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Diabetes Mellitus

Type 1 Diabetes (Insulin Dependent)

Jennifer Kong

Learning Objectives

By the end of this section, you will be able to:

  • Identify some risk factors of developing type 1 diabetes mellitus
  • Identify the manifestations of type 1 diabetes mellitus
  • Briefly describe the management of type 1 diabetes mellitus

 

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, making up <5% of all diabetes diagnoses.  There is somewhat of a genetic component to T1DM as research has demonstrated that certain genes are recognized to increase susceptibility to the development of T1DM. Similarly, current research suggests that environmental triggers also play a role in development of T1DM alongside genetics: colder climates, preceding viral infection, and dietary patterns during infancy.

T1DM involves loss of beta cells from the pancreas resulting in no insulin production. T1DM patients have insulin receptors. A combination of genetics and environmental triggers causes the body’s immune system to recognize beta cells as foreign and, as a result, the body eliminates the beta cells. This is a progressive condition, which culminates in lack of beta cells and consequently lack of insulin production. T1DM usually manifests in childhood or early adulthood, earning the alternate name “juvenille diabetes”. However, adults can develop T1DM. Thus the current name “Type 1: insulin-dependent diabetes” is more accurate.

 

Pathology of T1DM –  Upper panel: the immune system attacks the beta cells leading to a lack of insulin production.  Lower panel:  there is no insulin (purple triangles) circulating in blood.  Images created by Sarah Perkins under a CC BY NC license

 

T1DM causes hyperglycemia – Since there is no circulating insulin (purple triangles), the insulin receptors (blue) on tissues are not stimulated.  Thus there is nothing to stimulate glucose receptors (green) to allow glucose (gold hexagons) to enter the tissues.  As a result, the cells are deprived of glucose and glucose stays in the blood causing hyperglycemia.  Images created by Sarah Perkins under a CC BY NC license

Histologically, pancreatic tissue will be affected in T1DM. Autoimmune destruction of beta cells in the islets results in hyaline tissue being laid down to replace the missing beta cells. However, all other tissues will look normal as both the insulin receptors and glucose transporters are unaffected.

 

 

DHPLC Specimen PATH 425-125 – hyalinization of the islets of Langherhans; pancreatic tissue with H&E staining. Created by Jennifer Kong licensed under All rights reserved.

 

Revisit this link , from the “Anatomy and histology of the endocrine pancreas and glucose homeostasis” chapter to view an animation describing the role of insulin and the pancreas in diabetes mellitus.

Manifestations of Type 1 Diabetes

The clinical consequences are due to the lack of insulin in the blood circulation and eventually the lack of glucose uptake by the cells. The most common manifestations of T1DM are hunger, excessive urination, and thirst. This is also known as the 3P’s of diabetes: polyphagia, polyuria, & polydipsia. Normally, kidneys reabsorb all of the sugar that escapes into the filtrate (see AKI chapter for review). However, in hyperglycemia, there is too much glucose in the blood already so excess glucose stays in the filtrate. Excess glucose in the filtrate will retain water in the urine:  as a result a person with T1DM urinates an abnormally large and frequent quantity of ‘sweet’ urine. Since there is a loss of large quantities of fluid, the body becomes dehydrated and so thirst is unusually and continually present. Similarly, people with T1DM may also experience persistent hunger because the body cells are unable to access the glucose in the bloodstream due to lack of insulin (recall that the tissue’s insulin receptors are present and working appropriately). This may force tissues to use fat metabolism and gluconeogenesis to meet its energy needs. As a consequence, dangerous byproducts (e.g. acidic ketones) will increase in blood and tissues.

The inability of the tissues to uptake glucose from the blood circulation cause high heart rate, fast breathing, confusion/irritability, fatigue, and cold sweat as a consequence of low glucose metabolism inside the cells. In children, the inability to bring glucose into cells alongside lack of insulin will manifest as failure to thrive (i.e. grow and develop). Insulin promotes growth through IGF-1 and GH receptors and a direct lack of insulin can lead to unintended weight loss at a time when children should grow.
Due to the high blood sugar, a person with T1DM is more susceptible to infections – particularly oral & urinary outlets as there is a higher exposure to pathogens in those areas. Thus urinary tract infections and dental/gum disease are more likely in people with T1DM.

Management of Type I Diabetes

People with T1DM do not have beta cells, thus they can not  produce insulin. For this reason, synthetic insulin must be administered by injection or infusion to help regulate glucose homeostasis throughout the day.

Section Summary

Regardless of the cause, T1DM results in the loss of beta cells in the pancreatic islet tissue.  Thus there is no insulin released to be delivered to tissues.  At the tissue level, there is no increase in the number of glucose transporters in the plasma membrane (normally, it would respond to insulin receptor binding and activation) therefore, preventing glucose to enter the cell for metabolism.  The glucose stays in the blood leading to hyperglycemia.  Hyperglycemia affects all tissues in that:

  • It forces tissues to use fat metabolism and gluconeogenesis to meet its energy needs.  As a consequence, dangerous byproducts (e.g. acidic ketones) will increase in blood and tissues
  • Hyperglycemia causes an osmotic imbalance resulting in both glucose and excessive water to be lost in urine (i.e. polyuria).  As a consequence, thirst and dehydration will occur.
  • As insulin is needed to build tissues, there is no opportunity to gain tissue mass.  In a child, this would appear as “failure to thrive” and a slow growth rate.

Review Questions

1. Which factors are supported by research where T1DM susceptibility increases?

  • Certain genes, colder climates, and previous viral infections
  • Colder climates, diet during infancy, and overconsumption of sugar later in life
  • Preceding viral infection, diet during infancy, and warmer climates
  • Certain genes, diet during infancy, and warmer climates

2. Fill in the blanks.

T1DM is associated with a loss of pancreatic _____(alpha/beta/delta) cells and is usually diagnosed _____(earlier/later) in life. It can be identified as the body producing _____ (less/no/more) insulin compared to normal.

3. What are the 3 P’s that can be used to describe the manifestations of T1DM?

4. Which of the following are NOT typically signs of a person with T1DM? Select all that apply. 

  • Sweet smelling urine
  • Salty smelling urine
  • Dehydrated body
  • High heart rate
  • Cold sweats
  • Hot flashes
  • Loss of appetite
  • Increased infections

 

Answer Key

  1. Certain genes, colder climates, and previous viral infections
  2. Beta, earlier, no
  3. Polyphagia (excessive hunger), Polyuria (excessive urination), and Polydipsia (excessive thirst)
  4. Salty smelling urine, Hot flashes, Loss of appetite

License

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Pathology Copyright © 2022 by Jennifer Kong and Helen Dyck is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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