By raj

DIABETES
MELLITUS
INTRODUCTION
Diabetes mellitus is a clinical syndrome characterised by an increase
in plasma blood glucose (hyperglycaemia).
Defined as fasting plasma glucose ≥7mmol/L; or random glucose
≥11.1mmol/L
Results from:
 Insulin deficiency – inadequate secretion of insulin
 Insulin resistance – target tissue resistance to insulin

Acute hyperglycaemia marked symptoms, metabolic

decompensation
Chronic hyperglycaemia  microvascular and macrovascular
complications
TYPE 1 DIABETES
MELLITUS
Due to T-cell mediated autoimmune destruction of pancreatic beta
cells
Commonly occurs in childhood and adolescence, but can occur at
any age
Risk factors
 Genetic predisposition
 Environmental factors (poorly defined)
 Viral infections
 Dietary factors
 Obesity
TYPE 1 DIABETES
MELLITUS
TYPE 2 DIABETES
MELLITUS
Primary cause remains unclear
Pathogenesis:
 Insulin resistance
 Relative insulin deficiency due to pancreatic beta cell failure

Risk factors:
 Genetic predisposition
 Environmental factors
 Diet and obesity
 Age
 Women with prior GDM
 Comorbidities
CLINICAL FEATURES
Type 2 DM: many patients are asymptomatic
Hyperglycaemia symptoms:
 Thirst, dry mouth
 Polyuria
 Nocturia
 Tiredness, fatigue, lethary
 Change in weight (usually weight loss)
 Blurring of vision
 Pruritus vulvae, balanitis
 Nausea, headache
 Hyperphagia
 Mood change, irritability, difficulty in concentrating, apathy
CLINICAL FEATURES
GIT symptoms: Abdominal pain, change in bowel movements
accompanying acute DKA
Neuropathy (typically late): numbness and tingling sensation in both
hands and feet, bilateral, symmetric and ascending
Frequent/recurrent infections
EVALUATION OF
DIABETES MELLITUS
History Taking
 Specific symptoms
 Predisposition to diabetes
 Age, family history, ethnicity, overweight, physical inactivity, obstetric history of macrosomia/GDM
 Risk factors for complications
 Personal or family history of CVD, smoking, hypertension, dyslipidaemia, ESRF
 General symptoms review
 CVS, neurological symptoms, foot and toe problems, recurrent infections, bladder, sexual dysfunction,
depressive symptoms
 Lifestyle issues
 Smoking, alcohol, occupation, dietary habits, physical activity
EVALUATION OF
DIABETES MELLITUS
Physical Examination
 Weight, waist; BMI
 CVS: BP, pulses, precordial examination
 Eye: visual acuity, cataracts, retinopathy
 Feet: sensation, skin, pressure areas, interdigital lesions, bone deformities
 Peripheral nerves: Tendon reflexes, sensation (touch – with monofilament), vibration

Laboratory Investigations
 Baseline: FPG, HbA1c, RP, LFT, urinalysis, ECG
WHO SHOULD BE SCREENED?
•Individual who has symptoms (tiredness, lethargy,polyuria,polydipsia,weight
loss)
•relatives with T2DM
•BMI >23 kg/m2 or waist circmference >80 for female, >90 for male
•Central obesity
•Dyslipidemia (TG >2.8mmol/L HDL<0.9mmol/L)
•History of cardiovascular dz
•Hypertension(BP>140/90 or on theraphy for HPT)
•Impaired glucose tolerence (IGT) or impaired fasting glucose (IFG) on
previous testing
•1st degree relative with DM
 MANAGEMENTS
The overall aims of management are to improve quality of life and prevent
premature death:
1. Short term:
• Relief of symptoms and acute complications

2. Long term:
• Achievement of appropriate glycaemia
• Reduction of concurrent risk factors
• Identification and treatment of chronic complications
MANAGEMENTS
•Acute Complications
a) Hypoglycaemia
b) Hyperglycaemia

