This document discusses various types of diabetic comas including diabetic ketoacidosis (DKA), hypoglycemic coma, and hyperosmolar non-ketotic coma. It provides details on the etiology, pathogenesis, clinical presentation, and treatment principles for each type of coma. The document also describes classifications of acute and chronic diabetic complications and covers specific complications like nephropathy, retinopathy, neuropathy, and diabetic foot syndrome. Treatment protocols for diabetic ketoacidosis are outlined, focusing on insulin therapy, rehydration, electrolyte correction, and acid-base balance correction.

2. Medical Lecture Notes – All Subjects
USMLE Exam (America) – Practice

3. 1.1. Acute complications of DM.Acute complications of DM. Classification of diabeticClassification of diabetic
comas.comas.
2.2. Diabetic Ketoacidosis (DKA). Etiology, pathogenesis,Diabetic Ketoacidosis (DKA). Etiology, pathogenesis,
clinical pclinical presentationresentation and principle of treatment.and principle of treatment.
3.3. Hypoglycemic coma.Hypoglycemic coma.
4.4. Hyperosmolar non-ketotic coma (HNC).Hyperosmolar non-ketotic coma (HNC).
5.5. Lactic acidosis (LA).Lactic acidosis (LA).
6.6. Classification and pathogenesis of chronicClassification and pathogenesis of chronic
complications of DM.complications of DM.
7.7. Diabetic nephropathy.Diabetic nephropathy.
8.8. Diabetic retinopathy.Diabetic retinopathy.
9.9. Diabetic neuropathy.Diabetic neuropathy.
10.10. Syndrome of diabetic foot.Syndrome of diabetic foot.
11.11. Skin problems in patients with DM.Skin problems in patients with DM.

4. A comaA coma is a state of unconsciousness.unconsciousness.
A diabetic coma is a life-threatening diabetes
complication.
The acute metabolic complications of diabetesThe acute metabolic complications of diabetes
mellitus consist of:mellitus consist of:
diabetic ketoacidosis (DKA) or ketoacidotic
coma
hyperosmolar non-ketotic coma (HNC)
lactic acidosis (LA)/ lactacidotic coma
hypoglycemia / hypoglycemic coma.

5. Stage The name of the stage Clinical sings
I Obnubilation The patient is inhibited, the
consciousness is confused
II Stupor The patient falls asleep easily,
but he/she can contact
III Sopor The state of a sound sleep,
which is interrupted only during
severe stimuli action
IV Coma The complete absence of a
consciousness

6. The patient O., 34 years, is suffering from type 1 diabetes mellitus during
3 years. Several days ago she canceled the insulin. Patient lost
consciousness in the evening. She is hospitalized in the emergency
department.
Anamnesis of disease:Anamnesis of disease: Type 1 diabetes mellitus is diagnosed 3 years ago. She
was treated by insulin therapy (Aktrapid/Protafan) daily dose - 54 IU
subcutaneous. Diabetes mellitus was stable, hypoglycemia was absent. She
feels ill for 2 weeks: worsening acute abdominal pain and a 2 day history of
recurrent vomiting. The patient canceled the insulin therapy. She is
hospitalized in the emergency department without consciousness,after that she
is hospitalized in the endocrinology department. Anamnesis of life:Anamnesis of life: Physical
development in childhood was normal. She has history of diabetes mellitus in
several family members: grandfather and cousin. Allergic reactions were
absent. On examination:On examination: General conditions of patient is very heavy.
Meningeal signs are absent. Body weight - 57 kg. Height -178 cm. Body mass
index - 17,8 kg/m2
. Her temperature is 37.2 °C. The skin is dry. Muscular
weakness. Eyeballs are mild. Lymphatic nodes – can not be palpated.
Appearance of face: diabetic rubeosis. Kussmaul's respiration, the odor of
acetone from the mouth, tongue is dry, with fur of brown color. The borders of
relative and absolute heart dullness are normal. Pulse-120 beats/minutes The
loudness of heart tones amplified. The blood pressure - 80/45 mmHg. The
abdomen does not react to the palpation. The liver is + 2 cm. Anuria.
Laboratory tests:Laboratory tests: Glucose of the blood - 28 mmol/L, the reaction of urine to

7. KetosisKetosis (acetonaemia)(acetonaemia) – is a state characterised
by elevated levels of ketone bodies in the blood
Ketoacidosis (DKA)Ketoacidosis (DKA) – is a type of metabolic
acidosis which is caused by high concentrations
of ketone bodies. DKA is an extreme and
uncontrolled form of ketosis, which is a normal
response to prolonged fasting or hyperglycemia
Hyperketonemic coma -Hyperketonemic coma - the state ofthe state of
unconsciousness accompanying severeunconsciousness accompanying severe DKADKA

8. An acute state of absoluteAn acute state of absolute
or relative insulinor relative insulin
deficiency aggravated bydeficiency aggravated by
ensuing hyperglycemia,ensuing hyperglycemia,
dehydration, anddehydration, and
acidosis-producingacidosis-producing
derangements inderangements in
intermediary metabolism,intermediary metabolism,
including production ofincluding production of
serum acetone.serum acetone.
This results in high levels of
ketone bodies:ketone bodies:
acetone, acetoacetate andacetone, acetoacetate and
ββ--
hydroxybutyrate.hydroxybutyrate.

