L3-4. DM.pptx...................................................

DIABETES MELLITUS
ASSISTANT PROFESSOR DR BILAL NATIQ NUAMAN
CONSULTANT ENDOCRINOLOGIST
Al-Iraqia Medical College
2024

• Criteria for "acceptable" control includes the following:
(1) blood glucose levels of 90 to 130 mg/ dL (5-7 .2 mmol!L)
before meals and after an overnight fast,
(2) levels no higher than 1 80 mg/dL (10 mmol!L) 1 hour after
meals and 1 50 mg/dL (8.3 mmol!L) 2 hours after meals, and
(3) HbA1c levels less than 7% for nonpregnant adults.
Less stringent HbA1c goals may be appropriate in children, those
with a history of severe hypoglycemia, limited life expectancy,
and advanced microvascular and macrovascular disease. In
the elderly frail patient, an HbA1c target of approximately 8%
(preprandial blood glucose levels in the range of the 1 50-1 59
mg/dL) may be reasonable although formal evidence is
lacking.

• Dawn Phenomenon
• The dawn phenomenon is a normal rise in blood sugar as a person’s body prepares to wake up. In the early morning
hours, hormones (growth hormone, cortisol, and catecholamines) cause the liver to release large amounts of sugar
into the bloodstream. For most people, the body produces insulin to control the rise in blood sugar. If the body doesn’t
produce enough insulin, blood sugar levels can rise. This may cause high blood sugar in the morning (before eating).
•
• Somogyi Effect
• If the blood sugar level drops too low in the early morning hours, hormones (such as growth hormone, cortisol, and
catecholamines) are released. These help reverse the low blood sugar level but may lead to blood sugar levels that are
higher than normal in the morning.
• An example of the Somogyi effect is:
• A person who takes insulin doesn’t eat a regular bedtime snack, and the person’s blood sugar level drops during the
night.
• The person’s body responds to the low blood sugar by releasing hormones that raise the blood sugar level. This may
cause a high blood sugar level in the early morning.
Type 1 DM

diagnosis of the cause of prebreakfast hyperglycemia can be facilitated by self-monitoring
of blood glucose at 3 AM in addition to the usual bedtime and 7 AM
measurements. This is required for only a few nights, and when a
particular pattern emerges from monitoring blood glucose levels
overnight, appropriate therapeutic measures can be taken
.

• For hyperglycemia due to waning of overnight
basal insulin and/or dawn phenomenon, an
increase in the evening dose of the basal
insulin or shifting it from dinnertime to
bedtime (or both) can be effective.
• Prebreakfast hyperglycemia due to the
Somogyi effect can be treated by reducing the
dose of either intermediate- or long-acting
insulin analog at bedtime.

L3-4. DM.pptx...................................................

• Diabetic ketoacidosis
• Diabetic ketoacidosis (DKA) is a medical emergency and
remains a serious cause of morbidity.
• Ketosis results from insulin deficiency, exacerbated by
elevated catecholamines and other stress hormones,
leading to unrestrained lipolysis and supply of FFAs for
hepatic ketogenesis.
• Mortality in DKA is most commonly caused in children
and adolescents by cerebral oedema and in adults by
hypokalemia, acute respiratory distress syndrome and
comorbid conditions such as acute myocardial infarction,
sepsis or pneumonia.
• DKA may be precipitated by an intercurrent illness
because of failure to increase insulin dose.

• The cardinal biochemical features are:
• hyperketonaemia (≥ 3 mmol/L) and ketonuria
(more than 2+ on standard urine sticks)
• hyperglycaemia (blood glucose ≥ 11 mmol/L
(~200 mg/dL))
• metabolic acidosis (venous bicarbonate < 15
mmol/L and/or venous pH < 7.3).
• profound osmotic diuresis leading to dehydration
and electrolyte loss, particularly of sodium and
potassium.
• Potassium loss is exacerbated by secondary
hyperaldosteronism

• Average loss of fluid and electrolytes in
adult diabetic ketoacidosis of moderate
severity
Every patient in DKA is potassium-depleted, Plasma
potassium may even be raised initially ( due to
hemoconcentration, acidosis) soon after treatment is
started, there is likely to be a precipitous fall in the plasma
potassium ( dilution by IVF, insulin action, correction of
acidosis, continued renal losses).

