Diabetes

1. intermediate metabolic states between established diabetes& normal glucose balance
2. represent risk categories for future diabetes&/or macrovascular complications
3. can lead to any type of diabetes
4. increased risk of CV disease
5. little of no risk for microvascular disease
6. increased risk of progression to diabetes

Nota:

• -10% of diabetic population -rapid onset of symptoms -may start at any age: usually <30

1. absolute insulin deficiency due to beta-cell destruction

Nota:

• -90% of diabetic population -'silent' onset -75% obese -insulin resistance -low levels of insulin

1. relative insulin deficiency due to disorder of insulin action or secretion

1. insulin is a polypeptide hormone synthesized in Beta-cells of the pancreas
   1. stored as pro-insulin in granules in Beta-cells
   2. normal daily insulin secretion: 0.5 to 0.7/kg/24h

      Nota:

      • 1. K diffused down its conc gradient via ATP gated K channels: -intracellular potential mainteined  at fully polarised -ve level - min insulin secretion 2. high blood glucose levels around beta-cells 3. glucose enters beta-cells 4. increased production of ATP 5. Katp channels close - depolarisation of the cell 6. voltage gated Ca++ ch open 7. Ca influx into the cell 8. increased insulin secretion out of cell into portal circulation
      1. glucose levels 3.5 to 8mmol/L
         1. liver is a major organ for glucose homeostasis
            1. absorbs and stores glucose as glycogen
            2. gluconeogenesis
         2. insulin action: reduces glucose levels
            1. counter regulatory hormones
               1. glucagon
                  1. alpha cells in the pancreas
               2. growth hormone
               3. cortisol
               4. adrenaline
      2. stimulants
         1. glucose and other sugars
         2. amino acids
         3. glucagon-like peptide-1
         4. glucose dependent insulinotrophic peptide
         5. glucagon
      3. insulin targets
         1. liver
         2. skeletal muscle
         3. adipose tissue
      4. lack of insulin
         1. breakdown of fats-increased levels of free fatty acids(FFA)
            1. liver converts FFA to ketone bodies
               1. energy source for: brain, heart, skeletal muscle
                  1. acetone excreted by lungs - fruity smell
                  2. excess ketone bodies in blood - ketoacidosis
                     1. DEATH if left untreated
      5. low and constant level of basal insulin
         1. slight rise at night to suppress glucose output by the liver

1. neuropathy - peripheral nerver
2. erectile dysfunction
3. chronic foot complications
4. autonomic neuropathy - chronic constipation

1. diabetes first discovered in pregnancy irrespective of cause
   1. older women
   2. women with previous history of large babies
   3. insulin resistance and relative impairment of insulin secretion
   4. high risk ethnic groups