PATHOPHYSIOLOGY Flashcards
What is the origin of type 1 diabetes
Environmental trigger on a genetically susceptible individual
What is LADA
Type 1 diabetes presenting in adults
Genes linked to type 1 diabetes
HLA antigens in chromosome 6
Insulin gene polymorphisms on chromosome 11
PTPN22
IL2RA
CTLA-4
Environmental triggers for Type 1 diabetes
Early exposure to cow’s milk
Lack of breastfeeding
Gut bacteria
Certain viruses
Viruses that can trigger pathogenesis of type 1 diabetes in a agenetically susceptible individual
Rotavirus
Enterovirus
Which vitamin deficiency is more prevalent in type 1 DM
Vitamin D deficiency
Most common autoantibodies in type 1 DM
ICA - Islet Cell Autoantibodies
Other antibodies found in Type 1 DM apart from ICA
Antibodies formed to
Insulin
Glutamic acid decarboxylase 65 (GAD65)
Insulinoma-associated antigen 9 (IA-2)
Zinc transporter 8 (ZnT8)
Autoimmune disorders common in type 1 DM
Hashimoto’s thyroiditis
Graves’ disease
Addison’s disease
Vitiligo
Celiac sprue
Apart from insulin, which other hormone is deficient in type 1 DM
Amylin
What causes type 2 DM
Beta cell dysfunction coupled with insulin resistance
Why is type 2 diabetes polygenetic
many geenetic defects contribute to its pathogenesis
Defects in type 2 DM that impair glucose regulation (7)
- Deficiency and resistance to insulin
- Deficiency and resistance to incretins
- Excess glucagon secretion
- Increased hepatic glucose production
- Upregulation of SGLT2
- Systemic inflammation
- Diminished satiety
People with type 2 DM lose approximately ……….. of
β-cell function per year.
5% to 7%
Glucotoxicity occurs when glucose levels chronically exceed……………..
140
mg/dL (7.8 mmol/L)
What is glucotoxicity
When β-cell is unable to maintain sufficient
insulin secretion and, paradoxically, releases less insulin as glucose
levels increase
Causes of progressive beta cell loss in type 2 DM
(1) glucotoxicity
(2) lipotoxicity
(3) insulin resistance
(4) age
(5) genetics
(6) incretin deficiency.
What causes impaired glucose tolerance in the early stages of beta cell dysfunction
Deficient first-phase insulin release
Cause of decreased posprandial insulin secretion in type 2 DM
Impaired beta cell function
Diminished stimulus from gut hormones (mostly incretins)
How is abdominal fat different from subcutaneous fat
Presence of o excess lipids in non-adipose tissue
Abdominal fat is resistant to antilipolytic effects of insulin
Causes insulin resistance in type 2 DM
1.Release of excess free fatty acids by abdominal fat
2. Excess fat inhibits secretion of adiponectin
3. Oversecretion of inflammatory adipokines
4. Excess stored fatsalso causes adipocytes to become too large and inhibit further fat storage
how adoes abdominal fat causes insulin resistance
Which tissues or organs does insulin resistance affect
Muscle
Adipose tissue
Liver
Function of adinopectin
Suppresses the attachment of monocytes to endothelial cells,
thereby protecting against vascular damage.
Adipokines released in type 2 DM by Visceral adipose tissue
Plasminogen activator inhibitor-1
TNF-alpha
Interleukin-6
Resistin
Angiotensinogen
Role of resistin in type 2 DM
Causes insulin resistance
Surrogate market for visceral adipose tissue
Central obesity
Renal threshold for glucose in normal people and diabetics
Normal - 10 mmol/l
Diabetes- 12.2-13.3 mmol/l
What accounts for increased reabsorption of glucose in the proximal renal tubules in diabetes
Upregulation of the SGLT-2 receptors
What is type A insulin resistance
Clinical syndrome characterized by acanthosis nigricans,
virilization in women, polycystic ovaries, and hyperinsulinemia.
What is type B insulin resistance
When anti-insulin receptor antibodies block the binding of insulin
Clinical presentation of type 1 DM
Polyuria
Polydipsia
Polyphagia
Fatigue
Lethargy
Blurred vision
Components metabolic syndrome
Abdominal Obesity
Triglycerides
High LDL or Low HDL cholesterol
High blood pressure
Hyperglycaemia
Components metabolic syndrome
Abdominal Obesity
Triglycerides
High LDL or Low HDL cholesterol
High blood pressure
Hyperglycaemia
Components metabolic syndrome
Abdominal Obesity
Triglycerides
High LDL or Low HDL cholesterol
High blood pressure
Hyperglycaemia
Acute complications of diabetes or diabetic emergencies
Diabetic ketoacidosis in type 1
Hyperosmolar hyperglycaemic state for type 2
Hypoglycaemia
Microvascular complications of diabetes
Nephropathy
Neuropathy
Retinopathy
Macrovascular complications of diabetes
Cardiovascular disease
Cerebrovascular disease
Peripheral vascular disease
Combined macrovascular and microvascular complication
Diabetic foot problems
