This document discusses the etiology, pathogenesis, classification, diagnosis and clinical presentation of diabetes mellitus. It begins with an overview of normal insulin physiology and the mechanisms of insulin secretion. It then covers the classification of diabetes into type 1, type 2 and gestational diabetes based on etiology. The document discusses the pathogenesis of type 1 and type 2 diabetes in detail. It provides criteria for the diagnosis of diabetes, including symptoms and results of fasting plasma glucose, oral glucose tolerance and HbA1c tests. The document concludes with a discussion of laboratory tests used to diagnose and monitor diabetes.

1. Etiology, pathogenesis,Etiology, pathogenesis,
classification, early diagnosisclassification, early diagnosis
and clinical presentation ofand clinical presentation of
Diabetes MellitusDiabetes Mellitus

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

3. 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).

4. 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
--
++
++
++
++
--

5. 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

6. 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

7. 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

8. A glossary of terms will be usedA glossary of terms will 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.
Euglycemia or Normoglycaemia-Euglycemia or Normoglycaemia- normal blood glucose level
(fasting 3.3-5.5 mmol/L and 2 hour after meal less than 7.8 mmol/L).
Hypoglycemia-Hypoglycemia- low blood glucose level (<2.75 mmol/L).
Hyperglycemia-Hyperglycemia- 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).
Glycosuria-Glycosuria- high glucose in the urine.
Ketonuria-Ketonuria- ketone bodies in the urine.
PolyphagiaPolyphagia-- excess appetite.
PolyuriaPolyuria-- excess urinating.
Polydypsia-Polydypsia- excess drinking.

9. 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.

10. 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
MELLITUS
is carbohydrate intolerance resulting in
hyperglycaemia of variable severity with
onset or first recognition during
pregnancy.

11. 11
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
(or “juvenile-onset(or “juvenile-onset
diabetes”, "juvenilediabetes”, "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

12. Pathogenesis of Type 1 Diabetes MellitusPathogenesis of Type 1 Diabetes Mellitus
Viruses
Infection of β cellsInfection of β cells Systemic infectionSystemic infection
DirectDirect
cytolyticcytolytic
effectseffects
β cells necrosisβ cells necrosis Autoimmune β cells damageAutoimmune β cells damage
Type 1Type 1
Diabetes MellitusDiabetes Mellitus
Indirect immune effectsIndirect immune effects
• Viral antigens expressedViral antigens expressed
•β cell antigens alteredβ cell 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
β cell autoantigensβ cell autoantigens
(molecular mimicry)(molecular mimicry)

13. 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

14. 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

15. if one of theif one 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 diabetes mellitusSymptoms of diabetes mellitus
plusplus

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

17. THE ORAL GLUCOSE TOLERANCE TEST (GTT)THE ORAL GLUCOSE TOLERANCE TEST (GTT)
The oral GTT is a provocation test to examine the efficiency of the body to
metabolise glucose;
 provides information on latent diabetes states;
 distinguishes metabolically healthy individuals from people with impaired
glucose tolerance and those with diabetes;
the oral GTT is more sensitive than fasting plasma glucose (FPG) for the
diagnosis of diabetes. Nevertheless the final diagnosis of diabetes should
not be based on a single 2 h post-load glucose >11.1 mmol/L but should be
confirmed in subsequent days (FPG and/or casual glucose estimation).
is not used for the monitoring of day to day blood glucose control, which
is done by HbA1c, and repeated glucose measurement;
 is used mainly for diagnosis of impaired tolerance to glucoseimpaired tolerance to glucose (IGT) and in
epidemiological population studies, but is not recommended or necessary
for routine diagnostic use.
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:

