Etiology, pathogenesis, classification, early diagnosis, clinical presentation and differential diagnosis of Diabetes Mellitus. Metabolic syndrome

1. Lecture 1.Lecture 1.
Etiology, pathogenesis, classification,Etiology, pathogenesis, classification,
early diagnosis, clinical presentationearly diagnosis, clinical presentation
and differential diagnosis of Diabetesand differential diagnosis of Diabetes
Mellitus. Metabolic syndrome.Mellitus. Metabolic syndrome.
IRYNA KOSTITSKAIRYNA KOSTITSKA
Candidate of Sciences (Medicine)Candidate of Sciences (Medicine)
Associate professorAssociate professor of endocrinology chairof endocrinology chair

2. PLAN OF THE LECTUREPLAN OF THE LECTURE
1.1. Preface.Preface.
2.2. History of Diabetes Mellitus.History of Diabetes Mellitus.
3.3. Hormones of pancreas. Mechanisms secretion and theHormones of pancreas. Mechanisms secretion and the
actions of insulin.actions of insulin.
4.4. Definition of Diabetes Mellitus.Definition of Diabetes Mellitus.
5.5. Classifications of Diabetes Mellitus.Classifications of Diabetes Mellitus.
6.6. Etiology, pathogenesis of Diabetes Mellitus.Etiology, pathogenesis of Diabetes Mellitus.
7.7. Clinical presentation of Diabetes Mellitus.Clinical presentation of Diabetes Mellitus.
8.8. Early diagnosis of Diabetes Mellitus. Criteria ofEarly diagnosis of Diabetes Mellitus. Criteria of
diagnostics of diabetes mellitus and other types ofdiagnostics of diabetes mellitus and other types of
hyperglycemia.hyperglycemia.
9.9. Criteria of compensation of Diabetes Mellitus.Criteria of compensation of Diabetes Mellitus.
10.10. Differential diagnosis of Diabetes Mellitus.Differential diagnosis of Diabetes Mellitus.
11.11. Metabolic syndrome.Metabolic syndrome.

3. DMDM will surely be one of our most common and challenging
health problems in the 21in the 21stst
century.century.
One of the most challenging health problems facing theOne of the most challenging health problems facing the
world:world:
346 million people346 million people worldwide diagnosed in 20112011
55thth
leading causeleading cause of deathof death in developed countries
ComplicationsComplications – heart attacks, stroke, kidney failure,– heart attacks, stroke, kidney failure,
amputations and blindnessamputations and blindness
According to the World Health Organization (WHO),World Health Organization (WHO), the
number of global cases of DM is expected to increase in the
next 25 years25 years nearly 580 million people.nearly 580 million people.
Diabetes Mellitus (DM)Diabetes Mellitus (DM)
The name 'diabetes mellitus''diabetes mellitus' derives from:
GreekGreek:: 'diabetes''diabetes' – “siphon”– “siphon” or “to pass“to pass
through”through”
Latin:Latin: 'mellitus''mellitus' – “honeyed– “honeyed” or “sweet”“sweet”

4. History of Diabetes MellitusHistory of Diabetes Mellitus
First known reference comes from anFirst known reference comes from an
Egyptian papyrusEgyptian papyrus dating backdating back
to 1550 B.C.to 1550 B.C. Earliest known record of
diabetes mentioned on 3rd Dynasty Egyptian
papyrus by physicianphysician Hesy-RaHesy-Ra; mentions
polyuria as a symptom.
DiabetesDiabetes was named by the GreekGreek
physicianphysician AretaeusAretaeus between 30 andbetween 30 and
90 A.D.90 A.D.
400 B.C400 B.C.-Indian surgeon.-Indian surgeon SusrutaSusruta describes ‘honeyed‘honeyed
urines’urines’ produced by ‘big eaters of rice and sugar’.‘big eaters of rice and sugar’.

5. AvicennaAvicenna, a famous Arab, a famous Arab
physician, described thephysician, described the
complications of the disease andcomplications of the disease and
how it progressedhow it progressed
History of Diabetes MellitusHistory of Diabetes Mellitus
250 A.D.-250 A.D.- Apollinius ofApollinius of
MemphisMemphis coins the namecoins the name
‘diabetes’‘diabetes’

6. History of Diabetes MellitusHistory of Diabetes Mellitus
16741674 - Thomas WillisThomas Willis publishes
‘The Diabetes or Pissing Evil’.‘The Diabetes or Pissing Evil’.
Writes ‘those laboring with this‘those laboring with this
Disease, piss a great deal moreDisease, piss a great deal more
than they drink’than they drink’ asserting that all
diabetic urine ‘‘was wonderfullywas wonderfully
sweet as if it were imbued withsweet as if it were imbued with
Honey or Sugar’.Honey or Sugar’.
17981798 - John RolloJohn Rollo documents
excess sugar in blood and urine
18131813- Claude BernardClaude Bernard links
diabetes with glycogen metabolism

7. History of Diabetes MellitusHistory of Diabetes Mellitus
18691869- Paul LangerhansPaul Langerhans (German medical
student) finds islets in the pancreas, but is
unable to explain function.
French physician Apollinaire BouchardatApollinaire Bouchardat
recognized the importance of calorie intake
in the 1870s.in the 1870s.
18891889- Josef Baron von MeringJosef Baron von Mering and OskarOskar
MankowskiMankowski prove that diabetes develops when
they remove the pancreas of dogs.

