A chronic disease caused by absolute or relative insulin deficiency and accompanied by metabolic disorders, hyperglycemia and glycosuria.

Diabetes mellitus (DM), caused by absolute insulin deficiency, is called Insulin-dependent diabetes mellitus (IDD) or Diabetes mellitus type 1 (DM1).

Diabetes mellitus associated with insulin resistance is called Insulin-independent diabetes mellitus (IND) or type 2 diabetes mellitus (T2DM).

Dogs are ill with diabetes, less often cats, horses, pigs and other monogastric animals.

Insulin-dependent diabetes mellitus occurs in 75% of cases, one quarter is insulin-independent type of diabetes. In dogs and other animals, the differences between IDD and IND are often erased. Both types of diabetes usually require insulin therapy and have a tendency to ketoacidosis. In addition to these forms, diabetes has a syndrome of the so-called renal nephrogenic diabetes, there is physiological or feed glucosuria, caused by eating a large number of sugary foods. There is stressful hyperglycemia, pregnancy diabetes.

In animals with a multi-chamber stomach, the occurrence of diabetes mellitus is highly doubtful, although there is information about this in foreign literature. In particular, signs of diabetes mellitus in cows and gobies with inflammatory lymphocytic infiltration of Langerhans cells were observed. In cattle, often symptomatic renal glucosuria is observed, due to mycotoxic kidney damage and stress.

In addition to primary diabetes mellitus type 1 and 2, secondary hyperglycemia is possible as one of the signs of diseases of the pancreas, adrenal glands and other organs (glucogonoma, somatostatinoma, pancreatic cancer, etc.).

Etiology

Diabetes mellitus is a polyetiological, polymorbid disease. At the basis of the occurrence of the disease are two main etiological factors - genetic predisposition and adverse effects on the body environment. However, even with the presence of a genetically programmed basis of diabetes mellitus 1, the manifestation of the disease is possible only with the additional effect on this organism of certain exogenous factors. To date, more than 18 loci have been identified in the human genome (the area of ​​localization of a certain genetic element on the chromosome) associated with the risk of developing T1DM.

The provoking of the development of diabetes occurs under the influence of physical, biological and other factors that have an adverse effect on the maternal organism or in the postnatal period of development and growth.

Toxins of pathogenic fungi, viruses, poor-quality food and other causes that lead to metabolic disorders and the accumulation of peroxides in the body are of particular danger.

Type II diabetes mellitus is characterized by the detectability of the disease from generation to generation, which is characteristic of the dominant or autosomal dominant mode of inheritance.

Type II diabetes mellitus is mainly due to a defect in the insulin receptor genes, manifested in a decrease in the sensitivity of insulin receptors to peripheral tissues. The main precipitating factor in this case is obesity. The disease is more common in animals that are unevenly and abundantly fed, kept in room conditions, not walking enough, left for a long time alone. In obesity, insulin resistance is manifested in a decrease in the sensitivity of insulin to tissue, in particular, to fat, muscle, and liver. Insulin sensitivity in obese animals is significantly lower than in animals with optimal body weight. A chronically pronounced decrease in insulin sensitivity leads, at the beginning, to a compensatory increase in insulin synthesis, and then to depletion of pancreatic B cells, and therefore to type II diabetes. Contributing factors of diabetes mellitus type I and II can be long-term use of glucocorticoids, androgens, chlorpromazine, thyroid hormones, autoimmune disorders in autoimmune thyroiditis, diffuse toxic goiter (they find antibodies to pancreatic islet antigens). It has been reported that the content of animals (rats) on a diet without vitamin A leads to a significant increase in blood sugar levels.

Pathogenesis

In diabetes mellitus type I, due to insufficient synthesis of insulin, glucose utilization is reduced, its penetration into the cell is hampered, an increase in blood glucose (hyperglycemia) occurs.

It is known that glucose is one of the natural sources of free radicals. With normal glycemia, there are few of them and they do not have an adverse effect on the body, but with a pathologically elevated glucose concentration in the blood, there are many free radicals in the blood, toxemia appears.

