case 6 - introduction to type 2 diabetes Flashcards
what is diabetes mellitus
metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action or both
what is type 2 diabetes
metabolic disorder caused by insulin resistance and insulin deficiency resulting in hyperglycaemia
what is pre diabetes and how is it diagnosed
at high risk of developing type 2 diabetes:
Impaired glucose tolerance - IGT
Above normal glucose blood concentration after fasting (impaired glucose fasting - IFG)
Above normal HbA1c - 42-48 = pre diabetes and 48+ is diabetes
what is the epidemiology of type 2 diabetes
in 2015 there were over 415 million people with diabetes worldwide
Type 2 diabetes accounts for around 90% of cases
in the UK, around 3.9 million are diagnosed with diabetes in 2019
Steady increases in diabetes incidence and prevalence
who is type 2 diabetes the most common in
more common in men than in women
65+ age group most affected
Increasing numbers diagnosed under 40 years of age
Childhood type 2 diabetes incidence also increasing
what ethnicity is diabetes the most common in
3-5 times increased prevalence in ethnic minority groups vs white communities.
south asians
in spite of lower BMI, what do south asians have:
more abdominal fat
More insulin resistance + hyperinsulinaemia
Increased inflammatory reponse
Lower adiponectin
More dyslipidaemia
what is the morbidity and mortality causes in type 2 diabetes
cardiovascular disease is the cause of death in around 70%
Commonest cause of chronic kidney disease
Commonest cause of lower limb amputation
Commonest cause of blindness in working population
Non-alcoholic fatty liver disease and most common liver disease in the world
10% of the NHS budget
what is the pathophysiology of type 2 diabetes
- there are genetic predisposition and environmental risk factors
- these risk factors lead to obesity, which leads to insulin resistance
- this leads to decreased glucose uptake which then leads to hyperglycaemia
- then hyperglycaemia leads to type 2 diabetes
- also increased hepatic glucose output, caused by deranged insulin release can also lead to hyperglycaemia
what are the non modifiable risk factors of type 2 diabetes
age
Ethnicity
Family history
Low birth weight
History of GDM
what are the modifiable risk factors for type 2 diabetes
obesity -approximately 80% of the risk for developing T2DM
Hypertension - 20mmhg increase was associated with 58% increase risk of diabetes
Dyslipidemia - low HDL, high triglycerides
PCOS - elevated androgens and insulin resistance
Poor dietary habit
what is the linear relationship between obesity and type 2 diabetes
Visceral and abdominal fat have a much greater associated with type 2 diabetes than cutaneous fat
Variation in distribution of fat with age, ethnicity, and sex
Increased fat mass —> insulin resistance and type 2 diabetes
what are the genetics linked to diabetes
polygenic
The risk of developing the condition is as high as 70% if both parents have suffered from the condition
First degree relatives of individuals with type 2 diabetes are about 3 times more likely to develop the disease
Monozygotic twins, there is a 50-90% concordance for developing the condition
Environments —> genetics
what are the steps in the key pathophysiological processes
- insulin resistance
- insulin secretory defect
- increased production of glucose by the liver
- loss of incretin effect
- other mechanisms such as insulin feedback and CNS changes
what processes does insulin lead to
Insulin leads to a number of anabolic processes, such as building larger molecules from smaller molecules, which are crucial to cellular survival, the growth of cells and tissues and maintaining normal homeostasis
what is the insulin receptor
a modified tyrosine kinase receptor
describe the binding of this receptor and what happens
he insulin receptor is a modified tyrosine kinase receptor
when insulin, as the ligand, binds to the insulin receptor, you get the insulin signalling cascade
An important part of the insulin signalling cascade is the exocytosis of GLUT4 channels to the cell membrane and then the facilitated diffusion of glucose, which is in the blood of course, into the cell
Glucose is then used in glycolysis in cellular respiration so that we get energy
in insulin resistance, what else does this increased glucose lead to
hyperglycaemia
Increased lipolysis
Increased proteolysis
Increased hepatic gluconeogenesis
what else is this glucose used for in anabolic processes and cellular growth
cellular respiration
Proteins and lipid synthesis
Inhibit hepatic gluconeogenesis
Promote hepatic glycogen synthesis
what are the damaging molecules in obese people
free fatty acids
what are free fatty acids used as
used as a substrate, as an energy by the liver and gluconeogenesis is increased
what is there less of because of this free fatty acid accumulation around the liver
there is less insulin feedback
what is there more of because of these free fatty acids
there is more gluconeogenesis and more blood glucose
what happens in the muscles
the muscles will used more fatty acids instead of glucose, so there is less glucose taken up from the blood and therefore less glycogenesis
what is the relationship between free fatty acids and the beta cell
FFAs are toxic to the beta cell and therefore less insulin is released again leading to problems with hypoglycaemia
what mediators are increased with increased lipolysis
inflammatory mediators;
released by adipocytes:
- TNF alpha and IL-6
what kind of activity is increased with lipolysis
greater sympathetic activity
what happens to the beta cells as hyperglycaemia develops
beta cells secrete more insulin to deal with increase in glucose
what happens when the beta cell mass is depleted
insulin levels fall and there is secretory failure
what is shown during autopsy of patients with T2DM
increased deposition of amyloid within islet cells