8. History of Diabetes MellitusHistory of Diabetes Mellitus
1901 - Eugene Opie, an American
pathologist at Johns Hopkins
University, made the association
between the degeneration of these
cells, which had been named the
“islets of Langerhans,” and the onset
of diabetes.
1910-1910- English physiologist, SirSir
Edward Albert Sharpey-SchaferEdward Albert Sharpey-Schafer,
suggested that a single chemical
component was missing from the
pancreas of diabetics and called it
“insulininsulin”.

9. History of Diabetes MellitusHistory of Diabetes Mellitus
19221922- James Bertram CollipJames Bertram Collip
The first clinical tests on a
human patient were conducted
on a severely diabetic 14 year
old boy.
The Face of IDDMThe Face of IDDM
in 1920 wasin 1920 was
not encouragingnot encouraging
1923 -1923 - Frederick BantingFrederick Banting and CharlesCharles
HerbertHerbert BestBest awarded Nobel Prize for
Discovery and use of Insulin in the
treatment of IDDM.

10. History of Diabetes MellitusHistory of Diabetes Mellitus
Frederick BantingFrederick Banting John James RickardJohn James Rickard
MacleodMacleod
James BertramJames Bertram
CollipCollip
CharlesCharles
Herbert BestHerbert Best

11. Normal Insulin PhysiologyNormal Insulin Physiology
Produced within the
pancreas by β cells, islets
of Langerhans – identified
by Paul Langerhans in
1869.
Islets of Langerhans –
α cells – secrete glucagons,glucagons,
delta cells –
somatostatinsomatostatin
PP cells – pancreaticpancreatic
polypeptide.polypeptide.
Insulin is an anabolic
hormone.
Insulin is a polypeptide
(built from 51 amino acids:
Chain A consists of 21,
chain B of 30 amino acids. 2
chains linked by disulfidedisulfide
bondsbonds)
Daily pancreatic production
of insulin in the adult
individual to approximately
50 units ( 0.7–1.3 mg).

12. Mechanisms of insulin secretionMechanisms of insulin secretion
INSULININSULIN
Synthesis of glycogenSynthesis of glycogen
GLYCOLYSISGLYCOLYSIS
Glucose uptakeGlucose uptake
Blood glucoseBlood glucose
GLYCOGENOLYSISGLYCOGENOLYSIS
EpinephrineEpinephrine
GlucagonGlucagon
ACTHACTH
Growth hormoneGrowth hormone
GlucocorticoidsGlucocorticoids
--
++
++
++
++
--

13. The actions of insulinThe actions of insulin
 InsulinInsulin increases utilization of glucose by muscles and
adipose tissue, increases the synthesis of glycogen in the
liver and muscles, reduces glycogenolysis andglycogenolysis and
glyconeogenesisglyconeogenesis.
 In adipose tissue insulininsulin increasesincreases synthesis of the fatty acidsfatty acids,
promotes lipogenesis, lipolysis and synthesis of ketones.promotes lipogenesis, lipolysis and synthesis of ketones.
 InsulinInsulin facilitates protein metabolism, increases absorption ofincreases absorption of
amino acid, synthesis of the proteinsamino acid, synthesis of the proteins and reduces their
catabolism.
 InsulinInsulin also increases metabolism of the nucleotidesincreases metabolism of the nucleotides –
absorption and synthesis of nucleoid acids, as well as of RNA
and DNA increases.
 InsulinInsulin takes part in the process of growth and differentiationgrowth and differentiation
of all body tissuesof all body tissues. It supports their energy status, provides
differentiation, activation of the immunocompetent lymphocites,
due to the synthesis of the proteins and nucleotides the
processes of transcription and translation of genetic information

14. Action of Insulin on Various TissuesAction of Insulin on Various Tissues
MuscleMuscle AdiposeAdipose
↓↓ GlucoseGlucose
productionproduction
↑↑ Glucose transportGlucose transport ↑↑ Glucose transportGlucose transport
↑↑ GlycolysisGlycolysis ↑↑ GlycolysisGlycolysis ↑↑ Lipogenesis&Lipogenesis&
lipoprotein lipaselipoprotein lipase
activityactivity
↑↑ TGTG
synthesissynthesis
↑↑ GlycogenGlycogen
depositiondeposition
↓↓ IntracellularIntracellular
lipolysislipolysis
↑↑ ProteinProtein ↑↑ Protein synthesisProtein synthesis