9. Glucagon
↑↑Adenylate Cyclase
↑↑cAMP
↑↑ PKA activationPKA activation↑↑ PKA activationPKA activation
Phosphorylation of
phosphorylase
Phosphorylation of
F6P2-kinase
↑↑ Glycogenolysis
GLUCOSE
↓↓ F2,6-P
↑↑Gluconeogenesis
↑↑Lipolysis
↓↓Glycolysis
↓↓ 3 Carbon fragment
↓↓Malonil CoA
↑↑ FFA
KETONE BODIES

10. Pregnancy
Late diagnosis of
diabetes mellitus,
especially of type 1
Insulin therapy errors
(patient or doctor)
Infection
(pneumonia,
bacterial infections)
Insufficient control of
glucose blood level
Not prescribing insulin therapy
by indications under long-duration
type 2 diabetes mellitus
Intercurrent illness
(myocardial infarction, stroke,
pancreatitis, prostatitis)
Alcohol, drugs
(steroids, thiazide diuretics)
TraumaTrauma
Non-compliance with
insulin therapy (insulin infusion
catheter blockage)
Hunger (starvation)
Idiopathic (no identifiable cause)
Miscellaneous

11. Insulin deficiencyInsulin deficiency
↑↑ ProteolysisProteolysis
↑↑ Amino acidsAmino acids ↑↑ Nitrogen lossNitrogen loss
↓↓Glucose uptakeGlucose uptake ↑↑LipolysisLipolysis
HyperglycemiaHyperglycemia
Osmotic diuresisOsmotic diuresis
Hypotonic lossesHypotonic losses
GluconeogenesisGluconeogenesis
+ Glycogenolysis+ Glycogenolysis
Electrolyte depletionElectrolyte depletion
DehydrationDehydration
AcidosisAcidosis
↑↑ KetogenesisKetogenesis
↑↑ FreeFree
fatty acidsfatty acids
↑↑GlycerolGlycerol
↑ KetonemiaKetonemia
↑↑KetonuriaKetonuria

12. PolyuriaPolyuriaPolyuriaPolyuria
WeightWeight
lossloss
WeightWeight
lossloss
““Gap”Gap”
metabolicmetabolic
acidosisacidosis
““Gap”Gap”
metabolicmetabolic
acidosisacidosis
KetonemiaKetonemiaKetonemiaKetonemia
HHypeyper-r-
glycemiaglycemia
HHypeyper-r-
glycemiaglycemia
PolydipsiaPolydipsiaPolydipsiaPolydipsia
DKADKA

13. HYPERGLYCEMIAHYPERGLYCEMIAHYPERGLYCEMIAHYPERGLYCEMIA
KETONE BODIESKETONE BODIESKETONE BODIESKETONE BODIES
Polyuria and polydipsia
Blurred vision
Severe volume depletion
Electrolyte depletion
Eventual: renal hypoperfusion
hypotension and shock
Acidosis
Compensatory respiratory
alkalosis
(Kussmaul’s respiration)
Hypotension
Shock

14. Early signs:Early signs:
Feeling tired or
fatigued
Excessive thirst
and/or excessive
urination
Signs of dehydration
such as dry mouth
Facial flush
Patient odor are
characteristic acetone
(fruity smell or nail
polish)
Later signs:Later signs:
Nausea/vomiting
Abdominal pain
Loss of appetite
Flu-like symptoms
Confusion
Kussmaul's
respirations
Breath that smells
fruity (nail polish)
Fever
Unconsciousness

15. The patient feels an urge toto breathe deeplybreathe deeply, an "air
hunger", and it appears almost involuntary.
Kussmaul breathing develops as theKussmaul breathing develops as the acidosis growsacidosis grows moremore
severe.severe.
Indeed, Kussmaul originally indentified this type of
breathing as a sign of coma and imminent death in
diabetic patients.

16. Ketoacidotic
coma
Abdominal type
manifests itself
with dyspepsia,
acute abdominal pain
with muscle tension.
Occasionally pain can
be belting, accompanied
with vomiting.
During this neutrophilic
leukocytosis probable
acute appendicitis,
purulent peritonitis
may be falsely
suggested.
Cardiovascular type
displays throughdisplays through vascularvascular
collapse.collapse. Arterial andArterial and
venous pressurevenous pressure
is reducing, bloodis reducing, blood
influx to heartinflux to heart
is considerably decreasing,is considerably decreasing,
stroke volume andstroke volume and
cardiac output are lowering.cardiac output are lowering.
Extrasystole, atrialExtrasystole, atrial
fibrillation and atrialfibrillation and atrial
flutterflutter areare
frequent amongfrequent among
rhythm disturbances.rhythm disturbances.
Renal type
Protein, blood corpuscles
and cylinders appearance in urine;
Increase of blood urea and
residual nitrogen;
Hyposthenuria and isosthenuria;
Anuria.
Encephalopathic type
deep disturbances of brain functions,
including myelencephalon:
miotic pupils, absent corneal reflex,
Kussmaul's respiration
changes to hypopnoe,
arterial pressure is progressively reducing.

17. Mild Moderate Severe
Plasma
glucose,
mmol/L
> 13,9 > 18,9 > 20,0
Arterial pH 7,25 – 7,30 7,00–7,24 < 7,00
Urine
ketones
Positive
“+” or “++”
Positive
“++” or “++
+”
Positive “++
+” or “++++”
Serum
ketones
Positive Positive Positive

18. General treatment regimenGeneral treatment regimen includes:includes:
I. Elimination of insulin insufficiency, normalizationnormalization
of carbohydrate metabolismof carbohydrate metabolism and suppression of
ketone bodies formation;
II. Optimally fast rehydrationrehydration with the purpose of
blood volume adjustment and blood pressure
increase;
III.III. Electrolyte correction;Electrolyte correction;
IV.IV. Correction of acid-base balance;Correction of acid-base balance;
V.V. Diagnostics and treatmentDiagnostics and treatment of pathologicalof pathological
conditions whichconditions which caused diabetic comacaused diabetic coma
(infections, etc.).(infections, etc.).

