Pathology of Diabetes Mellitus Flashcards
What cells make up the endocrine part of the pancreas?
Islets of Langerhans
What do Beta cells secrete?
Insulin
What is the effect of insulin on fat?
Insulin binds to its receptor and drives glucose into the adipocytes
Outline the glucose metabolism pathway
Glucose increases
Insulin increases
Glucose uptake by cells increases
Glucose in serum decreases
What is the main theory in the aetiology of type I DM?
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
What is the infiltration of islet cells by lymphocytes and resulting inflammation known as?
Insulinits - the destruction of Beta cells, leading to decreased insulin and increased BG
What is believed to be the aetiology of type II DM?
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
What is the relevance of central adiposity in DM?
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
What is the result of increased free fatty acids in the blood due to central adiposity?
The stress response by insulin receptors makes them less willing to take up the insulin and thereby their sensitivity is reduced
What is the result of the reduced insulin sensitivity of the insulin receptors? What is needed to counteract this?
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
Why does hyperinsulinaemia occur in patients with central adiposity?
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
What does to the upper body visceral fat mass lead to?
Peripheral insulin resistance
Describe the genes which control insulin secretion and their relationship with increased insulin demand
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
What genes are thought to be linked with Type II DM in terms of insulin secretion?
Genes linked with Bets cell ‘high end’ output of insulin
In what circumstance will type II DM appear in a patient with central adiposity?
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
What is the annual mortality of patients with type II DM?
5.4%
By how much is life expectancy reduced in patients with type II DM?
By 5-10 years
What is the most common cause f death in type II DM patients?
MI
What is the major complication of type II DM?
Vessel disease (small and large)
What is the effect of DM on atherosclerosis?
It accelerates it
What is a suggested mechanism for how atherosclerosis is accelerated by DM?
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
Describe the pathological changes in arterioles in DM
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
What is another name for arteriolar disease?
Hyaline change
Where is hyaline change particularly damaging?
Kidneys, feet, eyes and in arterioles supplying nerves
What are the nodules of increased connective tissue around capillaries in DM called? Where can this extra tissue often be present?
Kimmelstiel-Wilson lesions
Glomerulus of the kidney
What is the relationship between small vessel disease and glycosyation of proteins?
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
What is the link between cross-linked advanced glycosylation products and small vessel disease?
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
