CURATION OF PATIENTS WITH HYPOGLYCEMIC AND HYPERGLYCEMIC COMA

Diabetes mellitus (DM) is a systemic disease that affects 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). 2. Hypoglycemic coma (HC).

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. Predisposing 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.

Pathophysiology of DKA Insulin deficiency (absolute or relative) ↓ glucose uptake ↑ proteolysis ↑ ↑ aminoa nitrogen cides loss ↑ lipolysis ↑ free fatty glycerol acids ↑ ketogenesis ↑ ketonemia ↑ ketonuria

Muscle breakdown weight loss Weakn ess

Hyperglycemia

Gluconeogenesis + glucogenolysis

Glucosuria Osmotic diuresis Hypotonic losses Diagnostic criteria 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. Electrolyte depletion

dehydration and acidosis

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 7,1. 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. Hyperpnoea 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 turgor 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, fixed 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. 2. A presumptive bedside diagnosis is justified if the urine is strongly positive for both glucose and ketones.

3. Different changes of electrolyte levels in the blood can be observed and does not reflect the actual total body deficits. 4. Serum amylase and transaminases can be elevated. 5. Leucocytosis occurs frequently in DKA and therefore cannot be used as a sole indication of infectious process. Types of DKA: - abdominal (diabetic pseudoperitonitis, false acute abdomen) is characterized by acute abdomen pain, dyspeptic signs with vomiting, leucocytosis and look like acute appendicitis or peritonitis; - cardiovascular type (characterized by vascular collapse, tachycardia, cyanosis, pain in the region of the heart, arterial fibrillation and is a result of decreased blood circulating volume due to the dehydration, in old patients with coronary arteries atherosclerosis); - cerebral (encephalopathic) type (can be found in old patients with cerebral vessels atherosclerosis, characterized by changing of Kussmaul breathing on superficial, absence of corneal reflexes and is a result of intoxication and brain edema); - renal (develops in patients with diabetic nephropathy and is characterized by proteinuria, hematuria, azotemia); - 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 patient’s history and physical examination often are adequate diagnostic techniques. The nurse monitors for the signs and symptoms of DKA

• checks blood pressure, pulse and respirations every 15 min until stable • records urine output, temperature and mental status every hour • assesses central venous pressure (when central venous catheter has been placed) usually every 30 minutes Primary nursing measures are • assessing the patients airway patence, level of consciousness, hydration status, status of fluid and electrolyte replacement and levels of blood glucose (laboratory or bedside glucose monitoring) – results of last indicate the efficacy of insulin replacement and establish when to switch from saline to dextrosecontaining solutions • After stabilization of patient’s condition monitoring vital signs and recording values every 4 hours is acceptable

Treatment Treatment of diabetic ketosis 1. Inhibition of ketogenesis can be achieved by exclusion of fat from diet and increasing quantity of high-calorie carbohydrates in meal. 2. Prescription only of short-acting insulin. Treatment of diabetic ketoacidosis and coma The most important factor to emphasize is the frequent monitoring of the patient both clinically and chemically. Initially, laboratory data should be obtained every 1 – 3 hours and less frequently once clinical improvement is noted. If the patient is in shock, stupor or coma, a nasogastric tube, especially if vomiting, and urinary catheter are recommended. Frequent assessment of potassium status is vital. A lead II electrocardiogram (ECG) can be provide a rapid assessment of hyperkalemia (peaked T waves) and hypokalemia (flat T waves and presence of U waves). Hyporeflexia and ileus are clinical indications of potassium deficiency. Careful observation of neurological status is vital to detect the infrequent but devastating presence of cerebral edema. The goals of therapy include:

The nurse checks for clinical indicators of fluid imbalance • Edema occurs with excess interstitial fluid and is not usually apparent until the interstitial volume has increased by at least 2 to 3 L.5 – 0. Insulin treatment DKA can be treated with low dose insulin regimens. Daily weights provide a good indication of fluid volume status. This is true in patients with renal failure who cannot excrete the extra volume. A rapid infusion of 0. After the initial infusion. Continuous intravenous infusion of . • Volume overload can cause an increase in blood pressure to the point of hypertension. • Orthostatic hypotension is an indication of volume depletion. 1 l/h for the first 1 to 2 hours) is given and then reduced to about 0. Initial intravenous administration of 10 to 14 units of short-acting insulin has to be prescribed for the patient during first hour.3 l/h if the blood pressure is stable and the urine follow is adequate. clinical assessments of hydration and circulation.. Reduction of hyperglycemia.g. 3.1. intravenous fluid therapy must be adjusted individually on the basis of urine output. the jugular venous pulsation may not be visible even with the patient lying flat (Toto. In volume depletion. Rehydration The average fluid deficit in adults with DKA is 3 to 5 l. Rehydratation. 2.9 % sodium chloride (e. jugular venous pulsation may not be visible at a 45-degree angle. Investigation of precipitating factors. treatment of complications. The addition of glucose to the intravenous solution is necessary for correction of tissue lipolysis and acidosis. 1998). determination of plasma electrolytes and glucose. One kilogram of body weight equals 1 L of fluid. When serum glucose level is about 11 – 13 mmol/l administration of 5 % glucose with insulin can be performed (1 to 2 unites of insulin on each 100 ml of 5 % glucose solution). Correction of: a) acid-base and b) electrolyte imbalance. An increased jugular venous pressure occurs with volume overload. 4. In severe volume depletion.

weakness and paralyses of intercostal muscles. the rate of insulin is doubled until a response is noted. This solution can be prepared in such way: 50 units of insulin have to be added to a 500 ml bottle with 0. 2 % potassium solution 150 ml 100 ml 75 ml 50 ml - .insulin in a dose 0. and as a result each 10 ml of solution will contain 1 Unite of insulin. When the serum glucose concentration reaches 11-13 mmol/l. In most patients the initial serum potassium is high. Treatment of electrolyte disorders Potassium should never be given until the state of renal function is known and until the serum potassium concentration is available. and the initiation of potassium replacement usually can be given in 2 hours after beginning of rehydration and insulin therapy.3. normal or elevated.5 gr.5. using hourly serum measurements as a guide (table 1). patients are placed in insulin regimen consisting of five injections of regular insulin. > 6mmol/l Potassium would to be infused during 3 – 5 hours. Blood glucose level should be maintained at about 11 mmol/l during intravenous therapy.9 % sodium chloride solution. atone of stomach and intestine. Correction of potassium balance Serum potassium level Potassium deficiency < 3 mmol/l 3 gr. 4 – 5 mmol/l 1.5 mmol/l) after an hour of infusion. But if there is a tendency for quicker decreasing the level of glucemia we have to decrease the dose of insulin in twice. 5 – 6 mmol/l 1 gr. 3 – 4 mmol/l 2 gr. If the glucose level does not improve (decrease on 3. insulin can be given subcutaneously (if plasma and urine persistently negative for ketones).9 % sodium chloride infusion has to be given after that. development of hypakalemic coma. Hypokalemia can lead to the disturbances of heart rhythm.1 unit/kg/hour in 0. Improvement usually is noted in 8 – 24 hours. Following stabilization of the clinical condition. Table 1.

So ketone bodies are themselves metabolized to bicarbonate once proper therapy is begun (fluids. magnesium deficiency can be treated by 10 % solution of MgSO4 prescription (6 – 8 ml each 3 hour under the control of blood pressure).5 % solution. The use of bicarbonate can be recommended only in the following cases: . You must remember that development of vascular collapse after initiation of therapy should suggest the presence of gramnegative sepsis or silent myocardial infarction. sudden headache.if life-threatening hyperkalemia. Bicarbonate would be to infuse at a rate of 100 to 300 ml of 2. If cerebral edema is diagnosed. . insulin) and exogenous administration of bicarbonate can overcorrect to alkalosis. . Some patients have premonitory symptoms (e. it should be looked for and. .cerebral edema (It is a rare and frequently fatal complication. if found. . .vascular collapse can be treated by mesatone (1 – 2 ml).when severe lactic acidosis complicates DKA.g.with severe acidosis (pH<7). high serum viscosity.since infection is one of the leading precipitating events of DKA. electrolytes. rapid decrease in the level of consciousness). especially when complicated by shock that is not responsive to appropriate fluid resuscitative measures in an attempt to improve cardiac output. glucocorticoides (dexametasone 4 mg two times a day). Prevention of hypokalemia can be made by intravenous droply infusion of 50 – 75 ml 2% potassium chloride solution on each 100 mmol of bicarbonate. Other therapeutic consideration: . Correction of metabolic acidosis The metabolic acidosis occurs due to insulin deficiency and dehydration. Some physicians believe that rapid osmotic reduction of plasma glucose should be avoided to minimize rapid osmotic changes. but in others acute respiratory arrest is the initial manifestation.vascular thrombosis (it is secondary to severe dehydration. . treated appropriately. and low cardiac output) – heparin (5000 unites 4 times a day)..Phosphate deficiency can be treated by potassium phosphate.

