Understanding Diabetes

Final Year CUCMS

Teaching module

Dr Nor Shuhaila
HPJ
 What is diabetes?
• Condition with elevated
blood glucose

• Diabetics have sugar

lying around in their
circulation but are
unable to utilize it fully
due to certain factors:-
o No insulin or not enough
insulin
o Enough insulin but
unable to function well
o Insulin resistance
GLUCOSE HOMEOSTASIS
 Classification (WHO)
• Type 1 (5-25% of cases): Pancreatic islet  cell deficiency
– Autoimmune (anti-glutamic acid decarboxylase, islet cell and insulin
antibodies
– Idiopathic
• Type 2 (75-95% of cases): Defective insulin action or secretion
– Insulin resistance
– Insulin secretory defect
• Others:-
– Genetic defects of  cells function
• Maturity Onset Diabetic of the Young (MODY) – chromocomal defects
– Genetic defects of insulin action
• Leprechaunism
– Diseases of exocrine pancreas
• Pancreatitis
• Pancreatectomy
– Secondary DM (Cushing’s, Acromegaly, Phaeochromocytoma etc)
The Development of Type 2 Diabetes

Causes of type 2 diabetes

Genetically induced  cell

malfunction and/ or
insulin resistance

Obesity Environmental
factors
Mild hyperglycaemia

 cell
malfunction Insulin
resistance

Type 2 DM
Who is at risk?
 Case
• Mr. AB, 40 yr old man
• No past history of any illness
• On routine annual health check advocated by
his company, he was found to have a fasting
blood glucose of 6.89 mmol/l.
• Upon further questioning, he has positive FH
of DM
– Both parents diabetics
– Elder brother, aged 54 yrs, also diabetic
 Case
• Does Mr. AB has diabetes?
a. YES
b. NO
c. PROBABLY AT RISK

• How do you diagnose diabetes?

• What one other test would you recommend?

 Case
• Mr. AB returned 2 weeks later for a repeat
blood glucose test
– FBS 6.5 mmol/l
– OGTT 9.0 mmol/l

• So does he have diabetes?

 Case
• Mr. AB was advised to watch his diet and start
cutting down his glucose intake.
• 1 year later, he presented to his private doctor
near his home with 2 months history of feeling
easily tired.
• What are your differentials?
 Differential diagnosis of lethargy
• Anaemia
• Diabetes
• Hypothyroidism
• Chronic renal failure
• Addison’s disease
• Cardiomyopathy/ cardiac failure
• Depression
 Case
• What other questions would you like to ask
Mr. AB?
 Symptoms of diabetes
 Complications of diabetes
• Majority asymptomatic
• 48% pts over 30 yrs of age
are unaware that they have
diabetes.
 Complications of diabetes
• Macrovascular
– Coronary artery disease
– Cerebrovascular disease
– Peripheral vascular disease
• Microvascular
– Nephropathy
– Retinopathy
– Neuropathy
– Dermopathy
 Case
• Mr. AB admitted that he has been getting up 3
to 4 times at night to pass urine.
• He is also often thirsty at those times and
drinks a glass of water each time.
• He has been overweight since secondary
school but has noticed that he is losing weight
and feeling weak over the 2-month period.
• Despite that his appetite is excellent.
 Case
• Further questioning revealed that he had
been having pain in both of his feet which is
worse at night; sometimes keeping him
awake.
• It was burning in nature and sometimes his
toes felt numb.
• His vision was blurry at times, especially in the
afternoon.
 Case
• As mentioned earlier, both his parents and
elder brother were diabetics. In addition, his
mother was on dialysis for renal failure.
• He is not on any medications. He denies taking
traditional medicines.
• He is married with 3 children.
• He smokes 10 cigarettes per day for past 15
years. He does not drink alcohol.
 Assessment of the newly diagnosed
patient: HISTORY
• Duration of symptoms e.g. thirst, polyuria,
weight loss
• Possible secondary causes of DM e.g.
acromegaly, Cushing’s
• Family history
• Presence of complication of DM
• Risk factors for developing complications eg
smoking, hypertension, hyperlipidaemia
 Case
• Weight 90 kg, height 160 cm. BMI?
• Pink
• Xanthelasma, no tendon xanthomata
• No Cushingoid/ acromegalic features
• BP 145/96 mmHg, PR 84 bpm reg
• CVS S1S2
• Lungs clear
• PA soft, non-tender, BS+
 Case
• No pitting pedal oedema
• Peripheral pulses all well palpable
• Reduced sensation to light touch and pin prick
over the toes and dorsum of both feet up to
ankles, and hands up to wrists.
• Absent ankle jerks.
• Fundoscopy: dot and blot haemorrhage.
Diabetic retinopathy
 The diabetic eye
Background retinopathy Maculopathy

Glaucoma Cataract
 The diabetic foot
Neuropathic and Ischaemic feet
of a diabetic.

Left ankle joint is deformed – Charcot’s joint.

Evidence of diabetic dermopathy.
Distal muscles of the lower limb are wasted.
Absence of body hair.
 Assessment of the newly diagnosed
patient: EXAMINATION
• Body mass index (BMI)
– Weight in kg divide by (height in meters)2
• Clues for secondary causes
• CVS (BP and peripheral pulses)
• Signs of autonomic and peripheral neuropathy
– Postural hypotension
– Loss of ankle reflex, distal muscle wasting and sensory loss
• Eyes – for retinopathy
• Skin – dermopathy, granuloma annulare, necrobiosis
lipoidica diabeticorum
 Case
• What can you deduce from the history and
physical examination?
• Mr. AB has symptoms of diabetes.
• Mr. AB has complications of diabetes
– Retinopathy
– Peripheral neuropathy
• Mr. AB has associated co-morbidities:
smoking, hypertension, hyperlipidaemia
 What investigations would you like to
do for Mr. AB?
a. FBS
b. HbA1c
c. RP
d. LFT
e. UFEME
f. ECG
g. All of the above
 Assessment of the newly diagnosed
patient: INVESTIGATION
• Renal profile – look for renal impairment
• Liver function test – fatty liver
• Thyroid function – associated thyroid disease
• Lipid profile – diabetic dyslipidaemia
• Urine for ketones, protein and if negative, for
microalbuminuria
• ECG in all type 2 diabetics
 How will you manage Mr. AB?

