Insulin Resistance - Symptoms, Causes, and Diagnosis

Insulin is a peptide hormone that is produced by the beta cells of the Langerhans islets of the pancreas. It is released into the bloodstream when the levels of glucose, free fatty acids, and amino acids in the blood rise. It promotes the absorption of glucose from the blood and the synthesis of fatty acids and glycogen (a form of glucose storage) in the liver. Insulin works as a typical hormone through cellular receptors that are present on most cells of the body. The largest number of receptors for insulin is found in fat cells, the liver, and striated muscles. Insulin is responsible for the proper distribution and utilization of energy-rich compounds. The transport of glucose into the cell is ensured by glucose transporters - GLUT, whose number on the cell depends on the level of insulin.

Insulin resistance is a condition in which tissues become less responsive to insulin, leading to an overproduction of this hormone by the body in an attempt to compensate for the excess glucose in the blood (hyperglycemia). This situation disrupts metabolic homeostasis and contributes to the development of many civilization diseases, such as type 2 diabetes. Insulin resistance has its roots in evolution, as it helped our ancestors survive in harsh conditions by conserving glucose resources. Unfortunately, in today's world, where we lead a different lifestyle than our ancestors, insulin resistance leads to many civilization diseases. This shows how insulin resistance cannot function in today's world. Insulin resistance is closely linked to obesity and metabolic syndrome, but it can also affect thin people.

There are three molecular mechanisms that lead to insulin resistance: pre-receptor, receptor, and post-receptor. The pre-receptor mechanism is caused by improper structure of insulin molecules, production of anti-insulin antibodies, increased insulin degradation or through the action of insulin resistance-promoting hormones. The receptor mechanism primarily results from a decrease in the number of insulin receptors on the surface of cells and/or changes in their structure. The post-receptor mechanism is associated with disturbances in intracellular signaling, e.g. through the attachment of insulin to the receptor. In case of the occurrence of any of the above-mentioned mechanisms, there are disturbances in the regulation of blood glucose levels, its storage, and increase of its level in the blood.

– impaired tolerance for glucose, – increased levels of lipids (total cholesterol, triglycerides), – high levels of uric acid in the blood, – hypertension, – abdominal obesity, – unexpected weight gain and difficulty losing it, – sudden attacks of hunger, – chronic fatigue, – difficulties maintaining focus.

Causative factors for insulin sensitivity include: metabolic syndrome, obesity (particularly in the abdominal area), hormonal disorders such as polycystic ovary syndrome (PCOS), thyroid disease, liver disease, excessive cortisol due to chronic stress, taking steroids or hormonal diseases, pregnancy, medications (e.g. glucosamine, progesterone, antiviral drugs, certain antibiotics), low level of physical activity, alcohol use and amino acid disorders, unhealthy diet, abdominal surgeries (e.g. bariatric), gut microbiome disorders, chronic inflammation and genetic predisposition. Cortisol has a significant impact on insulin production and the development of insulin sensitivity, it is a hormone produced by the adrenal cortex and helps the body in stressful situations. An excess of cortisol can result from chronic stress, taking steroids or hormonal diseases such as Cushing's disease or adrenal tumors. Cortisol affects carbohydrate metabolism in several ways: by disrupting glucose uptake in tissues, stimulating the release of glucose from glycogen in the liver, stimulating gluconeogenesis (the conversion of non-sugar compounds such as amino acids or lactic acid into glucose) and inhibiting insulin production. Chronic psychological stress is an independent factor in the development of insulin sensitivity and weight problems.

Due to the multidirectional effects of insulin on the body, insulin resistance affects the entire metabolism. Additionally, insulin resistance also affects progression in elevated beta cells. Disorders of the response of muscle and fat cells to insulin cause them to have a lower ability to consume glucose, resulting in hyperglycemia. Furthermore, in liver cells the inhibitory effect of insulin on glucogenogenesis is eliminated, which increases hyperglycemia. Moreover, insulin resistance forces the beta cells of the pancreas to secrete more insulin, resulting in an increased hormonal level. In this way, a vicious circle is created. Untreated insulin resistance can lead to the development of obesity, type 2 diabetes, circulatory diseases, non-alcoholic fatty liver disease, and metabolic syndrome. Insulin resistance is the main cause of type 2 diabetes and appears many years before its development. Fatty liver due to lipotoxicity leads to non-alcoholic fatty liver disease. The accumulation of fats can lead to the accumulation of fatty acids in internal organs and central obesity, which later also becomes a source of free fatty acids and drives the vicious circle. Insulin resistance accompanies many hormonal diseases due to the opposite effect of many hormones on insulin. An example is polycystic ovary syndrome (PCOS), where hyperinsulinemia and insulin resistance are important components of the pathomechanism that can lead to fertility disorders.

