Lecture 3 - types of diabetes

Question 1

What are the 3 major mechanisms that underlie hyperglycemic damage in diabetes mellitus?

Answer 1

1. ) protein glycosylation
2. ) Up regulation of polyol pathway
3. ) Dyslipidemia

Question 2

What is the polyol pathway?

Answer 2

The glucose entry to most cells is insulin dependant, and this glucose can be metabolised to sorbitol. It normal glucose, only little enters this pathway to become sorbitol. In hyperglycemia, there is excess sorbitol production which causes the depletion of NADPH and nitric oxide in endothelial cells. This increases oxidative stress and cell damage.

Question 3

Sysslipidemia causes macrovascular atherosclerorsis which ?

Answer 3

increases coronary, cerebral, peripheral artery diseases. It also increases LDL and TAGs but decreases HDL and reduces fibrinolytic activity.

Question 4

What are the consequences of arterial insufficiency or obstruction?

Answer 4

Myocardial infarction, stroke and peripheral arterial disease.

Question 5

Amputation risk with diabetes?

Answer 5

15-40 fold risk increase compared to non diabetic but 40-50 % of limb loss are preventable.

Question 6

What is diabetic retinopathy?

Answer 6

Vessel basement membrane deterioration. Causes ischemia and microhemorrhages.

Question 7

What is diabetic nephropathy?

Answer 7

Basement membrane thickening whihc causes hyperfiltration and inreases glomerular pressure. Progress microalbuminuria to proteinuria and eventually to end stage renal disease.

Question 8

What is sensory neuropathy?

Answer 8

It is the loss of sensation, abnormal sensation, pain of hands or feet. Can progress to partial or complete loss of sensitivity to touch and temperature. High risk of injury without pain.

Question 9

What is autonomic neuropathy?

Answer 9

Regulates sweating and perfusion to the limb. Results in loss of autonomic control which inhibits thermoregulatory function and sweating. The result is dry, scaly, and stiff skin that is prone to cracking and a portal of entry for bacteria.

Question 10

What is hypersomolar hyperglycemic nonketotic syndrome (HHNS)?

Answer 10

It is a life threatening medical emergency with a mortality rate of 50%. Basically, enough insulin is secreted to prevent ketosis but not enough to prevent hyperglycemia. Extreme hyperglycemia without acidosis will result in poor glucose uptake and increase hepatic glucose. Severe osmotic diuresis and severe loss of fluid and electrolytes. There will be a vascular collapse.

Question 11

What is diabetic ketoacidosis?

Answer 11

It is the complete lack of insulin and so there is unrestrained lipolysis and ketone synthesis. The blood glucose is over 250 mg/dl and ph less than 7.3. Blood bicarbonate is less than 15 mEq/l and ketones are present in blood and urine. There are electrolyte abnormalities.

Question 12

Why does oxidation not work in those with diabetes?

Answer 12

Becuase fatty acids go through the krebs cycle and make acetyl CoA. This can’t be used since diabetics can’t use sugars and so it is sent to other cells to be used as energy.

Question 13

Acetoacetic acid formation?

Answer 13

From condensation of two acetyl CoA molecules and made into acetone or Beta hydroxybutyric acid. Ketone levels in the body are increased but the tissue use is limited by oxaloacetate because it limits acetyl CoA entry into krebs cycle. So ketones build up and severe acidosis happens and that decreases blood ph, hypoxia and tachycardia.

Question 14

WHat is gestational diabetes?

Answer 14

It is a form of glucose intolerance diagnosed in some women during pregnancy. More common in obese women with a family history of diabetes and it requires treatment to normalise the maternal blood glucose levels to avoid complications with the infant. After this kind of diabetes, after pregancy, there is a 5-10% chance to get type 2 diabetes. Have 20-50% chance of developing diabetes in the enxt 5-10 years.

Question 15

Secondary causes of diabetes?

Answer 15

1. ) Acromegaly
2. ) Cushing syndrome
3. ) Thyrotoxicosis
4. ) Pheochromocytoma
5. ) Chronic pancreatitis
6. ) Cancer
7. ) Drug induced hyperglycemia

Question 16

What are some drug induced hyperglycemia?

Answer 16

1. ) beta blockers which inhibit insulin secretion
2. ) Calcium channel blockers which inhibit secretion of insulin
3. ) Corticosteroids - causes peripheral insulin resistance and gluconeogenesis
4. ) Protease inhibitors - inhibit the conversion of proinsulin to insulin
5. ) Thiazide diuretics - inhibit insulin secretion due to hypokalemia. Cause increased insulin resistance due to increased free fatty acid mobilisation.