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Endocrine > Type 1 Diabetes Pathophysiology > Flashcards

Type 1 Diabetes Pathophysiology Flashcards

1
Q

What is type 1 diabetes?

A

Absolute insulin deficiency

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2
Q

What causes type 1 diabetes?

A

An environmental trigger in a genetically susceptible individual mediated by autoimmune processes occurring in pancreatic beta cells

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3
Q

How is type 1 diabetes diagnosed?

A

Fasting glucose >= 7mmol/L, random glucose >= 11mmol/L and symptoms
Often diagnosed in history and presentation alone
GAD/IA2 antibodies and C-peptide may help

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4
Q

Is there a hereditary aspect to type 1 diabetes?

A

Yes = if both parents have type 1 diabetes then the risk of the child developing diabetes is 30%

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5
Q

What is HLA association with type 1 diabetes?

A

Represent 50% of familial risk

Highest risk genotypes confer 19 fold increase in risk

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6
Q

What are the two highest risk genotypes for HLA associated diabetes?

A

DR3-DQ2 and DR4-DQ8 = 95% of type 1 diabetics under 30 have one of both genotypes

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7
Q

How many factors have been identified that cause non-HLA type 1 diabetes?

A

47 factors

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8
Q

What can be some environmental triggers of type 1 diabetes?

A

Viral infection, maternal factors, weight gain

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9
Q

What are some environmental observations associated with type 1 diabetes?

A

Seasonality, timing of birth, only 10% with susceptible HLA develop diabetes

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10
Q

What are some antibodies associated with type 1 diabetes?

A

GAD65 antibodies
IA2 antibodies
IAA antibodies
ZnT8 antibodies

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11
Q

What are some features of GAD65 antibodies?

A

GABA production, 70-80% at diagnosis, increases with age, females <10

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12
Q

What are some features of IA-2 antibodies?

A

Unknown function, 60-70% at diagnosis, decreases with age, male

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13
Q

What are some features of IAA antibodies?

A

Regulates glucose, 50% at diagnosis, better in children

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14
Q

What are some features of ZnT8 antibodies?

A

Zn function in beta cells, 60-80% at diagnosis, better in older patients

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15
Q

What is the pathogenesis of type 1 diabetes?

A

Immune dysregulation
Variable insulitis and beta cell sensitivity to injury
Pre-diabetes then overt diabetes

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16
Q

What are some environmental triggers and regulators of type 1 diabetes pathogenesis?

A

IAA, GAD, loss of first phase insulin, glucose intolerance, C-peptide (positive/negative)

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17
Q

What are is the classical triad of symptoms of type 1 diabetes?

A

Polyuria (enuresis in children), polydipsia and weight loss

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18
Q

What are some general symptoms that may occur in type 1 diabetes?

A

Fatigue and somnolence, blurred vision, in established ketoacidosis, candidal infections (pruritus vulvae, balanitis)

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19
Q

What questions should you consider in a newly diagnosed diabetic?

A

Has diabetes been confirmed? If so, what type is it? (antibody testing)
Is hospitalisation required? (DKA, vomiting, severe ketonuria)
Are they are school/college/uni? If not, are they employed?
Do they drive?

20
Q

What occurs in the initial management of new patients?

A

Blood glucose and ketone monitoring
Carbohydrate estimation, regular DSN and dietician contact
Regular check of prevailing glycaemic control

21
Q

What is the target HbA1c range for diabetics?

A

48-58m/m

22
Q

What insulin regime are new type 1 diabetics usually put on?

A

Usually basal (once daily) - bolus (with meals) regime

23
Q

What is checked in an annual diabetic review?

A

Weight, blood pressure, bloods (HbA1c, renal function, lipids), retinal screening, foot risk assessment

24
Q

What should diabetics keep a record of?

A

Severe hypoglycaemic episodes, admissions for DKA

25
Q

How common is type 1 diabetes in young people?

A

Accounts for 90% of diabetes in patients <25

26
Q

What should intensive insulin therapy be delivered as part of?

A

A comprehensive support package

27
Q

What should an intensified insulin regime in adults include?

A

Either regular human or rapid acting insulin analogues

28
Q

What adult patients are basal insulin analogues recommended in?

A

Patients who are experiencing severe or nocturnal hypoglycaemia and who are using an intensified insulin regime

29
Q

What should insulin therapy for children and adolescents involve?

A

May use either insulin analogues (rapid acting or basal), regular human insulin and NPH preparations (or an appropriate combination of all of the above)

30
Q

What is the normal secretion of insulin after a meal?

A

Biphasic = rapid phase of pre-formed insulin lasts 5-10mins, slow phase lasts over 1-2hrs
Secreted into portal vein

31
Q

What is the rate of insulin secretion in the fasted state in normal patients?

A

0.25-1.5 units/insulin/hr

32
Q

What type of diabetes is most likely to cause neonatal diabetes?

A

Children diagnosed < 6 months old are more likely to have monogenic diabetes rather than type 1 diabetes

33
Q

What is LADA?

A

Latent onset diabetes of adulthood = young adults aged 25-40, male predominance, usually non-obese

34
Q

How is LADA diagnosed?

A

Presence of raised pancreatic autoantibodies in patients with “recently diagnosed” diabetes who don’t initially require insulin

35
Q

What are some features that indicate a diagnosis of LADA in a patient?

A

Autoantibody positive, associated autoimmune conditions, non-insulin requiring at diagnosis, sub-optimal control on oral agents

36
Q

What are some features of the diabetes that can occur in cystic fibrosis patients?

A

Occurs in >25% at 25 years, usually found in severe mutations, complications common, insulin therapy preferred

37
Q

How should cystic fibrosis patients be screened for diabetes?

A

Screening with OGTT from age 10 recommended

38
Q

What occurs in Wolfram syndrome (DIDMOAD)?

A

Diabetes insipidus, diabetes mellitus, optic atrophy, deafness, neurological abnormalities

39
Q

What occurs in patients with Bardet-Biedl syndrome?

A

Often very obese, polydactyly, hypogonadal, visual impairment, hearing impairment, mental retardation, diabetes, often have consanguineous parents

40
Q

What is the chance of a patient having type 1 diabetes when they have been diagnosed < 6 months old?

A

Less than 1%

41
Q

What is the risk of a patient having type 1 diabetes if there is a history of type 1 diabetes in their parents?

A

Between 2-4%

42
Q

How likely is a patient to have type 1 diabetes if they have detectable insulin production >= 3 years after diagnosis and are C-peptide positive with BG >8?

A

Between 1-5%

43
Q

How likely is a patient to have type 1 diabetes if they have undetectable pancreatic antibodies at diagnosis?

A

Between 3-30%

44
Q

What are some autoimmune conditions associated with diabetes?

A 
Common = thyroid disease, Coeliac (5% in T1DM), pernicious anaemia, Addison's disease, IgA deficiency
Rare = autoimmune polyglandular syndromes (both type 1 and 2 diabetes), AIRE mutations, IPEX syndrome
45
Q

What are some polyglandular endocrinopathies associated with diabetes?

A

Addison’s disease, vitiligo, primary hypogonadism and hypothyroidism, Coeliac, mild immune deficiency, primary hypoparathyroidism, pernicious anaemia, alopecia

Endocrine (42 decks)

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