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What Are the Causes and Genetic Components of Type 1 Diabetes?


Causes of Type 1 Diabetes

by dLife Editors

What is Type 1 Diabetes?

Diabetes is a metabolic condition characterized by an accumulation of sugar (glucose) in the body. It is caused by either insufficient insulin production or the body not being able to use insulin in the way it should.[1], [2]

There are two types of diabetes—type 1 diabetes and type 2. In this article, you’ll learn the characteristics of type 1 diabetes, its epidemiology, causes, diagnosis, and treatment options.

In type 1 diabetes, the pancreas is unable to produce insulin or produces very little amounts. Insulin is a hormone produced by the beta cells (β-cells) of the pancreas. β-cells are also known as the ‘islets of Langerhans’ for their tendency to form tiny clusters that are scattered throughout the pancreas. Insulin acts as a sugar regulator, enabling blood glucose to be transported to the cells where it is converted into energy. In people suffering from type 1 diabetes, the β-cells of pancreas that produce insulin are destroyed by the body’s own immune cells through an autoimmune mechanism.[1], [3]

A lack of insulin or getting insufficient amounts causes an accumulation of blood glucose in the body. It leads to the development of classic diabetes symptoms, including the following:

  • Increased thirst
  • Increased hunger
  • Frequent urination
  • Weight loss

When left uncontrolled, high blood sugar can also cause other complications, affecting the eyes, nerves, kidneys, and cardiovascular system.[1], [4]

The difference between type 1 and type 2 diabetes is that in type 1, the body does not produce insulin at all; this is why it is called ‘insulin dependent diabetes.’ In type 2 diabetes, the body produces insulin but the cells are not able to utilize the insulin produced; this is why it is commonly referred to as ‘insulin resistant diabetes.’ Over time, the body’s cells can develop insulin resistance in type 1 diabetes, too.[1],[5]

Diabetes is diagnosed by testing the level of blood sugar or A1C (glycated hemoglobin). An A1C reading measures the three-month average plasma glucose concentration in the blood. Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies (a type of protein produced by an individual’s immune system directed against one or more of the individual’s own proteins).[6],[7] When specific autoantibodies are found, a doctor can make the diagnosis of type 1 diabetes.

Epidemiology of Type 1 Diabetes

Type 1 diabetes is a rarer form of diabetes than type 2. Type 1 diabetes accounts for only five to 10 percent of all diabetes cases. Although it can occur at any age, it is more common in children and adolescents less than 15 years of age. This is why the condition was previously coined ‘juvenile diabetes.’[8],[9] The occurrence is similar in men and women, although in children it is more common in girls. Type 1 diabetes most commonly occurs during puberty. Because girls typically enter puberty earlier than boys, the condition is often diagnosed earlier in girls. After puberty, the incidence rate drops in women but continues to occur in men between the ages of 29 and 35. More than 500,000 children are currently living with this condition globally. The incidence of type 1 diabetes is increasing worldwide with close to 90,000 cases diagnosed in children each year.

The incidence rate of this condition varies between different countries. It is highest in Scandinavian countries followed by Europe, North America, and Australia. In Asian countries, such as India, China, and Japan, type 1 diabetes is a rare condition. The difference in incidence rate between these countries is likely due to differences in genetic susceptibility and environmental/lifestyle factors. The incidence rate differs even within the same countries. For example, children in Russia who suffered from a history of infections have shown a lower risk of developing type 1 diabetes than children who had the same genetic risk but a history of fewer infections.[4], [9], [10], [11], [12]

The American Diabetes Association has proposed an etiological classification of type 1 diabetes: type 1A (related to immune-mediated diabetes) and type 1B (non-autoimmune related/idiopathic kind). Due to increasing incidences of type 1 diabetes in adults in recent years, a third category has been introduced—it is known as latent autoimmune diabetes of the adult (LADA). Adults who develop LADA have the same symptoms as type 2 diabetes patients, but produce a unique antigen/protein called Human Leukocyte Antigen (HLA).[1], [2], [11], [12], [13]

Causes of Type 1 Diabetes: Genetics, Family History, and Environmental Factors

The exact causes of type 1 diabetes are not yet known. But genetics, family history, and environmental factors appear to play a role in the development of this serious health condition. In this section, we’ll examine each of the potential causes.

