Diabetes Mellitus

• Presented by Manam David HkawSeng Tu(330)

• RN – 321,328,330,335
 Contents
 Introduction
 Classification
 Diagnosis
 Complications
 Investigations
 Management
INTRODUCTION

A clinical syndrome with many causes which is

characterized by the presence of hyperglycemia
 Type 2 DM (around 90% of cases)
 Type 1 DM & others
 Presenting Features
Most cases are asymptomatic.

Acute – DKA(Hyperglycaemia), HHS

Subacute – Infection ( Pruritus Vulvae in female,

Balanitis in male )

Chronic – Microvascular, Macrovascular

Type 1 Diabetes Mellitus
 Autoimmune disorder
 T-cell mediated destruction of insulin-secreting
pancreatic ß cells
 Autoantibodies to islet cells
 Only when 80-90% of ß cell destruction – DM
symptoms
 Associated with other autoimmune diseases –
eg. Grave’s disease
Genetic factors
 HLA DR3, DR4, DQ
 Concordance rate between monozygotic twins-
30-50 %
Environmental factors

 Hygiene hypothesis- reduced exposure to microorganisms in

early childhood
 Viral infection- mumps, coxsackie B, retrovirus, rubella, CMV,
EBV
 Toxin – Dietary nitrosamines (smoked meats) & coffee
- Cow’s milk (Bovine serum albumin)
 Vitamin D deficiency ( But no clear cause-effect relationship
has been identified)
Pathogenesis of type 1 diabetes
 Type 2 Diabetes Mellitus
 Insulin resistance
 Pancreatic ß cell failure
-ß cell function loss by 50% in Type 2 DM at the time of
diagnosis

Genetic factors
 TCF7L2, TBC1D4 variation
 concordance rate between monozygotic twins-100%
Environmental factors
 Obesity ( BMI > 30 kg/m2 )
 Lack of physical activity
 Diet( high in saturated fats and refined carbohydrate )
 Economic deprivation, social disadvantages
 Excess alcohol consumption and smoking
Other risk factors

Age - old age

Ethnicity (Asian)

People with previous stress hyperglycaemia

Women with previous gestational diabetes

Natural history of type 2 diabetes
 Other forms of diabetes
Maturity Onset Diabetes of the Young(MODY)
- autosomal dominant, family history present

Latent autoimmune diabetes of adulthood(LADA)

- late onset type-1 diabetes, autoantibodies present

Pancreatic diabetes
- secondary to more generalized disease of pancreas
Diagnosis
Complications
ACUTE COMPLICATIONS

 Diabetic ketoacidosis(DKA)

 Hyperglycemic hyperosmolar state(HHS)/

Hyperosmolar non-ketotic diabetic coma(HONK)

 Hypoglycaemia (Blood Glucose < 3.9 mmol/L )

 Lactic acidosis (rare)

Chronic Complications
Diabetic Ketoacidosis(DKA)
 Definition
• Acute metabolic complication of diabetes that is a
consequence of absolute insulin deficiency

• Medical emergency
• Precipitated by underlying illness (most commonly UTI
and pneumonia) or physiological stress
Confirmation of Diagnosis of DKA
 Blood glucose >11 mmol/L or known diabetes
 Significant ketonemia (≥ 3mmol/L) or ketonuria (2+ or
more) and
 Metabolic acidosis (arterial pH < 7.3, venous
bicarbonate < 15mmol/L)
Hyperglycemic Hyperosmolar State(HHS)
DEFINITION
 A consequence of prolong relative insulin
deficiency
 Medical emergency
Characterised by
 Severe hyperglycemia (>30mmol/L )
 Hyperosmolality (>320mOsmol/kg)
 Dehydration without significant hyperketonemia
(<3mmol/L) or acidosis (HCO3 >15mmol/L)
 Usually affects elderly patients (Type 2 DM)

 Severe dehydration and hypernatraemia is common

 Mortality rates are 20% higher than DKA

Precipitating factors
 Infection – pneumonia, UTI, sepsis
 Medical stress (e.g. myocardial infarct, ischemic
stroke)
 Psychological disorders (depression, anxiety, eating
disorders)
 Drug therapy (e.g. glucocorticoids)
Hypoglycemia
• Following recovery, it is important to try to identify
a cause.

