TYPE1, AND TYPE2 DIABETES MELLITUS


                                   DIABETES  MELLITUS


Our body has trouble moving glucose, which is the type of sugar from





our blood into cells, this leads to high levels of glucose in our blood, and not enough of it, in our cells, and remember that our cells need glucose as a source of energy, so not letting the glucose enter means that the cells starve for energy, despite having glucose right on their doorstep.





In general, the body system controls that how much sugar gets into the cells with two hormones INSULIN and GLUCAGON. INSULIN is used to reduce blood glucose levels and GLUCAGON is used to increase blood glucose levels. Both of these hormones are produced by clusters of cells in the pancreas called ISLETS OF LANGERHANS. Insulin is secreted by beta cells in the centre of these islets and glucagon is secreted by alpha cells in the periphery of the islets.





Insulin reduces the amount of glucose in the blood by binding it to insulin receptors, embedded in the cell membrane of various insulin-responsive tissues, like Insulin is secreted by beta cells in the centre of these islets and glucagon is secreted by alpha cells in the periphery of the islets.

 and adipose tissue. when activated the insulin receptors, cause vesicles containing glucose transporter, these are inside the cell to fuse with the cell membrane. Allowing glucose to be transported into the cell.




Glucagon does exactly the opposite, it raises the blood glucose levels by getting the liver to generate new molecules of glucose from other molecules, and also break down glycogen into GLUCOSE. So that they all get dumped into the blood.

 DIABETES MELLITUS IS DIAGNOSED

When the blood glucose levels get too high, and this Type1 diabetes mellitus is seen among 10% of the world population.





There are two types of diabetes TYPE 1 & TYPE 2.

and the main difference between them is the underlying mechanism that causes the blood glucose levels to rise about 10% of people with DIABETES, which is type 1 and the remaining 90% of people with diabetes have type 2 diabetes.
In type1 diabetes, the body does not make enough insulin. The reason it is happening in type 1 diabetes there is a type for hypersensitivity response or a cell-mediated immune response, where a person's own T cells attack the pancreas.




Note:( The immune system has T cells that react to all sorts of antigens which are usually small peptides polysaccharides or lipids, and that some of these antigens are part of our own body cells).  It doesn't make sense to allow T cells to attack our own cells to hang around until there is this process to eliminate them, which is called self-tolerance.
 In type 1 diabetes. There is a genetic abnormality that causes a loss of self-tolerance among T cells, that specifically target the beta-cell antigens losing self-tolerance means that these T cells are allowed to recruit other immune cells and coordinate an attack on these beta cells.



Losing beta cells means less insulin, and less insulin means that glucose piles up in the blood, because it can't enter the body cells. One important group of genes involved in the regulation of the immune response is the human leukocytes antigen system (HLA). It is the group of genes on chromosome 6, That encodes the major histo-compatibility complex or MHC.



Which is a protein that is extremely important in helping the immune system. It recognises the foreign body molecules as well as maintaining self-tolerance MHC is like the serving platter that,  antigens are presented to the immune cells on interestingly people with type 1 diabetes often have specific HLA gene in common with each other. One is called( HLA dr3) and the other is called (HLA dr4). Not Everyone with HLA dr3 or HLA dr4 develop diabetes. In diabetes mellitus  type1; destruction of beta cells usually starts early in life but sometimes up to 90% of the beta cells are destroyed before symptoms crop up, for clinical symptoms of uncontrolled diabetes. That all sound similar to Polyphagia, Glycosuria, Polyuria and Polydipsia.





Let's go through them one by one, even though there is a lot of glucose in the blood. It cannot get into the cells which leave cells starved for energy. So in response, adipose tissue starts breaking up fat called lipolysis, and muscle tissue starts breaking down proteins, both of which result in weight loss. For those with uncontrolled diabetes, this catabolic state leaves people feeling hungry also known as   poly- phagia, ( poly means a lot, phagia means eating.)
Now with high glucose levels, that means, when blood gets filtered through the kidneys, some of It starts to spill into the urine called glycosuria, (glycol suffix to glucose and urea  to urine.)
Since glucose is osmotically active, water tends to follow it, it is resulting in an increase in urination that is called polyuria. (poly means a lot, urea to urine)
because of too much urination, diabetic patients become dehydrated and thirsty or Polydipsia. (poly means a lot and dips means thirst)
Diabetic patients, cannot tend to produce their own insulin and they can respond to insulin therapy which will become lifelong treatment. To regulate their blood glucose levels to enable their cells to use glucose.




Insulin is secreted by beta cells in the centre of these islets and glucagon is secreted by alpha cells in the periphery of the islets.

`KETOACIDOSIS

One serious complication with Type1 diabetes is ketoacidosis or (DKA). To understand this, let's see the process of lipolysis, where fat is broken down into free fatty acids, and the liver turns this fatty acid into ketone bodies like acetoacetic acid in beta hydroxyl-butyrate acid, Acetoacetic acid,( is a ketoacid) because it has a ketone group in a carboxylic acid group. Beta hydroxybutyric acid on the other hand it is not a ketoacid since its ketone group has been reduced to a hydroxyl group, these ketone bodies are important because they can be used by cells for energy, but they also increase the acidity of the blood that's why it is called ketoacidosis.






