Pathophysiology of diabetes mellitus type 2

1. PATHOPHYSIOLOGY OF
Adam Bilski
Palacky University
Olomouc
2019

2. WHAT IS DIABETES
MELLITUS?
a group of metabolic
disorders characterized
by high blood
sugar levels over a
prolonged period
DIABETES MELLITUS
polyuria sweet

3. INSULIN
This receptor consists of an alpha-subunit,
which binds the hormone, and a beta-subunit,
which is an insulin-stimulated, tyrosine-specific
protein kinase. autophosphorylation
Tissues non-sensitive to insulin are – CNS and Erythrocytes

4. Effect of insulin is also
INCREASE IN TRIGLYCERIDE
SYNTHESIS, it blocks
LIPOLYSIS (inhibits hormone
sensitive lipase)

NO KETONE BODIES
PRODUCED

NO KETOACIDOSIS in DM II

5. GLUCAGON
STIMULATED BY:
- low glucose in blood
- adrenalinę
- cholecystokinine
Promotes breakdown of LARGE STORAGE
MOLECULES into glucose (liver: glycogenolysis +
gluconeogenesis (lactic a. + noncarbohydrate mol.))
and fatty acids.
Its 7 PASS TRANSMEMBRANCE RECEPTOR
has 2 ends:
1 binding glucagon (outer)
2 activating intracellular proteins (inner)

6. 10% OF POPULATION HAS DIABETES
10% TYPE I 90% TYPE II
Type I – when body can’t produce
enough insulin
Type II –tissues don’t respond well to
insulin, which is also produced in too
low quantity.
These cells are insulin resistant
OTHER TYPES:
MODY – Maturity Onset Diabetes of the
Young (genetically inherited)
*For example, all overweight individuals have insulin resistance, but diabetes develops only in those who
cannot increase insulin secretion sufficiently to compensate for their insulin resistance. Their insulin
concentrations may be high, yet inappropriately low for the level of glycemia.*

7. ORGANISM HAS TROUBLE
MOVING GLUCOSE FROM
BLOOD  CELLS
ETIOPATHOLOGY
Combination of these, results in hyperglycemia
Insulin resistance is:
- missing receptors
- non-sensitive receptors
- intracellular problem (?)

8. CAUSES:
Insulin resistance (inherited, acquired)
→
beta cell hyperplasia, hypertrophy
→
↑beta cell secretion of insulin + amylin production
→
hyperinsulinemia, amyloid deposits within beta cells
→
beta cell exhaustion, dysfunction, atrophy + hypotrophy of pancreas
→
↓insulin production
→
hyperglycemia

9. RISK FACTORS:
Multifactorial - interaction between
genetic, environmental and behavioral
factors
- poor diet
- prediabetes
- polycystic ovary syndrome (PCOS)
- medications that adversely affect
glucose tolerance/↑blood glucose
levels (e.g. glucocorticoids, atypical
antipsychotics, thiazide diuretics)

10. ADIPOSE tissue releases free fatty acids and
adipokines  inflammation  insulin resistance
Oxidation of fatty acids
creates ketones that can
be used as energy source
by skeletal and cardiac
muscles, liver, kidneys,
and adipose tissue, thus
sparing glucose for
continued utilization by
brain and erythrocytes.
OBESITY
60-90% of patients

11. THEN YOU NEED THIS!

12. Hyperosmolar hyperglycemic state
(HHS) – high osmolarity, without
significant ketoacidosis

13. SIGNS AND
SYMPTOMS:
- polyuria
- polydipsia
- polyphagia
- glycosuria
- weakness,
- unexplained weight loss,
- blurred vision;
- acanthosis nigricans
(hyperpigmented
cutaneous patches)

14. Also patients might experience PARAESTHESIA -
burning sensation usually in legs, hands, arms
or feet

15. DIAGNOSING DIABETES:
1. Fasting glucose test:
PREDIABETES: 5,5 – 6,9 mmol/L
DIABETES: ≥ 6,9 mmol/L
NORMAL VALUES – 3.9 and 7.1 mmol/L
Prediabetes is a health
condition that means your
blood sugar level is higher
than normal, but not yet
high enough for you to be
diagnosed with diabetes.
✴︎✳︎
✱

16. 2. No fasting, anytime done glucose test: (mainly at emergency)
DIABETES: ≥ 11,1 mmol/dL
3. Oral glucose tolerance test:
Glucose is given (75g) and measured in interwals
(the most important one is after 2 hours)
PREDIABETES: 7,8 – 11,1 mmol/dL
DIABETES: ≥ 11,1 mmol/dL
4. HbA1c test:
checks proportion of hemoglobin with glucose stuck to its membranę proteins
(glycated hemoglobin)
PREDIABETES: 5,7– 6,4%
DIABETES: ≥ 6,5%

18. DAMAGE TO THE ORGANISM:

19. HYALINE ARTERIOSCLEROSIS
C3 enters into the arterial wall, it changes to another protein
called C3b.
The arterial wall, especially the subendothelium, is rich
in hyaluronic acid (HA).
Hyaluronic acid is a kind of sugar-based substance that acts
as a binding and lubricating agent.
C3b binds to HA and forms a 'glassy', or hyaline, precipitate.
This precipitation will eventually spread out and involve the
entire circumference of the artery and even the deeper
layers of the arterial wall, leading to the thickening and
hardening of the arterial walls, arteriosclerosis.
Hyaline arteriosclerosis is commonly found in the smaller
arteries of the following organs and tissues:
•Spleen
•Kidneys
•Liver
•Brain
•Pancreas
•Retina

20. DIABETIC RETINOPATHY
It’s the result of damage to the small blood vessels and
neurons of the retina.

21. DIABETIC NEPHROPATHY
Damage of kidneys (afferent and efferent arterioles), caused by high
blood pressure,
result of chronic hyperglycemia.
angiotensin
converting
enzyme
inhibitors
Angiotensin-receptor
blockers
High blood pressure
(hypertension) is a known
risk factor for kidney
disease and people with
diabetes are prone to
hypertension. The renin-
angiotensin system – which
helps regulate blood
pressure – is also thought
to be involved in the
development of diabetic
nephropathy.

22. NERVOUS SYSTEM MALFUNCTIONS
- Stocking glove distribution (loss of senses from toes and fingers). This pattern occurs
because nerve fibers are affected according to length of axon, without regard to root or
nerve trunk distribution.
- Autonomous NS pathology – increased sweating and passing gas
POOR BLOOD SUPPLY AND
NERVES DAMAGE

ULCERS APPEAR

AMPUTATION
the infamous DIABETIC FOOT