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Y2 - BRS - Endo > Type 2 Diabetes > Flashcards

Type 2 Diabetes Flashcards

1
Q

What is Type 2 Diabetes?

What is T2DM associated with and how can it be managed?

A

Condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia

Associated with obesity

Resultant chronic obesity may be initially managed by changes to diet, lifestyle, weightloss - may even be reversible

With time, glucose lowering therapy with insulin is required

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2
Q

What factors contributes to T2DM? (interactionist approach)

A 
Polygenic disease
Genetic vulnerability 
Trigger = obesity 
Resulting in insulin resistance
Leading to relative insulin deficiency 
Eventually - hyperglycaemia
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3
Q

Why might it be difficult to diagnose a patient with either T1DM or T2DM?

A

Patients may present with phenotypes of both

T2DM may present in youth / young adults

Diabetic ketoacidosis can also be a feature of T2DM

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4
Q

At what age can T2DM develop?

At what ages are there increasing numbers of T2DM?

A

Traditionally thought to be a condition of late adulthood - takes time for obesity / trigger to affect (genetic) vulnerability

Now good evidence that is can present throughout life

Increasing in all age groups, but rapidly in early-adulthood

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5
Q

What groups of people does T2DM affect most?

A

Greatest in ethnic groups that move from rural to urban lifestyle - Asian, Pacific-islanders, African-Caribbean

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6
Q

What are the stages of development of T2DM?

What can these stages be defined by?

A

Use fasting glucose levels; 2hr glucose (OGTT); HbA1c

Normal - =<6 mmol/L; =<7.7 mmol/L; =<42mmol/mol

Intermediate state - impaired fasting glycaemia; impaired glucose tolerance; pre-diabetes or non-diabetic hyperglycaemia

T2DM - >=7mmol/L; >=11mmol/L; >=48 mmol/mol

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7
Q

How does insulin resistance change over the 3 stages of T2DM?

A

Not a linear relationship all the way through, there is a curve

Slight increase when patient presents at normal stage

At intermediate stage, reach max insulin resistance

Plateau at T2DM stage

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8
Q

So why do patients reach T2DM if insulin resistance reaches it’s max at the intermediate stage?

A

Due to insulin production

At normal stage there is normal insulin production, which increases in production with the increasing insulin resistance

Insulin production peaks at intermediate stage

Then insulin production falls at T2DM

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9
Q

What are the different ways to diagnose DM?

A

Fasting glucose
2-hr glucose (OGTT)
HbA1c
Random glucose

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10
Q

What happens with beta-cell function during the intermediate stage?

A

Beta-cell function is already compromised

Beta-cells slowly die from apoptosis - this is due to the toxic environment created from the excess insulin production

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11
Q

How is Beta-cell function mesaured?

A

HOMA model - this is an index using fasting glucose and 2hr glucose (OGTT)

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12
Q

So is T2DM caused by insulin resistance, compromised beta cells, or both?

A

Both

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13
Q

What is the relative insulin deficiency in T2DM?

A

Insulin is produced by pancreatic beta-cells but not enough to overcome the insulin resistance = therefore relative deficiency

Explains why there is hyperglycaemia but not diabetic ketoacidosis

Enough insulin in circulation to suppress the reaction of fatty Acyl-CoA to ketones

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14
Q

What happens to beta cell function over a long duration?

A

Eventually, over many years, beta cell function will be non-existent - leads to diabetic ketoacidosis

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15
Q

What is the pathophysiology of T2DM?

A

Genes
Intrauterine environment and adult environment
Insulin resistance and insulin secretion defects
Fatty acids important in pathogenesis and complications

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16
Q

Why is T2DM heterogenous?

A

People develop T2DM at variable BMIs and progress differently

17
Q

What occurs at the IV glucose challenge between normal individuals and T2DM patients?

A

When glucose is given to participants:

In normal individuals, there is an initial first phase insulin release = sharp spike in plasma insulin |\_

This is lost in T2DM patients _____

18
Q

Does the hyperglycaemia in T2DM patients only come from the diet?

What else occurs in T2DM with the reduced insulin production and hepatic glucose production?

A

Reduced insulin action = less uptake of glucose into skeletal muscle

Hepatic glucose production is also increased due to both, a reduction in insulin action and increase in glucagon action (converting glycogen to glucose in the liver)

19
Q

How does the relationship between insulin resistance and insulin secretion change in normal individuals?

How does this change with T2DM patients?

A

High insulin sensitivity = decreased insulin production
Low insulin sensitivity = increased insulin production

In T2DM patients, they fall off the regular curve, so despite having low insulin sensitivity, they do not increase their insulin production to compensate for it

20
Q

What are the consequences of insulin resistance on the liver, skeletal muscle and adipocytes?

A

Liver = cannot uptake glucose as it is insulin dependent, excess glucose release from glycogenolysis

Skeletal muscle - cannot uptake glucose as GLUT4 receptor is insulin dependent

Adipocytes - cannot uptake glucose as GLUT4 is insulin dependent

Lack of insulin also increases the triglycerides in the blood as they cannot be broken down to NEFA and be taken up by adipocytes

21
Q

What do the excess of inflammatory adipokines cause?

A

They cause the inflammation that is involved in the pathophysiology of T2DM

22
Q

What is meant by the terms monogenic VS polygenic?

