Diabetes Mellitus Flashcards
Describe diabetes mellitus in one sentence
Abnormality of glucose regulation
What percentage of diabetes cases are type 1 or type 2?
10% are type 1
85% are type 2
5% are neither 1 or 2 - monogenic
Describe diabetes insipidus in one sentence
Abnormality of renal function (water)
What is a major characteristic of a series of metabolic conditions which are represented by Diabetes mellitus?
Hyperglycaemia
What are the consequences of exposure to chronic hyperglycaemia?
•Increased risk of micro vascular complications (small capillaries supplying areas such as the skin)
- can result in conditions such as atherosclerosis
•Long term macro vascular disease (such as heart attacks and strokes)
What test is best to help with diagnosing diabetes mellitus?
Glucose tolerance test
Why is plasma glucose not the best method to establish a diagnosis?
Plasma glucose levels vary throughout the day
What test measures residual glucose stuck to the surface of haemoglobin and gives an indication of glucose control over the past few weeks?
HbA1C test
What glycosylated haemoglobin test (HbA1C) value does not require a fasting sample?
> 48mmol/mol(6.5%)
What random plasma glucose (RPG) value, when measured on 2 occasions is diagnostic of diabetes?
> 11.1 mmol/L
What fasting plasma glucose levels are considered normal, impaired and diabetic before a Glucose tolerance test is carried out?
- Normal:
FPG<6.1 - Impaired fasting glucose:
FPG 6.1-7.0 - Diabetes:
FPG>7.0
What are the significant values for plasma glucose 2 hours after GTT (i.e after 75g of glucose is given after fasting) and what do they mean?
- <7.8 = normal
- 7.8-11.1= impaired glucose tolerance (IGT)
- > 11.1 = diabetes
What causes type 1 diabetes?
- Type 1 is an insulin deficiency
- caused by autoimmune destruction of pancreatic B cells
- genetic causes also evident
• type 1 diabetes in sibling = 6% risk vs 0.4% in gen pop
• monozygotic twins = 40%
• dizygotic twins = 10%
-Environmental causes evident
• migrants adopt incidence rate closer to that of new country
What factor determines the clinical presentation of type 1 diabetes?
- Rate of destruction of pancreatic B cells
- slow destruction can lead to confusion with type 2 diagnosis in a late presenting T1DM
- 80-95% of pancreatic B cells destroyed by time of presentation
What is the childhood incidence of type 1 diabetes?
25 in 100,000
- increasing by 4% each year
- higher in Europe, lower in Asia
What condition will usually be present in children with type 1 diabetes and why?
- Ketoacidosis
- body cells cannot access glucose for metabolism so they start to metabolise fat which results in ketones as the end product
What do low C-peptide levels indicate?
Low insulin secretion
What circulating antibodies can be present in type 1 diabetes?
- GAD - glutamic acid decarboxylase
- ICA - islet cell antibodies
- IAA - insulin autoantibodies
Describe childhood/adolescent onset of diabetes in terms of:
- peak incidence
- antibodies normally present
- Peak incidence at 10-14 years
- however up to 60% of cases occur after age 16 - Classic antibodies present in children/young adults
- higher ICA
- higher IAA
Describe adult onset of diabetes
- LADA - latent autoimmune diabetes in adults (>25 yrs of age)
- GAD associated - generally lower AB levels
- Less weight loss, less ketoacidosis
- May masquerade as non-obese type 2
- Variable period until insulin required
What are the symptoms of type 1 diabetes?
- Polyuria
- Polydipsia
- Tiredness
What is the acute presentation of type 1 diabetes?
- Hyperglycaemia with diabetic symptoms
2. Ketoacidosis (medical emergency)
What is the incidence of type 2 diabetes and what are associated factors of the disease?
What is the most common age threshold?
- 90% of all cases - prevalence tripled in 30 years
- strongly associated with obesity and inactivity
- 12% of US population estimated to have it - Usually found in patients over 40yrs old
- transition through impaired glucose tolerance
- maturity onset diabetes in the young is possible
• strong family history
- 100% concordance in identical twins with identical lifestyles
What is type 2 diabetes characterised by?
Defective and delayed insulin secretion and abnormal postprandial suppression of glucagon
What treatment has showing promising results in terms of remission of type 2 diabetes?
Bariatric surgery
What is an external factor that contributes to type 2 diabetes
Medication
- a large number of medications can cause hyperglycaemia and lead to development of diabetes
What metabolic changes occur in type 2 diabetes that involve insulin?
- Defect in insulin synthesis, secretion and action
- B cell response to hyperglycaemia is inadequate
- elevated basal insulin levels
- failure of gluconeogenesis suppression
- insulin stimulated glucose uptake is reduced
What other metabolic changes occur in type 2 diabetes?
- Inadequate release of incretins (GLP-1, GIP)
- Increased absorption of glucose from GI tract due to increased transporter - Defect in pulsatile insulin secretion
- portal vein and liver are the key targets - Strong association with High levels of visceral fat - unclear why
What is the collective term for all of the metabolic changes that occur in type 2 diabetes?
Insulin resistance
List physiological and metabolic consequences of type 2 diabetes
- Impaired glucose tolerance
- Hyperinsulinaemia
- Hypertension
- Obesity with abdominal distribution
- Dyslipidaemia (High VLDL, Low HDL)
- Procoagulant epithelial markers
- Early and accelerated atherosclerosis
Describe the onset of type 2 diabetes
- Gradual onset over many years
- usually IGT for some time
- often retinal damage at diagnosis (7-10yrs IGT)
- ability to secrete insulin falls with time
Describe the acute presentation of type 2 diabetes (this is rare)
- Rarely acute presentation
- polyuria, polydipsia, tiredness (usually present)
- unusual infections
- diabetic complications (cardiovascular)
What is the best way to slow the progression of type 2 diabetes?
Strict diet and exercise slows decline from impaired glucose tolerance (IGT)
What medications induce diabetes?
- Medicines that interfere with the secretion of insulin or glucagon
- medicines which alter tissue uptake of glucose
Examples:
- corticosteroids
- immune suppressants (cyclosporin, calcineurin inhibitors)
- cancer medication - imatinib, nilotinib
- antipsychotic medicines - clozapine, olanzipine, quetiapine
- antiviral - protease inhibitors
What other medical conditions can induce diabetes?
- Endocrine disease
- cushings disease/syndrome
- phaeochromocytoma (adrenaline tumour)
- acromegaly - Pregnancy - gestational diabetes
• risk factors
- overweight
- family history of diabetes
- some ethnic groups - Asian, Middle Eastern
- gestational diabetes in a previous pregnancy
• risk of developing type 2 diabetes mellitus in the future
