Physiology Of Altered Pancreatic Function And Managment Of Diabetes Flashcards
Effects of insulin deficiency on metabolism
Fat:
Lack of insulin leads to disinhibition of lipase
Induces break down of triacylglycerol-> glycerol and fatty acids
Glycerol used for gluconeogensis
Fatty acids decreased to acetoy coA in liver
Synthesis of ketone bodies
Protien:
Increased muscle protein degradation->increased amino acids-> increased ketone bodies
Carbohydrate: glucagon dominates-> increased glycogenolysis-> increased blood glucose-> increased ketone bodies
Kidneys max absorption-> glycosuria
Metabolic acidosis form ketones-> CNS Depression
Osmotic diuresis
Effects of metabolic hormones
Insulin-> decreased gluconeogensis and glycogenolysis, increased glucose uptake and use
Glucagon->increase glycogenoloysis and gluconeogensis, no effect on glucose uptake
Growth hormone-> no effect on glyconeogensis, increased gluconeogensis, desecreased uptake and use
Adrenaline-> increase glycogenolysis and gluconeogensis! decreased glucose uptake and use
Cortisol-> no effect on glycogenolysis, increased gluconeogensis and decrease uptake and used
Define diabetes mellitus and causes
Chorionic metabolic disorder characterised by hyperglycaemia
Caused by:
Type 1-> insulin deficiency 5-15%
Type 2-> impaired beta cell function and/or loss of insulin sensitivity 85-95%
Signs and symptoms of diabetes
Type 1 and 2: Thirst Polyuria, glycosuria Fatigue and malaise Blurred vision Infections Type 1: Weight loss Ketoacidosis Type 2: Lots of type 2 asymptomatic
Diagnostic criteria of diabetes
Normal glucose levels:
Fasting 48mmol/mol normal 20-42
Impaired glucose regulation
Pre diabetes:
Impaired glucose tollerance test:
Fasting 7.8 but 6.1 but <7
Type 1
Autoimmune Progressive destruction of beta cells Onset usually <40 Susceptibility genes, environmental triggers Rapid onset Weight normal or less Ketosis Treat with insulin
Type 2
Relative insulin deficiency Onset > 40 years Susceptibility genes, environmental triggers Gradual onset Complications at time of diagnosis in 25% Usually over weight No ketones Treatment: Diet 10-20% Tablets 60-70% Insulin 20%
Secondary causes
Endocrine: Cushings Acromegaly Phaeochromocytoma Pancreatic disease: Chronic pancreatitis Surgery Cystic fibrosis Tumour Genetic disorders: Downs sundown Parader willi Drug induced: Steroids Beta blockers Diuretics
Treatment strategy for type 2
Diet/life style interventions
Oral hypoglycaemic agent->
Metformin-> first line but contraindicated in renal impairment, GI side effects
Sulphonyourea-> ok if not overweight
Combination of both or one with T2D, exendiate, DPP4
Combination of three or add insulin
Add or increase insulin or insulin alone
Current type two drug therapy
Biguanides-> Metformin
Sulphonylureas-> glicazide, tolbutamide, glibendamide-> stimulates insulin secretion via blockade of islet beta cell ATP sensitive K channels
Prandial glucose regulators-> repaglinide, nateglinide-> rapid acting insulin secretagens
Thiaziluneduines-> proglitazone-> PPARyagonists-> insulin sensitisers
Alpha glucosidase inhibitors-> aeorbose-> delays digestion and absorption of starch and sucrose
DPP-4 inhibitors-> sitagliglipitin, vildsglipitin, saxaglipitin-> Incretins inhancers
Both promote satiety
Sodium glucose transporter 2-> dapsgliflozin-> SGLT2 inhibitor-> inhibits renal glucose reabsorption
Limitations of drug therapy
Used to augment effects of diet and exercise not replace
Many patients don’t reach target
Need for combination therapy
Long term used-> efficacy loss
Side effects of weight gain and hypoglycemia
Insulins
Animal-> porcine, bovine
Human-> semi synthetic->enzymatically modified porcine
recombinant-> e.cloli, yeast
Classification of insulin
Short acting: Soluble Analogues-> lispro, asport Intermediate acting-> isophane Long acting: Insulin, zinc suspension Analogues-> glurgine, detemir Biphasic->mix of short and intermediate acting Basal->long acting-> twice per day Bolus-> short acting-> before meals
