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.
Types of vascular complications ?
0 Microvascular complications
- retinopathy , nephropathy and neuropathy.
- linked to hyperglycemia - repeated hyperglycaemia will lead to repeated changes in cell metabolism (e.g increased sorbitol , AGE , DAG. This will leaf to cumulative changes in stable macromolecules (homeostasis interrupted )resulting in tissue damage
duration of diabetes + degree of glucose elevation have an affect on risk of developing this.
- independent accelerating factors e.g hypertension , hyperlipidaemia can accelerate progression of hyperglycaemia or tissue damage.
0 moderate or large (macrovascular complication - atherosclerosis )
What glucose transporter lines blood vessels ?
GLUT 1 found in endothelium - lining of BV found everywhere in the body.
hyperglycaemia will cause damage to capillaries and microcapillaries leading to organ damage.
What is Diabetic Neuropathy ?
Nerve damage
due high glucose levels.
Different forms :
Peripheral neuropathy - nerve damage effects feet , legs, arms , hands.
Autonomic neuropathy - damage to nerves that control internal organs. (effect automatic actions )
e.g. swallowing - peristaltic activity - no longer coordinated - dysphagia.
Cause damage to
0 heart rate , BP ,
0 digestive system
- effect GI ,
Stomach
motility (
Gastroparesis - stomach cannot empty properly - food passes through slowly as lack of muscle innervation) ,
0 bladder
0 sex organs - erectile dysfunction
0 sweat glands
0 eyes
0 ability to sense hypoglycaemia.
sensory neuropathy - damage to sensory nerves which detect touch and heat.
Motor neuropathy - damage to nerves affecting muscle movement.
Focal neuropathies - damage to single nerve - most often in hand, head, torso and leg.
polyneuropathy - effect many nerves in body
MOST COMMON PRESENTATION OF POLYNEUROPATHY :
- Distal symmetrical polyneuropathy - damaged nerve fibres are the most distal from CNS - the numbness/symptoms felt symmetrically in feet first —- > then up legs —-> upper extremities (as condition progresses over time )
SYMPTOMS :
0 Pain - even though there is loss of sensation
0 Paresthesias (pins and needles )
0 Numbness - loss of sensation
Damage to Schwann cells which make up myelin sheath on nerves .
- degeneration of schwann cells
- microvascular disease - reduce circulation to neurones - neurones become hypoxic - ischemia
What is gastropheresis ?
Chronic condition where stomach does not empty normally - more slowly.
CAUSE
- damage to nerves supplying muscle which control stomach emptying .
(due to poorly controlled type 1 or 2 diabetes ) - complication of surgery - gastrectomy , bariatric surgery (weight loss )
SYMPTOMS
0 feeling full quickly
0 nausea and vomiting
0 loss of appetite
0 weight loss
0 bloating
0 abdominal pain /discomfort
0 heartburn
symptoms can be mild /severe and tend to come and g.
Diabetes and inflammatory response.
Diabetics tend to not show a normal inflammatory response.
badly controlled diabetes causes thickening of basement membrane ——— > reduces ability of BV to dilate (normal vasodilation give rise to redness , heat, swelling - leaking of fluid (exudate)) ——– > this does not happen (non - normal inflammatory response).
Diabetic patient may not have normal inflammatory response if wound becomes infected
No :
- Redness
- Heat
- Swelling
- pain
Inflammatory response is the first step of wound healing.
High index of suspicion -
So you have to extra aware of wound infection in diabetic patient - look for subtle signs
- altered exudate
- smell from wound
etc.
Risk due to loss of sensation in diabetic patients ?
Can lead to :
Foot disease.
- Repeated lesion , ulceration , uncontrolled infection.
- Amputation.
loss of sensation - don’t realise that they have wounds — > become easily infected —– > if left untreated limb could be amputated
Diabetes can lower blood flow to foot due to large vessel atherosclerosis (peripheral arterial disease ) ——— > reduced blood flow to foot ——-> harder for sore / infection to heal ——–> infection does not heal ——-> gangrene , osteomyelitis (infection invades bone ).
Relates to fractures – might not know foot is fractured —-> fracture happens repeatedly —–> destruction of normal foot architecture —–> Charcot foot deformity.
typical case - ulceration (surrounded by callus formation ) on plantar surface of foot .
or underneath metatarsal head.
*note - Hyperglycaemia in diabetes induces cellular changes of vascular tissue which accelerate atherosclerotic process.
Diagnosis of Distal symmetrical polyneuropathy ?
Classic symptoms
- loss of ability to perceive pressure from a nylon filament
(thing that is pressed against sole of feet - patient asked if they can feel it )
Cardiac autonomic neuropathy ?
A type of neuropathy .
Damage to autonomic fibres supplying the heart and blood vessels - result in abnormalities in heart control and vascular dynamics.
Typical clinical manifestations :
- resting tachycardia
- diminished HR variability
- orthostatic blood pressure changes.
Patients at high risk of :
0 Myocardial infarction
0 Congestive heart failure
0 sudden cardiac death
- note - when a patient has diabetes - if they have other symptoms look for link as diabetes has a lot of complications.
