Acute complications of diabetes mellitus :

etiology, pathogenesis, diagnostic criteria, treatment

One of the most important tasks for a practice doctor is diagnosis and treatment of urgent states. The large diseases group, which might complicated with acute painful state and require urgent medical treatment, are diseases of endocrine system, and first of all – the diabetes mellitus, which is one of the leader in spreading of diseases structure. Therefore, only the knowledge of clinic symptomatology, diagnostic questions, differential diagnosis and treatment of an urgent state allows the doctor to render the appropriate and qualified treatment for patient.

Diabetes mellitus (DM) is a systemic disease that effects essentially every organ of the body. The fatal outcome is related to the development of acute or chronic complications.

Classification of acute complications of DM.

  1. Diabetic coma:

1)diabetic ketoacidisis (DKA);

2)nonketonic hyperglycemic-hyperosmolar coma (NKHHC);

3)lactoacidosis (LA).

  1. Hypoglycemic coma (HC).

At present there are three kinds of diabetic comas: ketoacidic, hyperosmic and lactacidemic. The medical tactics depends on the pathogenic of diabetic coma, therefore a pathogenic disease diagnosis has a special meaning. Yet to take into account that a diabetic ketoacidosis, hyperosmotic and hyperlactacidemical syndromes are rarer as a pure form. Usually two or even three pathogenic varieties in different combinations (including over the expressiveness degree of any syndrome) are appearing from the expressive diabetes decompensation beginning moment.

Diabetic ketoacidisis (DKA).

Before the area of insulin therapy, ketosis was the leading cause of death of patients with DM. Since insulin deficiency worsens the clinical picture and leads to metabolic abnormalities, the complication is more common in young diabetics. Despite insulin usage, mortality remains high (6 - 10 %).

DKA results from grossly deficient insulin modulation of glucose and lipid metabolism. A diabetes ketoacidic coma is one of the most dangerous complications and appears as a result of the growing insulin deficiency. The diabetic ketoacidosis development (DKA) is the more typical for IDDM. But it must be remembered that patient with IDDM may have DKA in cause of the present of stress situations and intercurrent diseases which lead to decompensation of diabetes mellitus.

Precipitating factors:

1)newly diagnosed diabetes (presenting manifestation);

2)inadequate administration of exogenous insulin;

3)increased requirements for insulin caused by the presence of an underlying stressful condition:

-an intercurrent infection (pneumonia, cholecyctitis);

-a vascular disorder (myocardial infarction, stroke);

-an endocrine disorder(hyperthyroidism, pheochromocytoma);

-trauma;

-pregnancy;

-surgery.

Predisposing factors of DKA development.

  1. Unrecognized diabetes mellitus.
  2. Treatment regime violation (an absence of accurate insulin doses correction).
  3. Infections and intoxication’s.
  4. Physical, psychological trauma.
  5. Surgical operations.
  6. Acute cardiovascular insufficiency, myocardial infarction, cerebral hemorrhage.
  7. Pregnancy.
  8. Prolonged starvation.
  9. The considerable change of diet, using of alcohol.
  10. Insulinresistance (antibodies formation or isolation and destruction of insulin during subcutaneous injection).
  11. Physical exercises (loading) during a chronic insulin deficiency.

Physical exercises may lead to the early and delayed hypoglycemia’s, increasing the glucose utilization and causing the more faster insulin absorption, which isn’t balanced with the liver increasing glucose production and supplementary food. There is less known the ability of physical exercises to cause ketoacidosis of those patients, who do not fully chronically receive insulin. Physical load stimulates a production of contrinsular hormones: adrenaline, STH, glucagon. These hormones mobilize glucose and fat and direct a metabolism in liver to the formation of ketones that may rapidly lead to the ketoacidosis during considerable insulin deficiency.

In the base of diabetic ketoacidosis and coma pathogenesis is the increasing insulin deficiency and as a consequence:

  1. The infringement of glucose utilization with tissues, cytolemme hypopermeability for glucose, decreasing of processes of its oxidation and energetic using by cell.
  2. The infringement of glycogen synthesis, at first of all in liver, that with combination with lipocain deficiency, leads to the fatty infiltration of liver.
  3. Increasing of the glycogen dissociation, the compensative formation of glucose of proteins and fats (gluconeogenesis).
  4. Hyperproduction of contrinsular hormones which having fatty - mobilized property: somatotrophin, catecholamines, and corticotrophin.
  5. Hyperproduction of the basic hormonal antagonist – glucagon which promotes to the glucose production increasing.
  6. Lipolysis increasing.

