Causes of Diabetes

Premise

Diabetes mellitus, or more simply diabetes, is a metabolic disease caused by alterations in insulin, a key hormone for maintaining normal blood glucose (sugar) levels.

There are different types of diabetes mellitus, some decidedly more common and known than others. The most common types include type 1 diabetes, type 2 diabetes and gestational diabetes; among the less common, however, are the so-called secondary diabetes and MODY diabetes.

The characteristic that all types of diabetes mellitus have in common is hyperglycemia, which is the high concentration of glucose in the blood.

Causes of diabetes

The causes of diabetes can be summarized in three points:

Low insulin availability. To understand: there is less insulin than the body would need for its proper functioning;
Prevention of normal insulin action. To understand: insulin is present, but the body cannot make good use of it;
Combination of the two factors mentioned above. To understand: there is little insulin in the body and it does not work properly.

In the next chapters of this article, the reader will find an accurate description of the causes of type 1 diabetes, type 2 diabetes and gestational diabetes.

Readers are reminded that producing insulin - the hormone around which diabetes mellitus revolves - are the beta cells of the islets of Langerhans of the pancreas .

Causes type 1 diabetes

Type 1 diabetes is an autoimmune disease . To cause it, in fact, is a malfunction of the immune system - that is, the organism's barrier against viruses, bacteria and other similar threats - which, recognizing as foreign the pancreatic beta cells of the islands of Langerhans, attacks them and destroys them.

Clearly, with the destruction of pancreatic beta cells in the islets of Langerhans, the insulin production system and the consequent insulin, which serves to regulate blood glucose levels, fail.

In short: the cause of type 1 diabetes is a reduced availability of insulin, due to the loss, by destruction, of the pancreatic cells responsible for the production of this hormone.

Based on their studies, doctors and subject matter experts believe that the onset of type 1 diabetes would depend on a combination of precise genetic factors, which give a certain predisposition to the development of the disease in question, and environmental factors, such as some viral infections or a certain dietary regime, which act as concretizing elements of the aforementioned predisposition.

Role of environmental factors on the appearance of type 1 diabetes

According to the most reliable theories, the genetic predisposition to type 1 diabetes would materialize in the real illness, at the moment in which the interested subject contracts a certain viral infection; in other words, subjects genetically predisposed to type 1 diabetes would develop the latter only after having contracted a certain viral disease.

Absurdly, always admitting that the theories in question are correct, if the contact between the genetically predisposed individual and the pathogenic agent triggering type 1 diabetes did not take place, the latter would not arise.

Details of how the immune system destroys the islands of Langerhans

In type 1 diabetes, abnormal antibodies, specifically called autoantibodies against pancreatic insula (" insula " means island), trigger the destructive process to damage the islets of Langerhans of the pancreas. In fact, in addition to attacking the pancreatic beta cells of the aforementioned Langerhans islands, these pancreatic insula autoantibodies act as activators of other "rebel" cells of the immune system, which complete the work of destruction.

What happens in type 1 diabetic?

In patients with type 1 diabetes, insulin production is drastically reduced, which in some cases can even be completely eliminated.

The only moment of the disease, in which it is still possible to observe satisfactory insulin secretion, is the initial phase, ie when type 1 diabetes appears.

The diagnostic confirmation of the presence of a certain secretory activity can arrive from the dosage in the blood of the so-called peptide C, an element constituting the insulin precursor.

Type 1 diabetes risk factors

In short, the risk factors for type 1 diabetes are:

A family history of type 1 diabetes;
Exposure to certain viruses;
Some dietary factors, such as the reduced intake of vitamin D or the early intake of cow's milk;
The origin from particular geographical areas, such as Sweden or Finland.

Causes type 2 diabetes

In type 2 diabetes, hyperglycemia may depend on two alterations: the unusual resistance of tissues to the action of insulin ( insulin resistance ) and the low production of insulin by pancreatic beta cells of the islets of Langerhans ( deficit of insulin secretion ).

These two alterations can act individually or, as happens in most circumstances, they tend to add up to one another; in any case, the final effect is always a condition of hyperglycemia.

It is interesting to point out to the reader that, in type 2 diabetes, the resistance of the tissues to the action of insulin involves an overstimulation of the Langerhans islands, which, however, are completely unprepared to fulfill even in a minimally satisfactory manner the demand for more insulin.

