Metabolic L2: Metabolic syndrome and diabetes Flashcards
What is metabolic syndrome?
highly complex and multifactorial disorder, which shares several common underlying mechanisms
What are the 3 common underlying mechanisms of metabolic syndrome (Met-S)?
- Fat accumulation (ectopic fat e.g. visceral/intra-abdominal fat)
- Impaired insulin sensitivity (i.e. insulin resistance), and
- Low-grade chronic systemic inflammation (the pro-inflammatory state).
- Anabolic and catabolic reactions irrgulated (normally –> more catabolic than anabolic)
What are the 3 pathophysiological effects (clinical diseases) of metabolic syndrome?
- Type 2 diabetes (T2d)
- Non-alcoholic Fatty Liver Diseases (NAFLD)
- Cardiovascular diseases (CVD)
Met-S is rapidly increasing in prevalence worldwide as a consequence of the continued ______‘‘epidemic’’
obesity
What are the 6 clinical features of Met-S?
- Impaired Glucose Regulation/Insulin Resistance
- Abdominal/Central Obesity
- Hypertriglycemia
- Low Levels of HDL Cholesterol
- Raised Blood Pressure
- Microalbuminuria
Once one part of metabolism is compromised, will have ____ impacts
secondary
What are characteristics of Impaired Glucose Regulation/Insulin Resistance?
DO NOT NEED TO KNOW SPECIFICS
Type 2 DM or impaired fasting glycaemia [≥6.1 mmol/L (110 mg/dl) or impaired glucose tolerance or glucose uptake below lowest quartile under hyperinsulinemia
What are characteristics of Abdominal/Central Obesity?
DO NOT NEED TO KNOW SPECIFICS
Waist/hip ratio 0.90 in. in men, 0.85 in. women or BMI > 30 kg/m2
What are characteristics of Hypertriglycemia?
DO NOT NEED TO KNOW SPECIFICS
≥ 1.7 mmol/L (150 mg/dl)
What are characteristics of Low Levels of HDL Cholesterol?
DO NOT NEED TO KNOW SPECIFICS
< 0.9 mmol/L (35 mg/dl) in men, <1.0 mmol/L (39 mg/dl) in women
What are characteristics of Raised Blood Pressure?
DO NOT NEED TO KNOW SPECIFICS
≥ 140/90 mm Hg
What are characteristics of Microalbuminuria?
DO NOT NEED TO KNOW SPECIFICS
≥ 20μg/min or albumin: creatinine ratio ≥ 30 mg/g
What is white fat?
- Under skin
- Easy to get rid of
What is brown fat?
- Visceral fat (sits around organs)
- Dangerous Very difficult to get rid of
________ the largest endocrine organ
Adipose tissue
_____ are the primary cell type of adipose tissue
Adipocytes
________ is a highly active metabolic and endocrine organ.
Adipose tissue
Adipose tissue is the primary site of storage for excess ______.
energy
An endocrine organ - synthesizing a number of _________ that regulate metabolic homeostasis.
biologically active compounds
What is the problem of extreme obesity in the long term?
- Dysregulation in tissue (fat stores)
- Releasing proinflammatory factors
- Affect other parts of the body
- Constantly alert and activated
- The body will try to re-balance this dysfunction
- Might have chances in insulin pathways = diabetes
- Cells in pancreas affected= stop producing insulin = diabetes
Insulin signaling regulates _____, _____ and _____homeostasis.
glucose, lipid; energy
Insulin has 3 major target tissues: _______, ______ and ______.
skeletal muscle, liver and adipose tissue
________ are overexpressed in the cells of these tissues,
Insulin receptors (IR)
Insulin resistance is defined where insulin levels are normal or elevated but target cells become less sensitive to insulin. What is the consequence?
Consequences:
- After a meal – hyperglycemia & compensatory hyperinsulinaemia
When the balance between glucose and insulin is disrupted (insulin resistance), what happens
- Increase glucose levels
- Receptors for insulin are not functioning anymore
- Glucose sits there
Why are skeletal muscles, liver and adipose tissue most affected by insulin?