The blood becomes acidic can have major effects throughout the body. The individuals can develop KUSSMAUL respiration which is deep and laboured breathing, as the body tries to reduce carbon dioxide out of the blood in an effort to reduce its acidity. cells, also have a transporter that exchanges its hydrogen ions or protons for potassium. When the blood gets acidic it's by definition loaded with PROTONS, which get sent into cells while potassium gets sent into the fluid outside cells.




Another thing to keep in mind is that, in addition to helping glucose enter the cells, insulin stimulates the sodium-potassium ATPase-which help potassium to get into the cells and so without insulin more potassium stays in the fluid outside the cells.
Both of these mechanisms lead to increased potassium in the fluid outside cells, which quickly makes it into the blood and causes hyperkalaemia, the potassium is then excreted. So over time even though the blood potassium levels remain high, overall stores of potassium in







the body, which includes potassium inside the cells starts to run low. Individuals will also have a high anion gap, which reflects a large difference in the unmeasured, negative and positive ions in the serum, largely due to the build-up of ketoacid. Diabetic ketoacidosis can happen even in people who have already been diagnosed with diabetes, and currently have some sort of insulin therapy.



In states of stress like in an infection, the body releases epinephrine, which in turn stimulates the release of glucagon, too much glucagon can tip the delicate hormonal balance of glucagon and insulin in favour of elevating blood sugars and can lead to a cascade of events, we just described increased glucose in the blood loss of glucose, in the urine, loss of water dehydration, and in parallel, the need for alternative energy, generation of ketone bodies, and ketoacidosis interestingly both ketone bodies break down into acetone and escape as a gas by getting breathed out the lungs, which gives us sweet fruity smell to a person's breath. In general, though that's the only sweet thing about this illness, which also causes nausea vomiting and if severe mental status changes, and acute cerebral oedema.




TREATMENT  of a DKA episode involves, giving plenty of fluids, which helps with dehydration.
Insulin helps Lower blood glucose levels and replacement of electrolytes like potassium. All of which help to reverse the acidosis.

TYPES 2 DIABETES





which is where the body makes
INSULIN, but the tissues don't respond as well to it the exact reason why cells
don't respond isn't fully understood essentially the body's providing the normal amount of insulin, but the cells don't move their glucose transporters to their membrane in response which remember is needed for the glucose to get into the cells. These cells, therefore, have insulin resistance some risk factors for insulin resistance are obesity lack of exercise and hypertension, the exact mechanisms are still being explored, for example, In excess of adipose tissue or fat is thought to cause the release of free fatty acids in so-called Adipo-kinase which are signalling molecules that can cause inflammation which seems related to insulin resistance. however many people that are obese are not diabetic so genetic factors probably play a major role as well we see when we look at twin studies as well.

with type-2 diabetes



increases the risk of developing type 2 diabetes, completely independently of other environmental risk factors. In type2 diabetes since tissues don't respond as well to normal levels of insulin, the body ends up producing more insulin, In order to get the same effect and move glucose out of the blood, they do this through beta-cell hyperplasia an increased number of beta-cells, and beta-cell hypertrophy, where they actually grow in size. All in this attempt to pump out more insulin. This works for a while and by keeping insulin levels higher than normal blood glucose levels can be kept normal called Normal glycaemia





                                                    






now along with insulin beta cells also secrete islet amyloid polypeptide or amylin so while beta cells are cranking out insulin they also secrete an increased amount of amylin over time Amylin builds up and AGGREGATES in the islets this beta-cell compensation though is not sustainable and over time those maxed out beta cells get exhausted and they become dysfunctional and undergo hypotrophy and get smaller as well as hypoplasia and die off as beta cells are lost in insulin levels decrease glucose levels in the blood start to increase in patients develop hyperglycaemia which leads to similar clinical signs that we mentioned before like





 polyphagia, glycosuria polyuria, polydipsia but unlike type 1 diabetes there's generally some circulating insulin in type 2 diabetes from the beta cells that are
trying to compensate for the insulin resistance means that the insulin glucagon balances such that diabetic ketoacidosis does not usually develop. having said that a complication called hyperosmolar hyperglycaemic state or HHS is much more common in type 2 diabetes