In the pathogenesis of type II diabetes, the main importance is attached to a defect in the receptor genes, manifested by a decrease in the sensitivity of insulin receptors of peripheral tissues to the action of insulin. The permeability of cell membranes to glucose decreases, and the activity of glucose transporter proteins decreases.

As with type 1 diabetes, so with type 2 diabetes, cells lack energy, amino acids and other substances. Under these conditions, hyperglycemic hormones - glucogon, adrenaline, glucocorticoids are involved in the pathological process. Under the influence of glucogon and adrenaline, the breakdown of glycogen is accelerated, gluconeogenesis increases, and the sensitivity of cells to insulin decreases. Enhanced gluconeogenesis is accompanied by the accumulation in the body of acetyl-CoA, ketone bodies, which have a negative effect on the central nervous system, endocrine organs, liver, kidneys, heart, etc.

With severe disease, especially with insulin-dependent diabetes mellitus, ketoacidosis, diabetic coma develops.

In diabetes affects the vessels, cells and tissues of various organs. The development of vascular pathology is associated with hyperglycemia with glucose toxicity. Diabetes mellitus is accompanied by progressive myocardiodystrophy, nephropathy, polyneuropathy, cataracts, and other complications.

High concentration of blood sugar and extracellular fluid leads to cell dehydration (osmosis), dry skin and mucous membranes, increased thirst, increased diuresis.

The increase in blood glucose is higher than the renal threshold, i.e. 9.5-10 mmol / l (170-180 mg%) in humans or more than 120 mg, 100 ml in dogs and cats, glucose enters the urine, and glucosuria develops.

Symptoms

The latent period of the disease occurs without marked clinical signs of the disease. EDS is more common in young animals, IND - in adults (in dogs 4-14 years old). The emaciation (cachexia) is characteristic more often of IDD, the preceding obesity - IND. During a clinical examination pay attention to the condition of the liver (hepatosis), eyes (cataract), pancreas (pancreatitis), heart (myol-cardiodystrophy) and other organs. Diabetes mellitus has a characteristic clinical symptoms with severe hyperglycemia and glucosuria. The mild form of the disease is accompanied by a moderate increase in blood sugar and its detection in the urine in low concentrations. The content of glucose in whole blood taken from sick dogs, pigs, horses on an empty stomach exceeds 95-120 mg% (5.25-6.6 mmol / l). Acetone bodies in the urine in the mild form of the disease are not detected by qualitative samples. Appetite is preserved, there is weakness, dry mucous membranes, a little thirst. With a severe form of the disease in an animal with a good appetite, an emaciation is established, especially in EDS, fatigue, sweating, dry skin and mucous membranes, strong thirst (polydipsia), frequent urination with an increase in the amount of urine by a factor of 2-3 and more. Often find bilateral cataract, weakening of vision and even blindness.

Furunculosis, eczema, necrosis of the tip of the tail, signs of myocardial dystrophy, fatty hepatosis, damage to the joints, etc. are observed. Severe hyperglycemia and glycosuria are characteristic of this form of diabetes mellitus.

Blood glucose reaches 200-300 mg% (12.2-16.65 mmol / l) and higher, in urine in horses -3-8%, in dogs -4-10%, in pigs - up to 6%. Relative density urine is 1,040-1,060, in the urine find a high concentration of acetone bodies (ketonuria). The smell of urine is sweetish, reminiscent of the smell of fruit and acetone. Along with hyperglycemia, glycosuria in severe forms of the disease establish a reduction in the reserve alkalinity of blood, an increase in the concentration of ketone bodies in the blood, and pH in the urine, and protein often appears due to kidney damage.

It is believed that healthy dogs have a fasting sugar level of 0.8-1.2 g / l; if it exceeds 2 g / l, it is developed diabetes. If the blood glucose level is in the range of 1.2-1.8 g / l, additional research is necessary. In the blood, urea, liver enzymes, pancreatic enzymes, cholesterol are determined. Conduct specific biochemical studies: plasma insulin, glycosylated hemoglobin, test for determining glucose tolerance.

