DIABETES MELLITUS

(DM)
Content
Definition,Pathophysiology & causes of DM
Types of DM
Symptoms
Management & Treatment
Complications of Diabetes

What is Diabetes Mellitus?

Persistent high blood sugar levels.
Diabetes is derived Greek word diabanein
that means "passing through," (excess urine)
Mellitus from Latin means honey the blood
& urine of a diabetic has a sweet taste.
It does not have a cure but can be managed.

Pathophysiology
Insulin is released into the blood by beta cells (cells) in the pancreas in response to rising levels
of blood glucose (e.g after a meal).
Insulin regulates uptake of glucose from the blood
into cells.
If insulin is absent or insufficient, glucose
accumulates in blood causing a metabolic
disorder called diabetes mellitus.

PANCREAS
|
ISLETS OF LANGERHANS

\
Beta cells
alpha cells

\
Insulin
Glucagon

\
Cells & liver glucose uptake
Glycogenolysis

Glycogenesis

Causes of diabetes
The absolute lack of insulin esp.in IDDM.
Insufficient production of insulin.
Production of defective insulin.
Inability of cells to use insulin properly and
efficiently especially cells of muscle and
fat tissues causing "insulin resistance."
This is the primary problem in NIDDM
A steady decline of beta cells

DM Risk factors
Obesity
DM family history of DM
Age greater than 45 years
Pregnancy diabetes or delivering a baby
weighing more than 3.5 kg
High blood pressure
High blood levels of triglycerides (a type of
fat molecule)
High blood cholesterol level

TYPES OF DM
Type 1 - insulin dependent diabetes mellitus
(IDDM)
Type 2 - non insulin dependent diabetes mellitus
(NIDDM),
Gestational Diabetes occurs during pregnancy

1. TYPE 1 (IDDM)
Also called childhood or juvenile diabetes
Is characterized by loss of beta cells due to
autoimmune destruction.
No preventative measure can be taken (Diet
and exercise cannot reverse or prevent it).
Insulin is the principal treatment and must be
continued indefinitely.

2. TYPE 2 (NIDDM)
Also known as adult or maturity-onset diabetes
It is due to defective insulin secretion &/or
insulin resistance or reduced insulin sensitivity.
Characterized by elevated levels of insulin in
the blood
Medications used improve insulin sensitivity or
reduce glucose production.
Obesity is known to predispose people for
insulin resistance

3. GESTATIONAL DIABETES
Occurs in pregnancy esp. after the 24th week.
Similar to type 2 diabetes, it involves insulin
resistance
The hormones of pregnancy cause insulin
resistance in genetically predisposed women.
It occurs in 2-5% of all pregnancies
Normally disappears after delivery
20-50% of these women develop type 2 diabetes
later in life, especially if they are overweight.
It requires careful medical supervision

Symptoms & clinical manifestation

The common symptoms of both IDDM and
NIDDM are:
- polyuria
- polydipsia - weight loss
- nephropathy - blurred vision

Common features of Type 1 are:

diabetic ketoacidosis, postural
hypotension and in severe cases coma.
Patients with type 2 diabetes may not
show any symptoms but chronic skin
infections are quite common

 High blood sugar levels loss of glucose in

the urine increased urine output
dehydration.
Dehydration increased thirst increased
water consumption.
Glucose not utilised body makes glucose
from stores weight loss despite an increase in
appetite.
Some untreated diabetes patients also complain
of fatigue, nausea and vomiting. Patients with
diabetes are prone to dev

MANAGEMENT
NIDDM
Life style changes-limit salt intake, loose
weight & exercise
Type 2 diabetes is usually 1st treated by :
Increase physical activity (exercise)
The diet (decrease carbohydrate intake)
Weight loss
Drugs
Insulin (can be used for both type I & II)
Oral antidiabetes (cannot be used in type I)

INSULIN
Insulin is required by all type 1 diabetic patients.
Types:
- bovine (beef)
- porcine (pork)
- human insulin.
Bovine insulin is more antigenic as it differs from
human insulin by 3 amino acids while porcine
differs by only one amino acid
Functions of Insulin
- helps glucose enter the cells,
- regulates the level blood sugar

Insulin preparations
Preparations are of three types:Short acting with rapid onset of action e.g soluble
(neutral) insulin (actrapid)
Intermediate acting e.g isophane insulin
Long acting with slow onset of action e.g insulin
zinc suspension Long acting with slow onset of
action e.g insulin zinc suspension