A

Monogenic - single gene mutation

Polygenic - multiple factors / genes, a risk that may be triggered later depending on other factors

23
Q

How can the individual genes contributing / affecting development of T2DM be investigated?

A

Compare DNA of T2DM patients against normal individuals

Look at SNPs - single nucleotide polymorphism

24
Q

How do individual SNPs Vs summation of SNPs affect development of T2DM

A

Individual SNPs = low risk, but summation of SNPs increases risk of T2DM

The more SNPs, the higher the prevalence of T2DM

25
Q

What is the role of obesity in the T2DM?

A

Major risk factor for T2DM
80% T2DM are obese
Fatty acids and adipocytokines important
Weight reduction useful treatment

Visceral adipocity > subcutaneous = risk for T2DM

26
Q

How does T2DM present clinically?

What are the risk factors for T2DM?

A 
Hyperglycaemia 
Overweight
Dyslipidaemia 
Fewer osmotic symptoms 
With complications 
Insulin resistance 
Later insulin deficiency 
Risk factors:
Age		
PCOS
High BMI		
Family Hx	
Ethnicity	
Inactivity
27
Q

What is the first line test for the diagnosis of T2DM?

A

HbA1c
1x HbA1c >=48mmol/L with symptoms
or 2x HbA1c >=48 mmol/mol if asymptomatic

28
Q

What is the hyperosmolar hyperglycaemic state?

A

Acute complication:

Absence of significant acidosis due to insufficient (not absent) insulin - sufficient insulin for suppression of lipolysis and ketogenesis

T2DM patients are v. dehydrated due to slow onset of osmotic symptoms - leads to high hyperglycaemia

29
Q

What is the management of T2DM?

A 
Diet
Oral medication 
Structured education 
May need insulin later 
Monitor HbA1c every few months
30
Q

What typically occurs in a T2DM consultation?

A

Gylcaemia monitoring: HbA1c. glucose monitoring if on insulin
Medication review
Weight assessment
Blood pressure
Dyslipidaemia (abnormal amounts of lipid in the blood): cholesterol profile
Screen for complications e.g. foot check (neuropathy), retinal screening (retinopathy)

31
Q

What are the dietary reccommendations and education?

A 
Total calories control
Reduce calories as fat 
Increase soluble fibre
Decrease sodium
Refine simple carbs to complex carbs
32
Q

What are the 4 key pathophysiology facets in T2DM?

What are the different strategies and solutions to target each of these pathophysiologies to treat T2DM?

A

Excess hepatic glucose production: reduce hepatic glucose production - Metformin

Resistance to action of circulating insulin: improve insulin sensitivity - metformin, thiozolidinediones

Inadequate insulin production for extent of insulin resistance: boost insulin secretion - sulphonylureas, DPP4-inhibitors, GLP-1 Agonists

Excess glucose in circulation: inhibit carbohydrate gut absorption, inhibit renal glucose resorption - alpha-glucosidase inhibitor, SGLT-2 inhibitor

Weightloss helps all issues

33
Q

What is Metformin?

How does it work?

What are some possible side effects?

A

Biguanide (oral T2DM medication), insulin sensitiser - first line if dietary / lifestyle adjustment has made no difference

Reduces insulin resistance
Reduced hepatic glucose output
Increases peripheral glucose disposal

GI side effects
Contraindicated in severe liver, severe cardiac or moderate renal failure

34
Q

What are Sulphonylureas?

How do they work to help treat T2DM?

A

Normal insulin release requires closer of the
ATP-sensitive potassium channel

Sulphonylureas eg gliclazide, bind to the ATP-sensitive potassium channel and close it, independent of glucose / ATP = boosts insulin production

35
Q

What is Pioglitazone?

How does it work?

What are some possible side effects?

A

Agonist in PPARs (Peroxisome proliferator-actived receptor)
Modifies insulin sensitivity

Adipocyte differentiation modified
Improvement in glycaemia and lipids

Side effects of older types hepatitis, heart failure, may cause weight gain (peripheral not central)

36
Q

What is GLP-1?

What are GLP-1 agonists?

What are DPP4- inhibitors and why do they work?

A

Gut hormone - stimulated insulin and suppresses glucagon, increases satiety
Short half-life due to degradation by enzyme DPP-4
Discovered when it was found that IV glucose does not increase plasma glucose as much as ingested glucose

GLP1 agonists: e.g. Liraglutide, Semaglutide - injectable – daily, weekly
Decrease [glucagon]
Decrease [glucose]
Weight loss - due to nausea and appetite suppression

DPP-4 inhibitor = increases half life of GLP-1 if the DDP is inhibited as it cannot breakdown the GLP-1
e.g. Gliptins

37
Q

What are SGLT-2 inhibitors?

How do they work?

A

e.g. Empagliflozin, dapagliflozin, canagliflozin work to lower HbA1c

Inhibits Na-Glu transporter, increases glycosuria
Improve CKD

38
Q

How can T2DM be remissed?

A
  1. Gastric bypass surgery - potential for remission of T2DM

2. Low-cal diet for 3-6 months has potential to induce remission - sustains for over 2 years

39
Q

What else can be managed alongside T2DM?

A

The risks that come with T2DM e.g. hypertension, dyslipidaemia (often raised cholesterol, triglycerides, and reduced HDL)

Y2 - BRS - Endo (22 decks)

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