Week 5: Diabetes (1) (DM, complications) Flashcards
glucose homeostasis
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
pancreatic islet cell
endocrine cell → B cells
diagnostic criteria for DM
- 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%
So why does glucose rise? 2 fundamental principle mechanisms
- Inability to produce insulin due to beta cell failure
- Insulin production adequate but insulin resistance prevents insulin working effectively and invariably linked to obesity
how does DM present
- 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
other types of diabetes
management of diabetes
Glycaemic control
Diet and exercise
Oral hypoglycaemic drugs
Insulins
Limiting cardiovascular risk by targeting risk factors
type 1 diabetes
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)
autoantibodies present in T1DM
islet cells- GAD65
Importance of ketones
- Ketone production is suppressed by insulin
- Except in presence of starvation
- Trace or +ketone in healthy starved people (serum or urine)
- Except in presence of starvation
- In absence of insulin, ketone production is activated – pt actually in starvation now
- Indication for immediate insulin therapy
Presentation of T1DM
- 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
Treatment of T1DM
- 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
Type 2 diabetes
- 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)
What cases insulin resistance to develop in T2DM
- Obesity- in particular central obesity (accounts for 85%)
- Muscle and liver fat deposition
- Elevated free fatty acids
- Physical inactivity
- Genetic influences
treatment of `dm
- 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
Lessons from bariatric surgery and very low calorie diets
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
Pharmacology of type 2 diabetes revision
- First line metformin (biguanide)
- second line
- sulfonylureas
- glicazide
- gliptin
- saxagliptin
- pioglitazone
- SGLT-2 inhibitor
- canagliflozin
- sulfonylureas
- insulins
- newer agents
- GLP 1 analogues
- DPP4 inhibitors
- Sodium-glycose co-transporter-2 inhibitors
Acute complications of DM
- Complications of hyperglycaemia
- Massive metabolic decompensation
- Diabetic ketoacidosis in type 1
- Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNS)
- Massive metabolic decompensation
- Complications of hypoglycaemia
- Coma
- Brain
- Needs glucose
- Caused by hypoglycaemic therapy
Chronic complications
- 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
symptoms of hypoglycaemia can be split into
autonomic
neuroglycopenic
general malaise
potential causes of inpatient hypoglycaemia
medical issue or reduced carbohydrate intake
acute complication of t1Dm
diabetic ketoacidosis
acute complication of t2DM
Hyperosmolar hyperglycaemic syndrome
presentation of diabetic ketoacidosis (triad)
hyperglycaemia
ketonemia
acidosis
why do ketones rise in diabetic ketoacidosis
- Enhanced lipolysis leads to uncontrolled ketosis- due to reduced absorption of glucose glucoseneogenesis nedded
- Large quantities of ketone bodies formed including:
- 3- beta hydroxybutyrates
- acetoacetic acid
- acetone
why does acidosis occur in ketoacidosiss
due to the ketones
key issues with DKA
- 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
general management of DKA
- 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.
- 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.
assessment of severity of DKA
manage all patients in an acute care bay
initial investigations for DKA
Comprehensive treatment f DKA
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
Insulin- fixed rate intravenous insulin infusion
- 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
fluid admin in DKA
Hyperosmolar hyperglycaemic syndrome (HHS)
Mortality worse than DKA
characteristic features
- hypovolemia
- marked hyperglycaemia (30 mmol/l or more) without significant hyperketonaemia) or acidosiss
- osmolality usually n320 osmol/kg or more
a mixed picture of HHS and DKA may occur
treatment goals of HHS
- 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
calcuation osmolality
2Na + glucose + urea
higher the osmole the more dehydrated
the higher the osmole the
more dehyrated
typical fluid and electrolyte losses in HHS
People with diabetes much more at risk of
peripheral artery disease
pathophysiology of PAD and DM
diagnosing PAD - history
examination for PAD
PAD and foot ulceration
chronic complications of DM
- 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
peripheral neuropathy
- Reduction in sensation and pain can cause
- Increased risk of ulceration
- Diabetic foot sepsis a risk
- Charcot’s foot
- Osteomyelitc
- Increased risk of ulceration
peripheral vascular disease
Reduced vascular supply to the lower limb- dry gangrene
diabetic neohropathy
- 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
Pathological changes in diabetic nephropathy
- Hyperfiltration/ capillary hypertension
- Happens before all over changes
- Glomerular basement membrane thickening
- Mesangial expansion
- Podocyte injury
- Glomerular sclerosis
hyperfiltration and hypertrophy in diabetic nephropathy
- 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
treatment of diabetic nephropathy
- 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
retinopathy
- 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
- Abnormality in microvasculature- dot to blot haemorrhage
coronary artery
define CKD
- Use eGFR
- Serum creatinine, age, sex, ethnicity
- eGFR<60
risk factor for CKD
- Glucose control
- BP
- Genetics
- Ethnicity
- Smoking
- Lipids
consequences of CKD
- Risk of progression to ESKD
- Cardiovascular disease
- More suspectable to AKI
- Drug overdose risk
management of CKD
Clinical signs and symptoms in diabetic nephropathy
-
Hyperfiltration & hypertrophy
- Increased GFR
-
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
- Microalbuminuria (aka moderately increased albuminuria)
- Overt proteinuria (aka severely increased albuminuria)
- ESRD
reversible causes of renal failure