. • The patient have to be taught by nurse to minimize the risk for dehydration by maintaining food and fluid intake.. The risk of starvation ketosis is reduced by a minimum daily carbohydrate intake of 150 g. • Liquids containing carbohydrate can be taken when the diabetic is unable to eat solid food. sometimes accompanied by seizures. the patient is instructed to take liquids containing both glucose and electrolytes (e.50 mg/kg/day divided q 4 – 6 h). and vomiting are present and as long as SMBG results are greater than 250 mg/dL (13. extreme dehydration. dexametasone (0. the nurse may instruct the patient to take additional rapid-acting (lispro) or short-acting (regular) insulin on the basis of SMBG results. Patient’s education • Investigation of the factors leading to DKA helps the nurse plan specific educational efforts. . But they are usually ineffective after the onset of respiratory arrest. • The patient have to check urine ketone levels when blood glucose levels exceed 300 mg/dL (> 16. Small amounts of fluid may be tolerated even when vomiting is present. • The nurse teaches the patient to perform self-monitoring of blood glucose levels (SMBG) every 4 to 6 hours as long as symptoms such as anorexia. soda pop. When nausea is present.7 mmol/L). and extreme hyperglycemia that is not accompanied by ketoacidosis.8 mmol/L). and sports drinks). NONKETONIC HYPERGLYCEMIC-HYPEROSMOLAR COMA (NKHHC OR HNC) HNC is a syndrome characterized by impaired consciousness. After consulting with the primary care provider. The patient should take 8 to 12 ounces (240 to 360 mL) of calorie-free and caffeine-free liquids every hour while awake.25 – 0.therapeutic maneuvers might include the use of : mannitol (1 – 2 g/kg intravenous over 20 min). diluted fruit juice. nausea.g.

mortality in patients with HNC has been very high (50 %) in most series. HNC usually develops after a period of symptomatic hyperglycemia in which fluid intake is inadequate to prevent extreme dehydration from the hyperglycemiainduced osmotic diuresis. e. Initially it was thought that patients with HNC produced enough insulin to prevent lipolysis and ketogenesis but not enough to prevent hyperglycemia.g. pancreatitis and renal failure. Death is usually due to an associated severe medical condition and not to the hyperosmolality..steroids increase glucogenesis and antagonize the action of insulin. Use of certain drugs has been associated with this condition: . azathioprine. e. except that ketoacids do not accumulate in the blood. propranolol. Suppression of lipolysis by hyperosmolality also has been proposed. urinary tract infection. . .The syndrome usually occurs in patients with type 2 DM. sometimes it is a complication of previously undiagnosed or medically neglected DM (type 2). The reason of this phenomenon is unclear. as well as cortisol and growth-hormone concentrations. In contrast to ketoacidosis. 4. diazoxide. . in patients with ketoacidosis has raised the possibility that the absence of ketosis may be the result of decreased cortisol and growth-hormone effects on lipolysis. The finding of lower plasma free fatty acids.g. Mortality has been associated with convulsions. The pathophysiology of HNC is similar to that of ketoacidosis. Predisposing factors 1. pneumonia. thiazides. who are treated with a diet or oral hypoglycemic agents. furosemide. pulmonary embolus. 3.other drugs.. 2.g.. deep vein thrombosis. HNC seems to occur spontaneously in about 5 – 7 % of patients. In 90 % of patients some degree of renal insufficiency seems to coexist.potassium-wasting diuretics (hypokalemia decreases insulin secretion). The concept was invalidated by finding similar inappropriately low plasma insulin concentrations in patients with the two syndromes. Infection (e. gram-negative sepsis) is underlying frequent precipitating cause.

Other medical conditions such as cerebrovascular accident. Because other underlying conditions (such as cerebrovascular accident and subdural hematoma) can coexist. usually in excess of 350 mOsm/l. 6. Extreme hyperglycemia (blood glucose levels from 30 mmoll/l and over are common. hyperreflexia. Polyuria. and generalized areflexia) are commonly present. subdural hematoma.g. 7. Laboratory findings 1. The osmolality can be calculated by the following formula: mOsm/l = 2(Na + K) = blood glucose/18 + BUN/2. A markedly elevated serum osmolality is present. 3. acute pancreatitis. Seizures occur in 5 % of patients and may be either focal or generalized. and patients are not acidic. 2. has been associated with HNC. other causes of coma should be kept in mind. Severe dehydration is invariably present. Findings associated with coexisting medical problems (e. The initial plasma bicarbonate averaged.8. and severe burns have been associated with HNC. Cushing disease. 3. especially in the elderly. 2. such as used in peripheral hyperalimentation or renal dialysis. renal disease. 3.. cardiovascular disease) may be evident. polydipsia. Serum ketones are usually not detectable. Endocrine disorders such as acromegaly. transient hemiparesis. Use of concentrated glucose solutions. weakness and progressive changes in state of consciousness from mental cloudiness to coma (present in 50 % of patients) occur over a number of days to weeks. HNC can be induced by peritoneal or hemodialysis. and thyrotoxicosis have also been associated with HNC. weight loss. . tube feeding. (Normal = 290 mOsm/l). Physical examination 1. Diagnostic criteria Signs and symptoms 1.5. Altered states of consciousness from lethargy to coma are observed. 2. 4. Various neurologic deficits (such as coma. 8.

5. Rehydration The average fluid deficit is 10 liters. 0. Serum potassium levels may be high (secondary to the effects of hyperosmolality as it draws potassium from the cells). .rehydration. . circulation and restore good urine flow. It is important to remember that it is the severe hyperglycemia and the concomitant obligatory shift of water from the intracellular to the intravascular compartment that prevents this latter space from collapsing at the time of severe fluid depletion.investigation of precipitating factors. if this suffices to stabilize the blood pressure. and improve the rate of urine production. the intravenous fluid can be changed to 0. 6. and acute circulatory collapse is a common terminal event in HNC. Treatment This condition is a medical emergency and the patient should be placed in an intensive care unit. The aim of this phase of intravenous fluid . Serum sodium may be high (if severe degree of dehydration is present).electrolytes replacement.45 % sodium chloride to provide some free water.45 % sodium chloride is used at a rate of 150 to 500 ml/hour depending on the state of hydration. Many of the management techniques recommended for a patient with DKA are applicable here as well.reduction of hyperglycemia. normal. potential hypovolimic shock (as fluid moves from the extracellular space back into the intracellular space) may occur. The goals of therapy include: . But potassium deficiency exists. . or low (from marked urinary losses from the osmotic diuresis). The immediate aims of treatment are to rapidly expand the contracted intravascular volume in order to stabilize the blood pressure. improve the circulation. With too rapid a correction of hyperglycemia. previous clinical response and the balance between fluid input and output. or high (when the marked shift of water from the intracellular to the extracellular space due to the marked hyperglycemia is present). Treatment is starting by infusion 1 to 2 liters of 0. treatment of complications. normal.9 % sodium chloride over 1 to 2 hours.

When the plasma glucose reaches the range 11 – 13 mmoll/l. Following recovery the acute episode. but rather to maintain stable circulation and renal function and to progressively replenish water and sodium at rates that do not threaten or cause acute fluid overload. Generally.45 % sodium chloride with careful serum potassium and ECG monitoring.therapy is not to attempt to rapidly correct the total fluid deficit or the hyperosmolality. Potassium replacement is usually started by adding 20 mmoll/l to the initial liter of the intravenously-infused 0. but this view is not universally accepted. It is important to remember that because of insulin therapy causes blood glucose levels to fall. this is changed to a 1 or 2 injection regimen. half of the loss is replaced in the first 12 hours and the rest in the subsequent 24 hours.05 – 0. initially some advocate delaying insulin therapy while infusion normal saline until vital signs have improved. Insulin therapy Insulin treatment in HNC is started by 10 to 20 unites of regular insulin intravenously as a bolus dose prior to starting the insulin infusion and then giving intravenously regular insulin in a dose of 0. other authorities recommend smaller doses of insulin. Thus. Treatment of electrolyte disorders Once urine flow has been reestablished. potassium should be added to begin repletion of the total body deficits. 5 % glucose should be added to the intravenous fluids to avoid the risk of hypoglycemia. patients are usually switched to adjusted doses of subcutaneous regular insulin at 4 to 6-hour intervals. water shifts into the cells and existing hypotension and oliguria can further aggravated.10 unites/kg/hour (many authorities routinely use the same insulin treatment regimens as for treating DKA. . When they are able to eat. and many obese type 2 diabetics with NHC require larger insulin doses to induce a progressive decrease in their marked hyperglycemia. because they believe that patients with type 2 DM are offer very sensitive to insulin.

pheformin therapy. Likewise. 2. The hallmark of LA is the presence of tissue hypoxemia. 3. and the pyruvic to lactic ratio is 10:1. which leads to enhanced anaerobic glycolysis and to increased lactic acid formation. a serious condition characterized by excessive accumulation of lactic acid and metabolic acidosis. LA predisposes to accumulation of beta-hydroxybutyric acid. so. Diagnostic criteria . Usage of bigyanids. The normal blood lactic acid concentration is 1mmol/l. in turn. The reaction is reversible and involves LDH in both directions. Predisposing factors 1. the deficiency of NAD impairs the conversion of beta-hydroxybutyric into acetoacetic acid. Pyruvic acid NADH Acetoacetic Lactic acid NAD Beta-hydroxybutyric Piruvic acid is converted into lactic acid by lactic dehydrogenase (LDH) in the presence of reduced nicotinamide adenine dinucleotide (NADH). An increase in lactic acid without concomitant rise in pyruvate leads to LA of clinical importance. Ketoacidosis (it is important to have a very high index of suspection with respect to presence of LA). LA results from decreased availability of NAD caused by lack of oxygen. the reaction for ketone bodies may be negative or slightly positive. which. is converted into NAD. Alcohol intoxication.LACTIC ACIDOSIS (LA) DM is one of the major causes of LA. 4. Thus. Heart and pulmonary failure (which leads to hypoxia). The conversion of acetoacetic acid into beta-hydroxybutyric acid also requires the oxydation of NADH. which does not react with acetest tablet.

Table 2. cardiovascular disease) may be evident. renal disease. Physical examination 1.Signs and symptoms 1. Age Type of DM Predisposing DKA Below 40 Type 1 > type 2 Insulin deficiency HNC Above 40 Type 2 Dehydration LA Above 40 Type 2 Hypoxia . and abdominal pain may be present. Poor skin tugor and dry skin may be prominent.. Acrocyanosis is common. nausea. HNC and LA. lassitude. 4. 4. drowsiness. Comparison of DCA. 5. Volume expanders and oxygen therapy are helpful treatment as well. LA can be treated with low dose insulin regimens with 5 % glucose solution infusion. Myalgia is common. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis. bicarbonate therapy should be used (intravenously-infused 2. Blood glucose level is not high 2. Findings associated with coexisting medical problems (e. Hypothermia is common in LA. 3. Glucosurea is absent. blood pressure is decreased. Kussmaul breathing (deep. vomiting.5 % sodium bicarbonates 1 to 2 l/day). Anorexia. Treatment of LA LA is treated by correcting the underlying cause. Symptoms of central-nervous-system involvement include headaches.g. Tachycardia frequently is present. 3. 2. Blood lactic acid is high.2. In severe cases. 3. sighing respiration) is present as respiratory compensation for the metabolic acidosis and is obvious when the pH is less than 7. Diagnostic criteria of different hyperglycemic coma are shown in table 2. 2. 4. Laboratory findings 1.

cardiovascular or pulmonary disease General Several days duration or less than 1 day About 15 % Several days duration About 85 % Less than 1 day About 90 % More acidic and less dehydrated.Thrombosis . elevated or low Normal. hyperventilation Rare Neurologic symptoms and signs Laboratory findings .blood pH .blood glucose .serum sodium . sometimes insulin Normal or about 10 – 11 mmoll/l Normal Normal Low Less than 7.factor Prodromes Underlying renal.serum bicarbonate .serum potassium .plasma ketones . Precipitating factors . no hyperventilation Very common More acidic and less dehydrated.Mortality Diabetes treatment after recovery More dehydrated and less acidic. elevated or low Low Less than 7.serum osmolality . elevated or low Normal Normal Over 350 mOsm/l ↓or normal Frequent 20 – 50 % Diet alone or oral agents.35 Less than 330 mOsm/l ↑ Rare 1 – 10 % Always insulin Very high (about 40 – 50 mmoll/l) Normal. Hypoglycemia represents insulin excess and it can occur at any time. hyperventilation Very common High (about 20 – 30 mmoll/l) + Normal. sometimes insulin HYPOGLYCEMIA It is a syndrome characterized by symptoms of sympathetic nervous system stimulation or central nervous system dysfunction that are provoked by an abnormally low plasma glucose level. elevated or low Normal.free fatty acids Complications: .35 Normal Normal Very rare About 90 % Diet alone or oral agents.

