T2DM Flashcards
What is the definition if Diabetis?
A state of chronic hyperglycamia suficcient to cause micorvascular and macrovascular complications
What does ketones in blood/urine show in T1/T2DM?
Normally present in T1DM, not in T2DM, but can be present in T2DM
What are the associated conditions of someone with T2DM?
•T2DM often involves weight, lipids and blood pressure
What are the diagnostic measurement of blood glucose for Diabetis and imparied glucose tolerance/impaired fasting glucose?
- Fasting
- 2h after meal
- Random time
Diabetis?
- Fasting glucose > 7mmol
- 2h after meal > 11.1 mmol
- At any time > 11.1 mmol
Impaired tolerance
- Fasting glucose > 6mmol
- 2h after meal > 7.6mmol
Explain the epidemiology of T2DM
- Diabetes is prevalent (10% at 60yr) Mostly T2DM
- Age is a risk factor but also caused by
- Prevalence of T2DM varies enormously
- Increasing prevalence
- Occurring and being diagnosed younger
- Greatest in ethnic groups that move from rural to urban lifestyle
What is the main characterisitic of T2DM?
It is a combination of insulin resistance and a relative insulin production (enough to swith down ketone production, not to reduce hepatic glucose output)
What is MODY?
Matuity onset of diabetis in the yound
–> ineffective ß-cell insulin production
–> single gene defect causing diabetis (Family history but no diabetis)
What is the role of genetic in T2DM?
- There is a genetic component, different in everyone
- Some might require very little outside influence to develop T2DM, some mith require more environmental influence
- Is made worse by obesity and some particular fatty acids
What is IUGR? What is its influence in T2DM?
Intra-uterine-growth restriction –>(lack of calories in utero) might modulate gene expression for rest of life and make people more predisponed to diabetis
(due to protein restrictions that are required in pancreatic development)
When does the insulin resistance in people with T2DM develop?
Normally already early, but only late detected
–> already causes dyslipidaemia and macorvascular complications early on
When does someone in T2DM required insulin?
When the ß-cells can’t keep up with the demand–> ß-cell failure
- leading to
- worseining of dyslipidaemia –> macrovascular complications
- hyperglycaemia –> microvascular complications
What happens naturally to insulin resistance and insulin secretion when you age?
- Insulin Resistance increases
- Insulin production decreases
How does T2DM present?
- Very different in everyone
- obesity
- hyperglycaemia
- dyslipidaemia
- present with aculte and chronic complications of diabetis
- might present with osmotic symptoms
- or infections –> high sugar attracts bacteria
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Explain the origin of dyslipidaemia in diabetis
Becaue of insulin resistance –> Fat cells break down Triglycerides (normally downregulated by insulin)
The NEFAs are turned into Small Dende VLDL –> dislipidaemia
Why does fasting glucose levels increase in someone with T2DM?
Because Hepatic glucose output is not supressed by insulin, due to insulin resistance
What is the prevalence of obesity in T2DM individuals?
80%
Through which factors does omental obesity influences the development of T2DM?
Through special Fatty acids and adipocstokines
What is the role of our micorbium in T2DM?
There is an associaton in
- Obesity, insulin resistance T2DM
- Microbiome modulates Host signaling via
- Bacterial lipopolysaccharides fermentation to short chain FA
- bacterial modulation bile acids
- Leading to antered siganling in Inflammation, and metabolic pathways
Which factors influence insulin resistance development?
- Intra-uterine environmen
- Adipocytokines
- Microbioata
- Diet, exercise
- Medication
What is the overall management of T2DM?
Aim: To treat symptoms and prevent complications to develop
- Education
- Diet
- Pharmacology
- complication screening
What is the recommended Diet in someone with T2DM?
- Control total calories –> weight
- increase complex Carbohydrates
- reduce total amount of fat
- if fat: encourage unsaturated
- increase soluble fibre
- Low salt –> Lower BP
Which factors need to be monitored and treated in T2DM?
- Weight
- Glycaemia
- Blood pressure
- Dyslidiaemia
What are possible pharmacological/surgical treatments of weith loss in T2DM?
- Orlistat
- decreases FA absorbtion
- GI lipase inhibitor
- Gastric bypass
Explain the physoiology of insulin secretion
- Glucose increases intracellulr ATP
- ATP blocks ATP regulated K+ channels –> less K+ outflow
- That causes an inflow of Ca2+ via change of membrane potential
- Ca2+ stimmulated insulin secretion
What is a treatment option for lean individuals with T2DM?
Why only for lean individuals?
Explain the molecular MOA
Sulfonylureas (Glibenclamide)
It stimmulates insulin secretion by directly altering the ATP dependant K+ channels
BUT–> the insulin secreted causes weight gain so only in lean patients/more effective in lean patients
What is THE DRUG in T2DM? How does it work?
Metformin
It makes cells more sensitive to insulin –> reduces Hepatic GO,
- Mainly for overweight patients where diet has not succeeded
What are the side effects and contra-indications for use of Metformin?
- GI side effects
- Not used in severe liver disease or cardiac failusre or mild renal failure
What is acarbose?
When is is used?
What is the MOA?
It is a •Alpha glucosidase inhibitor used in the treatment of T2DM
- prolonges absorbation of oligosaccarides therefore does not increase initial blood glucose as significantly –> slower absorbtion
- Allows insulin secretion to cope to overcome defective first phase insulin
What are Thiazolidinediones?
What is their MOA?
Used in treatment of T2DM –> make insulin work better (mainly in peripheral regions)
–> causes redistribution of fat from central to peripheral body parts
- Improvement in glycaemia and lipids
- Reduces vascular complications
What is the physiological role of Glucagon-like peptide 1?
Normally secreted by L-cells with every meal
It:
- Stimulates insulin, suppresses glucagon
- Increases satiety
Explain the use of GLP1 in diabetis
Is effective because it
- Increases Insuin
- Decreases Glucose output
- As injection : decreases weight
What are the two ways you could treat someone with GLP1 in T2DM?
- GLP1 agonist (injections)
- Long acting GLP-1 agonist
- Decrease [glucagon]
- Decrease [glucose]
- Weight loss
- Gliptins (DPPG-4 inhibitors)
- Increase half life of exogenous GLP-1
- Increase [GLP-1]
- Decrease [glucagon]
- Decrease [glucose]
- Neutral on weight
Explain the use of SGLT2-inhibitors in the treatment of diabetis
What is a brand name?
Empaglifozin
- Inhibits Na-Glu transporter, increases glycosuria –> more sugar peed out, not in circulation
What is the prevalence of Type 1 DM
0.25%
