diabetes

Question 1

what is diabetic mellitus ?

Answer 1

A common group of metabolic disorders that are characterised by chronic hyperglycaemia.

Question 2

what are the sources of glucose?

Answer 2

Sources of glucose:
Glucose absorbed in the diet.
Glucose from breakdown of glycogen (glycogenolysis).
Glucose from various non-carbohydrate carbon substrates, such as pyruvate, lactate, glycerol and glucogenic amino acids (gluconeogenesis)
Blood glucose levels are tightly regulated (3-8mM) by insulin and glucagon.

Question 3

what are the Prognosis and long-termcomplications associatedwith diabetes

Answer 3

People with diabetes have a reduced life expectancy:
life span is reduced by about one third.

Annual mortality rate of people with diabetes is 5.4%, twice that of those without.
Increase in mortality results from:
Increase in CVD incidence (3-5x risk).
Increase in renal failure (100x risk).

Increased morbidity:
Increased risk of blindness
Amputation

Question 4

increased glucose

Answer 4

increased insulin

Question 5

The pancreas senses bloodglucose levels andresponds:
what happens when there is low glucose + high glucose

Answer 5

Low glucose  glucagon secretion.
Glucose is liberated from stores in muscle, fat and the liver, it is synthesised from precursors and enters the bloodstream. Storage of glucose as fat and glycogen in muscle and the liver is stopped

High glucose  insulin secretion.
Glucose is removed from the blood stream and stored in fat and muscle, it is converted to fatty acids and glycogen in the liver. Glucose production by the liver is stopped.

Question 6

why can diabetes be compared to starvation?

Answer 6

Diabetes is metabolically similar to starvation.
Raised blood glucose levels but cannot use it/store it.

Question 7

what happens when there is a lack of insulin/response

Answer 7

Lack of insulin/insulin response leads to non-glucose energy sources being used.
Lipids, proteins etc.

Question 8

Reliance on these catabolic pathways leads to the formation of ketone bodies
Ketotic breath.
Acidosis (increased acidity in blood/tissues).

Increased lipolysis/ FFA production:
Hyperlipidaemia= cvd

Question 9

what are the types of diabetes

Answer 9

Primary diabetes is divided into:
Type I (previously ‘insulin-dependent’) – autoimmune – body don’t produce insulin
Type II (previously ‘non-insulin dependent’)

Gestational diabetes- only in pregnancy
Malnutrition-modulated diabetes

Question 10

what is type 1 diabetes

Answer 10

Type I diabetes is a polygenic auto-immune disorder, characterised by specific destruction of pancreatic beta-cells, which leads to complete insulin deficiency.  hormone replacement therapy

Question 11

what is type 2 diabetes

Answer 11

Type II diabetes is a polygenic disorder, characterised by a decrease in beta-cell mass, leading to a reduction in secretion, and peripheral insulin resistance.

Question 12

Non-modifiable risk factors for Type I and II diabetes

Answer 12

Family history (Type I and Type II diabetes):
Risk is increased if have mother (2%), father (8%) or sibling (10%) with Type I diabetes [ 30% risk if both parents have Type I diabetes].
Risk is increased if have one parent (15%), both parents (75%) or sibling (10%) with Type II diabetes.

Ethnicity (Type I and Type II diabetes):
Type I diabetes is more common in Northern European countries.
Type II diabetes is more prevalent in South Asian (6x), African or Afro-Caribbean (3x) and Chinese populations.

Age (Type II diabetes):
More likely to develop Type II diabetes if you are over 40 years old (25 years old if you are African or Afro-Caribbean, or Asian).

Other medical conditions (i.e. polycystic ovary syndrome, gestational diabetes, impaired glucose tolerance) may ꜛ risk of developing diabetes.

Question 13

Modifiable risk factors for Type I and II diabetes

Answer 13

Weight (Type II diabetes only):
80% of people diagnosed with Type II diabetes are overweight.
Lose 5% weight  reduce risk of diabetes by 50%.