19. II. RehydrationII. Rehydration
Fluids: Initial correction of fluid loss
is either by isotonic natrium
chloride (saline) solution or by
lactated Ringer solution, Acisoul,
Disoul, Reosorbilact.
Infused 1 liter over the first 30
minutes; Infused 1 liter over the
second hour; Infused 1 liter over
the following 2 hours; Infused 1 liter
every 4 hours, depending on the
degree of dehydration and central
venous pressure (CVP) readings.
During the first 8 hours ofDuring the first 8 hours of
treatment the volume oftreatment the volume of
transfused fluid should amounttransfused fluid should amount
to 3-4 liters.to 3-4 liters.
When blood sugar decreases to less
than 12 mmol/L12 mmol/L, saline solution is
replaced with
55 % - 400 ml glucose with 4 ml% - 400 ml glucose with 4 ml
solution Vitamin C, 5 ml panangin,solution Vitamin C, 5 ml panangin,
8 IU of Humodar R.8 IU of Humodar R.
I. Correction ofI. Correction of
hyperglycemiahyperglycemia
Only short (rapid)-acting insulin
(Actrapid, Humulin R, Humodar R,
Farmasulin HL) is used for
correction of hyperglycemia
Intensive Insulin TherapyIntensive Insulin Therapy::
A mix of 10 IU of Humodar R10 IU of Humodar R in 20 ml
of isotonic Natrium
Chloride solution (0,9 %-20.0 ml
NaCl) is used for intravenousintravenous
injection (i/v)injection (i/v)
OROR
0.15 unit/kg0.15 unit/kg I/V bolus initially, followed
by continuous I/V infusion of
0.1 unit/kg/h in 0.9% saline0.1 unit/kg/h in 0.9% saline
solutionsolution;;
10 IU of Humodar R intramuscular10 IU of Humodar R intramuscular
injectioninjection
Plasma glucose concentration is
11,0 mmol/ L -11,0 mmol/ L -

20. IV.IV. Correction of acid-Correction of acid-
base balancebase balance
Sodium bicarbonateSodium bicarbonate only is
infused if decompensated acidosis
starts to threaten the patient's life,
especially when associated with
either sepsis or lactic acidosis.
If sodium bicarbonate is indicated,
100-150 mL of 1.4% concentration
is infused initially. This may be
repeated every half hour if
necessary.
III.III. Electrolyte correctionElectrolyte correction
If the potassium levelpotassium level is
greater than 6 mmol/L, do not
administer potassium
supplement.
If the potassium level is 4.5 - 6
mmol/L, administer 10 ml/h10 ml/h
of potassium chloride.of potassium chloride.
If the potassium level is 3 - 4.5
mmol/L, administer 20 ml/h20 ml/h
of potassium chloride.of potassium chloride.
Monitor serum potassium levelsMonitor serum potassium levels
hourly, and the infusionhourly, and the infusion
must stop if the potassiummust stop if the potassium
level islevel is greater than
5 mmol/L.
V.V. Treatment of concurrent infectionTreatment of concurrent infection
In the presence of infection, administer proper antibioticsantibiotics guided by the
results of culture and sensitivity studies.
Starting empiric antibiotics on suspicion of infection until culture results are
available may be advisable.

21.  InfectionInfection
 Precipitates DKA
 Fever
 Leukocytosis can be
secondary to acidosis
 ShockShock
 If not improving with fluids
r/o MI
 Vascular thrombosisVascular thrombosis
 Severe dehydration
 Cerebral vessels
 Occurs hours to days after
DKA
 Pulmonary EdemaPulmonary Edema
 Result of aggressive fluid
resuscitation
 Cerebral EdemaCerebral Edema
 First 24 hours
 Mental status changes
 Tx: Mannitol
 May require intubation
with hyperventilation

22. HYPOGLYCEMIAHYPOGLYCEMIA is a syndrome characterized by
a reduction in plasma glucose concentration to
a level that may induce symptoms of low blood
sugar.
HYPOGLYCEMIC COMAHYPOGLYCEMIC COMA is an acute condition
progressing during rapid reduction of glucose
level in blood and abrupt lowering of glucose
utilization by brain.

23. Exogenous causesExogenous causes
--overdose of insulin
plus inadequate
- food intake,
increased exercise
-overdose of oral
hypoglycemic
agents
-alcohol
-other agents
(salicylates,
pentamidine, quinine))
Endogenous causesEndogenous causes
--insulinoma (neoplasm
of beta cells
of islet
of Langerhans)
- extrapancreatic
neoplasm (hepatomas,
tumor of GIT)
-critical illnesses
(heart, liver, kidney,
sepsis)
- inborn errors of
metabolism (fructose
HYPOGLYCEMIAHYPOGLYCEMIA

25. Blood glucose:Blood glucose:
4.6 mmol/L4.6 mmol/L Inhibition of insulin
secretion
3.8 mmol/L3.8 mmol/L Release of glucagon
and adrenaline
3.0 mmol/L3.0 mmol/L Hypoglycaemic
symptoms
< 2.8 mmol/L< 2.8 mmol/L Cognitive function
progressively
impaired

26. PalePale
DrowsyDrowsy
ClumsyClumsy
TremorTremor
CONVULSIONCONVULSION
HYPOGLYCAEMIAHYPOGLYCAEMIA
COMACOMA
SweatingSweating
AggresiveAggresive IrritableIrritable DetachedDetached
Pounding
heart rate
Pounding
heart rate
Innapropriate
behaviour
Innapropriate
behaviour

27. SYMPTOMS OF HYPOGLYCEMIASYMPTOMS OF HYPOGLYCEMIA

28. SIGNS & SYMPTOMSSIGNS & SYMPTOMS
OF HYPOGLYCEMIAOF HYPOGLYCEMIA
Mild Symptoms (<4.0 mmol/L)
Hunger
Sleepiness
Sweating
Shakiness
Changed behavior
Anxiety
Weakness
Paleness
Blurry vision
Dilated pupils
Increased heart rate/palpitations
Moderate Symptoms (<3.0 mmol/L)Moderate Symptoms (<3.0 mmol/L)
Excessive yawning
Extreme tiredness/fatigue
Confusion
Restlessness
Irritability/frustration
Sudden crying
Dazed Appearance
Refusal to take anything by mouth
As blood
glucose
levels
drop,
symptoms
become
more
severe
Severe SymptomsSevere Symptoms
Unconsciousness
Seizures
(convulsions)
Inability to swallow

29. Mild and moderateMild and moderate
low:low:
First check level of
blood glucose;
Treat immediately
with oral glucose
(15-20g);
Treat with high-
glycemic index (GI)
food;
Treat with proper
amount;
Re-Check level of
blood glucose in
15 minutes.
High-GI FoodsHigh-GI Foods
• Glucose TabletsGlucose Tablets
• Dry CerealDry Cereal
• PretzelsPretzels
• Graham CrackersGraham Crackers
• Vanilla WafersVanilla Wafers
• Jelly BeansJelly Beans
• GatoradeGatorade