• Unless the reason is clear, it is advised to reduce the

next dose of insulin by 10%-20%.
Lactic acidosis
 A rare but serious complication of DM with metformin
use or septicemia
 Blood lactate >5mmol/l
 Seek expert help
 Treat sepsis vigorously, maintain blood BP and tissue
perfusion
 Stop metformin
Chronic Complications
Microvascular complictions
1.Diabetic Retinopathy (Blindness is preventable!)
 Annual eye screening by ophthalmologist
 3-5 years after diagnosis of type1 DM
 From diagnosis of type 2 DM

Management
Gradual glycemic control
Referral to ophthalmologist for laser photocoagulation
2. Diabetic Nephropathy

• Microalbuminuria (progress to frank proteinuria)

- due to damage and thickening of GBM
• End stage renal failure
- due to progressive lost of glomeruli from nodular
glomerulosclerosis

About 30% of type-1 diabetes patient develop

diabetic nephropathy from 10-20 years after
diagnosis.
3. Diabetic Neuropathy
-Occurs in 25%-30% of DM patients within 10-15
years after diagnosis

 Somatic neuropathy
• Polyneuropathy
• Mononeuropathy
 Autonomic neuropathy
• Polyneuropathy
 Symmetrical , mainly sensory and distal
-glove and stocking sensory impairment
-diminished proprioception and vibration sense

 Asymmetrical, mainly motor and proximal

-progressive weakness and wasting of proximal
muscles of limbs (diabetic amyotrophy)
-severe pain on anterior aspect of leg
• Mononeuropathy

 3rd and 6th cranial nerve (resulting in diplopia)

 7th cranial nerve (resulting in Bell’s palsy)
 Femoral and sciatic nerves
 Nerve compression palsies
-Median nerve compression (carpal tunnel syndrome)
-Ulnar nerve compression
-Lateral popliteal nerve compression (foot drop)
 Autonomic neuropathy

1. Cardiovascular
-postural hypotension, resting tachycardia, fixed heart rate
2. Gastrointestinal
-gastroparesis (abdominal pain, felling of fullness, nausea,
vomiting), constipation, dysphagia, nocturnal diarrhoea
3. Genitourinary
-recurrent infection, sexual dysfunction, urinary incontinence
4. Sudomotor
-gustatory sweating, anhidrosis
5. Vasomotor
-feet feel cold, dependent edema, bullous formation
6. Pupillary
-decreased pupil size (pinpoint pupil), delayed or
absent reflexes to light
Diabetic foot disease
 Loss of protective sensation (due to neuropathy)
 Inadequate blood supply

 Ulceration is initiated by (often minor) trauma and most

ulcers developed at the site of callus skin
 Majority of ulcers are neuropathic or neuroischaemic
 Charcot neuroarthropathy
(A) 10g monofilament (B) Foot pulses(Dorsalis pedis & posterior tibial)
Macrovascular complications
 DM is a strong risk factor in the development of
atherosclerosis.
 DM is also associated with other cardiovascular risk factors
such as hypertension, obesity & dyslipidemia.
o CVA (cerebrovascular accidents)
-TIA, stroke
o CAD (coronary artery disease)
-stable angina, acute coronary syndrome
o PAD (peripheral arterial disease)
Other complications
1.Dermatological complications
-necrobiosis lipoidica
-diabetic dermopathy (red -brown flat-topped papules)
-xerosis (dry skin)
 2. Infectious Complications
Increased risk of certain infections, e.g. Candidiasis

Increased risk of severe forms of infections, e.g. Covid-19

Increased risk of opportunistic infections, e.g.

Emphysematous pyelonephritis
3. Rheumatological Complications

 Cheiroarthropathy, limited joint movement

 Dupuytren’s contracture

 Adhesive capsulitis

 Trigger finger
4. Pregnancy related complications

 Congenital anomalies

 Misscariage and still birth

 Macrosomia

 Neonatal hypoglycaemia
Investigations for DM
 Investigations for Diagnosis
- blood glucose (venous plasma concentration is most
reliable)
- HbA1c, autoantibodies, C-peptides
 Investigation for Complications
- DKA (urine & blood ketones, ABG & bicarbonate)
- HHS (plasma osmolality
- Nephropathy (urinalysis & renal function test)
- CAD (ECG, CXY, Echo) with Lipid profile
- CVA (CT Head, carotid doppler)
- Infection (FBC, C&S, ESR, CRP, CXY)
 Investigation for Management – RFT & LFT for metformin
Management
Non-pharmacological management

1. Patient education
 Self-management
 Outcome depends on cooperation by the patient
 Nature of diabetes and its complication
 Its treatment
2. Diet and lifestyle
 Plate model
 Reduce sugar and saturated fat
 Weight management
 Regular exercise
 Cessation of smoking
 Moderate alcohol consumption
 Self-Assessment of Glycemic Control
 People with type-2 diabetes, usually only need to self
test capillary blood glucose regularly if they require
insulin or sulphonylurea therapy.

