Diabetes And Hypoglycaemia Flashcards
How are blood glucose levels maintained?
- Via dietary carbohydrates, glycogenolysis and gluconeogenesis
Describe what happens in the fasting state?
- 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
Describe the plasma regulation with high blood sugar
High blood sugar -> Pancreas -> Insulin -> stimulates glycogen formation from glucose in liver -> lowers blood sugar
Describe the plasma regulation of low blood sugar
Low blood sugar -> Pancreas -> Glucagon -> Stimulates glycogen breakdown to glucose in liver -> Raises blood sugar
Describe the function and major metabolic paths for Insulin
- Promotes growth and storage
- Stimulates glucose storage in muscle, liver
- Stimulates protein & fatty acids synthesis
Describe the function and major metabolic paths for Glucagon
- Mobilises fuel and maintains blood glucose in fasting state
- Activates gluconeogenesis and glycogenolysis
- Activates fatty acid release
Describe the function and major metabolic paths for Epinephrine
- Mobilises fuels in Acute stress
- Stimulates glycogenolysis
- Stimulates fatty acid release
Describe the function and major metabolic paths for cortisol
- Changing long term
- Amino acid mobilisation, gluconeogenesis
Describe the function and major metabolic paths for growth hormones
- Inhibits insulin action
- Stimulates lipolysis
What is diabetes mellitus?
Metabolic disorder characterised by chronic hyperglycaemia, glycosuria (glucose in urine) and associated abnormalities of lipid and protein metabolism
State the 4 classifications of diabetes?
- 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.
Describe the key features of type 1 DM with its most common cause?
- 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.
Describe the pathogenesis of type 1 DM?
- 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
Describe how beta cells are destroyed via autoantodies?
VD
What does destruction of the pancreatic beta cells leads to and why?
- 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
State the metabolic complications of type 1 DM?
- 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
Describe key presentations of type 2 DM?
- Slow onset (months/years), Patients middle aged elderly - prevalence increase with age
- Strong familiar incidence
- Pathogenesis uncertain - insulin resistance; 3-cell dysfunction:
Describe the pathophysiology of type 2 DM?
- 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)
Describe the pathogenesis of hyperglycaemic hyperosmolar nonketotic
coma (HONK) state + its diagnosis?
VD
Describe the diagnosis of type 2 DM when symptoms are presented
- 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
Describe the diagnosis of type 2 DM when symptoms are aren’t present?
- Absence of symptoms -> test blood samples on 2 separate days
State the fasting plasma glucose + Oral glucose tolerance test values for individuals with Impaired Glucose Tolerance (IGT - prediabetic) + Impaired Fasting Glycaemia (IFG)?
- 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
What is the oral glucose tolerance test?
When should it be carried out?
- 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
Describe the oral glucose test
- Process
- 75g oral glucose
- test after 2 hour
- Blood samples collected at 0 and 120 mins after glucose
State the drugs used for the treatment of T2 DM?
- 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)
What does incretin do?
- Produces insulin
- Decreases glucose production in liver
Describe how glycaemic control is monitored and its aim?
- 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
State the long term complications of both type 1 and type 2 DM
- Micro-vascular disease -> retinopathy, nephropathy, neuropathy
- Macro-vascular disease -> related to atherosclerosis heart attack/stroke
- Exact mechanisms of complications are unclear
Define the plasma glucose range for hypoglycaemia
PG < 2.5 mmol
State the causes for hypoglycaemia
- Causes of hypoglycaemia
- Drugs are most common cause
- Common in type 1 diabetes
- Less common in type 2 diabetes taking insulin & insulin secretagogues
What does Insulin secretagogues do?
- Insulin secretagogues help your pancreas make and release (or secrete) insulin
- Insulin helps keep your blood glucose from being too high
What drugs can cause hypoglycaemia in individuals with diabetes?
- Types of sulfonylureas
- Exogeneous insulin & insulin secretagogues
- Glyburide, glipizide + glimepiride
What causes hypoglycaemia in individuals without diabetes?
- 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
State 3 factors which can induce hypoglycaemia?
- Ethanol
- Sepsis
- Chronic kidney disease
Explain how ethanol can cause hypoglycaemia
- inhibit gluconeogenesis, but not glycogenolysis
- HG follow several days alcohol binge with limited food intake
- Leads to Hepatic depletion of glycogen
Explain how Sepsis can cause hypoglycaemia
- Cytokine accelerated glucose utilization
- induced inhibition of gluconeogenesis in the setting of glycogen depletion
Explain how Chronic kidney disease can cause hypoglycaemia
- Mechanism not clear
- Impaired gluconeogenesis
- Decreased renal clearance of insulin + Decreased renal glucose production.
What is reactive hypoglycaemia and describe potential causes (3)?
- 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
Describe the signs of hypoglycaemia
- Neurogenic (autonomic) signs
- triggered by decrease in glucose levels
- Activated by ANS & mediated by sympathoadrenal release of catecholamines + Ach
Describe the symptoms of hypoglycaemia?
- Neuroglycopaenia = neuronal glucose deprivation in brain - Sign & symptoms:
- Confusion, difficulty speaking, ataxia, paresthesia, seizures, coma, death
