Metabolic Syndrome Flashcards
Metabolic syndrome is not a disease, rather it is a …
…cluster of physiological disorders.
Metabolic syndrome is characterised by the following symptoms:
- High blood pressure
- High insulin levels
- Excess body weight
- Abnormal cholesterol levels
In metabolic syndrome, the person displays …
… central obesity rather than general subcutaneous obesity
- Sometimes expressed as an apple rather than pear-shaped body phenotype
What were the conclusions of the study titled “The Metabolic Syndrome and Cardiovascular Risk”?
“The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality.”
The prevalence of metabolic syndrome increases with…
..age.
Metabolic syndrome affects less than […]% of people in their […] and […]% of people in their […]
Metabolic syndrome increases with age, affecting less than 10% of people in their 20s and 40% of people in their 60s.
Metabolic syndrome is generally more common among…
…Afro-Caribbean and Hisparnic lineages than among Caucasians.
A body mass index (BMI) greater than […] increases your risk of metabolic syndrome along with abdominal obesity
A body mass index (BMI) greater than 25 increases your risk of metabolic syndrome along with abdominal obesity.
Having a family history of type 2 diabetes mellitus or gestational diabetes (diabetes during pregnancy) can increase risk of…
…metabolic syndrome
A diagnosis of […], […] disease or […] can increase risk for metabolic syndrome
A diagnosis of hypertension, cardiovascular disease (CVD) or polycystic ovary syndrome
Waist circumference of Europid and Indo-Asian males with metabolic syndrome?
Europid males = >94cm
Indo-Asian = >90cm
Waist circumference of Europid and Indo-Asian females with metabolic syndrome?
Europid females = >80cm
Indo-Asian females = >80cm
The concept of metabolic syndrome (although not the name) was first suggested by…
…Gerald Reaven in 1988
The title of the article written by Geral Reaven in 1988 was titled …
…“The Role of Insulin Resistance in Human Disease”
It is generally thought that all the symptoms of metabolic syndrome start with …
…Insulin Resistance
The body attempts to keep the serum [glucose] within …
…strict limits using several different hormones.
Too high a [glucose] can lead to …
…osmotic problems with water being drawn in to the blood from the cells; this not only raises blood pressure, but is detrimental to cellular physiology.
Too low a [glucose] deprives…
… tissues that rely on the glucose as an energy source short of energy e.g. The brain, erythrocytes, renal medulla.
In maintaining serum (glucose), the major hormones involved are:
1) insulin
2) glucagon
3) incretins
In maintaining serum (glucose), the major organs involved are:
- islets of Langerhans of pancreas
- insulin sensitive organs: liver, muscle, - fat
- intestines
- Kidneys
For most people without diabetes, blood sugar levels before meals are between…
…3.0 to 5.5 mmol/L
- Frequently around 3.9 to 4.4 mmol/L.
Levels are maintained by the hormone …
…glucagon
Whats glucagon produced from?
α-cells of the islets of Langerhans situated in the endocrine pancreas
Glucagon is a …
… hormone
Glucagon stimulates…
…the liver.
Glucagon stimulates the liver to…
…breakdown stored glycogen to glucose and the synthesis of glucose by gluconeogenesis
After around 24 hours the liver glycogen store is …
…exhausted and the body relies totally on synthesis
Glucagon is generally signalling that …
…glucose levels in the body is restricted.
Some tissues have a significant requirement for…
…glucose
Some tissues have a significant requirement for glucose. These include:
- The brain
- Any cells that lack mitochondria (e.g. erythrocytes)
- Tissue where mitochondrial physiology may be impaired (e.g. the kidney)
glucagon stimulates …
…fatty acid release from adipocytes to fuel the other tissues
Glucose is the …
…preferred energy source for most tissues and the body seeks out sources.
- One of the reasons we often crave sweet foods.
ingestion of large quantities of glucose can…
…quickly raise serum levels to 2-3x basal levels
Such high levels of glucose in the body can be harmful in two ways:
1) Spontaneous glycation of proteins (see ageing)
2) Osmotic issues (see experiment)
- It is thus important to lower levels quickly
Insulin is …
…the hormone that lowers blood glucose levels
Insulin is the hormone that lowers blood glucose levels in several ways:
1) It instructs the liver to store glucose as glycogen
2) It instructs non-glucose dependent tissue to uptake and use glucose as an energy source.
3) It instructs muscles to store glucose as glycogen
4) It instructs adipose tissue to take up glucose and convert it to fatty acids (although this is minor)
Insulin also stops …
…adipose tissue from releasing fatty acids into the blood
There are […] phases of insulin release.