30. I. Correction of hypoglycemia:I. Correction of hypoglycemia:
20.0 - 60.0 ml of 40 % solution
glucose i/v
500 ml of 5 % solution glucose
i/v drip-feed
subcutaneous injection of
glucagon 1.0 ml
subcutaneous injection of
1.0 ml 0.1 % adrenaline
(epinephrine))
II. MetabolicII. Metabolic therapytherapy::
100 mg of cocarboxsilase
5.0 ml – 5 % solution of acidi
ascorbinici (Vit C)
1.0 ml – 5 % solution of Vit B 6
III. Prevention for brainIII. Prevention for brain
swelling:swelling:
15 % or 20 % solution
of mannitoli
i/v drip-feed 0.5 – 1.0 g/kg
if move convulsions:
5.0 – 10.0 ml 25 % solution of
magnesii sulfat
i/m injection
IV. SIV. Symptomatic therapyymptomatic therapy::
Low blood pressure:
0.3 – 0.5 ml 1.0 % solution of mezaton subcutaneous

31. is clinically defined by the presence of relative
insulin deficiency and hyperglycemia, usually
higher than 33,3higher than 33,3 mmol/Lmmol/L with associated
elevated serum osmolality (>300 mosm/kg),(>300 mosm/kg),
dehydration, and stupor, progressing to coma
if uncorrected, without the presence of ketosis
or acidosis.
Uncommon complication of type 2 diabetes mellitus.
ComplicationsComplications of HNCof HNC::
 Ischemia or infarction to any organ, including heart
and brain
 Thromboembolism
 ARDS/DIC or multiorgan dysfunction syndrome
 Cerebral edema (rare)

32. Conditions andConditions and illnessesillnesses
associated with HNC:associated with HNC:
−Myocardial infarction;
−Pneumonia;
−Pulmonary emboli;
−Sepsis;
−Acromegaly;
−Anesthesia;
−Burns;
−Cerebrovascular accident;
−Cushing syndrome;
−Hemodialysis and peritoneal dialysis;
−GI hemorrhage;
−Heatstroke;
−Hyperalimentation/total parenteral
nutrition;
−Hypothermia;
−Intestinal obstruction;
−Mesenteric thrombosis;
−Neuroleptic malignant syndrome;
−Pancreatitis;
−Renal insufficiency (chronic);
–Rhabdomyolysis;
–Subdural hematoma;
–Surgery (especially cardiac surgery);
–Thyrotoxicosis;
–Trauma;
–Urinary tract infection
Medications that may precipitateMedications that may precipitate
HNHNC:C:
Antiarrhythmics (encainide,
propranolol);
Antiepileptics (phenytoin);
Antihypertensives (calcium channel
blockers, diazoxide);
Antipsychotics (chlorpromazine,
loxapine);
L-asparaginase;
Corticosteroids;
Diuretics (chlorthalidone, ethacrynic
acid, thiazides);
Histamine-receptor blockers
(cimetidine);
Immunosuppressive agents

33. is based on characteristicis based on characteristic
clinical picture:clinical picture:
 Xerodermia, evident dryness
of mucous membranes;
 Apparent polyuria
(subsequently oliguria, anuria);
 Perceptible thirst, weakness,
adynamy;
 Skin turgor reduction;
 Eye balls softness at palpation;
 Somnolence;
 Polymorphic neurologic
symptomatology (speech
disturbances, nystagmus,
paresis, paralysis, cramps);
 Arterial hypertension, not
uncommon heart rate
disturbances
Laboratory diagnostics:
Significant hyperglycemia, up
to 55 mmol/L and more;
Absence of ketonemia;
Hypernatremia and
hyperchloremia;
Normal pH;
Increased blood osmolality
(360 mOsm/kg360 mOsm/kg).
Plasmic osmolarity (mOsm/l) =Plasmic osmolarity (mOsm/l) =
2× (Na2× (Na++
( mmol/L) + K( mmol/L) + K++
(mmol/L)(mmol/L)
+ glycemia (mmol/L) + 0,03 ×+ glycemia (mmol/L) + 0,03 ×

34. I. Rehydration:
Hypotonic 0,45% natrium
chloride (saline) solution
(considering high plasmic
osmolarity).
Usually 1-3 liters of solution is
infused during 2-3 hours.
During 1-2 days with the
speed of 200-300 ml/hour of
hypotonic solution.
II. Elimination of
insulin
insufficiency:
CommonlyCommonly 5-10 IU of rapid-
acting insulin are injectedare injected
at one time, further –at one time, further –
3-7 IU/hour (0,08-0,1 IU)
or 0,1 IU/kg/h..
At lowering ofAt lowering of glycemiaglycemia
level to 14,0 mmol/Llevel to 14,0 mmol/L
5 % glucose solutionsolution
is added and infusionis added and infusion
speed decreases tospeed decreases to 1-2
IU/hour..
III. Electrolyte balance recovery:
It is also necessary to control and correct
potassium (1,5-3 g/hour)
phosphates (80-120 mmol/day),
magnesium (6-12 mmol/l, i.e. 0,08-0,16 mmol/kg) levels.
IV. Treatment of concomitant diseases

35. Lactic AcidosisLactic Acidosis - consists of elevated lactic acid
(lactic acidemia ≥2.0 mmol/L) with acidosis
(pH ≤7.3) and without ketoacidosis.
Lacticemia syndromeLacticemia syndrome
is specific not only for diabetes mellitus; it can
develop under other severe pathological
conditions when there are presuppositions for
increased lactic acid formation and storage in
blood and tissues.