At present a ketoacidic coma is very severe complication of diabetes mellitus which is life – threatening for patient. During DKA mortality is 5-17%.

DKA develops then when insulin deficiency is combined with increasing activity of contrinsular hormones. Their effect (except STH) is showed very rapidly.

Glucagon increases hepatic glycogenosis and gluconeogenesis, during DKA its level increases on 400-500%. At increases the hepatic ketogenesis on 300%, independently on level of free fatty acids and also increases the lipolysis.

The catecholamines excretion is stimulated with activation of the sympathic nerval system, stress, acidosis, fever. The adrenaline level increasing stimulated glycogenolysis in liver and muscules, increases gluconeogenesis in liver, activates the lipase of fatty acids and secondary ketogenesis in liver. During insulin deficiency the increasing of blood CA leads to increasing of the glucose level in 5-7 ones higher then in normal.

The long increased STH level (acromegalia) leads to increasing production of glucose in liver, increases the lipolysis and ketogenesis.

Hyperglycemia causes osmotic diuresis and leads to dehydration, decreasing of electrolytes level and serum hypertony.

Patients, who are using the according to thirst liquid volume and having normal function of kidneys, have a moderately increasing of glycemia level during ketoacidosis, as in normal the kidneys may excreate glucose with the speed which is adequative to the increasing of glucose production.

Patients with vomiting or are in unconscious state can’t use enough liquid to level continuous osmotic diuresis which leads to dehydration and hypovolemia with decreasing of renal function.

It explains that fact only rehydration with solutions without insulin introducing, may to decrease the glucose level in half. The hospitalized patients with DKA have the loss of free water which is usually 10-15% (100-150 ml/kg of body weight) and depends on expressiveness and duration of disease. The hyperglycemia value presents about a dehydration and hypovolemia degree.

Hypovolemia makes more hardly the metabolic acidosis owing to two ways: the decreasing of tissue circulation and development of lactacidical acidosis, which may be 25% of acidemia during DKA. Also hypovolemia decreases the renal function and excreation of organic acids.

The osmotic diuresis during DKA leads to the passive electrolytes and water loss: Na – 5-13 m eq/kg, K – 4-10 m eq/kg, P – 0,5-4 m eq/l.

Every 100mg% (5,5 mmole/l) of the glycemia increasing decreases the sodium level in blood serum on 1,6 m eq/l.

Na = Na (measured) + 1,6 (glucose – 100)/100

Acidosis and catabolism of proteins stimulates the potassium excretion from cells. With urine the potassium is lossed because of increasing activity of aldosterone, stimulated with dehydration. During rehydration and insulin treatment may appears the hypokalemia (decreasing of serum hypertony, increasing of SHT, acidosis decreasing and potassium entering into a cell).

Clinical presentation.

Diabetic ketosis.

It is status which is characterized by increased level of ketones in blood, without clinical signs of dehydration and can be corrected by diet (fat restriction) and regular insulin injection.

DKA develops over a period of days or weeks.

Signs and symptoms.

  1. Polydipsia, polyuria and weakness are the most common presenting complaints.
  2. Anorexia, nausea, vomiting, and abdominal pain may be present and mimic an abdominal emergency.
  3. Ileus and gastric dilatation may occur and predispose to aspiration.
  4. Kussmaul breathing (deep, sighing respiration) is present as respiratory compensation for the metabolic acidosis and is obvious when the pH is less than 7.2.
  5. Symptoms of central-nervous-system involvement include headaches, drowsiness, lassitude, stupor and coma (only 10 % patients are unconscious).

Physical examination.

  1. Hypothermia is common in DKA. A fever should be taken as strong evidence of infection.
  2. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis, acetone may be detected on the breath (musty (fruity) odor to the breath).
  3. Tachycardia frequently is present, but blood pressure is usually normal unless profound dehydration is present.
  4. Poor skin tugor may be prominent depending on the degree of hydration.
  5. Hyporeflexia (associated with low serum potassium) can be elicited.
  6. Signs consistent with a “surgical abdomen” but which follow severe ketonemia can confuse the clinical picture.
  7. In extreme cases of DKA one can see hypotonia, stupor, coma, incoordination of ocular movements, fied dilated pupils, and finally death.
  8. Other signs from a precipitating illness can be present.

Laboratory findings.

  1. The hallmark of DKA is the finding of:

-hyperglycemia;

-ketonemia;

-metabolic acidosis (plasma pH and bicarbonates are decreased.

