type 1 diabetes

Question 1

what is the pathophysiology of type 1 diabetes

Answer 1

autoimmune condition in which insulin producing b-cells of pancreas are attacked and destroyed by the immune system.

Question 2

result of pathology in type 1 diabetes biochemiclaly and clinically

Answer 2

partial or complete defficiency of insulin production leading to hyperglycemia which requires life long treatment

Question 3

(ALSO see diagram on ppt slide 7) - what diabetes classifications did WHO verify in 2019? (5)

Answer 3

type 1
type 2
other
unclassified
during pregnanct

Question 4

what is monogenic diabetes?

Answer 4

some different types of diabetes in the “other” category that are all caused by a specific gene mutation (caused by one gene: monogenic).

so the genetic component is a direct cause rather than predisposition as in other types.

Question 5

what are some examples of monogenic diabetes?

Answer 5

MODY (maturity onset diabetes of he young) mitochondrial diabetes

Question 6

what type of diabates (1/ 2) can monogenic diabetes phenotypically present as? (what is the common misconception?)

Answer 6

can be both, in the past many people think mainly of type 2

Question 7

after what kind of condition can diabetes commonly follow?

Answer 7

pancreatic damage or other endocrine disease :ex. cystic fibrosis

Question 8

in what types of diabetes can you get diabetic ketoacidosis? and common misconception

Answer 8

both 1 and 2 (misconception: only in 1 )

Question 9

what age can t2d prenet in?

Answer 9

most common in older but can be childhood too

Question 10

can autoimmune diabetes present in later life?

Answer 10

YES latent autoimmune Diabetes in adults LADA, in every decade of life

Question 11

what is a difficulty experts face considering that type 1 can develop later in adults?

Answer 11

clinicians are faced with a challenge trying to differentiate adult onset type 1 diabetes form the much large number of cases of type 2

Question 12

what are the stages of development of type 1 diabetes? (look at graph slide 10 b-cell mass over age)

Answer 12

b cell mass normal:
1) genetic predisposition
2) potential precipitating event

b cell mass declining:
3) overt immunological abnormalities (ex. self antibodies present ect) - 1 autoantibody
normal insulin release

> or= 2 autoantibodies:
4) progressive loss of insulin release
glucose normal

5) overt diabetes
c- peptide present (representing: some self insulin )

6) no c peptide present

Question 13

which component(s) of the immune system are defective in type 1 diabetes?

Answer 13

both

Question 14

explain firefly process of autoimmunity in type 1 d (check diagram slide 13)

Answer 14

1) APC presents auto anitgen to CD4
2) CD4 T cell activates (b cell and ) CD8 t cell
3) cd8 goes to islets and starts lysing beta cells in pancreas expressing auto antigen
4) this is exacerbrated by inflammatory cytokines (released by the lysed cells?)
this is also supported by defective (wrongly trained from thymus) T reg cells that fail to supress autoimmunity

Question 15

do all type 1 diabetes patients eventually lose all their insulin production? does that matter in terms of treatment?

Answer 15

Some people with type 1 diabetes continue to produce small amounts of insulin
Not enough to negate the need for insulin therapy

however Even this little is good, in research they were less likely to have complicaitons and less likely to have low blood sigars after treat ect

Question 16

what us the gene that detemrones siceptibility to type 1 diabetes?

Answer 16

HLA-DR gene

Question 17

what allleles are significant risk?

Answer 17

DR3 DR4

Question 18

WHAT ALLeles only have slight risk?

Answer 18

DR1, DR5, DR8 (neutral/ slight risk)

Question 19

what alleles have different effects on specific ethnic groups?

Answer 19

DR9 (Risk in Chinese, Japanese, Korean descent)
DR7 (Protective. Risk in African descent)

Question 20

what are 4 categories of functions of loci that have been identified on people with t1d in gneome wide associations?

Answer 20

insulin production and metabolism,
immunity
b cell apoptosis protection
unknown function

Question 21

what are some factors that have been associated as evironmental triggers of t1d.