- chest pain in diabetes patient should be considered to be of myocardial orgin until proven otherwise.
any of these - unexplained :
- fatigue
- nausea
- vomiting
- edema
- hemoptysis - spitting of blood orginating from lungs / bronchial tubes
- arrhythmias
- cough
- dyspnoea - difficulty breathing - shortness of breath .
- diaphoresis - sweating excessive
These should alert clinician to possibility of silent MI (no recognised symptoms e.g chest pain , shortness of breath and other anginal symptoms - nausea , diaphoresis , vomiting etc. - symptoms are mild or none at all (rare ))
atherogenic dyslipidaemia - elevated levels of triglycerides + LDL (low HDL levels ) in diabetic patient leads to increased risk of Silent MI.
What is charcot foot ?
Charcot foot / arthropathy -
loss of sensation —– > dont feel damage to feet : fracture/ dislocation —–> continue to walk on it ——> untreated - foot changes shape.
changes to shape can happen rapidly and take long time to heal.
Delay in treatment can lead to severe deformity , foot ulcers , disability and in severe cases - amputation
once change in shape completed - irreversible .
What are the phases of Treatment of Charcot foot ?
Active phase - 0 to 3 months
- immobilisation , plaster cast - removable / non removable) - non -removable preferred -provides better support ,walking brace (to stop changes in shape) Non-removable lightweight fibre-glass cast of the lower limb - proffered (type of cast )
- Crutches / wheelchair too keep weight off foot.
Healing phase : 4 -8 months
- bones starting to heal . some weight can be put on foot
- foot remains in cast / walking brace
Rehabilitation - 8 months +
- bones strong - can bear weight
- special insoles, shoes worn - due to possible change in shape.
- surgery may be needed - if large change - amputation possible.
NICE -
1. arrange a weight-bearing X-ray of the affected foot and ankle.
(consider an MRI if the X-ray is normal but Charcot arthropathy is still suspected.)
- offer non -removable offloading device.
2nd line - removable offloading device ( if patient can t used non -removable )
- monitor treatment until resolved.
can refer to foot protection services.
- dont give bisphosphonates - apart from in clinical trial.
At annual diabietic review what are you looking for on the foot - t ensure nt present ?
0 Neuropathy (use a 10 g monofilament as part of a foot sensory examination).
0 Limb ischaemia
0 Ulceration.
0 Callus.
0 Infection and/or inflammation.
0 Deformity.
0 Gangrene.
0 Charcot arthropathy.
low risk of foot problems - anually check
moderate risk - every 3 -6 months
high risk - every 1 -2 months.
What is Diabetic Nephropathy/ kidney disease ?
Nephro - kidney
Pathy - disease
kidney disease caused by diabetes
Chronic complication - slow progression after diagnosis
Clinical presentation -
- increased Glomerular filtration rate (increased pressure state caused by hypertension + efferent vasoconstriction ) - (this stage is usually asymptomatic )
- Detectable Proteinuria - mesoganial expansion —> expansion of fenestration btw podocytes —–> more leaky (protein can get through into urine )
- Albuminuria - sign of possible
development of diabetic kidney
disease.
0 Microalbuminuria - 30 to 300 mg a
day in urine (sustained
microalbuminuria can be an early
sign
of kidney disease/ nephropathy)0 Progression to Macroalbuminuria - >300mg a day 0 progression to nephronic syndrome - > or equal to 3 kg/day. - decreased glomerular filtration rate
( cytokines , free radicals damage tubules and vasculature —- efferent vasoconstriction —-> Ischemia, atrophy of vasculature then tubules ——> decreased ability to filter blood ——> over time more nephrons die causing decreased filtration rate
if present 3 months in a row - chronic kidney disease. - End stage renal disease - permanent reduction in filtration rate.
* in later stages - can develop symptoms of uremia - blood in urine
0 nausea
0 vomiting
0 anoxeria
etc.
deterioration of proper functioning of the kidney.
Type 1 diabetics more likely than type 2 to progress to end- stage renal failure.
single most common cause of end stage renal failure - 50 % of cases.
Proteinuria - damage to glomerular basement membrane - increases permeability.
Causes of Diabetic Nephropathy ?
Hyperglycaemia causes hypertension —-> kidney dysfunction.
CAUSES
- Hypertension —–> increased pressure in arteriole system in kidneys —-> increases filtration rate .
- Hyperglycemia activates RAAS system within kidney ——> causing efferent vasoconstriction ——> abnormal - leads to increase in pressure.
0 efferent ateriole vasoconstriction
reduces blood flow to tubules of the
nephron
(cytokines + free radical produced
also damage nephron vasculature ) —
– > ischemia , cell death , atrophy of
tubules and vasculature —-. reduced
ability of kidney to filter blood. - Increased pressure ——>
- mesangial expansion ( damage and trauma cause by pressure, mesangial cells secrete cytokines that cause inflammation , oxygen free radical cause endothelial dysfunction —–> matrix invades gromerulli capillaries and produces Kimmelsteil Wilson nodules.