• hyperglycaemia does not correlate with the severity of the
metabolic acidosis
• Moderate elevation of blood glucose may be associated
with life-threatening ketoacidosis.
• In some cases, hyperglycaemia predominates and acidosis
is minimal, with patients presenting in a hyperosmolar
state
Clinical assessment
• salt and water depletion, with loss of skin turgor, furred
tongue and cracked lips, tachycardia, hypotension and
reduced intra-ocular pressure
• Breathing may be deep and sighing, the breath is usually
fetid, and the sickly-sweet smell of acetone may be
apparent.

• Mental apathy, confusion or a reduced conscious level
may be present, although coma is uncommon.
• Abdominal pain is sometimes a feature of DKA, particularly
in children, and vomiting is common.
• Serum amylase may be elevated but rarely indicates coexisting
pancreatitis.
• In infected patients, pyrexia may not be present initially because of
vasodilatation secondary to Acidosis.
Investigations
• Venous blood: for urea and electrolytes, glucose and
bicarbonate (severe acidosis is indicated by a venous plasma
bicarbonate < 12 mmol/L).
• Urine or blood analysis for ketones
• ECG.
• Infection screen: full blood count, blood and urine
culture, C-reactive protein, chest X-ray

Management
• Insulin
• A fixed-rate intravenous insulin infusion of 0.1 U/
kg body weight/hr is recommended
• rapid decrease in blood glucose should be avoided,
as this might precipitate hypoglycaemia and the
serious complication of cerebral edema,
particularly in children.
• When the blood glucose has fallen, 10% dextrose
infusion is introduced and insulin infusion
continued to encourage glucose uptake into cells
and restoration of normal metabolism.

• Restoration of the usual insulin regimen, by subcutaneous
injection, should not be instituted until the patient is
both biochemically stable and able to eat and drink
normally.
Fluid replacement
• In adults, rapid fluid replacement in the first few hours is
usually recommended
• Caution is recommended in children and young adults
because of the risk of cerebral oedema.
• correction of the extracellular fluid deficit with isotonic
saline (0.9% sodium chloride).
• If the plasma sodium is greater than 155 mmol/L, 0.45%
saline may be used initially.

Potassium
• Treatment with 0.9% sodium chloride with
potassium chloride 40 mmol/L is recommended if
the serum potassium is below 5.5 mmol/L and the
patient is passing Urine.
• If the potassium falls below 3.5 mmol/L, the
potassium replacement regimen needs to be
escalated.
Bicarbonate
• Adequate fluid and insulin replacement should
resolve the acidosis. The use of intravenous
bicarbonate therapy is currently not recommended.

• Additional measures
• Catheterisation if no urine passed after 3 hrs
• Central venous line if cardiovascular system
compromised
• Measure arterial blood gases and repeat
chest X-ray if O2 saturation < 92%
• ECG monitoring in severe cases
• Thromboprophylaxis with low molecular
weight heparin

Hyperglycaemic hyperosmolar state
Hyperglycaemic hyperosmolar state (HHS) is
characterised by:
• severe hyperglycaemia (> 30 mmol/L (600 mg/
dL)),
• hyperosmolality (serum osmolality > 320
mOsm/ kg),
• and dehydration in the absence of significant
hyperketonaemia (< 3 mmol/L) or acidosis (pH >
7.3, Bicarbonate > 15 mmol/L).

• in HHS, hyperglycaemia usually develops over a
longer period (a few days to weeks), causing
more profound hyperglycaemia and
dehydration.
• patients with HHS do not develop significant
Ketoacidosis , may be because insulin level ,
although low, can be sufficient to prevent
lipolysis and subsequent ketogenesis.
• Common precipitating factors include infection,
myocardial infarction, cerebrovascular events or
drug therapy (e.g. corticosteroids

• Poor prognostic signs include hypothermia, hypotension
(systolic blood pressure < 90 mmHg tachy- or bradycardia,
severe hypernatraemia (sodium > 160 mmol/L), serum
osmolality > 360 mOsm/kg, and
• the presence of other serious comorbidities.
• Mortality rates are higher than in DKA –
Principles of management of hyperglycaemic
hyperosmolar state
• Measure or calculate serum osmolality frequently (Plasma
osmolarity = 2[Na+ ]+[glucose]+[urea] The normal value is
280–290 mmol/L
• Give fluid replacement with 0.9% sodium chloride (IV).
• Use 0.45% sodium chloride only if osmolality is increasing,
despite positive fluid balance. Target fall in plasma sodium is ≤
10 mmol/L at 24 hrs.

