Type 1 Diabetes

Question 1

What is type 1 diabetes

Answer 1

Autoimmune disease
Beta cells affected in pancreas causing partial/complete deficiency in insulin thus hyperglycemia

Question 2

Difference in type 2

Answer 2

Acquired insulin resistance

Question 3

What is MODY

Answer 3

mature onset diabetes of the young
Usually monogenic diabetes

Question 4

What is LADA

Answer 4

latent autoimmune diabetes in adults

Question 5

When does type 1 DM develop

Answer 5

Usually in youth

Question 6

Cleavage product with insulin

Answer 6

Proinsulin cleaved into c peptide and insulin

Question 7

• steps of type I DM development?

Answer 7

genetic predisposition → environmental trigger → immune abnormalities but normal insulin → progressive loss of insulin release → overt diabetes with c-peptide → no c-peptide

• stage I: normal blood sugar, more than one autoantibodystage II: abnormal blood sugarstage III: clinical diagnosisstage IV: long standing type 1 diabetes

Question 8

Stages of type 1 dm

Answer 8

stage I: normal blood sugar, more than one autoantibody

stage II: abnormal blood sugar

stage III: clinical diagnosis

stage IV: long standing type 1 diabetes

Question 9

Where are beta cells located

Answer 9

Pancreatic islets of langerhanss, cytological changes after immune infiltration

Question 10

• clinical relevance of immune basis of disease?

Answer 10

other autoimmune conditions more common in self + relatives

more complete destruction of beta cells

possible immune modulation treatment in the future

Risk of autoimmunity in relatives

Question 11

Primary step in immune deficiency

Answer 11

autoantigen presented to autoreactive CD4+ T-lymphocytes

• CD4+ → activate CD8+ → lyse beta cells expressing auto-antigen

Exacerbated by pro inflammatory cytokines

Underpinned also by defects in T regulatory cells

Question 12

What happens after the autoantigen is presented to auto reactive CD4+ T lymphocytes

Answer 12

CD4+ → activate CD8+ → lyse beta cells expressing auto-antigen

Question 13

what aids this process?

Answer 13

Pro inflammatory cytokines expression and defects in T reg cells
Some beta cells can be ,left thus some insufficient insulin made

Question 14

What is the HLA-DR gene responsible for

Answer 14

MHC II

Question 15

Significance of different alleles

Answer 15

associated with different risk levels for diabetes, some dependent also on ethnicity

Question 16

possible environmental factors?

Answer 16

enteroviral infection, cow’s milk protein exposure, seasonal variation, microbiota changes

Question 17

what is the significance of pancreatic autoantibodies?

Answer 17

detectable in sera of those with type I at diagnosis. recommended as diagnostic tool

Question 18

Different types of autoantibodies include

Answer 18

insulin antibodies IAA
GAD-65 glutamic acid decarboxylase
IA-2 insulinoma associated 2 antibodies ZnT8 zinc transporter 8

Question 19

what is the diagnosis of diabetes based on?

Answer 19

presence of clinical features + ketones

Question 20

various effects of insulin deficiency?

Answer 20

protein lysis in muscles → amino acid metabolism

increased hepatic glucose output

lipolysis in adipocytes → glycerol + non-esterified fatty acids

Question 21

• how and where are ketone bodies usually formed?

Answer 21

from fatty acyl-CoAs in liver e.g. → acetyl-CoA, acetoacetate then acetone and 3OHXB forms ketone bodies

Question 22

hormonal regulation of ketone production

Answer 22

upregulated by glucagon and suppressed by insulin usually

Question 23

Principal aims of diabetes treatments

Answer 23

maintain glucose levels, avoid excessive hypoglycaemia

restore physiological insulin profile or close

avoid micro and macrovascular complications

prevent acute metabolic decompensation

Question 24

acute complications of diabetes?

Answer 24

diabetic ketoacidosis

hypoglycaemia from treatment

Question 25

chronic complications?

Answer 25

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

Question 26

physiological insulin profile characteristics?

Answer 26

prandial peak (i.e. after meals) with two phases (peak and mini peak) baseline insulin steady but not zero. This prevents ketoacidosis

Question 27

different types of insulin?

