Complications of diabetes Flashcards
Impact of diabetes mellitus at a cellular level ?
Damage to cells - GLUT 4 - insulin dependent - muscle and adipose cells cannot take up glucose , Glucose floods blood but can still enter the other cells as GLUT 1,2,3 are not insulin dependent.
Too much glucose in these other cells results in damage to these cells.
Consequences
1a. increased AGE - abnormal glycated end products.
( Glycation - binding of glucose to molecules irreversibly without enzymes )
- problems -
enzymes - altered/ inhibit cell function (not able to change shape due to heavy glucose molecule ) - Glycation vs Glycosylation
(Glycosylation - binding of glucose to molecule reversibility with enzymes )
1b. Circulating AGE deposits around the body e.g Kidney
0 produces inflammatory reaction —— > release of cytokines and growth factors ——– damage renal tissue , vasculature etc. (other organs too).
- Alternative oathway for conversion of glucose
Glucose ——— intermediates ——- > Soribitol.
Sorbitol - highly osmotic draws water into cell —–> cell lysis —–> release of free oxygen radicals —-> cellular damage.
- Hyperglycemia causes increased DAG (diacylglycerol - cell membrane receptor )
- Glucose binds to DAG —-> DAG activates protein Kinase C ( enzyme that catalyses phosphorylation of protein kinase C ) ——- > leads to altered cell function & altered gene expression ,increased growth factors —— > accumulation of unnecessary cells.
* (activation of protein kinase C (PKC) and increased diacylglycerol (DAG) levels initiated by hyperglycemia are associated with many vascular abnormalities in retinal, renal, and cardiovascular tissues. ) - just for notes
https: //diabetes.diabetesjournals.org/content/47/6/859.long
What types of complication of diabetes mellitus are there ?
Acute metabolic
- Hypoglycemia
Glucose need for respiration to produce ATP . Reduced / no ATP - cellular processes cannot happen
e.g pumps cannot work - lack of molecule transport.
- Hyperglycemia
0 DKA - Diabetic
Ketoacidosis
0 HHS - hyperosmolar
hyperglycemic
state
Chronic vascular -
chronic tend be vascular in nature while acute tend to be metabolic.
what is Hypoglycemia ?
Symptoms .
Low blood sugar level .
Causes
0 Iatrogenic - caused by healthcare professional / procedure e.g .
- insulin stimulatory drugs - e.g
sulfonylureas - drug
induced, parenteral (non -oral
) insulin. -insulin mediated
0 defect in counter regulatory casacde.
Symptoms :
can happen rapidly
- Neuroglycopenic symptoms
(neuroglycopenic - shortage of glucose
in the brain / nerve cells . No
GLYCOGEN in nerve cells -so no storage
of glucose - need continuous supply of
glucose )
0 Diziness
0 Tiredness
0 Headache
0 confusion
0 Difficulty concentrating
0 Difficulty speaking
0 seizures - if severe lead to coma
0 Coma - Neurogenic / Autonomic symptoms
- Autonomic nervous system wants prevent us going into coma and death so initiates a response that alerts us .
SYMPATHETIC OVERACTIVTY - lead
to catecholamine mediated symptoms
0 Palpitations
0 Tremor
0 Anxiety
Acetylcholine mediated -
0 Hunger
0 Sweating
0 Paresthesias - pins and needles - these mechanism are counter regulatory . Driving us to take in more calories.
What is the threshold for Hypoglycemia ?
blood glucose below or equal approx
70 mg /dl - mild
moderate - below or equal 54 mg/dl (3 mmol/)
severe - below or equal 40 mg /dl
A level below or equal 70 mg/dl - for diabetes patient- self monitored is a red flag - alert the patient or caregiver of possible hypoglycemia even if no symptoms
if had previous episodes in the past - the threshold at which they gain hypoglycemia will increase - so get hypoglycemia at higher blood glucose level
What are the different severities of Hypoglycemia ?
severe - low blood glucose that requires assistance from another person to treat - episode with neurocognitive impairment e.g:
- confusion .
- seizures ,
- intense nightmares -asleep
- loss of consciousness
- coma.
Documented symptomatic Hypoglycemia - Blood glucose below or equal 70mg/dl with symptoms. episode self managed.
Asymptomatic hypoglycemia - blood glucose below or equal to 70 mg /dl with no associated symptoms - dangerous due to lack of awareness.
Pseudo- hypoglycemia
Have typical hypoglycemia symptoms but blood glucose is above 70 mg/dl.
Hypoglycemia - why is dangerous .
Common cause of death for Type 1 diabetics.
prolonged low circulating glucose (below 15 mg /dl ) can cause :
0 brain
death
0
ventricular
arrhythmias.
*
Not as high a risk in Type 2 . However risk increases with duration of type diabetes - (progressive B cell failure & increased dependence of pharmological interventions )
Causes and risk factors of hyoglycemia ?
regular meal - missed or delayed (mismatch of exposure to insulin with actual level of blood glucose )
0 overdose of medication e.g insulin or insulin stimulatory drugs (sulfonyureas ) - (especially elderly )
0 exercise - dose of insulin not be reduced according to level of exercise - stenous exercise
0 alcohol
alcohol and exercise -
1 . alcohol prevent liver release of glucose into blood.
- exercise increases body’s insulin sensitivity
( require smaller amounts of insulin to lower blood glucose ).