- Liver is important for metabolism
- Skeletal muscles need lots of energy for day to day activities
- Adipose tissue is where we store excess energy (stored as fat)
- Since they are overexpressed –> insulin has the highest impact
Why is glucose “sitting” there without insulin a bad thing/problem since glucose helps produce ATP?
- There are other ways to store glucose
- Liver starts to overwork
- If insulin receptors are not working, when there are high level of glucose (short term) –> pancreas still produces insulin –> too much insulin (hormone) –> impact on the system
- People can go into a coma due to high levels of either insulin or glucose
- Good to produce energy but has to be within a reasonable range
- Over a certain range –> no longer beneficial –> can be dangerous
A _______ appears to be a central mechanism underlying the pathophysiology of MetS
chronic state of inflammation
Low grade chronic state of systemic inflammation drives the release of many _______ –> impact on the organs
pro-inflammatory factors
_______ factors actually drive the production of other factors from the white blood cells in the immune system –> impact and affect the organs
Pro-inflammatory
Why is there an impact/effect of the organs, since there is not actually inflammation in Metabolic syndrome?
- Since organs don’t know what they actually are receiving isn’t actually inflammation (they don’t have the info.
- Eg. don’t know they have diabetes, don’t know that they have eating a lot)
- Pro-inflammatory factors activated (usually release during infection)
- All body’s cells react as though there is an inflammation
- Becomes chronic inflammation –> damages cells, organs and tissues
________ carry lipids in the bloodstream
Lipoproteins
Protein component is called _______
apolipoprotein
What are the 4 types of lipoproteins?
- Very low density lipoproteins (VLDL)
- Known as “bad cholesterol”
- Intermediate density lipoproteins (IDL)
- Low density lipoproteins (LDL)
- High density lipoproteins (HDL)
- Known as “good cholesterol”
What are the 2 important types of lipoproteins out of ?
- Very Low density lipoproteins (VLDL)
- High density lipoproteins (HDL) – Known as “good cholesterol”
Elevated lipids can lead to _________ such as atherosclerosis
cardiovascular disease
Lipids can travel across the membrane through _______ (type of transport)
Passive diffusion (they can cross the layer of the cells present in muscosa)
Fat is _____ (hydrophobic/hydrophilic)
hydrophobic
Fats are carried as lipoproteins. Why do we need protein?
- Hydrophilic (okay to be around liquid)
- Being around the lipids = able to carry them around the body
What if we needed have proteins around fats (lipoproteins)?
Eg. Oil in water
- Small drops
- If didn’t have proteins around –> fat droplets would fuse together –> clog artery –> implications (possible death)
Why is too much fat not good for you?
Blocks arteries
Bad cholesterol can have an impact on the ______ of the artery and this can create ______.
epithelium; plague
Atherosclerotic lesions initiate with _______ causing modification of apolipoproteins containing _____ and _____
endothelial cell dysfunction; LDL; VLDL
What are 3 processes that occur as a result of lesions of epithelium of arteries? What is the consequence/problem of this?
- Damage of system
- Macrophages (immune system) activated
- But fat sits at the site of damage
- Since its made of proteins –> penetrate and form all together (bubble of fat together)
Problem: small arteries (eg. heart) ○ Site of inflammation (pro-inflammatory factors) Blocks arteries –> no blood flow through
What are 3 hormones that the endocrine pancreas secrete (produced in the pancreatic islets)?
- Insulin
- Glucagon
- Somatostatin
What are 2 cells of the exocrine pancreas?
- Chief
- Parietal
What cell type is insulin produced by?
β cells
What cell type is glucagon produced by?
α cells
What cell type is somatostatin produced by?
δ cells)
What is the function of insulin?
Lowers blood glucose levels
What is the function of glucagon?
