Causes of diabetes and mechanisms of its development

Both men and women suffer from diabetes mellitus . In 5% of cases, diabetes occurs before the age of 10 years and lasts a lifetime. Over the past decade, the percentage of morbidity in individual countries has increased significantly from 1 to 2. An increase in the total number of patients with diabetes depends largely on the early detection of this disease by methods of active medical examination, as well as due to a decrease in mortality from a diabetic coma. 

Etiology and pathogenesis . The occurrence of diabetes is possible with surgical removal of the pancreas, which leads to absolute insulin deficiency.
A decrease in the functional activity of islet b-cells , Langerhans can occur after acute and chronic pancreatitis. Septic processes in the abdominal cavity, local hemorrhage in the pancreatic tissue, severe infections, viral diseases can contribute to the death of the insulin apparatus.  

The development of sclerotic changes in small vessels that provide nutrition and oxygen supply to the islets of Langerhans causes insulin deficiency in old age. The appearance of tumors , cysts in the pancreatic tissue can also contribute to the violation of carbohydrate metabolism. 
 

Poisoning with toxic substances , medicines, food poisoning can cause acute diabetes mellitus. Chronic hepatitis , cirrhosis of the liver, inflammatory process in the gallbladder lead to reactive pancreatitis and impaired hormonal function of the pancreas. 
 

Theoretically, it is possible to admit the development of diabetes due to excessive production of glucagon by a-cells of the islets of Langerhans. Glucagon helps increase blood sugar and enhances the process of glycogenolysis. The increase in blood glucagopa causes relative insulin deficiency. The occurrence of diabetes mellitus in animals with prolonged administration of glucagop (S. M. Leites) was experimentally confirmed. At the time of a stressful reaction (physical injuries of the skull, mental injuries) under the influence of the sympathetic-adrenal system and coitrinsular hormones, the inhibition of the function of the insular apparatus occurs.  
  

Diabetes mellitus can occur with excessive production of pituitary growth hormone. Growth hormone, acting on the b-lipoprotein complex as an inhibitor of the hexokinase reaction, causes a violation of carbohydrate metabolism. Under the influence of growth hormone, hyperplasia of the islet apparatus may occur, which is later replaced by the depletion of its functional activity. 
  

In severe forms of acromegaly , patients with pituitary diabetes mellitus develop in 15–20% of cases (E. Ya. Vasyukova, N. A. Shereshevsky, S. G. Genes, etc.). Severe insulin-resistant forms of diabetes mellitus are observed with gigantism in the stage of acromegaloidization, when STH excessly enters the bloodstream (G. S. Zefirova).  
  

The occurrence of diabetes mellitus during the period of intensive growth in adolescence and youth can be due to an increased amount of growth hormone in the blood (M. I. Balabolkin, Z. I. Levitskaya, G. S. Zefirova, etc.). 

In some hypothalamic-pituitary syndromes, an increase in ACHT production causes diabetes mellitus due to an increased release of glucocorticoids by the adrenal cortex. In Itsenko-Cushing’s disease, steroid diabetes occurs in 10-12% of cases (E. A. Vasyukova, V. A. Krakow, R. William).  

The occurrence of steroid diabetes is possible with the formation of a tumor of the adrenal cortex (corticosteroma) and with adenomatosis of both adrenal glands. Steroid diabetes mellitus can occur with prolonged therapy with drugs of hormones of the adrenal cortex or their synthetic analogues (cortisone, predisolone, etc.). 

The effect of glucocorticoids on carbohydrate metabolism is manifested by increased catabolic processes. Proteins in the process of metabolism partially go into carbohydrates. Strengthening glucoeogenesis, impaired phosphorylation processes lead to hyperglycemia (S. M. Leites, S. G. Genes).  

Excessive intake of the hormone of the adrenal medulla — adrenaline and norepinephrine — into the blood stream contributes to hyperglycemia. With pheochromocytoma (a tumor of the adrenal medulla), an increased release of adrenaline and norepinephrine causes an increased tone of the sympathetic nervous system, increased glycogenesis and suppression of the function of the insular drug.  

Diabetes mellitus is observed in patients with toxic goiter, with a severe form of thyrotoxicosis. The toxic effects of thyroid hormones on the liver, pancreas and excitation of the sympathetic-andrenal system disrupt carbohydrate metabolism. The utilization of glucose by tissues is disrupted, there is an intense breakdown of glycogen in the liver, muscles. Pa with thyrotoxicosis, diabetes mellitus is difficult and difficult to compensate for. 

With pathological changes in enzyme processes, insulin in the blood stream can be inactivated. So, under the influence of the enzyme insulinase in the liver, the insulin molecule is destroyed. Proteolytic enzymes, violating the integrity of the insulin molecule, inactivate it.  

In the presence of pathological immunological processes, insulin activity decreases and glucose is not utilized by cells. The protein hormone insulin is bound by antibodies. The complex structure of the molecule is disturbed and insulin deficiency is detected. So, the protein factor of the blood – sinalbumin, combining with the α-chain of the insulin molecule, violates the ability of insulin to introduce glucose through the cell membrane. There are works that speak of hereditary transmission of the protein factor Sinalbumin and to some extent explain the hereditary forms of diabetes.  
 

In allergic processes , when tissue pathological conditions occur, a change in blood proteins may reveal ipsulin deficiency. The use of antihistamines can enhance the effects of insulin. 

The occurrence of diabetes can be the result of an overload of carbohydrates and other foods. Overeating leads to a compensatory release of insulin, which subsequently causes depletion of the insular apparatus (S. M. Leites, S. G. Genes, Joslin). In obese patients, pathological changes in carbohydrate metabolism are often observed and, in some cases, latent (latent) diabetes mellitus can become explicit.  
 

A study of heredity has shown the possibility of diabetes in children in families in which parents or relatives have diabetes (S. G. Genes, E. I. Zuckerstein, Falta). In unfavorable situations in children with a defective insular apparatus, carbohydrate metabolism is disturbed.    

There are many cases of diabetes in twins. A. Grollman cites data according to which about 5% of the US population, being homozygous for the gene, are susceptible to diabetes and, therefore, are potential patients with diabetes.  

In the physiological processes of fat metabolism of the liver, a lipocaic substance is actively involved (S. M. Dargstet, S. M. Leites, etc.). In severe forms of diabetes mellitus, along with a lack of insulin, a lack of a lipocaic substance is observed, which enhances fatty liver infiltration and contributes to the occurrence of ketoacidosis. In severe cases of diabetes, there is not only a great need for insulin, but also a need for lipocaine. 
  

With extrapancreatic insular insufficiency, insulin resistance often occurs due to the destruction of endogenous insulin and the inactivation of insulin administered for therapeutic purposes. In the body, the destruction of the insulin molecule or its binding to antibodies occurs, which disrupts the processes of glucose utilization. With insulin resistance pituitary and steroid diabetes mellitus occurs. In allergic conditions, cases of insulin resistance have been described, when the need for insulin per day exceeded 200 units. With cirrhosis of the liver, insulin-resistant diabetes mellitus is observed. The need for insulin in some patients exceeds 1,000 to 3,000 units per day. The introduction of large doses of insulin does not reduce high hyperglycemia. The insulin administered is apparently inactivated.  

With total removal of the pancreas, it is sufficient to administer 40-60 units of insulin to compensate for diabetes. With insulin-resistant diabetes mellitus, in some cases huge doses of insulin are administered without effect. False insulin resistance occurs when an injection is injected into places where sclerosing of tissues is observed due to multiple injections and insulin is not absorbed.