36. ComaComa is developing against a background
of hypoxia and stimulation of anaerobic glycolysis.
Lactate/pyruvate index increases (normally = 10/1).Lactate/pyruvate index increases (normally = 10/1).
Glycolysis and Beta OxidationGlycolysis and Beta Oxidation
AnaerobicAnaerobic-no O-no O22
AerobicAerobic-O-O22 presentpresent

37. TYPE A LACTIC ACIDOSIS::
CLINICAL EVIDENCE OF INADEQUATE TISSUE OXYGEN DELIVERYCLINICAL EVIDENCE OF INADEQUATE TISSUE OXYGEN DELIVERY
•Anaerobic muscular activity (sprinting, generalized convulsions)
•Tissue hypoperfusion (shock, septic, cardiogenic or hypotalaemic;
hypotension; cardiac arrest; acute heart failure; regional hypoperfusion
mesenteric ischaemia)
•Reduced tissue oxygen delivery or utilisation (hypoxaemia, carbon
monoxide poisoning, severe anaemia)
TYPE B LACTIC ACIDOSIS:
NO CLINICAL EVIDENCE OF INADEQUATETISSUE OXYGEN DELIVERYNO CLINICAL EVIDENCE OF INADEQUATETISSUE OXYGEN DELIVERY
•TYPE B1: Associated with underlying diseases (ketoacidosisketoacidosis, leukaemia,
lymphoma, AIDS)
•TYPE B2: Associated with drugs & toxins ((biguanidesbiguanides overdosage:overdosage:
phenformin and buforminphenformin and buformin, cyanide, beta-agonists, methanol, nitroprusside
infusion, ethanol intoxication in chronic alcoholics, anti-retroviral drugs)
•TYPE B3: Associated with inborn errors of metabolism (congenital forms of
lactic acidosis with various enzyme defects: pyruvate dehydrogenase
deficiency)

38. Myalgia
Rapidly progressing
cardiovascular insufficiency
leading to collapse development
Arterial hypotension
Brain hypoxia and impairment
of consciousness are brought
into the foreground.
Hyperventilation is typical still
dehydration is not rarely
apparent.
Tachypnoe can turn to
Kussmaul's respiration.

39. I.I. Restitution of normal acid-base balance:Restitution of normal acid-base balance:
Airway assessment or Hyperbaric oxygenation
i/v drop infusions of 2,5 % sodium bicarbonate solution 1-2 L/day,
at extreme stage of acidosis – 8,5 % sodium bicarbonate solution.
Reversal of acidosis is facilitated by i/v drop infusion.
CARBICARB is a combination of sodium carbonate and sodium bicarbonate
of 50-100 ml 1 % methylene-blue solution and trisamine
IV. Peritoneal dialysisIV. Peritoneal dialysis andand hemodialysishemodialysis
can be used sometimes for cleansing the blood of lactic acid.
III. Insulinotherapy:III. Insulinotherapy:
is realized in small
doses combining with
5 % glucose
solution
II. Treatment ofII. Treatment of
pathologicalpathological
conditions whichconditions which
caused coma:caused coma:
Thiamine (Vitamin B1)
50-100 mg i/v
followed by 50
mg/day p/o for
1-2 weeks

40. IndexIndex KetoacidoticKetoacidotic
comacoma
HyperosmolarHyperosmolar
comacoma
LactacidoticLactacidotic
comacoma
HypoglycemicHypoglycemic
comacoma
Age Whatever, mostly
young
Mostly senior Senior Whatever
Development of
a coma
Gradually
(3-4 days),
possibly 10-12
hours
Gradually
(10-12 days)
Mostly rapid Rapid
Anamnesis First time
diagnosed
diabetes or
diagnosis is
unknown
First time
diagnosed
diabetes or
diabetes
mellitus type 2
Diabetes
mellitus type
2 in
combination
with hypoxia-
conducted
diseases
Mostly diabetes
mellitus type 1,
treatment with
insulin
Respiration Kussmaul's
respiration
Tachypnoe,
hypopnoe
Kussmaul's
respiration
Normal or
slightly frequent
Skin condition Dryness, turgor
decrease
Dryness,
prominent turgor
decrease
Dryness Wet skin
Eye ball tonus Lowered Sharply lowered Slightly lowered Raised

41. IndexIndex KetoacidoticKetoacidotic
comacoma
HyperosmolarHyperosmolar
comacoma
LactacidoticLactacidotic
comacoma
HypoglycemicHypoglycemic
comacoma
Arterial blood
pressure
Decreased,
significantly
decreased
Significantly
decreased,
collapse
Significantly
decreased,
collapse
Normal
Acetone odor Prominent Absent or minor Absent Absent
Pulse Rapid Rapid, soft Rapid, soft Rapid
Clinical signs of
dehydration
Sufficiently
evident
Prominent Insignificantly
evident
Absent
Daily diuresis Polyuria Polyuria
transferring into
oliguria
Oliguria, anuria Normal
Glycemia Increased Significantly
increased
Normal or
moderately
increased
Significantly
decreased
Ketonemia Significantly
increased
Normal Normal or
moderately
increased
Normal

42. IndexIndex KetoacidoticKetoacidotic
comacoma
HyperosmolarHyperosmolar
comacoma
LactacidoticLactacidotic
comacoma
HypoglycemicHypoglycemic
comacoma
pH and blood
bicarbonates
Decreased Normal or
moderately
decreased
Significantly
increased
Normal
Blood urea Normal or
significantly
increased
Increased Moderately or
significantly
increased
Normal
Blood lactate Moderately
increased
Normal or
moderately
increased
Significantly
increased
Normal
Blood volume Significantly
decreased
Significantly
decreased
Normal or
moderately
decreased
Normal
Serum sodium
(Na) value
Normal or
moderately
increased
Significantly
increased
Normal Normal
Serum
potassium (K)
value
Normal or
decreased
Moderately
decreased
Normal Normal
Plasma
osmolarity
Increased Significantly
increased
Normal or
moderately
increased
Normal

43. Brain
Cerebrovascular disease
• Transient ischemic attack
• Cerebrovascular accident
• Cognitive impairment
Heart
Coronary artery disease
• Coronary syndrome
• Myocardial infarction
• Congestive heart failure
Extremities
Peripheral vascular disease
• Ulceration
• Gangrene
• Amputation
MacrovascularMacrovascular MicrovascularMicrovascular
Eye
Retinopathy
Cataracts
Glaucoma
Kidney
Nephropathy
Microalbuminuria
Gross albuminuria
Kidney failure
Nerves
Neuropathy
Peripheral
Autonomic