•Chronic Complications
a) Macrovascular
e.g. Cardiovascular, Cerebrovascular, Peripheral vascular systems
b) Microvascular
e.g. Nephropathy, Neuropathy and Retinopathy

CPG DM (2009), pg11

5 STEPS OF MANAGEMENT
1. Educate patient on the diagnosis
2. Educate patient on non pharmacological management
3. Educate patient on pharmacological management
4. Investigation plan
5. Follow up and safety netting
EDUCATION
•Patients should be made aware of:
• Symptoms: Common symptoms include polyuria, polydipsia, tiredness and weight
loss
• Precipitating factors (e.g. infection, intercurrent illness)
• Simple measures to avoid and manage the above
MANAGEMENT OF
EXISTING DM
•Meal timing should be regular and synchronized with medication time action.

•Consistent and evenly distributed total carbohydrate intake in a day.

•Monitor daily total carb intake.

•Test pre and post prandial glucose

•Limit intake of saturated and trans fatty acids as well as cholesterol to reduce risk of
CVD.

•Reduce sodium intake (< 2400mg sodium/day or 6g of salt/day)

 at least 150min/week of
PHYSICAL ACTIVITY
Exercise 5
days/week
moderate intensity
aerobic physical
activities

Increase in daily energy

90min/week of expenditure:gardening,mopping
vigorous aerobic the floor,walking up stairs
TARGET FOR CONTROL
PHARMACOLOGY
INTERVENTION
OHA (monotherapy)
Combined oral agents
Combined oral agents and insulin

CPG DM (2009), pg25-32

OHA (MONOTHERAPY)
Recommendations: Oral Agent Monotherapy
1. If glycaemic targets are not achieved (HbA1c < 6.5%, FPG < 6 mmol/L) with
lifestyle modification within 3 months, OAD agents should be initiated. [Grade
A]
2. In the presence of marked hyperglycaemia in newly diagnosed T2DM (HbA1c 6.5
– 8%, FPG 6 – 10 mmol/L), OAD agents should be considered at the outset
together with lifestyle modification. [Grade C]
3. Patients should be follow-up within 2-4 weeks to monitor the symptoms, to assess
the compliance and side effects of OAD and review the blood investigations
including fasting lipid profile. [Grade C]

There are currently five classes of OHA agents:

a) AGIs -acarbose
b) Biguanides -metformin
c) Dipeptidyl peptidase-4 (DPP-4) Inhibitors -sitagliptin
d) Insulin Secretagogues – Sus(eg/ gliclazide,glibenclamide) – Non-SUs or
Meglitinides (eg/ repaglinide,nateglinide)
e) Thiazolidinediones (TZDs)
 COMBINED ORAL
AGENTS
Recommendation: Combination of Oral Agents
1. Combination of oral agents is indicated in:
• Newly diagnosed patients with HbA1c 8 – 10%, FPG 10 – 13 mmol/L.
[Grade C]
• Patients who are not reaching targets (HbA1c <6.5%) after 3 – 6 months
on monotherapy. [Grade C]

Options for combined OHA therapy

Triple combination
SUs Biguanide
Biguanide Biguanide therapy
+ +
+ + SUs + biguanide +
Biguanides Thiazolidinediones
meglitinides AGIs thiazolidinediones
Or
Thiazolidine
or
diones
Or
SUs + biguanide
AGIs
+AGIs
If therapeutic goals are not met using the above combinations, switch to insulin+/- OHA
COMBINED ORAL AGENTS AND INSULIN
Recommendation: Combination of Oral Agents and Insulin

1. Combination of oral agents and insulin is indicated in:

• Newly diagnosed patients with HbA1c >10%, FPG > 13 mmol/L. [Grade C]
• Patients who are not reaching targets (HbA1c <6.5%) after 3 – 6 months on
optimal doses of combination therapy. [Grade C]