18. 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

19. Laboratory TestsLaboratory Tests
Fasting plasma glucose (FPG)Fasting plasma glucose (FPG)
Glycosylated Hemoglobin TestGlycosylated Hemoglobin Test (HbA1c, glycohemoglobin)(HbA1c, glycohemoglobin) - are proteins with glucose,
bound by nonenzymatic way. They precisely represent the extent of impairment of the
carbohydrate metabolism and serve as the basic index of quality of compensation of diabetes
mellitus. The level of HbA1c is determined by the method of chromatographychromatography using special
laboratory equipment. Level of HbA1c shows an average blood concentration during the
previous 2 – 3 month. Normal level of HbA1c is 4-6%.Normal level of HbA1c is 4-6%.
C-peptideC-peptide is a connective peptide between A and B by the chainlets of insulin.is a connective peptide between A and B by the chainlets of insulin. The level of C
– peptide is 1- of 2,8 mmol/ml1- of 2,8 mmol/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 plasma proteins, particilarly of the albumenis a product of glycosilation of the plasma proteins, particilarly of the albumen
which has a period of semilife of 14 days.which has a period of 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 endogenous insulin in a healthy man is one secretion of the endogenous insulin in a healthy man is on
averageaverage 5- 20 мкЕ /mL5- 20 мкЕ /mL in the fasted state.in the fasted state.
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.
Self-monitoring of blood glucoseSelf-monitoring of blood glucose by people with diabetes (Diabetes Control andDiabetes Control and
Complications TrialComplications Trial):blood glucose monitors / glucometers (Accu-Chek Sensor, Van Touch
Ultra and other ) and ccontinuous glucose monitoring system.ontinuous glucose monitoring system.

20. Laboratory TestsLaboratory Tests
URINE TESTS:URINE 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 Levels and Fractional UrineGlucose Levels and 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).

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

22. 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

23. 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:
MikroangiopathyMikroangiopathy - retinopathy, nephropthy, diabetic food.
MakrooangiopathyMakrooangiopathy - with the overwhelming defeat of large vessels
(heart, brain, feet).
Universal mikro- and makroangiopathy.Universal mikro- and makroangiopathy.
PolineuropathyPolineuropathy (peripheral, autonomous, visteral).
Encephalopathy.Encephalopathy.
V.V. Afection of other organs and systemsAfection of other organs and systems::
steatohepatosis, cataract,steatohepatosis, cataract,
dermatopathy, osteoartropathy anddermatopathy, osteoartropathy 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.

24. 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).

25. 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

26. 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

27. BrainBrain
Cerebrovascular disease
• Transient ischemic attack
• Cerebrovascular accident
• Cognitive impairment
Complications of Diabetes MellitusComplications of Diabetes Mellitus
HeartHeart
Coronary artery disease
• Coronary syndrome
• Myocardial infarction
• Congestive heart failure
ExtremitiesExtremities
Peripheral vascular disease
• Ulceration
• Gangrene
• Amputation
MacrovascularMacrovascular MicrovascularMicrovascular
EyeEye
Retinopathy
Cataracts
Glaucoma
KidneyKidney
Nephropathy
Microalbuminuria
Gross albuminuria
Kidney failure
NervesNerves
Neuropathy
Peripheral
Autonomic

28. Three Metabolic Pathways in the Pathogenesis of ChronicThree Metabolic Pathways in the Pathogenesis of Chronic
Complications of Diabetes MellitusComplications of Diabetes Mellitus
I.I. Non-enzymatic glycoslation:Non-enzymatic glycoslation: Glucose bonds to the amino groups of
proteins (reflected in glycosylated Hemoglobin A (HbA1c), repetitive
glycosylation eventually results in cross-linking of proteins leading to
dysfunction. These products accumulate in vessel walls.
Glycosylation also occurs with lipids and nucleic acids.
II.II. Intracellular hyperglycemia:Intracellular hyperglycemia: Some cells (nerves, kidney and
vascular endothelium) do not require insulin for the accumulation of
glucose; they have passive transport mechanisms and accumulate
glucose during hyperglycemic episodes. The accumulation of glucose
in excess levels results in the formation of some glucose metabolites
(fructose & sorbitol) that exert an osmotic effects drawing water
intracellularly eventually resulting in osmotic cell injury.
III.III. Activation of protein kinase C:Activation of protein kinase C: Activation of intracellular protein
kinase C (PKC) can be induced by the intracellular hyperglycemia of
diabetes mellitus. PKC activation results in:
– Production ofProduction of VEGFVEGF promoting vascular proliferation;promoting vascular proliferation;
– Increased deposition ofIncreased deposition of ECMECM & basement membrane;& basement membrane;
– Production of pro-coagulant molecules (plasminogen activatorProduction of pro-coagulant molecules (plasminogen activator
inhibitor) leading to reduced fibrinolysis and promoting thrombosis.inhibitor) leading to reduced fibrinolysis and promoting thrombosis.

