DIABETES, TYPE 1 AND TYPE 2 DIABETES MELLITUS.

  

DIABETES MELLITUS

Diabetes is the most widely recognised disease. Generally, when the body's hormonal capacity cannot process the sugar, it stays remaining in the blood, making harms the body's organs and the body's function. These hormones give rise to a significant increase in glucose in the blood. The cells need glucose as a source of energy to not allow the glucose to enter, which implies that the cells starve for survival, Despite having glucose right on their doorstep.

In general, the body system controls how much sugar gets into the cells with two hormones: INSULIN and GLUCAGON. Insulin is to reduce blood glucose levels, and Glucagon is utilised to build blood glucose levels. Clusters of cells produce these hormones in the pancreas, the gathering of cells called ISLETS OF LANGERHANS. Insulin is secret by beta cells in the centre of these islets, and Glucagon is secreted by alpha cells in the islets' periphery.

Insulin is the essential hormone to reduce the amount of glucose in the blood. It is embedded in the cell membrane of different insulin-responsive tissues by binding it to insulin receptors as insulin is secreted by beta cells in the centre of these islets.

Glucagon is released by alpha cells in the periphery of the islets and adipose tissue. When activated, the insulin receptors cause vesicles containing glucose transfers; these are inside the cell to fuse with the cell membrane. It permits glucose to transport into the cell. Glucagon does precisely the inverse, which raises the blood glucose levels by getting the liver to generate new molecules of glucose from other molecules and separate glycogen into GLUCOSE. Because of this destruction, the blood glucose level is increasing.

 TYPE 1 DIABETES AND TYPE 2 DIABETES MELLITUS, DIAGNOSIS

 

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

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

The main difference between type1 and type2 diabetes is the underlying mechanism. Approximately 10% of people with type1 diabetes and the remaining 90% of people have type2 diabetes.

 

Type1 Diabetes

 

In type1 diabetes, the body does not make enough insulin.  In type1 diabetes, there is a type of hypersensitivity response or a cell-mediated immune response, where the T cells of the patient attack the pancreas.

Note: (The immune system has T cells that react to all sorts of antigens, there are usually small peptides, polysaccharides or lipids, and some of these antigens are part of our body cells).  It does not make sense to allow T cells to attack our cells to hang around until this process eliminates them by body self-tolerance.

In type1 diabetes, it is a genetic abnormality, which causes a loss of self-tolerance among T cells. Specifically, target the beta-cell antigens. Losing self-tolerance means that these T cells allow recruiting other immune cells. They coordinate to attack these beta cells.

Losing beta cells mean less insulin, and less insulin means that glucose piles up in the blood because it cannot enter the body cells. An important group of genes regulating the immune response is the human leukocytes antigen system (HLA). The genes on chromosome6 encode the major histocompatibility complex (MHC).

This protein is essential in helping the immune system. It recognises the foreign body molecules, and maintaining self-tolerance (MHC) is like the serving platter that antigens are served to the immune cells on interesting people with type 1 diabetes, which often have specific HLA gene in common with each other. One is (HLA dr3), and the other is (HLA dr4). Not Everyone with HLA dr3 or HLA dr4 develops diabetes. In diabetes mellitus  type1, the destruction of beta cells usually starts early in life. Still, sometimes up to 90% of the beta cells are destroyed before symptoms crop up for clinical signs of uncontrolled diabetes. These are; Polyphagia, Glycosuria, Polyuria and Polydipsia.

 

Polyphagia, Glycosuria, Polyuria, Polydipsia

 

Let us go through them one by one, even though there is a lot of glucose in the blood. It cannot get into the cells, which leaves cells starved for energy. In response, the adipose tissue starts breaking up fat called lipolysis, and muscle tissue starts breaking down proteins, resulting in weight loss. For those with uncontrolled diabetes, this catabolic state leaves people feeling hungry, and a person eats a lot. These are known as polyphagia, ('poly' means a lot, 'phagia' means eating).

When the Blood glucose levels are very high, and the blood is filtered through the kidneys, some of the glucose starts to excrete into the urine. This process is called glycosuria (glycol suffix to glucose and urea is to urine). Since glucose is active in the blood, water tends to transfer, resulting in an increase in urination which is polyuria. ('Poly' means a lot, 'urea.' is urine) because of too much urination, diabetic patients become dehydrated and thirsty or have Polydipsia. ('Poly' means a lot, and 'dips' means thirst)

Diabetic patients cannot produce their insulin, and they can respond to insulin therapy which will become a 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 islets' periphery.

