Endo: Diabetes Flashcards
How many of world’s population have diabetes mellitus?
3%
Genetic defects causing B-cell dysfunction in Type 1 DM
Chr 2
Chr 7
Chr 12
Mitochondrial DNA
What type of pancreatic tissue is involved in its exocrine function?
Pancreatic acinar tissue
What type of pancreatic tissue is involved in its endocrine function?
Islets of Langerhans which produce glucagon, insulin and pancreatic polypeptide hormes
Therefore any condition destroying this tissue can cause secondary diabetes
Causes of secondary diabetes (7)
Chronic pancreatitis
Haemachromotosis
Endocrine issues (eg adrenal, pituitary tumours)
PREGNANCY
Drugs (eg corticosteroids)
ID (eg congenital rubella, CMV)
Other genetic disorders eg Down’s
Histology of chronic pancreatitis?
Loss of pancreas tissue, replaced by fibrous tissue
How many people over age of 55 have DM?
50%
Which auto-antibodies occur in DM type 1 and not DM type 2?
Auto-islet cell antibodies (HLA-D)
Which type of DM is HLA-D linked?
Type 1
What is the concordance in twins of both DM types?
50% in type 1
90-100% in type 2
Pathology of type 1 DM?
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
Histopathology of DM type 2
Insulin resistance with no inflammation of islets
Focal atrophy and amyloid deposits
Only mild beta cell depletion
How is insulin produced in the islet cells?
Increased levels of gluscose in blood are transported across cell boundary by GLUT-2 transporter
Results in production of preproinsulin and proinsulin, then insulin
Where is insulin stored?
In granules within islet cell
How does insulin affect a cell?
Attaches to insulin receptor on membrane
Leads to increased production of glucose transport units
More glucose uptake
Also, increased protein, DNA synthesis
Genetic factors contributing to type 1 DM? (5)
Northern europeans 1st degree relative (6%) Identical twin (50% HLA-D antibody HLA-DR3 or DR4
Components of autoimmune islet cell destruction in DM1
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
What percentage of DM type 1 patients have other autoimmune disease?
10-20% such as SLE or RA
Which viruses have been associated with triggering type 1 DM? (4)
?mumps
Measles
Rubella
Coxsackie B
Pathology of DM type 2?
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
Why is DM type 2 irreversible?
Beta cells become exhausted
In the early stages, before exhaustion, the condition is irreversible
What is the normal secretion pattern of insulin?
Puslatile and oscillating
How many type 2 DM pts are obese?
80%
What is non enzymatic glycosylation?
When products of glucose become linked with proteins (eg Hb in HbA1c)
or linked to collagen components (eg advanced glycosylation end products)
Pathogenesis of complications of Diabetes, why does high blood sugar cause damage?
Non enzymatic glycosylation (formation of HbA1c or AGE)
Intracellular hyperglycaemia with disturbances of polyol pathways and excess sorbitol and fructose in cells
Examples of complications in DM?
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
Eye complications in DM? (5)
Retinopathy Maculopathy Cataracts Glaucoma Blindness/visual impairment
What is insulinitis?
Leukocytes present within the islets
How does diabetes affect large vessels eg aorta?
Atherosclerosis Narrowing of vessels Ulceration Calcification Loss of elasticity Occluding of branches
Gender incidence of MIs in diabetic subgroup?
Male=female (in non diabetic group females have lower incidence if they are pre menopausal)
Why do vascular complications occur in diabetes?
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
How does diabetes affect the renal arteries?
Narrows the renal arteries, causing renal ischaemia and hypertension
How does diabetes affect basement membrane?
Diffuse thickening of basement membrane due to deposition of GLYCOGENATED COLLAGEN proteins
What is mesangial matrix?
Increases due to increased collagen deposition
Involved in diffuse glomerulosclerosis at the centre of the glomerulus
Narrows the capillary loops
Magenta staining
Histology: Increase of menagial matrix in glomerulus with nodular distribution
Kimmelstiel-Wilson lesion, typical of diabetic glomerulosclerosis
Results in decrease in glomerular blood flow and renal failure
What is hyaline arteriosclerosis?
Replacement of blood vessel media layer muscle with hyaline
How does hyaline arteriosclerosis affect the kidneys?
Narrows the afferent and efferent arterioles
What is papillary necrosis?
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
Why does nerve damage occur in diabetes?
Microangiopathy causes loss of blood flow to nerves and they are damaged
Skin complications in diabetes
Recurrent infections
*Necrobiosis lipoidica diabeticorum
Granuloma annulare
Pregnancy complications with diabetes
Pre-eclampsia
Large immature babies
Neonatal HYPOglycaemia
