Introduction to diabetes and Type I diabetes

Question 1

list some sources of glucose

Answer 1

1) Glucose absorbed in the diet
2) Glucose from breakdown of glycogen (glycogenolysis)
3) Glucose from various non-carbohydrate carbon substrates, such as pyruvate, lactate, glycerol and glucogenic amino acids (gluconeogenesis)

Question 2

what is the role of Glucose transporters (GLUTs) ?

Answer 2

1) Glucose transporters (GLUTs) facilitate glucose uptake into tissues.
2) As glucose levels rise, e.g. after a meal:
Increased uptake into liver and pancreas through low affinity transporter, GLUT2
3) Increased uptake into some tissues (muscle and adipose) following activation of insulin-dependent GLUT4

Question 3

what is the typical blood glucose level maintained between?

Answer 3

Typically blood glucose levels are maintained between between 3-8 mM

Question 4

which cells secrete glucose and insulin?

Answer 4

The pancreas secretes insulin and glucagon to regulate glucose levels

1) Alpha cells secrete glucagon
2) Beta cells secrete insulin

Question 5

The pancreas senses blood glucose levels and responds accordingly. what does the pancreas secrete when there are low levels of glucose in the body and what is the effect of this?

Answer 5

1) Glucagon secretion
2) Increase catabolic pathways:
- Increase glycogenolysis (muscle, liver)
- Increase gluconeogenesis (liver, all tissues)
- Increase lipolysis (adipose tissue)
- Inhibit glycolysis (liver)
3) Inhibit anabolic pathways:
- Glygogen synthesis, lipid synthesis

Question 6

The pancreas senses blood glucose levels and responds accordingly. what does the pancreas secrete when there are high levels of glucose in the body and what is the effect of this?

Answer 6

1) Insulin secretion
2) Increase glucose uptake (muscle, adipose tissue)
3) Increase anabolic pathways:
- Increase fatty acid synthesis (liver, adipose tissue)
- Increase glycogen synthesis (liver, muscle)
- Inhibit catabolic pathways

Question 7

what is diabetes metabolically similar to?

Answer 7

1) metabolically similar to starvation.
2) Raised blood glucose levels but cannot use it
3) Lack of insulin/insulin response leads to need for non-glucose energy sources to be used
- Lipids, proteins etc

Question 8

what is Diabetes mellitus? what are the two types? what causes it?

Answer 8

1) A common group of metabolic disorders that are characterised by chronic hyperglycaemia
2) Diabetes-associated hyperglycaemia arises from an insulin deficiency, insulin resistance or both
3) Primary diabetes is divided into Type I (insulin-dependent) and Type II (non-insulin-dependent)
4) Diabetes also can be secondary to other conditions (i.e. chronic pancreatitis or Cushing’s syndrome) or drug treatments (i.e. thiazide diuretics or corticosteroids)

Question 9

In general what causes type I diabetes?

Answer 9

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

Question 10

What causes type II diabetes?

Answer 10

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 11

outline the Non-modifiable risk factors for type I and type II diabetes

Answer 11

1) Family history: Risk is increased if have one parent (15%), both parents (75%) or sibling (10%) with type II diabetes
2) Ethnicity
3) Age (Type II diabetes)
4) Other medical conditions
5) weight (Type II diabetes only 80% of those diagnosed). Lose 5% weight and reduce risk of diabetes by 50%
6) Waist circumference (Type II diabetes only)
7) Sedentary lifestyle (Type II)
8) Social deprivation/low income

Question 12

outline the Symptoms of type II Diabetes

Answer 12

Symptoms of type II diabetes are often sub-acute and less marked: history of thirst, polyuria, increased apetite, lethargy, visual disturbances, infections etc. over several months

Question 13

summarise the Clinical signs of diabetes

Answer 13

1)Glucosuria (excretion of glucose in urine)
Exclude other causes (i.e. low renal threshold for glucose)
2) Hyperglycaemia (elevated blood glucose levels)
- Elevated random plasma glucose (≥11.1mmol/L)
- Elevated fasting plasma glucose (≥7mmol/L)
3) Impaired glucose tolerance
- Exclude other causes (i.e. certain medications, obesity, liver disease)
4) Complications of diabetes

Question 14

explain the Physiological basis for increased urinary output and thirst due to diabetes

Answer 14

When blood glucose levels are elevated:

1) water is drawn from interstitial spaces into the circulation to decrease blood osmolarity. This increase in blood volume is countered by increased urinary output.
2) 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.
3) Fluid and electrolyte losses resulting from polyuria , stimulate thirst

Question 15

explain the Physiological basis for weight loss and ketoacidosis due to diabetes

Answer 15

1) Fluid loss (dehydration) can contribute to weight loss
2) Without insulin, cells can’t 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
3) Utilisation of fat energy stores leads to the production of ketone bodies (energy source), which increase acidity of blood (ketoacidosis). Untreated, this can lead to coma.

Question 16

discuss the Prognosis and the long-termcomplications associated with diabetes.

Answer 16

1) Patients with diabetes have a reduced life expectancy compared to non-diabetic population
i. e. life span reduced by approx. 1/3
2) Annual mortality rate of diabetics is 5.4%, twice that of non-diabetics
3) Increase mortality results from:
- Increase CVD incidence (3-5X increased risk)
- Increase in renal failure (100X increased risk)
4) Increased morbidity
- Increased risk of blindness

Question 17

How is Diabetes mellitus diagnosed?