.tremulousness.faintness.. (Improvement in the cerebral nervous system manifestations will be with a rise in blood glucose.extreme activity. which is usually present when the patient awakes. . stupor.hypopituitarism and adrenal insufficiency. . .drug interaction.nervousness.palpitation. .and sometimes hunger. visual disturbances.liver or renal disease. .sweating.alcohol ingestion. . Diagnostic criteria Signs and symptoms Two distinct patterns are distinguished: 1) adrenergic symptoms (they are attributed to increased sympathetic activity and epinephrine release): . coma or seizures. .) A common symptom of hypoglycemia is the early morning headache. inappropriate behavior (which can be mistaken for inebriation). .irregular ingestion of food. 2) cerebral nervous system manifestations: confusion. . .

candy. The skin is cold. Hypoglycemic coma is commonly associated with abnormally low body temperature 4. Hyperreflexia can be elicited. Low level of blood glucose Treatment Insulin–treated patients are advised to carry sugar lumps. .Patients should be familiar with the symptoms of the hypoglycemia but some of them are not heralded by symptoms. Patient may be unconsciousness. 3. 2. or glucose tablets at all time. Laboratory findings 1. moist. Physical examination 1.

. followed by a continuous infusion of 5 % glucose (10 % glucose may be needed) until it clearly can be stopped safely. the patients have to drink a glass of fruit juice or water with 3 tbsp. i/m or i/v with next fruit juice or candy taken. 3) glucocorticoids and adrenaline are helpful as well. further injections are unlikely to be effective. of table sugar added or to eat candy.5 – 1 unit (0. If the patient does not respond to 1 unit of glucagon within 25 minutes. and to teach their family members to give such treatment if they suddenly exhibit confusion or inappropriate behavior: 1) glucagon 0.5 – 1 ml) s/c. Glucagon 2) an i/v injection of 20 or 100 ml of 40 % glucose.If the symptoms of hypoglycemia develop. and are not recommended.

The islets also contain many nerve endings (predominantly involuntary. The brain and blood cells are unresponsive to insulin. The most important target organs for insulin action are: the liver. nerves that monitor and control internal organs). These capillaries emerge and coalesce into small veins outside the islet. Table 2. Table 1. lipids and nucleic acids (table 2)). most of the pancreatic tissue is devoted to exocrine function. proteins. muscles and adipocytes. Each islet is supplied by one or two very small arteries (arterioles) that branch into numerous capillaries. in which digestive enzymes are secreted via the pancreatic ducts into the duodenum. and F (or PP) cells (table 1) and are located at the periphery of the islet. with the head lying immediately adjacent to the end the body and tail extending across the midline nearly to the spleen. or autonomic. The endocrine pancreas consists of the islets of Langerhans (named for the 19thcentury German pathologist Paul Langerhans). Anatomy and physiology of pancreatic gland Pancreatic gland is located in the upper abdomen. Biological effects of insulin Type of metabolism carbohydrate metabolism The effects of insulin  stimulation of glucose transport across muscle and adipose cell membranes  regulation of hepatic glycogen synthesis  inhibition of glucose formation – from glycogen (glycogenolysis) and – from amino-acid precursors (glyconeogenesis) . There are approximately one million islets that weigh about 1 gram Approximately 75% of the cells in each islet are insulin-producing beta cells. Production of hormones by pancreatic glands Cell type Endocrine product Alpha cells (A cells) glucagon Beta cells (B cells) insulin Delta cells (D cells) somatostatin F (or PP) cells pancreatic polypeptide Insulin is an anabolic hormone (promotes the synthesis of carbohydrates. delta. which are clustered centrally in the islet. The remainder of each islet consists of alpha. In adults.We recommended you to repeat general information about diabetes mellitus.

Table 3. DNA and RNF 1) stimulation of the intracellular flew of potassium. The action of insulin can be decreased by contra-insulin hormones (table 3). phosphate and magnesium in the heart. Action of contra-insulin hormones Hormone glucagon somatostatin glucocorticoids Action  stimulates glycogenolysis  stimulates glyconeogenesis  inhibits secretion of insulin  regulates glucose absorption from alimentary tract into blood  decrease of glucose utilization by tissues  stimulate glycogenolysis  stimulate glyconeogenesis  increase lipogenesis (in patients with insulin resistance)  inhibits β-cells secretion  stimulates glycogenolysis  stimulates ACTH secretion  stimulates α-cells (which secret glucagon)  increases activity of enzymes which destroy the insulin  stimulates glyconeogenesis  increases of glucose exit from the liver veins into blood  decreases of glucose utilization by tissues  stimulates glucocorticoides secretion and β-cells secretion  increase glucose absorption into blood  stimulate glycogenolysis  inhibit fat formation from the carbohydrates DIABETES MELLITUS catecholamines somatotropin ACTH thyroid hormones . 2) inhibition of inotropic and chronotropic action (unrelated to hypoglycemia).Protein metabolism Lipid metabolism Nucleic acids metabolism Other effects of insulin: The result of these actions is a reduction in blood glucose concentration  the transfer of amino acids across plasma membranes  stimulation of protein synthesis  inhibition of proteolysis  incorporation of fatty acids from circulating triglyceride into adipose triglyceride  stimulation of lipid synthesis  inhibition of lipolisis  stimulation of nucleic acid synthesis by stimulating the formation of adenosine triphosphate (ATP).

The disease is more common in persons after age 45. absence of enzyme. in certain ethnic groups. excessive quantity of contra-insulin hormones. mellitus means “sweet”.  insulin: abnormal insulin. insulin antibodies. (The pathologic process can be on the next levels:  beta cells: they can be not sensitive for the high level of glycemia. born from the mother with type 1 diabetes. etc. Prediabetes (risk factors or predispose factors):  obesity. and from the sick father – 1:15. Stages of diabetes mellitus development 1. Relative insulin insufficiency means that pancreas produces or can produce insulin but it doesn’t “work”. physical findings and laboratory abnormalities. which converts proinsulin into insulin. The clinical syndrome known as DM comprises a wide variety of symptoms.  receptors: decreased quantity of receptors or diminished binding of insulin. which develops due to absolute or relative insulin insufficiency and characterized by chronic hyperglycemia.Epidemiology. The term diabetes mellitus refers to the excretion of large quantities of sweet urine. and in those with a positive family history of DM: for a child. the pathophysiology is partly understood and treatment is unsatisfactory. Each 12-15 years the quantity of diabetics increases twice. risk to get diabetes is 1:50. changes of different systems and organs of patient. It is probably fair to state that about 4 to 7 percentage of the world population is affected with diabetes mellitus (DM). Diabetes mellitus – is an endocrine – metabolic disease. . Absolute insulin insufficiency means that pancreas produce insulin in very low quantities or doesn’t produce it at all (due to destruction of beta-cells by inflammation. Diabetes is an old word for siphon and means “dieresis”. in which multiple etiologic factors are involved. The hallmark of DM is hyperglycemia. in obese individuals. autoimmune process or surgery).

 idiopathic. 3. Etiologic classification of DM (WHO recommendations. Clinical manifestation of DM. . infectious hepatitis.  persons which were born with weight more than 4. cytomegalovirus. infection mononucleosis. hypertension. positive family history of DM.  women in which: = were born children with weight more than 4. =had abortions and dead child in anamnesis. Impaired glucose tolerance (latent DM). 2. . = rubella. Type 1* of DM (destruction of β-cells which mostly leads to absolute insulin insufficiency):  autoimmune.0 kg.0 kg. mumps. = furunculous.persons with: = atherosclerosis. 1999) I. = autoimmune diseases. Coxsackie virus.