Answer 21

-Enteroviral infections
-Cow’s milk protein exposure
-Seasonal variation: less patients showing up in summer
-Changes in microbiota

Question 22

at what stage of t1d are pancreatic autoantibodies most apparent in sera of patients? (why?: not in bullets but key for understanding)

Answer 22

at diagnosis, because down the line the more the b cells are destroyed over years., there isnt anything to attack any more really so antibodies decrease

Question 23

what does NICE recommend we use pancreatic autoantibody levels for? what specific antibodies/ substances?

Answer 23

diagnosis,
Insulin antibodies (IAA)
Glutamic acid decarboxylase (GAD-65) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2)
Zinc-transporter 8 (ZnT8)

Question 24

symptoms of t1d

Answer 24

4ts:
thirsty
thinner
tired
toilet polyuria and nocturia

blurring of vision
reccurent infections eg thrush

Question 25

signs of t1d (dont come holding some gun kon)

Answer 25

dehydration cachexia (muscle wasting) hyperventilation smell of ketones glycosuria ketonuria

Question 26

why may you have cachexia and weigh loss (one of the mechs) in t1d? (muscle wasting

Answer 26

because the body cant use glucose for energy so it uses stored fat (lipolysis resulting in nefa and gly) and protein from muscles (proteinolysis gives aas) also glycolysis from liver

Question 27

why may you hyperventilate in t1d?

Answer 27

if you have ketoacidosis, blood body tries to excrete as much co2 as possible by hyperventilating to make the blood less acidic (co2- carbonic acid in blood- acidic blood)

Question 28

what are the main components to make a t1d diagnosis and what are some aditional less essential ones?

Answer 28

1) clinical features 2) presence of ketones potentially also pancreatic autoantibodies and c peptide

Question 29

what does DKA stand for

Answer 29

diabetic ketoacidosis

Question 30

what are 3 ketone bodies

Answer 30

acetyl coA acetoacetate acetone + 3 OH-B

Question 31

in what organ/cell does the conversion of fatty acyl coa to ketone bodies happen?

Answer 31

in liver- hepatocyte

Question 32

which pancreatic hormone inhibits and which prommotes acyl coa to ketone body conv?

Answer 32

insulin inhibits glucagon promotes

Question 33

what is NEFA and what is fatty acyl coa

Answer 33

non esterified fatty acid (means not bound to acyl group- means free fatty acid), and fatty acil co ais bound...

Question 34

What is the role of NEFA in ketogenesis?

Answer 34

NEFA are another substrate (other than glucagon) that can be converted to ketone bodies

Question 35

what are the aims of type 1 diabetes treatment?

Answer 35

(glucose, insulin, ketones, complications) prevent acute metabolic decompensation (crises such as ketoacidosis ect.) restore a close to physiological insulin profile maintain glucose levels without excessive hypoglycaemia prevent microvascular (eyes) and macrovascular complications (ischaemic heart disease for ex.)

Question 36

complications of hyperglycemia acute

Answer 36

diabetic ketoacidosis

Question 37

complications of hyperglycaemia chronic 2 types and examples

Answer 37

macrovascular: ischaemic heart disease, cerebrovascular disease, peripheral vascular disease and microvascular : retinopathy, neuropathy, nephropathy

Question 38

what are the different methods of management of type 1 diabetes and what type of condition is diabetes considered in terms of management?

Answer 38

-self-managed condition - insulin treatment - dietary support / structured educations - technology (the new glu level monitor) - transplantation (pump)

Question 39

what is a physiological insulin profile (see slide 25)

Answer 39

insulin is never completely suppressed, there is basal insulin which has a flat profile prandial (post food) peak has 2 phases ( first is high peak, then lower peak then drops towards basal)

Question 40

In treatment, how is this pattern of insulin replicated?

Answer 40

1) different types of insulin given for the different insulin levels (prandial and basal) - short- quick acting/ long acting: basal (theres also an intermediate acting type) 2) different frequencies of administration for each type

Question 41

what is short acting insulin (molecular level) and examples of brands?

