Pathology of Diabetes Mellitus

Question 1

What cells make up the endocrine part of the pancreas?

Answer 1

Islets of Langerhans

Question 2

What do Beta cells secrete?

Answer 2

Insulin

Question 3

What is the effect of insulin on fat?

Answer 3

Insulin binds to its receptor and drives glucose into the adipocytes

Question 4

Outline the glucose metabolism pathway

Answer 4

Glucose increases
Insulin increases
Glucose uptake by cells increases
Glucose in serum decreases

Question 5

What is the main theory in the aetiology of type I DM?

Answer 5

Although not fully understood, it is believed that there is a failure of the body to differentiate its own cells from foreign ones, so an autoimmune attack damages Beta cells of the pancreas

Question 6

What is the infiltration of islet cells by lymphocytes and resulting inflammation known as?

Answer 6

Insulinits - the destruction of Beta cells, leading to decreased insulin and increased BG

Question 7

What is believed to be the aetiology of type II DM?

Answer 7

A combination of reduced tissue sensitivity to insulin (resistance) and an inability of the Beta islet cells to secrete very high levels of insulin

i.e. an overall failure to meet the demands of insulin prompted by very high BG levels

Question 8

What is the relevance of central adiposity in DM?

Answer 8

The expanded visceral fat mass results in increased free fatty acids in the blood BUT the patient is not yet diabetic
NB the reason for the increase in fatty acids is not understood

Question 9

What is the result of increased free fatty acids in the blood due to central adiposity?

Answer 9

The stress response by insulin receptors makes them less willing to take up the insulin and thereby their sensitivity is reduced

Question 10

What is the result of the reduced insulin sensitivity of the insulin receptors? What is needed to counteract this?

Answer 10

Some of the plasma glucose is absorbed into the cell but not all, so although there is the normal amount of BG at the outset, not enough is entered into cells = high BG
As a result more insulin is needed from the pancreas of these patients

Question 11

Why does hyperinsulinaemia occur in patients with central adiposity?

Answer 11

The decreased removal of glucose from the blood due to the reduced insulin receptor sensitivity results in a high insulin demand to allow more of the glucose to enter the cells to avoid hyperglycaemia and this higher secretion of insulin from the pancreas leads to hyperinsulinaemia

Question 12

What does to the upper body visceral fat mass lead to?

Answer 12

Peripheral insulin resistance

Question 13

Describe the genes which control insulin secretion and their relationship with increased insulin demand

Answer 13

There are many different genes which control insulin secretion, around 40-60 control insulin secretion relating to the pancreas

Some of the genes may promote insulin secretion at low levels but will fail to promote secretion at high levels, the number of these greater the number of these genes which are inherited the greater the failure of the pancreas to meet the increased insulin demand

Question 14

What genes are thought to be linked with Type II DM in terms of insulin secretion?

Answer 14

Genes linked with Bets cell ‘high end’ output of insulin

Question 15

In what circumstance will type II DM appear in a patient with central adiposity?

Answer 15

If there are enough efficient genes for the insulin to fail to meet the high demand the BG levels will be consistently elevated = Type II DM

Question 16

What is the annual mortality of patients with type II DM?

Answer 16

5.4%

Question 17

By how much is life expectancy reduced in patients with type II DM?

Answer 17

By 5-10 years

Question 18

What is the most common cause f death in type II DM patients?

Answer 18

MI

Question 19

What is the major complication of type II DM?

Answer 19

Vessel disease (small and large)

Question 20

What is the effect of DM on atherosclerosis?

Answer 20

It accelerates it

Question 21

What is a suggested mechanism for how atherosclerosis is accelerated by DM?

Answer 21

Glucoses attach to LDL, the glucose stops the LDL from binding to its receptor on liver cells tightly enough and is therefore not removed but the liver and so the lipoprotein and proteins stay in the blood which causes hyperlipidaemia

Question 22

Describe the pathological changes in arterioles in DM

Answer 22

Imagining a cross section of the lumen of an arteriole, the endothelial cells provide a foundation for the basal laminal cells to form around, and between these layers there is a space called the sub endothelial space. In the health subject, molecules can flux in and out of this space, but in DM, the molecules are able to enter but not easily leave the space. This leads to a build-up of these molecules trapper under the basal lamina and cause it to thicken, losing its elasticity and narrowing

Question 23

What is another name for arteriolar disease?

Answer 23

Hyaline change

Question 24

Where is hyaline change particularly damaging?

Answer 24

Kidneys, feet, eyes and in arterioles supplying nerves

Question 25

What are the nodules of increased connective tissue around capillaries in DM called? Where can this extra tissue often be present?

Answer 25

Kimmelstiel-Wilson lesions

Glomerulus of the kidney

Question 26

What is the relationship between small vessel disease and glycosyation of proteins?

Answer 26

Related to the theory of the glucose molecules attaching to the proteins, if the glucose molecules are attached via covalent bonds, they become Advanced Glycosylation End-products or AGE’s

Collagen may become glycosylated - (collagen is in normal basal ganglia). Albumin may also get into the sub endothelial space ads part of the normal flux in and out, however although normal collagen does not bing albumin, glycosylated collagen does, which leads to a build up of albumin in the sub endothelial space

Question 27

What is the link between cross-linked advanced glycosylation products and small vessel disease?

Answer 27

Glycosylated proteins are cross-linke, online normal proteins, this means that when they enter the sub endothelial they bind their neighbouring proteins, and unlike normal proteins become very difficult to remove and will persist in the vessel wall