Lecture 4

Acute complications of Diabetes Mellitus.

Diabetes mellitus (DM) is complicated by several urgent complications. They are
diabetic ketoacidosis, hyperosmolar coma, and hypoglycemia. Sometimes it causes
lactic acidosis, but it is very rare pathology.
Diabetic ketoacidosis.
Diabetic ketoacidosis (DKA) is a state of uncontrolled diabetes mellitus (DM) that
is caused by severe insulin deficiency. DKA is characterized by hyperglycemia
(usually grows more than 300 mg/dL or 16.7 mmol/L), ketosis (β-hydroxybutyrate
+ acetoacetate grows more than 5 mmol/L), and metabolic acidosis (arterial blood
pH is usually lower than 7.3).
DKA is severe pathology. In spite of adequate management, its lethality is 5-15%.
Etiology of DKA.
DKA frequently results from action of some precipitating factors. Treatment of
DKA includes revealing of these factors in due time and their elimination (if it is
possible). You should know the main precipitating factors of DKA very well. They
are listed below:
1. Relapse of any concomitant diseases (sharp inflammatory processes,
exacerbation of chronic diseases, infectious diseases, a sharp heart attack,
myocardial infarction, a stroke, etc.)
2. Surgical operations.
3. Traumas and injuries (mechanical, thermal, chemical, etc.).
4. Inadequate management of DM:
 unsuitable calibrated insulin syringes or malfunction of other insulin
injectors (syringe-pens or infusion pumps);
 permanent injection of insulin at the same place resulting to
lipodystrophia and low absorption of insulin from subcutaneous fat
tissue;
 use of expired insulin preparations;
 incorrect storage of insulin preparations (freezing, storage near heaters
or under direct solar radiation, etc.);
 replacement of insulin preparation by another one with different
pharmacokinetics;
 stopping of insulin therapy for the suicide;
5. Infringement of diet rules;
6. Psychological distress.
7. Pregnancy.

15-30% of DKA cases are the first appearance of DM onset. Sometimes

precipitating factors can not be revealed.
 SEVERE INSULIN DEFICIENCY

INHIBITION OF GLUCOSE UTILIZATION IN INSULIN DEPENDENT TISSUE

HYPEROSMOLARITY
HYPERGLYCEMIA ENERGY DEFICIENCY

DEHYDRATION OSMODIURESIS HYPERPRODUCTION OF

CONTRAINSULAR HORMONES
HYPOVOLEMIA LOSS OF
AND SHOCK ELECTROLITES Activation of glycogenolysis,
proteolysis, lipolysis
IMPAIRMENT OF HYPOXIA
CEREBRAL, RENAL
AND PERIPHERAL Activation of gluconeogenesis
BLOODFLOW HYPER and ketogenesis
PRODUCTION
OF LACTATE HYPERPRODUCTION OF
ANURIA
KETON BODIES
COMA
METABOLIC ACIDOSIS
Fig.1. Scheme of DKA pathogenesis
Pathogenesis of DKA.
Scheme of DKA pathogenesis is presented at fig.1. DKA is trigged by severe
insulin deficiency. Insulin dependent cells (adipocytes, myocytes, and hepatocytes)
can not utilize glucose without insulin. Lack of insulin causes energy deficiency in
insulin-dependent tissue. There is paradoxical “hunger in spite of glucose
profusion”. It accelerates production of antagonists of insulin (glucagon, cortisol,
growth hormone, etc.) alike any other starvations. Gluconeogenesis and
glycogenolysis are excessively increased. It results in intensive synthesis of
glucose and ketone bodies. Hyperketonemia causes metabolic acidosis.
Hyperglycemia increases plasma osmolarity and promotes osmotic diuresis.
Osmotic diuresis results in loss of electrolytes, extra- and intracellular dehydration.
Hypovolemia is developed. Circulating blood volume is decreased; perfusion of
cerebral, renal and peripheral tissue is worsened. Kidney hypoperfusion causes
anuria that is developed in terminal stage of DKA. Impairment of peripheral blood
flow results in hypoxia that is associated with increased lactate production.
Cerebral hypoxia, hyperosmolality, intracellular dehydration and severe metabolic
acidosis suppress function of CNS cells. There is development of sopor that is
gradually replaced by coma.

Clinical picture of DKA.

