DIabetes - Aetiology and Clinical features Flashcards
What are the genetic mutations most closely associated with type I diabetes?
- HLA-DR3-DQ2
- HLA-DR4-DQ8
- Both
What is the cause of type I diabetes mellitus?
Autoimmune destruction of pancreatic beta cells
What autoimmune diseases is type I diabetes associated with?
- Thyroid disease
- Coeliac Disease
- Addison’s disease
- Pernicious Aneamia
What age group does type I diabetes most commonly present in?
Children - peak incidence in adolescence
What is the chance of an identical twin of someone with Type 1 diabetes developing type 1 diabetes?
30-50%
What proportion of diabetes is type II diabetes?
90%
What are thought to be factors which increase the risk of developing type II diabetes?
- Age
- Obesity
- Ethnicity
- Family history
- Low birth weight
- Lack of exercise
- Alcohol excess
What is the metabolic syndrome?
A clustering of at least three of the five following medical conditions
- Abdominal obesity - BMI > 30 or increased waist circ
- High blood pressure - >/= 130/85
- High blood sugar - fasting glucose > 5.6 mmol/L
- High serum triglycerides - > 1.7 mmol/L
- Low HDL levels - <1.03 mmol/L male/<1.29 mmol/L female
It is associated with the risk of developing cardiovascular disease and type 2 diabetes
In essence, what pathophysiologically is occuring in type II diabetes?
Decreased insulin production + increased peripheral insulin resistance
In essence, what pathophysiologically is occuring in type I diabetes?
Insulin production ceases
What are the clinical features of diabetics as an acute presentation?
Classic triad:
- Polyuria
- Polydipsia
- Weight loss
Plus others
- Tiredness
- Blurred visions
- Erectile dysfunction
- Neuropathic pain
- Lethargy
- Frequent infection - thrush, UTI
What are secondary causes of diabetes?
- Steroids
- Pancreas - surgery, trauma, cancer, pancreatic destruction (CF, and haemochromatosis) Haemochromatosis, pancreatitis
- Endocrine - Cushing’s, Acromegaly, Phaeochromocytoma, hyperthyroidism, pregnancy
- Glycogen storage diseases
- Congenital Lipodystrophy
Why do individuals with diabetes get poluria?
Due to the osmotic diuresis that results when blood glucose levels exceed the renal threshold
Why can individuals with diabetes present with polydipsia?
Due to the resulting loss of fluid and electrolytes
Why do individuals present with weight loss in diabetes?
Due to fluid depletion and the accelerated breakdown of fat and muscle secondary to insulin deficiency.
What are the main ways individuals with diabetes can present?
- Acutely
- Subacutely
- As a consequence of complications
- Asymptomatically
How might someone with present with diabetes subacutely?
Clinical onset may be over several months or years:
- Thirst, polyuria and weight loss are typically present
- Patients may complain of:
- Lack of energy
- Visual blurring
- Pruritus vulvae
- Balanitis
What complications of diabetes might someone present with?
- Staphylococcal skin infections (ie low grade infections)
- Retinopathy noted by optician
- Polyneuropathy - tingling and numbness in the feet
- Erectile dysfunction
- Arterial disease - resulting in MI or peripheral gangrene.
What signs might you see in someone with diabetes?
- Weight loss
- Dehydration - reduced skin turgor
- Ketone breath
- Acnathosis nigricans
- Complications
- Retinopathy
What is the following?
Acanthosis nigricans - A grey-black, papillomatous thickening of the skin at the flexor areas. It is usually symmetrical and feels akin to velvet. Acanthosis nigricans (AN) is most common around the posterolateral neck, axillae, groin and abdominal folds.
What is the general mechanism behind the development of acanthosis nigricans?
The mechanism is complex, with most cases occurring in the presence of insulin resistance. This leads to hyperinsulinaemia, which in turn stimulates the proliferation of keratinocytes (which contain melanin) and fibroblasts.
What is maturity onset diabetes of the young?
MODY
Refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production.
MODY is often referred to as “monogenic diabetes” to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes and environmental factors
What are features of MODY?
Depends on mutation type:
- At birth - glucokinase mutation
- Adolescence - transcription factor mutations
Glucokinase - stable hyperglycaemia which can be dieat controlled
Transcription factors - progressive hyperglycaemia
Will present before age 25
What is the most common type of MODY?
HNF1A - decreased insulin secretion,
(HNF1B, HNF4A and glucokinase diabetes are less common)
What is latent autoimmune diabetes in adults (LADA)?
A form of diabetes mellitus type 1 that occurs in adulthood, often with a slower course of onset than type 1 diabetes diagnosed in juveniles. Adults with LADA may initially be diagnosed incorrectly as having type 2 diabetes based on their age, particularly if they have risk factors for type 2 diabetes such as a strong family history or obesity.
What are features of LADA that may help distinguish it from type II diabetes?
- Leaner build
- Rapid progression to insulin therapy following an initial response to other therapies
- Presence of circulating islet autoantibodies.
Tends to affect thsoe aged 30-50
What antibodies are diagnostic of LADA?
GAD antibodies
What features might help you distinguish between type I and type II diabetes?
- Type I - more likely to present acutely or in DKA, persistent hyperglycaemia despite modifications,
- Type II - often asymptomatic/poresent with complications in older patients
What conditions is type 2 linked with?
Alzeimers, PCOS, Cushing’s, pancreatic cancer
What blood test can show the difference between type 1 and type 2?
C peptide - C peptide is relaeased at the same time as insulin so is a useful marker of insulin production. (And obvs won’t be produced in type 1 because its type 1)
When does gestational diabetes develop in pregnancy?
2nd/3rd trimester - to do with hormonal changes from placenta, along with growth depands of foetus.
What neonatal problems can gestational diabetes predispose to
Macrosomia, respiratory distress, and hypoglycaemia