29. Diabetic NephropathyDiabetic Nephropathy
is nodular glomerulosclerosisis nodular glomerulosclerosis
and hyalinic atherosclerosis of small artery.and hyalinic atherosclerosis of small artery.

30. The stage of diabetic nephropathyThe stage of diabetic nephropathy
(by R. Holt and N. Hanley ,2007)(by R. Holt and N. Hanley ,2007)
Stages
Test
Albumin-Albumin-
uriauria
GFRGFR
(glomerularglomerular
filtration rate)filtration rate)
ml/minml/min
SerumSerum
creatininecreatinine
umol/Lumol/L
BPBP SignsSigns
NormalNormal <20
High/
normal
Normal
60/150
Normal None
MicroalbuminuriaMicroalbuminuria 20-300
High/
normal
Normal
60/150
Small
increase
None
PersistentPersistent
proteinuriaproteinuria
>300
Up to
15 g/day
Normal/
Decreased
High/
normal
80-120
Increased
+/-
Oedema
Renal impairmentRenal impairment
>300
Up to
15 g/day
Decreased
High
120-400
Increased
+/-
Oedema
EstablishedEstablished
Renal failureRenal failure
>300
Can fall
Decreased
++
Very high
>400
Increased
+/-
Oedema

31. Classification of diabetic retinopathyClassification of diabetic retinopathy
(by H. Turner and J. Wass, 2006)
I. Background retinopathyI. Background retinopathy
- microaneurysms;
- haemorrhages;
- hard exudates.
II. MaculopathyII. Maculopathy
- haemorrhages and hard
exudation in the macula area;
- reduced visual acuity with
no abnormality seen.
III. Preproliferrative retinopathyIII. Preproliferrative retinopathy
- soft exudates/cotton wool spots;
- intra-retinal abuormalities;
- venous abnormalities
(e.q. venous beading,
looping, reduplication).
IV. Proliferative retinopathyIV. Proliferative retinopathy
- new vessels on discs or within
1 disc diameter of it;
- new vessels elsewhere;
- rubeosis iridis (or neovascular
glaucoma).

32. Diabetic neuropathyDiabetic neuropathy
Thinning skin ofThinning skin of
food and shanksfood and shanks
Thinning ofThinning of
interosseousinterosseous
musclesmuscles
HyperhidrosisHyperhidrosis
or anhidrosisor anhidrosis
IncreasedIncreased
callus formationcallus formation
Muscle atrophyMuscle atrophy
““Hang down” foodHang down” food
Hair lossHair loss
in the lowerin the lower
extremitiesextremities

33. Diabetic Neuropathy Classification and StagingDiabetic Neuropathy Classification and Staging
(American Diabetes Association and American Academy of Neurology, 1988)(American Diabetes Association and American Academy of Neurology, 1988)
B. Autonomic neuropathyB. Autonomic neuropathy
1.1.Cardiovascular autonomicCardiovascular autonomic
2.2.Abnormal pupillary functionAbnormal pupillary function
3.3.Gastrointestinal autonomicGastrointestinal autonomic
neuropathyneuropathy
a.Gastroparesis
b.Constipation
c.Diabetic diarrhea
d.Anorectal incontinence
44..Genitourinary autonomicGenitourinary autonomic
neuropathyneuropathy
a.Bladder dysfunction
b.Sexual dysfunction
C. Focal NeuropathyC. Focal Neuropathy
1.Mononeuropathy
2.Mononeuropathy multiplex
3.Amyotrophy
I.I.Subclinical neuropathySubclinical neuropathy
A.A.Abnormal electrodiagnostic testsAbnormal electrodiagnostic tests
1.Decreased nerve conduction velocity
2.Decreased amplitude of evoked
muscle or nerve action potentials
A.A.Abnormal neurologic examinationAbnormal neurologic examination
1.Vibratory and tactile tests
2.Thermal warming and cooling tests
3.Other tests
A.A.Abnormal autonomic function testsAbnormal autonomic function tests
1.Abnormal cardiovascular reflexes
2.Altered cardiovascular reflexes
3.Abnormal biochemical responses to
hypoglycemia
II.II. Clinical neuropathyClinical neuropathy
A.A.Diffuse somatic neuropathyDiffuse 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

