treatment of T2D

Question 1

What is diabetes melitus?

Answer 1

group of diseases characterised by high levels of blood glucose due to defects in insulin production/action of insulin

Question 2

explain t1d

Answer 2

T1D is usually picked up on before the age of 30

-the cells that produce insulin are destroyed and as a result they are insulin dependent

Question 3

gestational diabetes?

Answer 3

occurs in pregnant women as the placenta produces hormones that induce insulin

there’s an increased risk of developing NIDDM

Question 4

T2D

Answer 4

t2d is usually picked up on in over 40’s

caused by lack of insulin production and action of insulin is insufficient

-eventually leads to beta cell failure

Question 5

how is diabetes mellitus tested?

Answer 5

fasting plasma glucose test

• fast overnight
• normal fasting blood glucose is 4-5.5mM
• Type 1/2 fasting blood glucose is 4-7 (72-126)
• over 106mg/dl or 5.9mM indicates diabetes

Oral glucose tolerance test:

• patient tested 2 hours after drinking something glucose rich like lucozade
• 7.8-11.1 indicates prediabetes
• over 11.1 means diabetes

Question 6

how is diabetes mellitus diagnosed?

Answer 6

Diagnosis 
blood glucose level above 11.1 mM (200mg/dL) on two occasions, or above 7 mM (126mg/dL) fasting
a level exceeding 11.1 mM 2 hours after an oral glucose load is also diagnosticabnormally elevated blood glucose: 
	  - excessive glycosylation (glycation)
	    of proteins (haemaglobin)
       - HbA1c
		Normal:Below 6.0%
		Prediabetes:6.0 to 6.4%
		Diabetes: 6.5% or over
	  - index of chronic hyperglycaemia

Question 7

what do different HbA1c results mean?

Answer 7

abnormally elevated blood glucose: 
	  - excessive glycosylation (glycation)
	    of proteins (haemaglobin)
       - HbA1c
		Normal:Below 6.0%
		Prediabetes:6.0 to 6.4%
		Diabetes: 6.5% or over
	  - index of chronic hyperglycaemia

Question 8

what causes ketoacidosis in t1d

Answer 8

carbohydrate stores in the liver are exhausted, protein is converted to glucose, and triglycerides are mobilised from fat tissues
- increased free fatty acids are converted to ketone bodies (3-hydroxybutyrate,
acetoacetate) in the liver resulting in ketoacidosis (metabolic acidosis)
- fatty acids ketone bodies can be utilised instead of glucose by many tissues
including the brain.

Question 9

what effects does hyperglycaemia have on the urine

Answer 9

because there is so much glucose, large amounts are disposed of via the urine which is called glycosuria, the urine contains large amounts of water( polyuria) and this makes patients thirsty so they drink more(polydipsia)

Question 10

T2D characteristics and symptoms

Answer 10

T2D is the deficiency of insulin compared to the needs of the body. This can be caused by:

• insufficient insulin secreted by the beta cells
• tissue that is desensitised to insulin
• low birth weight
• overstimulation of beta cells
• secretion on proinsulin instead od insulin

Abnormalities of the small blood vessels lead to kidney damage, retinal damage, and peripheral nerves leading to impaired sensation

Abnormalities of the large blood vessels lead to atherosclerosis, heart failure, stroke, loss of extremities, gangrene

-amputations

Question 11

what are the different generations of sulphonylureas

Answer 11

1st generation

(1) Orinase (tolbutamide)
(3) Tolinase (tolazamide)
(6) Diabinese (chlorpropamide)

2nd generation

(75) Glucotrol (glipizide)
(150) Glucotrol XL (ex. rel. glipizide)
(150) Micronase, Diabeta (glyburide)
(250) Glynase (micronized glyburide)

3rd generation
(350) Amaryl (glimepiride

Question 12

mechanism of action for sulphonylureas

Answer 12

sulphonylureas interact with receptors on the beta cells to block the KATP channel

this causes accumulation of k+ in the cell and therefore depolarisation which triggers voltage gated calcium channels to open and cause exocytosis of vesicles containing insulin

examples include :

• glimepride (3rd generation
• glipizide(2nd generation

Question 13

what is the biguanides mechanism of action

Answer 13

example or a biguanide is metformin

biguanides improve insulin’s ability to uptake glucose into cells especially muscle cells

• it improves insulin sensitivity
• used as monotherapy or with sulphonylureas

the mechanism of action is:

• Metformin enters cell through OCT1
• This causes an increase in AMP
• This activates AMPK
• AMPK: decreases gluconeogenesis, increases glucose uptakese and increases glycogen synthesis

OVERALL DECREASE IN BLOOD GLUCOSE

Question 14

what is the mechanism of action of Thiazolidinedoines(TZD’s/glitazones)

Answer 14

TZD’s increase insulin sensitivity

PPAR is part of the steroid hormone superfamily and it is a receptor

• when a TZD ligand binds to PPAR it forms a complex that binds to a region of DNA that regulates transcription of genes involved in glucose and fatty acid metabolism
• examples include pigotazone , muraglitazar

Question 15

alpha glycosides inhibitor mechanism or action?

Answer 15

alpha glycoside inhibitors inhibit the breakdown of starch and slow down glucose absorption

-this mechanism is already naturally occurring in fungus eg mushroom

Question 16

meglitinide mechanism of action

Answer 16

meglitinide blocks KATP on beta cells which in turn stimulates insulin secretion

-examples include repaglinide, nateglinide

Question 17

incretins

Answer 17

there are incretins naturally occurring in your gut eg GLP-1, GIP, CCK.

when you eat GLP-1 is stimulated and insulin is secreted which helps regulate blood glucose from the meal you just had.

• however GLP-1 is broken down by DPP4, therefore there are DPP4 inhibitors e.g. linagliptin, sitagliptin saxagliptin.
• However these DPP4 inhibitors cause cause heart failure by increasing cAMP and sympathetic stimulation of the heart and should be avoided in contraindicated patients
• theres also GLP analogues : Liraglutide