Diabetes mellitus, or simply diabetes, is a chronic disease that occurs when the pancreas is no longer able to make insulin, or when the body cannot make good use of the insulin it produces. Insulin is a hormone made by the pancreas, that acts like a key to let glucosefrom the food we eat pass from the blood stream into the cells in the body to produce energy. All carbohydrate foods are broken down into glucose in the blood. Insulin helps glucose get into the cells.
Not being able to produce insulin or use it effectively leads to raised glucose levels in the blood (known as hyperglycaemia). Over the long-term high glucose levels are associated with damage to the body and failure of various organs and tissues.
Diabetes, often referred to by doctors as diabetes mellitus, describes a group of metabolic diseases in which the person has high blood glucose (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both. Patients with high blood sugar will typically experience polyuria (frequent urination), they will become increasingly thirsty (polydipsia) and hungry (polyphagia).
Common symptoms of diabetes
The most common signs and symptoms of diabetes are:
Frequent urination
Have you been going to the bathroom to urinate more often recently? Do you notice that you spend most of the day going to the toilet? When there is too much glucose (sugar) in your blood you will urinate more often.
If your insulin is ineffective, or not there at all, your kidneys cannot filter the glucose back into the blood. The kidneys will take water from your blood in order to dilute the glucose - which in turn fills up your bladder.
Disproportionate thirst
If you are urinating more than usual, you will need to replace that lost liquid. You will be drinking more than usual. Have you been drinking more than usual lately?
Intense hunger
As the insulin in your blood is not working properly, or is not there at all, and your cells are not getting their energy, your body may react by trying to find more energy - food. You will become hungry.
Weight gain
This might be the result of the above symptom (intense hunger).
Unusual weight loss
This is more common among people with Diabetes Type 1. As your body is not making insulin it will seek out another energy source (the cells aren't getting glucose). Muscle tissue and fat will be broken down for energy. As Type 1 is of a more sudden onset and Type 2 is much more gradual, weight loss is more noticeable with Type 1.
Increased fatigue
If your insulin is not working properly, or is not there at all, glucose will not be entering your cells and providing them with energy. This will make you feel tired and listless.
Irritability
Irritability can be due to your lack of energy.
Blurred vision
This can be caused by tissue being pulled from your eye lenses. This affects your eyes' ability to focus. With proper treatment this can be treated. There are severe cases where blindness or prolonged vision problems can occur.
Cuts and bruises don't heal properly or quickly
Do you find cuts and bruises take a much longer time than usual to heal? When there is more sugar (glucose) in your body, its ability to heal can be undermined.
More skin and/or yeast infections
When there is more sugar in your body, its ability to recover from infections is affected. Women with diabetes find it especially difficult to recover from bladder and vaginal infections.
Itchy skin
A feeling of itchiness on your skin is sometimes a symptom of diabetes.
Gums are red and/or swollen - Gums pull away from teeth
If your gums are tender, red and/or swollen this could be a sign of diabetes. Your teeth could become loose as the gums pull away from them.
Frequent gum disease/infection
As well as the previous gum symptoms, you may experience more frequent gum disease and/or gum infections.
Sexual dysfunction among men
If you are over 50 and experience frequent or constant sexual dysfunction (erectile dysfunction), it could be a symptom of diabetes.
Treatment for Diabetes
Numbness or tingling, especially in your feet and hands
If there is too much sugar in your body your nerves could become damaged, as could the tiny blood vessels that feed those nerves. You may experience tingling and/or numbness in your hands and feet.
Oral diabetes drugs are usually reserved for use only after lifestyle measures have been unsuccessful in lowering glucose levels to the target of an HbA1c below 7.0%, achieved through an average glucose reading of around 8.3-8.9 mmol/L (around 150-160 mg/dL).
The lifestyle measures that are critical to type 2 diabetes management are diet and exercise, and these remain an important part of treatment when pills are added.