Several laboratory tests are used for the diagnosis of insulin unresponsiveness. The simplest method is the assessment of fasting blood glucose and insulin levels. Based on these two parameters, the following indicators can be calculated: HOMA (HOMA-IR, ang. homeostatic model assessment) is calculated according to the formula: fasting insulin concentration (mU/ml) × fasting glucose concentration (mmol/l) / 22.5 over 1 indicates insulin unresponsiveness, QUICKI (ang. quantitative insulin sensitivity index check) is therefore calculated on the basis: 1/ (log fasting insulin concentration (μU/ml) + log fasting glucose concentration (mmol/l)) below 0.34 indicates insulin unresponsiveness. The oral glucose tolerance test involves measuring glucose in the fasting state and after 120 minutes of ingesting 50 or 75 g of glucose. At the same time, it is possible to measure the insulin curve, i.e., simultaneous measurement of insulin levels, which provides a more complete clinical picture of the patient. The euglycemic clamp method is considered the „gold standard“ for assessing insulin unresponsiveness. The method involves intravenous administration of glucose and insulin to the patient, followed by measurement of glucose under conditions of hyperinsulinemia. Unfortunately, this method is time-consuming, expensive, and too burdensome for the patient, therefore, the previously mentioned methods are used in practice.

Insulin resistance can be treated pharmacologically with medications that increase tissue sensitivity to insulin, such as metformin, but it can reduce vitamin B12 levels, so it should be monitored in individuals taking this medicine. However, the most important aspect of treating insulin resistance is a change in lifestyle, including dietary therapy. If an insulin resistant individual is overweight, treatment should begin with weight loss. The diet for individuals with insulin resistance should focus on: – abstaining from alcohol, – consuming products with a low glycemic index to avoid sudden changes in glucose levels, – eating 4-5 meals per day at regular intervals and avoiding snacking between meals, – consuming fresh vegetables and prebiotic products (which promote the growth of beneficial gut bacteria), – supplementing probiotic bacterial strains that increase insulin sensitivity, such as Lactobacillus rhamnosus GG. Additionally, regular physical activity is also important, as it affects the insulin sensitivity of cells.

There are over fifty types of diet-related diseases. These ailments arise due to improper nutrition and insufficient physical activity. This means that they can be avoided by paying attention to a healthy lifestyle. The most common include type II diabetes, obesity, hypertension, tuberculosis, certain cancers, inflammatory bowel diseases, allergies. These diseases affect an ever-increasing number of people and also require a change in dietary habits. Diet is often the first step taken by professionals. It is important to eliminate the cause of the problem (by improving nutrition, introducing physical activity, caring for sleep hygiene, or reducing stress), sometimes in an early stage of the disease, e.g. diabetes, this is the only and sufficient therapeutic method. Unfortunately, in the case of a disease that has existed for a longer period of time, it may be insufficient. In this case, the diet is an excellent foundation for pharmacological therapy conducted by doctors. In the state of disease, the body's energy metabolism can vary depending on the disease. The body's needs in terms of individual nutrients can also change. When developing clinical diets, we take all these factors into account. We take into account diseases, constant treatment, doctor's recommendations, examination results, which allows us to better adapt the diet to the body's needs. Depending on the type of problem, we select the components of the diet, determine the energy balance, macronutrients, and micronutrients to satisfy the body's needs as much as possible. In clinical diets, we pay particular attention to the proper setting of macronutrients: proteins, fats, and carbohydrates. They can change depending on the health problem and require adjustments. The nutrition plan is based on easily available products with a low degree of processing, taking into account the seasonality of vegetables and fruits. We always take the client's preferences into account and have product substitutes available if needed. We are aware of the comfort of diet users, so we adapt the plans to their culinary possibilities, work hours, and time for meal preparation. A clinical diet is an excellent way to provide the body with energy and strength in the fight against disease. We create optimal conditions, deliver all necessary nutrients to the body, prevent deficiencies or balance existing ones, and improve digestive comfort.