Intro to Diabetes (M1 14/12)

Question 1

These are the LO’s dodo brain

Answer 1

1. Describe the pathology of diabetes mellitus and the long term complications of the disease
2. Describe the different types of diabetes, including secondary and genetically inherited
3. Describe the diagnostic criteria for glucose intolerance and diabetes mellitus
4. Describe the different clinical features of the different types of diabetes mellitus

Question 2

What does Diabetes Mellitus refer to?

Answer 2

• Diabetes means ‘to pass through’.
• Mellitus means honeyed.
• It refers to a number of different conditions, characterised by chronic hyperglycemia, resulting from either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced.
• This is diabetes that causes glucose in urine: mainly T1/ T2/ gestational diabetes.

Question 3

What is the pathology of type 1 diabetes?

Answer 3

1. In T1D beta cells are destroyed.
2. Auto-immune condition, there is a genetic predisposition then an enviromental trigger, like a toxin or virus, causes an immune response, and produced T-cells and anti-bodies that attach beta-cells.
3. After a meal, increased blood glucose levels are detected by the beta cells causing them to secrete insulin into the blood. This insulin will cause cells to take up and absorb the glucose to use for energy or it can be stored in the liver, thereby lowering blood glucose.
4. In T1D, no insulin is produced to tell the cells to take up the blood glucose so you get hyperglyceamia.

Question 4

What is the pathology of type 2 diabetes?

Answer 4

• Insulin resistance: produce insulin but body is resistant.
• Associated with obesity
• More common in some racial groups
• Interplay between genes and environment

Question 5

Describe the natural progression of type 2 diabetes

Answer 5

• Normally progresses over a decade
• To begin developing T2D you have to have a genetic predisposition, and a stressor like weight gain to cause changes in your glucoregulatory physiology.
• Initially, insulin resistance causes:

1. Changes in glucose (dysglyceamia) and lipid levels (dyslipideamia).
2. A decrease in HDL (good fat) and increase in trigylcerides.
3. An increase in systolic and diastolic BP.

• Insulin resistance causes a greater demand of insulin (need more insulin to have an effect due to downregulation of insulin receptors). At this stage people begin to have impaired fasting glucose and impaired glucose tolerance.
• The next stage is T2D, but some people can recover from this stage and return to normal glucose levels.
• In pre-diabetes there are microvascular complications (due to damage to small blood vessels) but in diabetes there are macrovascular (due to damage to larger blood vessels) as well.
• The delay between biochemical changes and T2D diagnosis is 5-10y.

Question 6

How do you diagnose diabetes?

Answer 6

1. ​If suspect T1D in patient they should have symptoms like polyuria, polydipsia (thirst) and unexplained weight loss. T2D may not have any symptoms.
2. A random glucose concentration is greater than 11.1 mmol/L
3. Or a fasting glucose conc is greater than 7 mmol/L
4. Do dipstick test for ketones. If there are ketones in blood/urine see at once and start insulin. They have T1D. If don’t have ketones in blood they have T2D, see next week for diet and tablets.

Question 7

What are the differences between T1 and T2 diabetes?

Answer 7

• T1D is acute (weeks or days) whereas the development of T2D is insidious (subtle, gradual).
• T1D patients are young - 30’s, whereas T2D patients are middle-aged.
• Symptoms for T1: waking up to pass urine, but T2D may have no symptoms.
• FH is normally negative in T1D, but positive in T2D.
• If have numb feet or dots on the back of eyes is T2 not T1.

Question 8

Define Diabetes Insipidus

Answer 8

• Diabetes means ‘to pass through’ in Greek
• Diabetes insipidus is a rare condition where you produce a large amount of urine and often feel thirsty.
• Diabetes insipidus isn’t related to diabetes mellitus (usually just known as diabetes). Nothing to do with insulin.
• Diabetes insipidus is caused by problems with a hormone called vasopressin (AVP), also called antidiuretic hormone (ADH).

Question 9

What is secondary diabetes?

Answer 9

• Diabetes caused by other conditions or medication
• Steriods can cause diabetes: make cells less sensitive to insulin.
• Pancreatitis and pancreatic surgery: if pancreas is removed, then will get T1D.
• Cushings syndrome: pituitary tumour.
• Phaeochromocytoma: tumour of adrenal gland.

Question 10

Describe genetic influence in T1 and T2D

Answer 10

Type 1

• 50% concordance between identical twins
• But 95% cases are sporadic: no FH
• Susceptibility with a genetic trigger
• Personal or family history of other auto-immune illnesses is common

Type 2

• Inherited genes and environment / life style

Question 11

Describe gestational diabetes

Answer 11

• This is diabetes diagnosed in pregnancy
• Occurs as a result of pregnancy related hormones increasing insulin resistance
• Associated with large babies and difficult labour
• Resolves after delivery of the baby
• Recurs in subsequent pregnancy
• Risk factor for Type 2 diabetes
• Tested for routinely in the UK at 26 – 28 weeks

More likely in women who are:

• overweight or obese
• have had gestational diabetes before
• have had a very large baby in a previous pregnancy (4.5kg/10lb or over)
• have a family history of diabetes
• are from a South Asian, Black or African Caribbean or Middle Eastern background

Question 12

How does insulin normally affect cells.

