• Chronic elevation of blood glucose levels leads to the endothelium cells taking in more glucose than normal damaging the blood vessels.

• 2 types of damage can be done - microvascular (due to damage to small blood vessels) and macrovascular (due to damage to larger blood vessels). • Blood vessels that take in more glucose, their base membrane becomes thicker but weaker – may burst or bleed!

Microvascular complications include damage to eyes (retinopathy) leading to blindness, to kidneys (nephropathy) leading to renal failure and to nerves (neuropathy) leading to impotence and diabetic foot disorders (which include severe infections leading to amputation).

Non-proliferative diabetic retinopathy: intraretinal microvascular abnormality (IRMA; green arrow), venous beading and segmentation (blue arrow), cluster haemorrhage (red circle),

Macrovascular complications include cardiovascular diseases such as heart attacks, strokes and insufficiency in blood flow to legs.

There is evidence from large randomized-controlled trials that good metabolic control in both type 1 and 2 diabetes can delay the onset and progression of these complications.

• Regulation of blood glucose level by insulin and glucagon - negative feedback control.

• Pancreatic receptors respond to high blood glucose levels by causing secretion of insulin.

• Insulin activates the conversion of glucose to glycogen in the liver decreasing blood glucose concentration.

Glucose Glygogen

INSULIN

GLUCAGON

• Pancreatic receptors respond to low blood glucose levels by producing glucagon.

• Glucagon activates the conversion of glycogen to glucose in the liver increasing blood glucose level.

•

• During exercise and fight or flight responses glucose levels are raised by adrenaline (epinephrine) released from the adrenal glands

• Adrenaline stimulating glucagon secretion and inhibiting insulin secretion.

Glucose Glygogen

INSULIN

GLUCAGON

ADRENALINE (epinephrine)

If someone can not control their blood glucose level – can elevate between 10-30 mmol/L (normal range has a concentration of 5 mmol/L), what is it called?

Diabetes! From last lesson -Vascular disease can be a

chronic complication of diabetes.

• Type 1 diabetes usually occurs in childhood.

• Type 2 diabetes or adult onset diabetes typically develops later in life and occurs mainly in overweight individuals. • 5-10% total diabetes from type 1

• 90-95% of total diabetes from type 2

Pancreatic cells NOT able to produce insulin

Cells have normal insulin receptors

Pancreatic cells able to produce insulinCells have less insulin receptors, so less sentive to insulin

Compare type 1 and type 2 diabetes

Stuck ... p189

Type 1 Type 2

% of cases

Stage of life usually occurs

Typical body mass of patient

Insulin production by pancreatic cells

Sensitivity of cells to insulin

Treatment

Use the video to think about the treatments ....

Compare type 1 and type 2 diabetes

Type 1 Type 2

% of cases 5-10% 90-95%

Stage of life usually occurs

Childhood Adulthood

Typical body mass of patient

Normal or underweight

Overweight or obese usually

Insulin production by pancreatic cells

No insulin made Insulin made

Sensitivity of cells to insulin

Sensitivity level normal as normal level of receptors

Lower level of receptors, so less sensitive

Treatment Regular monitoring and insulin injections

Diet controlled, increase exercise and lose weight

Use the video to think about the treatments ....

Now you have 4 patients;Diagnose them!

What happens to the extra glucose?

This is only an INDICATOR of diabetes ... Need a diagnostic test

By GLUCOSE TOLERANCE TEST Measures the capacity of the body to deal with

ingested (eaten) glucose Indirectly measures whether insulin is produced

normally

Fast for 8 hours (in order to see impact of glucose, so allows low level to start with)

Consume known mass of glucose – glucose load (250–300ml of glucose solution)

Monitor glucose levels over 2 hours, these plotted and interpreted..

In both types of diabetes individual blood glucose levels will rise rapidly after a meal.

Type I – remains high

Type II – delay of insulin response

The kidneys are unable to cope resulting in glucose being lost in the urine.

Testing urine for glucose is often used as an indicator of diabetes.

Indicator test vs. diagnostic test of tolerance curve

Insulin Glucagon

Activates the conversion of glucose to glycogen

Secreted during periods of low blood glucose, e.g. between meals and during exercise

Decreases blood glucose levels

Low levels continuously secreted, higher levels secreted after eating

Increases blood glucose levels

Activates the conversion of glycogen to glucose

Insulin GlucagonActivates the conversion of glucose to glycogen

Activates the conversion of glycogen to glucose

Decreases blood glucose levels

Increases blood glucose levels

Low levels continuously secreted, higher levels secreted after eating

Secreted during periods of low blood glucose, eg between meals and during exercise

Type 1 diabetes …

Type 2 diabetes …

A person with type 1 diabetes …

A person with type 2 diabetes …

A person with type 2 diabetes …

A person with type 1 diabetes …

…occurs later in life and mainly in obese people.

…produces insulin but their cells are less sensitive to it.

…is treated with regular doses of insulin.

…is unable to produce insulin.

…occurs mainly in childhood.

…is treated first with changes in diet, weight and exercise.

Type 1 diabetes…occurs mainly in childhood.

Type 2 diabetes…occurs later in life and mainly in obese people.

A person with type 1 diabetes…is unable to produce insulin.

A person with type 2 diabetes…produces insulin but their cells are less sensitive to it.

A person with type 2 diabetes …is treated first with changes in diet, weight and exercise.

A person with type 1 diabetes…is treated with regular doses of insulin.

• Regulation of blood glucose level by insulin and glucagon negative feedback.

• Pancreatic receptors respond to high blood glucose levels by causing secretion of insulin.

• Insulin activates the conversion of glucose to glycogen in the liver decreasing blood glucose concentration.

• Pancreatic receptors respond to low blood glucose levels by producing glucagon.

• Glucagon activates the conversion of glycogen to glucose in the liver increasing blood glucose level.

• During exercise and fight or flight responses glucose levels are raised by adrenaline (epinephrine) released from the adrenal glands stimulating glucagon secretion and inhibiting insulin secretion.

• A diabetic is unable to control their glucose levels.

• Vascular disease can be a chronic complication of diabetes.

• Type 1 diabetes usually occurs in childhood. • Type 2 diabetes or adult onset diabetes typically

develops later in life and occurs mainly in overweight individuals.

• A person with Type 1 diabetes is unable to produce insulin and can be treated with regular doses of insulin.

• In type 2 diabetes individuals produce insulin but their cells are less sensitive to it.

• This insulin resistance is linked to a decrease in the number of insulin receptors in the liver leading to a failure to convert glucose to glycogen.

• Glucose tolerance curves of normal and diabetic subjects can be used to assist understanding/ diagnosis

• In both types of diabetes individual blood glucose levels will rise rapidly after a meal and the kidneys are unable to cope resulting in glucose being lost in the urine.

Testing urine for glucose is often used as an indicator of diabetes.

The glucose tolerance test is used to diagnose diabetes.

The blood glucose levels of the individual are measured after fasting (not eating) and two hours after drinking 250–300ml of glucose solution.