9/2/2010

Understanding Diabetes
Final Year CUCMS
Teaching module

Dr Nor Shuhaila
HPJ

GLUCOSE HOMEOSTASIS

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

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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 (Cushings, Acromegaly, Phaeochromocytoma etc)

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The Development of Type 2 Diabetes

Causes of type 2 diabetes
Genetically i nduced cell
ma l function and/ or
i ns ulin resistance

Environmental
factors

Obesity

Mi l d hyperglycaemia
cel l
ma l function

Ins ulin
res istance

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

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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
OGTT

6.5 mmol/l
9.0 mmol/l

So does he have diabetes?

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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
Addisons disease
Cardiomyopathy/ cardiac failure
Depression

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Case

Majority asymptomatic
48% pts over 30 yrs of age
are unaware that they have
diabetes.

What other questions would you like to ask

Mr. AB?
Symptoms of diabetes
Complications of diabetes

Complications of diabetes
Macrovascular
Coronary artery disease
Cerebrovasculardisease
Peripheral vascular disease

Microvascular
Nephropathy
Retinopathy
Neuropathy
Dermopathy

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Case

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.

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.

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Assessment of the newly diagnosed

patient: HISTORY

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.

Duration of symptoms e.g. thirst, polyuria,

weight loss
Possible secondary causes of DM e.g.
acromegaly, Cushings
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+

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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

Glaucoma

Maculopathy

Cataract

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The diabetic foot

Neuropathic and Ischaemic feet
of a diabetic.

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
Left ankle joint is deformed Charcots joint.
Evidence of diabetic dermopathy.
Distal muscles of the lower limb are wasted.
Absence of body hair.

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

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What investigations would you like to

do for Mr. AB?
a.
b.
c.
d.
e.
f.
g.

FBS
HbA1c
RP
LFT
UFEME
ECG
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

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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

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Treating to target!

Case

Indications for oral hypoglycaemic agents

So Mr. AB has diabetes.

Which medication would you give to Mr. AB?
a.
b.
c.
d.
e.

Gliclazide
Metformin
Acarbose
Rosiglitazone
All of the above

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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?

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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?

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Insulin: summary

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.

Types of insulin Examples

Peak activity (hrs)

Insulin
analogue

Humalog (lispro)
Insulin Apartate
(Novorapid)

0.5 - 1.5

Short acting
(soluble
insulins)

Human Actrapid
Humulin S

1- 3

Intermediate
acting
(isophane
insulins)

Human insulatard 4 8
Human monotard (zinc added to it)

Long acting

Human Ultratard
Insulin Glargine
(Lantus)

Duration of action
(hrs)
<6

(so inject and eat

simultaneously)

<8

Onset 30 mins after

injection (so eat 20-30
mins after)

8 14

Onset 1-2 hrs after

injection.

6 24
Peakless

< 36
24 hrs

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.

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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 prebed 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.

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