Answer 12

1. Insulin binds to insulin receptor on cell
2. Causes GLUT4 to move to the cell surface membrane
3. GLUT4 binds with glucose.

Question 13

Why don’t we say insulin-dependant diabetes for T1D anymore?

Answer 13

• Because most people who take insulin are T2D who have to take it because medication is no longer working.

Question 14

What is genetic diabetes?

Answer 14

• 1-5% of diabetics have diabetes caused by a single gene abnormality.
• E.G. neonatal diabetes mellitus or Maturity Onset Diabetes of the Young (MODY)

In monogenic diabetes:

1. Diabetes often develops before the age of 25
2. Diabetes runs in families from one generation to the next
3. Diabetes may be treated by diet or tablets and does not always need insulin treatment

Question 15

Who is screened for diabetes?

Answer 15

• Overweight
• Vascular disease
• Hypertension
• Over 40
• Previous gestational diabetes
• People with pre-diabetic states

Question 16

What is HbA1c used for and what are the limitations?

Answer 16

• RBCs are permeable to glucose, glucose irreversibly attatches to haemoglobin to form glycated haemoglobin. Since RBC’s last 120 days, glycated haemoglobin reflects blood glucose levels over 2/3 months. People with chronic hyperglyceamia have an elevated hBa1C fraction (greater than or equal to 6.5%).
• Limited in gestational and T1 diabetes: not had it long enough to cause changes HbA1c
• Aneamia: low number of RBC’S or haemoglobin.

Question 17

What is the oral glucose tolerance test?

Answer 17

1. Patient told not to eat or drink 8/12 before test.
2. Blood tests at baseline/start)
3. Drink glucose
4. Test again at 120 minutes
5. Fasting state:
   
   1. normal range = 6.1 mmol/L or less
   2. Impaired fasting glyceamia if more than 6.1, but less than 7.1 mmol/L.
   3. diabetes = 7.1 or more
6. At 120 minutes:
   
   1. normal range = under 7.8
   2. Impaired glucose tolerance = 7.8 to 11.1 mmol/L
   3. diabetes = over 11.1

Question 18

How do symptoms develop in T1 diabetes?

Answer 18

In T1 diabetes, there is no insulin to take the glucose out of the blood and give it to the organs. So the body can’t use the glucose so is starving, see ‘fed and fasting states’:

• The liver acts like it is starving and makes glucose from glycogen and pyruvate (from gluconeogenic precursors) into the blood.
• The adipose tissue breaks down into free fatty acids which the body can use for energy in beta oxidation (exept the brain) or use it to make ketones
• Amino acids released from skeletal muscle can be used to make ketone bodies if ketogenic, or pyruvate and then glucose if gluconeogenic.

1. Lathargic (sleepy) and fatigue (lack of energy)
2. Glucose in urine because kidney’s overwhelmed by high glucose levels. This draws water out with it causing polyuria. This caused dehydration and thirst.
3. Diabetic ketoacidosis (ketones in blood from fatty acids being released from adipose tissue and converted to acetyl coA and them ketone bodies in liver).

Question 19

What are insulin receptors called?

Answer 19

GLUT4

Question 20

Complications of diabetes in the long-term (remember at start T2 doesn’t present with symptoms).

Answer 20

The microvascular (small blood vessels) complications are:

1. Retinopathy: diabetic’s eyes need to be examined regularly for cotton wool spots, haemorrages, microanyeurysms and macular thickening.
2. Neuropathy: Peripheral (far) complications include increased or decreased pain, painless injury and reduced reflexes. Autonomic neuropathy includes resting tachychardia and increased urination and erectile dysfunction.
3. Nephropathy: glomerulosclerosis and pylonephrosis (kidney infection).

Macrovascular.C:

1. Coranary: angina, CHF, dyspnoea (difficulty breathing).
2. Cerebrovascular. C: haemorrage, infarction and memory problems.
3. Peripheral vascular. C: atherosclorosis, gangrene (dead body tissue) and ulceration. Need regularly foot checks.

Question 21

Difference between endocrine and exocrine, give examples relating to the pancreas?

Answer 21

1. Exocrine: glands which secrete their products on to an epithelium rather than directly into the blood. Pancreas releases enzymes into the digestive tract to chemically digest food.
2. Endocrine: glands that secrete their substances directly into the blood stream.
3. Pancreas releases hormones that help with metabolism (life-sustaining chemical reactions) like insulin and glucagon.

Question 22

What causes insulin resistance in diabetes?

Answer 22

1. Weight: Complex interactions in fat tissue draw immune cells to the area and trigger low-level chronic inflammation. This inflammation can contribute to the development of insulin resistance, type 2 diabetes, and CVD.
2. Inactivity: normally, active muscles burn their stored glucose for energy and refill their reserves with glucose taken from the bloodstream, keeping blood glucose levels in balance.
3. Other causes of insulin resistance may include ethnicity; certain diseases; hormones; steroid use; some medications; older age; sleep problems, especially sleep apnea; and cigarette smoking.