T2DM Flashcards
Define diabetes
Diabetes mellitus can be defined as a state of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues, notably the retina, kidney, nerves, and arteries
What is the difference between T1DM and T2DM
T2DM is not ketosis prone
T2DM is not mild
T2DM often involves weight, lipids and blood pressure
What is the prevalence of T2DM
It varies enormously but is increasing and greatest in ethnic groups that move from rural to urban lifestyles
What gives useful metabolic insights into T2DM
MODY relatively uncommon but gives useful metabolic insights
What defects, environments and genes can cause or increase chances of T2DM
- Genes and intrauterine environment (intrauterine growth restriction increases chances of developing T2DM) and adult environment.
Insulin resistance and insulin secretion defects
What is important in the pathogenesis and complications of T2DM
Fatty acids important in pathogenesis and complications
What is MODY
Maturity onset diabetes of the young, an autosomal dominant condition with several hereditary forms (1-8) with a positive family history and obesity
What is MODY due to?
Ineffective pancreatic B cell insulin production due to mutations of transcription factor genes, glucokinase gene.
What have twin studies shown about diabetes
T2DM follows an almost autosomal dominant pattern whereas T1DM has less genetic input.
What is the presentation of T2DM
Obese, hyperglucaemic, dyslipidaemia, acute and chronic complications
What is the metabolic problems that cause T2DM
There is insulin resistance and insulin secretion deficits
What are the effects of fatty acids and how are they different in obesity and T2DM
In Obesity and T2DM they are elevated ↑ IR Whole body muscle and liver ↓ B cell function ↑ Liver TG secretion ↑ Organ fat, oxidative stress
What does TNF alpha and IL 6 do?
↑ IR Whole body and muscle
↓ adiponectin expression
What is the effects of leptin and what are the changes in it during obesity?
Elevated in obesity
↑ IR Whole body muscle and liver
↓ appetite
↑ metabolic rate
What are the effects of glucocorticoids
↑ 11β HSD-1 in fat
↑ fat cell size and IR
↑ glucose BP Lipids
What are the effects of endocannabinoids?
Insulin inhibits expression in fat
Fat IR > ↑ circulating EC
What are the effects of adiponectin?
↓ insulin resistance
Predictive of diabetes
What are the effects of visfactin and where is it found?
Visceral fat
↓ IR Whole body
What are the effects of apelin?
Insulin stimulates expression in fat
Elevated in hyper Insulin
CV effects
What are the effects of resistin and how are they different in obesity and T2DM
Elevated in obesity and T2DM
↑ IR Whole body and liver
↑ Liver TG secretion
What is the link between obesity and T2DM
- More than a precipitant
- Fatty acids and adipocytokines important
- Central or omental obesity
- 80% T2DM are obese
- Weight reduction useful treatment
What is the presentation of T2D
- Osmotic symptoms
- Infections
- Screening test
at presentation of complication - Acute; hyperosmolar coma,
- Chronic; ischaemic heart disease, retinopathy
What are microvascular complications of T2DM
Retinopathy
Nephropathy
Neuropathy
What are metabolic complications of T2DM
Lactic acidosis
Hyperosmolar
What are macrovascular complications of T2DM
Ischaemic heart disease
Cerebrovascular
Renal artery stenosis
PVD
What are complications of T2DM that can be due to treatment?
Hypoglycaemia
What is the basic management of T2DM
Education
Diet
Pharmacological treatment
Complication screening
Why do you treat T2DM
Symptoms
Reduce chance of acute metabolic complications (unlikely in T2DM)
Reduce chance of long term complications; good evidence base (UK prospective diabetes study or UKPDS)
What should patients with T2DM eat?
- 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 you monitor in T2DM
Weight
Glycaemia
Blood pressure
Dyslidiaemia
What is a new exciting study of a new treatment for diabetes
Gastric bypass - improved diabetes control. Adverse events and nutritional deficiency increased therefore larger and longer trials needed
What is metaformin?
A biguanide, insulin sensitiser that reduces insulin resistance
How does metaformin work
It reduces insulin resistance by a reduced hepatic glucose output and an increased peripheral glucose disposal
When is metaformin used
In an overweight patient w/ T2DM where diet alone has not succeeded
When should metaformin not be used?
If severe liver, severe cardiac or mild renal failure
What is acarbose?
An alpha glucosidase inhibitor that prolongs the absorption of oligosaccharides therefore allowing insulin secretion to cope, following defective first phase insulin
What is the side effect of acarbose
Flatus
What are thiazolidinedones
Peroxisome proliferator-actived receptor agonists PPAR-γ that are insulin sensitizers, mainly peripheral. Adipocyte differentiation modified, weight gain but peripheral not central. Improvement in glycaemia and lipids according to evidence based on vascular outcomes
What is an example of a thiazolidinedone
Pioglitazone
What are side effects of thiazolidinedones
Hepatitis, heart failure
What does GLP1 do?
Transcription product of proglucagon gene, mostly from L cell and secreted in response to nutrients in the gut
-> Stimulates insulin, suppresses glucagon SO Increases satiety and restores B cell glucose sensitivity
What are treatment options for T2DM
Metaformin Acarbose Thiazolidinedone GLP1 agonists DPPG4 inhibitors (gliptins) Empaglifozin
What are GLP1 based treatment options?
GLP1 agonist or Gliptins (DPPG4 inhibitor)
What do GLP1 agonists do? What are examples of them
Exenatide, liraglutide (Injectable) Long acting GLP-1 agonist Decrease [glucagon] Decrease [glucose] Weight loss
What do gliptins do (DPPG4 inhibitors)
Increase half life of exogenous GLP-1
Increase [GLP-1]
Decrease [glucagon]
Decrease [glucose]
What does empaglifozin do?
Inhibits Na-Glu transporter, increases glycosuria
leading to lower HbA1c
What are other aspects of the body that should be controlled in T2DM
- Blood pressure Possibly 90% T2DM Clear benefits to treatment - Diabetic dyslipidaemia Cholesterol ↑ Triglyceride ↑ HDL-Cholesterol ↓ Clear benefits to treatment
What is the problem with screening for diabetes
The mortality, morbidity and cost. The specifics of screening programmes are unclear and which tests should be done and how often in who
Can you draw a table comparing prevalence, typical age, onset, habitus, family history, geography, weight loss, ketosis prone, serum insulin, HLA association, Islet B cells and islet abs between t1 and t2 DM
lecure t2dm
How can insulin resistance lead to macrovascular disease
Insulin resistance leads to dyslipidaemia leading to increased mitogenic pathway leading to hypertrophy and increased BP leading to macrovascular disease