Increases blood glucose levels
Impacts glycogen stores in liver and muscles –> break down –> glucose
What is the function of somatostatin in endocrine and exocrine parts?
Inhibits insulin and glucagon secretion
Regulation to disinhibit/reduce amount of gastric juices (in exocrine)
Why does pancreatic cancer have such a high mortality rate?
• Affects both exocrine and endocrine system ○ GIT (digestion and absorption of nutrients) Metabolism
What is Diabetes Mellitus (DM) due to?
Due to lack of insulin secretion or action or both
What is Diabetes Mellitus characterised by?
chronic hyperglycaemia Unable to activate insulin –> constantly high glucose levels
What is the effect of chronic hyperglycaemia?
Unable to activate insulin –> constantly high glucose levels
What are the 3 types of diabetes?
- Type 1
- Type 2
- Gestational (women during pregnancy)
What are the 2 circumstances in diabetes?
- Decrease secretion of insulin but receptors (B cells are fine) –> type I 2. Production of insulin but receptors don’t respond –> type II
What is the prevalence of type I diabetes?
Most common form of diabetes in children “juvenile diabetes” (5% of all diabetes adult cases)
What is the prevalence of type II diabetes?
Most common form of diabetes (90-95% of all diabetes)
What is the prevalence of gestational diabetes?
Pregnant women (3-8%)
What is the cause of Type I diabetes?
Autoimmune disorder where the body’s immune system mistakenly destroys its insulin-producing cells, making the person unable to produce insulin which delivers sugar from bloodstream into cells
What is the cause of Type II diabetes?
A dual effect of resistance to action of insulin, combines with an inability to make enough insulin to overcome the resistance
What is the cause of gestational diabetes?
The hormones of pregnancy or a shortage of insulin
What are 5 characteristic information about Type I diabetes?
- Biggest impact
- No/very little production of insulin since “day” 1
- Very dangerous –> eating lollies (high sugar) –> no insulin to help the system–> system goes into shut down –> “diabetes induced coma”–> possible death
- Cure: injections of insulin for the rest of your life
- Rely on insulin
- Constantly need to check levels –> injections
- While insulin injections help, still have pro-inflammatory factors –> cause long term problems
What are 4 characteristic information about Type II diabetes?
- Lifestyle
- Obesity
- Have had a normal life and then get diabetes –> some changes
- Usually take tablets
What are 5 characteristic information about gestational diabetes?
- Quite common and increasing
- Imbalance of hormones during pregnancy
- Stop producing insulin –> baby might want lots of sugar/food (wants to grow)
- Mother constantly has high glucose levels
- After birth –> usually goes back to normal levels
- If poor lifestyle/obesity –> can remain permanent
What is the characteristic of insulin secretion in Type I DM?
None
What is the characteristic of insulin secretion in Type II DM?
Normal or increased
What is the age of onset in Type I DM?
Early
What is the age of onset in Type II DM?
Late-adult/obesity
What is the speed of onset in Type I DM?
Rapid
What is the speed of onset in Type II DM?
Slow
What is the percentage total diabetics in Type I DM?
10-20%
What is the percentage total diabetics in Type II DM?
80-90%
What is the defect in Type I DM?
destruction of β cells
What is the defect in Type II DM?
Insulin resistance
What is the treatment and management in Type I DM?
Insulin, exercise, diet
What is the treatment and management in Type II DM?
Weight reduction, diet, exercise, drug
What are the 3 long term effects of diabetes?
- Vascular damage
- Renal failure and blindness
- Neuropathies
Diabetics have a _____ (shorter/same/longer) life expectancy than the general population
shorter
How does life expectancy change with people with diabetes?
Depends on the patients ability to control circulating glucose levels.
Why is vascular damage a long term effect of diabetes?
Why is renal failure and blindness a long term effect of diabetes?
Why is neuropathies a long term effect of diabetes?
impaired blood flow damages nerves of the CNS and PNS
What are the 4 classes of oral anti-diabetics agents?