• rapid fluid replacement may precipitate cardiac failure
in patients with coronary artery disease.
• A key recommendation is that 0.9% sodium chloride
solution alone is used for initial treatment, and that
insulin is introduced only when the rate of fall in blood
glucose has plateaued.
• Initiate insulin IV infusion (0.05 U/kg body weight/hr)
only when blood glucose is not falling with 0.9%
sodium chloride alone OR if there is significant
ketonaemia (3β-hydroxybutyrate > 1 mmol/L or urine
ketones > 2+), to avoid rapid shifts in osmolality .
• Treat coexisting conditions
• Give prophylactic anticoagulation.

Hypoglycaemia
• Hypoglycaemia (blood glucose < 3.5 mmol/L (63 mg/ dL)) in
diabetes results in most circumstances from insulin therapy, less
frequently from use of oral insulin secretagogues such as
sulphonylurea drugs, and rarely with other anti-diabetic drugs.
• within 5 years of diagnosis, most patients with type I DM will have
lost their ability to release glucagon specifically
during hypoglycaemia. This is thought to result mainly
from loss of α-cell regulation by β cells.
• Also People with type 1 diabetes cannot regulate insulin once it is
injected subcutaneously,
• These two primary defects mean that hypoglycaemia occurs much
more frequently in people with type 1 and longer duration type 2
diabetes.

• symptoms of hypoglycaemia
Autonomic
• • Sweating
• • Trembling
• • Pounding heart
• • Hunger
• • Anxiety
Neuroglycopenic
• • Confusion
• • Drowsiness
• • Speech difficulty
• • Inability to concentrate
• • Incoordination
• • Irritability, anger

• Non-specific
• • Nausea
• • Tiredness
• • Headache
Risk factors for hypoglycemia
• Missed, delayed or inadequate meal
• unusual exercise
• Alcohol
• Errors in oral anti-diabetic agent or insulin dose/schedule.
• Poorly designed insulin regimen,
• Lipohypertrophy at injection sites
• Gastroparesis due to autonomic neuropathy
• Malabsorption, e.g. coeliac disease
• other endocrine disorder, e.g. Addison’s disease
• Factitious (deliberately induced)

Risk factors for severe hypoglycaemia
• Strict glycemic control
• Impaired awareness of hypoglycaemia( associated with longer
duration of DM. type I more than type II) due to cerebral
adaptation and low neuroglypenia S&S , also cerebral adaptation
has a similar effect on the counter-regulatory hormonal response
to hypoglycaemia.
• Age (very young and elderly)
• Long duration of diabetes
• Sleep
• C-peptide negativity (indicating complete insulin deficiency)
• History of previous severe hypoglycaemia
• Renal impairment
• Genetic, e.g. angiotensin-converting enzyme (ACE) genotype

Management
• Acute treatment of hypoglycaemia
Mild (self-treated)
• Oral fast-acting carbohydrate (10–15 g) is taken as glucose
drink or tablets
• This should be followed with a snack containing complex
Carbohydrate
Severe
• If patient is semiconscious or unconscious, parenteral
treatment is required:
• IV 75 mL 20% dextrose (= 15 g; give 0.2 g/kg in children)*
Or
• IM glucagon (1 mg; 0.5 mg in children)

• If the patient fails to regain consciousness
after blood glucose is restored to normal,
then cerebral oedema and other causes of
impaired consciousness – such as alcohol
intoxication, a post-ictal state or cerebral
haemorrhage should be considered.
• Cerebral oedema has a high mortality and
morbidity, and requires urgent treatment with
mannitol and high-dose oxygen.
• Following recovery, the patient should reduce
the next dose of insulin by 10–20%.

