 million by 2030 and 783 million by 2045, according to the International Diabetes Federation.

Almost one in two adults, or 44%, of 240 million people remain undiagnosed. The majority has type 2 diabetes.

Researchers from the Salk Institute revealed in 2015 that diabetes in elderly, lean animals, had a different cause and potential treatment, from obesity-related type 2.

The three current normal diabetes includes type 1, type 2, and gestational diabetes.

MODY, LDA

Two new diagnoses — MODY (maturity-onset diabetes of the young or type 5, and LDA (latent autoimmune diabetes in adults or type 4 — are new that they are often misdiagnosed.

Diabetes is often the result of obesity and poor diet choices, but for some older adults the disease might simply be a consequence of aging, researchers at the California-based Salk Institute stated.

“New research has discovered that diabetes—or insulin resistance—in aged, lean mice has a different cellular cause than diabetes that results from weight gain (type 2). And the findings point toward a possible cure for what the co-leading scientists, Ronald Evans and Ye Zheng, are now calling a new kind of diabetes (type 4),” according to a 2015 report.

“A lot of diabetes in the elderly goes undiagnosed because they don’t have the classical risk factors for type 2 diabetes, such as obesity,” said Evans, director of Salk’s Gene Expression Laboratory and senior author of the study.

“We hope our discovery not only leads to therapeutics, but to an increased recognition of type 4 diabetes as a distinct disease.”

Insulin resistance

In healthy people, the pancreas produces the hormone insulin, which signals cells to take sugar out of the blood after a meal. 

In people with diabetes, however, the cycle is broken. Either insulin is not produced in response to a meal or the muscle and liver cells don’t respond to the insulin — also known as insulin resistance.

Either way, the sugar stays in the bloodstream for a long time, leading to issues ranging from loss of limbs to death.

Type-1 appears in children when the pancreas stops producing insulin and type-2 conditions appeared when the body failed to respond to insulin and this was associated with being overweight.

The researchers wondered why some people developed the disease later in life without weight gain.

Mice experiment

Evans’ team, along with Zheng, an assistant professor in Salk’s Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, set out to compare the immune systems of healthy mice, those with obesity-related diabetes, and those with age-related diabetes. 

The mice with age-related disease, they found, had abnormally high levels of immune cells called T regulatory cells (Tregs) inside their fat tissue.

Mice with obesity-related diabetes, on the other hand, had normal levels of Tregs within the tissue, despite having more fat tissue.

Due to age, Tregs gradually accumulated fat. “And if the cells reached a tipping point where they completely block inflammation in fat tissue, they can cause fat deposits to build up inside unseen areas of the body, including the liver, leading to insulin resistance,” the study found.

“It turns out that for this type of diabetes, the treatment is not losing weight,” said Evans. “The treatment is actually losing these cells, and we show that it’s possible to do that.”

Interaction of Tregs

The researchers are working to find out exactly how Tregs interact with fat tissue and whether the immune cells accumulate in other organs during normal aging.

The Centers for Disease Control and Prevention defines diabetes as a chronic, long-lasting health condition that affects how your body turns food into energy. 

Type 1 diabetes is an autoimmune condition. People diagnosed with type 1 diabetes must take insulin because their immune system has attacked the insulin-producing cells in the pancreas blocking the production of insulin.

Type 2 diabetes is a condition in which the body becomes resistant to using insulin properly and efficiently. Over time, people with type 2 diabetes may stop making enough insulin, becoming insulin deficient.

Type 2 diabetes is associated with genetic and lifestyle factors.

Pregnancy

Gestational diabetes is a temporary condition where higher levels of hormones during pregnancy lower the body’s sensitivity to insulin, leading to blood sugar levels that are out of target range.

Type 3 diabetes is an anomaly, often linked with Alzheimer’s disease. This type is not an official diabetes diagnosis, nor is it currently used in the health care system. The theory is that insulin resistance in the brain is part of the progression with Alzheimer’s disease.

Type 5 diabetes, called Maturity onset diabetes of the young or MODY, is another type of diabetes that is directly attributable to a genetic condition. MODY occurs before 25 years of age.

MODY 5 is caused by a mutation of a single gene. The mutation causes pancreatic beta cells to function abnormally, leading to insufficient production of insulin. 

In some cases, insulin resistance develops. In addition, the pancreas may not produce enough digestive enzymes. Symptoms include frequent urination, excessive thirst, and dehydration.

The diagnosis of MODY 5 is made after observing the child’s symptoms and taking a history, including family history. If symptoms suggest diabetes, blood tests are done to measure glucose levels, how much insulin is made by the body, and the presence or absence of autoantibodies.

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