ALSO INCREASES :
- insulin absorption
- Increased glucose consumption
- increased metabolic rate up to 24 hrs following exercise
Alcohol + physical activity - dangerous for diabetics.
0 recent weight loss - adipocytes start to shrink - release cytokines which impact blood glucose by acting on activity of insulin.
impaired counter regulatory systems (to prevent decrease in blood glucose - glucagon , adrenaline , cortisol , growth hormone etc ).
0 rapid improvement of HBA1c into normal range
0 Youth
0 Altered conciousness
0 Type 1 with history of recurrent hypoglycemia
0 Medications that can induce Hypoglycemia :
Pentamidine - antiprotozoal - side effects - hypoglycemia very common.
Quinine - antimalarial - used to treat malaria ( quinine induced hypoglycemia - particularly in Falciparum malaria - most dangerous type - higher levels of parasites and death rate.
Non selective Beta blockers. - equal affinity for beta 1 and 2
e.g
0 Propanalol etc.
- note - cardioselective beta blockers - atenolol , metoprolol .
(less commonly associated )
0 illnesses occuring at the same time e.g.
- sepsis
- hepatic
- renal
- cardiac failure.
Name some aggravating causes of Hypoglycaemia in patients ?
Liver disease e.g cirrhosis etc. - impaired metabolism of drugs - prolongs hypoglycemic action
Renal (kidney ) disease - impaired clearance of drug from body - conc builds up and prolong action of drug e.g insulin
What is Ketosis -prone /Flatbush diabetes ?
type 2 diabetes present with diabetic ketoacidosis but dont have typical phenotype of autoimmune type 1 diabetes .
- uncommon form - characterised by severe reversible insulin deficiency .
note * Diabetic ketoacidosis can occur rarely type 2 in patients
- under extreme stress
- Flatbush diabetes.
precipitants/ causes of DKA and HHS ?
Either causes by decreased insulin supply or increased insulin demand
reduced supply
- inadequate insulin treatment
- non - compliance.
- new - onset diabetes.
Increased insulin demand
5 I ‘s
0 Infection e.g pneumonia , UTI’s , cellulitis
0 Inflammation e.g acute pancreatitis
0 Intoxification - alcohol
- cocaine
- metaphetamines
0 Infarction - acute myocardial infarction , cerebral infarction .
0 Iatrogenic causes -
- medicines :
Corticosteriods - ( increase blood glucose level increasing insulin demand. )
- Clozapine
- Atypical antipsychotics (AAP) / SGA - second generation antipsychotics )
(used to
treat
psychosis
in
Parkinson’s
disease
and
schizophrenia
resistant to
conventional
antipsychotics.
)
Olanzapine - schizophernia - combination therapy for mania.
Prevention of Bipolar disorder recurrence.
monotherapy for mania.
0 Thiazide diuretics
0 lithium
0 Sympathomimetics - drugs mimic / modify action endogenous catecholamines on SNS
e.g
Phenylephrine - synthetic - decongestant (treat stuffy nose and sinus congestion by common cold )
can also be adrenaline and noradrenaline .
( basically stressful events in diabetic patients )
0 Endocrinopathies : - cushings syndrome - Thyrotoxicosis - Acromegaly - Severe burns - hypo/hyper thermia
0 CVA - cardiovascular accident
0 Acute pulmonary embolism.
What medicines can cause DKA and HHS ?
- medicines :
Corticosteriods - ( increase blood glucose level increasing insulin demand. ) - Clozapine
- Atypical antipsychotics (AAP) / SGA - second generation antipsychotics )
(used to
treat
psychosis
in
Parkinson’s
disease
and
schizophrenia
resistant to
conventional
antipsychotics.
)
Olanzapine - schizophernia - combination therapy for mania.
Prevention of Bipolar disorder recurrence.
monotherapy for mania.
0 Thiazide diuretics
0 lithium
0 Sympathomimetics - drugs mimic / modify action endogenous catecholamines on SNS
e.g
Phenylephrine - synthetic - decongestant (treat stuffy nose and sinus congestion by common cold )
can also be adrenaline and noradrenaline .
Figures /theshold figures for DKA and HHS ?
DKA HHS
serum
GLU > 250 > 600
PH < 7.3 > 7.3
HCO3 < 18 > 18
Urine/
serum
ketones up down
anion
gap > 12 < 12
serum
osmol
-arity
variable > 320
DKA - characterised by ketoacidosis +dehydration (osmotic diuresis )
HHS - hyperosmolality + dehydration (due to osmotic diuresis )
HHS - just enough insulin to prevent the lipolysis and formation of free fatty acids leady to ketone formation
Symptoms of DKA ?
kussmals breathing - (breathe rapidly and deeply to compensate for acidemia )
- fruity breath - acetone
- nausea
- vomiting
- legarthy
- anorexia
- non -localizing upper abdominal pain.
symptoms of hyperglycaemia - ex. (not all )
- progressive polyuria (increased urination )
- progressive polydipsia (thirst)
Clinical findings DKA patient .
dehyrated DKA patiet
0 Dry skin an mucous e=e=membranes
o Tachycardia
0 raised Jugular venous pressure
0 Orthostatic hypotension
0 depressed mental function
0 Deep , rapid respirations - kussmals breathing
0 fruity breath - acetone (not always detectable /prresent )
Major risk factors of HHS ?
Older age - over 65 yrs
impaired cognition - impaired ability to recognise thirst and obtain access to water.