Late diabetes mellitus is manifested by signs of polymarbidity (damage to the adrenal glands, thyroid and other endocrine glands), diabetic neuropathy, pathology of the organs of sight, skin, kidneys, heart, liver, etc.

Diabetic neuropathy includes damage to the posterior roots of the spinal cord (ataxia), damage to individual peripheral nerves (paresis, loss of reflexes).

Pathology of the organs of vision up to blindness is very common in all types of diabetes. The retina, iris, cornea, etc. are affected. A cataract develops, less frequently glaucoma.

In patients with diabetes mellitus, dermatosis is noted: the appearance of various rashes (papules, blisters, furuncle, carbuncle), depigmentation, etc.

Late diabetic syndrome is nephropathy due to intercapillary glomerulosclerosis. Nephropathy is manifested by proteinuria, hypoalbuminemia, hypergammaglobinemia, hyperlipidemia. Later azotemia develops, the content of urea and creatine increases in the blood, that is, renal failure. Renal failure is accompanied by hyperkalemia, ECG changes. Diabetic nephropathy may be complicated by pyelonephritis (the appearance in the urine of microbial bodies, leukocytes, an increase in pH).

Heart disease is manifested by myocardiodystrophy, with relevant signs. Coronary artery disease is the main cause of myocardial infarction in late diabetes.

Severe adverse type 1 diabetes mellitus is diabetic coma. Causes of diabetic coma can be a sharp decrease in insulin synthesis, inadequate treatment of diabetes, stress, complications of an infectious disease (plague of carnivores, viral hepatitis, etc.).

The harbingers of diabetic coma are increased polyuria, polydipsia (thirst), anorexia, vomiting. Breathing is noisy, intermittent, there is a smell of acetone in the released air. The general condition is sharply depressed (sopor) or coma. Palpitations increased, arrhythmia. Polyuria, urine has a high relative density, contains a lot of sugar, acetone, protein. The level of sugar in the blood by orders of magnitude increases the permissible norms. In the blood, the concentration of urea, creatinine, total protein, hemoglobin, leukocytes is sharply increased, the insulin content is lowered.

In type 2 diabetes mellitus, hyperglycemia does not occur at the time of the disease, but is detected only when the body's compensatory mechanisms are ineffective. Type 2 diabetes begins early to detect hyperglycemia, gradually progresses, moving from the preclinical to the clinical stage.

Pathological changes

Dry skin, exhaustion, dehydration of tissues, dystrophic changes in the heart muscle, liver and other organs. In the pancreas often find rebirth and focal atrophy of the parenchyma. In the kidneys detect glomerulosclerosis, the defeat of small vessels (mainly capillaries).

Diagnostic criteria

The presence in the pedigree of fathers, mothers, sisters or brothers who have diabetes. The establishment of possible adverse factors affecting the body during different periods of ontogenesis.

The most characteristic clinical signs of the disease: thirst, polyuria, loss of appetite, emaciation, skin lesions, reduced visual acuity and hearing, tachycardia, arrhythmia, neuropathy, proteinuria. With diabetic coma - soporous or comatose state, loss of reflexes, intermittent noisy breathing, the smell of acetone in the exhaled air, anorexia, nausea, vomiting.

Laboratory research indicators

In insulin-dependent diabetes mellitus, high hyperglycemia, glycosuria, ketonuria, acidosis is possible; with insulin-dependent diabetes mellitus - moderate glycemia, glycosuria. In the mild form of diabetes mellitus, the glucose content in whole blood taken from dogs, pigs, horses on an empty stomach exceeds 95-120 mg / 100 ml (5.26-6.6 mmol / l); acetone bodies in the urine do not detect qualitative breakdown; reserve alkalinity at the level of the lower limit of the norm. It is believed that in healthy dogs glucose in blood taken on an empty stomach contains 0.8-1.2 g / l, and if it exceeds 2g / l, it is an advanced diabetes mellitus. Severe hyperglycemia and glycosuria are characteristic of severe diabetes mellitus, especially IDD. The glucose content in the blood reaches 12.2-16.65 mmol / l and higher, in the urine in dogs -4-10%, in pigs - up to 6%, horses - 3-8%. The relative density of urine - 1,040-1,060, it shows a high concentration of ketone bodies, protein. In the blood, low reserve alkalinity is established (from 40 vol.% CO2), albumin reduction, increase in cholesterol, urea, creatinine.

