Diabetes And Hypoglycaemia

Question 1

How are blood glucose levels maintained?

Answer 1

• Via dietary carbohydrates, glycogenolysis and gluconeogenesis

Question 2

Describe what happens in the fasting state?

Answer 2

• The Fasting state is a decrease in glucose levels for a prolonged period of time
• Insulin levels decrease causing an increase in liver gluconeogenesis
• This causes an increase in glucose production
• This causes lipolysis - proteoloysis (catabolism - release of glucose into the blood)
• Leads to a decrease in peripheral uptake

Question 3

Describe the plasma regulation with high blood sugar

Answer 3

High blood sugar -> Pancreas -> Insulin -> stimulates glycogen formation from glucose in liver -> lowers blood sugar

Question 4

Describe the plasma regulation of low blood sugar

Answer 4

Low blood sugar -> Pancreas -> Glucagon -> Stimulates glycogen breakdown to glucose in liver -> Raises blood sugar

Question 5

Describe the function and major metabolic paths for Insulin

Answer 5

• Promotes growth and storage
• Stimulates glucose storage in muscle, liver
• Stimulates protein & fatty acids synthesis

Question 6

Describe the function and major metabolic paths for Glucagon

Answer 6

• Mobilises fuel and maintains blood glucose in fasting state
• Activates gluconeogenesis and glycogenolysis
• Activates fatty acid release

Question 7

Describe the function and major metabolic paths for Epinephrine

Answer 7

• Mobilises fuels in Acute stress
• Stimulates glycogenolysis
• Stimulates fatty acid release

Question 8

Describe the function and major metabolic paths for cortisol

Answer 8

• Changing long term
• Amino acid mobilisation, gluconeogenesis

Question 9

Describe the function and major metabolic paths for growth hormones

Answer 9

• Inhibits insulin action
• Stimulates lipolysis

Question 10

What is diabetes mellitus?

Answer 10

Metabolic disorder characterised by chronic hyperglycaemia, glycosuria (glucose in urine) and associated abnormalities of lipid and protein metabolism

Question 11

State the 4 classifications of diabetes?

Answer 11

• Type 1: Deficiency in insulin secretion
• Type 2: Insulin secretion is retained but target organ resistant to its actions
• Secondary: Chronic pancreatitis, pancreatic surgery, secretion of antagonists
• Gestational: Occurs for first time in pregnancy
• Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy.

Question 12

Describe the key features of type 1 DM with its most common cause?

Answer 12

• Mostly children and young adults
• Sudden onset (days/weeks)
• Appearance preceded via ‘prediabetic period’ of several months
• CC -> Autoimmune destruction of Beta-cells in pancreas -> interaction between genetic + environmental factors -> strong link with HLA genes within the MHC region on chromosome 6.

Question 13

Describe the pathogenesis of type 1 DM?

Answer 13

• Destruction of B-cells starts with autoantigen formation
• AA presented to T-lymphocytes to initiate autoimmune response
• Circulating AutoAB present to various -cell antigens such as glutamic acid decarboxylase
• Tyrosine-phosphatase-like molecule, Islet auto-antigen
• Most common detected antibodies is islet cell antibody

Question 14

Describe how beta cells are destroyed via autoantodies?

Answer 14

VD

Question 15

What does destruction of the pancreatic beta cells leads to and why?

Answer 15

• hyperglycaemia: Absolute deficiency of insulin & amylin
• Amylin, a glucoregulatory peptide hormone co-secreted with insulin causes decreased blood glucose
• Leading to slowing gastric emptying, & suppressing glucagon output from pancreatic cells

Question 16

State the metabolic complications of type 1 DM?

Answer 16

• Insulin deficiency could lead to either:
• Increased lipolysis -> Increased free fatty acids -> Increased FFA oxidation -> Ketoacidosis (increase in ketone free bodies -> diabetic coma
• OR
• Hyperglycaemia-> Glycouria (Glucose in urine) -> Polyuria (increased urination) -> Volume depletion (more water loss) -> Diabetic coma

Question 17

Describe key presentations of type 2 DM?

Answer 17

• Slow onset (months/years), Patients middle aged elderly - prevalence increase with age
• Strong familiar incidence
• Pathogenesis uncertain - insulin resistance; 3-cell dysfunction:

Question 18

Describe the pathophysiology of type 2 DM?

Answer 18

• Primary beta cell failure (rare) -> Diabetes (first pathway)
• Genetic predisposition + Obesity lifestyle factors -> Insulin resistance ->
• Compensatory B cell hyperplasia (leads to normoglycaemia) ->
• Beta cell failure (leads to impaired glucose intolerance) ->
• B cell failure (late)

Question 19

Describe the pathogenesis of hyperglycaemic hyperosmolar nonketotic
coma (HONK) state + its diagnosis?

Answer 19

VD

Question 20

Describe the diagnosis of type 2 DM when symptoms are presented

Answer 20

• In the presence of symptoms: (polyuria, polydipsia & weight loss for Type I)
• Random plasma glucose ≥ 11.1mmol/I (200 mg/dl)
• OR Fasting plasma glucose (no food for 8 hr) ≥ 7.0 mmol/I (126 mg/dl)
• OR Oral glucose tolerance test (OGTT) - plasma glu ≥ 11.1 mmol/I

Question 21

Describe the diagnosis of type 2 DM when symptoms are aren’t present?

