Diabetes Flashcards
What is T2D?
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)
Symptoms of T2D?
Fatigue Weight Loss Increased Urine Blurred vision Increased hunger Thirst
Risk factors of T2D?
Heriditary (direct relative) South Asian/Middle Easter Old Age Men Obesity (80-85% risk) Low PA
What method was used to determine the genetic involvement of T2D?
GWAS - compare SNPs in control group (3000) and T2D (2000) - display results in manhattan plot to identify SNPs with significant difference between groups
What genes were identified to play a role in T2D?
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
What is the pathophysiology of T2D?
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
What drugs can we use to treat T2D?
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
What measurement do we use to diagnose T2D?
HBAC1 - 2-3 months of glucose in blood - 48mmol/mol
What complications can be associated with T2D?
Small vessel - retinopathy/nephropathy/neuropathy
Large vessel - CVD/stroke/Iscahemia
What was the outcome of the Diabetes Prevention programme? (DPP)
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.
What is the newcastle600 diet?
11 people with T2D given 600 calorie diet for 8 weeks - 7 free of T2D
What are the results of studies to investigate proponiate as a risk factor for T2D?
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.
