Diabetes Mellitus Types Insulin Glucagon

1. Diabetes mellitus

2. What is the Diabetes Mellitus?
 Diabetes mellitus is a
chronic disorder of
carbohydrate, fat and
protein metabolisms.

3. Classification of Diabetes Mellitus
Diabetes mellitus can be divided into
two major group
Primary DM
(idiopathic)
Secondary
DM
Type I DM
Type II DM
Chronic pancreatitis
Surgical
pancreatectomy

4. Primary DM
Type I Type II
Define as Insulin dependent Non-insulin
dependent
% of all cases of
primary DM
10-20% 80-90%
Age
Childhood,
purberty After 35 years
Symptoms
develop Rapidly Gradually

5. Type I Diabetes Mellitus

6. Incidence of type I DM

7. Defect: Absolute insulin deficiency
Mutation of HLA( Human Leukocyte
antigen) region on chromosome 6
Encode class II MHC antigens
Iniates autoimmune response.
Attack by T-lymphocytes
Insulitis: pancreatic cells are
inflammated
Destruction of β-cells.

8. Results:
Absense of
endogenous insulin
Persons with type I DM
have absolute
requirement for
exogenous insulin
injection
(IDDM-insulin
dependent diabetes)
Acute complication - DKA (diabetic ketoacidosis)
1. Metabolic acidosis
2. Ketonemia
3. Hyperglycemia
4. Diabetic coma

9. Type II Diabetes mellitus

10. Relative insulin deficiency due to:
increase insulinase activity
production of antibodies to insulin
production of antibodies to insulin
receptors
decerease sensitivity of
receptors to insulin
Deminished incretin tffects
Acute complication:
Hyperglycemic hyperosmolar state (HHS)

12. Causes of DM type II
Genetic
defects
Diseases of the
exocrine pancreas
Endocrinopathies Drug(chemical)
induced
Immune-
mediated
insulin
resistance
pancreatitis;
neoplasia,
trauma etc.
hyperthyroidism;
acromegaly etc
Glucocorticoids;
thiozides
Anti-insulin
receptor
antibodies
Other genetic syndromes associated with DM
Down syndrome,
Porhyrias
Gestational DM (during pregnancy)
Hungtinton chorea etc

13. Metabolic complications

14. Uncontrolled DM
Lack of insulin
deficiency of insulin
ANABOLISM CATABOLISMsecretion
of glucagon
Glucosuria
Osmotic diuresis
Lipolysis
Glycogenolysis
Ketonemia
Acidosis
Diabetic ketoacidosis
(type 1 DM predominantly)
DEATH
Hyperglycemia
Hyperosmolar blood

15. Hyperglycemia & glucotoxicity are
major pathogenic factors
Hyperglycemia due to
Pancreatic hormones
imbalance
glucagon effects
insulin effects
Overproduction of
glucose (liver)
Glycogenolysis
Gluconeogenesis
Reduced glucose uptake
by peripheral tissues
GLUCOTOXICITY

16. Hyperglycemia
uptake of
glucose by
insulin-dependent
tissue
uptake of
glucose by
insulin-independent
tissue
(sorbitol -fructose pathway) Muscles
Adipose tissue
kidney
Nervous system
Seminal vesicles, etc.
Lens
"CELLULAR
STARVATION"OSMOTIC INJURY OF
THE CELLS

17. Sorbitol Patway
Glucose Sorbitol Fructose
Sorbitol DHAldose
reductase
NADPH
NADP+
NAD+ NADH
can not pass
through the cell
membrane and trapped
inside the cell causing water retention due to
osmotic effect

18. Resulting in:
 Cataract formation
 Peripheral neuropathy
 Nephropathy
 Retinopathy
 Vascular problem

19. Metabolic disturbances: lipids
metabolism
AdipocyteBlood
TG
glycerol
Fatty acids
Liver
FAs
glucagon
Gluconeogenesis
ectopic formation
of TG
(liver, pancreas,
muscles, etc)
lipid storage
in the adipose tissue
Ketogenesis

20.  Adipocytes
secrete:
 Leptin –
regulates appetite
together with
insulin
Insulin
Leptin
production of NPY
(appetite-stimulating
neuropeptide Y) by
hypothalamic neurons
APPETITE

22. Classic triad of diabetes: - 3P
 POLYURIA: Glucose excreted in
urine increases urine volume
 POLYDIPSIA: Excessive
urination leads to increased
thirst due to dehydration
 POLYPHAGIA: “ Cellular
starvation” increases appetite.

23.  Additional symptoms may include
headache, blurred vision, and
fatigue.
 Sucseptible to infections:
 Cuts or sores that are slow to heal.
 Frequent yeast infections or
urinary tract infections.
 Itchy skin, especially in the groin
area.

24. Risk factors
 Overweight, defined
as a body mass index
(BMI) over 25.
* Sedentary lifestyle.
* Hyperlipidemia
 * High blood pressure
greater than 140 /90 in
adults.
* Smoking.

25. Controlled DM

26. 1. Specific diet
 Goal:
 Reduce caloric
intake
 Purpose:
 Reduce size of
adipose stores

27. 2. Active lifestyle without stress
 Moderate exercise
 Purpose:
 Increase lean body
mass
 Stress Reduction

28. 3. Drugs:
 Insulin-releasing
drugs
 Stimulate pancreas to
produce more
endogenous insulin
 Hepatic insulin
sensitizers
 Act selectively on the
liver, inhibit
glycogenolysis,
gluconeogenesis
 Insulin injection
(if needed)
 Glucose Testing