Diabetes mellitus type 1 & 2 (E&M) Flashcards
Define T1DM.
Metabolic disorder characterised by hyperglycaemia due to absolute insulin deficiency (–> lipolysis and ketogenesis) - develops due to destruction of pancreatic beta cells, mostly by immune-mediated mechanisms
When does T1DM manifest commonly?
Childhood
What gene is T1DM associated with?
HLA DR3/4
What may we see in Fx of someone with T1DM?
Autoimmune disease
Why are T1DM patients prone to ketoacidosis?
Do not have sufficient insulin to suppress ketone body production, whereas T2DM patients have enough for this
What autoantigens are associated with T1DM? (4)
- glutamic acid decarboxylase (GAD)
- insulin
- insulinoma-associated protein 2
- cation efflux zinc transporter
Define T2DM.
Progressive disorder defined by deficits in insulin secretion and increased insulin resistance that lead to abnormal glucose metabolism and related metabolic derangements
Insulin resistance (decreased insulin sensitivity) and relative insulin deficiency (insulin production reduces over time)
What causes T2DM?
Strong genetic component and association with obesity and a sedentary lifestyle
- genetic and environmental
- obesity
- pancreatic disease e.g. chronic pancreatitis
- endocrine disease e.g. Cushing’s, acromegaly, phaeochromocytoma, glucagonoma
- drugs e.g. corticosteroids, atypical antipsychotics, protease inhibitors
- circulating autoantibodies to the extracellular domain of the insulin receptor
What is mature onset diabetes of the young (MODY)?
- onset of T2DM <25 years old
- autosomal dominant inheritance
What do we often see in Fx of MODY?
Early onset diabetes
What are the general clinical features of diabetes mellitus? (7)
- hyperglycaemia
- polyuria
- polydipsia
- nocturia
- unexplained weight loss
- fatigue
- increased susceptibility to infection
How does T1DM present in 1/3 of cases?
Diabetic ketoacidosis is the 1st manifestation in 1/3 of cases
How does T1DM present specifically? (5)
- DKA
- nausea and vomiting
- abdominal pain
- Kussmaul breathing –> deep, rapid breathing
- sweet smelling breath
How does T2DM present specifically? (5)
- asymptomatic
- some may present with hyperosmolar hyperglycaemic state (HHS) - BGC very high >40mmol and severe dehydration and confusion
- acanthosis nigricans (hyperpigmentation)
- infections - candidal, skin, UTIs
- blurred vision
What might you see on examination of a patient with T2DM?
- necrobiosis lipoidica diabeticorum (well-demarcated plaques on shins or arms with shiny atrophic surface and red-brown edges)
- granuloma annulare (flesh-coloured papules coalescing in rings on back of hands and fingers)
- diabetic dermopathy (depressed pigmented scars on shins)
Why might gastroparesis happen in diabetes mellitus patients?
Neuropathy of vagus nerve
How might gastroparesis present in DM? (3)
- bloating
- vomiting
- erratic blood glucose control
What is the main risk factor for T1DM?
- genetic predisposition (HLA-DR3/4 variation)
- (geographical region, infectious agents, dietary factors = weak)
What are some risk factors for T2DM? (11)
- obesity
- hypertension
- South Asian/Afro-Caribbean ethnicity
- older age
- gestational diabetes
- Fx T2DM
- PCOS
- non-diabetic hyperglycaemia
- dyslipidaemia
- CVD
- stress
What are the 1st line investigations ordered for diabetes mellitus?
- fasting plasma glucose >/=7mmol/L
- HbA1c >/=48mmol/mol (not in children, pregnant, blood transfusions/abnormalities - may be falsely normal)
- oral glucose tolerance test (OGTT): 2-hour post-load glucose after 75g oral glucose >/=11.1mmol/L
- random plasma glucose >/=11.1mmol/L
- (T1DM in adults = clinical diagnosis)
What other investigations are considered for T1DM? (3)
- plasma or urine ketones
- C-peptide (should be low)
- autoimmune markers (autoantibodies to GAD, insulin, islet cells, islet antigens IA2 and IA2-beta, and zinc transporter Zn8)
What other investigations are considered for T2DM? (9)
- fasting lipid profile
- urine ketones
- ACR
- serum creatinine and eGFR
- ECG
- ankle-brachial pressure index (ABPI)
- random C-peptide
- autoantibody testing
- LFTs
What is HbA1c a measure of?
Average blood glucose over last 3 months
What HbA1c level is diagnostic of diabetes?
> =48 mmol/mol
What HbA1c level is pre-diabetes?
42-47 mmol/mol
What factors affect HbA1c reading?
- Lower than expected (due to reduced RBC lifespan):
- sickle cell
- G6PD deficiency
- hereditary spherocytosis
- Higher than expected (due to increased RBC lifespan):
- vitamin B12/folate deficiency
- iron deficiency anaemia
- splenectomy
What is the diagnostic criteria for diabetes mellitus?
- symptoms + random plasma glucose >=11.1mmol/L OR
- fasting plasma glucose >=7mmol/L OR
- plasma glucose >=11.1mmol/L 2h after 75g oral glucose OR
- HbA1c>=48mmol/mol
- if asymptomatic with abnormal HbA1c or fasting glucose: must be confirmed with a repeat abnormal reading on a different day before diagnosis
What is impaired fasting glucose (IFG) defined as?
6.1-6.9 mmol/L
What is impaired glucose tolerance (IGT) defined as?
- fasting plasma glucose <7.0mmol/L (IFG) AND
- OGTT 7.8-11.1mmol/L