Symptoms of DKA may be classified in several main clinical syndromes:
1. Insipidary syndrome. The syndrome includes polyuria and polydipsia those
are caused by osmotic diuresis.
2. Syndrome of intoxication. Intoxication is displayed by nausea, vomiting,
headache, anorexia, mialgia and sopor.
3. Syndrome of dehydration. It includes low skin turgor, soft tonus of
eyeballs, dry skin, tongue, and oral cavity. Rapid weight loss (several kg in
several days) usually results from dehydration too.
4. Syndrome of ketoacidosis. The syndrome is characterized by ketone odor
and Kussmaul respiration (i.e. deep, sighing hyperventilation).
5. Syndrome of CNS suppression. The drowsiness, sopor and coma are
common.
6. Abdominal syndrome. Stomachache and peritonism (i.e. slightly expressed
symptoms of peritoneum irritation) can be presented at ketoacidosis cases.
Acute erosive gastritis with “coffee lees” retching is possible. Gastric stasis
may be secondary to intracellular potassium depletion. Absence of bowel
sounds is possible. Abdominal syndrome causes false diagnosis of acute
abdomen. Differential diagnosis between them is difficult. Laparoscopy can
be useful for the right diagnosis. N.B! Any operations (except reanimation
ones - tracheotomy, stopping bleeding from a big artery etc.) are
 contraindicated in ketoacidosis state. The DKA cases should be properly
prepared for the operation. Conventional DKA treatment (rehydration,
insulin therapy etc.) is performed during several hours prior to a surgical
intervention. If there is no resolution of peritoneum irritation or there is
worsening of the abdominal state in spite of 3-4 hours of adequate DKA
treatment, true acute abdomen may be supposed.

Diagnosis of DKA
Preliminary diagnosis of DKA case is usually obvious and can be made at the
patient’s bedside. But it should be verified by same laboratory tests. The most
important tests are measurement of blood glucose and plasma ketones.
Typical laboratory finding of DKA cases may be classified in several groups:
 hyperglycemia from 16-17 to 33,3 mmol/L (more expressed
hyperglycemia is typical for hyperosmolar state);
 severe glycosuria and ketonuria (they may be absent if anuria is
developed);
 several times increased ketonemia (normal ketonemia should not exceed
1,72 mmol/L);
 elevated plasma osmolality (normal range within 285-300 mOsmol/L);
plasma osmolality does not exceeds 350 mOsmol/L (more elevated
osmolality is a symptom of hyperosmolar state);
 low arterial blood pH (normal range within 7,35-7,45);
 neutrophilia with shift to the left (it is caused by intoxication of ketone
bodies);
 secondary erythrocytosis that is caused by hemoconcentration;
 uremia that is caused by proteolysis (plasma urea and creatinine are
elevated);
 moderate proteinuria.

Plasma osmolality may be measured directly and calculated according to this

formula:

[PO] = 2*([Na+] + [K+]) +[Glu] + [U] + 0,03∙[Prt],

PO – plasma osmolality, mOsmol/L;

[Na+] – natriemia, mmol/L;
[K+] – kaliemia, mmol/L;
[Glu] – plasma glucose, mmol/L (1 mmol/L = 18 mg/dL);
[U] – blood urea, mmol/L;
[Prt] – proteinemia, g/L.
Potassium level, blood urea and proteinemia insignificantly modify plasma
osmolality. It is possible to apply a simplified formula of effective osmolality:

[EO] = 2*[Na+] + [Glu],

[EO] – effective osmolality, mOsmol/L;

[Na+] – natriemia, mmol/L;
[Glu] – plasma glucose, mmol/L (1 mmol/L = 18 mg/dL);

An ECG should be performed in the emergency room. ECG may give information
about ischemic heart disease or myocardial infarction. But more important, it
provides a yardstick fore subsequent electrocardiographic monitoring of acute
changes of plasma potassium level. More over, the baseline ECG is necessary
because acidemia can produce ECG changes by itself. Some of these changes can
mimic myocardial ischemia.

Management of Diabetic ketoacidosis.

INITIAL MEASURES
1. Clinical examination: blood pressure, pulse and ventilatory rate, skin turgor,
body temperature, search for infection, conscious state.
2. Blood for bedside measurement of glucose (test strips) and plasma ketones
(test strips or tablets).
3. Blood to laboratory for tests: glucose, creatinine, urea, electrolytes; arterial
pH, pO2, pCO2, Hb, white blood cells.
4. Blood, urine, throat swab for cultures.
5. If diagnosis suggested by bedside examination, start rehydration and insulin
therapy.