Waist circumference (Type II diabetes only):
Waist circumferences of >80cm in women, >90cm in Asian men or >94cm in white or black men is associated with increased risk of diabetes.

Sedentary lifestyle (Type II diabetes).

Social deprivation/low income:
People living in deprived areas of UK are more likely (2.5x) to develop diabetes.

Question 14

what are the symptoms of diabetes?

Answer 14

Symptoms of diabetes can vary in their severity.

Symptoms of Type I diabetes are often acute:
2-4 week history of thirst, polyuria, weight-loss, lethargy.

Symptoms of Type II diabetes are often sub-acute and less marked:
History of thirst, polyuria, lethargy, visual disturbances, infections, which occur over several months.

Question 15

what are the clinical signs of diabetes

Answer 15

Glucosuria (excretion of glucose in urine):
Exclude other causes (i.e. low renal threshold for glucose).

Hyperglycaemia (elevated blood glucose levels):
Elevated random plasma glucose (≥11.1mmol/L).
Elevated fasting plasma glucose (≥7mmol/L).

Impaired glucose tolerance:
Exclude other causes (i.e. certain medications, obesity, liver disease).

Complications of diabetes (e.g. retinopathy, foot ulcers can be taken as clinical signs).

Question 16

how can you diagnose diabties

Answer 16

Tests may include:
Detection of glucose in urine (not definitive).
Random venous plasma glucose test (≥11.1mmol/L is suggestive of diabetes).
Fasting venous plasma glucose test (≥7.0mmol/L is suggestive of diabetes).
Oral glucose tolerance test (is used if borderline diagnosis, or in gestational diabetes screening).
Glycated haemoglobulin (HbA1c) levels of ≥6.5% (48mmol/mol) in some people with diabetes (WHO, 2011).

Question 17

explain Fasting blood glucoselevels in the diagnosis of diabetes

Answer 17

When examining fasting plasma glucose levels in the general population, a skewed normal distribution is observed.

The classification of ‘abnormal’ and ‘normal’ is largely arbitrary.

Diagnostic cut-offs are set with reference to when the risk of microvascular complications increase (i.e. diabetic retinopathy).

Question 18

what is Oral glucose tolerancetesting (ogtt)

Answer 18

Considered to be the gold standard test for diagnosing diabetes, but OGTTs used vary between countries.

OGTT vary in how the test is performed: glucose load, timing of glucose measurements and so on.

Most accepted criteria are those proposed by the World Health Organisation (WHO) or the American Diabetes Association (ADA).

Question 19

interpreting blood glucose levels

Answer 19

normal - less than 6 (fasting) less than 7.8mmol/l (2h post prandial)
diabeties - more than 7 or 7 (fasting) more than than 11.1mmol/l (2h post prandial)
impaired glucose intolerance- less than 7 (fasting) 7.8 -11.1mmol/l (2h post prandial)
impaired glycemia - 6-6.9 (fasting)

Question 20

what causes Glycated haemoglobinand glucose levels

Answer 20

Exposure of red blood cells to glucose results in their haemoglobin (Hb) becoming irreversibly glycated.

The amount of glycated haemoglobin (HbA1c) can be used to estimate the average glucose levels that the red blood cells have been exposed to over a 1-3 month period.

Increased blood glucose levels lead to increased HbA1c levels

Question 21

what is hba1c

Answer 21

test measures the amount of blood sugar (glucose) attached to your hemoglobin

Question 22

what is type 1 and what are the risk factors

Answer 22

Auto-immune destruction of pancreatic beta cells means that no insulin is produced and insulin replacement therapy for life is required.

effect all age group

Family history:
Twin and family studies.
95% Type I diabetics have HLA DR-3 or DR-4 class II HLA antigens compared to 50% of non-diabetic population.

(HLA class II molecules on antigen-presenting cells bind to peptide antigens and present them to T helper cells).

