Diabetes mellitus

Dr.Sumaia Z.H.AbuElbasher
.MBBS.U N.UNVERSITY
MRCP. UK
Msc.C.PHARM.UMST
Objectives
1. State diabetes mellitus
2. Pathogenesis of DM.
3. Classifications
4. Clinical presentations.
5. Complications.
6. Management.
7. Emergencies.
Definition
• Diabetes mellitus is a clinical syndrome
characterized by hyperglycaemia due to
absolute or relative deficiency of insulin.

• Long-standing metabolic derangement can

lead to the development of complications of
diabetes, which characteristically affect the
eye, kidney and nervous system.
Types

Type I

Type II

MODY

Gestational DM
Pathophysiology
• Environmental factors interact with genetic
susceptibility to determine which people
develop the clinical syndrome, and the timing
of its onset.
Type I
• Associated with profound insulin deficiency
requiring replacement therapy.
• It is a T-cell-mediated autoimmune disease leading
to progressive destruction of the insulin-secreting β
cells.
• Classical symptoms of diabetes occur only when 80–
90% of β cells have been destroyed.
• Type 1 diabetes is associated with other
autoimmune disorders, including thyroid disease,
coeliac disease, Addison’s disease, pernicious
anaemia and vitiligo.
Type II
• Type 2 diabetes is only diagnosed after excluding
other causes of hyperglycaemia, including type 1
diabetes.
• Patients retain some capacity to secrete insulin but
there is a combination of resistance to the actions
of insulin followed by impaired pancreatic β-cell
function, leading to ‘relative’ insulin deficiency.
• Associated with insulin resistance.
• Older age
Features of the insulin resistance (metabolic)
syndrome
1. Hyper-insulinaemia
2. Type 2 diabetes or impaired glucose tolerance
(IGT)
3. Hypertension
4. Dyslipidaemia (↑LDL cholesterol, ↑triglycerides,
↓HDL cholesterol)
5. Non-alcoholic fatty liver
6. Central (visceral) obesity
7. Increased fibrinogen and uric acid.
8. Polycystic ovarian syndrome
Gestational DM
• 4% of pregnancies are complicated by DM: either pre-existing type 1
or 2 DM (<0.5%), or new-onset gestational diabetes (GDM) (>3.5%).
• All forms carry an increased risk to mother and foetus: miscarriage,
pre-term labour, pre-eclampsia, congenital malformations,
macrosomia, and a worsening of diabetic complications, eg
retinopathy, nephropathy.
• Risk of GDM :
1. Aged over 25
2. Family history
3. Weight gain
4. Non-Caucasian
5. HIV+ve
6. Previous gestational DM.
Other forms of DM
1. Pancreatic disease
• pancreatitis, haemochromatosis, cystic fibrosis.
2. Excess endogenous production of insulin antagonists
• Acromegaly, Cushing’s disease, thyrotoxicosis.
3. Genetic defects of β-cell function (e.g. maturity-onset
diabetes of the young (MODY), a rare autosomal
dominant disease, < 5% of diabetes cases
4. Drug-induced diabetes
• Corticosteroids, thiazides, phenytoin.
CLINICAL PRESENTATION
Clinical presentation
1. Fatigability.
2. Hyperglycemic symptoms
a. Polyurea
b. Polydipsia.
c. Weight loss.
2. Recurrent infections.
3. Complications.
Complications

Micro-vascular

Macro-vascular
Micro-vascular

1. Nephropathy .

2. Neuropathy .

3. Retinopathy .
Macro-vascular
1. Cardiovascular complication.

2. Cerebrovascular complication .
Investigations
1. Urine analysis.
2. Fasting blood sugar.
3. OGTT.
4. Random blood sugar.
5. HB A1c
6. RFT
7. ECG
Management