CONTINUED MEASURES
1. Glucose monitoring with test strip at bedside hourly and in laboratory in 2
and 6 hours, then every 4 hours.
2. Monitor K+ in laboratory in 2 and 6 hours, then every 6 hours.
3. Laboratory measurements of creatinine and electrolytes (in 3, 6, and 24
hours).
4. Frequent monitoring of pulse rate and arterial blood pressure (every half
hour for 4 hours, every hour for another 4 hours, then every 2-4 hours).
5. Monitoring of temperature (in 0, 2, 4, 6 hours, then every 6 hours).
INITIAL TREATMENT
DKA treatment consists of five elements. They are rehydration, insulin therapy;
correction of electrolytes balance, alkali infusion, and “other” measures.
Rehydration.
The importance of adequate early rehydration can not be overemphasized.
Adequate rehydration lowers blood glucose by itself. It is explained by
hemodilution and increasing of the renal glucose excretion. Rehydration improves
tissue perfusion and amplifies insulin action. More over, rehydration decreases
counterregulatory hormone secretion by itself.
The total water deficit of DKA cases is from 10% to 15% of total body weight (5-
12 L). Choose of solution depends on blood sodium level and glycemia.
Normal saline is applied in cases with blood sodium level that is lower than 150
mmol/L.
Half-normal (0.45%) saline is transfused in cases with natriemia grown more than
150 mmol/L.
Sodium saline is substituted by 10% glucose solution as soon as blood glucose
level becomes lower than 250 mg/dL (13.8 mmol/L),. It prevents development of
cerebral edema.
Cerebral edema is very dangerous complication of DKA. Its lethality exceeds 50%.
Cerebral edema is resulted from quick decrease of plasma osmolality that is
associated with fast decreasing of glycemia. Development of osmotic gradient
between cerebral liquor and plasma osmolality causes water relocation from blood
to cerebral tissue. It results in cerebral edema.
It is commonly transfused:
1st hour – 1 L/h
2nd-3d hour – 0.5 L/h
Subsequent hours – 0.25-0.30 L/h
Transfusion rate should be adequate to clinical states. Rehydration is performed
more slowly in the elderly patients. Its adequacy is controlled by central venous
pressure and diuresis (table 1).
Table 1
Accordance of central venous pressure and transfusion rate.