• Non-pharmacological
– Educate on diabetes (diabetes
educator)
– Diet (dietitian)
– Exercise ( at least 150 mins/
week)
– Weight loss if obese (5 – 10%
over 6 month)
• Pharmacological
– Oral anti-diabetic medications/
Insulin
Aim of management
 Dietary advice: standard diabetic diet
• < 10% of its energy in the form of saturated fat (< 8%
if hyperlipidaemic)
• < 30% from all fats
• 50-60% as carbohydrate which is mostly complex
cabohydrate, high fibre
• Sugar limited to about 25g/ day
• Sodium content < 6 g/ day in most people or < 3g/
day if hypertensive
• If overweight, reduce total intake to aid weight
reduction
• Alcohol consumption (empty calories) – reduce if
overweight or hypertriglyceridaemia
 Case
• Investigations are as follows:
• RBS 15 mmol/l
• FBS 9 mmol/l
• HbA1c 7.8%
• BU 5.6 Na 141 K 4.5 Creat 89
• ALT 45 AST 40 Alb 38
• TC 6.1 LDL 5.0 HDL 0.9 Tg 2.9
• UFEME prot 1+
• ECG LVH COMMENT
Treating to target!
 Case
• So Mr. AB has diabetes.
• Which medication would you give to Mr. AB?

a. Gliclazide
b. Metformin
c. Acarbose
d. Rosiglitazone
e. All of the above
Indications for oral hypoglycaemic agents
 Case
• Mr. AB was started on Metformin 250 mg BD
which was increased to 500 mg BD and
subsequently 1 gm BD as his blood glucose
was not adequately controlled.
• At 3 months, his results were as follows:
– FBS 11.0 mmol/l
– HbA1c 8.4%
• What is the next step of management?
How many classes of OADs are there?
 Case
• Mr. AB was given combination of Metformin
and Glibenclamide 1g/10 mg BD.
• HbA1c 8.5%, FBS 10 mmol/l after 3 months.
• What are you going to do?
 Insulin therapy
• Required in all type 1 DM
• In type 2 DM to achieve better glycaemic control or
for the relief of hyperglycaemic symptoms.
• Most insulin is in a biosynthetic human form (from
yeast/ bacteria) at a standard concentration U100
(100 units/mL).
• Can be given by s/c or i/v routes.
• Standard insulins come as 10ml vials for use with a
0.5 ml or 1.0 ml syringe or as 1.5 ml or 3.0 ml
cartridges for use in pen devices.
• Insulin itself is unmodified/ neutral or mixed with
agents such as zinc to alter its onset of action, peak
effect and duration of action.
 Insulin: summary
Types of insulin Examples Peak activity (hrs) Duration of action
(hrs)
Insulin Humalog (lispro) 0.5 - 1.5 <6
analogue Insulin Apartate (so inject and eat
(Novorapid) simultaneously)

Short acting Human Actrapid 1- 3 <8

(soluble Humulin S Onset 30 mins after
insulins) injection (so eat 20-30
mins after)
Intermediate Human insulatard 4 – 8 8 – 14
acting Human monotard (zinc added to it)
(isophane Onset 1-2 hrs after
insulins) injection.
Long acting Human Ultratard 6 – 24 < 36
Insulin Glargine Peakless 24 hrs
(Lantus)
 Biphasic/ premixed insulins
• Combinations of soluble/ neutral and isophane
insulins (mixtard)
• Amount of soluble insulin varies from 10-50%; 30%
being the most popular.
• Depending on its monocomponents, onset is
normally at 30 mins, peak effect at 2-6 hrs and
duration 8-12 hrs.
• Insulin analogue biphasic preparation also available.
 Insulin regimes (1)
• Twice daily free mixing
– 2/3 isophane, 1/3 soluble
– 2/3 of both pre-breakfast and 1/3 pre-evening meal
– problems of mixing them, pre-lunch hypos or pre-dinner
hyperglycaemia.
• Twice daily fixed mixture
– Mixtard 30/70 (30% soluble/ 70% isophane)
– Not ideal for pre-lunch control
– Indicated for type 2 DM with poor control.
– Reasonable starting dose 10-15 units pre-breakfast, 5-10
units pre-dinner.
 Insulin regimes (2)
• Basal bolus regime
– Soluble insulin/ insulin analogue pre-meals (3X) with pre-bed
isophane
– Adv: more flexible with meal times
– Larger no. of injections and need frequent capillary blood
glucose monitoring.
– Reasonable starting dose e.g 4-6 iu pre-meals, 6-8 iu pre-bed.
– If on insulin analogues, 2X daily isophane needed especially if
there is a long gap between lunch and evening meal.
 Insulin regimes (3)
• Continuous s/c insulin infusion
– Used in USA
– Insulin pumps
– Potential problems: pump failure, ketoacidosis and cannula
site infections.
– Soluble insulin given continuously via a s/c cannula into
the anterior abdomen.
• Insulin and oral agent mixtures
– BIDS – bed time insulin, day time tablets (isophane pre-
bed to give acceptable fasting sugars), starting dose 10
iu/night
– Insulin plus metformin (2g/day) – to reduce insulin
requirements and improve control without further weight
gain often seen if the insulin is continually increased.