  1. A presumptive bedside diagnosis is justified if the urine is strongly positive for both glucose and ketones.
  2. Different changes of electrolyte levels in the blood can be observed and does not reflect the actual total body deficits.
  3. Serum amylase and transaminases can be elevated.
  4. Leucocytosis occurs frequently in DKA and therefore cannot be used as a sole indication of infectious process.

Types of DKA:

-abdominal;

-vascular collapse;

-cerebral (encephalopathic);

-renal;

-mixed.

Differential diagnosis.

DKA must be distinguished from a variety of clinical conditions, particularly those in which central-nervous system function is altered and also associated with metabolic acidosis. The patients history and physical examination often are adequate diagnostic techniques.

Cardiac arrhythmia is the severest complication of the potassium homeostasis infringement. The DKA development in according with the modern data may be represented with following stages:

I stage of ketoacidosis ( DKAI ).

Pathogenesis. This stage is characterized with growing hyperglycemia, which is a result of insulin deficiency. At that time on the base increasing of sugar level in blood, cells face energetic starvation, as a deficiency doesn’t give possibility for cells to utilize the glucose.

The energetic cellular starvation of organism leads to activation of the endogenic glucose formation owing to the gluconeogenesis and glycogenes dissociation. These processes are stimulated with glucagon, catecholamines, glucocorticoids. But the glucose utilization by cells in this situation isn’t arranged of insulin deficiency, and a result of this the hyperglycemia is increased some more. Hyperglycemia is accompanied with the increasing of osmotic pressure of blood serum, cellular dehydration, polyuria, glucosuria (glucose begins to exreat in urine of the glycemia level is 10-11 mmole/l). Glucosuria causes the increasing of osmotic pressure of primary urine, that prevent it from reabsorbtion and intenities polyuria.

The compulsory factor of DKA pathogenesis is an activation of the ketonal bodies formation. The insulin deficiency and surplus of contrinsular hormones (in first of all – the somatotrophic having lipolytic effect) lead to the lipolysis activation and free fatty acids (FFA) contains increasing, which are the ketogenic substrate. Exept these, the synthesis of ketonic bodies – beta-oximalar and acetoacetic is owing to “ketogenic” aminoacids (isoleucine, leucine, valine), which are accumulated as a result of proteins catabolism in causes of insulin deficiency. The ketonical bodies accumulation leads to exhaustion of alkaline blood reserves and development of metabolitic acidosis. In first stage of DKA there is appearing the moderate acetonuria which may be inconstant.

Clinics. DKA, as a rule, develops slowly, during some days, on the diabetes mellitus decompensation base. During this stage there is the decreasing or loss of efficiency, muscular debility, appetite disappearance. There is appearing of headache, dispeptic effects (nausea, diarrhea). The polyuria and polydipsia grow. During an examination there are revealed dryness of skin, tongue and mucousal membrane of oral cavity, feeble oral smell of acetone, muscular hypotony, tachycardia, some dull cardiac tones, possibly the arrhythmia. Sometimes there is pain in abdomen, it may be palpated the painful and increasing liver.

Laboratory data.Hyperglycemia until18-20 mmole/l, glucosuria, ketonemia (untill 5,2 mmole/l) and ketonuria (ketonic bodies in urine – some positive). The aqueous electrolitic balance on this stage of DKA development is characterized with some hyperkaliemia (owing to the potassium excreation from cell) – until – 5 mmole/l. The potassium deficiency in cell is confirmed with ECG data (asymmetric decreasing of ST interval, the double – phasic T-wave, which may be negative). The acidic-alkaline state (AAS) doesn’t essentially change, but there is decreased the hydrocarbonaties contains until 19-20 mmole/l.

Treatment. Patients with diabetes mellitus on the first stage of DKA must be hospitalized into the endocrinal hospital department. There is important measure on this stage to change the diet regime. It is necessary to recommend easy-digested carbohydrates, fruit saps, honey. The common carbohydrates volume is increased until 70-75% for ketogenesis suppression. The hyperglycemia correction is because of the insulin of early effect, with small doses, not rarer than 6 ones per day (intramuscular). The insulin day doses is counted up owing to the 0,7-1,0 UN/kg of the factic body weight. For acidosis removal are prescribed the alkaline mineral waters (“Borzhomy”), dimephosphone, regidron. Are necessary also a cleansing enemas with 3% solution of sodium hydrocarbonate. As a rule, these measures are sufficiently for treatment of patients with DKA I stage. In case of the dehydration expressive signs to prescribe the intravenous solutions injection.

