clinical, workshops and labs Flashcards
What is diabetes mellitus?
- a metabolic disorder characterised by persistent hyperglycaemia
- in association w/ other cardiovascular risk factors
Why must blood glucose be regulated?
- hydrolysis/digestion of carbohydrates releases glucose absorbed across gut into blood
- low/high BGC levels disrupts cellular processes
- homeostatic control maintains safe BGC levels
- body has robust regulatory processes to prevent hypo- + hyperglycaemia
What is the normal range of blood glucose levels and when are they highest/lowest?
• BG levels 4 to 8mmol/l (70-100mg/dl)
• normally well controlled
- higher after meals
- lowest in morning (‘fasting’)
State the glucose concentration ranges for:
a) renal threshold (approx. at which glucose appears in urine)
b) fasting level diagnostic for diabetes
c) normal (fasting)
d) hypoglycaemic coma
a) 140-180mg/dL (hyperglycaemia)
b) 110-140mg/dL
c) 60-110mg/dL
d) 30-60mg/dL (hypoglycaemia)
What are the 3 key symptoms of diabetes?
- tiredness
- polydipsia (thirst)
- polyuria
(others; increased hunger, weight loss, lack of interest/concentration, blurred vision, frequent infections, slow-healing wounds)
Name some diagnostic tests for diabetes.
- urine dipstick test
- bloods sent for further testing:
• fasting BG levels
• oral glucose tolerance test - after 2 hours BGC should peak (at level)
• HbA1C levels
What is ketonuria?
a medical condition where ketone bodiespresent in urine
Describe the oral glucose tolerance test.
- can be used to help diagnose effect of medication on diabetes/pre-diabetes
- measures how well your body’s cells can absorb 75g glucose after 2 hours and used as a diabetes test
- tests for pre-diabetes, gestational diabetes, insulin resistance, reactive hypoglycaemia (low BG after meal)
Describe the HbA1c blood test.
- amount of glucose that combines w/ Hb ∞ total amount of sugar in system at that time
- RBCs survive for 8-12 weeks before renewal
- measuring glycated haemoglobin (or HbA1c) reflects avg. BGC over that duration, providing useful longer-term gauge of BG control
- if BGC has been high in recent weeks, HbA1c will also be greater
State the FPG, OGTT, HBA1C for those who are:
a) normal
b) pre-diabetes (ranges)
c) diabetes
(from the Oral Glucose Tolerance test)
a)
- FPG: <5.5 mmol/L
- OGTT: <7.8 mmol/L
- HBA1C: <42mmol/L (<6%)
b)
- FPG: 5.5-7.0 mmol/L
- OGTT: 7.8-11.1 mmol/L
- HBA1C: 42-47mmol/L (<6-6.4%)
c)
- FPG: >7.0 mmol/L
- OGTT: >11.1 mmol/L
- HBA1C: >47mmol/L (>6.4%)
What is required to diagnose diabetes (WHO)?
• typical symptoms of hyperglycaemia and:
- random venous plasma glucose: 11.1 mmol/l
- or fasting plasma glucose: 7.0 mmol/l
- or 2-hour plasma glucose 11.1 mmol/l (after 75 g OGTT)
• no symptoms
- at least 2 lab plasma glucose tests (or HbA1c) on different days w/in diabetic range
Describe the epidemiology of diabetes.
- increasing in UK
- prevalence shows ethnic variation: higher in UK Asian population
- years of life lost due to diabetes compared to other common diseases
- early detection + intervention key → before macro + microvascular complications
How is diabetes classified?
• type 1 (IDDM), 10%: immune-mediated or idiopathic
• type 2 (NIDDM), 77%: predominantly insulin-resistance or insulin secretory defect
• gestational diabetes mellitus (GDM), 12%
• other specific types, 1%:
- maturity onset diabetes in young (MODY)- mutation, strong familial inheritance
- genetic defects of insulin action
- diseases of exocrine pancreas
- endocrinopathies (pancreatic diseases)
- drug/chemical-induced diabetes (beta-blockers, corticosteroids, antipsychotics)
How many people in the UK are living with diabetes?
4.6 million
What is an exocrine and endocrine cell and how abundant are beta-cells?
- exocrinegland- secretes enzymes to break down proteins, lipids, carbohydrates and nucleic acids in food.
- endocrinegland- secretes hormones insulin and glucagon to control BGC throughout day
- B-cells are most abundant isletcells
Which profiles can help confirm diabetes and which value is essential?
- physiological nocturnal insulin and glucose profiles
- fasting BGC
Describe homeostatic regulation of BGC.
