What % of diabetic patients have T1DM?
15%
What is the most common ethnicity of patients with T1DM?
Caucasion
North European
What is the most common age of presentation of T1DM patients?
Puberty
But can be any age
What is the pathophysiology of T1DM?
Gradual destruction of Bcells due to autoimmunity
What is the most common subtype of T1DM?
Type 1A
Immune regulated form
90% have mutations in HLA genes on chromosome 6
Name a non genetic risk factor for T1DM?
Clean environment during childhood with little exposure to pathogens
Name 5 common symptoms of T1DM at presentation?
Polydipsia (increased thirst)
Increased urination (especially at night)
Weight loss/ fatigue
Itching around genitals/ bouts of thrush
Name 3 signs of diabetic patients seen at presentation?
Hyperglycemia
Glucosuria
Ketoneuria?
Name 6 emergency signs in a presentation of T1DM?
Loss of appetite/ N+V
Fever/ drowsy/ confused
Stomach pain
Fruity (pear drop) breath - ketoacidosis
What glucose levels (fasting and random) indicate possible diabetes?
Random glucose >11.1mmol/L
Fasting glucose >7mmol/L
What are the diagnostic criteria for T1DM when doing glucose tests?
ONE random/ fasting glucose out of range if symptomatic
TWO randon/fasting glucose out of range if asymptomatic
What HbA1c level is diagnostic of diabetes?
> 48mmol/L (6.5%)
Although result lower than this does not exclude diagnosis if glucose test disagrees
What is the treatment for T1DM?
Always need insulin!
Education/ healthy diet/ weight loss/ smoking cessation
What are the two different methods of insulin dosing?
Twice Daily: Intermediate insulin (isophane)
- Works within 2hrs, lasts 18-24hrs
Multiple Dose: Rapid acting insulin
- Best for Px with good understanding/ control
Px taking insulin on a multiple dose regimen should take their insulin when?
Before/ with a meal
What is the main type of twice daily insulin?
Hypurin isophane (either bovine or porcrine)
Name the two most common rapid acting insulins?
Novorapid
Humalog (works in 15mins)
Lasts 3-5hrs
What is analouge insulin?
Similar to human but with recominant DNA
Where AA’s have been changed to change insulin properties
What is HbA1c?
A reliable indicator of mean glucose levels over the last 120 days
Why can HbA1c be used to give estimates of glucose?
As glycation (adding of sugar) to the Hb occurs at a variable rate over an RBC’s 120 day lifespan, so proportions of glycated reflect how much sugar has been in the blood
What is the normal level of HbA1c?
4-6% (20-43mmol/L)
Name 8 symptoms of hypoglycemia?
Shaking/ sweating
Weakness/ confusion
Hunger/ tingling lips
Slurred speech/ unconciousness/ transient hemipariesis
How would you treat a hypoglycemic patient when in a hospital?
If mild treat sugary drinks/ food
Give 80ml of 20% glucose IV
How would you treat a hypoglycemic patient when not in a hospital?
If mild give sugary drinks/ food
1mg (1unit) glucagon intramuscular
Name 4 risk factors than can predispose a diabetic patient to have a ‘hypo’:
Exercise
Taking too much insulin
Drinking alcohol on an empty stomach
Skipping meals
What is the clinical definition of hyperglycemia?
Blood glucose >11.1mmol/L
What is the classic triad of symptoms of hyperglycemic Px?
Polyphagia (hunger)
Polydipsia (thirst)
Polyuria (frequent urination)
(Add diabetic symptoms/ dry mouth/ drowsiness)
Prolonged hyperglycemia can lead to (5)?
Diabetic ketoacidosis
Renal/ cardiovascular/ neural/ retina damage
What is the pathophysiology of T2DM?
Disorder of receptors (increased triglyceride levels can cause release of inflam proteins/cytokines which damage 2nd messengers). Hyperinsulinaemia initially compensates but this eventually leads to Bcell damage
What % of patients with DM have T2DM?
90%
What ethnicity is most subceptible to T2DM?
Afrocarribean
Name 7 RF’s for developing T2DM:
‘Central’ obesity/ lack of physical activity
Low fibre, high sugar diet/ metabolic syndrome
Family history/ Polycystic ovary syndrome
Low birth weight/ gestational diabetes
How does presentation of T2DM differ to those with T1DM?
Longer onset of symptoms
Px with T2 often present much later in life
Name 6 presenting complaints for Px with T2DM:
Polyuria/ polydipsia/ lethargy Boils/ prolonged infections Pruritus vulvae (itchy genitals)
What is the NICE recommended treatment pathway for Px with T2DM?
Diet control > metformin >
Metformin + sulfonylurea (or DPP-4 inhib if hypo risk)
> add thiazolidinedione or insulin
What is metformin, how does it act, when is it given and what is a possible SE?
Activates AMPK (AMP activated protein kinase) in the liver and muscle to upregulate GLUT-4 receptors Take orally w meals SE: Lactic acidosis
How do sulfonylurea drugs work?
Bind to ATP sensative K+ channels on B cells, this depolarises the cell and opens Ca2+ channels which increases insulin release
Name three sulfonylurea drugs:
Glimepiride / Glipizide / Tolbutamide
How do DPP-4 inhibitor drugs work?
