Report on Autoimmunity in Type 1 Diabetes: Causes and Treatments

This report provides a comprehensive overview of Type 1 diabetes mellitus, an autoimmune and organ-specific disease characterized by the destruction of insulin-producing beta cells in the pancreas. It explores the genetic susceptibility and inflammatory processes contributing to insulin deficiency, primarily affecting children and young adults. The report details the autoimmune mechanisms involved, the impact on carbohydrate and lipid metabolism, and the hormonal influences, including the roles of insulin, glucagon, and epinephrine, as well as the effects of cyclic AMP and protein kinase A. Symptoms such as weight loss, increased urination, and ketoacidosis are discussed, along with the associated complications. The report also highlights current treatment approaches like Diamyd, insulin therapy, and potential therapies like beta-cell replacement and islet transplantation, emphasizing the importance of lifestyle modifications. The references provided support the scientific basis of the report.

Autoimmunity with focus on Type 1 diabetes mellitus

Introduction:
Type 1 diabetes(Diabetes mellitus) is an autoimmune and organ specific
disease.Pancreatic islets were unable to produce required insulin or completely stop
insulin production by undergoing self destruction in pancreas.Individuals are genetically
susceptible due to inflammation resulting in insulin deficiency(Paschou et.al,2014).Type
1 diabetes is more often seen in children and young adult generation.It is most
prevalent in Northern European countries like Sweden and Finland followed by USA.
Type 1 diabetes mainly accounts 15% of the total population.The incidence rate is
increasing from 2% to 5 % every year and this is mainly because of unhealthy
environment.The nature of risk factors is currently under research investigation. (Floyel,
Kaur & Pociot, 2015).Beta cells undergo self destruction because of immune system
failure and it is observed in the age group between 11 to 13 years.Currently people
suffering from type 1 diabetes requires insulin injections for the rest of their lives in order
to remain alive.
Autoimmunity:
The immune system present in the body of an individual will undergo self destruction
mechanism of insulin producing beta cells and it is referred to as autoimmunity.Due to
this individual become sensitive and develop infections resulting in increased blood
glucose levels.This weakens the defense mechanism of the immune system and also
lead to other problems like body becoming more vulnerable to the infection,decrease in
blood flow and nerve gets damaged.Individuals suffering from this disease should be
injected with insulin into their body on a daily basis.Glycemic levels should be in control
in order to avoid the risks associated with diabetic condition (Cryer,2014).
It is necessary to slow down the self destruction process of beta cells in the pancreas
and for this treatment procedures like Diamyd is currently in use to stop or slow down
the autoimmune process of destruction in individuals(Donath,Hess & Palmer,2014). The
process to stimulate new beta cells generation is possible through combination of
Diamyd with other drugs.
carbohydrates & lipid metabolism pathways and correspondent hormones that are
activated and inhibited:
Type 1 diabetes is characterized by improper functioning of metabolism and are mainly
influenced by hormones and enzymes.There are several metabolic pathways which are
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regulated by maintaining balance between insulin at one side and epinephrine and
glucagon on other side.Cyclic AMP (cAMP),intracellular secondary messenger serve as
a parameter which maintains balance.
Cyclic AMP is formed by activation of adenylate cyclase by glucagon and
epinephrine.Cleavage of Cyclic AMP is enhanced by activation of phosphodiesterase by
insulin.If there is a lack of insulin it results in increase in Cyclic AMP level which further
activates Protein Kinase A.
Both Cyclic AMP and Protein Kinase A control the target protein fructose-2,6-
bisphosphate/phosphofructokinase-2 is referred to as bifunctional enzyme.
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Activation of bisphosphatase is enhanced by phosphorylation of bifunctional
enzyme.This lowers fructose-2,6 bisphosphate level and thus inhibits the process of
glycolysis and simultaneously initiates the activation of gluconeogenesis.
Glycogen metabolism also gets affected due to high Cyclic AMP levels which results in
inhibition of synthesis of glycogen and further there is increased breakdown.Though the
blood glucose levels are high, the activation of gluconeogenesis and breakdown of
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glycogen will result in glucose production.Thus enhances excess accumulation of
glucose.
The Protein kinase A and Cyclic AMP cascade activates the sensitive hormone lipase
which is present in fat tissue.Triglycerides gets broken down into glycerol and fatty
acids(free) with the help of enzyme lipase and are directed towards blood stream.The