Alfa-interferon). Myotonic dystrophy. Wolfram syndrome. MODY-2. Friedreich's ataxia. neoplasia.II. somatostatinoma)  drugor chemical-induced (Vacor**. Turner's syndrome. Gestation diabetes. glucagonoma. Lawrence-Moon Beidel syndrome. Porphyria. fibrocalculosis. Other specific types:  genetic defects of β-cells function (MODY-1. pancreatectomy. A genetic predisposition. Diazoxide. MODY-3. pheochromocytoma. III.  diseases of the exocrine pancreas (pancreatitis. Beta-adrenergic agonists. thyrotoxicosis. Exposure produces destruction of the beta cells of the pancreas. causing diabetes mellitus in survivors. Type 2 of DM (resistance to insulin and relative insulin insufficiency or defect of insulin secretion with or without resistance to insulin). etc). cystic fibrosis. antibodies for insulin. Type 1 is characterized by pancreatic islet beta cell destruction and absolute insulinopenia. aldosteroma. Nicotinic acid. Klinefelter's syndrome. conferred by diabetogenic genes on the short arm of chromosome C. lipoatrophic diabetes. Phenytoin. Prader-Willi syndrome. Pentamidine.  genetic defects of insulin action (insulin type A resistance. antibodies for insulin’ receptors)  Other genetic syndromes sometimes associated with diabetes (Down syndrome. Cytomegalovirus)  Uncommon forms of immune-mediated diabetes (“stiff-man. etc) IV. etc). Current formulation of the pathogenesis of type 1 DM includes the following: 1.Arabic numerals are specifically used in the new system to minimize the occasional confusion of type “II” as the number “11” **. either as part of it or in close proximity to the major histocompatibility complex (MMHC) region (more than 95 % of type 1 diabetes . Huntington's chorea.  endocrinopathies (acromegaly. Thyroid hormone. leprechaunism. Glucocorticoids. Rabson-Mendenchole syndrome. *. trauma. Thiazides.Vacor is an acute rodenticide that was released in 1975 but withdrawn as a general-use pesticide in 1979 because of severe toxicity. Cushing’s syndrome. hemochromatosis).  infections (Congenital rubella.

leading to slow. III. 2. V. Progression of autoimmune insulities with destruction of >50 % of β-cells.this occurs to lack of energy. II. 1986) I. An immune mechanism gone awry. HLA DR2 confers protection against the development of type 1 DM).as more water is excreted.individuals are HLA DR3. Osmotic diuresis induced by glucose results in polyurea and subsequent polydipsia. Pathophysiology of DM Defective polymorphonuclear function → infection ↑ Hyperglycemia → glucosurea → polyurea → dehydration Insulin lack ↓ Hyperosmolality Proteolysis → weight loss → muscle wasting → polyphagia Lipolysis → free fatty acid release → ketosis → acidosis Table 1. . . Putative environmental triggers (possibly viral infections (Coxsackie B. Increased proteolysis with  Polydipsia  Polyphagia  loss of weight . IV. Development of manifest DM (table 1). . rubella) or chemical toxins (nitrosourea compounds)) that in genetically susceptible individuals might play a role in initiating the disease process. Putative environmental triggers. on the other hand. VI.energy (calories) is lost as glucose in the urine. Total β-cells destruction. Loss of water itself also contributes to weight loss. Active autoimmune insulities with β-cells destruction. 3. A genetic predisposition or changes of immunity. DR4 or DR3/DR4. the body requires more water intake. either initiation of immune destruction or loss of tolerance. Stages of type 1 DM development (by Flier. The classic manifestation of diabetes mellitus Signs and symptoms  Polyurea Mechanism of their development .once plasma glucose concentration exceeds the renal threshold (about 180 ml/dl or 8 –9 mmol/l) glucosurea ensues. progressive loss of pancreatic islet beta cells and eventual clinical onset of type 1 diabetes.

accounting for 95 – 90 % of the diabetic population. Most investigators agree that genetic factors underlie 2 DM. physical activity. peripheral neuropathy with risk of foot ulcers. Long-term complications of diabetes include retinopathy with potential loss of vision. weakness . Individuals with type 1 DM are ketosis prone under basal conditions. but it can also occur in lean persons. . but none is specific to the disease. notably in muscle mass. Patients have dependence on daily insulin administration for survival.  fatigue and . The lesions resemble red plaques with distinct borders). Presenting signs and symptoms of type 2 DM include polyurea.mobilization of aminoacids leads to enhancement of protein catabolism and loss of weight. and stress are among the most commonly implicated environmental factors which play a role in the development of the disease. polyphagia. diet. Type 2 DM is the most common form of diabetes. Patients with diabetes have an increased incidence of atherosclerotic cardiovascular. and cerebrovascular disease. with the possible exception of necrobiosis lipoidica diabeticorum (it consists of skin necrosis with lipid infiltration and is also characteristically found in the pretibial area. Obesity. nephropathy leading to renal failure. Patients with DM are at risk of chronic complications developing (Chapter ???? tablers???).develops due to increased lipolysis which cause the release of  acidosis free fatty acids. peripheral arterial. and cardiovascular symptoms and sexual dysfunction. The onset of the disease is generally in youth. and autonomic neuropathy causing gastrointestinal. which are metabolized to ketones by the liver. amputations. genitourinary. but it can occur at any age.probably occur as a result of decreased glucose utilization and electrolyte abnormalities. polydipsia. the majority of individuals (80 – 85 %) are obese. Hypertension and abnormalities of lipoprotein metabolism are often found in people with diabetes. but it is probably not caused by defects at a single gene locus. and Charcot joints. intrauterine environment. Physical examination Skin The skin is a common target of DM. Many lesions can be observed.

involvement of the small vessels of the heart can lead to cardiomyopathy. gastritis with decreased secretion ability. arterioles. Bones Osteoporosis and osteoarthropaphy can be finding in patients with DM. particularly the coronary circulation. Cardiovascular system (CVS) Involvement of CVS. in the same quantity cases in both sexes. The skin is dry and itches. is common in patients with DM. Atypical (painless) forms of ischemic heart disease are common in diabetics. arteries. which is usually located on the buttocks. It has been suggested that in some patients with DM. Infections of the skin by bacteria and fungi.The most common skin lesion is diabetic dermopathy (it is characterized by brown. independent of narrowing of the major coronary arteries. look like eruptions (but is not really diabeticorum since it occurs in the patients with lipoprotein abnormalities. hepatosis and diarrhea are common in patients with DM. particularly hyperchylomicronemia. atrophic. Gastrointestinal tract Paradontosis. smoking and hyperlipoproteinemia. duration and severity of the diabetes. Several factors play a role in the high incidence of coronary artery disease seen in patients with DM. These include age of the patient. elbows and knees. gastroduodenitis. besides patients sometimes have xanthoma diabeticorum. Myocardial infarction is responsible for at least half of deaths in diabetic . Subcutaneous adipose tissue The abdomen type of obesity is common in patients with type 2 DM. whether or not patient has DM). The heart. and presence of other risk factors such as hypertension. hyperkeratosis. well-demarcated areas in the pretibial region which resemble sears). Sometimes generalized subcutaneous adipose tissue atrophy can be observed in diabetics. and capillaries can be affected. candidiasis of the external female genitalia. and nail disorders are common in the patients with DM but nothing is specific with regard to their development. Cardiovascular changes tend to occur earlier in patients with DM when compared with individuals of the same age.

retinitis.patients. Atherosclerosis of femoral. Diabetic microangiopathy of lower extremities can be on patients also. destruction of juxtaglomerular cells. Kidneys and urinary tract Renal disease include diabetic nephropathy. popliteal and calf larger arteries may lead to the diabetic macroangiopathy of lower extremities. pyelitis. and cataracts. lupus erythematosus. with exception of diabetic nephropathy. are not at all peculiar to DM and can be observed in many other conditions. chorioretinitis. This sugar may be subsequently converted into fructose by sorbitol dehydrogenase. these abnormalities. sinusitis. acute poststreptococcal and membranoproliferative glomerulonephritis. which presents as intermittent claudication. The epithelial cells of the lens contain the enzyme aldose reductase. . bronchitis. and mortality rate for the diabetics is higher than that for nondiabetics of the same age who develop this complication. The rise in intracellular osmolality leads to increased water uptake and swelling of the lens). necrosing renal papillitis. pyelonephritis. numbness. acute tubular necrosis. sympathetic-nervous-system dysfunction and volume expansion). which converts glucose into sorbitol. cystitis and others. cold extremities. Eyes Complications of the eyes include: diabetic retinopathy ceratities. Hypertension is common in patients with DM. pneumonia. Sorbitol is retained inside the cells because of its difficulty in transversing plasma membranes. focal glomerulosclerosis. Respiratory system Mucomycosis of the nasopharinx. tingling and gangrene. idiopathic membranous nephropathy. Obviously. nonspecific immune complex glomerulonephrities. Diabetic nephropathy can develop in patients with DM. The last one occurs commonly in the patients with longstanding DM and may be related to uncontrolled hyperglycemia (glucose metabolism by the lens does not require the presence of insulin. particularly in the presence of renal disease (as a result of atherosclerosis. tuberculosis are more common in patients with diabetes than in nondiabetics.

2.3 – 5.  blood for glucose determination is obtained from an anterior cubital vein before glucose ingestion and in 2 hours after ingestion.  subjects should remain seated. Conditions for performing an oral GTT have been standardized:  no special dietary preparation is required for an oral GTT unless the patient has been ingesting <150 gm/day of carbohydrate. and physical findings consistent with the disease should offer no difficulty in arriving at the correct diagnosis. On the other hand. Clinical manifestations of DM. 1) fasting serum glucose (if the value is over 6.5 – 6.1 7. and 1. Table 2.8 5. glucosuria. The presence of the marked hyperglycemia.1 >6.  the amount of glucose given is 75 g for adults (100 g pregnant women. a tendency to acquire infections. polyuria. Patient have to drink glucose dissolved in 250 ml of water.5 – 6.1 mmol/l (120 mg/dl) on two or more separate days.1 >11.8 5. Then give 150 – 200 gm carbohydrate daily for 3 days prior to test.1 <7. following overnight fast of 10 to 16 hours. the patient probably has DM). 2) the glucose tolerance test (GTT): If the diagnosis is still in doubt.5 <7. Laboratory findings.The diagnosis of DM The diagnosis of DM may be straightforward or very difficult. mmol/l Fast 2 hours after glucose intake 3. without prior coffee or smoking.  unrestricted physical activity should proceed the test. mild glucose intolerance in the absence of symptoms or physical findings does not necessarily indicate that DM is present. Interpretation of glucose tolerance test results Diagnosis Normal Impaired fast glycemia Impaired glucose tolerance Diabetes mellitus (table 3) The level of capillary blood glucose. polyphagia. polydipsia. lethargy. The diagnosis of DM include: 1.  test is performed in the morning.75 g/kg of ideal body weight for children). then perform a GTT (table 2).1 .8 – 11.