Ethnicity:
Northern European descent.

Question 23

what are the causes of type 1 diabeties

Answer 23

Type I diabetes is characterised by complete insulin deficiency.

Complete insulin deficiency normally results from autoimmune destruction of insulin-secreting pancreatic beta-cells.

Not fully understood what initiates the autoimmune beta-cell destruction.

The body’s immune system does not normally attack itself.

During the development of Type I diabetes in a genetically susceptible individual, something triggers the selective autoimmune destruction of pancreatic beta-cells.

Evidence that it is an autoimmune-mediated response stems from:
The association of Type I diabetes with other autoimmune disorders (i.e. coeliac disease, pernicious anaemia).
Evidence of chronic inflammation (T-cells and macrophages) in pancreatic islets of newly diagnosed patients.
The detection of circulating auto-antibodies (i.e. anti-insulin, anti-islet antibodies) before the onset of disease.

Question 24

what are the treatment goals for diabetes?

Answer 24

Preserve life.

Alleviate symptoms.

Achieve good glycaemic control to avoid long-term complications.

Avoid iatrogenic side effects (i.e. hypoglycaemia).

Question 25

Lifelong therapeutic Management of Type I Diabetes

Answer 25

Injected insulin replacement (firstline treatment)

Dietary modification
Low fat, high fibre, healthy diet that spreads nutrient load across day to avoid swings in blood glucose

Monitoring:
Insulin dose adjustment
Glycaemic control
Complications (e.g. eye, foot, CVD risk)

Exercise

Education

Psychosocial support

Question 26

type I diabetes: treatment

Answer 26

Treatment aims to provide insulin replacement in a way that mimics the insulin secretion pattern observed in individuals without diabetes.

In non-diabetics, insulin is secreted at a slow basal rate throughout the day but, in response to a meal, insulin secretion rises rapidly before returning to baseline levels within 2 hours.

Question 27

Complications of insulintherapy

Answer 27

Patients with newly diagnosed Type I diabetes can experience a partial remission phase, only requiring very low levels of insulin to maintain good glycaemic control.

Hypoglycaemia: the most common side-effect of insulin therapy.

Lipohypertrophy: accumulation of fat at injection sites due to local effects of insulin can affect insulin absorption (and is ‘unsightly’):
Avoid by rotating injection sites.

Insulin allergy (rare as insulin is now highly purified) can lead to atrophy of fat tissue and can affect insulin action.

Question 28

Monitoring in type I diabetes

Answer 28

Insulin therapy must be individualised.

Monitoring glucose levels (patient-led monitoring allows insulin doses to be adjusted accordingly):
May monitor capillary blood glucose levels before and/or 2 hours after meals, after exercise
Continuous glucose monitoring

Monitoring long-term glycaemic control (doctor-led HbA1c %).

Monitoring risk or development of long-term complications:
Regular eye screening, foot care, CVD screening, diet.

Question 29

Physiological basis fordiabetes SIGNS and symptoms

Answer 29

Signs and symptoms arise as a result of the elevated blood glucose levels in diabetes.

When blood glucose levels are elevated,
water is drawn from interstitial spaces into the circulation to decrease blood osmolarity. This increase in blood volume is countered by increased urinary output.
If the reabsorptive capacity of the renal tubules is exceeded, increased osmotic pressure in the tubules leads to reduced glucose and water reabsorption, leading to increased urinary output (osmotic diuresis) and glucosuria.

The loss of fluids and electrolytes due to polyuria, stimulate thirst.

—- Fluid loss (dehydration) can contribute to weight loss.

Without insulin, cells cannot absorb glucose from the blood. The body switches to using other sources of fuel (glycogen, fats and proteins):
Breakdown of fat and muscle energy stores can lead to weight loss.
Utilisation of fat energy stores leads to the production of ketone bodies (alternate energy source), which increase the acidity of blood (ketoacidosis). Untreated, this can lead to (hyperglycaemic) coma.