Which hormone has a hypoglycaemic action?
Insulin
Which hormones have a hyperglycaemic action?
Glucagon, adrenaline, cortisol, growth hormone
What are some causes of hypoglycaemia?
1) Exertion/exercise - skeletal muscle uses a lot of glucose
2) Fasting - no glucose entering from the gut
3) Excess exogenous insulin
4) Insulinoma (excess endogenous insulin)
5) Alcohol intake
- Causes an increase in endocrine pancreatic microcirculation, increasing insulin secretion
- Inhibits hepatic gluconeogenesis
What are some actions of insulin?
Stimulates glucose transport (muscle, adipose tissue)
Stimulates glycogen synthesis (liver, muscle)
Inhibits gluconeogenesis (liver)
Stimulates protein synthesis; antagonises proteolysis
Facilitates vasodilation
Stimulates K ion uptake into cells
Stimulates Na reabsorption in renal tubule
Activates lipogenesis (Liver, muscle, adipose tissue)
Inhibits fatty acid oxidation (Liver, muscle)
Inhibits lipolysis (Adipose tissue)
Acts as a growth factor and has effects on gene expression
How does the hypothalamus stimulate insulin secretion?
Lateral hypothalamus –> motor nuclei of vagus –> parasympathetic nerves to islet –> release of ACh, VIP, PACAP, GRP –> Insulin secretion
How does the hypothalamus inhibit insulin secretion?
Medail hypothalamus –> sympathetic motor neurones (cord) –> sympathetic nerves to islet –> release of noradrenaline, galanin, NPY –> Inhibits insulin secretion
What are some causes of hyperglycaemia?
Stress: chronically high cortisol and adrenaline
- Both hormones activate glycogenolysis in the liver
Absolute absence of insulin (Type-1 diabetes, T1DM)
- Autoimmune destruction of the pancreatic β-cells
- Dawn phenomenon in T1DM due to diurnal surge in cortisol
Relative insufficiency of insulin (insulin resistance leading to T2DM)
- Insulin is secreted, but tissues (or specific pathways) are not sensitive to it
What are the factors involved in the Insulin Resistance Syndrome?
- Decreased incretin effect
- Increased lipolysis
- Increased glucose reabsorption
- Decreased glucose uptake
- Neurotransmitter dysfunction
- Increased hepatic glucose production
- Increased glucagon secretion
- Decreased insulin secretion
How can you improve control of blood glucose?
- Improve insulin sensitivity (exercise, improved diet, insulin sensitisers)
- Stimulate endogenous insulin secretion
- Inhibit hepatic glucose production
- Prescribe exogenous insulin
What complications can arise from chronic hyperglycaemia in poorly controlled diabetes?
- Non-enzymic modification of proteins by glucose: glycation of haemoglobin (HbA1C)
- Sorbitol pathway overactivity; formation of osmotically active metabolites
- Disturbance of cellular redox state
- Impaired vasodilation
- Peripheral neuropathy; cataract; blindness; impaired kidney function
What are the actions of metformin?
Liver:
- decrease gluconeogenesis
- decrease glycogenolysis
- decrease oxidation of fatty acids
Muscle:
- Increase glucose uptake and oxidation
- Increase glycogenolysis
- Decrease oxidation of fatty acids
Define diabetes mellitus
A heterogenous complex metabolic disorder characterised by elevated blood glucose secondary to either resistance to the action of insulin or insufficient insulin secretion or both.
What are the 4 stages in the spectrum of diabetes according to WHO criteria?
Normal - HbA1c less that 42mmol/mol, Fasting Plasma Glucose < 6.1mmol/L
Impaired Fasting Glucose - FPG>6.1 mol/L but less than 7mmol/L
Impaired Glucose Tolerance - OGTT 2h glucose greater or equal to 7.8mmol/L but less than 11.1 mol/L (HbA1c of 42-47mmol/mol = high risk of diabetes)
DM - HbA1c 48mmol/mol and above, FPG above 7mmol/L OR OGTT 2h greater than 11.1 mmol/L
Who can you not use HbA1c for?
young patients (under 18), pregnant, acutely unwell, CKD or anaemia
How do T1DM patients tend to take their insulin?
Basal-bolus regime
What are the criteria for DKA?
D - diabetic - BM>11.1 (can be normal!)
K - ketonaemia (blood ketones >=3 or urine ketones >=3+)
A - acidosis pH < 7.3 or bicarb <=15
What are some causes of recurrent DKA?
- Insulin technique and sites
- Carb counting
- Alcohol
- Pregnancy
- Psychological and psychosocial difficulties eg. body image, needle phobia
- Nature of lifestyle
- Possible organic causes such as gastroparesis
- Iatrogenic causes eg. surgery
What are some oral hypoglycaemic agents?
- Decrease hepatic gluconeogenesis - Biguanides (metformin)
- Increase insulin secretion - sulfonylureas (eg. Gliclazide)
- Reduce insulin resistance - Thiazolidinediones (TZDs eg. pioglitazone)
- Prevent breakdown of GLP - DPP-4 inhibitors
- Promote glycosuria - SGLT2 inhibitors
- Decrease carbohydrate absorption - alpha-glucosidase inhibitor
What are the 4 key hormones responsible for glucose regulation?
Amylin Pancreatic beta-cells - Suppresses post-prandial glucagon secretion - Slows gastric emptying - Reduces food intake and body weight
Insulin Pancreatic beta-cells Promotes: - Glucose uptake by cells - Protein and fat synthesis - Use of glucose as energy - Suppresses post-prandial glucagon secretion
Glucagon Pancreatic alpha-cells Promotes: - Breakdown of liver glycogen stores - Hepatic gluconeogenesis - Hepatic ketogenesis
GLP-1
Small intestine L-cells
Promotes:
- Glucose-dependent insulin production
- Suppresses post-prandial glucagon secretion
- Slows gastric emptying
- Reduces food intake and body weight (increases satiety, hypothalamic level)
What is metabolic syndrome?
Metabolic syndrome is a cluster of the most dangerous CVD, diabetes and prediabetes, abdominal obesity, high cholesterol and high blood pressure
What are the diagnostic criteria for gestational diabetes?
- Fasting plasma glucose level of 5.6 mmol/L or above
or - 2-hour plasma glucose level of 7.8 mmol/L or above on the OGTT
What are some of the parameters of the pathophysiology of T2DM?
- Increased hepatic glucose production
- Increased glucagon secretion by islet alpha cells
- Decreased glucose uptake
- Increased lipolysis
- Impaired appetite regulation
- Decreased insulin secretion from beta cells
- Increased glucose reabsorption
- Decreased incretin effect
What is concordance?
A negotiated, shared agreement between clinician and patient concerning treatment regime(s), outcomes and behaviours; a more co-operative relationship than those based on issues of compliance and non-compliance
What is compliance?
The fulfilment by the patient fo the healthcare professional’s recommended course of treatment