Genetic Causes of Type 1 Diabetes

Type 1 diabetes is a polygenic disease; this means it is a disease that involves many genes. These gene groups are located on structures called chromosomes within the cell. These genes make proteins that help maintain our immune system, fighting off unwanted cells or infectious agents. Discrepancies in the functioning of these genes lead to a discrepancy in the synthesis of the proteins.

In the case of type 1 diabetes, the β-cells of the pancreas are regarded as external harmful agents by the body’s immune system, and the body seeks to destroy them. Around 20-40 different chromosomal gene groups have been linked to type 1 diabetes. The largest contributing gene for type 1 diabetes is called IDDM1; it is located in the Major Histocompatibility Complex (MHC) II region on chromosome six. This gene accounts for at least 40 percent of the familial hereditary cause of type 1 diabetes.[13], [14]

Family History’s Role in Type 1 Diabetes

Approximately one in every 250 children in the United States is born into a family already affected with type 1 diabetes. Children born into an affected family have a five percent increased risk of developing type 1 diabetes by age 20. In comparison, children with no such family history have only a 0.3 percent chance of developing this condition.

A child with a family history of type 1 diabetes can be classified further based on which family member has the disease. The chances of a child developing type 1 diabetes are as follows:

  • Five percent chance if the father has type 1 diabetes
  • Three percent chance if the mother has type 1 diabetes
  • Eight percent chance if the sibling has type 1 diabetes
  • 50 percent chance if the identical twin has type 1 diabetes

Children with affected immediate family members and affected first-degree relatives have a 20 percent risk of developing the condition.[13],[15] The percentages listed above are dependent on the number and type of discrepant genes inherited from either parent. These factors ultimately decide whether the condition will be dominant or recessive in a child. In the dominant condition, the child is more likely to get type 1 diabetes due to a higher combination of defective genes received.[11], [16]

Environmental Causes of Type 1 Diabetes

Despite the relevance of genetics and hereditary seen with type 1 diabetes, there are still cases that develop in children with unaffected families.[13] Although the genetic risk can be considered substantial, the influence and association of environmental factors cannot be ignored. These factors can be potential triggers, casual, or protective.[11] Take the case of identical twins, for example. When one twin develops type 1 diabetes, the other twin has a 50 percent chance of developing the condition and a 50 percent chance of not developing it. This statistic strongly suggests that in addition to genetic susceptibility, other factors like environmental exposure may also play a role in the onset of this condition.[16] As mentioned previously, this condition varies in occurrence in the same country due to differences in children’s infection history. Environmental factors are likely the cause.

Seasonal variations have been observed with more cases occurring in the autumn or winter months.[5] For this reason, vitamin D is thought to have a protective role in decreasing one’s susceptibility to type 1 diabetes (as more vitamin D is available in the summertime). Other factors that may act as triggers and increase one’s susceptibility to this health condition include the following:

  • A disturbance of microorganisms (microbiota) in the gut
  • Enterovirus infections
  • Certain bacterial infections

While some environmental factors act as triggers, others seem to safeguard the body from type 1 diabetes. For example, dietary agents like gluten seem to have a protective role. The timing of when these factors are introduced to the body play a significant role in the development or non-development of this life-changing condition. Ongoing research aims to gather more concrete evidence to support the relation between type 1 diabetes and environmental causes.[11]

Environmental influences may occur as early as in utero and may continue into the first few months or years of life, affecting the onset of antibody development against the β-cells of the pancreas. Physiological events like immune system development and normal turnover of β-cells also contribute to the pathogenesis of the condition.

Inherent dysregulation in the immune system, probably due to genetic susceptibility, leads to the self-destruction of β-cells and production of autoantibodies in the blood. However, not all individuals who develop this autoimmune dysregulation or produce these autoantibodies progress to the symptomatic stage of type 1 diabetes, developing symptoms of glucose intolerance. This variation could be attributable to the influence of environmental factors.[5],[17] Thus, the diverse nature of type 1 diabetes is an important aspect to consider. Because this blood sugar disease presents in some and not in others, researchers surmise that both genetics and the environment contribute to its onset.