Combining insulin and the following OAD agents has been shown to be effective in
people with T2DM:
• Biguanide (metformin)
• Insulin secretagogues (SUs)
• Insulin sensitizers (TZDs)
• a-glucosidase inhibitor (AGI)

Insulin dosage can be increased until target FPG is achieved. If HbA1c targets are
not achieved despite of normal FPG, then monitor post-prandial plasma glucose
(PPG). In children and adolescents: Long-acting or intermediate acting insulin may
be added at a dose of 0.5u/kg at bed-time.
GUIDELINES FOR INSULIN
USEE
Types of Insulin Regimes
•OAD agents + basal insulin or premixed insulin once a day
•Metformin + premixed insulin more than once a day
•Metformin + basal insulin + prandial insulin

Patient should be educated on:

•injection technique
•symptoms, treatment and prevention of hypoglycemia
•simple guidelines to self-adjust the insulin dose
•self-monitoring of blood glucose (SMBG)
REACHING GLYCAEMIC
TARGETS
To control Adjust
Pre breakfast glucose Pre bed intermediate acting insulin or long acting
analogue or pre-dinner premixed
2 hour post breakfast Breakfast intake or pre breakfast rapid acting or
morning premixed insulin analogue
Pre lunch glucose Morning tea or pre breakfast short acting insulin or
morning premixed insulin
2 hour post lunch Lunch intake or pre lunch rapid acting or morning
premixed insulin
Pre dinner Afternoon tea intake or pre lunch short acting insulin or
morning premixed insulin
Post dinner/pre bed Dinner intake or pre dinner rapid acting or pre dinner
premixed analogue or pre dinner premixed insulin*

* may cause hypoglycaemia in the

middle of sleep.
 CHRONI
ACUTE
COMPLICATION OF DM C
HYPERGLYCEMIA MACROVASCULAR

HYPOGLYCEMIA MICROVASCULAR
 CX
MICROVASCULAR
• Diabetic foot AND
• Erectile dysfunction MACROVASCULAR
COMBINATION OF
COMPLICATION
• Coronary heart disease
MACROVASCULAR
• Cerebrovascular disease
• Diabetic retinopathy COMPLICATION
• Diabetic nephropathy MICROVASCULAR
• Diabetic neuropathy
SCREENING
RETINOPATHY
- conducted at the time of diagnosis of T2DM and Annually
- Pregnant women with T2DM should have retinal examination during each
trimester
EYE EXAMINATION
- Visual acuity is assessed with a Snellen chart and any refractive error was
corrected
- Fundus examination must be conducted by using a direct ophthalmoscope to
improve sensitivity.