34. Clinical features of diabetic feetClinical features of diabetic feet
Neuropathic feet Ischemic feet
WarmWarm Cold/coolCold/cool
Dry skinDry skin Atrophic/often hairlessAtrophic/often hairless
Palpable foot pulsesPalpable foot pulses No palpable foot pulsesNo palpable foot pulses
No discomfort witulcerNo discomfort witulcer More pften tender/painfulMore pften tender/painful
Gallus presentGallus present
Clandication/Rest painClandication/Rest pain
Skin blanches on elevation andSkin blanches on elevation and
reddens on dependencyreddens on dependency

35. Classification of diabetic foot lesionsClassification of diabetic foot lesions
(from Wagner, 1983)
Grade 0Grade 0 High risk foot, no ulceration presentHigh risk foot, no ulceration present
Grade 1Grade 1 Superficial ulcer, not infectedSuperficial ulcer, not infected
Grade 2Grade 2
Deep ulcer with or without cellulitesDeep ulcer with or without cellulites
bat no abscess or bone involvementbat no abscess or bone involvement
Grade 3Grade 3
Deep ulcer with bone involvement orDeep ulcer with bone involvement or
abscess formationabscess formation
Grade 4Grade 4
Localized gangreneLocalized gangrene
(toe, forefoot, hell)(toe, forefoot, hell)
Grade 5Grade 5 Gangrene of the whole footGangrene of the whole foot

36. METABOLIC SYNDROMEMETABOLIC SYNDROME
a cluster of symptoms including central adiposity,a cluster of symptoms including central adiposity,
hypertriglyceridemia, hypertension,low levels ofhypertriglyceridemia, hypertension,low levels of
high-density lipoprotein (HDL) cholesterol, andhigh-density lipoprotein (HDL) cholesterol, and
elevated fasting plasma glucose levels, iselevated fasting plasma glucose levels, is
associated with increased risk for heart disease,associated with increased risk for heart disease,
type 2 diabetes mellitus, and cardiovascular and all-type 2 diabetes mellitus, and cardiovascular and all-
cause mortality.cause mortality.

37. Criteria for Metabolic SyndromeCriteria for Metabolic Syndrome
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

38. Examples of the diagnosis of diabetes mellitusExamples of the diagnosis of diabetes mellitus
► Type 1 Diabetes mellitus first diagnostic withType 1 Diabetes mellitus first diagnostic with
ketoacidosis (ketoacidosis (datedate – 15.09.08.)– 15.09.08.) in decompensation.in decompensation.
► Type 1 Diabetes mellitus medium degreeType 1 Diabetes mellitus medium degree inin
satisfactory compensation. Dsatisfactory compensation. Diabetic nephropathyiabetic nephropathy IIII
stage.stage. Background retinopathy.Background retinopathy.
► Type 1 Diabetes mellitus severe degreeType 1 Diabetes mellitus severe degree in satisfactoryin satisfactory
compensation. Dcompensation. Diabetic nephropathyiabetic nephropathy IV stage.IV stage.
Preproliferative retinopathy. DiabeticPreproliferative retinopathy. Diabetic NeuropathicNeuropathic
food grade 1.food grade 1. Diabetic diarrhea. Diabetic ketoacidicDiabetic diarrhea. Diabetic ketoacidic
comas in anamnesiscomas in anamnesis (years(years – 2006,2008– 2006,2008).). 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 2 Diabetes mellitus medium degreeType 2 Diabetes mellitus medium degree in badin bad
compensation.compensation.