Macrovascular Complications of Diabetes Mellitus Flashcards
What is macrovascular disease and what types of disease is it seen in?
Early widespread atherosclerosis Seen in: - ischaemic heart disease - cerebrovascular disease (stroke, aneurysm) - peripheral vascular disease
What is the earliest stage of atherosclerosis where we start to see clinical presentation of macrovascular disease?
Atheroma
- fibroatheroma and complicated lesion are the next two stages with complicated lesion causing possible occlusion or thrombosis
What are the mechanisms and features of the 6 stages of macrovascular disease (atherosclerosis)? (see table in the presentation)
Initial lesion - caused by macrophages, grows with lipid
Fatty streak - caused by build up of intracellular lipid, grows with more lipid
Intermediate lesion - now has extracellular lipid, grows with lipid
Atheroma - now has a core of extracellular lipid but lesion grows with smooth muscle hypertrophy (vessel itself now involved)
Fibroatheroma - core now has fibrotic/calcific layers and grows with collagen being added to these layers
Complicated lesion - final stage lesion, vessel now has surface defects or thrombolises, grows with thrombosis or haematoma
What is the clinical presence of each stage of atherosclerosis?
Initial lesion - silent
Fatty streak - silent
Intermediate - silent
Atheroma - can be overt or silent
Fibroatheroma - can be overt or silent but more likely overt than silent
Complicated lesion - overt (clinical effects clear; MI/thrombosis)
What is the ‘metabolic syndrome’?
A clustering of at least 3 out of 5 of the following medical conditions:
- Abdominal (central) obesity
- Elevated BP
- Elevated fasting plasma glucose
- High serum triglycerides
- Low HDL levels
What are the parameters of fasting glucose, HDL levels, waist circumference (omental obesity measure), and hypertension in someone with macrovascular disease or, at least, metabolic syndrome?
Fasting glucose
- >6.0mmol/L
HDL
- men <1.0
- women <1.3
Waist circumference
- men >102cm
- women >88cm
Hypertension
- BP >135/80
What are the 4 hormones/compounds associated with macrovascular disease that can be measured but are not always measured?
Insulin resistance
Inflammation CRP (C-reactive protein)
Adipocytokines
Urine microalbumin (test for endothelial damage, can predict later macrovascular disease)
How are the growth stages of the stages of atherosclerosis affected by insulin resistance?
Insulin resistance promotes dyslipidaemia (high LDL cholesterol) and high blood pressure
- all of these contribute to lesion growth in the early stages (initial lesion, fatty streak, intermediate lesion) of atherosclerosis
Insulin resistance’s mitogenic effects cause smooth muscle hypertrophy in the atheroma stage and influence the thrombotic mechanism in the complicated lesion stage
How does hyperglycaemia affect macrovascular disease progression and is it necessary?
Associated with the insulin resistance-mediated progressions
- not necessary or inevitable for the progression of atherosclerosis
- e.g. people who will die from heart attack and stroke don’t need and won’t have, in many cases, hyperglycaemia
What is the key concept relating hyperglycaemia and life expectancy?
Hyperglycaemia is associated with significantly reduced life expectancy
What has been found about the life expectancy in patients diagnosed at a variety of ages with diabetes?
There is a strong association showing that the younger a patient is diagnosed with diabetes, the less their life expectancy will be
- deaths will be from mainly cardiovascular disease
- insulin resistance and diabetes are both associated with higher and higher risk of chronic heart disease and MI
What is important about T2D through the years?
It gets worse NO MATTER HOW WELL YOU TREAT IT
- graph showing the increase in HbA1c in two patients where one was conventionally controlling their glucose and the other was intensively controlling their glucose, both kept ascending with the intensive control being 1% lower (which on a graph of HbA1c is a significant amount) but importantly both will have increasing risk of complications regardless of how well they treated their diabetes
What is the difference in hyperglycaemia’s effect on microvascular and macrovascular disease?
Microvascular disease has been shown to only really develop when there is elevated sugar where as Macrovascular disease is already prevalent and only increases slightly with increasing sugar
What is the key concept highlighting the difference in severity in microvascular and macrovascular disease?
Microvascular disease causes morbidity; macrovascular disease causes morbidity AND mortality
There are a few graphs and studies in the presentation showing mortality causes in those with diabetes, mortality over time compared with those with known ischaemic heart disease, post-MI survival in men comparing diabetics and non-diabetics, and finally, predicted rates of coronary heart disease based on ethnic differences. What are the 4 key points about all these graphs? (see Amber’s notes)
- Ischaemic heart disease accounts for 60% of mortality in diabetes patients, other causes are still there but often don’t live long enough to present with them (e.g. cancer)
- diabetic patients without prior MI have the same survival % as non-diabetic subjects WITH prior MI. suggests that many diabetic subjects already have ischaemic heart disease but we haven’t diagnosed it yet
- diabetic patient post-MI survival is much much reduced (in terms of months after MI) compared with non-diabetic post-MI survival rates
- white caucasians have a much lower rate of developing coronary heart disease than UK south asians who are far above the predicted risk line so ethnic differences must be taken into account when assessing a patient’s risk of ischaemic heart disease
