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Pre-proinsulin, Type 2 Diabetes, Weight gain, Insulin Resistance in T2D -…

- - - - Hepatocytes
      - Skeletal muscle
      - Adipocytes
        
        Insulin receptor
        
        2 alpha subuntis
        
        On exterior surface to bind insulin
        
        2 beta subunits
        
        Transmembrane components (extra, transmembrane & intracellular components)
        
        Intracellular part has tyrosine kinase activity
        
        Insulin binds
        
        Beta subunits add phosphate groups to tyrosine residues on each other (autophosphorylation)
        
        Receptor is now phosphorylated
        
        Binds and phosphorylates
        
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- - - - Rapid correction can cause vitreous swelling
        
        Vision may get worse over months before getting better - avoid buying glasses
- - - - Greater than 7mmol/L
    - - Greater than 11.1mmol/L
  - - - Fast overnight (8-14hrs)
        
        In the morning
        
        Baseline fasting blood glucose
        
        Greater than 7mmol/L
        
        If this is between 6.1 and 7mmol/L (grey area)
        
        High risk of developing T2D
        
        Impaired Fasting Glucose (IFG)
        
        Finish a 75g carb drink within 5mins
        
        Wait 2hrs
        
        Second blood glucose reading
        
        Greater than 11.1mmol/L (completely normal would be less than 7mmol/L)
        
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  - - - Prediabetes
    - - Diabetes
- - - - Glucokinase acts as a glucose sensor in pancreatic beta cells
        
        Defect
        
        Impairs insulin secretion in response to glucose
- - - - More common in T1D
    - - More common in T2D
        
        Involves
        
        Severe hyperglycaemia
        
        Glycosuria
        
        Osmotic diuresis
        
        Severe dehydration and volume depletion
        
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        Severe hyperosmolality
        
        Neurological symptoms
        
        NO significant ketoacidosis (as residual insulin sufficient to suppress lipolysis)
        
        Thus nausea and vomiting less common than DKA
  - - - Atherosclerotic diseases affecting large vessels
        
        MI
        
        Stroke
        
        Peripheral vascular disease
    - - Nephropathy
      - Retinopathy
    - - Arise from a combination of blood vessel disease, nerve damage, and metabolic defects
        
        Neuropathy
        
        Foot ulcers
- - - - Enter a pro-inflammatory state
        
        Start secreting Monocyte Chemoattractant Protein-1 (MCP-1)
        
        Attracts
        
        Monocytes in bloodstream
        
        Enter adipose tissue
        
        Differentiate into macrophages
        
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