Diabetes

Diabetes

1. pathophys

   • insulin -> decrease blood glucose lvls
     • control of this occurs in Beta-cell (direct response to portal glucose lvls) and is achived by:  -reducing hepatic glucose output -increasing peripheral glucose intake -a wide variety of other actions which regulate fat and protein metabolism -insulin produciton and activity are goverened principally by  1. circulating glucose lvls 2. diet 3. weight

2. diagnosis

   • WHO criteria
     • symps of hyperglycemia (eg polyruia, polydipsia, unexplained weight loss, visual blurring, genital thrush, lethargy) AND raised venous glucose detected once - fasting > 7mmol/L or random >11.1moml OR raised venous glucose on 2 separate occasions- fasting >7mmol/L, random >11.1mmol/L or OGtt- 2h valve >11.1 mmol/L
   • Real criteria
     • HBA1c
       • >48
         • normal <42
     • Fasting plasma glucose
       • >7 mmol/L
         • <6
     • random plasma glucose
       • >11.1 mmol/L
         • normal <7.8

3. T1

   • epidem
     • common (less common approaching equator)
   • autoimmune destruction of B-cells
   • characterised clinically by:
     • onset in youth (but can occur at any age)
       • peak at 4-5 and early teens
     • absolute req for insulin
     • rapid onset (wk-mo)
     • often precipated by concurrent illness
     • risk of ketoacidosis (DKA)
   • genetic/immunological considerations
     •  ; 50% concord only in identical twins
     • HLA DR3 and HLA DR4
     • evidence of immune activation w/destruction of B-cells (insulitis).
       • offers the possiblity of pre-clin diag +/-intervention?
   • cause
     • unknown
       • theories incl viruses (mumps, coxsakie B, measles) and cows milk/ breast milk
   • manage
     • adminstered insulin
       • individualised)
       • requires motivation, assisted by self-blood glucose monitoring
     • food + exercise
     • reduction of risk factors for complications
       • eg reduce BP

4. T2

   • epidemiology
     • common
       • 2-4% european adults
       • 10% elderly
       • 12-20% ethnic minories
   • characterised clinically by
     • onset in OLDER (uncommon before 35)
     • RELATIVE insulin deficiency (insulin insensitivity/resistance)
     • generally OVERWEIGHT
     • may be present for many years prior to diagnosis
     • rarely devel ketoacidosis but elderly in partic may devel HYPEROSMOLAR CRISIS (HONK)
   • genetic/histological considerations
     • BIG GENETIC LINK
       • almost 100% identical twin concordance
     • islet amyloid deposition
       • leads to 2ndry Beta-cell failure?
   • etiology
     • GENETICS +ENVIRONMENT espec obesity
   • Management principles
     • weight redution
     • approp diet
     • reduce risk factors for complics
       • eg decrease BP, statins
     • altered lifstyle
       • reqs high lvls motivation. diet, exercise, etc
     • most can be managed w/o drug therapy but few are
     • some req insulin (?slow onset type 1 diabetes?)

