Diabetes Flashcards

1
Q

What is T2D?

A

Non insulin dependent diabetes - 12.3 million at risk in the UK - increase of 55% between 2007 and 2025 - 90% of diabetes cases - preventable - most common in developing countries (LATAM/AFME)

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2
Q

Symptoms of T2D?

A
Fatigue
Weight Loss
Increased Urine
Blurred vision
Increased hunger
Thirst
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3
Q

Risk factors of T2D?

A
Heriditary (direct relative)
South Asian/Middle Easter
Old Age
Men
Obesity (80-85% risk)
Low PA
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4
Q

What method was used to determine the genetic involvement of T2D?

A

GWAS - compare SNPs in control group (3000) and T2D (2000) - display results in manhattan plot to identify SNPs with significant difference between groups

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5
Q

What genes were identified to play a role in T2D?

A

TCF7L2 - Biggest risk factor so far - Insulin secretion - experiments with siRNA showed silencing of the gene reduces insulin secretion - unsure why
KCNJ11 - E23K variant - blocks closing of ligand gates potassium channel - reduces depolarisation of cell - insulin secretion
PPARG - adipogenisis - insulin resistance
CDKAL2 - cyclin dependent kinase - turnover of cells - regulates number of b cells available for insulin secretion
FTO - Fat mass and obesity gene - regulates BMI - unsure on action however thought to regulate weight and fat mass through influencing food uptake - polymorphism impact on T2D dependent on region

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6
Q

What is the pathophysiology of T2D?

A

Insulin resistance - insulin has less of an effect at target cells - reduces uptake at muscle/fat cells and less effect on reducing release from liver

Hypertrophic Adipocytes - hypoxia - ER stress - inflammation:
Increased FFA - target visceral fat stores - inefficient metabolism - build up of DAG and ceramide intermediates - insulin resistance
Reduced adiponectin - reduced AMPK activation - reduced uptake at muscle
TNF-A - IRS-1 - reduces glucose uptake at muscle and fat cells

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7
Q

What drugs can we use to treat T2D?

A

Metformin - weight loss/complex 1 activity (reduce ATP/increase AMPK - increases glucose uptake at muscle/reduces release from liver)

Sulphonyreas - insulin secretagogues - blocks K channel - increases release - amaryl - not used when patient is overweight

GLP-1 - incretin - reduces gastric emptying and promotes insulin secretion - given with DDP4 inhibitor (januvia)

SGLT-2 inhibitor - increases glucose in urine - given with januvia

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8
Q

What measurement do we use to diagnose T2D?

A

HBAC1 - 2-3 months of glucose in blood - 48mmol/mol

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9
Q

What complications can be associated with T2D?

A

Small vessel - retinopathy/nephropathy/neuropathy

Large vessel - CVD/stroke/Iscahemia

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10
Q

What was the outcome of the Diabetes Prevention programme? (DPP)

A

Study involved people with prediabetes (raised fasting glucose levels) and split into three 3 groups; placebo, life-style changes (PA/diet - 7%weight loss and 150 mins exercise per week) and metformin (biguanide). Over 3 years - 58% reduction in incidence of diabetes in lifestyle group, 38% reduction in metformin group compared to placebo.

Shows that lifestyle changes are the best preventer of disease progression.

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11
Q

What is the newcastle600 diet?

A

11 people with T2D given 600 calorie diet for 8 weeks - 7 free of T2D

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12
Q

What are the results of studies to investigate proponiate as a risk factor for T2D?

A

Proponiate - bread/cheese

Mice: Short term found increased blood glucose, Long term found increased weight and insulin resistance. tested in Humans - placebo and propionate group - found short term increase in insulin resistance - more studies needed.

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