It must be noted that carly diagnosis and opportune treatment promote to prevention of the ketoacidosis beginning stage passing to the precoma which is vitally dangerous for patient.

Precomatous state (DKA II nd)

Pathogenesis.Following are the pathogenetic mechanisms: energetic cellular incompetence in causes of insulin deficiency is accompanied with activation of protein destruction which is leading to infringement of the nitrogen balance and promotes the azotemia development. It causes the increasing of endogenic glucose production from glycogene, fat and protein, is growing the glucosuria and polyuria owing to the osmotic diuresis. At first a glucosuria and hyperglycemia lead to cellular dehydration and then to general dehydration with decreasing of tissue and renal circulation and mineral deficiency (Na,K,Cl). The renal blood circulation infringement promotes to the ketoacidosis growing, because of kidney stopping the hydrocarbonic ion production (HCO3). Activation of ketoacidosis is increased with the metabolitic acidosis, which is accompanied with decreasing of the blood alkalinity and pH shifting. Stimulation of the respiratory center with hydrogen ions leads to the appearance of characteristic harsh infrequent breathing. Besides, as a result of the lipolysis activation in blood are accumulated FFA, non-etherificated fatty acids, tryglycerides, which increase blood viscosity and promote to infringement of hemorrhological blood properties and microcirculation insufficiency.

Clinics.On the DKA-II the general condition of patient is acute, deteriorated, rapidly grow thirst and polyuria. Patient is suffering of the progressive muscular debility and can’t individually move. It appears the pernicious vomiting and increased abdominal pain. There are often heart pains. During examination there are expressive xerodermia and xeromucous, rubeosis of face (as a result of capillary paresis). Tongue is dry, crimson or coated with brown fur, there is sharp fowl smell of acetone. Muscular tonus is decreased, the eyeboll tonus is decreased, too. Breathing begins infrequent, deep, harsh (Kussmaul respiration). From the side of cardiovascular system there are the following changes: rapid and soft pulse, tachycardia, dull heart sounds, may be the arterial hypertony. Hypokaliemia leads to the intestine motopity decreasing. As a result of intestine atony beginning it is strained off with its contents which is leading to appearance of painful syndrome. Except these, there is the tension of anterior abdominal wall. These changes may be a cause for false diagnosis of the “acute abdomen”. We must take into account that DKA is accompanied with leukocytosis with neutrophilia and formula shifting to the left (owing to hydrovolemia). Therefore the clinics of “acute abdomen”, that is confirmed with laboratory data, is seemed highly convincing. The result of this may be inexcusive laparatomy which making DKA tendency worse.

A peculiarities of the preceding diabetes mellitus tendency, patient age, accompanied diseases, Also as a causes character, which directly cause the acidosis, define the rapidness of its tendency, expressiveness and preclaiming in clinics that or other manifestations.

Due to these there are several forms of the precomatous state tendency.

Gastrointestinal (abdominal): there are spasmodic pains in epigastral and iliac regions acquiring then spilling character and seem on peritonitis, the defending tension of abdominal muscles, the restricting of this region during breathing (“acute abdominal” syndrome). Moreover, There are characterized by uncontrollable vomiting and vomitory reflexes with exceation of mucousal or mucous – bilious contents, which often acquiring the “coffee-ground” color (manifestations of the erosive toxic gastritis). Stools disturbances have enough steady and permanent character: persistent constipation’s are interchanged with profuse fetorical diarrheas with painful tenesmuses.

The causes of the hardlest abdomenalgia and pseudoperitonitis until present aren’t standed finally. One supposes that they are connected with stimulation of nodes of celiac plexus owing to the peritoneum vessels spasm. Others investigators assume those in causes of ketoacidic dehydration is developing the aseptic peritonitis. Some authors explain that pain is caused with spastical state of pylorus and intestine.

In some causes the painful sensations are connected with stretching of stomach owing to the toxic gastritis and transudation into its cavity of many liquid.

Abdominal pain caused with ketoacidosis lasts during 4-5 hours from the beginning of treatment. Often this form is found in young age.

Cardiovascular form: More oftenly it manifestetes in older age. The mean clinic manifestation is heavy collapse with considerable decreasing of arterial and venous pressure, tachycardia, weak pulse, different disturbances of cardiac rhythm, cyanosis and cold extremities. The cardiac asthma manifestations and sometimes the acute edema of lungs remind the clinic of acute myocardium infarction meeting during prolonged and hard tendency of diabetes mellitus.