then type 1 diabetes and it causes increased plasma osmolarity due to extreme dehydration and concentration of the blood to help understand, remember that glucose is a polar molecule that cannot passively diffuse across cell membranes. which means that it acts as a solute so when levels of glucose are super high in the blood meaning; it's hyperosmolar; State water starts to leave the body cells and enter the blood vessels, leaving the cells were relatively dry, in travailed rather than plump and juicy blood vessels, that are full of water lead to increased urination and total body dehydration and this is a very serious situation because the dehydration of the body's cells and in particular the brain, can cause a number of symptoms including mental status changes. in HHS you can sometimes see mild ketonaemia and acidosis but not to the extent that it's seen in DKA and in DKA you can see some hyperosmolarity so there's definitely overlap between these two syndromes besides type 1 and type 2 diabetes, there are also a couple other subtypes of  diabetes mellitus;
 gestational diabetes is when pregnant women have increased blood glucose which is particularly during the third trimester, although ultimately unknown the cause is thought to be related to pregnancy hormones that  interfere with insulins action on insulin receptors also sometimes people can develop
 drug-induced diabetes is where medications have side effects that tend to increase blood glucose levels. The mechanism for both of these is thought to be related to insulin resistance. Like type 2 diabetes, rather than an autoimmune destruction process, like in type 1 diabetes, diagnosed type 1 or type 2 diabetes is done by getting a sense for how much glucose is floating around in the blood and has specific standards, that, the World Health Organization uses very commonly a fasting glucose test is taken, where the person doesn't eat or drink except the  water that's okay for a total of eight hours and then has their blood tested for glucose levels  of

100 milligrams per decilitre to 125 milligrams per decilitre indicated pre-diabetes
and 126 milligrams per deciliter or higher indicates diabetes non-fasting
a random glucose test can be done at any time with 200 milligrams per decilitre

or higher is a red flag for diabetes. Another test is called an oral glucose tolerance test, where a person given glucose and then blood samples are taken at time intervals to figure out how well it's being cleared from the blood glucose. The most important interval, being two hours later levels of 140 milligrams per decilitre to 199 milligrams per decilitre, indicate pre-diabetes and 200 or above indicate diabetes, another thing know is that when blood glucose levels get high the glucose can also stick to proteins that are floating around in the blood or in the cells, so that brings us to another type of test; that can be done, which is the hba1c test.  which tests for the proportion of haemoglobin in red blood cells,  that has glucose stuck to it called glycated haemoglobin. hba1c levels of 5.7%--6.4% indicate pure-diabetes
and 6.5 per cent or higher indicates diabetes. this proportion of glycated haemoglobin doesn't change day to day as it gives a sense for whether the blood glucose levels have been high, over the past two to three months finally we have the c-peptide test which tests for by-products of insulin production if the level of c-peptide is low or absent it
means the pancreas is no longer producing enough insulin and the glucose cannot enter the cells for type one diabetes.  Insulin is the only treatment option for type 2 diabetes.
On the other hand lifestyle changes like weight loss and exercise, along with a healthy DIET, and oral anti-diabetic medication like metformin in several other classes can sometimes be enough,  to reverse some of that insulin resistance and keep blood sugar levels in check however if oral anti-diabetic medications fail type 2 diabetes can also be treated with insulin.
Something to bear in mind is that insulin treatment comes with a risk of hypoglycaemia,  especially if insulin is taken without meal symptoms of hypoglycaemia can be mild like weakness hunger and shaking but they can progress to a loss of consciousness in seizures in severe cases in mild cases drinking juices or eating candy or sugar might be enough to bring blood sugar up but in severe cases, intravenous glucose should be given as soon as possible the FDA has also recently approve




intranasal glucagon as a treatment for severe hypoglycaemia all right now over time. High glucose levels can cause damage to tiny blood vessels while the  microvasculature in arterioles, a process called hyaline arteriolosclerosis is where the walls of the arterioles develop hyaline deposits which are deposits of proteins and these make them hard and inflexible in capillaries, the basement membrane can thicken and make it difficult for oxygen to easily move from the capillary to the tissues causing hypoxia, one of the most significant effects is that diabetes increases the risk of medium and large arterial wall damage and subsequent atherosclerosis which can




lead to heart attacks and strokes which are major causes of morbidity and mortality for patients with diabetes.
In the eyes diabetes can lead to retinopathy and evidence of that can be
seen on a fundoscopic exam; that shows cotton-wool spots or flare haemorrhages and can eventually cause blindness.
In the kidneys the Aferrant and Efferent arterioles, as well as the glomerulus itself, can get damaged which can lead to Nephrotic syndrome that slowly diminishes





the kidney's ability to filter blood over time they can also need dialysis,  which also affects the functions of the nerves, which will lead to decrease sensation in toes and fingers(stocking-glove distribution)

it also causes autonomous nervous system malfunction, that system controls many functions; like sweating and passing gas. Finally, both the poor blood supply and nerve damage can lead to ulcer




 especially in the feet, they don’t heal quickly and in severe needed to amputate.
This is very important that if Diagnose with diabetes, control it with a healthy lifestyle.
Medications to reduce insulin resistance
If needed insulin therapy, when beta cells have been exhausted
TYPE1 diabetes cannot be prevented
While TYPE2 diabetes can be prevented.
Many people with diabetes can control their blood diabetes very effectively. And they are full of life, without any complications.







                                                         





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