Beyond Type 1 and Type 2 diabetes

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You’ve probably heard of Type 1 and Type 2 diabetes. But did you know there are several other types as well? As we get into Diabetes Awareness Month, it’s a great time to learn about the various forms of this extraordinarily common disease—and how they might affect you and your loved ones.

What we refer to today as “diabetes” was originally named “diabetes mellitus”— a marriage of the greek verb diabeinein which means “to go through,” and the Latin noun mellitus, meaning “sweet.” Recently, we’ve gained a better understanding of how diabetes develops, which has caused a series of re-classifications. Here, we’ll provide an overview of some of these classifications and their defining characteristics.

Ultimately, diabetes is a disease in which sugar regulation goes awry. Every cell in our body uses sugar as an energy source; however, too much or too little sugar can be problematic. Our bodies control the amount of sugar in the blood via a series of different proteins. One of these proteins is a hormone known as insulin, which is made in the pancreas and circulates throughout the body. This hormone helps cells remove sugar from the bloodstream. Diabetes develops when this regulatory system is disrupted; the factors leading to this disruption are what differentiates the various forms of diabetes.

Type 1 diabetes (T1D)

About 5-10% of people with diabetes have what is referred to as Type 1 diabetes (T1D). This form of the disease was once known as “juvenile diabetes” because it was typically diagnosed if a person showed symptoms of diabetes during childhood. Nowadays, diagnosis of T1D has less to do with age and more to do with certain biochemical features. These include the presence of markers in the blood that indicate autoimmunity against the pancreas. Autoimmunity means a person’s immune system begin to attack their own cells. T1D occurs when a person’s immune cells attack the pancreas, destroying the cells that produce insulin. As a result, people with T1D cannot produce sufficient amounts of insulin, causing them to struggle with the regulation of blood sugar levels. It’s not clear why the immune system becomes confused like this. Some evidence indicates that genetic variants can occur in regions of the DNA associated with immune cell function; however, these changes in the DNA are not able to induce T1D in the absence of other environmental factors.

Among the many names previously used for T1D, one is “insulin-dependent diabetes” which reflects how this form of diabetes is treated. Individuals with T1D primarily use insulin injections to manage their blood sugar levels.

Type 2 diabetes (T2D)

While people with T1D lack insulin producing cells, people with Type 2 diabetes (T2D) are able to produce insulin, but have lost sensitivity to it. With a decreased ability to respond to insulin, people with T2D have difficulty removing sugar from the blood. Among those diagnosed with diabetes, about 90-95% have T2D. This disease develops gradually over time and can usually be detected before it has progressed to the point of hospitalization. Unlike T1D, there is no autoimmune component in T2D. Because of this, T2D is usually diagnosed based on chronically elevated levels of glucose, a lack of autoimmune markers (biochemical evidence that indicates the body is attacking its pancreas) , and a later age of onset [1]. T2D development is a complex process that is not fully understood [1]. There have been large scale studies exploring potential genetic links with this disease which provided compelling evidence that inherited changes to the DNA are associated with a predisposition for T2D [2]. Although these links exist, it’s clear that environmental factors also play a role in disease development.

Historically, this type of diabetes was known as “adult-onset diabetes”. This has since been reclassified for a number of reasons including an increased prevalence of T2D in children and teenagers [3]. This trend, combined with an increased understanding of how different forms of diabetes develop, has contributed to the newer terminology of Type 1 and Type 2 diabetes.

In some respects, T1D and T2D can appear very similar. Sometimes, in people with T2D, pancreatic cells can effectively burn out as they try to overcome the body’s insensitivity to insulin4. Though the cause is unknown, when this happens pancreatic cells can die which mimics the pancreatic cell death observed in T1D.

A clear difference between T1D and T2D is the treatment commonly used. Whereas T1D is treated with insulin upon diagnosis, individuals with T2D can sometimes be treated with sulfonylurea or metformin [5]. These interventions help stimulate insulin production in the pancreas (sulfonylureas), prevent sugar release from the liver (metformin), and increase the body’s cellular responsiveness to insulin (metformin).

MODY, LADA, and gestational diabetes

There are other forms of diabetes, too. After T1D and T2D, there are three major forms known as Maturity Onset Diabetes in the Young (MODY), gestational diabetes, and Latent Autoimmune Diabetes of Adults (LADA).

