Dr Aidin Rawshani

What is reduced insulin sensitivity (insulin resistance)?

Contents

Insulin Resistance — about reduced insulin sensitivity, causes, complications and treatment

What is insulin?

Insulin is essential for life. It is a hormone that is important for metabolism. Knowing what insulin is, how it works and how it affects your body is important for your health.

Right next to the stomach is an organ called pancreatic (pancreas), where the hormone insulin is produced, which is then released from a unique cell type. The hormone insulin is produced by specialized cells in the body called beta cells.

These cells are scattered in small pancreatic “islets” called Langerhans islets where they occur together with 4 other interesting cell types. According to research, there are 5 types of cells in the Langerhans cell islets and they are called beta, alpha, delta, epsilon and PP cells.

Cells in the Langerhans Islands:

Cell typeProportion of Langerhans cell islesHormones that are secreted
Alfa-cell20 %Glucagone
Beta-cell70 %Insulin
Delta-cell < 10 %Somatostatin
Epsilon-cell< 1%Ghrelin
PP-cell (gamma)< 5%Pancreatic polypetide

The release of the hormone insulin depends on the levels of blood sugar and also the second hormone. In a healthy individual, insulin release is regulated very carefully so that the body balances its blood sugar.

What does insulin do?

Insulin is a hormone that allows the body’s skeletal muscles, adipose tissue and liver to absorb the sugar contained in the blood. Sugar (glucose) acts as energy for the cells or it can be converted into blood lipids when needed.

Insulin is a hormone that affects other important processes in addition to blood sugar metabolism, such as the breakdown of fat and protein. Insulin secretion is also stimulated to some extent by the amino acid concentration in the blood. Studies show that insulin is released precisely in conjunction or perhaps even shortly before food intake.

How is inuslin released:

Insulin is released in two different phases. The first phase is rapid and is easily triggered by rising blood sugar levels, insulin release lasts about 10 minutes. The second phase is more persistent, slow release that does not depend on glucose levels, the type of release lasts for hours.

The beta cell is called a “thermostat” because it records the levels of blood sugar in the body by absorbing sugar (glucose) from the blood. This is absorbed and converted into energy, as the energy levels rise in the beta cell, two substances accumulate, potassium and calcium. When these substances reach a certain level in the cell, insulin is released in response because this indicates high energy levels in the body.

Insulin release from our beta cells is also affected by insulin resistance. The beta cell becomes worse at recording what blood sugar levels are and therefore cannot balance insulin release.

What does glucagon do?

Glucagon is released from the alpha cell in the Langerhans cell corners and its purpose is to increase blood sugar levels as well as fatty acid levels. Glucagon is called a catabolic hormone and has the opposite effect to insulin because it raises blood sugar levels.

Glucagon stimulates the liver to convert glycogen to glucose. Glucagon thus potentiates gluconeogenesis and glycogenesis. Glucagon also regulates blood sugar production through a process called lipolysis in medical language.

How is glucagon released:

Low blood sugar levels lead to the release of glucagon (hypoglycemia). A variant of adrenaline (epinephrine) stimulates to the release, amino acids and some other hormones from the gastrointestinal tract. What other hormones regulate the release of glucagon.

In addition to insulin and glucagon, another hormone is released from the Langerhans cell corners called somatostatin – the hormone somatostatin slows the release of glucagon.

What does somatostatin, ghrelin and pancreatic polypeptide do?

Somastatin is released from the delta cell and its task is to reduce the release of insulin and glucagon. Ghrelin is a satiety hormone because it leads to hunger when it is released, when your body wants to raise blood sugar levels, it can make you hungry because after food intake the levels of blood sugar rise. The release of panreatic polypeptide leads to a decrease in gastric emptying and the secretion of gastric juice.

I bukspottkorteln (pankreas) finns små enheter som kallas Langerhans öar. Dessa öar består av grupper av celler, varav en cell kallas "beta cell". Beta-cellerna tillverka insulin som de frisätter till blodet. Frisättningen av insulin är särskilt uttalad i samband med en måltid. När insulin kommer ut i kroppen så påverkar det framförallt muskler, fett och lever. Dessa tre organ stimuleras av insulin så att de tar upp socker (glukos) som finns i blodet.
In the pancreas (pancreas) there are small units called the islets of Langerhans. These islands consist of groups of cells, one of which is called “beta cell”. The beta cells produce insulin that they release into the blood. The release of insulin is especially pronounced in conjunction with a meal. When insulin enters the body, it affects mainly muscles, fat and liver. These three organs are stimulated by insulin so that they absorb sugar (glucose) that is in the blood.

What is reduced insulin sensitivity (insulin resistance)?

A fundamental disorder in people with type 2 diabetes is insulin resistance. This condition means that the body’s cells react less to insulin and this leads to reduced absorption of sugar from the blood (glucose).

Almost 90% of all patients with type 2 diabetes exhibit insulin resistance and usually this condition precedes type 2 diabetes in time. Insulin resistance is seen in both prediabetes, impaired glucose tolerance, obesity, overweight and metabolic syndrome.