Non pharmacological

Pharmacological
Non pharmacological
1. Life style modification.
2. Nutritional advice.
3. Exercise.
4. Smoking cessiation
5. Foot care.
Diabetes Canada CPG – Chapter 13. Pharmacologic Glycemic Management 2018
of Type 2 Diabetes
Pharmacotherapy in Type 2 Diabetes
Checklist
 CHOOSE initial therapy based on glycemia
 START with metformin +/- others
 INDIVIDUALIZE your therapy choice based on
characteristics of the person with diabetes
and the agent
 REACH TARGET within 3-6 months of diagnosis
Pharmacological

Treatment DM

Cardiovascular risk
 Pharmacology of diabetes Mellitus

Oral hypoglycemic agents

Insulin

24
 Oral hypoglycemic agents

Insulin secretagogues

Insulin Sensitizers

25
Insulin secretagues

Sulphonylurease

None-Sulphonylurese

26
Insulin Sensitizers

.Biguanides

Thiazolidinediones

27
α-Glucosidases inhibitors

Acarbose

Miglitol

28
α-Glucosidases inhibitors

Acarbose

Miglitol

29
Incretin mimetics

Exenatide

Sitagliptin

30
Types of insulin
Ultra short or rapid acting

Short acting

Intermediate acting

Long acting

31
Types of insulin
Insulin type (trade name) Onset Peak Duration
BOLUS (prandial or mealtime) insulins
Rapid-acting insulin analogues (clear)
● Insulin aspart (NovoRapid®) 9–20min 1–1.5h 3–5h
● Insulin glulisine (Apidra®) 10–15min 1–1.5h 3.5–5h
● Insulin lispro (Humalog®) U-100 U-200 10–15min 1–2h 3–4.75h
● Faster-acting insulin aspart (Fiasp®) 4min 0.5-1.5h 3-5h

Short-acting insulins (clear)

• Insulin regular (Humulin®-R, Novolin® ge Toronto) 30min 2–3h 6.5h
• Insulin regular U-500 (Entuzity® (U-500) 15min 4-8h 17-24h

BASAL insulins
Intermediate-acting (cloudy)
• Insulin neutral protamine Hagedorn (Humulin® N, 1–3h 5–8h Up to 18h
Novolin® ge NPH)

Long-acting insulin (clear) 90min Not applicable U-100 glargine 24h,

• Insulin detemir (Levemir®) detemir 16–24h
• Insulin glargine U-100 (Lantus®) U-300 glargine >30h
• Insulin glargine U-300 (Toujeo®) degludec 42h
• Insulin glargine biosimilar (Basaglar®)
• Insulin degludec U-100, U-200 (Tresiba®)

PREMIXED insulins
Premixed regular insulin –NPH (cloudy) A single vial or cartridge contains a fixed ratio of insulin
• Humulin® 30/70 (% of rapid-acting or short-acting insulin to % of intermediate-acting insulin)
• Novolin® ge 30/70, 40/60, 50/50

Premixed insulin analogues (cloudy)

• Biphasic insulin aspart (NovoMix® 30)
• Insulin lispro/lispro protamine (Humalog® Mix25 and
Mix50)
2018 Diabetes Canada CPG – Chapter 13. Pharmacologic Glycemic Management
of Type 2 Diabetes
Initial choice of therapy
A1C <1.5% over target
A1C ≥ 1.5% over target
Initiate healthy behavior
interventions and start metformin
if not at target in 3 months
OR
Start metformin with healthy
behavior interventions
Start metformin with healthy
behavior interventions
AND
Consider second concurrent
agent
Diabetes Canada CPG – Chapter 13. Pharmacologic Glycemic Management 2018
of Type 2 Diabetes

Initial choice of therapy

Symptomatic • Polyuria
Hyperglycemia • Polydipsia
and/or • Weight loss
Metabolic • Volume depletion
Decompensation

Start INSULIN +/- metformin

Emergency

1. Dibetics ketoacidosis (DKA)

2. Hyperosmolar non ketotic (HONK)
3. Hpoglycemia