Endocrinology Flashcards
WHO definitions of DM
reduction in insulin action sufficient to cause level of hyperglycaemia which will result in microvascular pathology:
plasma glucose concentration (mmol/L): -fasting >7.0 (x2 or + symptoms) OR -2h post glucose load (or random glucose) >11.1 \+ -HbA1c > 48 mmol/mol
WHO definitions of impaired glucose tolerance (non diabetic hyperglycaemia)
blood glucose is raised above normal but not enough to cause microvascular damage:
plasma glucose concentration (mmol/L): -fasting <7.0 OR -2h post glucose load 7.8-11.1 \+ -HbA1c 42-47 mmol/mol
what does HbA1c represent
glycosylated haemoglobin (over a period of 3 months)
which kind of fat drives insulin resistance
abdominal obesity (visceral fat)
risk factors in insulin resistance diabetes
family history ethnicity (black african, south asian) age social deprivation diet composition lack of exercise overweight and obesity (visceral)
what is the twin cycle hypothesis in DMT2
pre existing insulin resistance: positive calori balance leads to:
liver cycle: increase liver fat –> resistance to insulin suppression of hepatic glucose production –> increase plasma glucose/ increase insulin secretion
pancreas cycle: increase liver fat –> increase VLDV triglyceride –> taken up by beta cells in pancreas: increase islet triglyceride–> decrease acute insulin response to food –> increase in plasma glucose
def polyphagia
excessive hunger or increased appetite
clinical presentation of diabetes
- symptoms of hyperglycaemia (thirst, polyuria, polyphagia, tiredness, weight loss + subacute Candida infection )
- hyperglycaemic emergency (diabetic ketoacidsis or HHS)
- diabetic complications (neuropathy, retinopathy, nephropathy, ACS, Stoke, PVD, erectile dysfunction)
- asymptomatic (present at cardiovascular disease review, NDH or gestational diabetes annual review, age related health check, other acute illness
different types of insulin
quick acting: route: subcutaneous injection/infusion, IV infusion
slow acting: route: subcutaneous injection only
(can have added chemical compounds added to slow the absorption i.e. isoprene, lente, soluble)
bi-phasic (mixes of QA and SA, ratio of 25/75 or 30/70)
(basal analogues)
what increases insulin sensitivity
reduced calorie intake increased islet function
weight loss
exercise
what are the different drugs for type 2 diabetes
- reduce insulin resistance (biguanides i.e. metformin and thiazolidenediones i.e. pioglitazone)
- increase beta cell activity (sulphonylureas i.e. gliclazide and meglitinides i.e. nateglinide)
- increase GLP1 activity (DPP4 inhibitors i.e. sitagliptin and ingrains, GLP1 agonists i.e. exenatide)
- slow glucose absorption (acarbose: alpha-glucosidase inhibitor)
- enhance glucose excretion (SGL2 inhibitors ie dapagliflozin)
- insulin supplementation
main side effects of diabetes drugs
- weight gain (all drugs that increase beta cell activity: sulphonylureas, meglitinides and insulin)
- hypoglycaemia (all drugs that increase beta cell activity: sulphonylureas, meglitinides and insulin)
- GI symptoms ie diarrhoea, nausea, abdo discomfort (metformin, incretins, acarbose)
- weight loss (metformin, incretins, SGLT2 inhibitors)
- random i.e. osteoporosis (pioglitazone), UTI (SGLT2 inhibitors)
what you check in your annual tests for diabetes
lipids UACR (urine albumin:creatinine ratio) eGFR foot exam refer to diabetic eye screening program
risk factors for microvascular diabetic complications
insulin resistance
genes
proportional to hyperglycaemia and hypertension
how does visual loss occur in diabetic eye disease
- capillary leakage
- capillary occlusion
stages of chronic kidney disease (CKD)
stage 1: microproteinuria: kidney damage with normal/increased GFR (GFR>90)
stage 2: mic/macroproteinuria: kidney damage with mid reduction GFR (GFR 60-90)
stage 3: macroproteinuria: moderate reduction GFR (GFR 30-59)
stage 4: macroproteineuria: severe reduction GFR (GFR 15-29)
stage 5: macroprotinuria: kidney failure ESRF (GFR<15)
minimising blindness in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: BM control, BP control
secondary prevention: early detection of sight threatening retinopathy (retinal screening), ALLC (anti VEGF), BM and BP control
salvage therapy: vitrectomy
minimising end stage kidney disease in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: BM control
secondary prevention: early detection of minimal nephropathy (UACR, eGFR), intensive BP control (<120/75, ACEi, A2RB), BM and vascular risk factor control
salvage therapy: diet, epo, ca, vitD, bicarbonate, early AVF, early transplantation, dialysis
minimising amputation in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: BM control, lifestyle (smoking, exercise, alcohol)
secondary prevention (early identification of ‘at risk’ feet, footwear protection programme, BM and vascular risk factor control
salvage therapy: prompt multidisciplinary high risk foot team, revascularisation, local amputation
minimising adverse pregnancy outcomes in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: pre-pregnancy BM control/folate
secondary prevention: intense retinal and renal screening/management
salage therapy: anomaly screening, foeti-placental monitoring
What is the link between between diabetes an cardiovascular disease?
Metabolic syndrome
Lifestyles
Subclinical inflammation (raised CRP, TNF-alpha, IL6)
Lipid excess and hyperglycaemia are toxic to beta cells
More?
Abnormalities of insulin secretion and action DMT2
Insulin resistance: associated with central obesity and intracellular triglyceride accumulation in muscle and liver (often NAFLD)
Pathophysiology: Decreased beta cell mass and islet amyloid deposition (it is cosecreted with insulin)
Hypersécrétion of insulin (blood insulin levels are higher than normal)
Insulin insufficiency: Increase gluconeogenesis and reduced glucose uptake by peripheral tissues
More
where does the parathyroid hormone act upon?
- kidneys (simulates tubules for increased reabsorption)
- bones (stimulates osteoblasts to release RANKL which stimulates osteoclasts to reproduce)
- gut (increase absorption of calcium)
what are the effects of hypercalcaemia?
NS:
- anxiety
- depresion
- cognitive change
- mantal changes
- lethargy
- coma
muscles (mainly gut smooth muscles)
- weakness
- cramping
- nausea, vomiting
- anorexia
heart: arrhythmias