CENTRAL VENOUS PRESSURE TRANSFUSION RATE

Low then 4 cm H2O 1.0 L/h

5-12 cm H2O 0.5 L/h
Grow then 12 cm H2O 0.25-0.30 L/h
Hourly transfused volume should not exceed hourly diuresis more than 0.5-1.0 L.
Too intensive rehydration causes left heart failure and pulmonary edema. Less
intensive one does not resuscitate of patients.
Insulin therapy.
Scheme of “big insulin doses” has not been applied since 1974. This scheme
rapidly decreases glycemia and plasma osmolality. It causes cerebral edema,
hypokalemia and hypoglycemia.
Nowadays there is only scheme of “small insulin doses”. Insertion of 0.1 unites of
insulin/kg of body weight every hour (6-8 U/h) upholds insulinemia that is
sufficient for inhibition of lipolysis and ketogenesis. This insulin injection rate
provides gradual decreasing of glycemia and prevents cerebral edema. As soon as
blood glucose level becomes lower than 250 mg/dL (13.8 mmol/L), insulin
injection rate is halved (3-4 U/h). Insulin injection rate is modified according to
bedside glucose estimations. As soon as glycemia exceeds 250 mg/dL (13.8
mmol/L) previously applied insulin injection rate is restored (6-8 U/h).
Insulin therapy of DKA is started from i/m injection of 16-20 U of rapid acting
insulin or i/v bolus of 10-14 U of the insulin. Subsequent therapy is performed
with i/v perfusion of 6-8 U/h of insulin. Sometimes permanent perfusion can not be
organized (no perfusor etc.). At this case perfusion may be replaced by i/v boluses
those are performed every hour. Insulin doses are the same (6-8 U/h).
Subcutaneous insulin injections are contraindicated in DKA cases. It is explained
by impairment of peripheral blood flow and low insulin absorption from
subcutaneous fat tissue.
Correction of electrolytes balance.
Osmotic diuresis causes loss of electrolytes. Their balance is deranged. The most
clinically significant electrolyte is potassium. Severe plasma potassium changes
may cause iatrogenic death. Hypokaligestia is presented in the most part of DKA
cases. Deficit of intracellular total body potassium is usually 3-12 mmol/kg of
body weight. Despite this, one third of DKA patients initially have hyperkalemia.
It is explained by dehydration and hemoconcentration. Both of them elevate
plasma potassium level and cover lack of potassium. Rehydration and insulin
therapy result in hemodilution, intracellular volume repletion, and restoring of
intracellular potassium transport. It decreases plasma potassium level and may
cause fatal cardiac arrhythmia. This is the reason of administration of potassium
chloride in DKA cases with normal plasma potassium level. But severe
hyperkalemia is very dangerous too; it causes ventricle fibrillation and asystolia.
ECG-monitoring is an important indicator of rapid changes of plasma potassium.
The DKA patient should be ECG-monitored at least in the early stages of therapy.
Early ECG-signs of hypokalemia are:
 slightly widened QT-interval;
  enlarged U-wave (higher than 1.5 mV);
 diffuse smoothing or inversion of T-wave.
Early ECG-signs of hyperkalemia are:
 high, sharp, triangle shaped, and symmetrical T-wave;
 shortened QT-interval;
 ventricle extrabeats.
Other ECG-signs are possible too, but they are vague.
Potassium chloride infusion rate depends of plasma potassium level and arterial
blood pH (table 2).
Table 2
Correction of plasma potassium changes in DKA cases.
Infusion rate of potassium chloride
Kaliemia, (gram of dry substance per hour*)
mmol/L arterial blood arterial blood arterial blood
pH is unknown pH < 7,1 pH > 7,1
< 3,0 3,0 3,0 2,5
3,0-3,9 2,0 2,5 2,0
4,0-4,9 1,5 2,0 1,2
5,0-5,9 1,0 1,5 0,8
> 6,0 no infusion
Remark: * - It is droplet infused 4% potassium chloride solution; 100 ml of the
solution contains 4 g of dry substances.

Alkali infusion.
Vigorous alkalinization has harmful consequences. It causes paradoxical fall in
cerebrospinal fluid pH, impaired oxyhemoglobin dissociation, and hypokalemia.
Paradoxical fall of cerebrospinal fluid pH is explained by selective permeability of
hematoencephalic barrier. The barrier is resistant for carbon acid anions and
permeable for carbon dioxide. Interaction of sodium bicarbonate (-HCO3) with
hydrogen ions (H+) produces carbon acid (H2CO3). Carbon acid is unstable
substance that is dissociated into water (H2O) and carbon dioxide (CO2). Carbon
dioxide permits hematoencephalic barrier and causes paradoxical fall of
cerebrospinal fluid pH. It escalates cerebral hypoxia and worsens patient’s state.
Human data suggest that bicarbonate has no benefit for DKA cases. Despite this, it
is usually considered sensible to give it in the severest cases. It is “step of dispirit”,
because arterial blood pH is lower than 6.8 causes lethal exit.
Sodium bicarbonate infusion is indicated if arterial blood pH is lower than 7.0 and
standard bicarbonate (SB) is lower then 5 mmol/L. 4% sodium bicarbonate
(NaHCO3) is transfused; transfusion rate is 2.5 ml/kg of body weight. Sodium
bicarbonate transfusion is accompanied by additional entering of 1.5-2.0 g of
potassium chloride (35-40 ml of 4% KCl solution). Intravenous bicarbonate
infusion must be stopped as soon as arterial blood pH exceeds 7.0.
“Other” measures
Infection, cerebrovascular accidents, acute myocardial infarction, and trauma are
curable precipitating factors of DKA. They must be diagnosed in duly time and
adequately managed.
If no urine passed in 4 hours, catheterize the patient.
Give 40 mg of furosemide if patient is oliguric.
Give antibiotics if infection is suspected or invasive procedures are going to be
used.
Institute nasogastric suction if patient is comatose or semiconscious.
Give oxygen if PO2 is lower than 80 mm Hg.
Heparinize (500 U subcutaneously every 4 hours) comatose or very hyperosmolar
(>350 mOsmol/L) patients.
Give blood or plasma expander, if systolic BP is less than 80 mm Hg in 2 hours.

