DH Flashcards
During fasting how does the liver make glucose?
→Glycogenolysis: - breakdown of glycogen store to glucose
→ Gluconeogenesis:- making glucose from non-glucose sources, e.g. lactate, alanine, fatty acids
Which cells in the pancreas release glucagon?
→ alpha cells
What are the roles of insulin on adipose tissue?
→ glucose uptake
→ lipogenesis
→ reduced lipolysis
What is the effect of insulin on muscle?
→ increased glucose uptake
→ increased glycogen synthesis
→ increased protein synthesis
What is the role of insulin in the liver?
→ reduced gluconeogenesis
→ increased glycogen synthesis
→ increased liponeogenesis
What are the functions of adrenaline in metabolism?
→ Mobilises fuels in acute stress
→ stimulates glycogenolysis;
→ stimulates fatty acid release
What are the functions of cortisol on metabolism?
→ Changing long term
→ amino acid mobilization
→ gluconeogenesis
What are the functions of GH in metabolism?
→ Inhibits insulin action
→ stimulates lipolysis
Define diabetes
→ a metabolic disorder characterised by chronic hyperglycaemia, glycosuria and associated abnormalities of lipid and protein metabolism
What are the 4 classifications of diabetes?
→ 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
What is the most common cause of Type1 DM?
→ autoimmune destruction of B-cells
→ strong link with HLA genes within the MHC region on chromosome 6
Which demographic is Type 1DM predominant in?
→ children and young adults
Describe the pathogenesis of Type 1 DM?
→ Destruction of B-cells starts with autoantigen formation
→ Autoantigens are presented to T-lymphocytes to initiate autoimmune response
What is the most commonly detected antibody associated with Type 1 DM?
→ the islet cell antibody
What are the three antigens that antibodies work against in Type 1 diabetes
→ glutamic acid decarboxylase (GAD);
→ insulin;
→ a tyrosine-phosphatase-like molecule
What is amylin?
→ a glucoregulatory peptide hormone co-secreted with insulin
→ lowers blood glucose by slowing gastric emptying,
→ suppressing glucagon output from pancreatic cells
What does amylin suppress?
→ glucagon output
What leads to ketoacidosis in Type 1 DM?
→ increased lipolysis
→ Increased free fatty acids (FFA
→ Increased FFA oxidation (liver
Describe the steps to diabetic coma
→ Hyperglycemia → Glycosuria → Polyuria → Volume depletion
What can lead to polyphagia?
→ hyperglycaemia
What can lead to polydipsia?
→ Volume
depletion
What are the presentations of Type 2 DM?
→ Slow onset (months/years)
Patients middle aged/elderly – prevalence increases with age
Strong familiar incidence
Pathogenesis uncertain – insulin resistance; β-cell dysfunction:
What can lead to HONK state?
→ increased gluconeogenesis
→ increased glycogenolysis
What is involved in the diagnosis of HONK state?
→ increased glucose
→increased osmolarity
→ reduced pH
What is involved in the diagnosis of diabetes in the presence of symptoms?
→ Random plasma glucose
→ Fasting plasma glucose
→ Oral glucose tolerance test (OGTT)
What is involved in the diagnosis of diabetes in the absence of symptoms?
→ test blood samples on 2 separate days
What is fasting defined as?
→ no caloric intake for at least 8 h
When should OGTT be carried out?
→ in patients with IFG
→ in unexplained glycosuria
→ in clinical features of diabetes with normal plasma glucose values
When are blood samples collected in OGTT?
→ at 0 and 120 mins after glucose
What is the stepwise treatment for T2D?
→ diet and exercise
→ oral monotherapy
→ oral combination
→ insulin +- oral agents
What are incretins?
→ 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
What are GLP-1 agonists?
→ work by copying, or mimicking, the functions of the natural incretin hormones in your body that help lower post-meal blood sugar levels
What are the drug treatments of T2DM?
→ Metformin: → Sulfonylureas → Thiazolidinediones: → SGLT2 inhibitors: → Incretin targeting drugs: DPP-4 inhibitors (prevent breakdown of natural incretins) → Synthetic GLP-1 analogues
What is the aim of monitoring glycaemic control?
→ to prevent complications or avoid hypoglycaemia
What is involved in self monitoring in DM?
→ Capillary blood measurement
urine analysis: glucose in urine gives indication of blood glucose concentration above renal threshold
What is HbA1C?
→ glycated Hb;
→ covalent linkage of glucose to residue in Hb.
Define hypoglycaemia
→ Defined as plasma glucose < 2.5 mmol/L
What are the causes of hypoglycaemia?
→ 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
What are some secretagogues that can cause hypoglycaemia?
→ glyburide,
→ glipizide
→ glimepiride
How does ethanol cause hypoglycaemia?
→ inhibit gluconeogenesis, but not glycogenolysis.
How does sepsis cause hypoglycaemia?
→ Cytokine accelerated glucose utilization and induced inhibition of gluconeogenesis in the setting of glycogen depletion
How does CKD cause hypoglycaemia?
→ impaired gluconeogenesis,
→ reduced renal
clearance of insulin
→ reduce renal glucose production.
What is reactive hypoglycaemia?
postprandial hypoglycaemia
What are some causes of reactive hypoglycaemia?
→ 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.
What are the neurogenic symptoms of hypoglycaemia?
→ triggered by falling glucose levels
→ activated by ANS & mediated by sympathoadrenal release of catecholamines and Ach
What are neuroglycopenic symptoms of hypoglycaemia?
→ result of brain neuronal glucose deprivation → confusion, → difficulty speaking, → ataxia, → paresthesia, → seizures, → coma, → death