All this, in addition to decree the increase in blood sugar above normal values, also determines the sharp acceleration of the process of decline, which involves pancreatic cells destined for the production of insulin.

In short: the possible causes of type 2 diabetes are the insensitivity of the tissues to the action of insulin and the progressive decline, up to the complete loss, of the islands' own ability to produce insulin.

As in the case of type 1 diabetes, even in the case of type 2 diabetes, doctors and scientists believe that the condition in question (with all its peculiarities described above) depends on a combination of predisposing genetic factors and environmental factors.

The most important environmental factors include:

Obesity . The increase in body weight leads to an increase in the synthesis of triglycerides, which, being in excess, also accumulate in pancreatic cells. The accumulation of triglycerides in pancreatic cells decreases the function of the latter;
A sedentary lifestyle . Scientific studies have shown that exercise hinders the onset of type 2 diabetes;
Aging . Reliable medical research has shown that advanced age contributes to the manifestation of genetic defects that are the basis of type 2 diabetes;
A diet rich in simple sugars . Absorption of simple sugars requires a lot of insulin. Therefore, in a person prone to diabetes mellitus, taking too many simple sugars has the effect of depleting the already limited capacity for genetic reasons of the pancreatic beta cells to produce insulin.
Hypertension ;
HDL cholesterol levels (the so-called "good cholesterol") less than or equal to 35 mg / ml;
Triglyceride levels greater than or equal to 250 mg / ml.

Very often, in people with type 2 diabetes, the decline in insulin production by the Langerhans islands began about 10 years before the diagnosis of the aforementioned disease, a diagnosis that usually occurs when the function of pancreatic beta cells is reduced by 70%.

What happens in type 2 diabetic?

In the type 2 diabetes patient, it is possible to see a particular phenomenon, for which the production of insulin is normal or even increased, but, despite this, does not satisfy the needs of the person concerned.

Prolonged insulin deficiency in the patient leads, in the long run, to a further worsening of the decreased sensitivity of body tissues to the action of the hormone. In other words, in the patient with type 2 diabetes, there is a progressive worsening of insulin resistance.

Type 2 diabetes risk factors

Briefly, the risk factors for type 2 diabetes are:

Overweight and obesity;
A sedentary lifestyle;
A family history of type 2 diabetes;
Belonging to the black, Hispanic, Indian American and Asioamerican race;
Advanced age;
A past history of gestational diabetes;
The polycystic ovary;
Hypertension;
High triglyceride levels and low HDL cholesterol levels.

Causes of gestational diabetes

Exclusive of the female world, gestational diabetes is a possible consequence of the hormonal upheavals that characterize the state of pregnancy .

Going into more detail, the insulin resistance resulting from the action of some placental hormones (insulin resistance that is not adequately counteracted by increased insulin production by the pancreatic islets of Langerhans) may be the cause of gestational diabetes. ).

In other words, gestational diabetes arises when, faced with the insulin resistance condition imposed by some placental hormones, the pancreas is not able to respond with increased insulin production (increased insulin production which, instead, takes place in pregnant women without gestational diabetes).

Some interesting facts about gestational diabetes

According to some statistics, gestational diabetes would affect 4-8% of pregnant women.

Generally, it is a transient condition, which disappears at the end of pregnancy; more rarely, it is a condition that can turn into type 2 diabetes.

Risk factors of gestational diabetes

In summary, the risk factors of gestational diabetes are:

Age over 25;
A family history of type 2 diabetes;
Overweight or obesity before pregnancy;
Belonging to the black, Hispanic, Indian American and Asian countries.

Causes secondary diabetes

Secondary diabetes is that type of diabetes mellitus resulting from diseases or particular conditions that are not purely pathological, which counteract the secretion or action of insulin.

Among the diseases capable of causing secondary diabetes, include:

Endocrine diseases, such as Cushing's syndrome, acromegaly, thyrotoxicosis resulting from a state of hyperthyroidism, pheochromocytoma, glucagonoma, somatostatinoma and aldosteronoma. In such circumstances, hyperglycemia is dependent on the excessive production of hormones with counter-insular activity (or insulin-regulating hormones), such as cortisol, growth hormone, thyroid hormones or adrenaline.
Pancreatic diseases, such as cystic fibrosis, chronic pancreatitis and pancreatic cancer.
Genetic diseases, such as Wolfram syndrome, myotonic dystrophy, Friedreich's ataxia, hemochromatosis, Down syndrome, Klinefelter syndrome, Turner syndrome, Huntington's chorea, Prader-Willi syndrome, glycogen storage disease, etc.
Congenital lipodystrophy, a medical condition characterized by the almost total absence of adipose tissue and the consequent accumulation of fat in a vital organ such as the liver and muscles.
Acanthosis nigricans, a dermatosis characterized by hyperkeratosis and hyperpigmentation.
Infectious diseases, such as cytomegalovirus or coxsackievirus B.