CONTINUED TREATMENT.
When patient is ready to eat, reinstitute short-acting, subcutaneous insulin therapy.
If patient is on intravenous insulin regimen, continue infusion for 1 hour after
subcutaneous insulin is given. Continue oral K+ replacement within 1 week.
Hyperosmolar hyperglycemic nonketotic coma.
Hyperosmolar hyperglycemic nonketotic coma (HONK) is a state of uncontrolled
DM that is caused by relative (mild or moderate) insulin deficiency. HONK is
characterized by excessive hyperglycemia (usually more than 600 mg/dL or 33.3
mmol/L), hyperosmolality (plasma osmolality more than 350 mmol/L, effective
osmolality exceeds 320 mOsmol/L), and absence of metabolic acidosis.
HONK occurs 10 times less frequently then DKA. But it is characterized by high
lethality that exceeds 30%. Late diagnosis and severe concomitant pathology
increase lethality to 60-70%. Despite of mild or moderate insulin deficiency, only
some cases of type 2 DM are complicated by HONK. Others are complicated by
DKA.
Etiology of HONK.
The main precipitating factors of HONK are listed below.
1. Dehydration that may be caused by different reasons (diuretics, vomiting,
and diarrhea).
2. Concomitant diabetes insipidus.
3. Blood loss, burns, renal failure.
 4. Water deprivation that is caused by inability to drink or lowered sense of
thirsty in elderly patient.
5. Ingestion of drugs that inhibits insulin secretion (corticosteroids, β-
adrenoblockers, calcium-channel blockers etc.)
Sometimes HONK is the first evidence of diabetes onset.

Pathogenesis of HONK.
Pathogenesis of HONK is not as obvious as pathogenesis of DKA. It is supposed
that liver has got the most part of endogenous insulin. Residual insulin secretion of
type 2 DM cases may be sufficient for suppression of lipolysis and ketogenesis into
the liver, but not enough for normal functioning of peripheral insulin-dependent
tissues (fat, muscles). Peripheral insulinopenia causes moderate energy deficiency
and slightly increased secretion of counterregulatory hormones. Glycogenolysis
and gluconeogenesis are activated not very intensively. Ketone bodies can be
successfully utilized by liver. They are not gained in to blood. Ketoacidosis is not
developed. But glucose production is permanently intensified and plasma glucose
level is gradually growing. Extreme hyperglycemia inhibits lipolysis by itself and
prevents ketogenesis. Osmotic diuresis results in hypovolemia that causes
secondary hyperaldosteronism. Hyperaldosteronism leads to the sodium retention
and hyperosmolality. Hypovolemia impairs kidney perfusion and decrease renal
excretion. It promotes retention of osmotic active substances (glucose, electrolytes
etc.). Their retention increases osmolality too. HONK is a serious, often lethal,
form of diabetic coma. But many HONK cases do not require insulin therapy after
the acute episode.
Clinical picture of HONK.
Symptoms of HONK may be classified in several main clinical syndromes:
1. Insipidary syndrome (polyuria and polydipsia).
2. Syndrome of dehydration (low skin turgor, soft eyeball tonus, dry skin,
tongue, and oral cavity). Dehydration symptoms are very frequently
underrated and explained by elderly age of the patient.
3. Syndrome of CNS suppression. Progressive fatigability is developed.
Hallucinations and delirium are possible. They are gradually replaced by
drowsiness, sopor and coma.
4. Syndrome of neurological manifestations. Elderly patients usually have
cerebral atherosclerosis. Hypovolemia impairs cerebral perfusion. It causes
changeable polymorphous focal neurological symptoms that can not be
distinctly specified. It leads to wrong diagnosis of cerebral stroke.
5. Syndrome of thrombophilia (different thromboses and thromboembolias
are common).
Diagnosis of HONK
In the comatose patient severe dehydration can be the only clue to the right
diagnosis. In conscious ones, the history and initial clinical examination often
suggest the diagnosis. Hyperventilation is usually absent, but inadequately treated
HONK can be complicated by lactic acidosis and development of hyperventilation.
HONK diagnosis is verified by very high blood glucose (600-2500 mg/dL or 33.3-
138.0 mmol/L), calculated osmolality that exceeds 350 mOsm/L, and arterial pH
more than 7.2. There is severe glycosuria, but no ketonuria.
Management of HONK.
HONK treatment consists of rehydration, insulin therapy; correction of electrolytes
balance, anticoagulants, and “other” measures. It is similar to DKA cases, but there
are some peculiarities.
Rehydration.
Rehydration is performed more intensively than in DKA cases.
It is commonly transfused:
1st hour – 1.0-1.5 L/h
2nd-3d hour – 0.5-1.0 L/h
Subsequent hours – 0.25-0.50 L/h
Its adequacy is controlled by central venous pressure and diuresis alike DKA cases.
Rehydration solution is chosen according to blood sodium level and glycemia.
 if sodium level is more than 165 mmol/L, rehydration is started from
2% glucose solution; normal and half-normal saline are
contraindicated;
 if sodium level 145-165 mmol/L, rehydration is started from half-
normal (0.45%) saline;
 as soon as sodium level becomes lower than 145 mmol/L, rehydration
is continued by normal saline;
 as soon as glucose level becomes lower than 13-14 mmol/L,
rehydration is continued by 5% glucose solution.