 

TYPE1 DIABETES KETOACIDOSIS (DKA)

 

One serious complication with Type1 diabetes is ketoacidosis (DKA). It is the process of lipolysis. In this process, the fat is broken down into free fatty acids. The liver turns these fatty acids into ketone bodies; that is, aceto-acetic acid turns into beta hydroxyl-butyrate acid, Aceto-acetic acid (is a ketoacid) has a ketone group in a carboxylic acid group. Betahydroxybutyric acid, on the other hand, is not a ketoacid since its ketone group has been reduced to a hydroxyl group. These ketone bodies are important because they are for cell energy, but they also increase the blood's acidity, called ketoacidosis.

The blood becoming acidic can have significant effects on the body. The individuals can develop KUSSMAUL respiration, which is deep and laboured breathing. The body tries to reduce carbon dioxide from the blood to reduce its acidity. The cells also have a transporter that exchanges its hydrogen ions or protons for potassium. When the blood gets acidic, it is by definition loaded with protons. These protons are sent into the cells while potassium is sent to the fluid outside the cells.

Another thing to keep in mind is that, in addition to helping glucose enter the cells, insulin stimulates the sodium-potassium ATPase-which helps potassium get into the cells. Without insulin, more potassium stays in the fluid outside the cells.

Both of these mechanisms lead to increased potassium in the fluid outside the cells, which quickly makes it into the blood and causes hyperkalaemia; over time, the blood potassium level remains high.

The body, which includes potassium inside the cells, starts to run low. Individuals will also have a high anion gap, reflecting a large difference in the unmeasured, negative, and positive ions in the serum, mainly due to ketoacid build-up. Diabetic ketoacidosis can occur even in people diagnosed with diabetes and who are having some insulin therapy.

During the state of stress, of an infection, the body releases epinephrine, which later stimulates the glucagon release. Too much Glucagon can tip the delicate hormonal balance of Glucagon and insulin to elevate blood sugars and lead to a cascade of events.

In type1 diabetes, the blood glucose levels are very high, and the increase in glucose excretion through the kidneys increases the secretion of glucose in the urine. The process of urination is frequent; and because of excessive water loss, the body becomes dehydrated. Therefore, it explains the need for alternative energy, and the generation of ketone bodies starts, and ketoacidosis will start. Interestingly both ketone bodies break down into acetone and escape as a gas by breathing out of the lungs, which gives a sweet fruity smell to a person's breath. Which also causes nausea and vomiting; if it becomes severe mental health status also changes, and acute cerebral oedema occurs.

TREATMENT OF DIABETES KETOACIDOSIS (DKA)

 

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 them help to reverse ketoacidosis.

 

TYPE2 DIABETES

 

In this type2 of diabetes, the body makes INSULIN, but the tissues do not respond to it; the exact reason the cells do not respond? The body provides the usual amount of insulin, but the cells do not move their glucose transporters to their membrane in response to glucose getting into the cells. These cells, therefore, have insulin resistance. Obesity and Hypertension are the contrary factors for insulin resistance diabetes.  Resulting in increased adipose tissues or the release of free fatty acids in the blood, Adipose-kinase, these signalling molecules, can cause inflammation in the patients.  However, in contrast, and the fact that many people who are obese do not have diabetes. Therefore, genetic factors probably play a significant role.

Type2 diabetes is entirely independently of other environmental risk factors. The tissues do not respond to normal levels of insulin. The body stops producing more insulin, getting the same effect, and moving glucose out of the blood; they do this through beta-cell- hyperplasia and an increased number of beta cells. Beta-cell hypertrophy grows in size. They pump out more insulin. It works for a while by keeping insulin levels higher than normal blood glucose levels, and normal glycaemia should be expected.

Now together with the insulin, beta cells also secrete islet amyloid polypeptide or amylin.  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. These beta cells' compensation is not sustainable; over time, beta cells are exhausted, become dysfunctional, and undergo hypotrophy. They become smaller in size, resulting in hypoplasia and die off, as beta cells are less due to insulin levels. They decrease glucose levels in the blood and start to increase glucose in the body. It also develops hyperglycaemia leading; however, some circulating insulin in type 2 diabetes from the beta cells are trying to compensate for the insulin resistance. It means that the insulin glucagon balances such as diabetic ketoacidosis do not usually develop.  A complication; hyperosmolar-hyperglycaemic state, or (HHS) is much more common in type2 diabetes than type1 diabetes. It causes increased plasma osmolality due to extreme dehydration and concentration of the blood.