free fatty acids are consumed directly to the ketogenesis and whereas glycerol to
gluconeogenesis pathway in liver (Jonsdottir et.al,2013).
Some of the symptoms associated with type 1 diabetes are loss of weight,feeling
hunger,fatigue,increased urination and thirst.When there is an increase blood glucose
levels,excess glucose produced is removed in the form of urine by the body.Blood gets
diluted by excess intake of water.Many individuals initially develop a condition called
ketoacidosis that occur due to cells which use alternative mechanisms in order to
produce energy resulting in producing ketoacids. Acid-base imbalance is possible as
the blood gets acidified due to keto acids. Due to this Individuals suffer from
vomiting,drowsiness and nausea.
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Due to high blood glucose levels the cells present in the immune system becomes
sensitive,in active and exhausted.This results in decreasing effective mechanism to
invade pathogens and cause skin,urinary tract or pneumonia related infections.The
presence of high blood glucose levels results in damage to the cells in blood vessels
and decrease the flow of blood leading to tissue death.
Type 1 diabetes condition lowers the pH of the body and exhibits more acidic property
and this is referred to as ketoacidosis.The body is unable to proper utilization of blood
glucose and results in conversion of fats into energy through ketoacidosis.Ketoacidosis
is generally diagnosed by means of blood test which detects ketones (Kanikarla-Marie &
Jain, 2016).
Ketoacidosis condition occurs gradually and the disease progress is very slow.Some of
the symptoms associated with ketoacidosis include nausea,pain in abdomen,feeling
exhausted,ketones presence in urine at elevated level,vomiting and breathing
problems.The individual needs to be treated otherwise the condition is fatal.
Conclusion:
Type 1 diabetes is wide spread autoimmune disease across the world and the
percentage of people getting affected is increasing every year.In order to minimize the
effects of the disease Insulin based therapy is proven to be vital contribution to fight
against type 1 diabetes but still there are few concerns like hypoglycemia and
hyperglycemia are found to affect the quality of life of patients.Main complications
related with type 1 diabetes include high blood glucose levels and low blood pH which is
due to alterations in lipid and carbohydrate metabolism that are influenced by
hormones(Vladu,Clenciu & Efrem,2017).It is necessary to minimize the complications
that are raised due to an imbalance in blood glucose levels by producing new beta cells
in the pancreas from cell sources of an individual thus it avoids immunosuppression.
Glycosylated hemoglobin(HbA1C) in order to present in normal range in diabetes
affected patients there is necessary for transplantation of pancreas organ.This will
improve the quality of life of a patient followed by prevention of recurrence of diabetes.In
addition to this individual is free from insulin and other dietary interventions.
Due to transplantation monitoring blood glucose levels frequently can be reduced but
however there are some disadvantages like immunosuppression and risks associated
with operation procedures.Replacement of beta cells,transplantation of islets were some
of the new therapies found to be promising and effective in avoiding autoimmune cells
present in pancreas (Storling & Pociot,2017).It is also important that individual needs to
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maintain a healthy lifestyle with dietary interventions and adequate exercise that could
help to minimize the effects and growth of diabetes.
References:
Cryer, P.E.(2014).Glycemic goals in diabetes: trade-off between glycemic
control and iatrogenic hypoglycemia. Diabetes,63(7),2188–2195.
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Donath, M.Y., Hess, C. & Palmer, E. (2014). What is the role of
autoimmunity in type 1 diabetes? A clinical perspective.
Diabetologia, 57,653–655.
Floyel, T., Kaur, S. & Pociot, F.(2015). Genes affecting beta-cell function
in type 1 diabetes. Curr. Diabetes Rep.,15,97.
Jonsdottir, B., Andersson, C., Carlsson, A., Delli, A., Forsander, G.,
Ludvigsson, J. (2013). Thyroid autoimmunity in relation to islet
autoantibodies and HLA-DQ genotype in newly diagnosed type 1
diabetes in children and adolescents. Diabetologia ,56,1735–42.
Kanikarla-Marie, P., & Jain, S.K.(2016). Hyperketonemia and ketosis
increase the risk of complications in type 1 diabetes. Free Radic
Biol Med.,95,268–277.
Paschou, S.A., Petsiou, A., Chatzigianni, K., Tsatsoulis, A.,
Papadopoulos, G.K.(2014). Type 1 diabetes as an autoimmune
disease: the evidence,Diabetologia,57, 1500–1501.
Storling, J., & Pociot, F.(2017). Type 1 diabetes candidate genes linked to
pancreatic islet cell inflammation and beta-cell apoptosis. Genes, 8,
E72.
Vladu, M., Clenciu, D., & Efrem I. C.(2017). Insulin resistance and chronic
kidney disease in patients with type 1 diabetes mellitus. Journal of
Nutrition and Metabolism. 2017;2017:5.
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