Insulin therapy
Patients with HONK are very sensitive to low doses of insulin. Insulin therapy is
started from intravenous injection of 2 U of rapid acting insulin per hour.
Sometimes, insulin is not injected on initial stages of therapy. Transfusion of half-
normal (0.45%) saline has its own hypoglycemic action. Unsatisfactory diminution
of blood-glucose in 4-5 hours of therapy is an indication to increase insulin dose to
6-8 U/h (the same routine as for the cases with DKA). The rate of insulin injection
has to be halved, if the rate of fall of glycemia exceeds 150 to 200 mg/dL (8-10
mmol/L) per hour. Decreasing of plasma osmolality should not exceed 10
mOsmol/L.
Correction of electrolytes balance
Despite no significant acidemia, there is large deficit of total body potassium (5-12
mmol/kg). This is caused by the long prodromal period, intracellular fluid
depletion, urinary loss, decreased insulin action, and hyperglycemia.
Correction of potassium deficiency is performed alike DKA cases.
Anticoagulants
HONK is frequently complicated by thrombosis and thromboembolia that often
results in lethal exits. Anticoagulation is indicated (for example Heparin 5000 U
two times daily intravenously).
Other measures
Many treatment measures are as described for DKA. Antibiotics and plasma
volume support are important.

Hypoglycemia
Hypoglycemia is a pathological state that is caused by glycemia decreasing. It is
characterized by compensatory hyperactivity of autonomic nervous system and
different severity of mental confusion including coma.
Etiology of hypoglycemia.
The main precipitating factors of hypoglycemia are listed below.
1. Abnormal insulin injection technique. (Using long needles for slim patients
resulting in intramuscular injection, 100 U/ml insulin solution injections by
syringe that is calibrated for 40 U/ml solution, insulin overdosing etc.).
2. Omitting or postponing of having meal.
3. Unexpected physical exertion. Every 30 minutes of moderate physical
exertion should be added by ingestion of one bread unit.
4. Ingestion of alcohol drinks. Ethanol metabolism and gluconeogenesis use
nicotinamide-adenine dinucleotide (NAD) as a proton receptor. Alcohol
ingestion depletes the liver NAD and inhibits gluconeogenesis. This causes
hypoglycemia that is manifested as coma).
Etiology of hypoglycemia.
Glucose is a unique energy source for neurons. Hypoglycemia causes energy
deficiency in neuronal tissue and derange CNS functioning. It initiates excessive
secretion of catecholamines that has reactive, compensatory character.
Catecholamines secretion is especially intensive in rapid falling of plasma glucose;
autonomic nervous system is activated. Some cases of hypoglycemia have no
reactive activation of autonomic nervous system (ingestion of β-adrenoblockers,
autonomic neuropathy with loss of adrenal medulla enervation, etc.).
Clinical picture of hypoglycemia.
Hypoglycemia symptoms may be divided in two big groups.
1. Neuroglycopenic symptoms: confusion, dizziness, headache, aberrant
behavior, blurred vision, seizure, loss of consciousness. The symptoms are
caused by erratic nutrition of CNS that can not utilize anything except
glucose.
2. Catecholamine-induced symptoms: pallor, sweating, palpitation,
tachycardia, widened pulse pressure, nausea, anxiety and hunger. All of
these symptoms may be attenuated or absent in the setting β-blockade,
autonomic neuropathy, or chronic hypoglycemia. Moderately decreased
hypoglycemia sometimes is not accompanied by epinephrine release.
Hypoglycemia may be accompanied by some other unspecific symptoms
(weakness, malaise, sweating, tremulousness, and anxiety). They can be relived by
food ingestion.

