Diabetes Flashcards
How many people in UK are obese? How many of these have diabetes?
1/3 are obese
1/3 of obese will get diabetes within 8 years
How many people in USA have diabetes?
10% (increasing)
Where is insulin made?
B cells in pancreas
Where is glucagon made?
A cells in pancreas
What do B cells in pancreas make?
insulin
What do A cells in pancreas make?
glucagon
What do D cells in pancreas make?
Somatostatin
How is insulin stored?
pro-insulin
what is cleaved off to create insulin?
C peptide - cleaved from proinsulin
What is an issue with injected insulin?
C peptide : insulin ratio is not 1 : 1
What are the sources of glucose?
Food and liver
What happens to glucose in body?
stored/used in muscles
excreted via kidneys if in excess
What does insulin do?
stops liver releasing glucose (liver stores glucose as glycogen or it can produce glucose)
encourages muscles to take up glucose
What is an ave blood glucose?
4-7 mmol/L
What can blood glucose be after large carb meal?
> 11 mmol/L
What can blood glucose be after lots of exercise?
Define diabetes
A metabolic disorder characterised by chronic hyperglycaemia resulting from defects in insulin secretion, insulin action or both
What are the relative causes for lack of insulin? x2
- reduced insulin production (autoimmune)
- insulin does not work as well
How does obesity affect insulin resistance?
increase weight = other hormones released = mutations to receptor and 2nd messengers = insulin doesn’t bind as well to receptors / 2nd messengers don’t work as well
= insulin resistance
What happens if not enough insulin produced?
- liver keeps working (including overnight)
- excess glucose excreted via kidneys (urine test)
- can’t get glucose into muscles (fatigue, weak muscles)
How is cut off point for blood glucose defined for diabetic?
epidemiology - define level of blood glucose that causes harm
- cohort studies
- oral glucose tolerance test
11M/m
When can blood glucose test be done? x3
fasting post pranial (after eating) random
When is there the largest difference in blood glucose between normal person and diabetic?
2 hours after eating
When is best time to do blood glucose test to diagnose diabetes?
2 hours after eating
At what blood glucose does the risk of retinopathy (disease of the retina) significantly increase?
11 M/m
What is the relationship between blood glucose and arterial disease?
Proportional - as blood glucose increases, so does arterial disease
What are the blood glucose thresholds for macrovascular damage?
IGT = macrovascular issues
- 6-7m/M when fasting
- 7-11m/M after eating
Diabetes = micro and macrovascular damage
- 7+m/M fasting
- 11m/M after eating
What are the blood glucose thresholds for microvascular damage?
Diabetes = micro and macrovascular damage
- 7+m/M fasting
- 11m/M after eating
How does glucose bind to Hb? What does it form?
glucose binds to terminal valine on Hb = HbA1c
What is the life time for Hb?
3 months
When can you do HbA1c test?
any time - full blood count taken. No need to fast
What does HbA1c tell you?
Blood glucose levels over previous 2-3 months
When should you not use HbA1c test?
- all symptomatic young ppl / children
- any age with suspected type 1
- short duration diabetes symptoms
- ppl at high risk of diabetes and acutely ill
- medication that causes rapid glucose rise eg corticosteroids
If you can’t use HbA1c test, what tests can you use?
Random / fasting / after food blood glucose test
What causes an inaccurate low HbA1c result?
- haemolysis - anaemia
- increased red cell TO due to
1. blood loss
2. HbS (sickle cell anaemia)
3. HbC (abnormal Hb structure)
What causes an inaccurate highHbA1c result?
- persistant HbF (thalassaemia) - ie faulty Hb
- uraemia (carbamylates Hb) - renal failure (not diabetes) - changes ability of cells to bind to glucose, therefore increase in blood glucose
What is normal range for blood glucose at
- fasting
- 2 hour post eating
- HbA1c?
Fasting =
What is IFG (impaired fasting glucose) range for blood glucose at
- fasting
- 2 hour post eating
- HbA1c?
Fasting = >6.1 /
What is IGT (impaired glucose tolerance) range for blood glucose at
- fasting
- 2 hour post eating
- HbA1c?
Fasting = 7.8 /
What is diabetic range for blood glucose at
- fasting
- 2 hour post eating
- HbA1c?