5. complications

   • acute
     • Diabetic Ketoacidosis (DKA)
       • cause
         • due to INADEQUATE circulating INSULIN (insulin deficiency -> body starves)
           • triggers: infect, missed insulin, onset of undiagd DM (usually)
         • use of fats for fuels, and inability (due to insulin lack) to clear fat breakdown products (acetoacetic acid + Beta-hydroxybutyrate)
       • presentation
         • often precipitated by illness
         • DEHYDRATION an important feature
         • onset over days weeks
         • in many centres carry a 5% mortality
         • symps
           • polyuria/polydypsia
           • vomiting
           • abdopain, anorexia
           • SOB
         • signs
           • tachycardia
           • hypervent
           • hypotension
           • sweet breath
           • confusion, unconsciousness
       • manage
         • treat underly cause
         • in large amounts (watch K+)
         • insulin admin in modest amounts
     • Hyperosmolar non-ketotic crisis (HONK)
       • etiology less clear
       • profound DEHYDRATION
       • usually in ELDERLY
       • more common in T2DM
       • often related to infect/sudden loss of mobility (stroke, etc)
       • onset over wks
       • manage principles
         • as for DKA but FLUID more important, LESS INSULIN req'd
     • Hypoglycemia
       • due to insuffic glucose supply in the face of ADEQUATE/EXCESS INSULIN
       • anyone on glucose loweirng hterapy (tablets/insulin)
       • presentation
         • rapid onset
         • EMERGENCY! brain dam + death in severe prolonged
         • symps/signs
           • autonomic- sweat, anx, hunger, tremor, palps, dizzy
           • neuroglycopenic- confusion, drowsy, visual trouble, seizures, coma
           • blood glucose <3mmol/L
       • 2 types
         • Fasting- b/c insulin
           • b/c increased activity, missed meal, accdental or non-accidental overdose
         • Post prandial
           • after gastic/bariatric surg or in T2DM
       • managment
         • rapid + adequate admin of soluble carb (lucozade, soda- small)
           • if can't swallow - IV 25-50mL glucose or glucagon 1mg IM if no IV access
         • occasionally glucagon req'd
         • always follow w/longer acting carb- Toast
   • chronic
     • NB- may be present at diagnosis w/T2DM
     • macrovascular
       • both types assoc'd w/increased risk of mac vasc disease: STROKE 2x, MI 4x
       • glycemic control NOT known to influence risk
       • reduction in other risk factors critical
         • smoking, BP, lipids, etc
       • diabetic amputations largely avoidable by identification of the 'at risk foot' + adequate preventive care
     • microvasc
       • both types affected
       • glycemic control MAIN risk factor
         • high glucose in blood damages small vssls
       • nephropathy
         • 30% T1DM
         • characterisitic histo appearances of glomerulus (glomerulosclerosis)
         • test: urine: creatinine ratio >30mg/mmol
         • progression can be slowed by BLOOD PRESSURE CONTORL
           • but <120 NOT bettter than <140 and has increased risk of serious adverse event from therapy
         • high risk of CHD
         • manage: inhibit renin-angiotensisn to protect kidneys
           • candesartan (AZA blocker, decrease albumin excr)
           • + can combine w/ ACEi
       • retinopathy
         • commonest cause of blindness in <65 in devel'd world
         • charac'd by ISCHEMIA and LEAKY vssls -> growth of NEWbut fragile VSSL -> HAEMORRHAGE scarring and traction
           • microaneurysms- dots
           • hameorrhages- blots
           • hard exudates- lipid deposits
         • at least 95% have retinopathy after 20y
         • blindness preventable by annual screening + early laser therapy
       • neuropathy
         • REFER EARLY! GOOD CARE SAVES LEGS
         • common (up to 30%)
         • due to combo of METABOLIC + VASCULAR factors
         • anesthesia leads to increased INCIDENTAL DAMAGE + ULCERATION of peripheris
         • glove + stocking classical
           • numbness, tingling, pain eg worse at night
             • treat: paracetamol -> tricyclic -> amitryptilline -> gabapentin -> capsaicin cream -> baclofen-> SSRI (avoiding weight bearing helps)
         • EXAMINE FEET REGULARLY
           • ischemia -critical toes +/- absent dorsalis pedis pulsex
           • periph neruopathy- inj or infect over pressure points (eg MTP heads)
           • foot ulceration- typically painless, punched out ulcer in area of thick callus +/- superadded infection
             • artierial ulcer
               • deep, well demarcated 'punched out', necrosis, over pressure point
             • venous ulcer - superficial, Gaiter's area (medial malleolus), poorly demarcated, sloughy
           • causes: -> cellulitis, abscess + osteomyelitis

6. treatment

   • Insulin regimes
     • def for T1, maybe T2
     • combos of short acting (4-6hrs), intermediate acting (8-12h) and long acting (18-24hr) insulins. like do basal long act w/additnal per meal or based on carbs
     • attemps to mimic physiological profiles
     • info on how to give info (for pts) to practice for explanation station (+ safety issues - hypos and hypers)
       • http://www.patient.co.uk/medicine/insulin
       • hypos
         • feeling shaky or anxious, sweating, pale, hungry, palpitations, feeling dizzy.
       • hypers
         • causes
           • eat more than normal, or have a fever, or take too low a dose of insulin
         • symps
           • sleepy, flushed, fruity smell on yourbreath, polyuria, polydipsia, anorexia
   • oral hypoglycemic agens
     • only for T2 DM
     • insulin sensitisers- metformin, gamma-PPR agonists (glitazones)
     • Beta-cell stimulants- sulphonyureas
     • DPP-4 inhibitors ('gliptins')
     • SLGT-2 inhibitors
   • GLP-1 agonists
     • only for T2
     • -exenatide, liraglutide, lixisenatide
     • glucagon-like peptide analogues
   • blood glucose monitor
     • see notes for how
     • premeal :4-7mmol/L post meal 1-2hr: <9 (or8.5if T1) 8hrs fasting: 5-7

7. other causes

   • steroids; anti-HIV durgs; newer antipsychotics; thiazides pancreatitis, panc surg removal, trauma, panc destruc (hemochromatosis, CF), panc cancer cushings, acromegaly, phaeocrhomocytoma, hyperthyroidism, pregnancy others: acanthosis nigricans LADA- laten autoimmune diabetes in adults (if ketotic +/- a poor response to oral hypoglycemics) Imparied glucose tolerance (IGT) impaired fasting glucose (IFG) gestational diabetes (4% of pregs) (increased birhtweight, neonatal hypoglycemia, sacral agenesis)