44. 66thth
leadingleading cause of death by diseasedeath by disease
Decreases lifeDecreases life expectancy of middle-aged people
by 5-10 yearsby 5-10 years
2-4 x greater risk2-4 x greater risk of death heart diseaseheart disease
 Compounding factors include: duration of disease,
glycemic control, HTN, smoking, dyslipidemia,
decreased activity, and obesity
Leading cause of blindnessLeading cause of blindness in 25-74 year olds
Leading cause of non-traumatic amputationsLeading cause of non-traumatic amputations
Responsible forResponsible for 25-30%25-30% of all new dialysisnew dialysis
patientspatients

45. HYPERGLYCEMIAHYPERGLYCEMIA
↑↑Intracellular glucoseIntracellular glucose
↑↑ AdvancedAdvanced
glycation endglycation end
productsproducts
↑↑ SorbitolSorbitol ↑↑DiacylglycerolDiacylglycerol
↑↑Fructose-Fructose-
6-phosphate6-phosphate
Aldose
reductase
AbnormalAbnormal
proteinprotein
functionfunction
AlteredAltered
cellcell
functionfunction
↑↑
CirculatingCirculating
AGEsAGEs
Renal,Renal,
vascular,vascular,
connectiveconnective
tissue effectstissue effects
Cytokines,Cytokines,
growthgrowth
factorsfactors
COMPLICATIONSCOMPLICATIONS
OF DIABETES MELLITUSOF DIABETES MELLITUS
Alterations
in redox
potential,
reactive
oxygen
species
Altered
cell
function
↑↑ Flux inFlux in
hexosaminehexosamine
pathwaypathway
↑↑
PlasminogenPlasminogen
activoractivor
inhibitor-1,inhibitor-1,
growthgrowth
factorsfactors
ProteinProtein
kinase Ckinase C
activationactivation
AlteredAltered
genegene
expres-expres-
sionsion
GrowthGrowth
factorsfactors
AlteredAltered
enzymeenzyme
functionfunction
endo-endo-
thelialthelial
nitricnitric
oxideoxide
synthasesynthase
??

46. GeneticsGenetics
EnvironmentEnvironment
• nutritionnutrition
• obesityobesity
• exerciseexercise
RetinopathyRetinopathy
NephropathyNephropathy
NeuropathyNeuropathy
BlindnessBlindness
Renal failureRenal failure
Insulin resistanceInsulin resistance
HyperinsulinemiaHyperinsulinemia
HypertensionHypertension
Decreased HDL-CDecreased HDL-C
Increased TGIncreased TG
AtherosclerosisAtherosclerosis
Coronary diseaseCoronary disease
LE amputationLE amputation

47. is nodular glomerulosclerosis
and hyalinic atherosclerosis of small artery.
Definitions of Abnormalities inDefinitions of Abnormalities in
Albumin ExcretionAlbumin Excretion
CategoryCategory Spot collectionSpot collection
(µg/mg creatinine)(µg/mg creatinine)
NormalNormal <30<30
MicroalbuminuriaMicroalbuminuria 30-29930-299
MacroalbuminuriaMacroalbuminuria
(clinical)(clinical)
≥≥300300

49. Stages
Test
Albumin-
uria
GFR
(glomerular
filtration rate)
ml/min
Serum
creatinine
umol/L
BP Signs
Normal <20
High/
normal
Normal
60/150
Normal None
Microalbuminuria 20-300
High/
normal
Normal
60/150
Small
increase
None
Persistent
proteinuria
>300
Up to
15 g/day
Normal/
Decreased
High/
normal
80-120
Increased
+/-
Oedema
Renal impairment
>300
Up to
15 g/day
Decreased
High
120-400
Increased
+/-
Oedema
Established
Renal failure
>300
Can fall
Decreased
++
Very high
>400
Increased
+/-
Oedema

50. Optimal therapy for diabetic nephropathy is prevention by control ofOptimal therapy for diabetic nephropathy is prevention by control of
glycemiaglycemia
Interventions effective in slowing progression from microalbuminuria toInterventions effective in slowing progression from microalbuminuria to
macroalbuminuria include:macroalbuminuria include:
(1) normalization of glycemia,(1) normalization of glycemia,
(2) strict blood pressure control,(2) strict blood pressure control,
(3) administration of ACE inhibitors or ARBs.(3) administration of ACE inhibitors or ARBs.
Modest restriction of protein intake in diabetic individuals withModest restriction of protein intake in diabetic individuals with
microalbuminuriamicroalbuminuria 0.8–1.0 g/kg per day or0.8–1.0 g/kg per day or
macroalbuminuriamacroalbuminuria < 0.8 g/kg per day< 0.8 g/kg per day
Nephrology consultation should be considered when the estimatedNephrology consultation should be considered when the estimated
GFR <60 mL/min per 1.743 mGFR <60 mL/min per 1.743 m22

51. I. Background retinopathy
- microaneurysms;
- haemorrhages;
- hard exudates.
II. Maculopathy
- haemorrhages and hard
exudation in the macula area;
- reduced visual acuity with
no abnormality seen.
III. Preproliferrative retinopathy
- soft exudates/cotton wool spots;
- intra-retinal abuormalities;
- venous abnormalities
(e.q. venous beading,
looping, reduplication).
IV. Proliferative retinopathy
- new vessels on discs or within
1 disc diameter of it;
- new vessels elsewhere;
- rubeosis iridis (or neovascular
glaucoma).

52.  Blurred or distorted vision or difficulty reading.
 FloatersFloaters or flashes of light in your field of vision.
 Partial or total loss of vision or a shadow or veil
across your field of vision.
 Pain in the eye.