Answer 21

• Absence of symptoms -> test blood samples on 2 separate days

Question 22

State the fasting plasma glucose + Oral glucose tolerance test values for individuals with Impaired Glucose Tolerance (IGT - prediabetic) + Impaired Fasting Glycaemia (IFG)?

Answer 22

• Impaired glucose tolerance: FPG >7 mmol/L + OGTT = 7.8 - 11.1 mmol
• Impaired plasma glycaemia: FPG = 6.1 to 6.9 mmol/L + OGTT < 7.8mmol/L

Question 23

What is the oral glucose tolerance test?
When should it be carried out?

Answer 23

• Used in FPG ‹ 7.0 mmol/L -> tests glucose tolerance status.
• OGTT should be carried out -> in patients with IFG, in unexplained glycosuria + in clinical features of diabetes with normal plasma glucose values

Question 24

Describe the oral glucose test

Answer 24

• Process
• 75g oral glucose
• test after 2 hour
• Blood samples collected at 0 and 120 mins after glucose

Question 25

State the drugs used for the treatment of T2 DM?

Answer 25

- Metformin (decreases gluconeogenesis) - Sulfonylureas (Increases activity of B cells - Increase insulin release) - Thiazolidinediones (reduces insulin resistance) - SGLY2 inhibitors (Decrease glucose reabsorption from kidney - increase glucose excretion) - Incretin targeting drugs (prevents breakdown of natural incretins)

Question 26

What does incretin do?

Answer 26

- Produces insulin - Decreases glucose production in liver

Question 27

Describe how glycaemic control is monitored and its aim?

Answer 27

- Aim: prevent complications or avoid hypoglycaemia - Self-monitoring encouraged - Capillary blood measurement urine analysis: glucose in urine gives indication of blood glucose concentration above renal threshold - 3-4 months: blood HbA1c (glycated Hb; covalent linkage of glucose to residue in Hb - Others -> urinary albumin -> index of risk of progression to nephropathy

Question 28

State the long term complications of both type 1 and type 2 DM

Answer 28

- Micro-vascular disease -> retinopathy, nephropathy, neuropathy - Macro-vascular disease -> related to atherosclerosis heart attack/stroke - Exact mechanisms of complications are unclear

Question 29

Define the plasma glucose range for hypoglycaemia

Answer 29

PG < 2.5 mmol

Question 30

State the causes for hypoglycaemia

Answer 30

- Causes of hypoglycaemia - Drugs are most common cause - Common in type 1 diabetes - Less common in type 2 diabetes taking insulin & insulin secretagogues

Question 31

What does Insulin secretagogues do?

Answer 31

- Insulin secretagogues help your pancreas make and release (or secrete) insulin - Insulin helps keep your blood glucose from being too high

Question 32

What drugs can cause hypoglycaemia in individuals with diabetes?

Answer 32

- Types of sulfonylureas - Exogeneous insulin & insulin secretagogues - Glyburide, glipizide + glimepiride

Question 33

What causes hypoglycaemia in individuals without diabetes?

Answer 33

- Drugs: alcohol, quinolone, quinine, beta blockers, ACE inhibitors + IGF-1 - Endocrines disease - cortisol disorder - Inherited metabolic disorders, e.g. hereditary fructose intolerance - Insulinoma - tumour of pancreatic beta cells

Question 34

State 3 factors which can induce hypoglycaemia?

Answer 34

- Ethanol - Sepsis - Chronic kidney disease

Question 35

Explain how ethanol can cause hypoglycaemia

Answer 35

- inhibit gluconeogenesis, but not glycogenolysis - HG follow several days alcohol binge with limited food intake - Leads to Hepatic depletion of glycogen

Question 36

Explain how Sepsis can cause hypoglycaemia

Answer 36

- Cytokine accelerated glucose utilization - induced inhibition of gluconeogenesis in the setting of glycogen depletion

Question 37

Explain how Chronic kidney disease can cause hypoglycaemia

Answer 37

- Mechanism not clear - Impaired gluconeogenesis - Decreased renal clearance of insulin + Decreased renal glucose production.

Question 38

What is reactive hypoglycaemia and describe potential causes (3)?

Answer 38

- Postprandial hypoglycaemia causes decreased blood sugar are recurrent, Occurs within 4 hours after eating.. - unknown cause - benign tumour in the pancreas - Leads to overproduction of insulin, too much glucose used up by tumour, deficiencies in counter-regulatory hormones

Question 39

Describe the signs of hypoglycaemia

Answer 39

- Neurogenic (autonomic) signs - triggered by decrease in glucose levels - Activated by ANS & mediated by sympathoadrenal release of catecholamines + Ach

Question 40

Describe the symptoms of hypoglycaemia?

Answer 40

- Neuroglycopaenia = neuronal glucose deprivation in brain - Sign & symptoms: - Confusion, difficulty speaking, ataxia, paresthesia, seizures, coma, death