Week 5: Diabetes (1) (DM, complications) Flashcards

1
Q

glucose homeostasis

A

When you eat, your body breaks food down into glucose. Glucose is a type if sugar that is your body’s main energy source.

  • As blood glucose rises, the body sends signals to the pancreas, which releases insulin
  • Insulin (B-cells) binds to insulin receptors, unlocking the cell so glucose can pass into it
  • Most glucose is used for energy right away
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2
Q

pancreatic islet cell

A

endocrine cell → B cells

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3
Q

diagnostic criteria for DM

A
  • Normal range- 3.3- 7 mmol/l
  • Diagnosis
    • Symptoms (retinopathy, neuropathy etc) plus one abnormal result or
    • Two abnormal results at different times (at least week)
  • Glucose levels
    • Fasting >7.0 mmol/l and/or
    • 2 hours after 75g glucose >11.1 mmol/l
    • Hba1c >6.5%
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4
Q

So why does glucose rise? 2 fundamental principle mechanisms

A
  1. Inability to produce insulin due to beta cell failure
  2. Insulin production adequate but insulin resistance prevents insulin working effectively and invariably linked to obesity
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5
Q

how does DM present

A
  • hyperglycaemia
    • polyuria
    • polydipsia
    • blurry vision
    • urogenital infections- thrush
  • Symptoms of inadequate energy utilisation
    • tiredness, weakness, lethargy, weight loss
  • Severity will depend upon the rate of rise of blood glucose as well as the absolute levels of glucose achieved
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6
Q

other types of diabetes

A
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7
Q

management of diabetes

A

Glycaemic control

Diet and exercise

Oral hypoglycaemic drugs

Insulins

Limiting cardiovascular risk by targeting risk factors

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8
Q

type 1 diabetes

A

absolute insulin requirement

  • Autoimmune destruction of beta cells leading to absolute insulin deficiency
    • Associated with other autoimmune disease- e.g. thyroid
  • 5-10% of all diabetes
  • Genetic predispotion
  • Rate of beta cells destruction variable – very rapid to rarely years (LADA syndrome- insidious presentation with mild weight loss, but present of autoantibodies)
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9
Q

autoantibodies present in T1DM

A

islet cells- GAD65

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10
Q

Importance of ketones

A
  • Ketone production is suppressed by insulin
    • Except in presence of starvation
      • Trace or +ketone in healthy starved people (serum or urine)
  • In absence of insulin, ketone production is activated – pt actually in starvation now
    • Indication for immediate insulin therapy
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11
Q

Presentation of T1DM

A
  • Rapid onset (usually weeks)
  • Weight loss
  • Polyuria
  • Polydipsia
  • Late presentation- may be vomiting due to ketoacidosis

Patient

  • Young usually under 30
  • Elevated venous plasma glucose
  • Presence of ketones
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12
Q

Treatment of T1DM

A
  • Exogenous insulin
    • Intermediates, rapid, mixtures, analogues
    • Numerous devices for admin
  • Giving by subcutaneous injections several times per day
  • Adequate pt education
    • Lifestyle
    • Home blood glucose monitoring
    • DAFNE course
    • Regular HbA1c testing and complications screening
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13
Q

Type 2 diabetes

A
  • Cause – environment and not genetics has caused this epidemic
  • Pancreas may not produce enough insulin
    • relative insulin deficiency
    • or your cells do not use insulin properly
    • the insulin cannot fully unlock the cells to allow glucose to enter (insulin resistance)
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14
Q

What cases insulin resistance to develop in T2DM

A
  • Obesity- in particular central obesity (accounts for 85%)
  • Muscle and liver fat deposition
  • Elevated free fatty acids
  • Physical inactivity
  • Genetic influences
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15
Q

treatment of `dm

A
  • Lifestyle
    • WEIGHT LOSS!!!!!!
  • Non-insulin therapies (oral hypoglycaemic drugs)
    • Biguanides
    • Sulphonylureas
    • GLP1 analogues
    • SGLT2
  • Antiobesity drugs- orlistat
  • Insulin
  • Patient education and ability to monitor results of therapy
  • Look for other vascular risk – BP, lipids, smoking exercise, diet
  • Surveillance for chronic complications
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16
Q

Lessons from bariatric surgery and very low calorie diets

A

Restrictive low calorie diets seem to help reduce liver fat and help revert diabetes

  • Fasting blood glucose returns to normal
    • Within 7 days before any weight loss
    • Liver fat content decrease with low calorie dieting
      • Return to normal insulin sensitivity
    • This changing in step with decreasing pancreatic fat content NORMALISING B cell function
    • Over 8 weeks first phase insulin release and maximal rates of insulin release return to normal
    • T2D can be considered as a potential reversible metabolic disorder precipitated intraorgan fat
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17
Q

