Week 7 - Diabetes Mellitus Flashcards
What type of hormone is insulin?
Peptide hormone
-51 amino acids
Where is insulin produced?
- B cells of the islets of Langerhans of the pancreas
- also produce glucagon and pancreatic polypeptide
How does insulin take affect and what effect does it have?
- released in to blood stream from the B-cells of the islets of Langerhans in the pancreas
- bind to cell membrane receptors of target cells
- regulates glucose uptake and metabolism
Which cells require insulin and why?
- skeletal muscle cells and fat cells require insulin to absorb glucose
- both types can accumulate large carbohydrate reserves
Which cells don’t require glucose and why?
- neurons and a variety of other cells don’t require insulin to absorb glucose
- can’t accumulate significant carbohydrate reserves
What are the actions of insulin?
- uptake of glucose by cells
- uptake of amino acids by cells
- increased glycogen synthesis
- increased synthesis and esterification of fatty acids
- decreased lipolysis, proteinolysis and gluconeogenesis
How is insulin release controlled?
Mainly direct feed back
- B-cells absorb glucose via glucose transporter GLUT2
- complex metabolic pathway releases pre-synthesised insulin
Some autonomic control
Also released by cholecystokinin derived from enteroendocrine cells of intestinal mucosa
What are the acute consequences of insulin deficiency?
- hyperglycaemia
- ketosis (raised ketone levels)
- acidosis (excessive blood acidity)
- hyperosmolar state
What are the chronic consequences of insulin deficiency?
- CV disease
- nephropathy
- neuropathy
- retinopathy
What types of diabetes mellitus are there?
- type 1
- type 2
- gestational
- secondary (direct consequence of something e.g. giving steroids)
Explain diabetes mellitus type 1
Autoimmune destruction of B-cells
- probably triggered by viral infection (coxsackie/rubella)
- susceptibility partly dependant on HLA gene subtypes (HLA-DR3/DR4)
- classically starts in childhood, though adult onset is not rare
What are the classical symptoms of type 1 diabetes?
- polyuria (production of abnormally large volumes of dilute urine)
- polydipsia (abnormally great thirst)
- hunger
- weight loss
(Can be seen in DM type 2 but often camouflaged by other symptoms)
How does polyuria occur as a symptom in DM type 1?
- normal for glucose to be secreted into the urine in the glomerulus at normal concentrations (all of this glucose is reabsorbed in the proximal renal tubule)
- threshold for reabsorption is about 10mmol/l - higher concentrations lead to glycosuria (excess sugar in the urine)
- glycosuria leads to osmotic polyuria
- polyuria leads to polydipsia
Explain DM type 2
Pathophysiology complicated:
- peripheral insulin resistance
- B-cell response to glucose delayed or absent
- insulin concentrations normal or high
Strong association with lifestyle
What is gestational diabetes?
- insulin resistance, probably triggered by hormonal changes of pregnancy
- genetic predisposition
- resolves with delivery
What are the risk factors for gestational diabetes?
- maternal age
- family history of DM type 2
- African or North American native
- previous gestational diabetes
- previous baby over 4kg
- smoking
What are the dangers of gestational diabetes for the mother?
- greater risk of DM type 2 later in life
- hypertension
- pre-eclampsia or eclampsia (condition which one or more convulsions occur in a pregnant women suffering from high BP)
- obstructed labour
What are the dangers of gestational diabetes for the child?
- risk of DM type 2 later in life
- risk of obesity later in life
- macrosomia - big body
- neonatal hypoglycaemia
- neonatal jaundice
- respiratory distress syndrome
What can cause secondary diabetes mellitus?
- chronic pancreatitis
- cystic fibrosis
- pancreatic surgery
- haemachromatosis
- endocrine disease e.g. Cushing’s syndrome
- drug therapy e.g. corticosteroids
How is diabetes diagnosed biochemically?
Criteria:
-fasting plasma glucose level at or above 7.0mmol/l
- plasma glucose at or above 11.1mmol/l two hours after a 75g oral glucose load
- random plasma glucose at or above 11.1mmol/l
- glucose tolerance test
What are the acute presentations of diabetes mellitus?
Ketoacidosis Hyperosmolar non-ketotic state Hypoglycaemia (insulin overdose, can lead to coma and death) Diabetic foot (can lead to general sepsis and death)
What is ketoacidosis?
- rapid breakdown of fat and protein releases ketones (including acetone) and acids in to the bloodstream
- DM type 1 and rarely type 2
- can lead to coma and death
What is hyperosmolar non-ketotic state?
- severe dehydration
- DM type 2
- can lead to coma and death
What are the chronic presentations of diabetes mellitus?
- macrovascular (ischaemic heart disease, stroke, peripheral vascular disease)
- microvascular (retinopathy, neuropathy, nephropathy)
- cataracts
What is diabetic retinopathy?
Proliferation of blood vessels in the retina
-retinal haemorrhages
Macular oedema
-fluid exudation into retina
Microaneurysms
Hyperglycaemia alone can cause visual disturbance, but this isn’t diabetic retinopathy
What is diabetic neuropathy?
Microangiopathy of vasa nervosum
-(peripheral numbness or tingling, occasional neuropathic pain, muscle weakness, autonomic neuropathy (vomiting, diarrhoea, constipation, incontinence, impotence, anorgasmia, postural hypotension))
Microangiopathy of glomerular capillaries
- pathology: nodular and diffuse glomerulosclerosis
- clinical: chronic renal failure or nephrotic syndrome; hypertension
What are the two types of diabetes and what are they caused by?
Diabetes mellitus
- deficiency to insulin
- resistance to effects of insulin
Diabetes insipidus
-deficiency of ADH
What is angiopathy?
Disease of blood vessels
So microangiopathy is disease of blood vessels affecting small blood vessels in the body