- list the tests

Answer 17

The tests used to diagnose diabetes are the same for type 1 and type 2 diabetes (if asymptomatic require 2 tests to confirm diagnosis).

1) Detection of glucose in urine (not definitive)
2) Random venous plasma glucose test (≥11.1mmol/L suggests diabetes)
3) Fasting venous plasma glucose test (≥7.0mmol/L suggests diabetes)
4) Oral glucose tolerance test (used if borderline diagnosis or in gestational diabetes screening)
5) Glycated haemoglobulin (HbA1c) levels of ≥6.5% (48mmol/mol) in some patients

Question 18

what is considered to be the gold standard test for diagnosing diabetes?

Answer 18

1) the oral glucose tolerance tests (OGTTs) : vary between countries.
2) Oral glucose tolerance test vary in how the test is performed (i.e. glucose load, timing of glucose measurements)

Question 19

describe the Oral Glucose Tolerance Test

Answer 19

1) The oral glucose tolerance tests measures our body’s response to a glucose.
2) After fasting overnight (12hrs; water only), a fasting blood glucose reading is taken.
3) A glucose solution is consumed within 5 minutes
4) Blood glucose levels are measured at 120 minutes after consumption of glucose.

Question 20

what are the venous plasma levels of an normal individual when fasting and 2 hours after a meal (post-prandial)

• what are the likely levels in diabetes?
• what levels are seen in impaired glucose tolerance
• what levels are seen in impaired fasting glycaemia

Answer 20

1) normal:
- fasting <6.0mmol/l
- post-prandial <7.8mmol/l
2) diabetes:
- fasting >7.0mmol/l
- post-prandial >11.1mmol/l
3) impaired glucose tolerance:
- fasting <7.0mmol/l
- post-prandial 7.8-11.0mmol/l
4) impaired fasting glycaemia
- fasting 6.0-6.9mmol/l

Question 21

Exposure of red blood cells (RBCs) to glucose results in their haemoglobin becoming irreversibly glycated. what can we use this to measure?

Answer 21

1) The amount of glycated haemoglobin (HbA1c) can be used to estimate the average glucose levels that the RBCs have been exposed to over a 1-3 month period
2) Increased blood glucose levels lead to increased HbA1c levels
3) An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. Widely accepted as a measure of good glycaemic control, the lower the better

Question 22

what percentage of diabetic cases are type I?

Answer 22

1) Represents about 10% of all cases of diabetes
2) Can affect all age groups but juvenile onset is most common. More likely to develop type II diabetes if you are over 40 years old (25 years old if you are black or Asian)

Question 23

list the risk factors of Type I diabetes

Answer 23

1) Family history: 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]
2) Ethnicity: Northern European descent more common in type I. Type II diabetes is more prevalent in South Asian (6X), African or Afro-caribbean (3X) and Chinese populations

Question 24

describe the symptoms of Type I diabetes

Answer 24

1) Short onset duration of illness ( 2-4 weeks)
2) Increased thirst and hunger
3) Increased frequency of urination (especially at night)
4) Unexplained weight loss
5) Fatigue
(With presentation with classical symptoms, only need one plasma glucose test result suggesting diabetes to confirm diagnosis)

Question 25

summarise the treatment goals for those with Type I diabetes

Answer 25

1) Preserve life
2) Alleviate symptoms
2) Achieve good glycaemic control to avoid long-term complications
4) Avoid iatrogenic side effects (i.e. hypoglycaemia)

Question 26

outline the management of type I diabetes

Answer 26

1) Insulin replacement
2) Dietary modification
3) Exercise
4) Education
5) Monitoring: Glycaemic control, complications
6) Psychosocial support

Question 27

summarise the diabetic diet

Answer 27

active dietary management to maintain good glycaemic control and to reduce risks of CVD

1) Low in fat (<30% total caloric intake; reduce intake of saturated fats)
2) Low in simple sugars
3) Include moderate intake of low glycaemic index and complex carbohydrates (reduces fluctuations in blood glucose)
4) High in fibre

Question 28

how is insulin secreted in a non-diabetic individual?

Answer 28

1) 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.
2) in type I insulin replacement should mimic the insulin secretion pattern observed in non-diabetic individuals

Question 29

discuss the complications of insulin therapy

Answer 29

1) newly diagnosed type I diabetes can experience a partial remission phase, only requiring very low levels of insulin to maintain good glycaemic control
2) Hypoglycaemia
3) Lipohypertrophy (accumulation of fat at injection sites due to local effects of insulin) can affect insulin absorption ( and unsightly). Avoid by rotating sites of injection
4) Insulin allergy (rare as insulin is now highly purified) can lead to atrophy of fat tissue and can affect insulin action

Question 30

outline the monitoring of a type I diabetic patient

Answer 30

1) Insulin therapy must be individualised
2) Monitoring glucose levels (patient-led monitoring allows insulin doses to be adjusted accordingly)
3) Monitoring long-term glycaemic control (%HbA1c)
4) Monitoring risk or development of long-term complications:
- Regular eye screening for retinopathy
- Footcare
- CVD screening