ENDO; Lecture 15, 16, 17 and 18 - Type 1 DM, Type 2 DM, Microvascular complications and Macrovascular complications and the Diabetic Foot Flashcards
What are the different types of diabetes?
Type 1 and T2, MODY, Latent autoimmune diabetes in adults (LADA)
What is the WHO classification of obesity?
What is the pathogenesis of T1DM?
How is T1DM a relapsing-remitting disease?
The immunological response to T1D is cyclic. An increase in the numbers of autoreactive effector T cells is controlled by an increase in the number of regulatory T cells. However, over time, a gradual disequilibrium of the cyclical behavior could occur, leading to the number of autoreactive effector T cells surpassing the number of regulatory T cells, which would no longer be capable of containing autoreactive effector T-cell responses and thereby lead to a decline in pancreatic islet function
What happens in T1DM?
Beta-cells are destroyed so increased number of immune cells and inflammatory factors present
Which HLA genes do you need to have genetic susceptibility to T1DM?
NB: DR3, DR4 are important
What are the environmental factors that affect T1DM?
Though to have infection type of onset as it is more common in winter months
Which blood markers should you test in T1DM patients?
What is the presentation of diabetes?
What happens if there is a lack of insulin?
If you lack insulin, then protein breakdown isn’t stopped, glucose isn’t taken up by the muscles, fats get broken down to make more glucose
What happens if there is no insulin acting on adipocytes?
Can also produce a lot of ketones in the body, which are the ones that produce ketoacidosis
How is T1DM treated?
Reduce early mortality, avoid acute metabolic decompensation -> need exogenous insulin to preserve life with ketones defining insulin deficiency; preventing long term complications like retinopathy, neuropathy, nephropathy, vascular disease
What diet should T1DM patients have?
Reduce calories as fat and refined carbs, increase calories as complex carbs and soluble fibre; balanced distribution of food over course of day with regular meals and snacks
How does insulin treatment work?
Short acting insulin given with meals, made from human insulin or insulin analogue (lispro, aspart, glulisine); Long acting for background levels given non-c bound to zinc or protamine OR insulin analogue (Glargine, Determir, Degludec)
How long does Short/long acting insulin last?
SAI 4-6, LAI 12h
How have insulin analogues been modified?
Genetically engineered to alter absorption, distribution, metabolism and excretion
What is an insulin pump?
Continuous insulin delivery, preprogrammed basal rates and bolus for meals; doesn’t measure glucose, no completion of feedback loop -> no new needle every time
What are islet cell transplants?
Much better glucose control
How do we check glucose levels?
Capillary monitoring -> pricking the finger; MiniLink transmitter -> on the abdomen but not as reliable; measure HbA1c
What is HbA1c?
In red cells and reacts with glucose irreversibly; lifespan of RBC is 120d so it can be measured for around 4 months -> determine the rate of glycation, faster in some individuals -> however can be unreliable in Hbopathy and renal failure; forms ideal measure of long term glycaemic control and has been shown to be related to risk of complications, also lowering HbA1c associated lower risk of complication particularly microvascular complication
What is ketoacidosis?
Rapid decompensation of t1DM causing hyperglycaemia, metabolic acidosis
Why is hyperglycaemia caused in ketoacidosis?
Reduced tissue glucose utilisation, increased hepatic glucose production
Why is metabolic acidosis caused in ketoacidosis?
Circulating acetoacetate and hydroxybutyrate, osmotic dehydration and poor tissue perfusion
What are the causes of ketoacidosis?
Now presentation, insulin omission, infection/other illness
What is hypoglycaemia?
Plasma glucose of <3.6 mmol/L, severe hypo = any hypo needing help of another person to treat
How can hypo’s affect the patient?
Most mental process impaired at <3mmol/L, consciousness impaired at <2mmol/L, severe hypo may contribute to arrhythmia and sudden death; may have long-term effects on the brain, recurrent hypos result in loss of warnings
Who do hypos affect?
Main risk factor is quality of glycaemic control, more frequent in patients with low HbA1c
When do hypos occur?
Anytime but often a clear pattern, pre-lunch hypos common, nocturnal hypos very common but not recognised
Why do hypos occur?
Unaccustomed exercise, missed meals, inadequate snacks, alcohol, inappropriate insulin regime
what are the symptoms and signs of hypoglycaemia?
x
How do you treat hypoglycaemia?
What is T2DM?
State of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues, notably the retina, kidney, nerves, and arteries -> Not ketoacidosis prone, not mild and often involves weight, lipids and blood pressure
How do you screen for diabetes?
You do a fasting glucose and glucose tolerance
What is the epidemiology of T2DM?
What is the pathophysiology of T2DM?
What is MODY?
How do microvascular/macrovascular diseases come about?
How does T2DM genetic input appear?
Behaves as an autosomal dominant condition; light birth weight associated as well
How does insulin resistance and secretion change during age in T2DM?
How does T2DM present?