 People with type-1 diabetes, blood glucose testing 1–

4 times daily (depending on the intensity of the
prescribed regimen) helps guide insulin dosing and to
manage diet, exercise and illness.
Pharmacological management
 Type 1 diabetes is managed with insulin from the
time of diagnosis
 Type 2 diabetes lifestyle advice then drug therapy
Targeted HbA1c – 53mmol/mol (both Type-1 & 2)
Drugs to reduce hyperglycaemia
 Biguanides – metformin
 SGLT-2 inhibitors
 Incretin-based therapies – DPP-4 inhibitors & GLP-
1 receptors agonists
 Sulphonylureas
 Thiazolidinediones
Metformin
 Widely used as first-line therapy for type 2 diabetes
 Start at low dose (500 mg twice daily)
 Maintenance dose (1000 mg twice daily)

MOA
 Insulin sensitizer (  insulin sensitivity)
 Decreased absorption from the intestine
 Reduce hepatic glucose production
 Increase insulin-mediated glucose uptake
Advantages
 Weight loss
 Does not cause hypoglycaemia
 Decrease plasma lipid level ( LDL & VLDL )

Side effects
 GI side effects - anorexia, nausea, vomiting,
abdominal pain, diarrhea, taste disturbance
 Lactic acidosis
 Decrease B12 & Folate absorption

Contraindication – renal impairment (eGFR<30ml/min)

SGLT-2 inhibitors
( Dapagliflozin, empagliflozin and canagliflozin )
 With other agents second-line after metformin

MOA
 Inhibits sodium and glucose co-transporter in
proximal tubule  glycosuria  reduce blood sugar
Advantages
 Reduce CVS risk
 Also have reno-protective effect

Side effects
 Genital infection
 UTI
Incretin-based therapies
1.DPP4 inhibitor
( Sitagiptin, linagliptin, alogliptin, vildagliptin and
saxagliptin )
 Useful in combination with other drugs to get HbA1c
to target

MOA
 Inhibit dipetidyl peptidase 4
2. GLP1 receptor agonist

( Exenatide, liraglutide, semaglutide and dulaglutide )

 Now recommend should be started earlier (even
before metformin), in individuals at high risk of a
cardiovascular event
Advantages
 Weight loss
 Low risk of hypoglycaemia
 Low CVS risk

Disadvantages
 Increase risk pancreatitis or pancreatic cancer
 Expensive
 Sulphonylureas
( Glibenclamide, Glimepiride, Gliclazide, Glipizide )

 Used as add-on to other glucose-lowering therapy

MOA
 Insulin secretagogues ( promote pancreatic beta cell
insulin secretion)
Advantages
 Less GI side effect

Side effects
 Weight gain
 Hypoglycaemia
 Allergy
Thiazolidinediones
( Pioglitazone )

MOA
 PPAR- agonists
 Increase insulin sensitivity

Side effects
 Exacerbates cardiac failure by causing fluid retention
 Increase risk of bone fracture
 Possibly bladder cancer
 Weight gain
Insulin therapy
INDICATIONS
For all patients with type 1 diabetes

For patients with type 2 diabetes

- that is not adequately controlled by diet and/ or oral
hypoglycaemic agents
- with complications ( e.g., diabetic ketoacidosis,
gangrene of extremities )
- during stress ( surgery, child birth & infection )

During pregnancy
 Insulin types
1.Rapid acting insulin analogues
 Lispro, aspart, glulisine, fiasp

2.Short-acting
 Regular soluble insulin

3.Intermediate-acting
 Isophane ( NPH ), lente

4.Long-acting insulin analogues

 Glargine, detemir, degludec
 Insulin regimens
 Subcutaneous injection therapy

I. Once-daily regimen

II. Twice-daily regimen

III. Multiple daily insulin injection(MDI)/Basal bolus

regimen

IV. Continuous subcutaneous insulin

infusion(CSII)/Infusion pump
Intravenous injection therapy
- Fixed rate insulin infusion (FRII)
- Variable rate insulin infusion (VRII)/Insulin
sliding scale
 Other methods

• Sensory-augmented CSII therapy (artificial pancreas)

• DIY-APS ( Do it yourself artificial pancreas system )

 Side effects of insulin therapy
 Hypoglycaemia
 Weight gain
 Peripheral oedema
 Insulin resistance ( antibodies )
 Local allergy (rare)
 Presbyopia (Far-sightedness)
 Hypokalaemia
 Lipohypertrophy or lipoatrophy at injection sites
 Transplantation
Goals
 Facilitate independence from insulin
 Reduce complications and improve quality of life

Types
1. Simultaneous pancreas-kidney (SPK) transplant or
pancreas-after-kidney (PAK) transplant
2. Pancreas transplant alone (PTA)
3. Islet transplantation
After transplantation, life long immunosuppression is
needed.
 References
 Davidson’s principles and practice of medicine 24th
edition
 Oxford Handbook of Clinical Medicine, 10th edition
 Myanmar Diabetes Association
 Diabetes Canada 2018 clinical practice guidelines
 Lecture notes on Pharmacology Sixth Edition
THANK YOU