Diagnosis of Type 1 Diabetes

In addition to the typical symptoms of hyperglycemia (high blood sugar), the following clinical tests aid in the diagnosis of the disease:

  1. Fasting blood glucose level at or above 7.0mmol/l (126mg/dl)
  2. Postprandial (post-blood glucose) level at or above 11.0mmol/l (200mg/dl)
  3. Glycated hemoglobin at or above 48mmol/mol[18]

Type 1 diabetes can be distinguished from type 2 by the presence of various autoantibodies in the blood. These are some of the autoantibodies doctors look for and the tests they order when diagnosing type 1 diabetes:

  1. Islet cell antibodies, insulin antibodies, glutamic acid decarboxylase (GAD), zinc transporter autoantibodies (ZnT8). The presence of different types of autoantibodies increases the risk of developing symptoms of type 1 diabetes like hyperglycemia.[19]
  2. C-peptide testing can detect the amount of insulin produced by the pancreas, a key factor in diagnosing type 1 diabetes.
  3. Genetic testing, such as HLA subtyping, provides health experts with more details for understanding the disease.[20]

Type 1 Diabetes Treatment

Type 1 Diabetes Treatment

The key to managing type 1 diabetes is controlling blood sugar levels, ensuring that they are maintained in the normal range. Because insulin levels are low in people with type 1, insulin should be provided in the form of an injection.

Three main ways in which Type 1 Diabetes is treated:

Treating Type 1 Diabetes with Insulin

It is important to note three things while taking insulin injections:

  • There is an onset time for insulin to work. Onset time refers to the time needed for injected insulin to reach the blood and start its action.
  • There is a peak time when the action of injected insulin reaches its maximum effect.
  • The duration for how long insulin works after its initial onset.[10]

The different types of insulin that can be given are rapid-acting, regular-acting, or long-acting. The doctor suggests a dose using the above criteria and his or her expertise in treating diabetes. The dosage is taken by injecting a needle into the skin or using an insulin pump.[10]

Treating Type 1 Diabetes with Dietary Changes

It is important for people with type 1 diabetes to understand how the food they eat affects their blood sugar. Diet plans should focus on the type and quantity of carbohydrate eaten in order to match the insulin intake and maximize the nutrition achieved in each calorie. Knowing the role of carbohydrates, proteins and fats can help a type 1 diabetes patient create a healthy diet plan; the assistance of a dietician or diabetes educator is crucial in devising such a plan. People with type 1 diabetes typically benefit from eating more of the following foods:

  • Fresh vegetables
  • Whole grains
  • Healthy proteins like fish, beans, and chicken

To prevent blood sugar fluctuations, it is recommended that people with type 1 diabetes limit their intake of sweets and processed foods.[10], [20]

Treating Type 1 Diabetes with Exercise

Exercise is an important part of treating type 1 diabetes. However, both children and adults with type 1 need to be careful and monitor their blood sugar before, during, and after exercise. During exercise, the muscles use insulin to access blood sugar for energy. Therefore, insulin levels can become low during exercise, causing low blood sugar. It is important to have snacks during exercise to prevent blood sugar from dropping too low.

On the flip side, exercise may also trigger a release of stored glucose from the liver. This can lead to higher than expected blood sugar. Because of these potentially dangerous fluctuations, it’s key to regularly monitor blood glucose during exercise to assess whether it goes up or down.[10], [11], [20] 

Sources

[1]      M. Clark, C. J. Kroger, and R. M. Tisch, “Type 1 Diabetes: A Chronic Anti-Self-Inflammatory Response,” Front. Immunol., vol. 8, no. December, 2017.

[2]      G. S. Eisenbarth, “Update: Update in type 1 diabetes,” J. Clin. Endocrinol. Metab., vol. 92, no. 7, pp. 2403–2407, 2007.

[3]      “What is Diabetes? | NIDDK.” [Online]. Available: https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes. [Accessed: 23-Jan-2018].