People with type 1 diabetes cannot use oral pills for treatment, and must instead take insulin.
How do oral drugs lower glucose levels?
Metformin is the most widely used oral antihyperglycemic drug and reduces the amount of glucose released by the liver into the bloodstream.
Oral antihyperglycemic drugs have three modes of action to reduce blood glucose levels:3
- Secretagogues enhance insulin secretion by the pancreas
- Sensitizers increase the sensitivity of the peripheral tissues to insulin
- Inhibitors impair gastrointestinal absorption of glucose.
Each class of antihyperglycemic drug has a different adverse event or safety profile, and side effects are the main consideration when it comes to choosing a medication.
Possible side effects range from weight gain, through gastrointestinal ones such as diarrhea, to pancreatitis and more serious problems. Hypoglycemia is also a possible adverse event.2
What oral drugs are available for type 2 diabetes?
No one particular choice of oral hypoglycemic is considered the most effective form of treatment - the decision over which drug to use is instead based on:
- Consideration of the adverse side effects
- Convenience and overall tolerability
- Personal preference.
In reality, weighing up each drug is something to do in partnership with a prescriber - guidelines partly drawn up by the American Diabetes Association list a great number of advantages and disadvantages for each of the available drug treatments, including the consideration of cost.2
The use of a single drug can be escalated to combination therapy with a second drug in an effort to improve glycemic control.1,2
Metformin is usually the first treatment offered, however, and it is the most widely used oral antihyperglycemic. Metformin is a sensitizer in the class known as biguanides; it works by reducing the amount of glucose released by the liver into the bloodstream and increasing cellular response to insulin. A metformin pill is usually taken twice a day.
This drug is a low-cost antihyperglycemic with mild side effects that can include diarrhea and abdominal cramping. Metformin is not associated with weight gain or hypoglycemia.
Sulphonylureas are secretagogues that increase pancreatic insulin secretion. There are several drug names in this class
- Chlorpropamide
- Glimepiride
- Glipizide
- Glyburide
Again, the choice of drug is an individual one. In the case of sulphonylureas, the choice depends on daily dosing and the level of side effects. These drugs are associated with weight gain and hypoglycemia.
Glitazones (also known as thiazolidinediones) are sensitizers - they increase the effect of insulin in the muscle and fat and reduce glucose production by the liver.
Two glitazones are available: pioglitazone and rosiglitazone. These drugs can have the side effects of weight gain or swelling and are associated with increased risks of heart disease and stroke, bladder cancer and fractures.
In the UK, rosiglitazone was withdrawn from the market over concerns about adverse events.4 In 2015, it remains available in the US, with information on its safety provided by the US Food and Drug Administration (FDA).
Alpha-glucosidase inhibitors are intestinal enzyme inhibitors that block the breakdown of carbohydrates into glucose, reducing the amount absorbed in the gut.
Available as acarbose and miglitol, they are not usually tried as first-line drugs because of common side effects of flatulence, diarrhea and bloating, although these may reduce over time.
Dipeptidy peptidase-4 (DPP4) inhibitors include alogliptin, linagliptin, saxagliptin and sitagliptin.
Also known as gliptins, DPP4 inhibitors have a number of effects, including stimulating pancreatic insulin (by preventing the breakdown of the hormone GLP-1). They may also help with weight loss through an effect on appetite.
These drugs do not increase the risk of hypoglycemia. Mild possible side effects are nausea and vomiting.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors include canagliflozin and dapagliflozin. They work by inhibiting the reabsorption of glucose in the kidneys, causing glucose to be excreted in the urine (glycosuria).
SGLT2s may also cause modest weight loss. Side effects include urinary infection.
Meglitinides include repaglinide and nateglinide. They stimulate the release of insulin by the pancreas. Meglitinides are associated with a higher chance of hypoglycemia and must be taken with meals three times a day. As a result, these drugs are less commonly used.
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