Endo: Diabetes

Question 1

How many of world’s population have diabetes mellitus?

Answer 1

3%

Question 2

Genetic defects causing B-cell dysfunction in Type 1 DM

Answer 2

Chr 2
Chr 7
Chr 12
Mitochondrial DNA

Question 3

What type of pancreatic tissue is involved in its exocrine function?

Answer 3

Pancreatic acinar tissue

Question 4

What type of pancreatic tissue is involved in its endocrine function?

Answer 4

Islets of Langerhans which produce glucagon, insulin and pancreatic polypeptide hormes

Therefore any condition destroying this tissue can cause secondary diabetes

Question 5

Causes of secondary diabetes (7)

Answer 5

Chronic pancreatitis
Haemachromotosis

Endocrine issues (eg adrenal, pituitary tumours)

PREGNANCY
Drugs (eg corticosteroids)

ID (eg congenital rubella, CMV)

Other genetic disorders eg Down’s

Question 6

Histology of chronic pancreatitis?

Answer 6

Loss of pancreas tissue, replaced by fibrous tissue

Question 7

How many people over age of 55 have DM?

Answer 7

50%

Question 8

Which auto-antibodies occur in DM type 1 and not DM type 2?

Answer 8

Auto-islet cell antibodies (HLA-D)

Question 9

Which type of DM is HLA-D linked?

Answer 9

Type 1

Question 10

What is the concordance in twins of both DM types?

Answer 10

50% in type 1

90-100% in type 2

Question 11

Pathology of type 1 DM?

Answer 11

AUTOIMMUNE immunopathological mechanism

Severe insulin deficiency and inflammation or insulitis of islet cells early in the disease

These develop marked atrophy and fibrosis with beta cell depletion

Question 12

Histopathology of DM type 2

Answer 12

Insulin resistance with no inflammation of islets

Focal atrophy and amyloid deposits

Only mild beta cell depletion

Question 13

How is insulin produced in the islet cells?

Answer 13

Increased levels of gluscose in blood are transported across cell boundary by GLUT-2 transporter

Results in production of preproinsulin and proinsulin, then insulin

Question 14

Where is insulin stored?

Answer 14

In granules within islet cell

Question 15

How does insulin affect a cell?

Answer 15

Attaches to insulin receptor on membrane

Leads to increased production of glucose transport units

More glucose uptake

Also, increased protein, DNA synthesis

Question 16

Genetic factors contributing to type 1 DM? (5)

Answer 16

Northern europeans
1st degree relative (6%)
Identical twin (50%
HLA-D antibody
HLA-DR3 or DR4

Question 17

Components of autoimmune islet cell destruction in DM1

Answer 17

Pre-clinical phase of islet destruction and insulitis, with presence of CD8 and CD9 macrophages

Increase in class 1 MHC and aberrant expression of class 2 MHS

Islet cell autoantibodies

Other autoimmune diseases

Question 18

What percentage of DM type 1 patients have other autoimmune disease?

Answer 18

10-20% such as SLE or RA

Question 19

Which viruses have been associated with triggering type 1 DM? (4)

Answer 19

?mumps
Measles
Rubella
Coxsackie B

Question 20

Pathology of DM type 2?

Answer 20

Genetic predisposition and obesity.

Genetic defects lead to deranged insulin secretion

With obesity, the peripheral tissues develop insulin resistance and are unable to adequately use glucose present in blood

Leads to hyperglycaemia

Question 21

Why is DM type 2 irreversible?

Answer 21

Beta cells become exhausted

In the early stages, before exhaustion, the condition is irreversible

Question 22

What is the normal secretion pattern of insulin?

Answer 22

Puslatile and oscillating

Question 23

How many type 2 DM pts are obese?

Answer 23

80%

Question 24

What is non enzymatic glycosylation?

Answer 24

When products of glucose become linked with proteins (eg Hb in HbA1c)

or linked to collagen components (eg advanced glycosylation end products)

Question 25

Pathogenesis of complications of Diabetes, why does high blood sugar cause damage?

Answer 25

Non enzymatic glycosylation (formation of HbA1c or AGE) Intracellular hyperglycaemia with disturbances of polyol pathways and excess sorbitol and fructose in cells

Question 26

Examples of complications in DM?

Answer 26

Macrovascular: MI, Hypertension, atherosclerosis, CHD, PAD, arrythmias, cardiomyopathies Microvascular: Microangiopathy, cerebral infarcts, haemorrhage, retinopathy, cataracts, glaucoma, gangrene, nepthrosclerosis, glomerulosclerosis, pyelonephritis Nervous system: peripheral neuropathy and autonomic neuropathy

Question 27

Eye complications in DM? (5)

Answer 27

``` Retinopathy Maculopathy Cataracts Glaucoma Blindness/visual impairment ```

Question 28

What is insulinitis?

Answer 28

Leukocytes present within the islets

Question 29

How does diabetes affect large vessels eg aorta?

Answer 29

``` Atherosclerosis Narrowing of vessels Ulceration Calcification Loss of elasticity Occluding of branches ```

Question 30

Gender incidence of MIs in diabetic subgroup?

Answer 30

Male=female (in non diabetic group females have lower incidence if they are pre menopausal)

Question 31

Why do vascular complications occur in diabetes?

Answer 31

Partly due to raised blood lipids Low level of protective HDLs Increase in thromboxane A2, which increases platelet stickiness, and leads to thrombosis Hyaline arteriolosclerosis

Question 32

How does diabetes affect the renal arteries?

Answer 32

Narrows the renal arteries, causing renal ischaemia and hypertension

Question 33

How does diabetes affect basement membrane?

Answer 33

Diffuse thickening of basement membrane due to deposition of GLYCOGENATED COLLAGEN proteins

Question 34

What is mesangial matrix?

Answer 34

Increases due to increased collagen deposition Involved in diffuse glomerulosclerosis at the centre of the glomerulus Narrows the capillary loops Magenta staining

Question 35

Histology: Increase of menagial matrix in glomerulus with nodular distribution

Answer 35

Kimmelstiel-Wilson lesion, typical of diabetic glomerulosclerosis Results in decrease in glomerular blood flow and renal failure

Question 36

What is hyaline arteriosclerosis?

Answer 36

Replacement of blood vessel media layer muscle with hyaline

Question 37

How does hyaline arteriosclerosis affect the kidneys?

Answer 37

Narrows the afferent and efferent arterioles

Question 38

What is papillary necrosis?

Answer 38

A rare condition seen in diabetics Associated with some painkillers Due to inflammation of the kidney and ischaemia causing necrosis of the papilla Dead papilla passes into ureter and can cause obstruction

Question 39

Why does nerve damage occur in diabetes?

Answer 39

Microangiopathy causes loss of blood flow to nerves and they are damaged

Question 40

Skin complications in diabetes

Answer 40

Recurrent infections *Necrobiosis lipoidica diabeticorum Granuloma annulare

Question 41

Pregnancy complications with diabetes

Answer 41

Pre-eclampsia Large immature babies Neonatal HYPOglycaemia