True diabetes should be differentiated from renal glucosuria, diabetes insipidus, alimentary glycosuria. Renal glucosuria can be associated with lipoid nephrosis, glomerulonephritis, pyelonephritis, and damage to the tubules of the kidney apparatus, as a result of which glucose reabsorption is reduced in provisional urine. When renal glucosuria "renal diabetes" blood sugar is in the normal range and below it.

With diabetes insipidus hyperglycemia and glycosuria, ketonuria does not happen, the relative density of urine is very low.

Alimentary glucosuria appears when eating a large amount of sugar-rich feed after a long fast. It disappears when normal feeding is established.

Treatment

In all forms of the disease, a strict diet is prescribed using a variety of benign feeds. Horses give hay grass, mash of bran, crushed oats, carrots. For dogs, buckwheat, rice, barley, oatmeal porridge, vegetable soups, lean meat, fish, cottage cheese, milk, cabbage, beets, carrots, liver (10-15g), black bread with vegetable oil are used. Rations should contain easily digestible fiber, protein, moderate amounts of sugar and starch. Feed reception fractional. Dietary fibers are widely used: cellulose, cellulose, hemicellulose, pectin, bran, lignin, buformin. Under the influence of fiber in patients with diabetes mellitus, glycemia is reduced and insulin levels increase.

Treatment of diabetes mellitus is aimed at achieving normal blood glucose levels (normoglycemia), elimination of vascular and other complications.

Drug treatment of type 1 diabetes mellitus (IDD) is based on the lifelong use of insulin.

Insulin preparations share:

  • According to the degree of purification: standard and highly purified monocomponent MC;
  • By origin: animal and human, which is produced by recombinant genetic engineering;
  • For the duration of action: extremely short-acting insulin (lispro-humologist), short-acting, intermediate-acting and long-acting. In addition, use insulin mixed action. Insulin is administered subcutaneously.

Short-acting insulin is regular crystalline insulin (Actrapid MC, Humulin R). Onset of action within 20-25 minutes after administration, duration of 6-8 hours. Short-acting insulin treatment is usually combined with intermediate and long-acting insulin. Monotherapy with these drugs is carried out in diabetic ketoacidosis.

Intermediate-acting insulin (Semilente MC, NPH, Lente MC, Lente letin, Humulin, etc.). Onset of action in the period from 40 minutes to 2 hours, duration 18-24 h.

Long-acting insulin (Ultralente MC, Ultratard HM, Humulin U, etc.). The onset of action after 4-6 hours from the introduction, the peak after 12-22 hours, the duration of action is 30-36 hours. Insulin is used less frequently than others because of the possibility of prolonged and prolonged hypoglycemia.

Mixed insulins (mixed, humulin, novolin) are a combination of short insulin and intermediate insulin action.

LLC Intervet offers the drug Kaninsulin R, containing two forms of porcine insulin: short and long-acting. Short-acting insulin allows you to achieve a therapeutic effect, which is especially important with a sharp increase in blood glucose levels. By the time of the decrease in the activity of short-acting insulin, its long-acting insulin action begins, the short prolongs the therapeutic effect of insulin to 24 hours. The optimal ratio of short and long-acting insulin is 30% and 70%. Apply 1 time per day before feeding. 1 ml of the preparation contains 40 IU of insulin. Modified short-acting insulins include Lispro and Aspart, long-acting - Glargin. Insulins Lizpro and Aspart are recommended for the treatment of type 1 diabetes mellitus.

Compared with human insulin, glargine (commercial name Lantus) has two additional arginine molecules in the terminal B-chain and glycine instead of arginine in the 21st position of the A-chain. As a result, Lantus forms precipitates, which leads to a slowdown in its adsorption from the injection site. Enter once a day. T.A. Kurova reports on the effectiveness of insulin use, Lantus, Humalog, Novo-Rapid (Problems of endocrinology 2006, T. 52, No. 3).