TREATMENT
- Maintain tight glycaemic and blood pressure control
- Refer to an ophthalmologist is necessary for the following situations:
1. Unexplained poor vision
2. Diabetic retinopathy greater than occasional microaneurysms
3. Macular oedema or hard exudates within the macula
Refer urgently to an ophthalmologist
~ Sudden visual deterioration, new vessels on fundoscopy, rubeosis iridis,
vitreous haemorrhage, retinal detachment
RETINOPATHY
Initial assessment should be done at the time of dx of T2DM
subsequently anually
 Pregnant woman – each trimester
(not for GDM, unless dx in first trimester)
TREATMENT
Risk factor modification
 Tight control of Blood glucose
 BP
 Serum lipids
 Lifestyle factors
NOT A CONTRAINDICATION to aspirin therapy
Laser photcoagulation (standard practice)
Anti- VEGF -> improve visual acuity, avoid vision loss in pt with
Diabetic macular edema
 Ranibizumab / Afilibercept
 Adverse effect : increase in intraocular pressure, endopthalmitis
NEPHROPATHY
Diabetic Nephropathy (DN) is a major cause of chronic kidney disease (CKD)
The diagnosis of DN is made clinically by the presence of proteinuria
(microalbuminuria/overt proteinuria)
RECOMMENDATIONS FOR SCREENING
1. Screening for proteinuria should be performed at diagnosis and annually.
2. Urine should be screened for proteinuria with conventional dipstick on an early
morning urine specimen.
3. If urine dipstick for proteinuria is negative, screening for microalbuminuria should
be performed on an early morning urine specimen
4. If microalbuminuria is detected, confirmation should be made with 2 further tests
within 3 to 6 months
5. If microalbuminuria is not detected, re-screening should be performed annually.
1. Screening for proteinuria should be performed at diagnosis and annually.
2. Referral to nephrologist should be made if the serum creatinine exceeds
200 μ mol/L and earlier in patients with haematuria, nephritic syndrome,
absence of retinopathy (where the diagnosis of diabetic nephropathy may
be in doubt), difficult to control blood pressure and worsening renal
function.
3. Target BP in diabetics should be ≤130/80 and ≤125/75 in patients with
proteinuria >1g/day.
4. ACEIs or ARBs should be initiated in patients with microalbuminuria or
proteinuria.
 If microalbuminuria detected, repeat test within 3-6months
 If negative, annual screening should be continued
 Screening :
 Urine dipstick test
 Urine-Albumin creatinine ratio
(Men >2.5mg/mmol, Women >3.5mg/mmol)
Equivalent to 24 hour urine collection >20mg/L
Referreal to nephrologist
 Estimate d GFR <30ml/min/ Serum Cr >200 umol
 Heavy proteinuria
(urine protein >3g/day or Urine protein : creatinine ratio >0.3g/mmol)
 Hematuria
 Rapidly declining renal function
 Resistant hypertension
 Suspected renal artery stenosis
 Other suspected causes of CKD
 Pregnant or when prenancy is planned
SCREENING
- Diabetic peripheral neuropathy may be diagnosed reasonably accurately by
bedside clinical methods namely:
a) 10-g Semmes-Weinstein monofilament pressure sensation

NEUROPATHY
b) 128 Hz tuning fork vibration perception (on-off or absolute)
c) Ankle jerks (deep tendon reflexes)
d) Pin prick
Diabetic peripheral neuropathy may be defined as “the presence of symptoms and/or signs of
peripheral
- Performed nerveannually.
at least dysfunction in people with diabetes after the exclusion of other causes”.
- Can be prevented by maintaining good glycaemic control
TREATMENT
- Relief of symptoms includes the use of anticonvulsant agents e.g. gabapentin,
lamotrigine, carbamazepine or tricyclic antidepressants e.g. amitriptyline
- Achieve tight glycaemic control.
 RISK FACTORS FOR
FOOT ULCERS : RELEVANT EDUCATION FOR
- Previous amputation PATIENTS:
- Past foot ulcer history • In the presence of feet with reduced
DIABETIC FOOT
- Peripheral neuropathy
- Foot deformity
sensation, look at feet daily using a
mirror to detect early ulcerations.
• Wear flat, soft and well fitted shoes to
- Peripheral vascular disease
avoid callosities.
- Visual impairment
• Ensure no foreign objects in the shoes
- Diabetic nephropathy before putting feet in.
(especially patients on dialysis)
• Have one pair of shoes for indoor use
- Poor glycaemic control as well.
- Cigarette
DIABETIC smoking
FOOT :
1. Examine feet of patients at least once every year to identify individuals
who would then require intensive education on self care to avoid ulcers and
amputations.
2. To detect clinically relevant neuropathy, at least use a 10g monofilament.
RECTILE DYSFUNCTION
Consistent or recurrent inability of a male to attain or maintain penile erection
sufficient for sexual performance
RISK FACTORS :
 Age
 Duration of DM
 Poor glycemic control
 Smoking
 HPT
 Dyslipidemia

