Type 2 Diabetes Mellitus Flashcards
Define Diabetes Mellitus
A state of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues, notably the retina, kidney, nerves, and arteries
Describe the features of T2DM that may distinguish from T1DM
T2DM is not ketosis prone
T2DM is not mild
T2DM often involves weight, lipids and blood pressure
Describe the epidemiology of T2DM
10% at 60yr Increases with age Varies enormously Increasing prevalence Being diagnosed younger Greatest in ethnic groups that move from rural to urban lifestyle
Describe the pathophysiology of T2DM
Maturity Onset Diabetes of the Young is relatively uncommon
Genes + intrauterine environment + adult environment
Insulin resistance and insulin secretion defects
Fatty acids important in pathogenesis and complications
Describe MODY
Maturity onset diabetes of the young
Several hereditary forms (1-8)
Autosomal dominant
Ineffective pancreatic B cell insulin production
Mutations of transcription factor genes, glucokinase gene
Positive FH, no obesity
Specific treatment for type
Describe metabolism and the presentation of T2DM
Heterogeneous Obesity Insulin resistance and insulin secretion deficit Hyperglycaemia and dyslipidaemia Acute and chronic complications
Describe the metabolism of glucose in diabetes
Converted to glycogen in muscle
- Taken to an adipocyte
- Lipolysis to form triglycerides
- Glycerol and NEFA produced
- Glycerol taken to liver
- Glycerol + glycogen -> glucose
- NEFA chopped -> VLDL-TG (Very low density lipoprotein triglyceride - Atherogenic)
What are the effects of T1DM on fatty acids
Elevated Increase: Whole body muscle and liver Liver TG secretion Organ fat, oxidative stress
Decreased B cell function
What substances are involved in T1DM mechanisms
Fatty acids Glucocorticoids Endocannabinoids Adiponectin Visfatin Apelin Resistin Leptin TNF-alpha IL-6
Describe the association of obesity with T2DM
Fatty acids and adipocytokines important
Central or omental obesity
80% T2DM are obese
Weight reduction useful treatment
How are perturbations in gut microbiota involved in T2DM
Obesity, insulin resistance T2DM
- Lipopolysaccharides fermented by gut bacteria
- Short chain FA
- Enter circulation and modulate bile acids
- Modulate host metabolism (i.e. cause obesity) and are involved in adipocytokine pathways (modulating insulin resistance)
Describe the presentation of T2DM
Osmotic symptoms
Infections
Acute; hyperosmolar coma,
Chronic; ischaemic heart disease, retinopathy
What are the microvascular complications of T2DM
retinopathy
nephropathy
neuropathy
What are the microvascular complications of T2DM
Ishcaemic heart disease
Cerebrovascular
Renal artery stenosis
PVD
What are the metabolic and treatment complications of T2DM
Lactic acidosis
Hyperosmolar
Hypoglycaemia
What are the basic management focuses for T2DM
Education
Diet
Pharmacological treatment
Complication screening
Describe the diet recommended to T2DM patients
Control total calories/increase exercise (weight)
reduce refined carbohydrate (less sugar)
increase complex carbohydrate (more rice etc)
reduce fat as proportion of calories (less IR)
increase unsaturated fat as proportion of fat (IHD)
increase soluble fibre (longer to absorb CHO)
Address salt (BP risk)
What should be monitored in T2DM
Weight
Glycaemia
Blood pressure
Dyslidiaemia
Describe Metformin
Insulin sensitiser (biguanide) Given when diet has not succeeded Reduces insulin resistance Reduces hepatic glucose output and increases peripheral glucose disposal No weight gain GI side effects
What are the contraindications for Metformin
Severe liver failure
Severe cardiac failure
Mild renal failure
Describe glibenclamide (sulphonylurea)
Makes pancreas secrete more insulin by blocking ATP sensitive potassium channel -> influx of calcium -> insulin secretion
Causes weight gain and hypoglycaemia
Describe acarbose
Alpha glucosidase inhibitor
Prolongs absorption of oligosaccharides (carbs)
Allows insulin secretion to cope with first phase insulin loss
Side effects flatus
Describe thiazolidinediones
PPAR-γ agonists Pioglitazone Insulin sensitizer, mainly peripheral Peripheral weight gain Improvement in glycaemia and lipids Side effects of older types hepatitis, heart failure
Describe glucagon like peptide-1
Secreted in response to nutrients in gut by L cells
Stimulates insulin, suppresses glucagon
Increases satiety
Restores B cell glucose sensitivity
Short half life, rapid degredation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)
Describe GLP-1 agonists
Exenatide, liraglutide Injectable Long acting GLP-1 agonist Decrease [glucagon] Decrease [glucose] Weight loss
Describe DPPG-4 inhibitors / Gliptins
Increase half life of GLP-1
Not as effective as GLP-1 agonist
Describe empaglifozin
Inhibits Na-Glu transporter, increases glycosuria 0 glucose resorption reduced
HbA1c lower
Describe the changes in insulin resistance and insulin secretion with age
(childhood unknown)
Decrease in secretion and increase in resistance throughout childhood
Slight increase in secretion then decrease rapidly (non-linear)
Resistance increases linearly after childhood
What are the effects of insulin resistance
- Unable to stop the breakdown of triglycerides -> glycerol release from adipocytes -> NEFA formation
- Dyslipidaemia - stimulates the mitogenic pathway, increasing smooth muscle hypertrophy -> increase in BP
- Damages beta cells -> gradual beta cell failure so insulin cannot be produced to cover the decreased insulin sensitivity -> hyperglycaemia
- Loss of 1st phase insulin
2nd phase insulin can still be produced, but takes longer and is immature -> hyperglycaemia - Absolute insulin deficiency
