Diabetes

Diabetes Mellitus

Diabetes mellitus is a metabolic disorder characterised by hyperglycemia due to defects in the production or action of the insulin.
Diabetes mellitus occurs when the patient's Insulin is either absent, not present in high enough quantities for the boy's needs, or not used correctly by the body.  Insulin is a hormone that is produced by specialised cells (Beta cells) of the Pancreas. In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, an individual's blood glucose level rises. In response to this increase, the Pancreas normally releases more insulin into the bloodstream to to help glucose enter the cells of the body and lower blood glucose levels after a meal. When the blood glucose levels are lowered, less insulin is released from the Pancreas. In healthy individuals, this regulatory system helps to keep blood glucose levels in a tightly controlled range. However, in patients with diabetes, insulin secretion is abnormal, resulting in high levels of blood glucose (hyperglycemia) which must be treated.

According to the American Diabetes Association  the different cases of diabetes mellitus can be classified as:

Type 1 Diabetes 

It is also known as insulin-dependent diabetes mellitus. It can be due to an auto-immune response against the pancreatic beta cells preventing the production of insulin.  Many cases of Type 1 diabetes have non-identified etiology so they are considered to be idiopathic. This type of Diabetes is managed by the individual injecting themselves with insulin prior to eating a meal, the amount of insulin injected should be adjusted according to the sugar content of that particular meal. There are three different groups of insulin available to patients:

1. human insulin which is synthetically made to be a match to human insulin
2. analogue insulin which has a slightly altered molecular order
3. animal insulin which is not commonly used in modern medicine although some patients claim that his type of insulin makes them more aware of hypos or generally works better for them.

Within these 3 different groups there are six main types of insulin:

1. Rapid-acting analogues - can be injected before, with or after food as they have a peak action between 0 and 3 hours. These types of insulin only last long enough to work for the meal at which they were taken.
2. Long-acting analogues - these last for around 24 hours and as such tend to be taken once or twice a day to build up a level of background insulin. They can be taken without food as they do not have a peak action time.
3. Short-acting insulins -  these have a peak action of 2 to 6 hours but can last for 8 hours. They should be taken around half an hour before eating to deal with the ride in blood glucose that eating the meal will cause.
4. Medium- and long-acting insulins -  like long-acting analogues, these are taken once or twice a day to provide background insulin or can be taken in combination with short-acting insulins/rapid-acting analogues. Their peak activity is between four and 12 hours and can last up to 30 hours.
5. Mixed insulin – short-acting and medium-acting insulin combined.
6. Mixed analogue – rapid-acting analogue and medium-acting insulin combined 
   

Type 2 Diabetes 

It is also known as non-insulin dependent diabetes mellitus and is caused due to insulin no longer triggering its signalling cascade. Increasing obestiy in the world is making this type of diabetes increasingly common.

Type 2 Diabetes is prevalent in certain indigenous populations including the Pima Indians in the USA and Aborigines in Australia. This is thought to be due to several environmental factors such as the western diet and obesity but a "faulty gene" is also though to be contributory though has not yet been identified.

This type of diabetes is often managed through diet control but can be supplemented with the use of insulin or medication taken to lower blood glucose levels. One example of a drug which is commonly used is Metformin. This causes AMP kinase activation which in turn down-regulates mammalian target of rapamycin (mTOR) signalling pathway.

Other Specific Types of Diabetes 

• Genetic defects of the β-cell (e.g. insulin gene defects)
• Genetic defects in insulin action (e.g. insulin receptor mutations)
• Diseases of the exocrine pancreas (e.g. Cystic fibrosis)
• Endocrinopathies (e.g. Cushing syndrome)
• Drug-induced diabetes (e.g. glucocorticoids)
• Infections (e.g. congenital rubella)
• Genetic syndrom es associated with diabetes (e.g. Down's syndrome)
  

Gestational diabetes mellitus (GDM) 

It normally occurs during the 3rd trimester of pregnancy.
50 % of women who get GDM usually get Type 2 diabetes later on in life.

Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) 

In pateints with IGT there is a loss in insulin sensitivity leading to hyperinsulinism. It is an intermediate state where the glycemia is not high enough to be considered diabetes but being higher than the normal levels.

Diabetes Insipidus

Nephrogenic diabetes insipidus is caused by mutations in aquaporin 2. Usually AQP2 is trafficked to the cell membrane where it facilitates the reabsorption of water into the cell. In the diseased state the channels are retained inside the cell resulting in the inability to control the concentration of urine being produced .