As for the non-pathological conditions capable of inducing secondary diabetes, these include:

The constant intake of some specific drugs, including thiazide diuretics, corticosteroids, atypical antiepileptics and protease inhibitors.
Pancreaectomy, or total or partial surgical removal of the pancreas. Generally, this surgical operation is due to a serious pancreatic disease (eg, tumor).
Exposure to certain toxins or chemicals, such as phthalates or pesticides, and excessive air pollution.

Causes diabetes MODY

The wording " MODY diabetes " includes a series of forms of diabetes, the cause of which is the mutation of one of those genes fundamental for the correct production of insulin, by pancreatic beta cells of the islets of Langerhans.

Examples of monogenic diseases with dominant autosomal transmission, MODY forms of diabetes are characterized by moderate hyperglycemia and onset at a young age.

Curiosity: what does MODY mean?

The abbreviation MODY is the English acronym of Maturity Onset Diabetes of the Young, which in Italian could translate as "diabetes of young adulthood".

Pathophysiology

Before describing the pathophysiology of diabetes mellitus in general, some information on insulin is needed:

Insulin is the main hormone in the human body that regulates the passage of glucose from the blood to: the liver, muscles (except the smooth ones) and adipose tissues. This is the reason why insulin plays a central role in all types of diabetes mellitus.
For the human body, glucose is equivalent to fuel for a car.
In humans, the main sources of glucose are three: food absorbed in the intestine, the process of glycogenolysis (degradation of glycogen into glucose) and the process of gluconeogenesis (synthesis of glucose from non-glucose precursors, such as amino acids).
As anticipated, insulin plays a key role in regulating glucose levels in the human body. In fact, it is able to: inhibit the degradation of glycogen (ie glycogenolysis) or gluconeogenesis, stimulate the entry of glucose into adipose and muscle tissue and, finally, promote glycogen synthesis (ie the assembly of glycogen from glucose ).
Insulin secretion belongs to the beta cells of the islets of Langerhans, located in the pancreas.
The beta cells of the islets of Langerhans are activated, producing insulin, when blood glucose levels (blood sugar) increase.
Logically, the same pancreatic cells deactivate, temporarily ceasing to produce insulin, when the levels of glucose in the blood are decidedly poor; furthermore, in these circumstances, another hormone, glucagon, comes into play which acts in the opposite way to insulin, inducing the degradation of glycogen into glucose.
If the amount of insulin available is insufficient for the body's needs (deficiency of insulin secretion), and / or if the body's tissues respond poorly or do not respond at all to the action of insulin (insulin resistance) or, finally, if insulin is defective (due to a genetic defect) - all of these conditions, which can cause diabetes mellitus - lack the possibility of absorption of blood glucose by the liver, muscles and adipose tissue. The effect of the permanence of glucose in the blood is the rise beyond the normal level of blood glucose levels (hyperglycemia).

In all types of diabetes mellitus, blood sugar is elevated as fast, as and even more after meals .

When blood glucose is so high as to exceed the ability of the kidneys to eliminate it (180 mg / dl), glycosuria appears, that is glucose in the urine. If of considerable magnitude, the glycosuria determines the increase of the osmotic pressure of the urine and the inhibition of the reabsorption of water by the kidneys, with a consequent final increase in the production of urine ( polyuria ) and the loss of liquids with the latter .

The diabetic polyuria explains the simultaneous presence of polydipsia, that is the sensation of intense thirst.

In patients with diabetes, when blood glucose reaches very high concentrations, it can react and bind to certain proteins in the body, including hemoglobin . In the biological field, this process (non-enzymatic union between glucose and proteins) is called glycation .

Glycation significantly alters the biological functions of the proteins involved and, in the diabetes mellitus patient, appears to have a key role in the onset of typical long-term vascular complications, known as microangiopathy and macroangiopathy .