Fasting = >7.0mmol/L
2 hr = >11.1mmol/L
HbA1c = 48
what is the most common test for diabetes?
HbA1c
What causes IFG?
Unknown
Maybe glucose sensitising
What is the risk of IFG progressing to diabetes?
50% = diabetes 50% = rtn to normal
What other diseases are IFG pt likely to get?
Unknown
What is treatment for IFG?
Healthy diet
Yearly glucose checks
How do you prevent progression from IFG to diabetes?
Unknown
What causes IGT?
Insulin resistance
What is the risk of IGT progressing to diabetes?
50% = diabetes 50% = rtn to normal
What other diseases are IGT pt likely to get?
risk of heart disease
cerebral vascular disease
What is treatment for IGT?
diabetic diet
Yearly glucose checks
Tx for cardiac risk
How do you prevent progression from IGT to diabetes?
Exercise weight loss (2kg)
What are the classifications of diabetes?
type 1 - insulin deficiency
type 2 - insulin resistance
gestational diabetes
What else can cause type 1 symptoms?
destruction of pancreas - cancer, alcohol
alcohol can cause recurrent pancreatisis
What else can cause insulin resistance?
Receptor abnormalities
- Leprechaunism (aka Donohue syndrome) - genetic disorder
- insulin resistant syndromes type A and B
- excessive hormones - Cushings, Acromegaly
What type of ppl get type 1?
younger, thinner, fitter ppl
incidence, prevalence, M:F of type 1?
incidence - 1 in 10,000
prevalence - 10 in 10,000
M=F ????CHECK
What plays more of a role in type 1 - genetics vs environ
both genetic and environ
50% other twin get type 1
What is type 1 disease progression?
exposure antigen
expression of antibodies
diabetes
Presentation of type 1?
polyuria (bed wetting) thirst dehydration weight loss (0.5-1 stone in a week) ketoacidosis - muscle burns fat - coma
If you have antibodies against b cells, what % get type 1?
90%
exercise may be able to help reduce risk (can alter immune system)
What is freq detected in type 1 diabetes?
DR3 + DR4+
What is normal insulin range?
4-35 UNITS?!
What is background level of insulin?
4 UNITS?!
Why are new insulins better?
quicker to peak and to disappear
What other insulin delivery methods are there?
insulin pumps
- continuous insulin given
- less hypos, less insulin
- time consuming, costly
- can add sensor to skin to detect insulin and glucagon levels - automatic
Inhaled insulin
- similar to asthma inhalers
- small trials, only 1/10 dose absorbed, long term safety not known
Islet cell transplant
- cells put into LIVER
- no need for insulin
Pancreas transplant
- attached to small intestine in pt (originally also attached to duodenum/small intestine)
Define glucagon
Hormone produced by alpha cells in pancreas.
Released when low blood glucose
promotes liver to breakdown glycogen to glucose in liver
Define glycogen
Liver stores glucose as glycogen
Glucagon causes liver to breakdown glycogen to glucose when blood glucose low
What do you do if type 1 needs a SHORT operation?
give half normal dose of morning insulin
first on list
monitor sugars
cover antibiotics
What do you do if type 1 needs a LONG operation?
In hospital
first on list
sliding scale insulin (ie progressive increase of insulin dose pre-meal / night time) AND IV glucose AND K+
Cover antibiotics
incidence, prevalence, M:F of type 2?
incidence - 1 in 1,000 NB half undiagnosed
prevalence - 10 in 1,000 (1 in 100)
F>M ????CHECK
What plays more of a role in type 1 - genetics vs environ
Genetics
90% twins get type 2
If insulin resistance is high (ie type 2), how can you rtn them to normal?
Increase insulin secretion
What is link between birth weight and type 2?
lower birth weight = increase risk diabetes and heart disease
What is link between genetics and weight gain and type 2?
People that are 60% over the ideal weight have an increased risk of having poor insulin sensitivity if their parents had type 2.
NB ppl at ideal weight have same insulin sensitivity regardless of whether parents had type 2.
If you have a normal weight, how does your risk of getting diabetes change?
It doesn’t.
Risk of diabetes increases if you’re overweight
What is worse - upper or lower body obesity?
Upper body - eg abdomen
What is the two step model for diabetes?