15. Effects of insulin deficiencyEffects of insulin deficiency
Metabolic defects Chemical abnormalities Clinical abnormalities
Carbohydrate MetabolismCarbohydrate Metabolism
1.Diminished uptake of glucose by tissues such as
muscle, adipose tissue and liver
2. Overproduction of glucose (via glycogenolysis and
glyconeogenesis) by the liver
Hyperglycemia
Polyuria, polydipsia,
polyphagia
Blurred vision,
Diminished mental
alertness
Protein MetabolismProtein Metabolism
1.Diminished uptake of amino and diminished synthesis
of protein
2. Increased proteolysis
Negative nitrogen balance
Elevated levels of branch
chain amino acids
Elevated blood urea
nitrogen level
Elevated potassium level
Loss of muscle
mass
Weakness
Fat MetabolismFat Metabolism
1.Increased lipolysis
2.Decreased lipogenesis
3.Increased production of triglycerides
4.Decreased removal of ketones and increased ketone
production
Elevated plasma fatty
acids level
Elevated plasma glycerol
level
Hypertriglyceridemia
Elevated plasma and
urine ketones
Loss of adipose
tissue
Exudative
xanthoma
Lipemia retinalis
Pancreatitis
(abdominal pain)
Hyperventilation
metabolic acidosis

16. A glossary ofA glossary of termsterms will be usedwill be used
GlycogenesisGlycogenesis -- the process by which glycogen is formed from
glucose.
GluconeogenesisGluconeogenesis –– the formation of glucose, especially by the liver,
from noncarbohydrate sources, such as amino acids and the glycerol
portion of fats.
Lipogenesis(adipogenesis)-Lipogenesis(adipogenesis)- production of fat, either fatty
degeneration or fatty infiltration. The normal deposition of fat or the
conversion of carbohydrate or protein to fat.
LipolysisLipolysis –– the metabolic process of breaking down lipids release
free fatty acids, the major oxidative fuel for the body.
EuglycemiaEuglycemia oror NormoglycaemiaNormoglycaemia-- normal blood glucose level
(fasting 3.3-5.5 mmol/L and 2 hour after meal less than 7.8 mmol/L).
HHypoglycemia-ypoglycemia- low blood glucose level (<2.75 mmol/L).
HHyperglycemia-yperglycemia- high blood glucose level.
HyperinsulinismHyperinsulinism -- high a level of insulin in the blood.
Impaired Glucose Tolerance (IGT)Impaired Glucose Tolerance (IGT) -- blood glucose levels higher
than normal but not high enough to be called diabetes (prediabetes).
GGlycosuria-lycosuria- high glucose in the urine.
KKetonuria-etonuria- ketone bodies in the urine.
PPolyphagiaolyphagia-- excess appetite.
PPolyuriaolyuria-- excess urinating.
PPolydypsia-olydypsia- excess drinking.

17. CLINICAL CASECLINICAL CASE
The patient B., 26 years old complainscomplains
of weight loss (8 kg during 6 months), moderate dryness in the mouth,
gingival hemorrhage, thirst, polyuria (diuresis - 5 L/day), growing the
weakness. He feels ill for 5 months. Anamnesis of life:Anamnesis of life: Physical
development in childhood was normal. He had history of diabetes mellitus in
several family members: mother and grandfather. Allergic reactions were
absent. Objectively:Objectively: General conditions of patient is middle heaviness.
Body weight - 68 kg. Height -188 cm. BMI – 19,4 kg/m2
. His temperature is
36.6 °C. The skin and mucosas are moderately dry, considerable grow thin,
especially muscles. Boils on thigh. Tongue is dry. Type of breathing is
abdominal. The borders of relative and absolute heart dullness are normal.
Pulse – 76 beats/ min, rhythmical, BP- 130/80 mmHg. The loudness of heart
tones amplified. Stomach is soft, liver doesn’t increased. Urination –
accelerating, mainly in the night. Lab studies:Lab studies: the fasting level of glucose-
14 mmol/L; the level of the HbA1c – 10%; the glucosuria - 22 g/L; reaction
of urine to acetone - negative.
What is the most likely diagnosis?What is the most likely diagnosis?

18. DefinitionDefinition
DIABETES MELLITUS (DM)DIABETES MELLITUS (DM)
(World Health Organization )(World Health Organization )
The term DMDM describes a metabolic disorder of multiple
etiology characterized by chronic hyperglycemia with
disturbances of carbohydrate, fat and protein metabolism
resulting from defects in insulin secretion, insulin action,
or both.
DMDM is a group of metabolic (endocrine) diseases, resulting
from a variable interaction of hereditary and environmental
factors, wich is presented by hyperglycaemia following
absolute or relative insulin insufficiency that causes
metabolic manifestations reflected in a tendency toward
accelerated non – specific atherosclerosis, macro- and
microangiopathy, neuropathy, increased susceptibility to
infection.