Diagnosis of hypoglycemia
Diagnostic criteria of hypoglycemia:
1. Symptoms of confusion, aberrant behavior, dizziness, loss of consciousness,
or seizure;
2. Plasma glucose concentration lower than 40 mg/dL (2.2 mmol/L);
3. Relief of the symptoms with administration of glucose.
Hypoglycemia severity is classified in this way:
 Light hypoglycemia – patient relieves hypoglycemia without anybody’s
assistance.
 Severe hypoglycemia – patient is unconscious (hypoglycemic coma) or
needs to have somebody’s help.

Management of Hypoglycemia.
Conscious patient (light hypoglycemia) must eat some simple carbohydrate (1-2
bread units). It may be sweet tea, juice, several pieces of sugar, candies, jam etc.
Unconscious patients with hypoglycemic coma are treated by i/v injection of 40-60
ml of 40% dextrose solution. Intravenous injection can be fulfilled only by enough
skillful people. Sometimes it can not be made. This case may be managed by i/m
injection of 1 mg of glucagon. I/m injection can be performed by patient’s relatives
or neighbors. There is special “Glucagon hypo kit” that contains 1 mg of glucagon.
If patient is not awakened after glucose injection, cerebral edema or scull injury
may be supposed.
Long time hypoglycemic coma may result in encephalopathy development with
mental disorders. The severest cases result in cerebral decortications, cerebral
edema and lethal exit.
In elderly patient, hypoglycemic coma is associated with high risk of myocardial
infarction and cerebral stroke (ECG registration, ALT, AST measuring, arterial
pressure control are to be performed).
Lactic acidosis
Lactic acidosis is a pathological state that is caused by increased lactate production
or (and) its lowered elimination. It is characterized by severe metabolic acidosis
and cardio-vascular insufficiency.
Etiology of lactic acidosis.
Lactic acidosis is commonly classified according to clinical evidence of tissue
hypoxia and diminished perfusion.
Classification of lactic acidosis.
Type A: There is evidence of clinical tissue hypoperfusion (it is caused by anemia,
hemorrhage, congestive heart failure, grand mal seizures, carbon monoxide
poisoning etc.
Type B: There is no evidence of clinical tissue hypoperfusion (it is subdivided into
four groups):
Type B1: Associated with underlying disease (diabetes mellitus, liver disease,
malignancy, sepsis, thiamine deficiency, uremia etc.)
Type B2: Associated with drugs, toxins, and metabolites (alcohols, biguanides,
cyanide, isoniazid, salicylate etc.
Type B3: Associated with hereditary disease (type 1 glycogen storage disease).
Type B4: Miscellaneous
Modern biguanides (metformin) have low toxicity. Metformin is 10 times less
dangerous then phenformin. Lactic acidosis occurs in biguanides treated cases with
concomitant hepatic, renal, or cardiac disfunction. It is a very rare pathology.
Clinical picture of lactic acidosis.
Lactic acidosis development is taken from several hours to several days. The first
symptoms are weakness, increasing fatigability, salivation, and sense of metal into
the mouth. Intensive myalgias, and chest pain appears later. The above mentioned
symptoms are gradually accompanied by nausea, vomiting, sopor, stupor, and
coma. Lactic acidosis causes hyperventilation and cardiovascular insufficiency.
History of cardiovascular disease is typical. Recent cerebrovascular accident or
myocardial infarction is possible.
Diagnosis of Lactic acidosis
Lactic acidosis is a common cause of a high anion-gap acidosis.
The anion gap (AG) is defined as the difference between the serum concentration
of sodium minus sum of chloride and bicarbonate:
AG = Na+ - (Cl- + HCO3-), with normal values 8-16 mmol.
Lactic acidosis diagnosis is confirmed by laboratory investigation:
 Blood lactate is more than 5 mmol/L
 Arterial pH is lower than 7.2
Treatment of Lactic Acidosis
Treatment of lactic acidosis is unsatisfactory; lethality is 50-80%. Lethal exits
result from severe cardiovascular insufficiency, fatal arrhythmias, or paralysis of
breath center.