For medical purposes, insulins are offered for oral use - a polyacrylic hydrogel and tablets based on a hydrogel substrate, coated with a gastro-insoluble shell. Both drugs immobilized insulin when administered orally give a certain hypoglycemic effect. When using the gel form, the time to achieve the maximum effect is 90 minutes after taking the drug; when using the tablet form, this time was almost twice as long and the action lasts longer.

Insulin Dosing

Insulin preparations contain a certain amount of hubbub expressed in ED or in IU. In the treatment of EDD, the daily dose of insulin is 0.5–0.6 U per 1 kg of body weight (for horses, 100–200 U; for dogs, 5–20 U). Begin treatment with small doses, gradually bring them to normalize the level of glucose in the blood plasma. Insulin dosing is controlled by blood glucose.

According to the literature, the ideal glycemic curve is from 0.8 to 1.2 g / l. The glucose level of 1.0-2.0g / l during the treatment period of dogs and cats is considered sufficient. In cats with diabetes, the initial dose of insulin (porcine, human) is 0.25-0.5 IU / kg. The therapeutic effect of medium-acting insulin in cats varies between 10-14 hours, therefore, they are prescribed twice a day. In case of insulin overdose, hypoglycemia may occur. Along with insulin in the light form of the EDM, it is possible to use glucose-lowering drugs.

Treatment of type II diabetes mellitus (IND) begins with a diet and use of glucose-lowering drugs for oral administration. It is recommended to choose a drug that provides the desired level of glucose in the blood when it is used as a monotherapy. If the blood glucose level cannot be reduced using a single oral glucose-lowering drug, you can additionally prescribe a second drug from another group, quickly increasing its dose to achieve the desired effect.

If therapy with oral hypoglycemic drugs is ineffective, it is recommended to additionally prescribe evening injection of long-acting insulin, transfer the patient to multiple insulin injections with different duration of action, or connect a third oral antidiabetic drug.

Such a principle of treatment of type II diabetes mellitus can obviously be used in veterinary medicine.

According to the chemical composition and the mechanism of action on the body, the sugar-reducing preparations of oral administration are divided into 2 groups: sulfanilamide and biguanides. Sulfonamides are sulfonylurea derivatives. These include: first-generation drugs - tolbutamide (butomid, orabet), carbutamide (bukarban, oranil); second generation glibenclamide (antibet, dianthi, genglib), glycide, glyburide; third generation - glimepiride (Amaril (R)).

Sulfanilamide (sulfaniluretic) drugs stimulate insulin secretion, inhibit glucogon production and reduce the flow of glucose from the liver into the bloodstream, increase the insulin sensitivity of insulin-dependent tissues due to stimulation of receptor withdrawal. The duration of action of drugs of the sulfonamide group is from 6 to 24 hours. Preparations in this group are used individually or in combination.

The group of biguanides (guanidine derivatives) includes metformin (gliformin, glycon, glucophage, sioform-850), buformin (adebit, silybin retard). The duration of the action of glycone, metformin 6-8 hours, glucophage, metformin BMS, silybin retard - 10-12 hours. The sugar-reducing effect of the biguanides is due to the increased utilization of glucose by muscle tissue by enhancing anaerobic glycolysis in the presence of insulin. Glucophagus has a prophylactic hypoglycemic effect. Effective acrbase (glucoic), which inhibits the activity of glucosidase in the intestine, enzymes that break down di - and polysaccharides to glucose and reduce the level of glucose in the blood. Approximate daily dose of glucobay 0.5-1.0 mg / kg body weight. Contraindications: pregnancy, ulcerative colitis, etc. Dosages of sugar-lowering drugs are selected individually, focusing on the doses used in humane medicine and the degree of glycemia.