Inactivates the enzyme which inactivates GLP-1 (an incretin)
- This increases levels of GLP-1 which along with GIP causes the incretin effect
Name 2 DPP-4 inhibitor drugs:
Linagliptin/ Saxagliptin
How do thiazolidinediones act? Give an example drug
Act on intracellular receptor PPAR-Y to decreases hepatic glucose production and increase uptake and use in muscle
E.g Pioglitazone
What is the common presentation of diabetic ketoacidosis?
Diabetic symptoms (+ dehydration )
Drowsy/ confused/ fruity breath
Tachycardia/ hyperventilation/ hypotension
How common is gestational diabetes, what care should be taken to ensure women are protected?
Roughly 1in35 pregnancies- commonly in 2nd trimester
Ensure all high risk women are screened
Monitor and advise on diet, treat if needed (insulin)
What is the pathophysiology of diabetic retinopathy?
Usually in 2nd decade of disease Vascular microaneurysms (permeability changes etc lead to blood flow changes and ischemia)
What is the most common presentation of diabetic neuropathy?
Distal symmetrical polyneuropathy, starting with distal sensory loss
What is the pathophysiology of diabetic foot ulcers?
Loss of sensation = more trauma
Anhidrosis = drying and skin damage
Disordered proprioception = abnormal weight bearing
What are common diabetic dermatological problems?
The most common skin manifestations of DM are protracted wound healing and skin ulcerations
Where is acetyl-coA converted into ketone bodies in diabetic ketoacidosis?
Mitochondria
Soluble insulin produces what effect?
Rapid acting and short lasting
How are insulin preperations made to act over longer time periods?
Precipitating insulin with protamine or zinc
What % of T2DM will ultimately take insulin as part of the treatment?
33%
Which brain area links the osmoreceptors in the ant hypothalamus with the ADH releasing cells in the post pituitary?
Supraoptic nuclei
Which two area’s of the brain regulate hunger?
Lateral nuclei of hypothalamus = feeding centre (stimulation = hunger)
Ventromedial nuclei of hypothalamus = satiety centre (stimulation = feel full)
Multiple hormones released from the gastrointestinal tract and adipose tissue converge to regulate food intake as well as energy expenditure- where is this?
Arcuate nuclei
Which of the ketone bodies can’t be used by the cells and converted back to acetyl-coA, what happens to it?
Acetone
Instead it is expired via the lungs
What is the pathophysiology of diabetic nephropathy?
Renal hypertrophy associated with incr GFR (as afferent arteriole becomes more dilated), this raises intraglomerular pressure and damages cappilaries causing glomerular sclerosis
What are some common signs of diabetic nephropathy? (3)
Microalbuminuria (1st) > intermittenent albuminuria (2nd) > proteinuria (3rd)
Hyperlipidemia/ generalised oedema
How should diabetic nephropathy be treated?
ACEI
Aim below 130/80mmHg
What is the pathophysiology of diabetic neuropathy?
Hyperglycemia can lead to build up of ‘sorbitol’ and fructose in schwann cells- this leads to demyelination
How does diabetic neuropathy usually present?
Loss of vibration/ pain/ temp (usually feet before hands)
Feeling of walking on cotton wool
Balance impaired in the dark (less proprioception)
What is the pathophysiology of diabetic foot and how common is it?
10-15% of diabetic patients
Due to combination of ischemia (macrovascular), infection and neuropathy
(Black feet = vascular problem)
How should you treat diabetic foot?
Keep weight off ulcers
Treat with AB’s if needed
How common is diabetic eye disease?
90% of T1DM Px go on to develop
What is diabetic retinopathy?
Nerve damage to retina/ iris damage
Due to intramural pericytes death and basement membrane thickening (so less blood supply to nerves)
What are cateracts?
Denaturing of proteins in the lens render it opaque
increased risk in diabetes and ketosis
What is the recommendation for all patients with diabetes in regards to observing for opthalmic changes?
All diabetic Px should have yearly eye screening
How does blood glucose testing equipment work?
Has ‘glucose oxidase’ which catalyses the reaction of glucose to gluconic acid. Gluconic acid is measured and then the equipment converts this into a glucose level
Where should the Px prick when doing a glucose test?
Side of finger
How often should Px with T2DM which is controlled by diet/ oral agents measure their glucose?
Once/twice per week
How often should Px on insulin treatment check their glucose levels?
~12 hours after long acting insulin dose or
~ 90mins-2hrs after short acting insulin dose
2-4x per day
What % of patients on insulin therapy die due to their diabetes?
86%
What are the three main causes of death in diabetic patients?
CVD- 70%
Renal- 10%
Infection- 6%
Name 4 macrovascular complication of diabetes?
Stroke
MI
Foot gangrene
Atherosclerosis
Name 3 BV area’s commonly affected by microvascular disease in diabetes?
Retina
Kidney
Nerve sheaths
(often ~10-20 years post diagnosis)
Why do alcohol binges predispose to hypoglycemic attacks?
Alcohol reduces the livers ability to cope with change to glucose levels in plasma so there’s reduced release of glucose into the blood when your drunk.
What is the best test to determine a Px’s glucose control over the last 2-3hours?
Glucosuria test
Which test would best establish a patient’s current level of glycaemic control?
Blood glucose test
Which test would best establish a Px’s long term level of glycaemic control?
Haemoglobin A1c test
What is the most common SE of metformin?
GI disturbance
What is the most common SE of sulfonylurea’s?
Hypoglycemia
Px w T1DM should aim for what blood glucose levels (pre and post prandial)?
Pre: 4-7mmol/L
Post: Under 9mmol/L
What is the clinical definition for hypoglycemia?
Glucose levels under 3mmol/L