At the molecular level, this condition entails multiple pathological changes. The insulin receptor is a receptor that is found in several of the body’s different cells and it appears that the receptor and its subunits are impaired, in addition, changes occur inside the cell that make them less sensitive to insulin. Thus, higher concentrations of insulin in the blood are required to cause normal biological reactions, over time the insulin sensitivity becomes worse and the reserves of the hormone insulin run out in the pancreas.

What characterizes insulin resistance?

In particular, there are three important criteria for an individual to be considered to suffer from insulin resistance.

1. Elevated levels of a particular type of blood lipid

Free fatty acids usually lead to other disorders in the blood lipid picture, with lower levels of “good” blood fats (HDL cholesterol) and elevated levels of triglycerides bound to higher risk of cardiovascular diseases. Overall, the levels of different blood lipids increase in people with insulin resistance.

An interesting hypothesis is that elevated levels of free fatty acids cause poisoning (lipotoxocot) in the beta cell which is likely to impair production and contribute further impaired blood sugar metabolism.

2. Elevated blood sugar levels

A classic finding in people with insulin resistance is that they have elevated blood sugar levels (hyperglycaemia). This leads to an increased risk of diabetes-related complications.

3. Elevated levels of insulin in the blood

To compensate for the reduced insulin sensitivity in the body’s tissues, pancreatic release more insulin, this eventually leads to reduced release of the hormone because the reserves run out, the hormone cannot be produced forever because the beta cells have poor regeneration capacity. Some also suggest that elevated insulin levels have negative effects on blood vessels.

How to diagnose insulin resistance?

  • Fasting insulin levels in the blood
  • Glucose load test (OGTT) that involves recording blood sugar during fasting and then 2h after sugar intake (75 mg)
  • Gold standard method is a method called “hyperinsulinemic euglycemic clamp”
  • Two other known methods are the calculation of something called HOMA- IR and HOMA-BETA

HOMA är ett begrepp för en formel som beräknar antingen insulinresistens ute i kroppens vävnader alternativt graden av dysfunktion i beta-cellerna.

Symptoms and clinical findings

  • Individuals with reduced insulin sensitivity are usually overweight or have palpable central abdominal obesity.
  • Often high blood pressure or lipid disorders.
  • Poor blood sugar metabolism (obesity, prediabetes, impaired glucose tolerance) Most often, there are no obvious symptom.
  • Prolonged fatigue, Individuals with established cardiovascular diseasesSome research studies show that the blood has a greater tendency to clotting (coagulating) in people with insulin resistance.
  • Heredity for type 2 diabetes.
  • Over the age of 45 is a risk factor.
  • Metabolic syndrome — high blood lipids (LDL-C), low levels of good Blood fats (HDL-C), increased triglycerides, high blood pressure, central abdominal obesity with or without cardiovascular disease
  • Polycystic ovary syndrome (PCOS)
  • Increased corticosteroids (Cortisone therapy, Cushing’s syndrome)
  • Increased urination

Supplementary blood tests for the investigation of reduced insulin sensitivity

  • A blood test called C-peptide, fasting blood sugar (FP-glucose), long-term blood sugar (HbA1c)
  • Blood lipids, kidney function, blood pressure and smoking habits.
  • Symptoms or signs such as established cardiovascular disease

Important causes of the development of insulin resistance

  • Sedentary lifestyle
  • Diet
  • Genetics
  • Environment

Insulin resistance in turn leads to obesity through several different ways, such as inflammation.

How to treat reduced insulin sensitivity (insulin resistance)?

Lifestyle changes

Increased exercise and improved diet are a central cornerstone in the treatment of insulin resistance. This forms the basis in any treatment of the condition. This can slow both the development of insulin resistance and type 2 diabetes.

Drugs for reduced insulin sensitivity

Metformin is considered to improve insulin resistance by about 20%. The effect is mainly due to reduced sugar production from the liver. The treatment is well suited for obese people with or without type 2 diabetes. Many do not tolerate metformin due to gastrointestinal side effects. The risk of side effects is reduced if the dose is increased with a long time.

Glitazones have been shown to reduce fat levels in the liver, which is likely to reduce insulin resistance in the body, some in the state of insulin resistance is that the liver’s ability to sense blood levels is impaired, called hepatic insulin resistance (liver insulin resistance). The medicine binds to a receptor inside the cell nuclei, which then activates a gene that is involved in the sugar and blood fat metabolism. Different cells of the body become better at absorbing sugar.

Other treatment

A multifactorial risk factor control is the best for people with metabolic disorders.

  • Blood pressure should be in the range of 135 in systolic and 80 in diastolic (135/80).
  • Treat high blood lipids with blood-lowering therapy (statins) with a target level of 2.5 mmol/L for LDL.
  • Protect the kidneys with good antihypertensive therapy (ACE inhibitors or ARBs).
  • It remains a discussion if anti-coagulant medication should be used as primary prophylaxis for patients with type 2 diabetes.
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