19. Etiologic Classifications of Diabetes Mellitus
TYPE 1
DIABETES
MELLITUS
β-cell destruction, usually leading to
absolute insulin deficiency.
idiopathic type 1 - refers to rare
forms of the disease with no known
cause.
immune-mediated diabetes - an
autoimmune disorder in which the
body's immune system destroys, or
attempts to destroy, the cells in the
pancreas that produce insulin.
TYPE 2
DIABETES
MELLITUS
predominantly insulin resistanceinsulin resistance with
relative insulin deficiency or
predominantly an insulin secretory defect
with/without insulin resistance.
GESTATIONAL
DIABETES
is carbohydrate intolerance resulting in
hyperglycaemia of variable severity with
onset or first recognition during
pregnancy.

20. 20
InsulinindependentInsulinindependent
((adult-onset diabetesadult-onset diabetes))
 HeredityHeredity
InactivityInactivity
ObesityObesity
Insulin resistanceInsulin resistance
More common in adultsMore common in adults
after 35 yearsafter 35 years
Treatment: diet, sugarTreatment: diet, sugar
lowering drugslowering drugs
InsulindependentInsulindependent
((oror ““juvenile-onsetjuvenile-onset
diabetesdiabetes”,”, "juvenile"juvenile
diabetes," anddiabetes," and
"ketosis-prone"ketosis-prone
diabetes")diabetes")
 AutoimmuneAutoimmune
 GeneticsGenetics
(HLA-B8, B15(HLA-B8, B15 ))
 More commonMore common
in younger thanin younger than
35 years or children35 years or children
 Treatment: diet,Treatment: diet,
insulininsulin

21. Pathogenesis of Type 1 Diabetes MellitusPathogenesis of Type 1 Diabetes Mellitus
Viruses
Infection ofInfection of ββ cellscells Systemic infectionSystemic infection
DirectDirect
cytolyticcytolytic
effectseffects
ββ cells necrosiscells necrosis AutoimmuneAutoimmune ββ cells damagecells damage
Type 1Type 1
Diabetes MellitusDiabetes Mellitus
Indirect immune effectsIndirect immune effects
• Viral antigens expressedViral antigens expressed
•ββ cell antigens alteredcell antigens altered
•Expression of cytokinesExpression of cytokines
or HLA antigensor HLA antigens
•Activation of immuneActivation of immune
responseresponse
•Breakdown of immuneBreakdown of immune
tolerancetolerance
•Immune response crossImmune response cross
reacts withreacts with
ββ cell autoantigenscell autoantigens
(molecular mimicry)(molecular mimicry)

22. Insulin Resistance: Receptor and Postreceptor Defects
Peripheral tissues
(skeletal muscle)
Hyperglycemia /Hyperglycemia /
Type 2 DMType 2 DM
Pancreas
Liver
Impaired insulin secretion
Increased glucose
production
X
Insufficient glucose
disposal
Pathogenesis of Type 2 Diabetes MellitusPathogenesis of Type 2 Diabetes Mellitus
GeneticsGenetics
EnvironmentEnvironment
obesity;obesity; hypodynamia;hypodynamia;polyphagiapolyphagia

23. CRITERIA FOR DIAGNOSISCRITERIA FOR DIAGNOSIS
POLYDIPSIAPOLYDIPSIA
RAPID WEIGHT LOSSRAPID WEIGHT LOSS
POLYURIAPOLYURIA
HYPERGLYCEMIAHYPERGLYCEMIA
> 11.1 mmol/L> 11.1 mmol/L
DIABETES
DIABETES
SYM
PTO
M
S
SYM
PTO
M
S
DIABETES
DIABETES
SYM
PTO
M
S
SYM
PTO
M
S

24. ifif one of theone of the
following is presentfollowing is present
Casual plasma glucoseCasual plasma glucose
(is(is
defined as any time of thedefined as any time of the
day, without regard to theday, without regard to the
interval since the last meal)interval since the last meal)
> 11.1 mmol/L> 11.1 mmol/L
Fasting plasma glucoseFasting plasma glucose > 7.0 mmol/L> 7.0 mmol/L
2-hour plasma glucose2-hour plasma glucose
during an oral glucoseduring an oral glucose
tolerance testtolerance test
>11.1 mmol/L>11.1 mmol/L
Symptoms of diabetesSymptoms of diabetes mellitusmellitus
plusplus

25. Manifestation ofManifestation of
diabetes mellitusdiabetes mellitus
ConsiderableConsiderable
generalgeneral
weaknessweakness
ThirstThirst
(polydipsia)(polydipsia)
GlucosuriaGlucosuria
IItch of skintch of skin
andand
genitalsgenitals
PolyphagiaPolyphagia
Weight lossWeight loss
PoliuriyaPoliuriya
HyperglycemiaHyperglycemia

