Type 2 Diabetes Mellitus Flashcards
What is T2DM?
Relative insulin reduction and insulin insensitivity.
What can cause T2DM?
Genetics- very strongly linked
Obesity
Insulin insensitivity
What is the blood chemistry of T2DM?
Hyperinsulinemia
Hyperglycemia
What causes hyperinsulinemia in T2DM?
Increased body mass requiring more insulin
Insulin insensitivity requiring more insulin for normal function
How does the insulin profile change as the disease progresses?
Drops as beta cells wear out.
What does beta cell failure lead to?
Decreased insulin secretion and effect Decreased muscular glucose uptake Increased lipolysis Increased gluconeogenesis Increased glucagon secretion
How does T2DM usually present?
Often obese Slow onset Microvascular disease Unexplained weight loss Fatigue Recurrent infection Blurred vision Foot damage
How do you diagnose T2DM?
Fasting blood glucose
OGTT
Random blood glucose + symptoms
What additional factor can be used to support T2DM diagnosis?
HbA1c
What are the ranges for fasting blood glucose?
<6mmol/l normal
6.1-6.9mmol/l prediabetes
>7mmol/l diabetes
What are the ranges for OGTT?
<7.7mmol/l normal
7.8-11 mmol/l prediabetic
>11.1 mmol/l diabetic
What must a random blood glucose be for diabetes to be diagnosed?
> 11.1 mmol/l
Plus symptomatic
What are the ranges for HbA1c?
<41 normal
42-47 prediabetic
>48 diabetic
Who should be tested regularly for T2DM?
BMI >25 w/1+ of: 1st degree relative affected Black, Latino, Asian, Pacific islander CVD Hypertension HDL < 35mg/dl Polycystic ovary disease Physical inactivity
What are the treatment options for diabetes?
Weight loss
BP control
Drugs
Insulin
What is the best treatment for diabetes?
Weight loss and exercise
What BP control drug is claimed to be the best for diabetic control?
ACEI
What are the 4 mechanism by which drugs can control diabetes?
Increase insulin secretion
Increase insulin sensitivity
Slow glucose absorption
Enhance renal glucose excretion
What classes of drugs increase insulin secretion?
Sulfonylureas
Incretin mimics
Glinides
Gliptins
How do sulfonylureas work?
Bind to SUR1 causing Kir6 closure
Give some example of sulfonylureas
Tolbutamide
Glibenclamide
Gliclazide
Glipizide
What are three benefits of sulfonylureas?
Reduce microvascular complications
Well tolerated
Oral
What are three negatives of sulfonylureas?
Can cause hypo
Weight gain- ~2kg
Urine retention
How do incretin mimics work?
Mimic GLP-1
Give some examples of incretin mimics
Exenatide
Liraglutide
What are five benefits of incretin mimics?
Increase insulin secretion Suppress glucagon secretion Slow gastric emptying Decrease appetite Modest weight loss
What are three of the negatives of incretin mimics?
Nausea
Pancreatitis
Subcut injection
How do glinides work?
Similar to SUs but augmented by glycemia
What do glinides end in?
-glinide
Give three benefits of glinides?
Oral
Rapid onset (1h to max, 4 to offset)
Less likely to cause hypo
When should you not use glinides?
Severe hepatic impairment
Pregnant
Breast feeding
How do gliptins work?
Inhibit DDP-4 enzyme which breaks down incretins
What do gliptins end in?
-gliptin
Give four benefits of gliptins?
Oral
Once daily
Weight neutral
No hypo
Give a negative of gliptins?
Nausea
How can gliptins be used?
In monotherapy
With Su or metformin
What classes of drug can increase insulin sensitivity?
Biguanides
Glitazones (TZD)
What is the only biguanide in use?
Metformin
What is metformin?
Biguanide
How does metformin work?
Reduced hepatic gluconeogenesis
Increases skeletal muscle glucose uptake (similar to exercise)
Reduces carb absorption
Increases FA oxidation
Give five benefits of metformin
Oral Reduces microvascular complications No hypo Weight loss Good in combo
Give two negatives of metformin
GI upsets
Lactic acidosis
Who should you not give metformin to?
Alcoholics
Severe hepatic or renal dysfunction
What must you have to be given metformin?
Normal hepatic and renal function
How do glitazones work?
Increase insulin sensitivity by genetically increasing signalling.
What is the only glitazone licenced in the UK?
Pioglitazone
When is pioglitazone used?
In combo with metformin or SUs
Give three positives of pioglitazone
FA taken up into adipocytes- healthier
Increased glucose uptake
No hypo
Give four negatives of pioglitazone?
Weight gain
Fluid retention
Hepatotoxicity
Increased bone fractures
What is the only drug class that inhibits glucose absorption?
Glucosidase inhibitors
Name a glucosidase inhibitor?
Acarbose
How do glucosidase inhibitors work?
Inhibit alpha glucosidase which breaks down monosaccharides thus preventing absorption
Give a benefit of glucosidase inhibitors
No hypo
Give two negatives of glucosidase inhibitors
Not very effective
GI upsets- Diarrhoea and flatulence etc
When should glucosidase inhibitors be used?
Only in those with poor lifestyle and drug control.
What is the only class of drug this increases renal excretion of glucose?
SGLT2 inhibitors
How do SGLT2 inhibitors work?
Inhibit the SGLT2 channel in the proximal nephron resulting in less glucose reuptake
What do SGLT2 inhibitors end in?
-liflozin
Give three positives of SGLT2 inhibitors
Lowers blood glucose
Low risk of hypo
Calorie loss
Give a negative of SGLT2 inhibitors?
Dehydration
What drugs are first line T2DM treatment?
Metformin
SUs in those who cannot tolerate metformin
What drugs are second line T2DM treatment?
SUs
TZD/glitazones- If hypoglycemia is a concern
Gliptins- If weight gain is a concern
What drugs are third line T2DM treatment?
TZD/glitazones
Gliptins- If weight gain is a concern
Insulin- For rising HbA1c
Incretin analogues- Only if BMI >30