- eventually leads to hypertrophy and matrix accumulation within mesangial ) ——> matrix i
- fenestration btw foot processes to expand —–>
- increased permeability (leaky )
* basement membrane thickens.
* mesangial cells - specialised cells in kidney . make up the mesangium - thin membrane that supports capillaries in nephron - glomerulus.
(activation happens regardless of if the normal blood flow/ fluid volume there )
What is non - albuminuric kideny disease?
progression to chronic kidney disease with the absence of albuminuria.
- more likely to occur in older patients with type 2 diabetes with multiple renal risk factors - hypertension , obesity , dyslipidemia.
Screening for diabetic nephropathy ?
diabetic patient should be screen annually .
measurement of albumin in on the spot urine sample. - test urine albumin / creatine ratio
sensitive immunoassay - detect microalbuminuria.
positive test - if levels of albumin - 30 to 200 mg per gram of creatine are detected in 2 -3 test in 6 months indicates possible diabetic nephropathy.
Treatment of diabetic nephropathy
Blood pressure medication - blood pressure should be lowerred to lowest achievable point - slow down decline of GFR and proteinuria.
Type 2 :
under 80 - aim for < 140 / 90
above 80 - <150/80
Type 1 - aim for:
- 135/ 85 - if patient has albuminuria
= 130 / 80 - has 2 or more features of metabolic syndrome.
ACE inhibitors / angiotensin - 11 receptor antagonist.
monotherapy or combined
in type 2 diabetes - for black afro/ carribean - you dont do what you usually do e.g calcium channel blocker first.
What is diabetic retinopathy ?
Retina - blood vessel and nerve cells - prime targets of hyperglycaemia.
cause damage to the Retina.
common cause of blindless in diabetes.
retino - retina
pathy - disease
disease of retina caused by diabetes.
3 stages -
- Diabetes without retinopathy -
Hyperglycemia causes osmotic damages to retinal pericytes - cells that wrap around endothelial cells of BV (found all over body . In retina regulate blood flow amongst other things.))
- look normal in ophthalmoscope - only visible under microscope - don’t really have symptoms / not detectable.
2. Pre - Proliferative diabetic Retinopathy - can be asymmotatic.
Pericyte damage ——> weakened capillary walls —–> formation of micro -aneurysms in microvasculature ( microvasculature not visible on eye exam - but the microaneurysm can be seen ) ——>
MICROANEURYSM - normally 1st of diabetic retinopathy .
part 2 -
pericyte damage —–> increased vascular permeability - capillaries leaky ——-> lipids , protein leak out into retinal tissue - no reabsorption ——-> forms Hard exudates.
(APPEARS as yellow fleck on the retina on eye examination )
- Proliferative retinopathy - vascular proliferaion throughout the rertina.
damage ——> ischemia —— > retina compensates for ischemia by producing growth factor (VEG - F )to produce new blood vessel. However , BV abnormal so - failed compensation.
these vessels - have numerous branches and more likely to rupture - can invade vitreous causing movement —-> leads to tearing of retina from base (traction retinal detachment - can cause permanent vision loss )
severe - can cause retinal detachment , vitreous haemorrhage.
Symptoms of Diabetic retinopathy ?
0 gradually worsening vision
0 sudden vision loss
0 floaters
0 blurred /patchy vision
0 eye pain /redness
0 blindness severe - if left untreated.
Treatment of Diabetic retinopathy ?
Annual eye examination for diabetes patients.
- diabetes without retinopathy - early and aggressive control of blood glucose level - ( this in most cases is not enough - despite well controlled blood glucose can progress )
- Non -proliferative DR (NPDR) -
If asymptomatic - control blood sugar -
if symptoms develop e.g blurred vision , floaters give :
VEG F inhibitors to be prevent neovascularisation and progression to proliferative stage .
Proliferative Diabetic Retinopathy - Laser photocoagulation
- laser used to stop growth of new BV - to prevent retinal detachment or vitreous haemorrhage and thus blindness.
Sudden vision loss should be investigated immediately in diabetic patients.
- Type 1 and 2 patients with proliferative retinopathy should avoid strenuous exercise.
How do you avoid Hypoglycaemia when exercising - diabetics?
0 gentle physical a ctivity - carry glucose only
0 Moderate
exercise -
- Take extra carbohydrate e.g 2 biscuits
0 Reduce insulin by 20 % priot to exercise
0 Combination of both.
Prolonged exercise e.g 1 -4 hours
0 30 % reduction in insulin (big)+ added carbohydrate after 1 hour.
longer than 4 hours
- very big reduction in insulin - 50 %
+ additional carbohydrates as snacks.
excercise and Ketoacidosis ?
excercise - risk factor for ketoacidosis .
excercise causes increased secretion of conteregulartory hormones - oppose action of insulin cortisol and adrenaline - so increased risk of ketoacidosis.
if ketosis present - strenuous exercise should be avoided - patient’s urine will also test positive for ketones.
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