Type I Diabetes Mellitus Flashcards
What can cause type I DM?
- Autoimmune destruction of the pancreas gland - beta cells are attacked by the innate immune response
- Genetic predisposition - not all cases of monozygotic twins (30% concordance) - must be environmental element
- Virus infection - hypothesis, molecular mimicry
What are the differences between type I and II DM?
Type I = insulin deficiency
Type II = insulin resistance
What is the major treatment for type I diabetes?
Insulin
How was insulin manufactured before the 60s?
Dog and other animal pancreatic ducts where ligated
This destroyed the pancreatic gland and exocrine funciton
Islets were preserved - isolated islets and insulin
What is polyuria?
Large amount of urine produced by the body
What happens if sodium concentration is not correct in the body?
Cerebral oedema in hyposmolarity
What are the complications of type I diabetes?
- Microvascular complications - endothelial damage caused by hyperglycemia
- Macrovascular complications
What is the major target for type I diabetes?
Tight control of serum glucose concentration
Tight glucose control = risks associated with diabetes are reduced
What are the consequences of hypoglycemia?
Coma and brain damage
What are the microvascular complications of DM type I?
Diabetic retinopathy - vascular damage leads to angiogenesis causes retinal damage
Diabetic nephropathy - increases glomerular P and basement membrane thickens leading to loss of protein in the urine
Peripheral neuropathy - accumulation of sorbitol in cells (cannot leave via GLUT) and causes glycation of structural proteins like collagen
What are the treatments for diabetic nephropathy?
Control of blood pressure
Inhibition of renin-angiotensin system
What is a presentation of diabetic neuropathy in diabetic patients?
Foot ulcers
What are macrovascular complications in type I DM patients?
Stroke
Ischaemic heart disease
Peripheral vascular disease - atherosclerosis
What are preventative measures patients can undertake to prevent peripheral vascular disease?
Management of risk factors like
Blood pressure
Lipids
Cigarette smoking
What effect does strict control of glucose levels have on microvascular and macrovascular complications?
Microvascular complications decreased when glucose levels were strictly controlled
Macrovascular complications were not affected significantly when glucose levels were strictly controlled
If too controlled - hypoglycemia, pathogenesis worsened
What is the future of type I DM treatment?
Iselt cell transplantation
Stem cell transplantation
How does islet cell transplantation take place?
- Receive pancreas from non-living donor
- Digested using collagenase
- Extract beta cells
- Radiological access to the portal vein of the recipient - locate via US
- Use a catheter to inject the solution - lodge and engraft in the liver
- B cells will start to produce insulin
What are the risks of islet cell tranplantation?
Thrombosis of the portal vein
Bleeding
Immunosuppressants - cancer and metabolic syndrome
Which sources can be used for stem cell transplantation?
- Human embryonic stem cells
2. Induced pluripotent stem cells
What are induced pluripotent stem cells?
Fibroblasts that have been reprogrammed through transcription
What are the steps to producing insulin in stem cell transplantation?
Have to differentiate the stem cells under the right circumstances to produce insulin
They express the reverse diabetic phenotype
What is important to do in stem cell transplantation?
Make sure the stem cells are not susceptible to injury by the autoantibodies that caused injury in the first place
What is a transcription factor in mature beta cells?
MAFA
