The Aetiology and Treatment of Type 2 Diabetes Mellitus Flashcards
What tests are performed to diagnose diabetes and what are the defining values?
Fasting Blood Glucose: Normal < 6 Impaired Fasting Glucose = 6-7 Diabetes > 7 Glucose Tolerance Test (2 hr measurement) Normal < 7.8 Impaired Glucose Tolerance = 7.8-11.1 Diabetes > 11.1
State three factors that influence the pathophysiology of T2DM.
Genetics
Intrauterine environment
Adult environment
How is the intrauterine environment important in the pathogenesis of T2DM?
There will be epigenetic changes that take place in utero, which affect blood glucose control in the future
What is MODY?
Mature onset diabetes of the young (8 types)
It is autosomal dominant
Ineffective pancreatic beta cell insulin production
Caused by mutations of transcription factor genes (glucokinase gene)
Positive family history with NO obesity
What can modulate insulin resistance through adult life beforesomeone develops diabetes?
Adipocytokines
What type of babies are more likely to develop T2DM in later life?
Small babies (low birth weight) This is due to intrauterine growth restriction
How does insulin resistance lead to hypertension?
Insulin resistance leads to a compensatory hyperinsulinaemia
Though the insulin doesn’t affect the glycaemic control pathway, it stimulates the mitogenic pathway causing smooth muscle hypertrophy –> high blood pressure
What eventually happens to the beta cells in T2DM?
Insulin resistance damages the beta cells and eventually results in beta cell failure
Describe how beta cell reserve and insulin resistance change with age.
Beta cell reserve decreases with age and insulin resistance increases
Describe the presentation of a typical patient with T2DM.
Obese (80%)
Insulin resistance and insulin secretion deficit
Hyperglycaemia and dyslipidaemia
Acute and chronic complications
What dietary changes can someone with T2DM make to reduce the effect of the missing first phase insulin release?
Complex carbohydrates – release glucose more slowly
Describe glucose clearance and hepatic glucose output in T2DM.
Glucose clearance is decreased
Hepatic glucose output is increased
What normally happens to insulin secretion as insulin resistance increases?
Insulin secretion increases to compensate for the increased insulin resistance
Which adipocytes are particularly marked for breakdown of triglycerides?
Omental adipocytes (this is why omental fat correlates with risk of heart disease)
What happens to fatty acids when they go into the liver?
They cannot be used to make glucose so they are converted to very low-density lipoproteins (VLDLs), which are highly atherogenic
Describe how gut microbiota is implicated in T2DM.
They may be important in host signalling – they ferment various lipopolysaccharides to produce short chain fatty acids, which enter the circulation and modulate bile acids (so they can also affect host metabolism)
They are also important in inflammation and adipocytokine pathways
What is a very common side effect of diabetes treatment?
Weight gain
Which diabetes treatment does not cause this problem?
Metformin
What are the potential complications of T2DM?
Stroke Myocardial Infarction Neuropathy Retinopathy Nephropathy Hypoglycaemia
What dietary measures are recommended for someone with T2DM?
Decreased fat (particularly saturated fats) Decreased refined carbohydrates Increased complex carbohydrates Increased soluble fibre Control total calories/increase exercise
What is orlistat and why is it sometimes used in T2DM?
Pancreatic Lipase Inhibitor
It reduces the break down of fats in the intestines thus reducing the absorption of fats
State 5 classes of drugs that are used to treat T2DM and state how they work.
Metformin – insulin sensitiser (biguanides)
Sulphonylureas – makes the existing pancreas produce more insulin
Alpha-glucosidase inhibitors – prolongs the absorption of glucose from the intestine
Thiazolidinediones – addresses peripheral insulin resistance (muscle and fat)
GLP-1 agonists and DPIV inhibitors – increase insulin secretion
When should you NOT use metformin?
Severe liver failure
Severe cardiac failure
Mild renal failure
Name one sulphonylurea.
Glibenclamide
Given to lean patients with T2DM
Explain how sulphonylureas work.
They bind to receptors and block the ATP-sensitive K+ channel
This leads to Ca2+ influx, which causes insulin release
Name one alpha-glucosidase inhibitor. Explain how it works and state some side effects.
Acarbose
It prolongs the absorption of oligosaccharides and allows the body to cope with the loss of first phase insulin
Side effect: it means that some sugars get to the colon and are fermented –> flatus
Name on thiazolidinedione. What are its effects?
Pioglitazone
These are peroxisome proliferator-activated receptor (PPAR-) agonists
These are insulin sensitises mainly in peripheral tissues (leads to peripheral weight gain)
What does GLP-1 do?
Responsible for the incretin effect
Stimulates insulin and suppresses glucagon
What breaks down GLP-1?
Dipeptidyl peptidase-4 (DP-IV)
What class of drugs prolong the duration of GLP-1?
Gliptins
They inhibit DP-IV
What effect do long-acting GLP-1 agonists and gliptins have on weight gain?
GLP-1 agonists = weight loss
Gliptins = neutral
What other pharmaceutical interventions must be considered with T2DM patients?
Many T2DM patients also have dyslipidaemia and hypertension, which need to be dealt with as well
What can occur during pregnancy to identify women who are at high risk of getting diabetes in the future?
Gestational diabetes