NB: Short & long acting can be combined to

ensure rapid onset with long action e.g.
mixture of soluble insulin and isophane insulin
(human mixtard)

Pharmacokinetics
Insulin undergoes extensive FPE.
Metabolism: mainly liver and kidney.
Soluble insulin has a duration of action
of 4-8 hours and can be given thrice
daily
Intermediate acting ones require BD
dosing
Insulin is mostly given half an hour
before a meal (why)

Adverse effects of Insulin

Hypoglycemia (most common),
symptoms include palpitations,
tremor, tachycardia hunger and
sweating
Thickening of subcutaneous tissue
can occur at injection sites (advise
patient to change injection site often)
Systemic allergic reaction do occur
but rarely

ORAL ANTIDIABETES DRUGS

The oral antidiabetes drugs are of two kinds:
Sulphonylureas
Biguanides
NB: are not used in type 1

SULPHONYLUREAS
MoA:
- increase cell sensitivity to glucose
- increases tissue sensitivity to glucose
Secondary failure can occur after
months or years of treatment due to
decline in cell function.
Pharmacokinetics: they undergo hepatic
metabolism with some having active
metabolites

Sulphonylureas contd
Glibenclamide has a short elimination
half-life but has a long biological effect
due to slow distribution
Adverse effects: hypoglycaemia and
weight gain
Dose: glibenclamide is usually in a dose
of 5 mg daily (max 15mg)
Interactions: effects may be enhanced
by alcohol.

BIGUANIDES
MoA: inhibit hepatic gluconeogenesis.
Pharmacokinetics: Metformin is not
hepatically metabolized and is totally
renally eliminated.
S/Es: GI disturbance eg anorexia,
nausea abdominal discomfort and
diarrhoea

Biguanides contd
Dose: Metformin 500 mg TID, with meals
(max 3g )
Interactions: metformin use with alcohol
increases lactic acidosis risk
NB: Metformin is the drug of choice in
overweight patients

OTHER ANTIDIABETES
Acarbose
MoA: Inhibits intestinal alpha glucosidases
Delays the digestion and absorption of starch
and sucrose
Can be used on its own or as an adjunct to
metformin or Sulphonylureaus
Should be taken before the meal with water or
chewed with food.
S/Es: flatulence, diarrhea, abdominal distention
& pain, abnormal liver function tests.

Other antidiabetes contd

Nateglinide and Repaglinide stimulate
insulin release
They have rapid onset of action and
Short duration of activity
To be administered shortly after main
meal
Thiazolidinediones eg pioglitazone,

rosiglitazone. They reduce peripheral

insulin resistance. May be used alone or
with metformin and sulphonylureas.

Complications of Diabetes
Eye disease ( Cataract, retinopathy ) do
routine checks toprevent blindness.
Nephropathy (due to protenuria,
decreaase in glomerular filtration rate,
increased microalbumin)
Neuropathy ( nerve dermage )
Diabetic foot (counsel patients to prevent)
Hypertension
Hypoglycaemic or insulin-induced coma
Hyperglycaemic coma or diabetic coma

CONCLUSION & SUMMARY

Risk Factors For Diabetes Mellitus:
-Family histry, HPT, age>45,pg,
obesity,high cholesterol
Treatment of Diabetes Mellitus
Type 1:- Diet, exercise and Insulin.
Type 2
* Diet and exercise alone
* Diet, exercise and hypoglycaemic agents
* Diet, exercise plus insulin (oral
hypoglycemic agents may also be used).

Treating Diabetes with HPT

Target Bp is 130/80
Advantage of propranolol : blocks
glycogenolysis.
ACE inhibitors e. g. Captopril and
Enalapril have a protective effect on the
kidneys and should be used for
hypertension or when proteinuria is
present.

 FBS fasting blood sugar (after 8-10hr fast, in

the mourning) 3.9 to 5.5 mmol/L normal,
(5.6 to 6.9 mmol/L) pre diabetes, (>7.0
mmol/L) diabetes.
A normal blood glucose level is less than 6.1
mmol/L, when measured after a fast.
The glucose levels we aim for less than 7
mmol/L

Role of pharmacy personnel in DM

management
Counsel & emphasis on the need &
advantages of life style modification.
Monitor patients blood sugar levels and
encourage patients to do self monitoring.

Questions
What is the normal blood glucose level.
What glucose level do you aim at when
treating DM.
Which is the best therapy for gestational
diabetes?