BIOM30001 Lecture Notes - Lecture 3: Kupffer Cell, Regression Analysis, C-Jun N-Terminal Kinases
Syndrome X/Syndrome X Plus
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Dysmetabolic syndrome
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Insulin Resistance syndrome
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Plurimetabolic syndrome
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Cardiometabolic syndrome
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Dyslipidaemic hypertension
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Hypertriglyceridaemic waist
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Deadly Quartet
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An obese hypertensive diabetic by any other name
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Metabolic syndrome: presence in one individual of multiple cardiovascular risk factors
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Obesity
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Insulin resistance/glucose intolerance
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Hypertension
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Dyslipidaemia
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All agree on the core components of the metabolic syndrome:
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However key criteria differ between groups
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Mandatory component: High insulin levels, an elevated fasting blood glucose or an
elevated post meal glucose
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a waist to hip ratio of greater than 0.9
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BMI of at least 30 kg/m2
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waist measurement over 94 cm
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Abdominal obesity as defined by:
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Triglyceride level of at least 1.7 mmol/L
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HDL cholesterol lower than 0.9 mmol/L
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Blood pressure of 140/90 or above (or on treatment for high blood pressure).
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With at least 2 of the following criteria:
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WHO Definition
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NCEP (National cholesterol education program) - ATP III criteria
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Europid >=94cm men, >=80cm women
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Asian (not Japanese) >=90cm men,>=80cm women
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Japanese >=85cm men, >=90cm women
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Mandatory component: Central obesity - waist circumference ethnicity specific
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IDF (International Diabetes Federation) Criteria - Used the most (Should probably
remember)
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Definitions of the Metabolic Syndrome
3: Metabolic syndrome: definitions and causes
Wednesday, 29 July 2015
8:44 PM
Frontiers Page 1
Japanese >=85cm men, >=90cm women
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Women put weight on around hips and thighs
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20% of women put weight on around the abdomen
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All men put weight on around the abdomen
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Fat around hips and thighs is not metabolically harmful
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BMI does not discriminate against location of fat
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Central obesity because not all fat are the same
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Ethnic specificity is due to the relative risk of developing diabetes. (i.e. Japanese
are more likely to develop diabetes than Europeans for the same obesity level)
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Triglycerides >1.7mmol/L or on specific treatment
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HDL cholesterol <1.03mmol/L in men, <1.29 in women or on specific treatment
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Blood Pressure >/= 130/85 or on treatment
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Fasting blood glucose >/=5.6mmol/L or previously diagnosed T2DM
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Plus two or more of other criteria:
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LDL = bad cholesterol
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HDL = good cholesterol
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You want high HDL and low LDL.
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LDL is taken up in cells, but this uses up receptors. Once a cell has enough LDL, it express
no more receptors for uptake
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If high levels are present, LDL is free to circulate in blood
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Macrophage oxidise LDL in blood to form plaques.
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Ideal Cholesterol levels are less than 5.5mmol/L
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Ideal LDL levels <2.6mmol/L
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High LDL levles >3.4mmol/L
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Ideal HDL level >1,5mmol/L
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Bad HDL levles <1mmol/L
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Aside: Cholesterol
LDL receptors on liver cells/extrahepatic tissue that take up LDL (limited capacity of LDL uptake) ->
too much LDL = macrophage turns LDL into plaques, causing vessels to stiffen and hypertension
Increased insulin resistance -> increased insulin levels -> increases HDL break down -> nothing to
reduce LDL levels in blood
65 yo male
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BP 180/100 (hypertensive), PR (pulse rate) 90 AF (atrial fibrillation - makes you short of
breath and puts you at risk of stroke because the top chambers of the heart do not
empty and clots can form)
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Waist circumference 103cm
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Total cholesterol 6.5 (high), LDL 4.5 (high), HDL 0.6 (low), TriGlyceride 2.3 (high)
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HbA1c is a test for how good your sugar has been for the past 3 months
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When sugar is high, it enters the RBC and covalently bonds to Hb. If we measure
what percentage of Hb sugar is attached to, it gives us an indirect measure of
blood glucose levels because RBC live for about 3 months
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HbA1c Target = 7%
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At 8%, risk of complications is quite high
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Diabetic with FBG 15 (fasting blood glucose) and an HbA1c 12%
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Smokes 20/day with 50 year pack history
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Family history of Diabetes and IHD (Ischaemic Heart disease)
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Mr McDonalds
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Case studies
40 yo male
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BP 138/90, PR 60 SR (sinus-rhythm)
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Waist circumference 103cm
Mr Smith
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Frontiers Page 2
Waist circumference 103cm
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Total cholesterol 4.5, LDL 2.0 (good), HDL 1.02 (slightly low) TG 1.8 (slightly high)
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FastingBloodGlucose 5.6 (not diabetic)
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Non smoker
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No family history of Diabetes and IHD
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Yes, both have the metabolic syndrome using each of the criteria
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Do they have the metabolic syndrome?
