Lec13 Type 2 Diabetes Mellitus Flashcards
What is diabetes mellitus
A condition where blood glucose is above an internationally accepted level
Describe the usually clinical diagnosis with respect to blood and HbA1c respectively
Glucose equal or greater than 11.1mmol/l and symptoms
Glucose equal or greater than 11.1mmol/l in two tests
HbA1c equal to or greater than 4mmol/mol
In a 75g oral glucose tolerance test, describe the parameters of diagnosing DM:
Fasting plasma glucose =/ > 7mmol/l
2 hour plasma glucose =/> 11.1mmol/l
In a 75g oral glucose tolerance test, describe the parameters of diagnosing IGT
2 hour glucose between 7-11mmol/l
In a 75g oral glucose tolerance test, describe the parameters of diagnosing IFT
Fasting glucose between 6-6.9mmol/l
What is Type 2 DM
A common condition characteristic of hyperglycaemia due to the inability of the pancreatic beta cell to produce enough insulin to regulate plasma glucose concentration and insulin resistance
What is the exocrine function of the pancreas?
To make digestive enzymes
What is the endocrine function of the pancreas?
To make insulin and glucagon in the Islets of Langerhans to maintain plasma glucose
What causes damage to the islet cells in Type 2 dDM?
Amyloid deposition in the beta islet cells
What causes the deposition of amyloid in the beta cells?
Islet amylin polypeptide polymers (amylin is co secreted with insulin) secreted from pancreatic islet beta cells converted to amyloid deposits in T2DM
In T2DM, the islet is characterised by:
A deficit in beta cells
Increased beta cell apoptosis
Extracellular amyloid deposits derived from IAPP
What does conversion of IAPP to amyliod and deposition of the amyloid involve?
Conversion of the IAPP-37 to beta fibrils involves changes in molecular conformation, cellular biochemistry and diabetes related factors
What is the aetiology of T2DM?
Genetic - Polygenic
Epigenetic - foetal programming –> maternal hyperglycaemia leading to IUGR due to nutrient deficiency and reduced beta cell mass in the baby
What are the other possible etiological factors in T2DM?
Sox5 gene - regulates beta cell phenotype and is reduced in T2DM causing beta cell regression Old age Other pancreatic pathology Change in gut microbiota Glucotoxicity and lipotoxicity
Why do people become insulin resistant?
Over indulging
Obesity
Increased access to food - e.g. fast foods
What is the cause of insulin resistance?
Visceral fat is metabolically active
& responds to adrenaline and noradrenaline - breaks down into FFAs which change the lipid profile
Epicardial adipose tissue
Ectopic fat
What is ectopic fat and what is the problem with it?
An endocrine organ producing:
- FFAs causing insulin resistance and atherogenic lipids
- Cytokines causing insulin resistance and inflammation of atheroma
- procoagulant factors (PAI1)
What is a vital statistic in diagnosis of DM?
Waist circumference - central obesity due to visceral fat causes insulin resistance
Visceral fat around the pancreas prevents normal insulin production
What happens when diabetic patients go on diets?
The excess fat around the pancreas is reduced and beta cells work better when the pt goes on diets - seen on MRI scans
How do you prevent complications?
Prevent the diabetes
- get BMI >23
- exercise
- healthy diet
List 10 consequences of prolonged hyperglycaemia
Increased susceptibility to infection, retinopathy, (maculopathy/ cataracts) chronic renal failure, neuropathy, neuropathic ulcer, cheiroarthropathy (glycosylation of connective tissue), cataracts, coronary artery disease due to glycosylated HDL -> myocardial infarction, peripheral vascular disease
A reduction of HbA1c by 1% leads to a:
37% reduction in chances of microvascular complications
How do you treat T2DM?
Prevent the diabetes
Control/improve hyperglycaemia
Reduce the cardiovascular risk factors
Screen for complications and treat early
Describe the treatment regime for DM2.
Lifestyle factors – better quality diet, increased exercise, smoking cessation
Pharmacotherapy – Reduce insulin resistance, increase insulin levels (increase production/provide replacement, treatment for any concomittant dyslipidaemia/hypertension/other CV risk factors
What screening could you carry out for the patient?
Diabetic eye screening
Kidney function - measure protein in urine
control blood pressure with ACE inhibitors and ARBs
Diabetic foot screening - screen for neuropathy and vascular disease
What are the goals of T2DM treatment?
Lifestyle modification Screen for complications Special clinics for complications - foot, eye, renal HbA1c 6.5-7.5% = 38-58mmol/mol BP 120-140/80 LDL <2.0mmol Non HDL cholesterol <2.78
Goals must be tailored to the individual, why?
Pregnant women - need tight control of plasma glucose
Older adults - reducing glucose conc induces falls –> hip fractures & over treating can cause cause heart attacks
What types of surgery can be given to T2DM
Sleeve gastrectomy
Roux en Y bypass
Gastric band