Remember that glucose is a polar molecule that cannot passively diffuse across the cell membranes. It acts as a solute. Keeps the level of glucose very high in the blood and makes a hyperosmolar state. Water starts to leave the body cells and enter the blood vessels, leaving the cells relatively dry rather than plump and juicy blood vessels. These vessels are full of water, which leads to increased urination and total body dehydration, which is a dire situation, the dehydration of the body's cells and the brain. It can cause several symptoms, including mental state changes. In (HHS), you can sometimes see mild ketonaemia and acidosis. But not to the extent that it's seen in Diabetes-Keto-Acidosis and in (DKA) you can see some hyper-osmolality, so there's an overlap between these two syndromes besides type1 and type2 diabetes, there are also a couple other sub-types of diabetes.

PREGNANCY-INDUCED DIABETES

 

When pregnant women have increased blood glucose levels, mainly during the third trimester, the cause is unknown and thought to be related to pregnancy hormones that interfere with insulin receptors' action.

DRUG-INDUCED DIABETES

 

 People develop drug-induced diabetes. Sometimes medications have side effects, which tend to increase blood glucose levels. The mechanism for both of these is related to insulin resistance. To diagnose type1 or type2 diabetes by taking the blood samples to check the amount of blood glucose levels floating in the blood. They have their specific standards that the World Health Organization uses very commonly a fasting glucose test, where the person doesn't eat or drink except the water that is permissible for a total of eight hours  of fasting, and then their blood is tested for glucose levels resulting in;

One hundred milligrams to one hundred twenty-five milligrams per decilitre (100-125) mg indicate pre-diabetes.

One hundred twenty-six milligrams per deciliter or higher suggests diabetes non-fasting.

A random glucose test can be done at any time with 200 milligrams per decilitre. If this ratio is higher, it is a dangerous sign of diabetes.

Another test is; an oral glucose tolerance test, to test it give sugar orally and testing the blood at intervals to check how quickly random sugar clears from the blood. If the result is obtained between 140mg -199mg, it shows the state of pre-diabetes. The test result above 200mg confirms diabetes.  When blood glucose level gets higher, the glucose can also stick to proteins floating around in the blood or the cells, requiring another type of test; the Hba1c test.  This test is for the proportion of haemoglobin in red blood cells, and this glucose is stuck into red cells, called glycated haemoglobin. (Hba1c levels of 5.7%--6.4% indicate pure diabetes and 6.5percent or higher indicates diabetes). If this glycated haemoglobin does not change after a few days, then we have the C-peptide test tests for by-products of insulin production if the level of c-peptide is low or absent.

 The pancreas is no longer producing enough insulin, and the glucose cannot enter the cells for type1 diabetes.  Insulin is the only treatment option for type 2 diabetes.

In addition to this, the lifestyle changes like weight loss and exercise, along with a healthy diet and an oral anti-diabetic medication like metformin reverse some of that insulin resistance and keep blood sugar levels in check. However, if an oral anti-diabetic drug fails, insulin can also treat type2 diabetes.

Insulin treatments have some risk of hypoglycaemia, especially if insulin is taken without a meal. Hypoglycaemia symptoms can be occurring; these are mild weakness, hunger and shaking, but they can progress to a loss of consciousness in seizures in severe cases. Whereas in mild cases, drinking juices or eating candy or sugar might be enough to bring blood sugar up, intravenous glucose should give to the patient as soon as possible in severe cases.

The FDA has also recently approved intranasal Glucagon as a treatment for severe hypoglycaemia.  High glucose levels can cause damage to tiny blood vessels. While the microvasculature in the arterioles, it is a process called hyaline arteriolosclerosis.  Where the wall of the arterioles develops hyaline deposits, these are the protein deposits. These make them stiff and inflexible in capillaries; the basement membrane can thicken and make it difficult for oxygen to move from the vein to the tissues causing hypoxia. One of the most significant effects is that diabetes increases the risk of medium arterial and large arterial walls being damaged, and subsequent atherosclerosis can lead to heart attacks and strokes that are significant causes of morbidity and mortality for patients with diabetes.

In the eyes, diabetes can lead to retinopathy and evidence. You can see it on a fundoscopic exam; that shows cotton-wool spots or flare haemorrhages and can eventually cause blindness.

In the kidneys, the Afferent and Efferent arterioles and the glomerulus itself can be damaged. It can lead to Nephrotic syndrome which slowly diminishes the kidney's ability to filter blood over time. It leads to dialysis; it also affects the nerves' functions, which will lead to decreased sensation in toes and fingers (stocking-glove distribution). It also causes autonomous nervous system malfunction. This system controls many functions, like sweating and passing gas.  The insufficient blood supply and nerve damage can lead to ulcers, especially in the feet; they do not heal quickly and are severely needed to amputate. If diagnosed with diabetes, control it with a healthy lifestyle. Medications are to reduce insulin resistance. If needed, insulin therapy is useful when beta cells become exhausted. It is challenging to prevent TYPE1 diabetes, while TYPE2 diabetes is easy to avoid.