Answer 41

either exact molecular replicate of human insulin (actrapid) or insulin analogue (lispro, aspart, glulisine)

Question 42

what is long acting insulin (molecular level)+ brands

Answer 42

either insulin bound to zinc or protamine (neutral protamine hagedorn (NPH) OR insulin analogue (glargine, determir, degludec)

Question 43

what is the typical basal bolus regime

Answer 43

3/d prandial: short acting after each meal 1/ d long acitng OR 2/ day if intermediate acting is used

Question 44

what does the insulin pump do (doses/ freq and method) and what do you have to do?

Answer 44

general: insulin delivered in subcutaneous space for bolus insulin: 1) you need to actively set it for when you have meals 2) pump can do continuous delivery (meaning not just injection at once, it can give the dose slowly over a few minutes/ hour?) of short acting insulin analogue for long acting: 1) programme the device to deliver fixed units/ hour throughout the day (basal)

Question 45

what are some benefits of the insulin pump and what is the single greatest benefit

Answer 45

variable basal rates : biggest benefit extended boluses greater flexibility

Question 46

what are the 3 principles of dietary advice for people with t1d?

Answer 46

1) dose adjustment for carbohydrate content food 2) all patients should recieve training for cRBOHDRATE COUNTING 3) substitution of refined carbohydrate containing foods where possible

Question 47

nice guidlines dor type 1 diabetes (training patients related) 3 points

Answer 47

All people with type 1 diabetes should be offered a Structured Education Programme e.g. DAFNE (dose adjustment for normal eating) but many others 5 day course on skills and training in self-management

Question 48

what is a hybrid closed loop system

Answer 48

implant of 2 devices that commnicate: 1) real time continuous glucose sensor (new thing) 2) glucose pump: a) will use an algorithm to calc insulin req from gluc level

Question 49

Is hybrid closed loop system available on NHS?

Answer 49

yes

Question 50

where do you get the cells for a islet cell transplant?

Answer 50

1) isolate human islets from pancreas of deceased donor

Question 51

where do you transplant the derived islet cells form donor?

Answer 51

Transplant into hepatic portal vein

Question 52

what other action is required for islet cell transplant to work

Answer 52

life long immunosupression

Question 53

what procedure increases the survival of pancreas graft?

Answer 53

a simultaneous pancreas and kidney transplant: transplanting the pancreas graft ALONG WITH KIDNEYs (we dont know why exactly) again requires life long immunosupression

Question 54

what is the aim/ benefits of transplants?

Answer 54

try to restore physiological insulin production to the extent that insulin can be stopped Even if incomplete, often results in better control

Question 55

limitations fo transplants

Answer 55

Limitations: availability of donors, complications of life-long immunosuppression

Question 56

how do people without the continuous glucose monitoring device monitor glucose levels?

Answer 56

with capillary (finger prick) blood glucose monitoring

Question 57

what does HBA1c reflect and why so?

Answer 57

last 3 months of glycaemia bc thats the lifepsan of a rbc and HBA1c is basically glycated haemoglobin

Question 58

what is a disadvanatge of HbA1c?

Answer 58

-Biased to the 30 days preceding measurement means that if reflects more the glu levels in the past 30 days bc old glycated rbcs are starting to get replaced by new rbcs

Question 59

what is the difference between glycosylation and glycation and which process ois relevant to HbA1c

Answer 59

glycosylation is enzymatic- glycation is non enzymatic so its a linear chemical reaction relevant is glycation

Question 60

what is the first step of the glycation reactions of hb? is it fats or slow ? is it an equillibrium?

Answer 60

N-terminal valine residue b-chain and glucose -----> <----- (equilibrium) Schiff base its fast- takes hours

Question 61

what is the second step of the glycation reactions of hb? is it fats or slow ? is it an equillibrium?

Answer 61

slow-takes days Schiff base----> Amadori product (HbA1c)

Question 62

is this glycation a reversible reaction?