CHRONIC COMPLICATIONS OF DIABETES
• Excess mortality in diabetes is caused mainly by large
blood vessel disease,(Macrovascular disease)
myocardial infarction, stroke, angina, cardiac failure
and intermittent claudication.
• diabetic microangiopathy. contributes to mortality
through renal failure caused by diabetic nephropathy,
and is responsible for substantial morbidity and
disability: for example, blindness from diabetic
retinopathy, difficulty in walking, chronic ulceration
of the feet from peripheral neuropathy, and bowel
and bladder dysfunction from autonomic neuropathy.

• The histopathological hallmark of diabetic
microangiopathy is thickening of the capillary
basement membrane, with associated
increased vascular permeability, which occurs
throughout the body.
• The development of the characteristic clinical
syndromes of diabetic retinopathy,
nephropathy, neuropathy and
accelerated atherosclerosis is thought to result
from the local response to generalised vascular
injury.

Diabetic retinopathy
• Diabetic retinopathy (DR) is one of the most
common causes of blindness in adults
between 30 and 65 years of Age.
• The prevalence of DR increases with duration
of diabetes

Pathophysiology
• Hyperglycaemia increases retinal blood flow and
disrupts intracellular metabolism in retinal
endothelial cells and pericytes .
• This leads to impaired vascular autoregulation,
increased production of vasoactive substances and
endothelial cell proliferation.
• The resulting capillary hypoperfusion and closure
cause chronic retinal ischemia, stimulating the
production of growth factors, including vascular
endothelial growth factor (VEGF) (causing retinal
leakage and exudation).

Risk factors for diabetic retinopathy
• Long duration of diabetes
• Poor glycaemic control
• Hypertension
Clinical features
two stages: non-proliferative (‘background’) and proliferative.
non-proliferative DR
• are microaneurysms and retinal haemorrhages
• As DR progresses cotton wool spots, venous beading and
intra-retinal microvascular abnormalities can be seen this
stage is referred to as pre-proliferative DR.

• proliferative DR, which is characterised
• by growth of new blood vessels on the retina or optic
disc .
• The new vessels are abnormal and often bleed, leading
to vitreous haemorrhage, subsequent fibrosis and
scarring, and finally tractional retinal detachment.
• In addition to proliferative and non-proliferative DR,
• patients may also develop clinically significant macular
oedema (CSMO) this can occur at any stage of DR and
is characterised by increased vascular permeability and
deposition of hard exudates in the central retina. CSMO
is the most common cause of loss of vision in people
with diabetes.

• ‘rubeosis iridis’,may obstruct the drainage angle of the
eye and the outflow aqueous fluid, causing secondary
glaucoma
• Sudden visual loss occurs with vitreous haemorrhage or
retinal detachment.
Management
• Good glycemic (HbA1c around 53 mmol/mol (7%)
• control and an appropriate blood pressure (< 130/ 80
mmHg) should be maintained to prevent onset and delay
progression of diabetic eye disease
• ranibizumab, a monoclonal antibody fragment that binds
to VEGF-A and is antiangiogenic; it is used for diabetic
macular oedema.

Other causes of visual loss in people with
diabetes.
• These include cataract,
• age-related macular degeneration,
• retinal vein occlusion,
• retinal arterial occlusion,
• non-arteritic ischaemic optic neuropathy
• and glaucoma.

Diabetic nephropathy
About 30% of patients with type 1 diabetes
have developed diabetic nephropathy 20
years after diagnosis.
Risk factors for diabetic nephropathy
I. Poor glycaemic control
II. Long duration of diabetes
III. Presence of other microvascular
complications

4 . Pre-existing hypertension
5 . Family history of diabetic nephropathy
6 . Family history of hypertension
• Diabetic nephropathy most common causes of end-stage
renal failure in developed countries.
Pathologically
• the first changes coincide with the onset of
microalbuminuria and include thickening of the
glomerular basement membrane and accumulation of
matrix material in the mesangium.
• Subsequently, nodular deposits are characteristic, and
glomerulosclerosis worsens as heavy proteinuria develops,
until glomeruli are progressively lost and renal function
deteriorates.

