L20: Diabetes & Hypoglycaemia

Question 1

During fasting how does the liver make glucose?

Answer 1

→Glycogenolysis: - breakdown of glycogen store to glucose

→ Gluconeogenesis:- making glucose from non-glucose sources, e.g. lactate, alanine, fatty acids

Question 2

Which cells in the pancreas release glucagon?

Answer 2

→ alpha cells

Question 3

What are the roles of insulin on adipose tissue?

Answer 3

→ glucose uptake
→ lipogenesis
→ reduced lipolysis

Question 4

What is the effect of insulin on muscle?

Answer 4

→ increased glucose uptake
→ increased glycogen synthesis
→ increased protein synthesis

Question 5

What is the role of insulin in the liver?

Answer 5

→ reduced gluconeogenesis
→ increased glycogen synthesis
→ increased liponeogenesis

Question 6

What are the functions of adrenaline in metabolism?

Answer 6

→ Mobilises fuels in acute stress
→ stimulates glycogenolysis;

→ stimulates fatty acid release

Question 7

What are the functions of cortisol on metabolism?

Answer 7

→ Changing long term
→ amino acid mobilization

→ gluconeogenesis

Question 8

What are the functions of GH in metabolism?

Answer 8

→ Inhibits insulin action

→ stimulates lipolysis

Question 9

Define diabetes

Answer 9

→ a metabolic disorder characterised by chronic hyperglycaemia, glycosuria and associated abnormalities of lipid and protein metabolism

Question 10

What are the 4 classifications of diabetes?

Answer 10

→ Type 1
→ Type 2: Insulin secretion is retained but there is target organ resistance to its actions

→ Secondary: chronic pancreatitis, pancreatic surgery, secretion of antagonists

→ Gestational

Question 11

What is the most common cause of Type1 DM?

Answer 11

→ autoimmune destruction of B-cells

→ strong link with HLA genes within the MHC region on chromosome 6

Question 12

Which demographic is Type 1DM predominant in?

Answer 12

→ children and young adults

Question 13

Describe the pathogenesis of Type 1 DM?

Answer 13

→ Destruction of B-cells starts with autoantigen formation

→ Autoantigens are presented to T-lymphocytes to initiate autoimmune response

Question 14

What is the most commonly detected antibody associated with Type 1 DM?

Answer 14

→ the islet cell antibody

Question 15

What are the three antigens that antibodies work against in Type 1 diabetes

Answer 15

→ glutamic acid decarboxylase (GAD);
→ insulin;
→ a tyrosine-phosphatase-like molecule

Question 16

What is amylin?

Answer 16

→ a glucoregulatory peptide hormone co-secreted with insulin
→ lowers blood glucose by slowing gastric emptying,
→ suppressing glucagon output from pancreatic cells

Question 17

What does amylin suppress?

Answer 17

→ glucagon output

Question 18

What leads to ketoacidosis in Type 1 DM?

Answer 18

→ increased lipolysis
→ Increased
free fatty acids 
(FFA
→ Increased FFA 
oxidation (liver

Question 19

Describe the steps to diabetic coma

Answer 19

→ Hyperglycemia
→ Glycosuria
→ Polyuria
→ Volume 
depletion

Question 20

What can lead to polyphagia?

Answer 20

→ hyperglycaemia

Question 21

What can lead to polydipsia?

Answer 21

→ Volume

depletion

Question 22

What are the presentations of Type 2 DM?

Answer 22

→ Slow onset (months/years)

Patients middle aged/elderly – prevalence increases with age

Strong familiar incidence

Pathogenesis uncertain – insulin resistance; β-cell dysfunction:

Question 23

What can lead to HONK state?

Answer 23

→ increased gluconeogenesis

→ increased glycogenolysis

Question 24

What is involved in the diagnosis of HONK state?

Answer 24

→ increased glucose
→increased osmolarity
→ reduced pH

Question 25

What is involved in the diagnosis of diabetes in the presence of symptoms?

Answer 25

→ Random plasma glucose → Fasting plasma glucose → Oral glucose tolerance test (OGTT)

Question 26

What is involved in the diagnosis of diabetes in the absence of symptoms?

Answer 26

→ test blood samples on 2 separate days

Question 27

What is fasting defined as?

Answer 27

→ no caloric intake for at least 8 h

Question 28

When should OGTT be carried out?

Answer 28

→ in patients with IFG → in unexplained glycosuria → in clinical features of diabetes with normal plasma glucose values

Question 29

When are blood samples collected in OGTT?

Answer 29

→ at 0 and 120 mins after glucose

Question 30

What is the stepwise treatment for T2D?

Answer 30

→ diet and exercise → oral monotherapy → oral combination → insulin +- oral agents

Question 31

What are incretins?

Answer 31

→ help the body produce more insulin only when it is needed → reduce the amount of glucose being produced by the liver when it is not needed

Question 32

What are GLP-1 agonists?

Answer 32

→ work by copying, or mimicking, the functions of the natural incretin hormones in your body that help lower post-meal blood sugar levels

Question 33

What are the drug treatments of T2DM?

Answer 33

``` → Metformin: → Sulfonylureas → Thiazolidinediones: → SGLT2 inhibitors: → Incretin targeting drugs: DPP-4 inhibitors (prevent breakdown of natural incretins) → Synthetic GLP-1 analogues ```

Question 34

What is the aim of monitoring glycaemic control?

Answer 34

→ to prevent complications or avoid hypoglycaemia

Question 35

What is involved in self monitoring in DM?

Answer 35

→ Capillary blood measurement | urine analysis: glucose in urine gives indication of blood glucose concentration above renal threshold

Question 36

What is HbA1C?

Answer 36

→ glycated Hb; | → covalent linkage of glucose to residue in Hb.

Question 37

Define hypoglycaemia

Answer 37

→ Defined as plasma glucose < 2.5 mmol/L

Question 38

What are the causes of hypoglycaemia?

Answer 38

→ Drugs are the most common cause; → quinolone, quinine, beta blockers, ACE inhibitors and IGF-1 → endocrine disease → inherited metabolic diseases eg hereditary fructose intolerance → sepsis

Question 39

What are some secretagogues that can cause hypoglycaemia?

Answer 39

→ glyburide, → glipizide → glimepiride

Question 40

How does ethanol cause hypoglycaemia?

Answer 40

→ inhibit gluconeogenesis, but not glycogenolysis.

Question 41

How does sepsis cause hypoglycaemia?

Answer 41

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

Question 42

How does CKD cause hypoglycaemia?

Answer 42

→ impaired gluconeogenesis, → reduced renal clearance of insulin → reduce renal glucose production.

Question 43

What is reactive hypoglycaemia?

Answer 43

postprandial hypoglycaemia

Question 44

What are some causes of reactive hypoglycaemia?

Answer 44

→ benign (non-cancerous) tumour in the pancreas may cause an overproduction of insulin, → too much glucose may be used up by the tumour itself. → deficiencies in counter-regulatory hormones: e.g. glucagon.

Question 45

What are the neurogenic symptoms of hypoglycaemia?

Answer 45

→ triggered by falling glucose levels → activated by ANS & mediated by sympathoadrenal release of catecholamines and Ach

Question 46

What are neuroglycopenic symptoms of hypoglycaemia?

Answer 46

``` → result of brain neuronal glucose deprivation → confusion, → difficulty speaking, → ataxia, → paresthesia, → seizures, → coma, → death ```