Answer 27

human insulin (actrapid), insulin analogues e.g. Lispro, Aspart, Glulisine → short acting, take with meals zinc or protamine bound e.g. NPH, insulin analogues e.g. Glargine, Determir, Degludec → long acting, background/basal - short-acting = 3x a day after meals long acting - 1x a day

Question 28

When to take different types of insulin

Answer 28

short-acting = 3x a day after meals long acting - 1x a day Or twice daily intermediate acting insulin

Question 29

What do insulin pumps do

Answer 29

continuous delivery of short acting insulin into subcutaneous space

Question 30

principles of dietary education in diabetes?

Answer 30

carb counting, adjusting dosage based on food carbohydrate content, try sub refined carb foods with complex carb foods - insulin pump that can detect glucose intake → calculate and adjust insulin dose

Question 31

what are closed loop systems?

Answer 31

insulin pump that can detect glucose intake → calculate and adjust insulin dose

Question 32

- how does transplantation work as a treatment option?

Answer 32

islet cell transplants → islets isolated from deceased donor → transplant into hepatic portal vein simultaneous pancreas and kidney transplants However require lifelong immunosuppresion

Question 33

How are glucose levels monitored

Answer 33

capillary blood glucose continuous glucose monitoring via pump HbA1c

Question 34

What is HbA1C

Answer 34

glycated haemoglobin → reflects last 3 months of glycaemia

Question 35

what factors can throw off HbA1c accuracy?

Answer 35

altered erythropoiesis e.g. increased in iron/B12 deficiency. Decrease in high epo,iron,b12,reticulocytosis haemoglobinopathies/altered haemoglobin may increase/decrease variable glycation e.g. increased in excess alcohol,chronic renal failure and decreased Intra erythrocyte pH variable in genetic factors, and low in aspirin, vit C/E,certain haemoglobinopathies erythrocyte destruction increased HbA1c in splenectomy and increased erythrocyte life span, decreased in haemoglobinopathies,splenimegaly,drugs such as antiretroviral ribavirin and dapsone

Question 36

how is diabetic ketoacidosis diagnosed?

Answer 36

blood pH < 7.3, ketones (urinary or capillary) increased, HCO3- < 15 mmol/L, glucose > 11 mmol/L Can be a presenting feature of new onset type 1 diabetes and can occur in those who have diabetes (acute illness,missed insulin dose, inadequate insulin dose)

Question 37

numerical definition of hypoglycaemia?

Answer 37

glucose less than 3.6 mmol/L

Question 38

what defines severe hypoglycaemia?

Answer 38

situation requires 3rd party assistance

Question 39

When can severe hypoglycemia become a problem

Answer 39

excessive frequency (can get worse), impaired awareness, nocturnal/recurrent severe hypoglycaemia Leads to seizures/coma/death Impacts cognition,driving,day to day function and emotional wellbeing

Question 40

Who is at risk of hypoglycemia

Answer 40

everyone with type I DM, especially if: meals missed, exercise too much, alcohol, inappropriate insulin regime/dose adjustment, low hbA1c or lack of training around dose adjustment for meals

Question 41

- how is hypoglycaemia acutely managed?

Answer 41

- if concerned about swallow? IV access → 20% glucose If unable to give via iv then subcutaneous injection of glucagon - if swallow intact? (Alert vs drowsy oral carbs → buccal glucose rapid acting juice or sweetse.g. hypostop, glucogel longer acting sandwhich → complex carbs If aware and swallow intact Rapid acting give sweets or juice Long acting give sandwiches If deteriorating then give IM glucagon

Question 42

How does DKA pt present

Answer 42

Hyperglycemia Low insulin

Question 43

How often should HBA1C be checked

Answer 43

Every 3-4 ,months

Question 44

Symptoms and signs of diabetes type 1

Answer 44

Symptoms-Polyuria polydipsia blurring of vision recurrent infections weight loss and fatigue Signs-dehydration cachexia hyperventilation smell of ketones glycosuria ketonuria

Question 45

Adrenergic and neuroglycopaenic symptoms

Answer 45

Adrenerguc Tremors Palpitations Sweating Hunger Neuroglycopaejic Somnolence Confusion In coordination Seizures Coma

Question 46

What do you give of the pt has hypoglycemia abd deteriorating

Answer 46

1mg glucagon