Management
• The presence of established microalbuminuria or overt
Nephropathy should prompt vigorous efforts to
1. aggressive reduction of blood pressure
2. aggressive cardiovascular risk factor reduction
• ACE inhibitors, and AT II recepter bloker have been shown
to provide greater protection than equal blood pressure
reduction achieved with other drugs due to reduction in
the angiotensin II-mediated vasoconstriction of efferent
arterioles.
• in glomeruli ,The resulting dilatation of these vessels
decreases glomeruli filtration pressure and therefore the
hyperfiltration and protein leak.

• Both ACE inhibitors and ARBs increase risk of
hyperkalemia and, in the presence of renal artery
stenosis , may induce marked deterioration in renal
function. Therefore, electrolytes and renal function
should be checked after initiation or each dose
increase.
• Non-dihydropyridine calcium antagonists
(diltiazem, verapamil) may be suitable alternatives
Halving the amount of albuminuria with an ACE or
ARB results in a nearly 50% reduction in long-term
risk of progression to end-stage renal disease.

Diabetic neuropathy
• Although there is some evidence that the
central nervous system is affected in long-
term diabetes, the clinical impact of diabetes
is mainly manifest in the peripheral nervous
system.
• it affects between 50 and 90% of patients
with diabetes, and of these, 15–30% will
have painful diabetic neuropathy (PDN).

Symmetrical sensory polyneuropathy
• This is frequently asymptomatic. The most common
clinical signs are diminished perception of vibration
sensation distally, ‘glove and stocking’ impairment of all
other modalities of sensation ,and loss of tendon reflexes
in the lower limbs.
• In symptomatic patients, sensory abnormalities are
predominant. Symptoms include parasthesia in the feet
(and, rarely, in the hands), pain in the lower limbs (dull,
aching and/or lancinating, worse at night, and mainly felt
on the anterior aspect of the legs), burning sensations in
the soles of the feet, cutaneous hyperaesthesia and an
abnormal gait (commonly wide-based).

• Weakness and atrophy, in particular of the
interosseous muscles, may develop, leading to
structural changes in the foot with loss of lateral and
transverse arches, clawing of the toes and exposure
of the metatarsal heads.
• characteristic features include foot ulcers and
Charcot neuroarthropathy
Asymmetrical motor diabetic neuropathy
• Sometimes called diabetic amyotrophy, this presents
as severe and progressive weakness and wasting of
the proximal muscles of the lower (and occasionally
the upper) limbs.

• It is commonly accompanied by severe pain, mainly felt
on the anterior aspect of the leg, and hyperaesthesia and
parasthesia.
• Sometimes there may also be marked loss of weight
(‘neuropathic cachexia’).
• Tendon reflexes may be absent on the affected side(s).
Sometimes there are extensor plantar responses.
• and the cerebrospinal fluid protein is often raised. This
condition is thought to involve acute infarction of the
lower motor neurons of the lumbosacral plexus.
• Although recovery usually occurs within 12 months, some
deficits are permanent.
• Management is mainly supportive.

Mononeuropathy
• Either motor or sensory function can be affected within a
single peripheral or cranial nerve mononeuropathies are
severe and of rapid onset, but they eventually recover.
• The nerves most commonly affected are the 3rd and 6th
cranial nerves (resulting in diplopia), and the femoral
and sciatic nerves.
• Nerve compression palsies are more common in
diabetes, frequently affecting the median nerve, giving
the clinical picture of carpal tunnel syndrome.
• Lateral popliteal nerve compression occasionally causes
foot drop

Autonomic neuropathy
• This is not necessarily associated with peripheral
somatic neuropathy.
• Parasympathetic or sympathetic nerves may be
predominantly affected in one or more visceral
systems.
• autonomic neuropathy is less clearly related to poor
metabolic control than somatic neuropathy, and
improved control rarely results in improved
symptoms.
• Within 10 years of developing overt symptoms of
autonomic neuropathy, 30–50% of patients are dead,
many from sudden cardiorespiratory arrest.

