diabetes mellitus

summary on diabetes mellitus.

i've decided to put the point-format text because sometimes its so big that its difficult to read (whoever free enough to really look through this)

Diabetes Mellitus

• definitions
  • diabetis is not a single disease
  • it is a group of metabolic disorders sharing the common underlying feature of hyperglycemia
  • hyperglycemia in diabetes occurs through
    • defects in insulin secretion
    • insulin action
    • both of the above
• epidemiology
  • nearly 7% of population affected
  • 1/3 of whom are diagnosed
• diagnosis
  • Mamapatho criteria - any ONE of these 3
    • a random blood glucose concn of 200mg/dL
      or higher, with classical signs and symptoms
      a fasting blood glucose concentration of 126mg/dL
      or higher on more than one occasion
      an abnormal OGTT in which the glucose concentration
      is 200mg/dL or higher 2 hours after 75mg glucose
  • WHO criteria
    • symptoms of hyperglycemia
      • polyuria
      • polydipsia
      • unexplained weight loss
      • visual blurring
      • genital thrush
      • lethargy
    • its either of the two-
      • 1
        • raised venous glucose
          • detected once
          • fasting >7mmol/L or random >11.1mmol/L
      • 2
        • raised venous glucose on 2 separate occasions
          • fasting >7mmol/L
          • random >11.1mmol/L
        • OGTT - 2h value >11.1mmol/L
• classification
  • type 1 DM
  • type 2 DM
  • genetic defects of B-cell function
  • genetic defects in insulin processing or insulin action
  • exocrine pancreatic defects
  • endocrinopathies
  • infections
  • drugs
  • genetic $ associated with DM
  • Gestational Diabetes
• normal actions of insulin
  • regulated by 3 processes
    • glucose production in liver
    • glucose uptake and use in peripheral tissue (mainly muscle)
    • actions of insulin and antagonizing hormones like glucagon
  • principal metabolic function of insulin
    • increase rate of glucose
      transport into certain cells in body
      • muscle cells
      • adipocytes
      promote lipogenesis
      inhibit lipid degradation
      • in adipocytes
      promote amino acid uptake and protein synthesis
      inhibit protein degradation
      also some mitogenic functions
      • initiation of DNA synthesis
      • stimulation of growth and differentiation
• pathogenesis of DM1
  • autoimmune disease
    • islet destruction caused by
      • T lymphocytes
        • reacting against pooly defined B-cell antigens
      • locally produced cytokines damage B-cells
      • autoantibodies against a variety of B-cell antigens
        • insulin decarboxylase
        • glutamic acid decarboxylase
    • reduction in B-cell mass
  • commonly develops in childhood
  • manifest at puberty
  • progressive wtih age
  • genetic predisposition
    • at least 20 chromosomal regions
    • class 2 MHC molecules on chromosome 6p21 (HLA-D)
• pathogenesis of DM2
  • insulin resistance
    • defined as a resistance to the effects of insulin on
      • glucose uptake
      • metabolism
      • storage
    • universal finding in diabetic fat people.
  • B-cell dysfunction
    • reflect disability of the cells to adapt
      themselves to the chronic demands
      of peripheral insulin resistance and
      increased insulin secretion
      qualitative b-cell dysfunction
      • loss in the normal pulsatile oscillating pattern of insulin secretion
      quantitative b-cell dysfunction
      • decrease in b-cell mass
      • islet degradation
      • deposition of islet amyloid
  • sedentary lifestyle
• morphology of diabetes late complications
  • pancreas
    • insonstant and rarely of diagnostic value
    • more distinctive changes in type1 than in type 2
    • alterations
      • reduction in number & size of islets
        leukocytic infiltration of islets
        type2 DM there may be a subtle reduction in islet cell mass
        increase in number & size of islets
        in non-diabetic newborns of DM mothers
  • macrovascular lesions
    • accelerated atherosclerosis affecting
      aorta and large and medium sized arteries
      MI most common cause of death in DM patient 
      gangrene of lower extremes 100 times more
      common in diabetic than in general population
      larger renal arteries also affected
      hyaline arteriosclerosis
  • microangiopathy
    • diffuse thickening of basement membranes
      • skin
      • skeletal muscles
      • retina
      • renal glomeruli
        • markedly thickened tortuous afferent arteriole
        • the amorphous nature of thickened vascular wall evident
      • renal medulla
  • diabetic nephropathy
    • renal failure second only to MI as cause of death in DM
    • 3 lesions encountered
      • glomerular
      • pyelonephritis
        • necrotizing papilitis
      • renal vascular lesions
      • diffuse mesangial sclerosis
      • nodular glomerulosclerosis
        • 
  • ocular manifestations
    • total blindness
    • retinopathy
      • constillation of changes that are considred
        by many ophtalmologists to be virtually diagnositc of disease
    • cataract
    • glaucoma
    • proliferative retinopathy
  • diabetic nephropathy
    • central
    • peripheral
      • most frequent pattern of involvement
      • symmetric neuropathy of lowe extreme that affect both motor and sensory function
      • disturbances in bowel and bladder function
      • sexual impotence
    • diabetic mononeuropathy
      • sudden foot drop
      • wrist drop
      • isolated cranial nerve palsies
• pathogenesis of complications
  • non-enzymatic glycosylation
    • process by which glucose
      chemically attch itself to free amino acids
      measurement of glycosylated hemoglobin
      level in blood useful in management of Dm
      gives good index of the average blood
      glucose level over 120-day lifespan of glucose
      Advanced Glycosylation End-products (AGEs)
      • accelerate Atherosclerosis
        plasma protein e.g. albumin bind to theglycated
        basment membrane, causing diabetic nephropathy
        plasma proteins are modified by AGE
        • release of cytokines and GFs from
          macrophages and mesangial cells
          increased endothelial permeability
          increased procoagulant activity on
          endothelial cells and macrophages
          enhanced proliferation and synth
          of ECM by fibroblasts and SMCs.
    activation of protein kinase C
    • down-stream effects
      • production of pro-angiogenic molecules
        • vascular endothelial GF
        • implicated in neovascularization in diabetic retinopathy
      • pro-fibrogenic molecules
        • transforming GF B
          • depots of ECM and BM material
    intracellular hyperglycemia with
    disturbances in polyol pathways
    • in tissues that do not require insulin for glucose transport
    • hyperglycemia leads to increase in intracellular glucose
      • metabolised by aldose reductase to...
        • sorbitol
        • fructose
    • increased Intracellular osmolarity and water influx
      • increased oxidative stress
        • diabetic neuropathy
• clinical features
  • DM1
    • polyuria
    • polydipsia
    • polyphagia
    • weight loss
    • diabetic ketoacidosis
  • DM2
    • polyuria
    • polydipsia
    • older presentation (>40)
    • frequently obese
    • weakness
    • weight loss
    • hyperosmolar nonketotic coma
      • severe dehydration
      • due to disablement by stroke / infection etc
  • complications
    • MI
    • Diabetic nephropathy
      • microalbuminemia
      • macroalbuminemia
      • end-stage renal disease
      • require dialysis / renal transplant in by 20 years
    • visual impairment
      • retinopathy
      • glaucoma
      • cataract
    • diabetic neuropathy
      • sensorimotor neuropathy
      • loss of pain
        • development of ulcers
      • autonomic dysfunction
        • impediments in bowel and bladder
    • increased succeptability to infections
      • gangrene
      • bacteriemia
      • pneumonia