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Diabetes
By Sophie Lewis
Classification
• Diabetes Mellulitus (DM)
– A syndrome of chronic hyperglycaemia due to relative
insulin deficiency, resistance or both
• Diabetes Inspidus (DI)
– a condition characterized by excessive thirst and
excretion of large amounts of severally dilute urine
– 2 common types Central deficiency in ADH and
nephrogenic diabetes insipidus caused by insensitivity
of the kidneys to ADH
Epidemiology
DM affects more than 120 million people
worldwide
Anatomy
Retroperitoneal organ
originating from the
foregut
Divided into the:
•Head
•Neck
•Body
•Tail
Blood Supply
•Splenic +Hepatoduodenal
arteries
•Portal + Splenic veins
Endocrine gland (islets
of Langerhans)
•α-glucagon
•Β-insulin
•δ-somatostatin
Exocrine glanddigestive enzymes
Insulin Vs Glucagon
Type 1 Diabetes
Absolute insulin deficiency
It can present at any age (predominately
children, particularly at puberty)
Caused by a mix of hereditary (polygenic) and
environmental factors (viruses)
• HLA-associated immune-mediated organ
specific disease (autoantibodies directed at
pancreatic islets)
Type 2 diabetes
• Insulin resistance and deficiency
Combination of genetic and environmental
factors
Gradual insidious onset
Increase in glucose stimulates β cells
increase insulin production down regulation of
receptors= reduced glucose utilization
β cells try to compensate but become exhausted
impaired glucose tolerance
Secondary diabetes
Diabetes that is a result of another underlying
medical condition:
• Pancreatic disease-CF, chronic pancreatitis
• Endocrine-Cushing’s, Acromegaly,
thyrotoxicosis
• Drug induced-thiazide diuretics,
corticosteriods, TB drugs
Gestational Diabetes
Diabetes which presents for the first time during
pregnancy
Normal physiology to develop some insulin
resistance to allow glucose to reach the fetus
but can become exaggerated
Clinical presentation
Acute (2-6 weeks)
Weight loss
Polyuria +Nocturia
thirst
Subacute (several months)
• Lack of energy
• Visual blurring
• Pruritus and balanitis (candida infections)
Diagnosis
• Clinical presentation
• Fasting plasma glucose >7.0mmol/l
• Random plasma glucose >11.1mmol/
• The oral glucose tolerance test (borderline cases
and gestational diabetes)
• Hb1Ac-measures glucose over the past 3-6
months- >6.5% or 48mmol/1mol
Complications
Macroangiography
-CVD, MI, Stroke
Microangiography
• Nephropathy
• Neuropathy
• Retinopathy
Pathophysiology
• High glucoseglycated proteins (collagen in the interstitial
matrix)= abnormal function (increase in LDL
absorptionatheroma)
• Polyol pathwayglucosesorbitolfructose
(increase in intracellular osmolalityinflux of water and
impairment of the ion pumps)
The reaction consume NADPH=free radicals=oxidative stress
• Increase in protein kinase C activityVEGF-new vessel
production, an increase pro-inflammatory mediators and
an increase in endothelin + decrease in
NO=vasoconstriction
Nephropathy
HyperinfiltrationIncreased thickness of the
basement membrane
(note ACE inhibitors are beneficial)
Patient presents with nephrotic syndrome and
glomerlusclerosis (IgA)
-proteinuria, hypoabluminaemia, odema
Kimmelstiel-Wilson’s lesion
Neuropathy
• Axonal loss= increase in nerve conduction
distance
• Thickening of the basement membrane
Thought to be caused by a combination of
oxidative stress and glycated proteins affecting
both the nerves and blood supply
Retinopathy
• Leaky vesselsmicroaneurysmsocclusion of
vessels
• Haemorrhages
• Proliferative and non-proliferative
Treatment
Insulin Treatment
• Bolus dosage
• Short acting
• Long acting
Infusion devices
(disadv-infection
and DKA is broken)
Complications
• At the injection site-painful, red lesions and
lipohypertrophy
• Weight gain
• Hypoglycaemia
– Blood glucose <3mmol/L
– Sweating, tremor, palpitations, pale, drowsy, clumsy,
inappropriate behavior, confusion, coma
– Treatment
• Mild-fasting acting glucose followed by slower releasing
glucose
• Severe- intramuscular glucagon (1mg) or IV glucose
Tablet Treatments
Glitazones/thiazolidinediones
-regulates the expression of metabolism
of GLUT 4 receptors in adipose tissue
(increase glucose uptake) roseglitazone
Adipose tissue
Biguanides
-reduce
hepatoglucogenesis
-increase glucose uptake
metformin
Liver
Pancreas
Post-prandial glucose regulation
-acts on K+ pump (but different
site) nateglinide
α-glucosidase
-inhibits α-glucosidase in the gut reducing
CHO absorption reducing post prandial
glucose peaks
Sulphonylureas
-inhibits ATP dependent K+
pump=Ca2+ influx
-increases the secretion of
insulin glicaside
Incretins
-DDP-4 inhibitor binds to binding site
+prevents GLP-1 breakdown
-GLP-1 stimulate β-cells
Small intestine
Measuring Metabolic Control
• Urine tests (not as good as testing blood
glucose)
• Home blood glucose testing (finger prick)
• Glycosylated haemoglobin (HbA1c)
DKA
Acid/base balance
2-5% mortality
Biggest complication=cerebral oedema
Generally only found in patients with type 1
diabetes
Acidaemia pH <7.3
Triad of symptoms
Hyperglycaemia<11.1mmol/L
Ketonaemia (<3mmol/L) or ++ urine
Mechanism
A lack of insulinrise in glucose in the bloodhyperglycaemia
proteins
Cells
Lipids
=ketones
Ketones produces an acidosisKussmaul
breathingexhuastioncoma
The plasma glucose reaches the renal threshold causing glucose to be
excreted by the kidneysosmotic diuresis and
glycosuradehydrationcoma
Insulin is also important in regulating the Na/K pump. Intracellular K
becomes lowhypokalamic (but noraml levels in blood due to
kidneys tight control)
Note: need to give K when treating the patient as insulin move K into
the cells
Clinical presentations
Treatment
• Fluids to correct dehydration-0.9% saline,
40mmol K added to each bag, strict fluid balanceNG tubes and catheter with fluid balance chart
and check electrolytes and glucose every hour
• Insulin-0.1U/Kg intravenous insulin infusion, aim
to reduce glucose by 3mmol/L per hour
(fasterrisk of cerebral oedema)
• Introduce 10% glucose when BMs <14-prevent
hypos
• Treat underlying cause
HONK
• Extreme hyperglycaemia (>40)
• Serum hyperosmolarity (>340)servre intracellular
dehydration
• Causes altered mental state, neurological signs, coma is
rare
• No ketosis as low levels of insulin prevent lipolysis but
levels are insufficient to reduce blood glucose
• Complications-thromboembolic events, infarctio,
cerebral oedema, multiorgan failure
• Overall mortality up to 30% (more than DKA-elderly
population)