L13 - Type 2 diabetes Flashcards
Blood clinical diagnosis of diabetes
- Glucose = or > 11.1 mmol/l + symptoms
- Glucose = or > 11.1 mmol/l x 2
- HBA1c = or > 48 mmol/mol (6.5%)
- Lower value does not exclude diabetes
Which cells cannot produce enough insulin in type 2 diabetes
- Islet beta cells
What is the islet characterised by in type 2 diabetes
- A deficit in beta-cells
- Increased beta-cell apoptosis
- Extracellular amyloid deposits derived from IAPP
What is islet amyloid polypeptide (IAPP, amylin) secreted by
- IAPP is secreted from pancreatic islet beta-cells and converted to amyloid deposits in type 2 diabetes
Type 2 diabetes - aetiological features
- Genetic
- Polygenic
- Fetal programming (epigenetic), maternal hyperglycaemia, intrauterine growth retardation
- Reduced beta cell mass
Type 2 diabetes - less common aetiological features
- Beta cell regression ( Sox 5 gene )
- Old age
- Other Pancreatic Pathology
- Change in the gut microbiota
- Glucotoxicity & Lipotoxicity
- later effects
Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
Type 2 diabetes mellitus pathophys
Reduced incretin effect, glucotoxicity, lipotoxicity –> endocrine gland, beta cell problem –> hormone (insulin) –> organs - fat, liver and muscle resistant
What is epicardial fat a strong risk factor for
- Epicardial fat is a strong factor for vascular disease
Why is ectopic fat a problem
Ectopic fat - A problem
An ‘endocrine’ organ producing
• Free fatty acids
- Insulin resistance
- Atherogenic lipids
· Cytokines
- Insulin resistance
- Inflammation
· Procoagulant factors (PAI1)
Excess fat in which organ is specific to T2DM
- Excess fat in the diabetic pancreas is specific to T2DM and important in preventing normal insulin production
Prevalence of type 2 diabetes in the uk
- 4.6 million people
- 12.3 million at risk
What is type 2 diabetes mostly attributed to
- BMI > 23
- Lack of exercise
- Unhealthy diet
Side effects/morbidity related to type 2 diabetes
- Hyperglycaemia per se
- Dysregulation of lipid metabolism
- High levels of proinflammatory cytokines
- High levels of free radicals
- Increased susceptibility to infection
Effect of high glucose levels on the retina
- High glucose levels for long durations can cause maculopathy/retinopathy
Link between HBA1c levels and cataract risk
- 1% reduction in HBA1c reduces cataract risk by 19%
What is diabetic nephropathy
- Diabetic nephropathy (DN), also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus
- Protein loss in urine due to damage to the glomeruli may become massive, and cause a low serum albumin with resulting generalised body swelling (edema) and result in
What type of ulcers can form as a result of high blood glucose levels
- Neuropathic ulcers
Link between haemoglobin A1C and microvascular complications
In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy
What is cheiroarthropathy
Diabetic cheiroarthropathy (Limited Joint Mobility, or LJM) is a cutaneous condition characterized by thickened skin and limited joint mobility of the hands and fingers, leading to flexion contractures, a condition associated with diabetes mellitus
- This occurs due to glycosylation of connective tissue
Features of bone in type 2 diabetes
- Mechanically weaker
- Increased fractures x2
- In spite of normal bone density
Proinflammatory and anti-inflammatory effects of lipoprotein classes and inflammation
All the major lipoprotein classes impact in some way on the inflammatory process that leads to development of atherosclerosis. The triglyceride-rich lipoproteins—chylomicrons, very low density lipoprotein (VLDL), and their catabolic remnants—and low-density lipoprotein (LDL) are potentially proinflammatory, whereas high-density lipoprotein (HDL) is potentially anti-inflammatory.
Prevention/treatment of T2DM
- Lifestyle manouvres
- Treatment of dyslipidaemia and hypertension
- Use of aspirin
Screening measures - eyes
- Retinal photography
- Laser treatment when required
Screening measures - kidneys
- Measure urine albumin (EMU)
- Control blood pressure
- ACE inhibitors and ARBs
Screening measures - feet
- Screen for neuropathy and vascular disease
Goals of type 2 diabetes mellitus treatment
· Lifestyle Modification · Screen for complications · Special clinics for complications • Foot, Renal, Eye · HbA1c 6.5 – 7.5 % (48 – 58 mmol/mol) · BP 120 -140 /80 · LDL < 2.0 mmol/l · Non HDL cholesterol < 2.78
Metabolic/obesity surgerical treatments for type 2 diabetes
- Sleeve gastrectomy
- Roux en Y bypass
- Gastric band
Objectives of pharmacological interventions in treating type 2 diabetes
- Reduce insulin resistance
- Increase insulin production/secretion
- Provide insulin replacement
In which conditions is HbA1c not useful for diagnosis of diabetes mellitus
haemoglobinopathies haemolytic anaemia untreated iron deficiency anaemia suspected gestational diabetes children HIV chronic kidney disease people taking medication that may cause hyperglycaemia (for example corticosteroids)
Diagnosis of impaired fasting glucose
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
Further tests for individuals with impaired fasting glucose
People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT
HbA1c in pre diabetes
42-47 mol/mol or fasting glucose 6.1-6.9 mmol/l