hepatic.The major indication for an oral GTT is to exclude or diagnose DM (mostly type 2) in those suspected of having diabetes although fasting or symptomatic hyperglycemia is absent. indometacin. polyneuropathy. 7) acetonurea. The criteria of DM do not apply to patients treated with drugs that can impair glucose tolerance (e. Instrumental investigations usually are used to diagnose chronic complications of DM. 5. or to have infections.g. 2. nicotinic acid. 6) glucose level in urine. Table 3.. 6. oral contraceptives containing synthetic estrogenes) or to patients who develop nausea. oral hypoglycemic . 8) blood lipids and others. sweating.. 3.g. 3. The level of HbA1c >6. Various conditions (other than DM) and drugs can cause abnormalities in the oral GTT. thiazids. 5) C-peptide (it is not affected by antibodies to exogenous insulin and is used to distinguish type 1 and 2 DM if there is still a need after clinical determination).. glucocorticoids. retinopathy). moderate (over 40) Gradual Stable Rare develops Obesity in 80-90%of patients Diet. 4) islet cell antibody levels will be positive prior to any insulin administration in 60 – 80 % of patients with type 1 DM. e. in patients with a clinical condition that might be related to undiagnosed DM (e.5% estimate diagnosis of DM and may be alternative method of DM diagnostic criteria in compare to GGT).g. diet Type 2 DM Old. Age Beginning of disease Duration Ketosis. 4. faintness or pallor during the test. renal and endocrine disease that impairs glucose tolerance. Differential diagnosis of type 1 and type 2 DM Signs 1. ketoacidosis Body weight Treatment Type 1 DM Young (under 40) Acute Labile Often develops Decreased or normal Insulin. 3) glycohemoglobin (HbA1c) (This test is an indicator of blood sugar control during the previous 2-to-3-month period.

frequent hypoglycemia complications can be last stages of longobserved (but not last term (chronic) stages*) complications are present** * . autonomic diabetic neuropathy. Season of disease beginning 9. ** . Spreading Moderate. Connection with HBAsystem 10. etc. Late complications 13.nonproliferative stage of diabetic retinopathy. /l (4 %) ketosis is common. Degrees of severity (table 4) 8. Mortality 14. diabetic nephropathy on stage of proteinurea or chronic renal failure. moderate.4 – 14. diabetic foot syndrome. Level of insulin and Cpeptide 11. severe Frequently autumn-winter period Present Decreased or absent Present in 80-90% of patients on first year Microangiopathies Less than 10% 10-20% Mild. Antibodies to β-cells 12. severe Absent Absent Frequently normal level Absent Macroangiopathies More than 20% 80-90% Table 4. Degrees of severity of DM Criteria compensation can be achieved by mild Diet Degree of severity moderate oral hypoglycemic agents (in patients with type 2 DM) or insulin (in patients with type 1 DM) 8. /l (2 %) 14.0 40 gr. diabetic neuropathy. etc. mmol/l Glucosuria Complications Acute complications 8.preproliferative or proliferative stages of diabetic retinopathy.0 20 to 40 gr.4 20 gr. diabetic nephropathy on stage of microalbuminurea. /l (2 – 4 %) ketosis can occur Severe by insulin or oral hypoglycemic agents fast serum glucose level. Stages of compensations: proneness to ketosis does not occur long-term are rare or only (chronic) functional stages complications can be observed . postinfarction cardiosclerosis. stroke.agents or insulin 7.

5 mmol/l during the day and comatose or precomatose status are absent). Compensation. Comatose or precomatose statuses are absent. decompensation ** >7. Comatose or precomatose status are present. Fast serum glucose is high. 2. 5.0% 6. mmol/l **Criteria of decompensate stage: 1. 3.0 mmol/l in old patients or which have cardiovascular disorders) (table 5). Fast serum glucose level is normal (but can be under 7.5 >6.5 . Glucosuria is present.0 7. 2.4-5.5 *The level of glucose in capillary blood. Glucose in urine is absent. Subcompensation.0 6.1 – 7.1 – 7.5%. 5.1. 4.1 – 7. % <7.0 8.1 – 6. Criteria of carbohydrate metabolism compensation in patients with DM Criteria compensation subcompensation HBA1c. Table 5.5 – 8. Glucose level fluctuation is over 4. 3. 3.0 7. HbA1c <7. Duration of DM 1.5 Postprandial glucemia (in 2 7. Comatose and precomatose statuses are absent.5 mmol/l during the day . 6.5 Fast glucemia* 5. Decompensation. Criteria of subcompensative stage 1.0 hours after meal intake) Glucemia at bedtime 6.1 – 9. 2. Patient hasn’t new complains. HbA1c 7. Criteria of compensative stage 1.0 >7.0 – 6. Patient may have new complains. Glucose level fluctuation is under 4.4-5.0 – 7.4-5. 4.5 mmol/l during the day. Stabile (glucose level fluctuation is under 4.5 >9.

Mechanism of formulation of diagnosis is shown in table 6.peripheral . the heart. Formulation of diagnosis Disease Peculiarity type or as a result of degree of severity Type.subcompensation .ischemic .ischemic heart disease (type) . vessels. Diabetic nephropathy IV stage.5 mmol/l during the day or comatose and precomatose status are present).autonomic (type) . stage of subcompensation.central .or to show a cause (in a case of another types of DM) . Diabetic angiopathy: 1. Classification of chronic (long-term) complications of DM I.mild . severe degree.severe . Microangiopathy: . Diabetic preproliferative retinopathy.compensation .moderate .angiopathy of lower extremities (stage) . stage or degree -1 -2 .retinopathy (stage on each eye) . Diabetic peripheral neuropathy.nephropathy (stage) . the nervous system. Secondary arterial hypertension.4-5.neuropathic . the kidneys.angiopathy of lower extremities (stage) .mixed degree in a case of presence stage Diabetes mellitus diabetic microangiopathy diabetic neuropathy diabetic macroangiopathy syndrome of diabetic foot arterial hypertension dyslipidemia concomitant diseases Example of diagnosis. Chronic (long – term) complications The long-term degenerative changes in the blood.2. Diabetes mellitus type 1. There is a causal relationship and the level of the metabolic control. moderate degree.decompensation . II stage. Labile (glucose level fluctuation is over 4. Table 6.heart failure (stage according NYHA) . and the eyes as responsible for the most of the morbidity and mortality of DM.

is present in up to 20 % of type 2 DM patients at diagnosis. Macroangiopathy: 1) ischemic heart disease. Diabetic retinopathy is classified according to the changes seen at background during ophthalmoscope examination with pupils dilated (Table 1). 3) angiopathy of lower extremities. II. 2) nephropathy. Diabetic neuropathy. but it can lead to processes that cause blindness (e. 3) central.g. Diabetic retinopathy Dibetics need careful ophthalmologic examination (at least yearly) by ophthalmologist experienced with diabetes. Background retinopathy (the initial retinal changes seen on the ophthalmoloscopic examination) does not significantly alter vision.1) retinopathy. Table 1. 2) visceral (autonomic). Evidence of retinopathy.. About 85 % of all diabetics eventually develop some degree of retinopathy. 1) peripheral. Classification of diabetic retinopathy Stage of diabetic Type Characteristic of changes . rarely present at diagnosis in type 1 DM. 2. 2) angiopathy of lower extremities. macular edema or proliferative retinopathy with retinal detachment or hemorrhage.

secondary rubeos glaucoma.0%). i. Treatment of diabetic retinopathy 1.ischemic Preproliferative retinopathy .. vitreous hemorrhage.exudative .gliose the same changes as in nonproliferative stage but large quantity of retinal hemorrhages.e.exudative . retinal microaneurysms. hard and soft exudates. subatrophy of eyeball and others. and metabolic abnormalities particularly of lipids.vascular . small quantity of hemorrhages an ischemic zones Adhesion of the vessels to the vitreous leads to retinal detachment. because there are direct relationships between stage of diabetes mellitus compensation and development of diabetic retinopathy. have been implicated.  hypocholesterol agents (lipamid. 2.  anabolic agents (nerabol 5 mg.5 – 2 month.hemorrhagic . Genetic predisposition. Compensation of carbohydrate metabolism (HbA1C<7.neovascular .hemorrhagic . The mechanisms involved in the development of retinopathy are not clearly known. 5 years after recognition of this complication 50 % of the patients are blind. nerabolil 1mg/week 1. hypoxia.ischemic Proliferative retinopathy . . lovostatin).vascular . intraretinal microvascular abnormalities and macular edema a hallmark of this complication is neovascularization.retinopathy Nonproliferative (background) retinopathy . growth hormone. Treatment in nonproliferative stage include:  angioprotectors. The prognosis is extremely poor. growth of new vessels in areas of hypoperfusion. retabolil 1ml/3 weeks 3 – 6 times).

but it can course the nephrotic syndrome prior to the development of uremia. I. fibrin). antioxydative therapy (emoxipin. Laser photocoagulation (local. trental). Table 2.mesangial changes due to accumulation of immunoglobulins II. a deposition of hyaline material in the lumen of the afferent and efferent glomerular arterioles.normoalbuminuria (<30 mg/day) .A. criocoagulation or vitrectomy with endolazercoagulation. 3. PP. Arteriolar hyalinosis.high GFR.  vitamins B . which have to performed by ophthalmologist in preproliferative and proliferative stage of retinopathy. .increased renal blood circulation. IgM). Hyperfunction of kidneys . complement and other nonimmunologic proteins (lipoproteins. panretinal). 1) nonproliferative retinopathy: Diabetic nephropathy Diabetic neuropathy it is specific damaging of kidney vessels in diabetics and characterized by nodule or diffuse glomerulosclerosis development. .high or normal GFR. Initial nephropathy . Stage of initial changes of kidney structure (IgG. E. . . Classification of diabetic nephropathy by Mogensen Stage of diabetic nephropathy Characteristic .hypertrophy of kidneys.microalbuminuria (30 to 300 mg/day). . is an almost pathognomic histological lesion of DM (table 2). focal. It is usually asymptomatic until end stage renal disease develops. .  anticoagulants.increased glomerular filtration rate (GFR*) (> 140 ml/min).normoalbuminuria III. Nephropathy develops in 30 to 50 % of type 1 DM patients and in small percentage of type 2 DM patients.

