What is Diabetes? In a properly functioning organism, the pancreas is an exocrine organ (it produces pancreatic juice rich in digestive enzymes) and an endocrine organ, which produces mainly insulin and amyline as well as glucagon, somatostatin or pancreatic polypeptide. The main role of insulin is to lower blood glucose levels. This is due to the activation of a number of processes, including: increasing the transport of glucose to the inside of muscle, fat and liver cells, as well as inducing glycogenogenesis and triglyceride production in adipose tissue, and inhibits gluconeogenesis, glycolysis, lipolysis and proteolysis. It is worth noting that insulin regulates the metabolism of fats and carbohydrates. Pancreatic β-islet cells physiologically, pulsate, secrete insulin. Its greatest amounts are excreted in the morning and after a meal. In order to better understand the topic of the article, some basic points are explained.
An important concept inherent in diabetes is insulin resistance, it consists in the lack of an appropriate response of cells to the correct level of insulin, mainly muscles, liver and adipose tissue. In healthy patients in the liver, insulin should limit glucose production, but when insulin resistance is resistant, the liver inappropriately releases glucose into the bloodstream, causing hyperglycaemia. Insulin is an ANABOLIC hormone, i.e. it inhibits lipolysis and at the same time increases the deposition of free fatty acids in adipose tissue. Therefore, patients with insulin resistance have a much harder time losing weight.
Diabetes diagnosis – PARAMETERS
When analyzing venous blood glucose results, it is helpful to first explain the basic concepts that are crucial in interpreting the results:
random glucose – concentration of glucose in blood taken at any time of the day, regardless of the meal,
fasting glucose – blood concentration in the sample taken 8-14 hours after the last meal,
OGTT – Oral Glucose Load Test.
Normal fasting blood glucose: 70-99 mg / dL (3.9-5.6 mmol / L)
Hypoglycaemia – blood glucose <2.5 mmol / L (<45 mg / dL)
Fasting blood glucose abnormal: 100-125 mg / dL (5.6-6.9 mmol / L)
Diabetes mellitus – fasting blood glucose:> 126 mg / dL (> 7.0 mmol / L)
Types of diabetes
Diabetes mellitus is a chronic metabolic disease in which, as a result of insulin deficiency or defective insulin structure or tissue insensitivity to insulin, there is an increase in blood glucose (hyperglycemia), glucose secretion into the urine (glucosuria) and a disturbance in the metabolism of carbohydrates, lipids and proteins. Type 2 diabetes is much more common in patients with diabetes. There are the following types of diabetes:
Type 1 diabetes – It occurs in approximately 10% of diabetes cases. It usually affects young people. It is characterized by rapid, sudden development and a tendency to ketosis. The cause of hyperglycaemia is a lack of insulin production due to damage or destruction of the β-cells of the pancreatic islets by autoantibodies. For this reason, it is called insulin-dependent. In the absence of insulin, the body’s cells are forced to use other energy sources, such as proteins or fats, and as a consequence, they are intensively broken down, resulting in the formation of ketone bodies, which acidify the blood and cause the development of ketoacidosis and diabetic coma. The typical initial symptoms of type 1 diabetes are increased thirst (polydipsia), frequent urination (polyuria), bedwetting (nocturia), weight loss, acetone odor, purulent skin infections, urinary tract infections and poor wound healing.
The mainstay of type 1 diabetes therapy is the use of INSULIN. The exact types and rules of administration will be described in the next article.
Type 2 diabetes. It accounts for about 90% of all cases of diabetes. It is a heterogeneous process, it may result from many reasons related to insulin secretion disorders (e.g. transformation of proinsulin into insulin, pulsatile insulin release), target cell resistance to insulin (e.g. disorders of the structure or function of insulin receptors. Therefore, it is called non-insulin dependent). there is an abnormal reaction of tissues to insulin, ie insulin resistance. The disease progresses much slower than in type 1 diabetes and is not prone to ketosis. In 80% of T2D is associated with overweight, lack of physical activity. Unfortunately, it is very often diagnosed too late. because for many years our body is able to compensate for metabolic disorders and does not cause any symptoms. Early detection allows us to avoid a number of serious complications.
Diabetes treatment effectiveness is monitored not by measuring glycaemia but by measuring glycosylated hemoglobin. The goal of pharmacotherapy is to achieve a glycated hemoglobin concentration below 7%.
The basis for the prevention and treatment of type 2 diabetes at any stage is a diabetic diet, regular physical activity and maintaining a healthy body weight.
The drug of the first line is METFORMIN (Glucophage, Metformax, Siofor, Formetic), the dose of which is gradually increased. Medicines containing metformin or its combinations should be taken with or immediately after a meal. Metformin prolonged-release single-component tablets (Glucophage XR, Metformax SR) should be administered with the evening meal. The effects of metformin should be expected within a few days of starting treatment up to 2 weeks. If there are contraindications to its use, e.g. alcoholism, respiratory failure, failure of the organs of the brain and heart, then other groups of drugs are used:
– sulfonylurea derivatives: gliclazide (Diaprel MR), glimepiride (Amaryl, Glibetic, Symglic), glycidon, glipizide. Their mechanism of action is based on the increase in insulin secretion by the pancreas irrespective of the meal, which may contribute to the occurrence of hypoglycaemic events. Therefore, they were used only while maintaining the activity of the pancreas. These compounds have also been documented to stimulate weight gain.
– DPP-4 (gliptin) inhibitors: linagliptin (Trajenta), sitagliptin (Januvia, Ristaben, Janumet), vildagliptin (Galvus). They are used regardless of the meal. They only stimulate insulin secretion when blood glucose levels are elevated.
– phlosins – SGLT2 inhibitors: dapagliflozin (Xigduo), epagliflozin (Jardiance, Synjardy), ertugliflozin (Steglujon). They increase the elimination of glucose by the kidneys and thus reduce its concentration in the blood.
– thiazolidinediones (glitazones): pioglitazone. They increase the sensitivity of tissues to insulin. They should be used during a meal or between meals.
– α-glucosidase inhibitors: acarbose (Adeksa, Glucobay). Their mechanism of action is based on the inhibition of the breakdown of complex sugars into simple carbohydrates, which reduces the absorption of glucose from the gastrointestinal tract, which reduces the level of glucose in the blood after a meal.
If, despite the therapy, I am unable to obtain the appropriate therapeutic effect, I use a combination therapy consisting of 2 drugs or 3 with the addition of acarbose. Third-line pharmacotherapy includes simple insulin therapy.
In addition to the above-mentioned types of diabetes, there are many others, for example: LADA (autoimmune diabetes with slow intensity), MODY (caused by a mutation in the glucokinase gene) or gestational diabetes.
Diabetes is a very serious disease that affects more than 2 million Poles. It is called a disease of civilization for a reason. Untreated, it leads to serious complications that threaten our life. We should remember about systematic glycemic control and if we notice any disturbing symptoms, we should immediately consult professionals.
E. Mutschler, G. Geisslinger, H. K. Kroemer, P. Ruth, Mutschler Pharmacology and Toxicology.
A. Szczeklik, P. Gajewsk, Interna Szczeklik.
Pharmacodynamics, a textbook for Students of Pharmacy