Pharmacology of type 2 diabetes revision

A
  • First line metformin (biguanide)
  • second line
    • sulfonylureas
      • glicazide
    • gliptin
      • saxagliptin
    • pioglitazone
    • SGLT-2 inhibitor
      • canagliflozin
  • insulins
  • newer agents
    • GLP 1 analogues
    • DPP4 inhibitors
    • Sodium-glycose co-transporter-2 inhibitors
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18
Q

Acute complications of DM

A
  • Complications of hyperglycaemia
    • Massive metabolic decompensation
      • Diabetic ketoacidosis in type 1
      • Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNS)
  • Complications of hypoglycaemia
    • Coma
    • Brain
    • Needs glucose
    • Caused by hypoglycaemic therapy
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19
Q

Chronic complications

A
  • Macrovascular or large vessel disease
    • Cerebrovascular, cardiovascular, peripheral vascular disease (stroke, heart attack, intermittent claudication, gangrene)
  • Microvascular or capillary disease
    • Retinopathy- blindness
    • Nephropathy- need for renal replacement therapy
    • Neuropathy- erectile dysfunction, foot ulceration, diarrhoea, constipation, painful peripheral neuropathy
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20
Q

symptoms of hypoglycaemia can be split into

A

autonomic

neuroglycopenic

general malaise

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21
Q

potential causes of inpatient hypoglycaemia

A

medical issue or reduced carbohydrate intake

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22
Q

acute complication of t1Dm

A

diabetic ketoacidosis

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23
Q

acute complication of t2DM

A

Hyperosmolar hyperglycaemic syndrome

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24
Q

presentation of diabetic ketoacidosis (triad)

A

hyperglycaemia

ketonemia

acidosis

25
Q

why do ketones rise in diabetic ketoacidosis

A
  • Enhanced lipolysis leads to uncontrolled ketosis- due to reduced absorption of glucose  glucoseneogenesis nedded
  • Large quantities of ketone bodies formed including:
    1. 3- beta hydroxybutyrates
    2. acetoacetic acid
    3. acetone
26
Q

why does acidosis occur in ketoacidosiss

A

due to the ketones

27
Q

key issues with DKA

A
  • hyperglycaemia
  • acidosis due to ketones
  • dehydration due to osmotic diuresis and vomiting
  • electrolyte loss due to osmotic diuresis – sodium and potassium
  • mortality is increase
  • cerebral oedema
  • electrolytes disturbances- hypokalaemia
  • co-morbid states
28
Q

general management of DKA

A
  1. Correct dehydration evenly over 48 hours. This will correct the dehydration and dilute the hyperglycaemia and the ketones. Correcting it faster increases the risk of cerebral oedema.
  2. Give a fixed rate insulin infusion. This allows cells to start using glucose again. This in turn switches off the production of ketones.

Other important principles:

  • Avoid fluid boluses to minimise the risk of cerebral oedema, unless required for resuscitation.
  • Treat underlying triggers, for example with antibiotics for septic patients.
  • Prevent hypoglycaemia with IV dextrose once blood glucose falls below 14mmol/l.
  • Add potassium to IV fluids and monitor serum potassium closely.
  • Monitor for signs of cerebral oedema.
  • Monitor glucose, ketones and pH to assess their progress and determine when to switch to subcutaneous insulin.
29
Q

assessment of severity of DKA

A

manage all patients in an acute care bay

30
Q

initial investigations for DKA

A
31
Q

Comprehensive treatment f DKA

A

involve diabetes specialist team at earliest possible stage

Immediate management upon diagnosis: hour 1

  • IV 0.9% sodium chloride
  • fixed rate intravenous insulin infusion (FRIII) 0.1 units per kilogram body weight
  • hourly BG monitoring

60 minutes to 6 hours

  • clear blood of jetones
  • maintain potassium in normal rnage
  • avoid hypoglycaemia
  • conisder catheterisation
  • cinsider NG tubing
  • conitnous cardiac monitoring
  • treat co-morbidities

Conversion to subcutaneous insulin

  • When ketones <0.6 mmol
  • Ready to eat
  • pH of >7.3 9 no nevidence of acidosis
32
Q

Insulin- fixed rate intravenous insulin infusion

A
  • estimate weight if not known
  • actrarapid or Humulin S 50 units made up to 50mls with 0.9% sodium chloride
  • infuse at 0.1 uits/kg/hour
  • if normally takes long actin basal insulin continue
33
Q

fluid admin in DKA

A
34
Q

Hyperosmolar hyperglycaemic syndrome (HHS)