I. All adult males with diabetes over the age of 40 should be asked about ED.
II. Phosphodiesterase-5 (PDE-5) inhibitor should be offered as first-line
therapy if there are no contraindications.
III. Referral to a specialist in ED should be considered for men who do not
respond to PDE-5 inhibitors or for whom the use of PDE-5 inhibitors is
contraindicated.
 DIABETIC
Hypoglycaemia EMERGENCIES
DKA (Diabetic Ketoacidosis)
Hyperglycaemic Hyperosmolar State (HHS)
HYPOGYLYCAEMIA
Hypoglycaemia is defined by either one of the following two
conditions:
a) Low plasma glucose level (<4.0 mmol/L).
b) Development of autonomic or neuroglycopenic symptoms in
patients treated with insulin or OADs which are reversed by caloric
intake.
RISK FACTORS OF
HYPOGLYCAEMIA:
a) Advancing age
b) Severe cognitive impairment
c) Poor health knowledge
d) Increased A1c
e) Hypoglycaemia unawareness
f) Long standing insulin therapy
g) Renal impairment
h) Neuropathy
 MANAGEMENT
In mild to moderate hypoglycaemia where the individual is able to self-treat,
he/she should ingest 15 grams of simple carbohydrate (e.g 1 table spoon of
honey, ¾ cup of juice, 3 tea spoon of table sugar) and repeat blood glucose
after 15 minutes. If the level at 15 minutes is still <4.0 mmol/L, another 15
grams of carbohydrate should be taken.

In severe hypoglycaemia where the individual is still conscious, he/she should

ingest 20 grams of carbohydrate and the above steps are repeated.

In severe hypoglycaemia and unconscious individual, he/she should be given

20–50 mL of D50% intravenously over 1–3 minutes. Outside the hospital
setting, a tablespoon of honey should beadministered into the oral cavity.
NOCTURNAL
HYPOGLYCAEMIA
This risk is higher especially in the elderly
Both physiologic and behavioural defences against hypoglycaemia have
been shown to be further compromised during sleep.
The clinical manifestations are vague, and may include:
a) poor sleep quality
b) vivid dreams or nightmares
c) waking with chills or sweating
d) morning headache
e) chronic fatigue
f) mood changes and
g) nocturnal convulsions
Undetected nocturnal hypoglycaemia can promote hypoglycaemia unawareness, blunt
counterregulatory responses, create anxiety, reduce quality of life and increase treatment
costs. It can also result in negative outcomes such as falls, accidents and arrhythmias.
DEFINITION OF DKA
•Diabetic ketoacidosis (DKA) is a complex disordered metabolic state
characterised by hyperglycaemia,acidosis, and ketonaemia.
•DKA usually occurs as a consequence of absolute or relative insulin deficiency
that is accompanied by an increase in counterregulatory hormones (ie, glucagon,
cortisol, growth hormone, epinephrine).
•This type of hormonal imbalance enhances hepatic gluconeogenesis and
glycogenolysis resulting in severe hyperglycaemia, enhanced lipolysis increases
serum free fatty acids that are then metabolised as an alternative energy source
in the process of ketogenesis.
•Subsequently lead to accumulation of large quantities of ketone bodies and
subsequent metabolic acidosis.
•Ketones include acetone, 3-beta-hydroxybutyrate, and acetoacetate. The
predominant ketone in DKA is 3-betahydroxybutyrate.
INVESTIGATIONS
•Urinalysis-this is to detect the presence of glucose, ketone bodies and
pH of the urine. ( presence of glucose, ketone 3+)
•Glucometer -this is to measure the level of the glucose in this patient
particularly random blood glucose. The random blood glucose should
be more than 11mmol/L
•Arterial blood glucose –showed metabolic acidosis where the level of
bicarbonate ion is less than 15mmol/L and the pH is less than 7.30
OTHER INVESTIGATIONS
•Full blood count particularly white blood cell to check for any
infection
•Renal profile- to check the electrolytes level in this patient because
he developed vomiting which can cause electrolytes losses and also
the check the level of the urea in this patient as indicator for
dehydration
•Liver function test, to check for any derangement of the liver
enzymes
•Chest x-ray- to rule out any pneumonia infections
•ECG- any changes in T waves especially in hyperkalaemia that
showed tall tented T waves.
 MANAGEMENT IN DKA
The main aims for fluid replacement are:
1. Restoration of circulatory volume
2. Clearance of ketones
3. Correction of electrolyte imbalance
A fixed rate IVII calculated on 0.1 units/ per kilogram infusion is
recommended. It may be necessary to estimate the weight of the patient.
Insulin has the following effects:
1. Suppression of ketogenesis
2. Reduction of blood glucose
3. Correction of electrolyte imbalance
METABOLIC TREATMENT
TARGET
1. Reduction of the blood ketone concentration by 0.5 mmol/L/hour
2. Increase the venous bicarbonate by 3 mmol/L/hour
3. Reduce capillary blood glucose by 3 mmol/L/hour
4. Potassium should be maintained between 4.0 and 5.0 mmol/L
 MANAGEMENT OF DKA