26. THE ORAL GLUCOSE TOLERANCE TESTTHE ORAL GLUCOSE TOLERANCE TEST (GTT)(GTT)
TheThe Testing for Diabetes in Asymptomatic Patients;Testing for Diabetes in Asymptomatic Patients;
GTT should be considered in all adults who are overweight (BMI ≥25 kg/m2
) and have additional
risk factors:
• Physical inactivity
•First-degree relative with diabetes
•High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American,
Pacific Islander)
•Women who delivered a baby weighing >5 kg or were diagnosed with GDM
•Hypertension (≥140/90 mmHg or on therapy for hypertension)
•Women with polycystic ovarian syndrome (PCOS)
•A1C ≥5.7%, IGT, or IFG on previous testing
•Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis
nigricans)
•History of CVD
Preparation of the patient:Preparation of the patient:
Three days unrestricted, carbohydrate rich diet and activity.Three days unrestricted, carbohydrate rich diet and activity.
No medication on the day of the test.No medication on the day of the test.
12-h fast.12-h fast.
No smoking.No smoking.
Glucose load: Adults 75 g in 300 – 400 mL of water.
Children: 1,75 g/Kg up to 75 g glucose
Solutions containing glucose and oligosaccharides are commercially available.
For interpretation of results, refer to Table:For interpretation of results, refer to Table:

27. Criteria of diagnostics of diabetes mellitusCriteria of diagnostics of diabetes mellitus
and other types of hyperglycemia (WHO, 1999)and other types of hyperglycemia (WHO, 1999)
Diagnosis
Concentration of glucose, mmol/L
Whole blood Plasma
Venous Capillary Venous Capillary
Diabetes mellitus:Diabetes mellitus:
Fasting level
In 2 hours after
glucose load
≥6.1
≥10.0
≥ 6.1
≥11.1
≥7.0
≥11.1
≥7.0
≥12.2
Impaired toleranceImpaired tolerance
to glucose:to glucose:
Fasting level
In 2 hours after
glucose load
<6.1
6.7-10.0
<6.1
7.8-11.1
<7.0
7.8-11.1
<7.0
8.9-12.2
Impaired glycemia inImpaired glycemia in
the fasted statethe fasted state
5.6-6.1 5.6-6.1 6.1-7.0 6.1-7.0

28. Laboratory TestsLaboratory Tests
Fasting plasma glucose (FPG)Fasting plasma glucose (FPG)
GGlycosylatedlycosylated HHemoglobinemoglobin TTestest ((HbA1c, glycohemoglobinHbA1c, glycohemoglobin))
- It is produced by nonenzymatic condensation of glucose
molecules with free amino groups on the globin component of
hemoglobin. Level of HbA1c shows an average blood
concentration during the previous 2 – 3 month. NormalNormal
level oflevel of HbA1cHbA1c is 4-6%.is 4-6%.
C-peptideC-peptide is a connective peptide between A and B by theis a connective peptide between A and B by the
chainlets of insulin.chainlets of insulin. The level of C – peptide is 1- of 2,81- of 2,8
mmol/mlmmol/ml, it is determined by radioimmune test kits. The level
of c-peptide in type 1 diabetus mellitus is reduced.
FructosamineFructosamine is a product of glycosilation of the plasmais a product of glycosilation of the plasma
proteins, particilarly of the albumen which has a period ofproteins, particilarly of the albumen which has a period of
semilife of 14 days.semilife of 14 days. Normal level is less then 0,285 mmol/LNormal level is less then 0,285 mmol/L.
Immunoreactive insulin -Immunoreactive insulin - the secretion of the endogenouse secretion of the endogenous
insulin in a healthy man is on averageinsulin in a healthy man is on average 5- 205- 20 мкЕмкЕ /mL/mL in thein the
fasted state.fasted state.

29. Laboratory TestsLaboratory Tests
Insulin autoantibodyInsulin autoantibody (IAA), glutamic acid decarboxylaseglutamic acid decarboxylase
(GADA), islet cell antibodiesislet cell antibodies ( ICA) ,-now replaced by
tyrosine phosphatase autoantibodiestyrosine phosphatase autoantibodies (IA-2,IA2-b) are the
most commonly used tests .
Self-monitoring of blood glucoseSelf-monitoring of blood glucose by people with diabetes
(Diabetes Control and Complications TrialDiabetes Control and Complications Trial):blood glucose
monitors / glucometers (Accu-Chek Sensor, Van Touch Ultra
and other ) and ccontinuous glucose monitoring systemontinuous glucose monitoring system..
Fasting lipid profileFasting lipid profile (14 hours): total cholesterol, HDL
cholesterol, triglycerides, and LDL cholesterol.
Renal and liver function tests:Renal and liver function tests: serum creatinine and blood
urea nitrogen (BUN) levels, and a glomerular filtration rate
(GFR); albumin, bilirubin, AST, ALT.