A

Mortality worse than DKA

characteristic features

  1. hypovolemia
  2. marked hyperglycaemia (30 mmol/l or more) without significant hyperketonaemia) or acidosiss
  3. osmolality usually n320 osmol/kg or more

a mixed picture of HHS and DKA may occur

35
Q

treatment goals of HHS

A
  • treat underlying cause
  • normalise osmolality
  • replace fluid and electrolyte losses
  • normalise blood glucose

prevention of

  • arterial or venous thrombosis
  • cerebral oedema
  • foot ulceration
  • central pontine myelinolysis
36
Q

calcuation osmolality

A

2Na + glucose + urea

higher the osmole the more dehydrated

37
Q

the higher the osmole the

A

more dehyrated

38
Q

typical fluid and electrolyte losses in HHS

A
39
Q

People with diabetes much more at risk of

A

peripheral artery disease

40
Q

pathophysiology of PAD and DM

A
41
Q

diagnosing PAD - history

A
42
Q

examination for PAD

A
43
Q

PAD and foot ulceration

A
44
Q

chronic complications of DM

A
  • Macrovascular or large vessel disease
    • Cerebrovascular, cardiovascular, peripheral vascular disease (stroke, heart attack, intermittent claudication, gangrene)
  • Microvascular or capillary disease
    • Retinopathy- blindness
    • Nephropathy- need for renal replacement therapy
    • Neuropathy- erectile dysfunction, foot ulceration, diarrhoea, constipation, painful peripheral neuropathy
45
Q

peripheral neuropathy

A
  • Reduction in sensation and pain can cause
    • Increased risk of ulceration
      • Diabetic foot sepsis a risk
    • Charcot’s foot
    • Osteomyelitc
46
Q

peripheral vascular disease

A

Reduced vascular supply to the lower limb- dry gangrene

47
Q

diabetic neohropathy

A
  • Most common ESRD
  • Caused by glomerulopathy not glomerulonephritis

Thickened basement membrane of the glomerulus- filtering function of tissue is damaged – loss of protein (albumin) in urine

  • Early stage- protein urea (microalbuminuria)- use albustix
48
Q

Pathological changes in diabetic nephropathy

A
  1. Hyperfiltration/ capillary hypertension
    1. Happens before all over changes
  2. Glomerular basement membrane thickening
  3. Mesangial expansion
  4. Podocyte injury
  5. Glomerular sclerosis
49
Q

hyperfiltration and hypertrophy in diabetic nephropathy

A
  • Occurs early
  • Related to hyperglycameia
    • Reabsorption of glucose couple with reab of sodium
    • More glucose reabsorbed therefore more sodium reabsorbed
    • Less sodium left in tubule by DCT
    • Macula densa senses reduction in delivery of NaCl
    • Activation of RAAS
    • Vasodilation of afferent arterial and vasoconstriction of efferent arterial hyperfiltration due to increased hydrostatic pressure
  • Glomerular hypertension
  • Increases GFR
50
Q

treatment of diabetic nephropathy

A
  • Tight blood glucose control <48 mmol/mol (6.5%)
  • Tight blood pressure control
    • No particular genet shown to be better with. normal albuminuria
  • SGLT-2 inhibitors
  • Not smoking
  • Statin therapy
51
Q

retinopathy

A
  • Small vessels are damaged- ischaemia or retina
    • Abnormality in microvasculature- dot to blot haemorrhage
      • If in macula maculopathy loss of central vision
    • Chronic causes of blindness: new vessels result due to chronically ischaemic retina- new vessels are friable- they haemorrhage  blinded very rapidly
52
Q

coronary artery

A
53
Q

define CKD

A
  • Use eGFR
    • Serum creatinine, age, sex, ethnicity
    • eGFR<60
54
Q

risk factor for CKD

A
  • Glucose control
  • BP
  • Genetics
  • Ethnicity
  • Smoking
  • Lipids
55
Q

consequences of CKD

A
  • Risk of progression to ESKD
  • Cardiovascular disease
  • More suspectable to AKI
  • Drug overdose risk
56
Q

management of CKD

A
57
Q

Clinical signs and symptoms in diabetic nephropathy

A
  1. Hyperfiltration & hypertrophy
    • Increased GFR
  2. Latent stage
    • Normal albuminuria
    • GBM thickening & mesangial expansion
    • Variable mesangial expansion / sclerosis
    • Increased GBM thickening
    • Podocyte changes
    • GFR normal
    • Diffuse glomerular histopathological changes
    • Systemic hypertension
    • Falling GFR
  3. Microalbuminuria (aka moderately increased albuminuria)
  4. Overt proteinuria (aka severely increased albuminuria)
  5. ESRD
58
Q

reversible causes of renal failure

A