T2DM Flashcards
What is T2DM?
A combination of insulin resistance and beta cell failure resulting in hyperglycaemia
Which groups of people does T2DM have a high prevalence in?
Ethnic groups that are moving from a rural to an urban lifestyle (South and East Asia)
What are the three measurements used for glucose levels in assessing T2DM?
Fasting Glucose, 2-Hour Oral Glucose Tolerance Test (OGTT), HbA1c
Name the values/terms for fasting glucose at a normal, intermediate and T2DM stage
Fasting Glucose - <6.1 mmol/L /
Impaired Fasting Glycaemia / >7 mmol/L
Name the values/terms for OGTT at a normal, intermediate and T2DM stage
Normal <7.7mmol/L ,
Intermediate - Impaired glucose tolerance , >11mmol/L
Name the values/terms for HbA1c at a normal, intermediate and T2DM stage
Normal - <42mmol/mol .
Intermediate - Pre-diabetes , >48mmol/mol
What is the type of insulin deficiency in T2DM called?
Relative insulin deficiency - not enough insulin production to overcome resistance
however usually enough insulin to prevent formation of ketones
How does T2DM cause its effects on glucose secretion & absorption?
Insulin resistance and beta cell dysfunction lead to proinflammatory visceral fat, leading to decreased glucose uptake by adipocytes & skeletal muscle and increased hepatic glucose production
Howcan T2DM eventually lead to DKA
Long term diabetes causing insulin production to become completely compromised - insulin dependent
glucose toxicity to the pancreas can cause acute illness
What is a hyperglycaemic clamp?
A test of measuring insulin sensitivity and secretion by increasing glucose dose
How does T2DM affect the prandial peak of insulin release?
first phase insulin release is lost, very small peak
What happens to hepatic glucose production in T2DM and why?
Reduction in insulin action and an increase in glucagon action - increases HGO
How does T2DM lead to glucose toxicity
Glucose insufficiently removed due to low insulin levels
Formation of glucose via the action of glucagon on the liver
How does the relationship between insulin secretion and insulin sensitivity present in a control?
If you have a higher sensitivity of insulin, you will not secrete much insulin. This is an exponential relationship (even at extremely high sensitivity you still need a basal insulin level similar to others)
How does the relationship between insulin secretion and insulin sensitivity change in a person with T2DM?
Reduced insulin sensitivity, however insulin secretion is not at the high level it should be - described as ‘falling off the curve’
Consequences of insulin resistance
Glucagon increased -> HGO increase
insulin dependent muscle glucose uptake is depleted
Adipocytes prod more NEFA causing triglyceride levels to increase
Monogenic diabetes
single gene mutation - MODY
born with it
Polygenic diabetes
T1DM/T2DM
polymorphisms increase the risk of diabetes
Associations with T2DM
Obesity - especially visceral fat
Intrauterine environment - being the offspring of a woman with gestational diabetes,
growth retardation, low body weight increases action of fat prod genes
What are 7 presentations of T2DM?
Hyperglycaemia,
Overweight,
Dyslipidaemia,
Fewer osmotic symptoms,
Complications of T2DM,
Insulin Resistance,
Later Insulin Deficiency
What are 6 risk factors of developing T2DM?
Age, BMI, Ethnicity, PCOS, Genetics, Inactivity
What is the first line screening test for T2DM, how many readings do you need, and why is this chosen?
HbA1c, need two tests of HbA1c > 48 if asymptomatic,
one test if symptomatic
more convenient to take blood supply in clinic than to do a fasting glucose test
What is the glycaemic state often correlated with renal failure?
Hyperosmolar Hyperglycaemic State
Hyperosmolar Hyperglycaemic State
Insufficient insulin for prevention of hyperglycemia, but sufficient to prevent lipolysis and ketogenesis
osmotic diuresis causes serious dehydration
Can also be caused by MI, infection
Management of T1DM
Exogenous insulin
self monitoring glucose
education
Management of T2DM
diet
oral meds
education
remission/reversal - drastic diet (800 calories daily) or gastric bypass surgery
What are the 5 parts of assessment in T2DM consultations?
Weight, BP, glucose, Cholesterol, Complications (feet, retina)
Drug to reduce HGO
metformin
Drug that improves insulin sensitivity
Metformin and pioglitazone
Drug that boosts insulin secretion
Sulphonylureas
DPP-4 inhibitors
GLP1 agonists
Drug that inhibits glucose reabsorption
SGLT-2 inhibitor
Metformin
First line if dietary/lifestyle changes haven’t worked
Reduces insulin resistance causing an increase in HGO
GI side effects
contraindicated in severe liver, cardiac, renal failure
Sulphonylureas
Boost insulin secreting capability of b cells
bind to ATP sensitive K+ channel and close it
Pioglitazone
Insulin sensitizer
causes peripheral weight gain
side effects bladder cancer, heart failure
GLP-1
gut hormone
stimulates insulin and suppresses glucagon
increases satiety
short half life due to degradation by DPP4
Incretin effect
Oral glucose causes greater insulin production than IV glucose
DPP-4 inhibitors
dipeptidyl peptidase-4
increase half life of exogenous GLP1
decrease glucagon/glucose
no effect on weight
SGLT inhibitors
Inhibits Na-GLu transporter -> more glycosuria
weight loss, lower hba1c
lowers mortality
improves CKD