53. To reduce risk or slow progression of retinopathyTo reduce risk or slow progression of retinopathy
Optimize glycemic controlOptimize glycemic control
Optimize blood pressure controlOptimize blood pressure control
To an ophthalmologist knowledgeable and experiencedTo an ophthalmologist knowledgeable and experienced
in management, treatment of diabetic retinopathyin management, treatment of diabetic retinopathy
Laser photocoagulation therapyLaser photocoagulation therapy

54. Diabetic neuropathyDiabetic neuropathy
Thinning skin of
food and shanks
Thinning of
interosseous
muscles
Hyperhidrosis
or anhidrosis
Increased
callus formation
Muscle atrophy
“Hang down” food
Hair loss
in the lower
extremities

56. B. Autonomic neuropathy
1.Cardiovascular autonomic
2.Abnormal pupillary function
3.Gastrointestinal autonomic
neuropathy
a.Gastroparesis
b.Constipation
c.Diabetic diarrhea
d.Anorectal incontinence
44..Genitourinary autonomicGenitourinary autonomic
neuropathyneuropathy
a.Bladder dysfunction
b.Sexual dysfunction
C. Focal Neuropathy
1.Mononeuropathy
2.Mononeuropathy multiplex
3.Amyotrophy
I.Subclinical neuropathy
A.Abnormal electrodiagnostic tests
1.Decreased nerve conduction velocity
2.Decreased amplitude of evoked
muscle or nerve action potentials
A.Abnormal neurologic examination
1.Vibratory and tactile tests
2.Thermal warming and cooling tests
3.Other tests
A.Abnormal autonomic function tests
1.Abnormal cardiovascular reflexes
2.Altered cardiovascular reflexes
3.Abnormal biochemical responses to
hypoglycemia
II. Clinical neuropathy
A.Diffuse somatic neuropathy
1.1.Sensorimotor or distal symmetricalSensorimotor or distal symmetrical
sensorimotor polyneuropathysensorimotor polyneuropathy
a.Primarily small-fiber neuropathy
b.Primarily large-fiber neuropathy
c.Mixed

57. To assess protective sensation
or feeling in the foot, a nylonnylon
monofilamentmonofilament (similar to a
bristle on a hairbrush) attached
to a wand is used to touch the
foot.
128 Hz tuning fork128 Hz tuning fork
for testing of vibration
perception.
CalibratedCalibrated
Neurotip testNeurotip test -
assesses reduced
sensation to
sharpness/ pain in
small nerve fibres.
Temperature
differentiation
using TipTherm®TipTherm®, place
one end against the
patients foot and hold for
three seconds.
NeuropadNeuropad
Leave in place for 10
minutes. In the well
hydrated patient, the
plaster is blue colour
should change to pink.
Discriminator 2Discriminator 2
PointPoint
for determining
sensory loss.

58. Improved glycemic controlImproved glycemic control should be aggressively pursued and willshould be aggressively pursued and will
improve nerve conduction velocityimprove nerve conduction velocity
Risk factors for neuropathy such as hypertensionhypertension and
hypertriglyceridemiahypertriglyceridemia should be treated
Avoidance of neurotoxinsAvoidance of neurotoxins (alcohol) and(alcohol) and smokingsmoking, supplementation, supplementation
with vitamins for possible deficiencies (Bwith vitamins for possible deficiencies (B1212, folate;ect.), and, folate;ect.), and
symptomatic treatment are the mainstays of therapysymptomatic treatment are the mainstays of therapy
Chronic, painful diabetic neuropathy is difficult to treat but may respondChronic, painful diabetic neuropathy is difficult to treat but may respond
toto AntidepressantsAntidepressants such as amitriptyline, desipramine,amitriptyline, desipramine,
nortriptyline, imipraminenortriptyline, imipramine
Anticonvulsants:Anticonvulsants: gabapentin, pregabalin, carbamazepine,gabapentin, pregabalin, carbamazepine,
lamotriginelamotrigine
Selective serotoninnorepinephrine reuptake inhibitorsSelective serotoninnorepinephrine reuptake inhibitors such as
duloxetineduloxetine

59. SYMPTOMATIC NEUROPATHYSYMPTOMATIC NEUROPATHY
Exclude nondiabetic etiologiesExclude nondiabetic etiologies
Stabilize glycemic control (insulin not always required in type 2 DM)Stabilize glycemic control (insulin not always required in type 2 DM)
Tricyclic drugs (AMITRIPTYLINE 25-150 mg before bed)Tricyclic drugs (AMITRIPTYLINE 25-150 mg before bed)
Anticonvulsants (GABAPENTIN typical dose 1.8 g/day)Anticonvulsants (GABAPENTIN typical dose 1.8 g/day)
Opioid or opioid-like drug (TRAMADOL, OXYCODONE)Opioid or opioid-like drug (TRAMADOL, OXYCODONE)
Consider pain clinic referralConsider pain clinic referral

60. Neuropathic feet Ischemic feet
Warm Cold/cool
Dry skin Atrophic/often hairless
Palpable foot pulses No palpable foot pulses
No discomfort witulcer More pften tender/painful
Gallus present
Clandication/Rest pain
Skin blanches on elevation and
reddens on dependency

62. Lateral radiograph depictsLateral radiograph depicts
neuropathic destruction of the naviculocuneiform joint (arrow)
in a 52-year-old diabetic man. Neuropathic osteoarthropathy
typically involves the medial column
of the foot earlier and more frequently than the lateral column.