- plasma glucose levels increase → plasma insulin levels increase
- exogenous glucose levels increase → endogenous glucose levels should decrease
- homeostatic maintenance of constant, stable blood glucose concentration (approx 3.3-6.7mmol/l)
- insulin secretion constantly adjusts to achieve this
Name some other important actions of insulin and what excess glucose can lead to.
• lipid metabolism
• cell growth
• protein synthesis
- leads to osmotic diuresis
What is insulin and what effect does it have on GLUT 4?
- a peptide hormone
- binds to its transmembrane insulin receptor
- increases GLUT 4 surface expression
- GLUT4:
• insulin-regulated glucose transporter
• transports glucose into cell
• ensures rate of glucose entry into β-cells is ∞ [extracellular glucose]
What does the insulin signal transduction cascade also results in?
- hexokinase activation so glucose is phosphorylated
- and glycolysis is initiated
Describe the effects of GLUT4 after food on a molecular level.
- rise in BGC after meal, stimulates insulin secretion from B-cells
- insulin binds to IRs on muscle and fat cells
- leads to phosphorylation of IRS-1
- triggers insertion of GLUT4 into cell membrane and uptake of glucose into cell
(IRS = insulin receptor substrate)
State the 5 stages of insulin release from a β-cell.
- glucose that enters β-cell is metabolised via glycolysis (Kreb’s cycle)
- metabolism of glucose produces high ratio of ATP
- increased intracellular ATP:ADP ratio closes ATP-sensitive K⁺ channels preventing K⁺ ions from leaving cell by facilitated diffusion (leading to build-up of intracellular K⁺ ions) so inside of cell becomes -VE w.r.t outside, leading to depolarisation of cell membrane.
- upondepolarisation, voltage-gatedCa2⁺ channelsopen, allowing Ca2⁺ ions to move into cell by facilitated diffusion
- significantly increased amount of Ca2⁺ ions in cells’ cytoplasm causing release previously synthesized insulin (stored in vesicles) into blood
(see notes for diagram)
Describe glucagon release.
• glucagon is a peptide hormone secreted from α-cells of pancreas in response to:
- low BGC
- sympathetic ANS activation in exertion
• glucagon receptors not as abundant on cells throughout body
• liver cell membrane receptors are main targets
What is the role of amylin?
- co-secreted with insulin from pancreatic β-cells in ratio of 100:1
- plays role in glycaemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-meal (post-prandial) spikes in BGC
What is the relationship between amylin with glucagon and insulin with glucagon?
- synergistic; amylin and glucagon can be produced together
- insulin and glucagon can never be produced together
What happens if insulin and glucagon mechanisms are not controlled at each level?
- low levels- hypoglycemia
- high level- hyperglycemia
- persistently high levels: indicative of diabetes
Describe Type 1 Diabetes (IDDM) including its prevalence, risk factors, environmental agents and genetic factors.
• prevalence:
- 0.5% of UK population
- all ethnic groups affected
- 5-10% of those with diabetes
• Risk Factors
- viruses - enteroviruses (infectious diseases e.g. polio), coxsackie (HFMD), rubella
• environmental agents - cow’s milk protein, nitrites (processed + cured meats)
• genetic factors i.e. HLA types (DQ2/DQ8 celiac disease genes)
Describe Type 2 Diabetes including its prevalence and risk factors.
• risk factors (multifactorial): - genes - environment - obesity - viruses – Hep C • prevalence: - 90% of people w/ diabetes - approx 6.5% of UK population - overrepresented in non-european ethnic groups - uncommon in children
State some medical complications associated with diabetes.
- microvascular; eye, kidneys, neuropathy
- macrovascular; brain, heart, extremities
- microvascular complications (cause disability)
- retinopathy- abnormal blood flow
- neuropathy- damage to peripheral nerves
- nephropathy- damage to kidney vessels
- small vessel arteriopathy
- erectile dysfunction
- absent foot pulses (no reflexes)
- ischaemic skin changes (foot)
- abnormal vibration threshold (foot) *Loss of protective sensation
State some macrovascular diseases (cause disability and premature death) which are associated with diabetes.
• coronary artery disease • cerebrovascular disease • abnormal ECG • hypertension • intermittent claudication • peripheral vascular disease* - 2–3 x increased risk of fatal stroke - 2–4 x increased risk of fatal heart disease - 15 x increased risk of amputation
State some cardiovascular risk factors related to diabetes.
- hypertension
- dyslipidaemia
- obesity
How can the risks of type 2 diabetes be managed (monitoring glycaemic control)?
• blood glucose - short-term - day-to-day variation • glycated proteins - fructosamine test: glycated albumin (approx 2 weeks) - HbA1c: 8-12 weeks • other glycated products - advanced glycated - end-products - proteins and lipids