.kidney.blood hypertension.org/professionals/kdoqi/gfr_calculator.glomerular filtration rate. Cocrofta – Gaulta formula and other useful calculators http://www. . and declines with age. 2) CKD2 (Mild) – GFR of 60 to 89 mL/min/1.normal or decreased GFR. using Modification of Diet in Renal Disease (MDRD).0%). 5) CKD5 Kidney failure .decreased GFR.73m2 and no proteinuria. V. and body size.persistent proteinurea (>500 mg/day). .73m2.73m2. Nephropathy or nephrotic stage . . Normal kidney function – GFR above 90mL/min/1. 3) CKD3 (Moderate) – GFR of 30 to 59 mL/min/1. sex. because there are direct relationships between stage of diabetes mellitus compensation and development of diabetic nephropathy.cfm The severity of chronic kidney disease (CKD) is described by five stages. .73m2 with evidence of kidney damage. The GFR is the best test to measure the level of kidney function and determine your stage of kidney disease.GFR less than 15 mL/min/1.73m2 Treatment of diabetic hephropathy Stages I-III 1. Chronic renal failure or uremia . Normal GFR varies according to age. 4) CKD4 (Severe) – GFR of 15 to 29 mL/min/1..periods of blood hypertension IV. It can be found by Reberg – Tareyev test.73m2 with evidence of kidney damage. There are several different techniques used to calculate or estimate the glomerular filtration rate (GFR or eGFR).signs of intoxication *GFR . Compensation of carbohydrate metabolism (HbA1C<7. 1) CKD1 – GFR above 90mL/min/1.persistent blood hypertension .increased serum creatinine.

8gr/1 kg of patient’s weight). 4. Correction of electrolyte’s level: potassium. Diabetic angiopathy of lower extremities Atherosclerosis of large vessels (macroangiopathy) leads to intermittent claudication.GFR< 15 ml/min. Nonclinic stage Functional stage Characteistic Changes could be find only during instrumental examination It is characterized by cold extremities. II. cold extremities and other symptoms which can be also find while arteriols and capillaries are affected (microangiopathy (table 3)). numbness. Table 3. 5.serum potassium > 6. . Moderate restriction of animal protein in diet (≤ 1gr/1 kg of patient’s weight). 4. Enterosorbtion. Terminal stage 1.5 mmol/l. Classification of lower extremities’ angiopathy Stage I. Stage IV 1-3 . calcium. 3. Correction of dyslipedemia (while present). 2. (contraindicated during pregnancy). . 7. . Transplantation of kidney. Correction of secondary anemia. 6. peritoneal dialysis. ACE-inhibitors or ARA in suppressive doses in patients with normal blood pressure and therapeutic while it more than 130/80 mm. Stage V 1-5 – as in stage IV.severe hyperhydration with risk of lung edema development.Hg. tingling. Restriction of animal protein in diet (≤ 0.as in stage I-III. Indications for extracorporal renal replacement therapy: .increasing of protein – energy insufficiency.2. phosphorus. . Extracorporal renal replacement therapy: hemodialysis.

hypo. Surgical therapy (in specialized department).vasodilators. deformities Medicaments therapy 1. . or other complications of DM are present. . Peculiarities of ischemic heart disease in diabetics 1. 6. 2. Smoking.or atrophy of muscles. ulcers. Decreasing of extremities ischemia: . 3. early detection of risk factors. Often can observe atypical forms (without pain).0%). Male: female = 1:1 (nondiabetics = 10:1). The prognosis is even worse if ketoacidosis. calluses. Diabetic patients have more complications of MI (arrhythmias. 3. infections. 2. Frequency of myocardial infarction (MI) and mortality is higher in diabetics than that in nondiabetics of the same age. Antibacterial therapy (in a presence of ulcers). 6. Correction of hypertension. 4.pain during physical examination III. diminished pulses. 5. gangrene Treatment of diabetic angiopathy of lower extremities Patient have to be educated in foot care. ulcers. 5. Treatment of dislipidemia.anticoagulants and antiaggregative preparations (under the control of coagulogram and retina). cardiogenic shock and others) than nondiabetic ones. exposed nails. 4. Cardiovascular changes tend to occur earlier in patients with DM when compared with individuals of the same age. Organic stage It is characterized by trophyc changes: dry skin. Compensation of carbohydrate metabolism (HbA1C<7.

There are three types of radiculoneuropathy: distal polyradiculoneuropathy (It is characterized by symmetrical sensory loss. weight loss is common. . Central neuropathy (1) encephalopathy is characterized by decreased memory. reflexes are decreased. truncal polyradiculoneuropathy (It is an asymmetric.Diabetic neuropathy It is an old clinical observation that the symptoms of neuropathic dysfunction improve with better control of DM. hyporeflexia. 2)myelopathy). paresthesia and hyperesthesia.). II. inadequate actions and others. diabetic gastroparesis (It leads to the irregular food absorption and is characterized by nausea. Classification of diabetic neuropathy I. and characterized by pain (which is worse at night). truncal monoradiculoneuropathy (It is usually involves thoracic nerves and the findings are limited to the sensory abnormalities in a radicular distribution.). burning of heels and soles. III. dry and cold. The skin becomes atrophic. headache. vomiting.). decreased response touch.). early satiety. hair loss may be prominent. pain at night and during the rest. Peripheral polyneuropathy (radiculoneuropathy). The decreased response to touch and pain predisposes to burns and ulcers of the legs and toes. Accumulation of sorbitol and fructose in the diabetic nerves leads to damage of the Schwann cells and segmental demyelization. muscular weakness involves the muscles of the anterior thigh. lending support to the idea that hyperglycemia plays an important role. Visceral dysfunction: 1) gastrointestinal tract: esophageal neuropathy (It is characterized by segmental distribution with low or absent resting pressure in the low or absent resting pressure in the lower esophageal sphincter and by absence of peristalsis in the body of the esophagus.). bloating and abdomen pain.

6. multivitamins. etc). and infection.). Inhibitors of aldose reductase (sorbinil). malabsorption and fecal incontinence. Sulfate-containing preparations: ɑ. vertigo. carbamazepin (Tegretol). 3) sexual disorders: retrograde ejaculation (which is caused by dysfunction of the pelvic autonomic nervous system). amitriptyline. 5.lipoid acid (dialipon. 7. faintness. tachycardia (but it does not occur in response to hypotension because of sympathetic involvement). postural diarrhea). analgetics. 3. unitiol. and sometimes decreased libido. and syncope upon assumption of the upright posture and is caused by failure of peripheral arteriolar constriction). In patients with encephalopathy nootropil. impotence. Treatment of diabetic neuropathy 1. Symptomatic therapy (. tiogamaturbo). gabapentyn. Vasodilators. 4. magnitolazerotherapy and others). phenytoin.- involvement of the bowel (It is characterized by diarrhea (mostly at night time. Vitamin B-complex. Diabetic foot is divided on three types: of vascular . neuropathy. 2) urinary tract: neurogenic vesicle dysfunction (It is characterized by insidious onset and progression of bladder paralysis with urinary retention. sodium thiosulfate. berlition. constipation. Diabetic foot Appearance of diabetic foot is caused by a combination insufficiency.0%). non-steroid anti-inflammatory drugs. Compensation of carbohydrate metabolism (HbA1C<7. 4) cardiovascular system (diabetic cardioneuropaty): orthostatic hypotension (It is characterized by dizziness. Physiotherapy (inductotermia. piracetam have to be prescribed/ 8. 2.

ischemic. . particularly impairment of afferent pain proprioceptive impulses. .. and flattening of the longitudinal arch.mixed. external rotation. Peculiarities of ischemic and neuropathic diabetic foot Sign Temperature skin Color of the skin Pulsation peripheral vessels Edema Sensibility Ulcers Gangrene Treatment absent partly decreased or normal peripheral (distant). Neuropathic arthropathy (Charcot’s joints) is characterized by painless swelling of the feet without edema or signs of infection. aversion. This arthropathy is associated with sensory involvement. The foot becomes shorter and wider. 2) diabetic arthropathy. Peculiarities of diabetic foot types are shown in table 4. painful dry can be present decreased or absent under the pressure. of lower neuropathy .neuropathic: 1) non-ulcer changes and foot ulcer. no painful moist pallor or cyanotic on decreased or absent normal or pink normal of Ischemic the decreased Neuropathic normal look treatment of diabetic look treatment of diabetic angiopathy extremities TREATMENT OF DIABETES MELLITUS. Table 4.

Diet. Exercise program. 2. Balanced diet (diet should include physiologic meal components: carbohydrate comprises 50 – 60 % of total calories. Nontraditional methods of treatment. fat – 24 – 25 % and protein – 16 – 15 %). Phytotherapy (plant’s therapy). Oral hypoglycemic agents or insulin (indications for each vary with the type of DM and severity of the disease). Prophylaxis of acute and chronic complications. 1. 3. Treatment of DM has to be individualized and includes such methods: 1. The main principles of diet. Diet is the keystone of the treatment of the DM. Patient must understand the importance of differing life-style. which are the major cases of excess morbidity and mortality in diabetics.The treatment of patients with DM is very important and may be difficult because of problems in achieving of normal glucose control. The main principles of DM therapy. Achievement and maintenance of normal or reasonable body weight. 3. 2. Achievement of DM compensation. Because there is good evidence that hyperglycemia conveys risks for all of the common long-term complications of DM. 2. Maintenance (preservation) of working capacity. Physician has to educate. the importance of its control. Education of the patients about the nature of the disease. Normal-calorie diet in patients with type 1 DM (35-50 kcal/kg of ideal weight (weight = height – 100)) and low-calorie diet in obese persons (mostly in patients . motivate and monitor progress. 1. 4. 5. 6. all aspects of self-management and routine practices to minimize the development or severity of the diabetes’ complications. Maintenance of metabolic status at normal level or as close to normal as possible (especially blood glucose and lipid concentration). 4.