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Framingham 10 year risk CHD case 1: >30% (this is just some formula)
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Framingham 10 year risk CHD case 2: 1%
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Do they have the same risk? Absolutely not
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Apart from lifestyle modification treatment would be vastly different for each case and
would involve treatment of individual risk factors
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Would the diagnosis of the metabolic syndrome result in the same treatment for each case or
would treatment be different from treating individual risk factors?
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Because we don’t know what the basis of the syndrome or biological cause is - What is the
mandatory component?
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NCEP ATPIII guidelines lipid centric
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IDF and WHO definitions are insulin resistance centric
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Because each group has its own interest - Both in the etiology of the syndrome, the outcomes
it predicts and the treatments we should be instigating
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Because we are still determining its role as a predictive tool
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Does it change the future risk?
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Which risk does it predict?
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Does it change our management?
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So is it a syndrome? Does the diagnosis of the metabolic syndrome add anything on top of the
sum of its parts?
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The term "metabolic syndrome" refers to a clustering of specific cardiovascular disease
(CVD) risk factors whose underlying pathophysiology is thought to be related to insulin
resistance.
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Since the term is widely used in research and clinical practice, we undertook an
extensive review of the literature in relation to the syndrome's definition, underlying
pathogenesis, and association with CVD and to the goals and impact of treatment.
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Imprecisely defined,
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There is a lack of certainty regarding its pathogenesis, and
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There is considerable doubt regarding its value as a CVD risk marker.
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While there is no question that certain CVD risk factors are prone to cluster, we found
that the metabolic syndrome has been:
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Our analysis indicates that too much critically important information is missing to
warrant its designation as a "syndrome."
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Until much needed research is completed, clinicians should evaluate and treat all CVD
risk factors without regard to whether a patient meets the criteria for diagnosis of the
"metabolic syndrome."
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Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal:
joint statement from the American Diabetes Association and the European Association for
the Study of Diabetes. Diabetes Care. 2005 Sep;28(9): 2289-304.
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i.e. labelling an individual with metabolic syndrome doesn't add clinical utility, since CV risk
can be calculated from individual components present
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Why so many definitions?
Is there one biological basis? A hypothesis (not proven definitively)
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Insulin Signalling
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Aetiology
Frontiers Page 3
Document Summary
An obese hypertensive diabetic by any other name. Metabolic syndrome: presence in one individual of multiple cardiovascular risk factors. All agree on the core components of the metabolic syndrome: Mandatory component: high insulin levels, an elevated fasting blood glucose or an elevated post meal glucose. With at least 2 of the following criteria: Abdominal obesity as defined by: a waist to hip ratio of greater than 0. 9. Bmi of at least 30 kg/m2 waist measurement over 94 cm. Blood pressure of 140/90 or above (or on treatment for high blood pressure). Ncep (national cholesterol education program) - atp iii criteria. Idf (international diabetes federation) criteria - used the most (should probably remember) Mandatory component: central obesity - waist circumference ethnicity specific. Central obesity because not all fat are the same. Women put weight on around hips and thighs. 20% of women put weight on around the abdomen. All men put weight on around the abdomen.