Answer 62

no

Question 63

other reasons why HBa1c is not a perfect measurement

Answer 63

(slide 36)

Question 64

what is used to guide insulin doses?

Answer 64

self-monitoring of blood glucose results at home and HbA1c results every 3-4 months

Question 65

what are acute complications from type 1 diabetes?

Answer 65

Diabetic ketoacidosis Uncontrolled hyperglycaemia Hypoglycaemia

Question 66

what are acute complications of t1d

Answer 66

Diabetic ketoacidosis Uncontrolled hyperglycaemia Hypoglycaemia

Question 67

when is ketoacidosis more common? (type of diabetes and phase in disease)

Answer 67

new onset type 1 diabetes (but can occur in any type)

Question 68

what are some triggers of ketoacidosis

Answer 68

Acute illness Missed insulin doses Inadequate insulin doses

Question 69

is ketoacidosis life threatening?

Answer 69

yes

Question 70

Diabetic ketoacidosis diagnosis. (4 things)

Answer 70

pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L

Question 71

how common (not percentage expected just describe) is hypoglycaemia in type 1 diab patients?

Answer 71

To some extent an inevitable feature of the self-management of type 1 diabetes bc: Lost normal physiology and homeostasis’

Question 72

numerical def of hypoglycaemia

Answer 72

(variable) <3.6 mmol/L

Question 73

what is meant by severe hypoglycaemia?

Answer 73

any event requiring 3rd party assistance (this just means you lose ability to self manage, doesn’t mean you have too low level of glu-

Question 74

when can hypoglycaemia become a problem>?

Answer 74

Excessive frequency Impaired awareness (unable to detect low blood glucose) (lack of adrenergic symptoms ) (i think this is severe hypoglycaemia) Nocturnal hypoglycaemia (this is also severe) Recurrent severe hypoglycaemia

Question 75

risks of hypoglycaemia

Answer 75

Seizure / coma/ death (dead in bed) Impacts on emotional well-being Impacts on driving Impacts on day to day function Impacts on cognition

Question 76

role of HbA1c in hypoglycaemia identifiction?

Answer 76

HbA1c itslef may not be helpful

Question 77

what are some risk factors for hypoglycaemia

Answer 77

Exercise Missed meals Inappropriate insulin regime Alcohol intake Lower HbA1c Lack of training around dose-adjustment for meals

Question 78

strategie sto support problematic hypoglycaemia

Answer 78

Indication for insulin-pump therapy (CSII) May try different insulin analogues Revisit carbohydrate counting / structured education Behavioral psychology support Transplantation

Question 79

acute management of hypoglycaemia if alert and orientated

Answer 79

Oral Carbohydrates Rapid acting; juice / sweets Longer acting; sandwich

Question 80

acute management of hypoglycaemia: Drowsy / confused but swallow intact

Answer 80

Buccal glucose e.g. Hypostop / glucogel Complex carbohydrate

Question 81

acute management of hypoglycaemia:Unconscious or concerned about swallow

Answer 81

IV access 20% glucose IV 20% glucose IV

Question 82

if Deteriorating / refractory /insulin induced /difficult IV access?

Answer 82

consider IM /SC 1mg Glucagon

Question 83

is giving cake a good way to spike sigars?

Answer 83

no, if has fat, slows doen glu bsorption, you want pure sugar like choc, sweets ect

Question 84

why important language matters

Answer 84

What you tell them they think of that after bc they carry the diseas ewith them, so its better to use motivating language this matter sbc its a self managed disease, so psych infl how well they manage themselves

Question 85

phrases to avoid

Answer 85

poor control’ ‘diabetes sufferer’ ‘not coping’ ‘poor compliance’ ‘how’s your control’ ‘they’re diabetic’ ‘you can’t eat that’

Question 86

more motivaitn emowering stuff

Answer 86

person living with diabetes’ ‘it sounds like your diabetes has been challenging to manage recently’ ‘what are your thoughts on your recent glucose levels’ ‘let’s talk through different options and see what suits you’