Sometimes (mostly in obese diabetics) achievement and maintenance of normal body weight may be enough to eliminate the need for oral hypoglycemic agents or insulin.with type 2 DM (20 – 25 kcal/kg of ideal weight)). margarine in diet. . We try to decrease weight in obese patients on 1-2 kg/month by such diet. increase poultry and fish. lunch – 10 %. Increasing the quantity of high fiber-containing foods (fruits (exclusion: banana. encourage skim milk-based cheeses. not more than 2 – 3 eggs weekly. in which breakfast comprises 30 % of total calories. Sometimes patients need second breakfast (when they have a tendency to develop hypoglycemia). butter. supper – 20 %. dinner – 40 %. Alcohol should be avoided as much as possible because it constitutes a source of additional calories. So. Should be used skim or low-fat milk. white bread. Oral hypoglycemic agents. whole grain flours. 5. (Obesity leads to insensitivity of muscle and adipose tissue to insulin. Regimen has to be consist of 4 – 5 – 6 small feedings a day. Patients need 40 g fibers per day. the diet should be planned in such way that the patient can follow it for the rest of his or her life without starving or becoming malnourished. alcohol). bran. presumable as the result of decreased binding of insulin to its plasma membrane receptor. The defect in insulin binding and secretion is corrected by weight reduction.) 3. it may worsen hyperglycemia. biscuits. 4. 7. Hyperglycemia is the face of increased insulin secretion and hyperlipoproteinemia are secondary to this abnormality. 6. vegetables. decrease red and brown meats. Limiting of meat fat. and it may potentiate the hypoglycemic effects of insulin and oral hypoglycemic agents. Inadequate control of hyperglycemia by the diet and exercises interventions suggests the need for a good glucose-lowering agent. cereal grains. (The most frequent regimen consists of 4 feedings a day. Exclusion of high-calorie carbohydrates (sugar. In such case it comprises15 % of the total calories and we decrease the quantity of calories of the first breakfast and dinner). grapes).

second generation: Glibenclamide (Maninil (3. Commonly used oral hypoglycemic agents Group of oral hypoglycemic agents Insulin sensitizers Insulin secretagogues Oral hypoglycemic agents Increase sensitivity of tissues biguanides to insulin thiazolidinediones sulfanilureas Stimulation of insulin secretion non-sulfanylureas insulin stimulators Incretin mimetics . Gliquidon. Table 2.08)). 2 mg).third generation: Glimepiride (Amaryl (1 mg. . therefore can be used in renal failure Action: . Minidiab (5 mg)).Oral hypoglycemic agents are useful only in the chronic management of patients with type 2 (table 1). .5 mg. Table 1. Duration of action.5-20 16-24 1-2 Glimepiride 1-8 24 1 Gliquidone* 30-120 8-10 1-3 * mostly metabolized by liver (5% excreted with urine.first generation: Tolbutamide.mimic the exenatide natural hormones in your body liraglutide that lower blood sugar vildagliptine Incretin enhansers – stimulate sitagliptine incretin hormones effects saxagliptine Inhibite gastrointestinal tract acarbose absorption Mechanism of action Incretin modulators Alpha-glucozidase inhibitors Sulfanilureas (table 2) include: . Glipizide (Glurenorm (0. Gliclazide (Diamicron (0.5-3.0 16-24 1-2 Glibenclamide 2. Daonil (5 mg)). 95%goes with bile into intestine). times/day mg hours Gliclazide 80-240 8-12 1-3 Gliclazide MR 20-120 24 1 Glipizide 2. Tolazemide. Acetohexamide (now are not used in treatment of the diabetics).03). 5 mg). Chlorpropamide. Commonly used sulphonylureas Preparation Recommended dosage.

. Indications:  patients with type 2 DM (over the age of 35 – 50 years) who do not suffer severe metabolic abnormalities (hyperglycemia). heart.  leucopenia (decreasing of the quantity of white blood cells.  coma and precoma.  allergy.  III – IV stages of angiopathy (but Glurenorm can be used in patients chronic renal failure.  trauma.increasing number of the receptors to insulin. platelets). ketosis or hyperosmolality.stimulation of glycogen synthesis. cerebral diseases.decreasing of glycogenolysis and glyconeogenesis.increasing of the β-cells sensitivity to the glucose and as a result higher secretion of glucose. .] Contraindications:  type 1 DM. . 2) nonpancreatic influence: .normalization of receptors’ sensitivity to insulin.  pregnant diabetics or lactation. Side effects:  hypoglycemia (hypoglycemic effect of sulfanilureas will be the most obvious in 7 – 12 days from the beginning of the treatment).decreasing of glucagon secretion and others. major. .  acute infections.  blood diseases.  [duration of diabetes less than 15 years. . . .1) influence on the pancreatic gland: .  influence on gastrointestinal tract (nausea and others).stimulation of the exocytosis of insulin by insulocytes. because of gastrointestinal tract excretion).increasing of glucose transportation inside muscle cells.

Duration of action.  pregnant diabetics.  acute and chronic liver and kidney diseases with decreased function. occurs in approximately 5 % of patients. Indications: Obese patients with type 2 DM.  anorrhexogenic effects.  decreasing of glyconeogenesis. primary or secondary failure. . Commonly used biguanides Preparation metformine Action: Recommended dosage. They can be used with the combination of sulfanilureas when sulfonylureas alone have proved inadequate to treat DM.  stimulation of anaerobic and partly aerobic glycolis.) Biguanides (table 3): Metformine (Siofor 500. (The usual starting dose is 500 mg 12 – hourly with meal increasing gradually to max 1 g 8-hourly. lipogenesis. (Primary failure defined as an inadequate response during the first month of treatment with maximum dosage. 850 mg). times/day mg hours 500-3000 8-12 3  inhibition of gastrointestinal glucose absorption.  increasing the quantity of insulin’s receptors. with middle severity of the disease without ketosis. Secondary failure may be due to nonadherence to eihter diet or sulfanilurea therapy.  old age.  status with hypoxemia. to disease progression. Contraindications:  heart and lung disease with their insufficiency (chronic heart and lung failure). or to loss of efficacy of the agent. Secondary failure is defined as a recurrence of hyperglycemia after an initial satisfactory response.  enhancing glucose transport into muscle cells. Bufarmin. Adebit.) Table 3 . lactation.

abdominal bloating.18).5 mg 15 – 20 min before each meal. Contraindications:  Chronic gastrointestinal disorders: pancreatitis.  gastrointestinal tract disorders. 100 mg). Side effects:  flatulence.  partly reducing fasting glucose levels by indirectly stimulating insulin secretion in patients who retain β-cell function (and acarbose has a protective effect on βcells). maximum dose is 4 mg before each meal).06.2 mg). Non-sulfanylureas insulin stimulators (table 5) Repaglinide (Novonorm 0. Duration of action.  lactoacidosis. 0. Alpha-glucosidase inhibitors (table 4) Acarbosa (Glucobay 50. (Starting dose is 0. Commonly used alpha-glucosidase inhibitors Preparation Acarbose Action: Recommended dosage.12.  lowering of pastprandial glucose level (postprandial “spikes” in blood glucose are increasingly implicated as a major cause of cardiovascular complications). 1 mg. alcoholism. diarrhea. hepatitis. usually with first bolus f food).  coma and precoma.5 mg. Nateglinide (Starlix 0. miglitol. Table 4 . 0. (It is taken with each meal. . times/day mg hours 150-300 6-8 6-8  inhibition of gastrointestinal tract absorption (blocation of α-glucozidase). colitis. Side effects:  allergy.

Commonly used non-sulfanylureas insulin stimulators Preparation Repaglinide Nateglinide Action:  these drugs stimulates insulin production at meal times.  plasma half0life is less than 1 hour/ Indications:  can be used in elderly with type 2 DM (due to short half-life) and in renal impairment (because it is metabolized in liver). times/day mg hours 15-45 16-24 1 Action of thiozolidindiones  Agonist to the receptors of the nucleus PPARγ of the fat. Commonly used thiozolidindiones Preparation pioglitozon Recommended dosage. Recommended dosage.015.5-16 3-4 3-4 120-480 3-4 3-4 Thiozolidindiones (table 6) Pioglitazon (Actos. muscle tissues and the liver.  transient elevation of liver enzymes. Pionorm) Dose in 1 tabl. 0. times/day mg hours 0.  Increasing of the insulas amount.  Increasing of insulin synthesis in the b-cells. Duration of action.  very rapidly absorbed from the intestine and metabolized in liver. 0.Table 5 .  rash. . Duration of action.03.  visual disturbances. 0. Side effects:  hypoglycemia.045. Rosiglitazon is not used due to side effects Table 6 .  Increasing of the glucose passage to these tissues.

 Anemia.  Heart failure. biguanides. . when diet and exercises are no effective. Prevents the pancreas from giving out glucagon. Action: “incretin effect” is attributed to the insulinotropic action of gut hormones.  Pregnancy. liraglutide (Victoza) – subcutaneous injection daily.  Decreasing of triglycerides. Side effects of thiozolidindiones  Hypoglycemic conditions (rarely). This may make feel less hungry and more satisfied after a meal. lactation.  Allergic reactions to the drug.  Obesity.  Decreasing of gluconeogenesis. Incretin mimetics Exenatide (Byetta). Indications to thiozolidindiones usage  DM type 2. specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). insulin in case of their insufficient efficacy Contraindications to thiozolidindiones usage  Diabetic coma. teenagers.  Children.  Acute and chronic diseases of the liver. This drug lowers blood sugar levels only when they rise too high. ketoacidosis.  Peripheral edema.    Allows pancreas to release insulin. Increasing of glycogen synthesis in the liver. precoma. Helps to slow the rate at which stomach empties after eating.  Using with sulfanilureas.

times/day mg hours 5 24 1 50-100 100-200 10-12 16-24 2 2 thereby extending their period of action by inhibing of dipeptydpeptidase IV (DPPIV). Incretin enhansers (table 7) Onglyza 5 mg Galvus 50 mg Yanuvia 25 mg. 50 mg.  stomch pain. Indications:  can be used in type 2 DM patients. Side effects:  nasopharyngitis.  mild headache. Side effects:  nausea (is usually worse during the first few weeks of treatment and gets better over time). Recommended dosage. Commonly used inhibitors of DPP IV Preparation saxagliptine (onglyza) vildagliptine (galvus) sitagliptine (yanuvia) Action:  Suppress the degradation of a variety of bioactive peptides. Duration of action. . 100 mg Table 7 .Indications:  can be used in type 2 DM patients.  weight loss. including GLP-1.  diarrhea.  pancreatitis.