[4]      “Symptoms & Causes of Diabetes | NIDDK.” [Online]. Available: https://www.niddk.nih.gov/health-information/diabetes/overview/symptoms-causes. [Accessed: 09-Feb-2018].

[5]      M. A. Atkinson, G. S. Eisenbarth, and A. W. Michels, “Type 1 diabetes.,” Lancet (London, England), vol. 383, no. 9911, pp. 69–82, Jan. 2014.

[6]      J. L. Chiang, M. S. Kirkman, L. M. B. Laffel, A. L. Peters, and Type 1 Diabetes Sourcebook Authors, “Type 1 diabetes through the life span: a position statement of the American Diabetes Association.,” Diabetes Care, vol. 37, no. 7, pp. 2034–54, Jul. 2014.

[7]      “Diabetes Tests & Diagnosis | NIDDK.” [Online]. Available: https://www.niddk.nih.gov/health-information/diabetes/overview/tests-diagnosis. [Accessed: 09-Feb-2018].

[8]      D. Daneman, “Type 1 diabetes.,” Lancet (London, England), vol. 367, no. 9513, pp. 847–58, Mar. 2006.

[9]      A. Katsarou, S. Gudbjörnsdottir, A. Rawshani, D. Dabelea, E. Bonifacio, B. J. Anderson, L. M. Jacobsen, D. A. Schatz, and Å. Lernmark, “Type 1 diabetes mellitus,” Nat. Rev. Dis. Prim., vol. 3, p. 17016, Mar. 2017.

[10]    “Type 1 Diabetes (Juvenile Diabetes) Causes, Symptoms, Treatments.” [Online]. Available: https://www.webmd.com/diabetes/type-1-diabetes#1. [Accessed: 09-Feb-2018].

[11]    T. L. Van Belle, K. T. Coppieters, and M. G. Von Herrath, “Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies,” Physiol. Rev., vol. 91, no. 1, pp. 79–118, Jan. 2011.

[12]    D. M. Maahs, N. A. West, J. M. Lawrence, and E. J. Mayer-Davis, “Epidemiology of type 1 diabetes.,” Endocrinol. Metab. Clin. North Am., vol. 39, no. 3, pp. 481–97, Sep. 2010.

[13]    E. Bonifacio and A. G. Ziegler, “Advances in the Prediction and Natural History of Type 1 Diabetes,” Endocrinol. Metab. Clin. North Am., vol. 39, no. 3, pp. 513–525, Sep. 2010.

[14]    F. Pociot and M. F. McDermott, “Genetics of type 1 diabetes mellitus,” Genes Immun., vol. 3, no. 5, pp. 235–249, Aug. 2002.

[15]    H. Turner, J. A. H. Wass, and K. Owen, Oxford handbook of endocrinology and diabetes. .

[16]    “Is Diabetes Genetic? The Hereditary Risk of Type 1 Diabetes.” [Online]. Available: https://www.webmd.com/diabetes/diabetes-type-1-genetics#1. [Accessed: 09-Feb-2018].

[17]    M. Rewers and J. Ludvigsson, “Environmental risk factors for type 1 diabetes.,” Lancet (London, England), vol. 387, no. 10035, pp. 2340–2348, Jun. 2016.

[18]    “Summary of revisions for the 2010 Clinical Practice Recommendations.,” Diabetes Care, vol. 33 Suppl 1, no. Supplement 1, p. S3, Jan. 2010.

[19]    M. Knip, R. Veijola, S. M. Virtanen, H. Hyöty, O. Vaarala, and H. K. Akerblom, “Environmental triggers and determinants of type 1 diabetes.,” Diabetes, vol. 54 Suppl 2, no. suppl 2, pp. S125-36, Dec. 2005.

[20]    “Type 1 Diabetes (Juvenile) Symptoms, Diet, and Life Expectancy.” [Online]. Available: https://www.medicinenet.com/type_1_diabetes/article.htm#which_specialties_of_doctors_treat_type_1_diabetes. [Accessed: 09-Feb-2018].

What Are the Causes and Genetic Components of Type 1 Diabetes?
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