The first hour- correct any hypotension

•second to six hours ( the aim is to lower down the level of the ketone
by 0.5 mmol/L/h and glucose 3mmol/L/hour and increase the level of
bicarbonate by 3mmol/L/hour
•six- 12 hours (assess for any complications of the treatment such as
hypoglycaemia, or cerebral edema. Look for the level of the
potassium)
•12-24 hours (resolution of the DKA when the patient started to eat
orally)
COMPLICATIONS OF DKA
Hypokalaemia and hyperkalaemia
•No potassium should be prescribed with the initial fluid resuscitation or if the
serum potassium level remains above 5.5 mmol/L.
•However, potassium will almost always fall as the DKA is treated with insulin,
thus it is recommended that 0.9% sodium chloride solution with potassium 40
mmol/L (ready-mixed) is prescribed as long as the serum potassium level is
below 5.5 mmol/L and the patient is passing urine.
Hypoglycaemia
•Common mistake is to allow the blood glucose to drop to hypoglycaemic
levels.
•Result in a rebound ketosis driven by counter-regulatory hormones and
lengthens duration of treatment
•Once the blood glucose falls to 14 mmol/L intravenous glucose 10% needs to
be commenced to prevent hypoglycaemia
3. Cerebral oedema and pulmonary oedema
Cerebral oedema associated with DKA is more common in children than in
adults.
Maybe influenced by the rate of the fluid administrations.
Elderly patients and those with impaired cardiac function are at particular risk
and monitoring of central venous pressure should be considered.
HYPERGLYCAEMIC
HYPEROSMOLAR STATE
(HHS)
It has higher mortality in compared to DKA and vascular
complications such as myocardial infarction, stroke or peripheral
arterial thrombosis are common.
Rapid changes in osmolality in the treatment may also be the prcipitant
of osmotic demyelination syndrome.
HHS may progress over many days while DKA occurred within hours.
Diagnostic criteria:
1. Hypovolaemia
2. Marked hyperglycaemia (blood glucose >30mmol/l)
3. Osmolality (>320mosmol/kg)
 PRECIPITATING FACTORS
FOR HHS
1. Infections and sepsis
2. Thrombotic stroke
3. Intracranial haemorrhage
4. Silent myocardial infarction
5. Pulmonary embolism

Management Goals:
6. Normalise the osmolality
7. Replace fluid and electrolytes imbalance
8. Normalise the blood glucose level
9. Prevention of the complications
 MANAGEMENT
-normalize the osmolality
-replace fluid and elecrolyte losses
use NS 0.9% for fluid replacement
hyperK,hypoK,hypoMG are common electrolyte imbalance
the rate of fall of plasma sodium should not exceed 10mmol/L in 24 hours.
Rapid sodium correction can worsen the cerebral oedema and can cause
osmotic demyelination syndrome
-Normalise blood glucose
iv infusion insulin might effective as some patient sensitive to insulin and rapis
insulin administrationcan lead tocrashing of glucose level
(the fall of glucose should be no more than 5mmol/L)
THANK YOU