Type2 Diabetes Miellitus

Question 1

What is Diabetes Miellitus? (define)

Answer 1

Constant state of hyperglycemia causing micro and macrovascular damage (retinopathy, nephropathy, cappilopathy, nerves)

T2DM is not ketone prone-because insulin is produced
T2DM is not “mild”-involves lipids, blood pressure, and arthropathies

Question 2

What is the cutoff for blood glucose for diabetes/prediabetes?

Answer 2

Fasting sugar 6-7 -pre. Above 7-diabetes

2h after 75mg glucose test-7.8-11.1->pre. above 11-diabetes

Question 3

What is the difference between pre-diabetes and diabetes?

Answer 3

Pre-diabetes patients dont tend to have microvascular complications but can have lot of the macrovascular

Question 4

Describe pathophysiology of T2DM, using MODY as an exemple

Answer 4

MODY has several AD inherited (8 variants)
MODY-usually ineffective Insulin production (can produce enough or cant sense blood glucose)-BUT no obesity

In t2DM-genetic disease but not sure what the genes
Causes insulin resistance (possibly via adiopocytokines)-and starts in 20 and grows worth. Adult obesity progress it, and certain FA seem to be very important
Insulin resistance causes metabolic dislipedimia AND mitotic growth => macrovascular issues
Eventually, B cell failure-> causes dislipedemia to be worse, and hyperglycemia (-> microvascular)
B cell failure can become absolute-and need insulin intake

Question 5

How important is the genetic component of T2DM?

Answer 5

70% of twins-homozygous-will develop t2dm if the other has it
t1 is actually less genetic

Question 6

What is the role of in utero nurishment in the chances to get t2DM?

Answer 6

using weight at one year, thinner children (<8.86 kg) had a 22% chance to develop T2DM-in utero proteins seem to have an important role in allowing proper pancreas development
(larger children had only 6% chance)

Question 7

How does insulin resistance and insulin production change with age (for everyone)

Answer 7

IR increases with age, and production goes down with age
in most people, the meeting/breaking point is after your death-like 110 yo
But in T2DM-happens earlier
and both play some role

Question 8

What are the presentations of t2DM

Answer 8

Obesity/central adiposity, Heterogenous (variable)
Insulin resistance AND/OR lack of insulin,
Dylsepedemia, Hyperglycemia

Presents acutely from complications (found when presents with heart attack/blindness)

Question 9

What is happening metabolically in t2DM?

Answer 9

Adipose tissue in omental area can drain directly to liver so most important (rather than arms and legs)
Releases large amounts of glycerol-(as insulin resistance)-makes more glucose in liver
Glycogen is also chopped to make glucose
fatty acids come to liver to make ketones and other
WITH RESISTANCE: hepatic glucose output is normal, but then glucose isnt taken in by muscle-and isnt switched off after meals
With resistance, might just have more FA (VLDL), but as gets worse-glucose rise

Question 10

Which is more important in t2DM-insulin resistance or production of insulin?

Answer 10

BOTH-depends on people
But as you develop diabetes, the production of insulin decreases-periodically at first, chronically after
AND the resistance is also there
makes hepatic glucose production rise, and makes blood glucose rise

Question 11

What is the role of obesity in t2DM?

Answer 11

Adipose tissue is VERY important to t2DM
Also obesity and t2DM are very linked (80% of t2DM are obese at diagnosis-and weight loss good treatment)
Probably more than a precipitant

Question 12

What is the role of the gut microbiome in t2DM?

Answer 12

More association than causation
But strong link between the gut microbiome and obesity
Possibbly via fatty acid production, possibly via bile salt production and modulation of inflammatory pathways

Question 13

Why does treatment of t2DM increase your weight? whcih one doesnt

Answer 13

Treatment can stop patient peeing out 75g of sugar a day-means it stays
metformin is the only one that doesnt cause that weight gain

Question 14

List all the different factors important to development of t2D

Answer 14

Intrauterine feeding reduced insulin resistance
Genes can reduce insulin production
Microbiota and adipocytokes
Diet and exercise
and then medication-to try and correct them (until absolute B cells-

Question 15

What are common presentations of t2DM?

Answer 15

Osmotic symptoms, infections, as part of as screening, but most commonly because of the complications-acute or chronic

Question 16

What are the microvascular complications of t2DM

Answer 16

Retino, nephro, nevo

Question 17

What are the macrovascular T2dm?

Answer 17

heart disease, cerebral vascular, CKD, PVD

Question 18

What are metabolic complications of t2dm

Answer 18

lactic acidosis, hyperosmolar

Question 19

What is the basic management plan of t2Dm?

Answer 19

Education, diet, drugs, and constant screen for complications

Question 20

what is the basis of the diet for t2Dm?

Answer 20

more complex carbo, less simple
Less fat as energy, and more unsaturated fats (olive oil)
increase soluble fibre
adress salt for blood pressure

Question 21

What are the 4 issues you want to monitor in t2DM? How can you manage them pharmacologically

Answer 21

Weight, glycemia, blood pressure and dyslipedimia
orlistat (lipase inhbitor-stops fat absoption)
other 2 have been taken off market
Gastric bypass-very effective in patients (also reduces hormonal)
Metformin-makes insulin work better
Insulin-reduce hepatic glucose output
Sulphynoureas-B cells produce more insulin
a-glucosidase inhbitors-slows down gluc absorbtion
thialozadinediones-reduce insulin resistance
Glucagon-like peptide-benefit endogenous B cells
SGLT2 inhbitor-increase glycouria

Question 22

Why is metformin such a good drug?

Answer 22

In overweight patient where diet isnt enough
first line-increases insulin sensitivity (centrally and periphery (hepatic output and peripheral intake)s
side effect of diahhoae

Question 23

How doe sulphanureas help treat t2DM?

Answer 23

They bypass the glucose sensing part of the B cells, leading to opening of the Ca channel-and releasing the insulin
Need working B cells
But cause weight gain-work best in lean patient
eg: gilbenclamide

Question 24

Why are a-glucosidase inhbitors good for t2DM

Answer 24

Acabose inhibits a-glucosidase, so instead of glucose being taken in in 20 mins, it takes 2h-so the low 1st phase insulin is not as important
good but cna cause fermentation in large intestine-flatulence

Question 25

Why are Thialozedinediols good for t2dm?

Answer 25

Makes insulin work better-mainly peripheral
Distribute weight from omental to rest
improve glycemia and lipids
also has good vascular outcomes

Question 26

What are the benefits of using GLP-1 for treating t2Dm?

Answer 26

When eaten, glucose has a larger effect on insulin
thats cause of GLP-1-produced by L cells -stimulates insulin, decrease glucagon
causes weight loss as it reduces appetite
Either use agonists-injection
Or gliptins (DPPG inhbitors)-oral

Question 27

Why is SGLT2 inhbitors good for t2dm?

Answer 27

inhbitis Na/Glucose transporter in convuluted tubule of the kidney, so more glucose peed out-lowers glucose well
Importantly, lowers death and heart failure (might be cause of na)
Eg: Empaglifozin

Question 28

can treatment stop the progession of t2DM?

Answer 28

No-in the end most will need insulin
But in old people-dont really care as much
in young people-want to be very tight control

Question 29

What are 2 parts of control of t2DM that cant be forgotten?

Answer 29

blood pressure (b blockers, etc)
and dyslipedimia (statins)