63. Grade 0Grade 0 High risk foot, no ulceration present
Grade 1Grade 1 Superficial ulcer, not infected
Grade 2Grade 2
Deep ulcer with or without cellulites
bat no abscess or bone involvement
Grade 3Grade 3
Deep ulcer with bone involvement or
abscess formation
Grade 4Grade 4
Localized gangrene
(toe, forefoot, hell)
Grade 5Grade 5 Gangrene of the whole foot

64. For all patients with diabetes, perform an annual comprehensive foot examination toFor all patients with diabetes, perform an annual comprehensive foot examination to
identify risk factors predictive of ulcers and amputationsidentify risk factors predictive of ulcers and amputations
InspectionInspection
Assessment of foot pulsesAssessment of foot pulses
Test for loss of protective sensation:Test for loss of protective sensation:
10-g monofilament plus testing any one of10-g monofilament plus testing any one of
Vibration using 128-Hz tuning forkVibration using 128-Hz tuning fork
Pinprick sensationPinprick sensation
Ankle reflexesAnkle reflexes
Vibration perception thresholdVibration perception threshold
Provide general foot self-care education. Use multidisciplinary approach:Provide general foot self-care education. Use multidisciplinary approach:
Individuals with foot ulcers, high-risk feet;Individuals with foot ulcers, high-risk feet;
especially prior ulcer or amputationespecially prior ulcer or amputation

65. Compensation ofCompensation of
diabetes mellitusdiabetes mellitus
Antibiotic therapyAntibiotic therapy Local therapyLocal therapy
The first stage is directed at
LOCAL CURELOCAL CURE
of vulnerary defects
discharge of damage’s
part of foot
ANTIOXIDANTANTIOXIDANT
αα-lipolic acid:-lipolic acid:
DIALIPON
THIOGAMMA
BERLITHION
THIOCTACID
Vitamin group B:Vitamin group B:
VITAXON
MILGAMMA
NEUROBION
NEUROVITAN
LAZAR THERAPYLAZAR THERAPY
At the second stage of SDF
it is indicated to use
Antibacterial therapyAntibacterial therapy
Local cureLocal cure
Footed dischargeFooted discharge
The treatment of the patient
at the 3-5 stagesthe 3-5 stages of SDF
is organized in surgicalin surgical
hospital.hospital.

66. LESIONLESION COMMENTSCOMMENTS
Periungual
telangiectasia
Linear telangiectasia due to loss of capillary loops and
dilation of remaining capillaries In diabetes, often
associated with nail fold erythema, fingertip tenderness,
and “ragged” cuticles
Necrobiosis
lipoidica
Nonscaling plaques, yellow atrophic center, surface
telangiectasia, erythematous or violaceous border
Occurs mainly in pretibial region
Bullosis
diabeticorum
Asymptomatic, noninflamed bullae on dorsa and sides
of lower legs Men affected more often than women
Treatment is symptomatic and conservative.
Vitiligo Skin depigmentation, with no area of predilection
Markedly more common in type 1 diabetes In a diabetic
patient, a possible warning sign for polyglandular
autoimmune syndrome
Lichen ruber planus On the skin, flat, polygonal, erythematous lesions; in
the mouth, white stripes with reticular pattern. Occurs
mainly on wrists and dorsa of feet and lower legs

67. LESION COMMENTS
Yellow nails Yellow discoloration most evident on distal end of the hallux
nail Occasionally seen in the elderly or in onychomycosis
Diabetic thick
skin
Asymptomatic, measurably thicker skin Fingers and hands
most often affected Appearance ranges from pebbling over
the knuckles to diabetic hand syndrome May represent
diabetic scleredema, with peau d’orange appearance and
decreased sensitivity to pain and touch in affected areas
Acrochordons
(skin tags)
Small, pedunculated, soft lesions, most often on eyelids,
neck, and axillae Treatment not necessary, but can be
removed with grade 1 scissors, cryotherapy,
electrodessication
Diabetic
dermopathy
Atrophic, scarring, hyperpigmented macules on the extensor
surface of lower legs
Acanthosis
nigricans
Velvety-looking hyperpigmented plaques, especially in body
folds May be related to high levels of circulating insulin

68. LESION COMMENTS
Acquired perforating
dermatosis
Dome-shaped papules and nodules with hyperkeratotic plug
Can affect limbs, trunk, dorsal surface of hands Seen in
patients with kidney failure or type 2 diabetes or both, and to
a lesser extent in type 1 diabetes
Calciphylaxis First appears as localized redness and tenderness, then as
subcutaneous nodules and necrotizing skin ulcers Usually
occurs in vascular regions with thicker subcutaneous
adipose tissue
Eruptive xanthoma Crops of yellow papules with an erythematous halo Usually
occurs on extensor surfaces and the buttocks Associated
with high levels of triglyceride-rich lipoproteins Treatment:
lesions tend to resolve with control of carbohydrate and lipid
metabolism
Granuloma annulare Association with diabetes has been hypothesized but not
clearly established Oval or ring-shaped lesions with a raised
border of skin-colored or erythematous papules.

69. Toenail FungusToenail Fungus
(onychomycosis)(onychomycosis)
Corns
Callus
General appearance
of necrobiosis
lipoidica
Lichen ruber planus
Erythema
exsudativum
multiforme
Erythema
nodosum
Acanthosis nigricans

70. ► Type 1Type 1 Diabetes mellitusDiabetes mellitus first diagnosticfirst diagnostic withwith
ketoacidosisketoacidosis ((datedate – 15.09.12.) in decompensation.– 15.09.12.) in decompensation.
► Type 1Type 1 Diabetes melitusDiabetes melitus medium degree inmedium degree in
satisfactory compensation. Dsatisfactory compensation. Diabetic nephropathyiabetic nephropathy
II stage. Background retinopathy.II stage. Background retinopathy.
► Type 1Type 1 Diabetes mellitusDiabetes mellitus severe degree in satisfactorysevere degree in satisfactory
compensation. Dcompensation. Diabetic nephropathyiabetic nephropathy IV stage.IV stage.
Preproliferative retinopathy. DiabeticPreproliferative retinopathy. Diabetic NeuropathicNeuropathic
food grade 1.food grade 1. Diabetic diarrheaDiabetic diarrhea. Diabetic ketoacidic. Diabetic ketoacidic
comas in anamnesiscomas in anamnesis (years(years – 2010,2011– 2010,2011).). ChronicChronic
pyelonephritis intensification stage.pyelonephritis intensification stage.
► Type 2 Diabetes mellitus mild degree in goodType 2 Diabetes mellitus mild degree in good
compensation. Metabolic syndrome. Obesity class I.compensation. Metabolic syndrome. Obesity class I.
Hypertension.Hypertension.
► Type 2Type 2 Diabetes mellitusDiabetes mellitus medium degree in badmedium degree in bad
compensation.compensation.