MODY: It is believed that about 1-5% of diabetics have MODY, a heritable form of diabetes whose symptoms can resemble T1D, T2D, or gestational diabetes [6]. Although this form of diabetes is typically associated with childhood or early adulthood, it can affect people of all ages including neonates (a case where it is referred to as neonatal diabetes) all the way through to middle-aged adults. MODY is known to be caused by a number of DNA variants that can occur in 13 different genes. Each of these genes function in the regulation of blood glucose levels. MODY is detected, in part, through the use of genetic testing for these DNA variants. You can read more about MODY—and how a product offered in the Helix Store can help detect it—here.

Treatment of MODY can vary depending on the DNA variant underlying the disease. For some forms of MODY, physical activity and dietary intervention are sufficient while other forms may require sulfonylureas or insulin.

Gestational diabetes: Approximately 5% of pregnant women develop gestational diabetes (although this number can differ depending on demographics and the diagnostic criteria used) [7]. The causes of gestational diabetes are not fully understood, but may stem from a combination of pregnancy related hormones and a high BMI. While most women return to optimal blood glucose states after giving birth, gestational diabetes does increase the risk of developing T2D after giving birth. In some cases, MODY can resemble gestational diabetes, and depending on the MODY subtype, the treatment could be different than the treatment for gestational diabetes. Treatment of gestational diabetes can include physical activity and dietary intervention. In some cases, insulin, metformin, or sulfonylurea therapy may also be used [7].

LADA: LADA may represent the most prevalent form of autoimmune diabetes [8]. Similarly to MODY, LADA also resembles features of T1D and T2D. This form of the disease is characterized by the presence of autoimmune markers, a lack of immediate need for insulin, and an older age of onset. LADA initially resembles T2D, but the presence of autoimmune markers indicate that it is closely related to T1D.

Treatments for LADA are not fully established but may include insulin therapy. Initially, insulin therapy is not needed; however, people with LADA progress to insulin dependence faster than individuals with T2D. Unlike T2D, research is showing that people with LADA may not benefit from sulfonylureas [8,9].

Diabetes is a complex disease that affects millions of people. The many nuances that help define each type of diabetes can seem overwhelming, but knowing what support resources are available and understanding the different types of the disease can be a big step towards managing it. Genetic testing can help differentiate between the different types of diabetes and, in some cases, may help identify those at risk of developing the disease.

References

1. Pippitt, Karly, et al. “Diabetes Mellitus: Screening and Diagnosis.” American Family Physician, 15 Jan. 2016, www.aafp.org/afp/2016/0115/p103.html.

2. Fuchsberger, Christian et al. “The Genetic Architecture of Type 2 Diabetes.” Nature 536.7614 (2016): 41–47. PMC. Web. 2 Nov. 2017.

3. “Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012.” New England Journal of Medicine, vol. 377, no. 3, 2017, pp. 301–301., doi:10.1056/nejmc1706291.

4. Prentki, Marc, and Christopher J. Nolan. “Islet Β Cell Failure in Type 2 Diabetes.” Journal of Clinical Investigation 116.7 (2006): 1802–1812. PMC. Web. 2 Nov. 2017.

5. Wilmot, Emma, and Iskandar Idris. “Early Onset Type 2 Diabetes: Risk Factors, Clinical Impact and Management.” Therapeutic Advances in Chronic Disease 5.6 (2014): 234–244. PMC. Web. 2 Nov. 2017.

6. Gardner, Daphne SL, and E Shyong Tai. “Clinical Features and Treatment of Maturity Onset Diabetes of the Young (MODY).” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 5 (2012): 101–108. PMC. Web. 2 Nov. 2017.

7. Kampmann, Ulla et al. “Gestational Diabetes: A Clinical Update.” World Journal of Diabetes 6.8 (2015): 1065–1072. PMC. Web. 2 Nov. 2017.

8. Laugesen, E, J A Østergaard, and R D G Leslie. “Latent Autoimmune Diabetes of the Adult: Current Knowledge and Uncertainty.” Diabetic Medicine 32.7 (2015): 843–852. PMC. Web. 2 Nov. 2017.

9. Stenström, Gunnar, et al. “Latent Autoimmune Diabetes in Adults.” Diabetes, American Diabetes Association, 1 Dec. 2005, diabetes.diabetesjournals.org/content/54/suppl_2/S68/.