There are two phases of insulin release.
Mechanism of insulin?
1) About 11,000 insulin vesicles in a β-cell
2) About 770 attached to membrane
3) 55 are ready to be released and form the first phase
4) 715 can be released fairly rapidly and form the second phase
The amount of insulin released is …
…crucial
Release too little incretins and you…
…risk glycation and osmotic issues
Release too much incretins and …
…glucose levels may drop so low that the function of the brain and other glucose-dependent tissues may be effected.
Incretins are …
…hormones secreted by the gastro-intestinal tract in proportion to the glucose content of an ingested meal.
These incretins thus inform …
…the endocrine pancreas as to the expected glucose influx.
Conclusions of the study titled “Incretin release form gut is acutely enhanced by sugar but not by sweeteners in vivo.”
“In summary, we were unable to find any evidence that artificial sweeteners acutely induce incretin release in vivo. Therefore, while parallels have been drawn between nutrient-sensing pathways in the oral cavity and gut, our findings do not support the concept that gut incretin-secreting cells sense luminal carbohydrates via a pathway analogous to that by which the tongue senses sweetness.”
Conclusions of the study titled “Hyperinsulinemia: Cause or Consequence”?
“Artificial sweeteners that are also frequently present in modern foods were found to impact insulin secretion. Shown here is insulin secretion at basal and two stimulatory concentrations of glucose in response to saccharin, aspartame, and sucralose … All stimulated basal secretion acutely, but saccharin was most potent and also inhibited glucose-stimulated secretion. Interestingly, only saccharin stimulated basal secretion at concentrations that might be achieved by high levels of consumption, for example, in diet beverages.”
“Using cultured INS-1 cells, we screened substances that have entered our food supply in recent years and identified common lipid food additives that increased insulin secretion at basal glucose levels including monoacylglycerides. They are formed and degraded in the gut, and by lipoprotein lipase in peripheral tissues, and are commonly added in small quantities as emulsifiers and preservatives. The ability of mono-oleoylglycerol (MOG) to stimulate insulin secretion at basal glucose was concentration dependent and significant at a concentration as low as 25mmol/L.”
How many types of insulin resistance?
Two types:
(and either or both can be mentioned in the various definitions of metabolic syndrome)
Raised basal level of glucose in blood after …
…fasting
What happens to basal level of glucose after fasting?
Raised basal level of glucose in blood after fasting
Raised basal level of glucose in blood after fasting is defined as…
…a blood glucose concentration of between 6.1-7.0 mmol/L - A pre-diabetic state
Due to hepatic resistance…
- Liver does not recognise the instruction to store glucose
- Instead stays in a glucagonic state pumping glucose in to blood; serum [glucose] rises
Impaired Glucose Tolerance (IGT) is defined as follows:
- A subject is given 75g of glucose as an oral glucose tolerance test (OGTT)
- IGT is diagnosed if serum [glucose] is between 7.8-11.1 mmol/L after 2 hours.
Impaired glucose tolerance (IGT) is due to…
…muscle insulin insensitivity
Describe muscle insulin insensitivity.
- Muscles poorly absorb glucose.
- Since muscle mass makes up a significant sink for glucose, serum [glucose] remains high
IFG has a …
…low phase I secretion, but normal phase II
IGT has a …
…normal phase I secretion and an abnormal phase II
IGT = ?
Impaired Glucose Tolerance (IGT)
IFG = ?
Impaired Fasting Glucose (IFG)
An added complication is …
…β-cell decline.
In many individuals insulin output potential …
…declines
In many individuals insulin output potential declines. This can effect:
- This can in effect mimic insulin resistance
- In this case the insulin-sensitive cells do not have enough exposure to insulin to initiate a response; as opposed to not being able to initiate a response when insulin is present.
β-cell decline may be due to …
…over work
Why might B-cell decline be due to over work?
- High serum [glucose] continually activates the β-cells
- Leading to fatigue/death
Metabolically active cells become …
…damaged more quickly
Metabolically active cells become damaged more quickly – possibly due to …
…greater exposure to free radicals generated by high mitochondrial activity
In tissues such as the liver these cells are…
…regenerated
Lifestyle causes …
…hepatic insulin sensitivity
Blood glucose levels rise as a result of…
…glucose synthesis
β-cells respond to raised [glucose] by …
…producing more insulin
Readily releasable vesicles are therefore depleted leading to…
…a low phase I response
Phase II response is…
…normal
Higher insulin production leads to…
…β-cell decline leading to muscles not being able to respond (IGT)
Go read…
… slide 45 and 46 and 47