What is the relationship between insulin secretion and glucose tolerance?
Secretion deteriorates with progressive impairment of glucose tolerance
What contributes to increased fasting glucose in T2DM?
/impaired glucose disposal and increased hepatic glucose production -> diminished ability to store or oxidize glucose in muscle due to impaired insulin activity reduces the metabolic clearance rate of glucose (top graph), and an excessive amount of glucose is converted to lactate.1 Lactate then returns to the liver to be metabolized back to glucose (Cori cycling). The early increase in FPG in the progression to T2DM is often a result of Cori cycling from the previous night’s meal.
What is the glucose flow in insulin resistance?
High hepatic glucose output and dyslipidaemia
Which factors are affected in T2DM?
How does obesity affect T2DM?
More than precipitant, central/omental obesity, 80% of T2DM are obese -> weight reduction is useful treatments as FA and adipocytokines are important
How do preturbations in gut microbiota affect T2DM?
Occurs in obesity and insulin resistance, host signalling, bacterial lipopolysaccharides fermentation to short chain FA, bacterial modulation bile acids -> causes inflammation and signaling metabolic pathways are changed
What is a common side effect of diabetes treatments?
Weight gain, which is undesirable -> mechanism is different with each agent but with secretagogues, increased insulin levels reverse the catabolic effects of diabetes, leading to increases in weight. Thiazolidinediones (TZDs) increase adipocyte proliferation and also cause fluid retention, both of which can result in weight gain.
How do different risk factors affect T2DM onset?
How does T2DM present?
Osmotic symptoms, infection, screening test, at complication = acute: hyperosmolar coma; chronic: IHD, retinopahy
What are the complications in T2DM?
What is the basic management of T2DM?
Education, diet, pharmacological treatment, complication screening
What part of T2DM do you treat?
Symptoms, reduce chance of acute metabolic complications and chance of long term complications; education
What should T2DM eat?
Control total calories/increase exercise (weight), reduce refined carbs (less sugar), increase complex carbs (more rice), reduce fat as proportion of calories (less IR), increase unsaturated fat as proportion of fat (IHD), increase soluble fibre (longer to absorb carbs)
How do you monitor T2DM treatment?
Weight, glycaemia, BP, dyslidiaemia
What drugs should you use to treat liver, pancreas, obesity, GI, muscles in T2DM?
What is metformin and what is its function?
Where does glibenclamide work on and what is it?
Sulphonylurea -> insulin secretagogue; lean patients with T2DM where diet alone hasn’t succeeded, s/E hypoglycaemia, weight gain
What is Acarbose?
What are thiazolidinediones?
What is GLP-1?
What is the difference between GLP-1 and gliptins (DPPG-4 inhibitor)?
LHS = GLP-1
What is empagliflozin?
What other aspects of control are needed to be thought about in T2DM?
What are the risk factors associated with Diabetes mellitus?
How do you screen for diabetes?
Can be difficult to know when to screen
Which intervention works the best with T2DM - Placebo, Metformin, Lifestyle?
How are diabetes T1 and T2 compared?
If glycaemic control isn’t good enough then what happens to relative risk of retinopathy, nephropathy, neuropathy, microalbuminuria?
What are the mechanisms of glucose damage?
How does hyperglycaemia affect the body in DM?
x
What can appear in background diabetic retinopathy?
Hard exudates (cheese colour, lipid), microaneurysms (dots), blot haemorrhages
What is preproliferative diabetic retinopathy?
Cotton wool spots (soft exudates), retinal ischemia
What is proliferative retinopathy?
Visible new vessels on disk or elsewhere in retina
What is maculopathy?
Hard exudates near the macula, same disease as background but near macula and can threaten direct vision
How do you manage proliferative diabetic retinopathy?
Pan-retinal photocoagulation
How do you manage maculopathy?
Problem around macula so need only a grid of photocoagulation (NOT PRPC)
What are the negative effects of Angiotensin 2?
What are the different types of diabetic neuropathy?
How does the neuropathy initiation progress occur?
x
What can autonomic neuropathy cause?
Psotura hypotension (disabling, collapsing on standing), cardiac autonomic supply (case reports of sudden cardiac death)
What are the sequences of atherosclerosis?
x
How do different types of atheroma form?
What is the metabolic syndrome?
Insulin resistance is implicated in non-diabetic macrovacular disease
What is hyperglycaemia associated with?
Significantly reduced life expectancy
What is the relative risk of CV events in people with diabetes?
What are the causes of death of the general popn c.f. diabetics?
What are the risk factors for macrovascular disease?
What are the different blood-glucose lowering therapy?
How do you manage blood pressure?
How do you manage blood lipids?
How do you manage the foot ulcers?
Hyperglycaemia, hypertension, dyslipidaemia, stop smoking, education
How do you do preventative management for foot ulcers?
What is the difference with osteomyelitis and active charcot?
What are the physiological symptoms of DKA?
What are the risks and dangers of giving bicarbonate?