Management options for peripheral
• sensorimotor and autonomic neuropathies
• Pain and paraesthesiae from peripheral somatic
neuropathies
• Intensive insulin therapy (strict glycaemic control)
• Anticonvulsants (gabapentin, pregabalin,
carbamazepine, phenytoin)
• Tricyclic antidepressants (amitriptyline, imipramine)
• Other antidepressants (duloxetine)
• Substance P depleter (capsaicin – topical)
• Opiates (tramadol, oxycodone)

• Postural hypotension
• Support stockings
• Fludrocortisone
• NSAIDs
• α-adrenoceptor agonist (midodrine)
Gastroparesis
• Dopamine antagonists (metoclopramide, domperidone)
• Erythromycin
• Gastric pacemaker; percutaneous enteral (jejunal) feeding
Diarrhoea
• Loperamide
• Broad-spectrum antibiotics
• Clonidine
• Octreotide

Constipation
• Stimulant laxatives (senna)
Atonic bladder
• Intermittent self-catheterisation
Excessive sweating
• Anticholinergic drugs (propantheline, poldine, oxybutinin)
• Clonidine
• Topical antimuscarinic agent (glycopyrrolate cream
Erectile dysfunction
• Phosphodiesterase type 5 inhibitors (sildenafil, vardenafil,
tadalafil) – oral
• Dopamine agonist (apomorphine)
• Implanted penile prosthesis

The diabetic foot
• Foot ulceration occurs as a result of trauma (often trivial) in
the presence of neuropathy and/or peripheral vascular
disease , with infection occurring as a secondary
phenomenon.
• multiple components are involved .Ischaemia alone
accounts for a minority of foot ulcers in diabetic patients,
with most being either neuropathic or neuro-ischaemic.,
• Charcot neuro-arthropathy is a progressive condition
affecting the bones and joints of the foot; it is characterised
by early inflammation and then joint dislocation,
subluxation, and pathological fractures of the foot.

Diabetic foot management
• primary prevention and treatment of an active problem.
• to grade a patient’s risk: a 10 g monofilament should be used to
assess sensation at five points on each foot, and foot pulses
should be palpated (dorsalis pedis and/or posterior tibial)
• Once a foot ulcer develops, patients should ideally be referred
to a foot team, involving a
• diabetes specialist, a podiatrist, a vascular surgeon and an
orthopedic surgeon.
• Treatment involves: débridement of dead tissue; treatment with
antibiotics if required, as infection can lead to gangrene;
• pressure relief using dressings; use of specialised orthotic
footwear;

• angiography, as revascularisation by angioplasty or
surgery may be required to allow the ulcer to heal.
• If severe secondary infection or gangrene, an
amputation may be required.
• Acute Charcot arthropathy almost always presents
with signs of inflammation – a hot, red, swollen foot
• it can be difficult to differentiate from osteomyelitis.
Magnetic resonance imaging (MRI) of the foot is
often helpful.
• The mainstay of treatment for an active Charcot foot
is immobilisation and, ideally, avoidance of weight-
bearing on the affected foot.

• Surgery and diabetes
• Patients with diabetes are reported to have up to 50%
higher peri-operative mortality than patients without
diabetes.
• in untreated or poorly controlled diabetes, the uptake of
metabolic substrate into tissues is significantly reduced,
catabolism is increased and, ultimately, metabolic
decompensation in the form of diabetic ketoacidosis
may develop in both types of diabetes.
• In addition, hyperglycaemia impairs wound healing and
innate immunity, leading to increased risk of infection.
also DM patients more likely to have underlying pre-
operative morbidity, especially cardiovascular disease.

Pre-operative assessment
1. Assess glycaemic control
• Consider delaying surgery and referral to the diabetes
team if HbA1c > 75 mmol/mol (9%).
(an upper limit for an acceptable HbA1c should be between 64 and
75 mmol/ mol (8 and 9%).
2• Assess cardiovascular status
• Optimise blood pressure
• ECG for evidence of (possibly silent) ischaemic heart disease and to
assess QTc
3.Assess foot risk
• Patients with high-risk feet should have suitable pressure relief
provided during post-operative nursing
4.plan for the patient to be first on the list

L3-4. DM.pptx...................................................

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