If lactic acidosis occurs, treatment should include vigorous alkalinization (with
careful watch of plasma potassium and calcium levels), circulatory support,
treatment of the cause, and dialysis as necessary to accommodate the inevitable
sodium load.
As soon as lactic acidosis is established, 45 mmol (50 ml of 8.5% solution) of
sodium bicarbonate must be infused intravenously. 180 mmol of bicarbonate is
infused for another 4 hours. Other agents, such as buffer tromethamine and the
oxidizing agent methylene blue, have been tried but probably not help.
Oxygen inhalation is performed through nasal catheter. In hyperglycemia cases
insulin is injected.
Alas, nowadays it is obvious that the most effective treatment of lactic acidosis is
its prevention.
Differential diagnosis of acute complications of DM.
Criteria of differential diagnosis are resumed in table 3.
This is the most important about diabetic acute complication management.
Thank you for your attention!
 Table 3
Differential diagnosis of acute episodes of DM
Type of acute episodes of DM
Criterion Hyperosmolar hyperglycemic
Hypoglycemia Diabetic ketoacidosis Lactic acidosis
nonketotic coma
Age any any elderly elderly
slow (3-7 days, in severe
Development Fast (some minutes) inflammation cases it may be slow (10-14 days) usually rapid (some hours)
developed in 12-24 h)
insulin overdosing, hypoxia that is caused by
omitting or stopping of insulin therapy, dehydration that is caused by pulmonary or heart failure,
postponing of having inadequate insulin injection diuretics, vomiting, diarrhea, anemia; liver and kidney
History meal, unexpected technique, intercurrent diseases , burns, bleeding, water deprivation; diseases, ingestion a lot of
physical exertion, surgical operations, traumas, steroids ingestions; biguanides in spite of
ingestion of alcohol psychological stress, pregnancy pure renal excretion contraindication for its taking;
drinks may be without DM
dry skin & oral cavity, low skin dry skin & oral cavity, low skin dry pale skin, sometimes it is
Skin pale, moist
turgor, rubeosis turgor pale-cyanotic
normal or slightly non-deep with
Breathing Kussmaul respiration Kussmaul respiration
increased frequency increased frequency
Eye ball tonus normal low low normal or a little bit lowered
lowered (may be increased in
Blood pressure increased or normal lowered very low, collapse
initially hypertensive cases)
Keton odor no intensive no no
increased, it is possible oliguria increased, it is possible oliguria
Daily diuresis normal oliguria, anuria
(anuria) in terminal stage (anuria) in a terminal stage
lower than excessively elevated
Glycemia elevated normal or moderately elevated
2.8-2.2 mmol/L (more than 33 mmol/L)
normal or excessively elevated normal or normal or
Ketonemia
slightly elevated (more then 5 mmol/L) slightly elevated slightly elevated
 Table 3
Continuation.
Type of acute episodes of DM
Criterion Hyperosmolar hyperglycemic
Hypoglycemia Diabetic ketoacidosis Lactic acidosis
nonketotic coma
Age any any elderly elderly
normal state or
Natriemia normal level excessively elevated normal
slightly elevated
decompensated metabolic
decompensated metabolic acidosis
acidosis that is partially
that is partially compensated by normal state or
Basal acid balance normal state compensated by
hyperventilation with compensated acidosis
hyperventilation with
respiratory alkalosis
respiratory alcalosi
Arterial blood pH normal state normal state normal state lowered
Partial CO2
normal level normal state or lowered normal state normal state or lowered
pressure
Actual
normal level lowered normal state or lowered lowered
bicarbonate (AB)
Standard
normal level lowered normal state or lowered lowered
bicarbonate (SB)
Basal excess (BE) normal state negative normal state or slightly negative negative
excessively elevated normal state or
Plasma osmolality normal level elevated
(more 350 mOsmol/L) slightly elevated
creatinine and
normal level elevated or normal state elevated differently elevated
plasma urea
Lactate of blood normal level moderately elevated normal state or elevated excessively elevated