Top ten countries for estimated number of

adults with diabetes, 1995 and 2025

Country

1995 (millions)

Rank
1
India
2
China
3
U.S.
4
Russian Fed.
5
Japan
6
Brazil
7
Indonesia
8
Pakistan
9
Mexico
10
Ukraine
All other countries

19.4
16.0
13.9
8.9
6.3
4.9
4.5
4.3
3.8
3.6
49.7

Total

135.3

Country

2025 (millions)

India
China
U.S.
Pakistan
Indonesia
Russian Fed.
Mexico
Brazil
Egypt
Japan

57.2
37.6
21.9
14.5
12.4
12.2
11.7
11.6
8.8
8.5
103.6
300.0
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DIABETES MELLITUS
Cardio metabolic syndrome
Characterized by persistent
Hyperglycaemia due to absolute or
relative deficiency of insulin/ insulin
resistant.

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CLASSIFICATION
Primary
Type 1 or insulin dependent diabetes
mellitus (IDDM)
Type 2 or non-insulin dependent
diabetes mellitus (NIDDM)

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 Other specific types of diabetes

Pancreatic Disease
e.g.
Pancreatitis, Haemochromatosis,
Neoplastic disease, Pancreatectomy,
Cystic Fibrosis

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 Excess endogenous production of

hormonal antagonist to insulin
Growth hormone Acromagaly
Glucocorticoids Cushings Syndrome
Thyroid hormones Hyperthyroidism

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 Catecholamines
Phaeochromocytoma
Human placental lactogen
Pregnancy
Glucagon Glucagonoma
Counterregulatory hormones Severe
burns, trauma

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 Medication
e.g. corticosteroids, thiazide diuretics,
phenytoin

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 Associated with genetic syndromes

didmoad-diabetes insipidus, diabetes
mellitus, optic atrophy, nerve deafness
lipoatrophy, muscular dystrophies,
downs syndrome, klinefelters syndrome,
turners syndrome

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ENVIRONMENTAL FACTORS

Bovine serum albumin (cows milk)

Viruses
Stress
Auto immune

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Gestational Diabetes

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PATHOPHYSIOLOGY of type 2
diabetes
Complex mechanism
Combination of resistance to action of insulin.
Impaired pancreatic beta cell function.

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Visceral Fat Topography

Visceral Fat

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INSULIN RESISTANCE

Excessive production of glucose in liver.

Under utilization of glucose in skeletal muscles.
Due to resistance to action of insulin.
Hyperinsulinmia Water and Sodium

retention Hypertension

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 Associated, obesity, dyslipidaemia (increased LDL

and low HDL) metabolic syndrome
Presence of obesity is amplifier of the insulin
resistance

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Natural History of T2DM

Post Meal Glucose

350
250

Glucose

Fasting Glucose

150
50

Insulin Resistance

300

Relative 200
Function
100
0

At risk for
Diabetes
-10

-5

Insulin Level

Beta Cell Failure

0

10

15

20

25

30

Years of Diabetes
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Major Factors Involved In

Pathogenesis of T2DM
Insulin Resistance
-Acquisition of visceral obesityleads to
Lipotoxicity, & impaired Insulin signaling
Beta Cell Secretory Defects
-Impaired first phase insulin release
secondary to Lipotoxicity, Glucotoxicity, & loss
of Incretion secretion
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Proinsulin
Ca2+-dependent
endopeptidases

Insulin

C peptide

MW

PC2
(PC3)

A Chain

B Chain
PC3

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Insulin Release: Normal Levels

Units: 1 U = 36 g, i.e. 28 U/mg
Daily secretion in humans: 40 - 50 U
Basal plasma insulin: 12 U/ml
Postprandial insulin: up to 90 U/ml
120

Meal

100
80
60

80

40

Basal
Minutes 0

20

30

60

90

120

Insulin, U/ml

Glucose, mg/dl

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Insulin metabolism
Secreted into portal circulation
50%

of degradation in liver
50% of degradation in other target tissues
and kidney
Enzymatic degradation follows receptormediated endocytosis
Plasma

half-life: 3 - 5 min.