30. Lima Blood Sugar AnalyserLima Blood Sugar Analyser
the technological base of lima is the non-invasive measurementthe technological base of lima is the non-invasive measurement
via infrared radiationvia infrared radiation
Freedom Meditech promises glucose-Freedom Meditech promises glucose-
monitoring eye scannermonitoring eye scanner

31. Laboratory TestsLaboratory Tests
URINE TESTSURINE TESTS::
GlucosuriaGlucosuria appears in the urine of a healthy man when
glycemia rises above kidney threshold that corresponds the
level of glycemia ofglycemia of 8.8- 9.0 mmol/L.8.8- 9.0 mmol/L.
Glucose LevelsGlucose Levels and Fractional Urineand Fractional Urine ("block urine")-("block urine")- urine
that a person collects for a certain period of time during
24 hours.
KetonuriaKetonuria when decompensation of diabetes mellitus occurs,
”ketone” bodies present in urine. Determination of ketonuria is
conducted by the test strips ( «Ketostiks», «Keto- Diastiks»).
Microalbuminuria and proteinuria:Microalbuminuria and proteinuria: the early stage of
albuminuria is clinically defined as an albumin excretion rate of 30-
300 mg/24 hours (20-200 g/min).

32. IndividualIndividual
glucometersglucometers
Ketostiks
(Bayer)
Glucose +Glucose +
Keton bodiesKeton bodies

33. Clinical classification of diabetes mellitus (A.S. Efimov, 1998)Clinical classification of diabetes mellitus (A.S. Efimov, 1998)
I. Type of Diabetes mellitus:I. Type of Diabetes mellitus:
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Gestational diabetes mellitus
II.II. Forms (degree) of severity:Forms (degree) of severity:
MildMild
MediumMedium
SevereSevere
III.III. State of compensationState of compensation::
GoodGood
SatisfactorySatisfactory
Bad or DecompensationBad or Decompensation
IV. Presence of chronic diabetic complications:IV. Presence of chronic diabetic complications:
MikroangiopatMikroangiopathyhy - retinopathy, nephropthy, diabetic food.
MakrooangiopathyMakrooangiopathy - with the overwhelming defeat of large vessels
(heart, brain, feet).
UniversalUniversal mikro-mikro- andand makroangiopamakroangiopathy.thy.
PolineuropathyPolineuropathy (peripheral, autonomous, visteral).
Encephalopathy.Encephalopathy.
V.V. Afection of other organs and systemsAfection of other organs and systems::
steatohsteatohepatoepatosis, cataract,sis, cataract,
dermatopadermatopathy, othy, osteoartropasteoartropathy andthy and
other.other.
VI.VI. AcuteAcute complications of diabetescomplications of diabetes
mellitus:mellitus:
diabetic ketosis, ketoacidosis (DKA,diabetic ketosis, ketoacidosis (DKA,
ketoacidotic coma), hyperosmolarketoacidotic coma), hyperosmolar
(nonketotic) coma, lactacidotic coma,(nonketotic) coma, lactacidotic coma,
hypoglycemic coma.hypoglycemic coma.

34. In UkraineIn Ukraine there are three degrees (forms)three degrees (forms) of severity of manifest
diabetes mellitus. Abroad this classification is not used.
The major criteria at the estimation of the severity degree are susceptibility
to ketoacidosis, hypoglycemic comas, the dosage and the character of
oral hypoglycemic preparations, which are necessary for achievement and
permanent keeping of the state of compensation of disease.
MILD DEGREE:MILD DEGREE:
the absence of comas in anamnesis, only diet therapy
(patients with type 2 diabetes mellitus).
MEDIUM DEGREE:MEDIUM DEGREE:
diet, oral hypoglycemic preparations or insulin in daily doses is 60 IU
(at most), chronic complications (diabetic angioneuropathy of various
intensity and localization).
SEVERE DEGREE:SEVERE DEGREE:
diet, insulin therapy more than 60 IU a day, presence of comas in
anamnesis and serious form of chronic complications (angioneuropathy,
nephropathy, retinopathy and others).

35. Criteria of compensation of type 1 diabetes mellitusCriteria of compensation of type 1 diabetes mellitus
(European Group on the Type 1 Diabetes, 1998)(European Group on the Type 1 Diabetes, 1998)
Criteria Healthy Adequate
control
Inadequate
control
Glucose (mmol/L)Glucose (mmol/L)
Fasted stateFasted state 4.0-5.0 5.1-6.5 >6.5
After the mealAfter the meal 4.0-7.5 7.6-9.0 >9.0
Before sleepBefore sleep 4.0-5.0 6.0-7.5 >7.5
GlycosilatedGlycosilated
haemoglobin (%)haemoglobin (%)
<6.1 6.2-7.5 >7.5

