Diabetes Type 2 Flashcards

1
Q

What factors cause insulin resistance?

A

Genetic risk

Obesity

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2
Q

What is LADA?

A

Latent autoimmune diabetes in adults

  • need be aware aware that there are cases where diabetic ketoacidosis is a feature of T2DM, and it may be present in the youth
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3
Q

What is monogenic diabetes?

A

Can present phenotypically as type 1 or type 2 e.g. MODY mitochondrial disease

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4
Q

Which country as the highest projected prevence?

A

India

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5
Q

Whats a normal fasting glucose vs a T2 fasting glucose?

A

<6mmol/L

vs

> 7mmol/L

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6
Q

What is a normal 2 -hr glucose vs a T2?

A

<7.7 mmol/L

vs

> 11mmol/L

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7
Q

What happens to Beta cell function after T2DM?

A

If treatment is started, function % may increase by a very small %. then it will decrease a few years after being on treatment steadily

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8
Q

What does it mean to have relative deficiency of insulin?

A

Insulin is being produced but not enough to overcome insulin resistance

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9
Q

In which cases may T2DM have complete insulin deficiency?

A

Long duration T2, beta cell failure may progress to complete deficiency

Usually they are started on Insulin at this point and do not stop as they are at risk of ketoacidosis

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10
Q

How can genetics cause B cell failure *as a factor of T2?

A

IUGR or involving obesity/fatty acids which are both affected by genetics

Can cause insulin resistance adipocytokines

And these cause B cell failure

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11
Q

What happens to first phase insulin in T2?

A

is lost : plasma levels do not shoot up although they start slightly higher

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12
Q

How does T2 diabetes affect skeletal muscle uptake?

A

Less glucose uptake due to reduced insulin

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13
Q

How to T2DM affect hepatic glucose production?

A

Increased due to a reduction in insulin action and increase in glucagon action

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14
Q

What physiological processes contribute to a high fasting plasma glucose in T2DM?

A
  • impaired glucose removal
  • Increased hepatic production
  • inability to oxidise and store in muscles due to bad insulin

= reduction in metabolic clearance rate of glucose

–> excess glucose turned into lactate which enters Cori cycle and turns back into glucose * this results in the increased fasting glucose e.g. from last nights meal

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15
Q

How can glucagon result in hepatic glucose production in T2DM?

A

excessive glucagon mediated glucose output cause gluconeogenesis

and this is supported by inadequate insulin which causes an influx of substances like glycerol and free fatty acids to live also increasing gluconeogensis

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16
Q

What does the graph of insulin sensitivity by insulin secretion look like and how does this differ for T2DM

A

Reciprocal graph

Those people have ‘fallen off the curve’ and for a given degree of insulin sensitivity they secrete less insulin

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17
Q

Which inflammatory adipokines are in excess?

A

TNF-a IL-6

Glucocorticoids

Visfatin

Adiponectin

Endocannabinoids

Leptin

Resistin

Apelin

Fatty acids

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18
Q

What does TNF-a IL-6 do in T2DM?

A
  • -> lipolysis
  • -> VLDL secretion
  • -> insulin R

decreases adiponectin expression

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19
Q

What does adiponectin do in T2DM?

A

Decrease insulin resistance and is predictive of diabetes

20
Q

What does Visfatin do in T2DM?

A

Visceral fat

Decreased insulin R in whole body

21
Q

What does Glucocorticoids do in T2DM?

A
  • -> 11B HSD-1 in fat
  • -> fat cell size and IR

–> glucose BP lipids

22
Q

What does ENdocannabinoids do in T2DM?

A

Insulin inhibits expression in fat

fat resistance > circulating EC ?

23
Q

What does Leptin do in T2DM?

A

Elevated in obesity

resistance increases in body, muscle, liver

appetitie decreaser

metabolic rate increaser

24
Q

What does resistin do in T2DM?

A

Elevated in obesity and T2DM

Insulin resistance in whole body and liver

Liver TG secretion increaser

25
What do fatty acids do in T2DM?
``` Elevated in obesity and T2DM --> IR Whole body muscle and liver decreases B cell function --> Liver TG secretion --> Organ fat, oxidative stress ```
26
What does Apelin do in T2DM?
Insulin stimulates expression in fat elevated in hyperInsulin Cardiovascular effects
27
What is SNPs?
single nucleotide polymorphisms - each individual SNP has only a mild effect on risk - cumulative effect of all SNPs have a bigger effect
28
What are the presentations of T2DM?
- Hyperglycaemia - Overweight - Dyslipidaemia - Fewer osmotic symptoms - With complications - Insulin resistance - later insulin deficieny
29
What is considered during the diagnosis of Type 2?
Osmotic symptoms Infections Screening test At presentation of complication All above can be reasons to look into diagnostic testing: - 1 HbA1c with symptoms - 2 HbA1c is asymptomatic
30
What type of complications may a potential diabetic present with?
Acute: Hyperosmolar hyperglycaemic state Chronic : ischaemic heart disease, retinopathy
31
Which type of px present with hyperosmolar hyperglycaemia state?
Renal failure insulin is insufficient to stop hyperglycaemia but enough to suppress lipolysis + ketoacidosis often identifiable precipitating event e.g. infection, MI
32
What is checked during a T2DM consultation?
Glycaemia HbA1c, medication review Weight assessment Blood pressure Dyslipidaemia- cholesterol profile Screening for complications
33
Why is Metformin given?
- Reduces the excess hepatic glucose production - lowers the glucose resistance of insulin so increases sensitivity * GI side effects
34
What does Thiozolidinediones do?
- lowers the glucose resistance of insulin so increases sensitivity
35
What do Sulphonylureas, DPP4-inhibitors. GLP-1 Agonists do?
Boost insulin secretion
36
What does Alpha glucosidase inhibitor and SGLT-2 inhibitor do?
inhibit carb gut absorption and inhibit renal glucose resorption to reduce excess glucose in circulation
37
What is metformin contraindicated?
Severe liver, severe cardiac, moderate liver failure
38
What is the mechanism of action of sulphonylureas?
Bind to ATP sensitive potassium channel and close it, independent of glucose releasing insulin
39
What is Pioglitazone?
Peroxisome proliferator-activated receptor agonists peripheral adipocyte differentiation modified = insulin sensitizer glycaemia and lipid improvements vascular outcomes side effects of older types hep, heart failure
40
Which glucose lowering therapy causes most weight gain?
Thiozolidinediones
41
What is GLP-1?
glucagon like peptide gut hormone secreted in response to nutrients transcription product of pro glucagon gene, from L cell increases satiety short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 used in DM treatmentq
42
What effects do GLP-1 agonists have?
decrease glucagon decrease glucose weight loss - injectable - e.g: liraglutide, semaglutide
43
What is Gliptins?
DPPG-4 inhibitor (inhibits enzyme) increases half life of exogenous GLP-1 Increases GLP-1 Decrease glucagon decrease glucose neutral on weight
44
What do SGLT-2 inhibitors do?
inhibits Na-Glu transporter, increases glycosuria e.g. Empagliflozin, Canagliflozin, Deapagliflozin HbA1c lower lowers all cause mortality and heart failure improve CKD
45
What may allow remission of T2DM?
Gastric bypass surgery very low cals - 800 daily for 3-6 months can induce remission
46
Why is lipid management important?
Total cholesterol raised Triglycerides raised HDL cholesterol reduced Clear benefit to lipid-lowering therapy