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Diabetes Mellitus

Type 2 Diabetes (Non-Insulin Dependent)

Jennifer Kong

Learning Objectives

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

  • Identify some risk factors of developing type 2 diabetes mellitus
  • Identify the manifestations of type 2 diabetes mellitus
  • Briefly describe the management of type 2 diabetes mellitus

 

Type 2 diabetes mellitus (T2DM) accounts for approximately >90% of all diagnoses of diabetes. About 80 to 90 percent of people with T2DM are overweight or obese; however, there are also genetic and lifestyle factors that cause T2DM.
In T2DM, cells become resistant to the effects of insulin:  thus, tissues will not allow glucose to enter the cell and the glucose remains in the blood. In response, the pancreas will increase insulin production. Eventually the pancreas can’t keep up with insulin production, resulting in elevated blood glucose. This is considered to be the pre-diabetes stage: rising blood glucose with normal or increased insulin production. However, over time, the beta cells will ‘burn out’ and insulin production drops and blood glucose dramatically rises.

T2DM causes hyperglycemia – Although insulin (purple triangles) can be made and there are insulin receptors on tissues (blue), the receptors do not recognize and/or refuse to be stimulated by insulin.  Thus there is nothing to stimulate glucose transporters (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 ND license

Because of the gradual, yet continuous,  rise of blood glucose, prediabetes and diabetes have an insidious onset.  Prediabetes, although a serious health condition, will result in higher than normal blood glucose levels, but not high enough yet to be officially diagnosed as T2DM. Similarly, the signs and symptoms are easily ignored or explained since it can take years for T2DM to be diagnosed. In the developed world, it is estimated that approximately  1 in 3 adults have prediabetes. Of those with prediabetes, less than 20% of them know that they have the condition.
What makes tissue insensitive to insulin?  It depends on whether it is an inheritable (genetic) cause or acquired during lifetime:

Genetic causes:

  • Insulin receptors are present in all tissues but are made less effective to respond to insulin. As a result, glucose can’t enter the tissues even though insulin is made in appropriate amounts. In this situation, blood glucose levels will still be high, despite exercising regularly and eating a healthy diet. Genetic cause will result in a family history of T2DM in close relatives.
  • Like all organs, the pancreas will lose function as we age. The risk for pancreatic insufficiency (i.e. can’t make enough insulin) increases at middle age (>45 yo).
  • Some ethnicities are more at risk for T2DM – regardless of the aformentioned lifestyle causes. First Nation peoples, Asians, and African Americans are at higher risk for T2DM.

Acquired insulin resistance:

  • An overabundance of circulating nutrients, such when glucose and fat (e.g. overweight, physical inactivity, poor diet, exposed to gestational diabetes in utero) are constantly available to tissues cause continuous release of insulin. As a result, tissues will ‘ignore’ insulin and don’t take up any more nutrients, becoming insulin resistant.
  • Medications that affect glucose homeostasis (e.g. steroid treatment for inflammation ), body metabolism (e.g. lipid lowering drugs), damage beta cells (e.g. certain antipsychotics, chemotherapy) or alter potassium levels that affects insulin secretion (e.g. diuretics) might produce an overabundance of circulating nutrients or reduced insulin release, both of which can contribute to decreased tissue responsiveness to insulin (insulin resistance).

Clinical Manifestations of Type 2 Diabetes

As  blood glucose rise due to insulin resistance, the signs and symptoms are more insidious. T2DM can occur at any age, but is more common in adulthood. Like with T1DM, the common signs of diabetes (hunger, thirst, & frequent urination) develop gradually – such that patients might not notice as abnormal changes occur.
As you will see in a later chapter, patients with T2DM might not know they have diabetes until a diabetic complication (most often in the eye, kidney, or nerve) brings them in for health care and diagnosis.

Management of Type 2 Diabetes

In many cases, T2DM can be managed by weight loss, physical activity, and a healthy diet.  However, if blood glucose levels still can not be managed with lifestyle interventions, medications can be used to improve tissue sensitivity to insulin or promote insulin release.  However if the beta cells are exhausted, exogenous insulin will be required to help in managing T2DM.

Muscle contraction promotes glucose uptake – The action of muscle contraction and movement promotes the uptake of glucose (gold hexagons) through the glucose receptors (green) of tissues.  This occurs with insulin present (purple triangles).  As a result, blood sugar levels lower and the tissues get glucose. Images created by Sarah Perkins under a CC BY ND license 

Section Summary

T2DM is the most common form of diabetes.  The pancreas can make insulin but the tissues do not respond to it. Consequently, the tissues do not take in sugar from the blood, resulting in chronic high blood glucose levels. Common manifestations are excessive thirst, hunger, and urination.  T2DM is most commonly caused by lifestyle factors (e.g. overweight, medications) leading to an overabundance of nutrients; however, there are some genetic factors (e.g. ethnicity, family history) that may make T2DM more likely. T2DM can be managed with a combination of exercise, diet modifications, and medications to improve tissue sensitivity to insulin.

Review Questions

1. Which of the following is false:

  • T2DM is a result of the pancreas not being able to produce insulin.
  • T2DM makes up the majority of diabetes diagnoses.
  • T2DM can take many years to develop.

Fill in the blanks with the following words:

glucose/sugar, higher, lower/decreased, glucose/sugar, beta

In T2DM, _____ cells in the pancreas are unable to keep up with the required insulin production since cells in the body have difficulty uptaking _____ due to _____ sensitivity to insulin. The blood _____ levels therefore remain _____ than normal.

3. In T2DM, the pancreas is still able to produce insulin, but the insulin receptors in the body are less effective. As a result, the blood glucose levels are low.

  • True
  • False

4. Which of the following are possible ways to help reverse T2DM? Select all that apply.

  • Weight loss
  • Physical activity
  • Healthy diet
  • Steroid treatment for inflammation
  • Diuretics
  • Lipid lowering drugs
  • T2DM is not reversible

 

Answer Key

  1. T2DM is a result of the pancreas not being able to produce insulin
  2. beta, glucose/sugar, lower, glucose/sugar, higher
  3. False
  4. Weight loss, physical activity, healthy diet

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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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