DIabetes - Aetiology and Clinical features

Question 1

What are the genetic mutations most closely associated with type I diabetes?

Answer 1

• HLA-DR3-DQ2
• HLA-DR4-DQ8
• Both

Question 2

What is the cause of type I diabetes mellitus?

Answer 2

Autoimmune destruction of pancreatic beta cells

Question 3

What autoimmune diseases is type I diabetes associated with?

Answer 3

• Thyroid disease
• Coeliac Disease
• Addison’s disease
• Pernicious Aneamia

Question 4

What age group does type I diabetes most commonly present in?

Answer 4

Children - peak incidence in adolescence

Question 5

What is the chance of an identical twin of someone with Type 1 diabetes developing type 1 diabetes?

Answer 5

30-50%

Question 6

What proportion of diabetes is type II diabetes?

Answer 6

90%

Question 7

What are thought to be factors which increase the risk of developing type II diabetes?

Answer 7

• Age
• Obesity
• Ethnicity
• Family history
• Low birth weight
• Lack of exercise
• Alcohol excess

Question 8

What is the metabolic syndrome?

Answer 8

A clustering of at least three of the five following medical conditions

1. Abdominal obesity - BMI > 30 or increased waist circ
2. High blood pressure - >/= 130/85
3. High blood sugar - fasting glucose > 5.6 mmol/L
4. High serum triglycerides - > 1.7 mmol/L
5. 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

Question 9

In essence, what pathophysiologically is occuring in type II diabetes?

Answer 9

Decreased insulin production + increased peripheral insulin resistance

Question 10

In essence, what pathophysiologically is occuring in type I diabetes?

Answer 10

Insulin production ceases

Question 11

What are the clinical features of diabetics as an acute presentation?

Answer 11

Classic triad:

• Polyuria
• Polydipsia
• Weight loss

Plus others

• Tiredness
• Blurred visions
• Erectile dysfunction
• Neuropathic pain
• Lethargy
• Frequent infection - thrush, UTI

Question 12

What are secondary causes of diabetes?

Answer 12

• Steroids
• Pancreas - surgery, trauma, cancer, CF, Haemochromatosis
• Endocrine - Cushing’s, Acromegaly, Phaeochromocytoma, hyperthyroidism, pregnancy
• Glycogen storage diseases
• Congenital Lipodystrophy

Question 13

Why do individuals with diabetes get poluria?

Answer 13

Due to the osmotic diuresis that results when blood glucose levels exceed the renal threshold

Question 14

Why can individuals with diabetes present with polydipsia?

Answer 14

Due to the resulting loss of fluid and electrolytes

Question 15

Why do individuals present with weight loss in diabetes?

Answer 15

Due to fluid depletion and the accelerated breakdown of fat and muscle secondary to insulin deficiency.

Question 16

What are the main ways individuals with diabetes can present?

Answer 16

• Acutely
• Subacutely
• As a consequence of complications
• Asymptomatically

Question 17

How might someone with present with diabetes subacutely?

Answer 17

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

Question 18

What complications of diabetes might someone present with?

Answer 18

• Staphylococcal skin infections
• Retinopathy noted by optician
• Polyneuropathy - tingling and numbness in the feet
• Erectile dysfunction
• Arterial disease - resulting in MI or peripheral gangrene.

Question 19

What signs might you see in someone with diabetes?

Answer 19

• Weight loss
• Dehydration - reduced skin turgor
• Ketone breath
• Acnathosis nigricans
• Complications
• Retinopathy

Question 20

What is the following?

Answer 20

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.

Question 21

What is the general mechanism behind the development of acanthosis nigricans?

Answer 21

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.

Question 22

What is maturity onset diabetes of the young?

Answer 22

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

Question 23

What are features of MODY?

Answer 23

Depends on mutation type:

• At birth - glucokinase mutation
• Adolescence - transcription factor mutations

Glucokinase - stable hyperglycaemia which can be dieat controlled

Transcription factors - progressive hyperglycaemia

Question 24

What is latent autoimmune diabetes in adults (LADA)?

Answer 24

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.

Question 25

What are features of LADA that may help distinguish it from type II diabetes?

Answer 25

• Leaner build
• Rapid progression to insulin therapy following an initial response to other therapies
• Presence of circulating islet autoantibodies.

Question 26

What features might help you distinguish between type I and type II diabetes?

Answer 26

• Type I - more likely to present acutely or in DKA
• Type II - often asymptomatic/poresent with complications in older patients