Approximate doses for dogs: butamide (tolbutamide, diabetol, orabet) and bucarbon (carbutamide, nadizan, orabetic, oranil) - 20-25mg / kg 2 times a day; Glybutid (Adebit, Sulubin, Butylbiguanide) - 3-4 mg / kg 2 times a day. Appointment of glucose-lowering drugs begin with a minimum dose, increasing it to normalize blood glucose. Then the dose can be reduced and left at this level, maintaining a normal concentration of sugar in the blood. As mentioned above, hypoglycemic drugs are used for a long time. When oral hypoglycemic drugs do not inhibit the increasing level of glucose in the blood, they switch to a combined method of treatment, i.e., hypoglycemic drugs are combined with insulin therapy. The use of insulin is controlled by the sugar content in the blood, preventing its sharp decline in order to avoid hypoglycemic coma.

For ketoacid coma, only simple insulin on the saline solution is administered intravenously slowly or intramuscularly or subcutaneously. An intravenous insulin is administered to dogs for 5-10 IU / h, subcutaneously and intramuscularly for 20 IU, then every hour for 5-10 IU until the glycemia decreases to 11-13 mmol / l. After a decrease in blood glucose to the indicated values, they switch to subcutaneous insulin administration. To restore the acid-base balance and water-electrolyte metabolism in a ketoacidotic coma, an isotonic solution of sodium chloride, a 2.5% solution of sodium bicarbonate, and Ringer-Locke solution are injected intravenously. With a sharp decrease in blood sugar concentration, intravenously injected 5% glucose solution 100 ml / h. 0.1% adrenaline crustaceans are injected subcutaneously: -3-5ml horses; dogs 0.1-0.5 ml. For collapse, mezaton, norepinephrine, and caffeine are prescribed; for heart failure, strophanthin and korglikon are prescribed.

  1. Mezaton intravenous drip horses -0.04-0.08 mg / kg; dogs -0.08-0.1mg / kg. 1% solution mezatona before intravenous diluted in 250 ml of 5% glucose solution. Intramuscularly or subcutaneously mezaton administered: horses at a dose of 0.1-0.2 mg / kg; dogs -0.5-1.0 mg / kg.
  2. Norepinephrine hydrochloride intravenous drip in the approximate dose of 0.04 mg / kg in the form of a 0.2% solution of the diluted in 500ml 5% glucose solution.
  3. Caffeine sodium benzoate subcutaneously 20% solution to horses at a dose of 10-20 ml; dogs and cats 0.5-2.0 ml (18-19mg / kg) 3 times a day.
  4. Korglikon 0,06% solution intravenously slowly: for horses - 4-5 ml; dogs - 0.5-1ml. Before the introduction of the drug is dissolved in 20 ml of 40% glucose solution.
  5. Strofantin K intravenous drop of a 0.025% solution in doses: for horses - 0.004-0.07 mg / kg; dogs - 0.009-0.08 mg / kg. The solution is diluted 10-20 times in 20 or 40% glucose solution or in 0.9% sodium chloride solution.

Phytotherapy

Pumpkin seeds and fruits have the sugar-lowering effect, hawthorn, centaury, oats, peas, plantain, bean gills and bean seeds, black currant leaf, licorice, buckwheat. In medical practice, special fees are recommended: "Afrazetin", the collection of MMA. Sechenov - bilberry leaf and shoots, bean leaves, wild rose fruits, nettle leaf, plantain, chamomile flowers, calendula, motherwort herb, St. John's wort, yarrow root, licorice root, root and rhizome of equal inyas (extract 1:40).

Prevention

Moderate feeding on diets with a diverse set of feed. Avoid overfeeding and obesity. To organize daily broods of dogs, departure of horses. To maintain a normal level of insulin in the body, dogs are recommended to give 50% of the daily feed intake at lunchtime and 25% each in the morning and evening. Regularly conduct medical examinations of working dogs and breeding horses. Perhaps the use of infusions or decoctions of medicinal herbs: blueberries, zamanihi, Ginseng, Eleutherococcus. Glucophagus (metformin), an antihyperglycemic agent from the biguanide group, has a certain prophylactic effect, which improves peripheral insulin sensitivity of the tissues, reduces the glucose production of the liver by influencing gluconeogenesis, reduces glycogenolysis, and inhibits glucose absorption in the intestines.

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