such as glucagon. cortisol. Coli) by recombinant DNA technology. 3) influence on the immune reactivity. growth hormone and prolactine may be reduced with human insulin. Contamination of small amounts (to 2 %) of other pancreatic hormones. 2) treatment of chronic diabetics complications. except for slightly faster onset of the action. Synthetic human insulin does not have great advantages over purified pork insulin. and secretion of epinephrine. Causes of . The resulting “humanized pork” insulin has the amino acid sequence of human insulin (Actrapid. was the rule. alanine in the 30 position of the B chain of pork insulin is substituted enzymatically by threonine. or by separate fermentation in which A and B peptide are synthesized first and then joined into insulin (Humulin. Subsequent purification have yielded purer (almost 100 %) preparations of beef insulin. with a biologic activity of 26 to 28 units/mg as compared to 22 to 24 units/mg for the older preparations. and pancreatic polypeptide. cough. In the first.5 mg and Siofor 400 mg Plant’s therapy (phytotherapy). C peptide. Two procedures have been utilized. The most recent development has been the preparation of biosynthetic human insulin. Monotard made by Novo-Nordisk). proinsulin. pork insulin. 1) hypoglycemic action. somatostatin. The synthetic hormone has the potential to be less antigenic than the pork insulin. the most commonly used preparations consisted of a combination of pancreatic bovine and porcine insulin. or combination of two. Lilly). The hormone can be produced by single fermentation in which proinsulin is made first and then cleaved into insulin and C peptide. Hypokalemia. Combined preparates  Glibomet consists of Maninil 2. The second approach involves synthesis by Escherichia coli (E. Insulin Insulin has been available for the treatment of patients with DM since 1921. C-peptide suppression. For many years.

h 1–4 6 – 12 Duration of action. 9). and newly diagnosed young diabetic patients. Peak of action. h 0. h 5 . Insulin preparations Group Short-acting Preparations Humodar R Actrapid HM Iletin Humodar B Protaphan HM Humulin L Monotard MC Ultratard HM Ultralong Humodar C15 Mixtard 30 HM Monodar C-30 Onset. and the major difference in their duration of action (Table 8. lipodystrophy.5 14 – 20 20 – 36 Depends on quantity of components Table 9. A multitude of insulin preparations and insulin analogues are available. peak and duration of action are applicable to normal non-insulin-treated subjects.potential use for human insulin include resistance to exogenous insulin.5 – 2. Insulin analogues Group Ultra-short. h 0. Table 8.0 Peak of action.5 – 1. all the types can be injected only subcutaneously. h 5–8 18 – 26 Intermediateacting 1-3 Long-acting Combined preparations 4-8 0.5 Duration of action. Only short-acting insulins should be given intravenously. gestation diabetes. Anticipated short-term administration. Figures on onset.acting (insulin analogues for rapid onset of insulin action) Long-acting inulin Preparations Humalog Hovorapid Epaidra Lantus Levemir Detmir Onset. h 3-4 1 nonpeaked 24 Indications for insulin therapy . beef or pork insulin allergy.10 min.

.5 unite of insulin per kilogram of body weight (0.8 – 1. 1/3 in the evening and then make correction due to the glucose blood level.hypoglycemic reactions may be decreased or prevented because smaller doses of insulin are needed. coma.  surgery.1. Some patients with type 2 DM:  uncontrolled diabetes by diet or oral hypoglycemic agents.6 – 0.  pregnancy and lactation. It using three or four shots of short-acting insulin (1/3 of total daily dose) plus intermediateacting (2/3 of total daily dose) insulin daily is started as soon as possible in an attempt to “rest” the damaged islet cells and help to “induce” a remission (“honeymoon” phase). 2/3 of the total daily dose we give before lunch.  II – IV stages of angiopathy. 2. Initiation and modification of insulin therapy to achieve diabetic control. (Other commonly used insulin treatment algorithms: 1.on the next years is 0.  acute and chronic liver and kidneys disease with decreased function. Insulin doses should be given 30 minutes before meals to allow for adequate absorption of regular insulin. Other advantages include the following: .0 unite/ kg of body weight. . The last is better.  infection diseases.more physiologic match of insulin to meals is achieved.3 – 0. All patients with type 1 DM. . Single prebreakfast injection of intermediate-acting insulin.5 – if the patient with ketosis or DKA).  ketoacidosis. We can use traditional or multiple component insulin program. The daily insulin requirement in patients: .  acute heart and cerebral diseases.on the first year of the disease is 0.

Table 10.3 units/kg/day and in some. Short-acting insulin ½ hour before each meal and a small dose of intermediateacting insulin at bedtime.2/3 – before breakfast. 5.and short-acting insulin: . as well as the need to reinforce the concept that type 1 DM is a lifelong illness without potential for true remission. is not discontinued during this time because of potential development of insulin allergy. 1/3 – short-acting. 4. Before lunch short-acting Before dinner short-acting At bedtime intermediateacting long-acting long-acting insulin analogue long-acting insulin analogue long-acting insulin analogue short-acting short-acting ultra short-acting insulin analogue ultra short-acting insulin analogue short-acting short-acting ultra short-acting insulin analogue ultra short-acting insulin analogue . 2/3 of it – intermediate-acting.2. Combination of intermediate. It results from a partial recovery of islet cell function (as measured by C-peptide). . to no requirement for insulin at all. however. Insulin administration. It occurs within 1 – 3 month after diagnosis and can last from weeks to a few month during which time insulin requirements fall drastically to less than 0. Regimens of insulintherapy Before breakfast intermediateacting + shortacting short-acting short-acting ultra short-acting insulin analogue ultra short-acting insulin analogue + long-acting insulin analogue ) Some words about “honeymoon” stage. 3. The same schemes are shown in table 10. 1/3 – before lunch+dinner. 1/3 of daily dose before dinner. Combination of long-acting (in prebreakfast time) and short-acting insulin (1/2 hour before each meal.single prebreakfast injection of 2/3 intermediate-acting + 1/3 of short-acting. Intermediate-acting insulin: prebreakfast injection of 2/3 total daily dose.

Hypoglycemia.  adrenal insufficiency. 5) exercise accelerates insulin absorption (before planned exercise program patient has to decrease insulin dose or take more caloric diet).  alcohol ingestion.  hypopituitarism. Insulin is stable at room temperature.  liver or renal disease.  genetically engineered pseudo-beta-cells. but refrigeration of the vial while not in use is recommended. This complication represents insulin excess and it can occur at any time (frequently at night (common symptom: early-morning headache)). 1.Some particularities of insulin therapy: 1) insulin acts faster when is administrated intravenously.  islet replacement therapy. 3) it is necessary to change the insulin injection site (because the absorption is more rapid from the new sites). Side effects (complications) of insulin therapy.  pancreatic transplantation. Precipitating factors:  irregular ingesting of food.  extreme activity. . 4) the most rapid absorption from the abdomen.  drug interaction. Future directions in improving glycemic control:  nasal insulin preparations. 2) subcutaneous and intramuscular absorption of insulin is decreased in the dehydrated or hypotensive patients.

 1 mg of glucagon administrated subcutaneously.  therapy with oral contraceptives. Treatment: some have recommended an earlier injection in the morning (5 – 6 a. These include burning and itching at the site of insulin injection. growth hormone).  changing of standard insulin to pure pork insulin or to human insulin. cortisol.m.  in extreme cases – glucocorticoids.  gradual reduction of insulin dose in future. Treatment:  antihistamines. Insulin resistance. Sampling of glucose levels throughout the night might help differentiate the two conditions. Clinical status characterized by insulin resistance:  obesity.  to receive intravenous glucose. and most suggest a late evening (before bedtime) injection of intermediateacting insulin. Somogyi effect (Somogyi phenomenon. because of activation of counterregulatory hormones. 2. Treatment: gradual reduction of insulin dose. purpura and anaphylactic reaction. rebound effect) It is caused by overinsulinization: hyperglycemia proceeded by insulin – induced hypoglycemia. Hypoglycemia causes an increase in the secretion of the counterregulatory hormones (glucagon. Allergic reactions.m. 3. epinephrine.). vasculaties. Dawn phenomenon Many patients with type I DM demonstrate an early morning (4 – 8 a. . It may be confused with the Somogyi phenomenon. skin rash.Treatment (preventing coma):  to eat candy or to drink sweet orange juice (when the symptoms develop).) rise in glucose levels. which inhibit insulin secretion and increase glucose output by the liver (as a result of the stimulation of glucogenolysis and glucogenesis).

Exercise program. Non-true insulin resistance may be caused by long-time injections of insulin into the one site. which occur at the site of insulin injection. Exercises must be clearly planned and depend on patient’s abilities and the physical condition.  acromegaly.lowering blood glucose concentration. .  acanthosis nigricans. 4. glucocorticoid therapy. exclusion of the competition’s elements. Exercise is an excellent adjunct to diet therapy.  chronic liver or renal disease.  Cushing’s syndrome. Lipodystrophy It is atrophy or hypertrophy of the adipose tissue.decreasing insulin requirements. but it is very ineffective when used as the sole weight-reducing modality. .potentiation the beneficial effects of diet and other therapy. 1) the nature of DM and importance of metabolic control. 2) the principles and importance of good nutrition and reasonable exercise program. Exercises may be valuable adjunct to the management of the DM by: . . Patient’s education. Mostly they need to reduce the insulin dosage by 20 – 25 % on the day that strenuous exercises is planned.  the usage of human insulin. patients should carefully monitor glucose level and taking of insulin. To prevent hypoglycemia. Treatment:  changing the site of injection.

1. – published by Merck Research Laboratories. Mohammad Inam Danish Short Textbook of Medical Diagnosis and Management (Third Edition). – Pakistan.3) the principles of adequate foot. 2008 – 496 p. 1. dental and skin care. 1926 – 2058. 4) treatment of DM during the periods of illness. 2009 – P. 6) recognition of hypoglycemia. its causes and methods of prevention. Petro M. 2006 – P. Bodnar/ Vinnytsya “Nova Davidson’s Essentials of Medicine /edited by J. 2. 2002 – 653 p. There are several specialized sanatoriums in Truscavets. The Merck Manual of Diagnosis and Therapy (eighteenth Edition)/ Robert Berkow and others.329 – 414. 7) the importance of general and specific measures to minimize in the best possible way diabetic complications and maintain of good overall health. Edinburg. Myrgorod. Odessa with specialized school for diabetics Literature: Textbook of Endocrinilogy/ edited by prof. Alastair Innes. Elsevier. Additional. 5) techniques of insulin administration and measurement of urine and blood glucose level (if taking insulin). . B. UK . Knyha”. 3.

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