Diabetes Lecture 1: Type 1 Diabetes: Flashcards
What does GLUTS (glucose transporters do)
Facilitate glucose uptake into tissues
What should the typical glucose levels be maintained at
3 to 8 mM
What happens after the body eats a meal
Increased uptake of glucose into liver and pancreas through low affinity transporter- GLUT-2
Increased uptake of glucose into some tissues (muscle and adipose) following activation of insulin dependent GLUT-4
What does a low Km and high Km value represent
Low Km= high affinity
High Km= low affinity
What is the role of the pancreas
Secretion of insulin and glucagon to regulate glucose levels
What do the alpha and beta cells do
Alpha: secretion of glucagon
Beta: secretion of insulin
If there is low glucose, how does the body react
Glucagon secretion
Increase catabolic pathways Increase Glycogenolysis (muscle and liver) Increase Gluconeogenesis (liver and all tissues) Increase lipolysis (adipose tissue) Inhibit glycolysis (liver)
Inhibit anabolic pathways- glycogen synthesis and lipid synthesis
If there is high glucose, how does the body react
Insulin secretion
Increase anabolic pathways
Increase fatty acid synthesis (liver, adipose tissue)
Increase glycogen synthesis (liver, muscle)
Inhibition of catabolic pathway- gluconeogenesis, lipolysis (muscle, liver, adipose tissue)
What is diabetes mellitus and how does it arise
A common group of metabolic disorders, characterised by chronic hyperglycaemia
Arises from insulin deficiency, insulin resistance or both
What is type 1 diabetes definition
A polygenic disorder characterised by immune destruction of pancreatic beta cells that leads to complete insulin deficiency
What is type 2 diabetes definition
A polygenic disorder characterised by decrease in beta cell mass, leading to a reduction in secretion and peripheral insulin resistance
What are the non modifiable risk factors of diabetes
Family history (increased if mother, father or sibling have it)
Ethnicity
Type 1:
more common in northern european countries
Type 2:
South asian
African or afrocaribbeans
Chinese
Age:
Over 40 more likely to develop type 2 diabetes or 25 if black or asian
Medical conditions:
Polycystic ovary syndrome
Gestational diabetes
Impaired glucose tolerance
What are the modifiable risk factors for diabetes
Weight- type 2 only
Increased waist circumference
Sedentary life style (type 2)
Social deprivation and low income
What are the symptoms of type 1 diabetes
2-4 history of thirst
Polyuria
Weight loss
Lethargy
What are the symptoms of type 2 diabetes
History of thirst
Polyuria
Weight loss
Lethargy
Visual disturbances
Infections
What are the clinical signs of diabetes
Glycosuria- glucose in urine
Hyperglycaemia
More or equal to 11mmol/l (random plasma glucose)
More or equal to 7mmol/l (fasted plasma glucose)
Impaired glucose tolerance
Excludes certain medications, obesity, liver disease
Complications of diabetes
What are the physiological basis for blood glucose levels being elevated in diabetes, explain in detail
Water drawn from interstitial spaces into the circulation to decrease blood osmolarity
Increase in blood volume is countered by increased urinary output
When reabsorptive capacity of renal tubes is exceeded, there is an increased osmotic pressure in tubules (reduced glucose and water reabsorption)
Therefore fluid and electrolyte losses result from polyuria which stimulates thirst
What are the physiological basis for fluid loss leading to dehydration and weight loss in diabetes, explain in detail
No insulin means cells cannot absorb glucose from blood- must use other sources like glycogen fats and proteins
Breakdown of fat and muscle leads to weight loss
Using fat sources leads to production of ketone bodies- can increase blood acidity known as KETOACIDOSIS
Why do diabetic patients have a reduced life expectancy and mortality rate
Increased cardiovascular disease
Increase renal failure
Increased morbidity and increased risk of blindness
When diagnosing diabetes, what is a good indicator with the HbA1c levels of diabetes
HbA1c level of more than or equal to 6.5% (48mmol/mol)
What is considered normal and impaired fasting blood glucose level
Normal: 2-6 mmol/L
Impaired: 6-7 mmol/L
How do you measure oral glucose tolerance testing
Fasting over night (12 hours, water only), a fasting blood glucose reading is taken
Glucose solution consumed
(75g of oral glucose in 250 to 300mL) within 5 minutes
Blood glucose levels measured at 120 minutes after consumption of glucose
Why is HbA1c level a good indicator
Exposing red blood cells to glucose results in them becoming irreversibly glycated
Therefore can be used to estimate average glucose levels
What is the evidence showing that type 1 diabetes is an autoimmune response
Association of type 1 with other autoimmune disorders (coeliac disease)
Evidence of chronic inflammation in cells and macrophages in islets of newly diagnosed patients
Detection of circulating auto-antibodies before disease onset
- anti-insulin
- anti-islet antibodies
What are the treatment goals
Preserve life
Achieve good glycemic control which avoids long term complications
Avoid iatrogenic side effects (hypoglycaemia)
Alleviate symptoms
How do you manage type 1 diabetes
Insulin replacement
Dietary modification
Exercise
Education
Monitoring
Psychosocial support
What should the diabetic diet contain
Less fat and saturated fats
Low in simple sugars
High in fibre
How should you treat a type 1 diabetic patient
Provide insulin replacement in a way that mimics insulin secretion pattern seen in normal people- released at slow basal rate all date
Eat meal, rises rapidly before dropping after 2 hours
What are the complications of type 1 diabetic patients
Patient can experience partial remission phase- only requires low levels of insulin for good maintenance of glycemic control
Hypoglycaemia
Lipohypertrophy- accumulation of fat at injection sites due to local insulin effects
Insulin allergy
How do you monitor a type 1 diabetic patient
Can monitor capillary blood glucose levels before and/or 2 hours after meals after exercise
Monitor long term glycemic control (doctor led HbA1c levels)
Monitor risk of developing long term complications:
regular eye screening for retinopathy
Cardiovascular disease screening
Diet