36. Criteria of compensation of type 2 diabetes mellitusCriteria of compensation of type 2 diabetes mellitus
(International group, 1999)(International group, 1999)
Indices Compensation
GoodGood SatisfactorySatisfactory BadBad
Glycemia mmol/L:
Fasting
Postprandial
4.4-6.1
5.5-8.0
6.2-7.8
8.1-10.0
>7.8
>10.0
Glycosilated haemoglobin (%) <6.5 6.5-7.5 >7.5
Total cholesterol, mmol/L <4.8 4.8-6.0 >6.0
Triglicerides, mmol/L <1.7 1.7-2.2 >2.2
Body mass index, kg/m2
men
women
<25
<24
25-27
24-25
>27
>25
Blood pressure, mm Hg
systolic
diastolic
<120
<80
120-140
80-90
>140
>90

37. Correlation of A1C with EstimatedCorrelation of A1C with Estimated
Average Glucose (eAG)Average Glucose (eAG)
HbA1C (%)HbA1C (%) Mean plasma glucoseMean plasma glucose
(mmol/L)(mmol/L)
66 7.07.0
77 8.68.6
88 10.210.2
99 11.811.8
1010 13.413.4
1111 14.914.9
1212 16.516.5
Contains the correlation between A1C levels and mean plasma glucose (PG)Contains the correlation between A1C levels and mean plasma glucose (PG)
levels based on data from the international A1C-Derived Average Glucoselevels based on data from the international A1C-Derived Average Glucose
(ADAG) with type 1 and type 2 diabetes(ADAG) with type 1 and type 2 diabetes

38. Differential diagnosis of Diabetes MellitusDifferential diagnosis of Diabetes Mellitus
Symptomatic HyperglycemiaSymptomatic Hyperglycemia
in patientin patient
with Hyperthyroidismwith Hyperthyroidism
Symptomatic HyperglycemiaSymptomatic Hyperglycemia
in patient within patient with
PheochromocytomaPheochromocytoma
Symptomatic HyperglycemiaSymptomatic Hyperglycemia
in patient within patient with
Cushing’s DiseaseCushing’s Disease
Renal (Nondiabetic)
Glucosuria
Symptomatic HyperglycemiaSymptomatic Hyperglycemia
in patient within patient with
Cushing’s syndromeCushing’s syndrome
Symptomatic HyperglycemiaSymptomatic Hyperglycemia
in patient that usein patient that use Medications such asMedications such as
diuretics , phenytoin , and high-dosediuretics , phenytoin , and high-dose
glucocorticoidsglucocorticoids ectect
Diabetes InsipidusDiabetes Insipidus

39. CLINICAL CASECLINICAL CASE
The patient G., a 45 year old is concerned she may have
diabetes mellitus. She had diabetes during her last pregnancy
managed with diet. Lately she has been feeling tired but
otherwise has no complaints. Her mother and one of her two
sisters already have diabetes treated with tablets. She has been
overweight since her last pregnancy and has taken a tablet for
blood pressure for the last 2 years. She is obese, body mass
index 34.5 kg/m2.
Blood pressure is 140/90 mmHg, but otherwise
her examination is normal. She undergoes a testing and her
fasting glucose is 9.4 mmol/L. Obese, strong family history,
aged in 40s, previous history of diabetes in pregnancy all point
to type 2 diabetes mellitus.

40. METABOLIC SYNDROMEMETABOLIC SYNDROME
Also known asAlso known as Cardiovascular Dysmetabolic Syndrome,Cardiovascular Dysmetabolic Syndrome,
Insulin Resistance Syndrome, Syndrome X, The DeadlyInsulin Resistance Syndrome, Syndrome X, The Deadly
quartet, Cardiometabolic Syndrome, Beer Belly Syndrome,quartet, Cardiometabolic Syndrome, Beer Belly Syndrome,
Reaven’s SyndromeReaven’s Syndrome
a cluster of symptomsa cluster of symptoms including centralincluding central adiposity,adiposity,
hypertriglyceridemia, hypertension,low levels of high-hypertriglyceridemia, hypertension,low levels of high-
density lipoprotein (HDL) cholesterol,density lipoprotein (HDL) cholesterol, and elevated fastingand elevated fasting
plasma glucose levels, isplasma glucose levels, is associated withassociated with increased riskincreased risk
for heart disease, type 2 diabetes mellitus,for heart disease, type 2 diabetes mellitus, andand
cardiovascular and all-cause mortalitycardiovascular and all-cause mortality..

41. SHORT HISTORY OF SEARCH FORSHORT HISTORY OF SEARCH FOR
METABOLIC SYNDROMEMETABOLIC SYNDROME
1923:1923: Kylin describes clustering of hypertension, gout, andKylin describes clustering of hypertension, gout, and
hyperglycemiahyperglycemia
1988:1988: Reaven describes “Syndrome X” – hypertension,Reaven describes “Syndrome X” – hypertension,
hyperglycemia, glucose intolerance, elevated triglycerides, andhyperglycemia, glucose intolerance, elevated triglycerides, and
low HDL cholesterollow HDL cholesterol
1998:1998: WHO defines “metabolic syndrome” as clustering ofWHO defines “metabolic syndrome” as clustering of
hypertension, low HDL, hypertriglyceridemia, insulin resistance,hypertension, low HDL, hypertriglyceridemia, insulin resistance,
glucose intolerance or type 2 diabetes, high waist-to-hip ratio,glucose intolerance or type 2 diabetes, high waist-to-hip ratio,
and microalbuminuriaand microalbuminuria
2001:2001: NCEP ATP III provides clinical definition of “metabolicNCEP ATP III provides clinical definition of “metabolic
syndrome”syndrome”