There are 2 steps where risk of getting diabetes can be reduced through DIET, EXERCISE and reducing OBESITY (between steps 1/2 and 2/3)
- genetic predisposition
- Insulin resistance (IGT)
- Relative lack of insulin
- diabetes / hyperglycaemia
What are the non-metabolic presentation of diabetes?
ie diabetic complications
- blurred vision (sugar in ant eye)
- CVA (cerebrovascular accident - aka stroke)
- angina / MI
- intertrigo (rash in skin folds / chafing)
- UTI
- Pruritis vulvae / balanitis (itchy female/male genitals)
- peripheral vascular disease
- peripheral neuropathy
- foot ulcers
What are the metabolic presentation of diabetes?
thirst, polyurea (less acute than type 1)
Treatment for thin people with type 2?
- diet
- exercise
Sulphonylureas
+ Metformin
+ newer drugs
Insulin
Treatment for overweight people with type 2?
- diet
- exercise
- lose weight
Metformin
+ sulphonylureas
+ newer drugs
Insulin
How does sulphonylureas work?
increases insulin release from pancreas
What is indication for sulphonylureas?
Thin type 2 ppl not responding to diet
What are side effects of sulphonylureas?
- hypoglycaemia (40% get this)
- weight gain (decrease blood glucose = increase hunger)
- nausea, anorexia, vomiting
- alcoholic flushing
- skin rash
Name 3 types of sulphonylureas
Tolbutamide
Glibenclamide
Gliclazide
How does metformin work?
sensitises muscles, so increase glucose uptake
What is indication for metformin?
overweight type 2
- not assoc with weight gain
What are side effects of metformin?
nausea, vomiting, diarrhoea
Vit B12 malabsorption
Lactic acidosis
Advantages of metformin?
- cheap
- may protect against cancer
How do thiazolidinediones work?
increases insulin sensitivity
increases muscle uptake
decreases secretion from liver
How do you take thiazolidinediones?
Only licensed for use with other drugs
What are side effects of thiazolidinediones?
- hypo ?
- liver damage
- fluid retention
- weight gain
Give one example of a thiazolidinediones
Rosilitizone
What is a contraindication of thiazolidinediones?
don’t take if family history of bladder cancer
What drugs affect absorption and can used to treat diabetes?
Acarbose - alpha glucosidase inhibitor
- slow glucose absorption
- no hypos
- flatulence
Orlistat - lipase inhibitor
- inhibits pancreatic and gastic lipase (enz which breakdown lipids in GI tract)
- reduces weight and cholesterol
- no hypos
- flatulence
How does Acarbose work?
alpha glucosidase inhibitor
- slow glucose absorption
- no hypos
- flatulence
How does Orlistat work?
lipase inhibitor
- inhibits pancreatic and gastic lipase (enz which breakdown lipids in GI tract)
- reduces weight and cholesterol
- no hypos
- flatulence
Why does acarbose and orlistat give flatulence?
stops complex carb breakdown - reduced glucose uptake from GI tract
- increased glucose in large intestine = fermentation = wind
What are 2 new concepts in managing diabetes?
- the gut
2. kidneys
What is incretin?
hormones that decrease glucose levels by increasing insulin from pancreas.
eg GLP-1
What is the incretin effect?
If glucose taken orally (not via IV) then levels of insulin will increase (measured via increase in c-peptide in blood). Therefore gut releases incretins (eg GLP-1) which increases insulin released from pancreas.
What is GLP-1
an incretin hormone that decrease glucose levels by increasing insulin from pancreas.
How does GLP-1 work?
- after ingesting food, GLP-1 is secreted from L cells, pancreas
- stimulates beta cells in pancreas to secrete more insulin
- suppresses alpha cells in pancreas to reduce postpranial glucagon secretion
- liver reduced glucose output
- stomach slows gastric emptying - stops hunger
- brain promotes satiety (fullness), reducing appetite
How long is GLP-1 around for?
4 mins
Enzyme breaks it down
can block enz - GLP-1 inhibitor / agonist
What happens to incretin effect in type 2?
it is reduced
- ie not enough insulin secreted
name the enz that degrades GLP-1
DPP-4
Name DPP-4 inhibitors
Sitagliptin Linagliptin Alogliptin Vildagliptin Saxagliptin
_____gliptin
SIT on a LINe of ALOG and play the SAX and VILin!