42. INSULIN RESISTANCE IS LINKED TO A RANGE OFINSULIN RESISTANCE IS LINKED TO A RANGE OF
CARDIOVASCULAR RISK FACTORSCARDIOVASCULAR RISK FACTORS
Atherosclerosis
HyperglycemiaHyperglycemia
DyslipidemiaDyslipidemia
HypertensionHypertension
Damage to bloodDamage to blood
vesselsvessels
ClottingClotting
abnormalitiesabnormalities
InflammationInflammation
InsulinInsulin
resistanceresistance
IR
Zimmet P. Trends Cardiovasc Med 2002; 12:354–362.

44. Obesity, Metabolic Syndrome, Type 2 DiabetesObesity, Metabolic Syndrome, Type 2 Diabetes
Mellitus and Cardiovascular DiseaseMellitus and Cardiovascular Disease
ObesityObesity
Cardiovascular disease
Metabolic syndromeMetabolic syndrome
Insulin resistanceInsulin resistance
4× Risk
DiabetesDiabetes

45. DIET
DIET
-- ++
++
++
++
VesselsVessels HeartHeart KidneysKidneys
Vasoconstriction Cardiac outputCardiac output Na+Na+
reabsorptionreabsorption
BLOOD PRESSUREBLOOD PRESSURE
++ ++ ++

46. Risk factorRisk factor Defining levelDefining level
Abdominal obesity
(waist
measurement)
BMI > 30 kg/mBMI > 30 kg/m22
Men: Greater than 102 cm102 cm
Women: Greater than 88 cm88 cm
Triglycerides 2.2 mmol/L or higher2.2 mmol/L or higher, or
taking medicine for high
triglycerides
Total cholesterol 5.2 mmol/L or higher5.2 mmol/L or higher
Blood pressure 130/85 mm Hg or higher130/85 mm Hg or higher, or
taking medicine for high blood
pressure
Fasting blood glucose 6.1 mmol/L or higher6.1 mmol/L or higher, or
taking medicine for high blood
sugar
Criteria forCriteria for MMetabolicetabolic SSyndromeyndrome
Metabolic syndrome ICD-9-CM code: 277.7Metabolic syndrome ICD-9-CM code: 277.7

47. CComponentsomponents of the Metabolic Syndromeof the Metabolic Syndrome
ComponentsComponents
NCEP ATP III,NCEP ATP III,
≥3≥3
20012001
IDF, WC + ≥2IDF, WC + ≥2
20052005
AHA/NHLBI,AHA/NHLBI,
≥3≥3
20052005
WaistWaist
circumferencecircumference
(WC), cm(WC), cm
>102 (m) >88 (f)>102 (m) >88 (f)
Europid ≥94 (m) ≥80 (f)Europid ≥94 (m) ≥80 (f)
S. Asian ≥90 (m) ≥80 (f)S. Asian ≥90 (m) ≥80 (f)
Japanese ≥85 (m) ≥90 (f)Japanese ≥85 (m) ≥90 (f)
>102 (m) >88 (f)>102 (m) >88 (f)
TG, mmol/LTG, mmol/L ≥≥ 1.71.7 ≥≥1.71.7 ≥≥1.71.7
HDL-C,HDL-C,
mmol/Lmmol/L
<<1.031.03 (m) <1.29 (f)(m) <1.29 (f) <1.03 (m) <1.29 (f)<1.03 (m) <1.29 (f) <1.03 (m) <1.29(f)<1.03 (m) <1.29(f)
BP, mm HgBP, mm Hg ≥≥130/130/≥≥8585 ≥≥130 OR130 OR ≥≥8585 ≥≥130 OR130 OR ≥≥8585
FPG, mmol/LFPG, mmol/L ≥≥6,16,1 ≥≥5.65.6 ≥≥5.65.6

48. Examples of the diagnosis of diabetes mellitusExamples of the diagnosis of diabetes mellitus
► Type 1Type 1 Diabetes mellitusDiabetes mellitus first diagnosticfirst diagnostic withwith
ketoacidosisketoacidosis ((datedate – 15.09.12.)– 15.09.12.) in decompensation.in decompensation.
► Type 1Type 1 Diabetes mellitusDiabetes mellitus medium degreemedium degree inin
satisfactory compensation.satisfactory compensation.
► Type 1Type 1 Diabetes mellitusDiabetes mellitus severe degreesevere degree in satisfactoryin satisfactory
compensation.compensation.
► 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 degreemedium degree in badin bad
compensation.compensation.