Circulates as free monomer

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WHAT IS NEW
Intra-abdominal or central adipose tissue is metabolically
active.
Release large quantities of FFA.
Compete with glucose as fuel supply for oxidation
inhance insulin resistance

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 Central adipose tissue release number of

hormone (adipokines) act on specific receptor
influence on insulin sensitivity.
Visceral adipose tissue drain to portal vein
influence on liver insulin sensitivity
gluconeogenosis and hepetic lipid metabolism.
ROLE OF EXERCISE
Inactivity is associated with down regulation of
insulin sensitive kinase increased FFA (in
muscles)

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Pancreatic Beta Cell Failure

In early stage Decreased in total mass of
pancreatic islet tissue Pancreatic cell damage.

What is new
Deposition of amyloid in beta cell beta cell
destruction.

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Hypothesis
Polypeptide (Amylin) is secreted together with
insulin.
Form insoluble fibrils of amyloid Destruction
of beta cells.
Number of beta cell reduced to 20-30% but
alpha cell mass unchanged glucogen
secretion increased hyperglycemia.

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Other Factor
GENETIC PREDISPOSITION
Many genes are involved.
More than 200 .. Gene are found.
Three gene polymorphism
Genefor PPARY (Beta cell K ATP channel.
Onchromosoe 1g, 12g 20g

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ENVIRONMENTAL FACTOR
Obesity Risk increased when BMI is > 30 kg m2
Overeating total calorie content (sweat foods
and carbohydrate)
Lack of exercise

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METABOLIC DISTURBANCE
Slow onset of relative insulin deficiency
Lipolysis and glucose uptake is maintained so dont
occur weight loss and keto acidosis.
In type-II diabetes hyperglycemia develops slowly over
months or years renal threshold rises osmatic
symptoms less marked

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GHB

Clinical Feature

Polyuria and thirst

Weakness or fatigue
Polyphagia and weight loss
Blurring of vision
Vulvovaginitis or pruritus
Nocturnal enuresis
Asymptomatic
May presented with acute complication
May presented with late complications
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Clinical history, physical exam, ambient glucose levels and
degree of ketosis usually suffice appropriate diagnostic
Classification.
In equivocal setting.
a) C-peptide or insulin level (low in type I DM)
b) Glutamic acid decarboxylase a.b
c) Pancreatic islet cell a.b (+ in 90% of new onset type 1
D.M)

All action Allow correct classification

31

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Clinical Examination
Physical Exam. must include height, weight, blood pressure.
Vision measurement and exam. of eye grounds.
Baseline neurological and cardiovascular exam. should be obtained.
The foot exam. should include peripheral pulses, sensation .
Skin exam. for diabetic dermopathy.

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 Laboratory Evaluation For Newly Diagnosed Diabetes

Urinanalysis,
Fasting glucose & Random Blood glucose
OGTT
HbA1C,
Fractusamine Test

Other Investitagation

Lipid profile,
, Creatinine,
Electrolytes, TSH.

ECG for patient over 40 years.

should be measured annually.

33

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Criteria for Diagnosis

Fasting plasma glucose > 126 mg/dl, or
Symptoms plus random plasma glucose >
200 mg/dl, or
Two-hour plasma glucose > 200 mg/dl on
OGTT of 75 gm glucose

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Criteria for Diagnosis

Normal

Impaired

Diagnosti
c

Fasting

< 110

110 125
IFG

126

OGTT

< 140

140 199
IGT

200

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Indications For OGTT

1.
2.

Patients with Impaired Fasting Glycemia (IFG)

Pregnant women and postpartum (in women with GDM)
* OGTT is performed using a 75 oral glucose load in
the morning after a noncaloric 8hr fast. Water is allowed
but not coffee or smoking.

Types of Curves when performing OGTT

Normal curve
IGT
Diabetic curve
Lag storage curve
Flat curve

1.
2.
3.
4.
5.

36

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Pre-diabetes
1.

2.

Impaired Fasting Glucose (IFG)

FPG 100mg/dl (5.6 mmol/L) to 125 mg/dl (6.9 mmol/L)
Impaired Glucose Tolerance (IGT)
2 hr plasma glucose 140mg/dl (7.8 mmol/L) to 199 mg/dl
(11.0 mmol/L)
Both IFG and IGT are risk factors for future diabetes and for
cardiovascular disease and associated with insulin resistance
and
metabolic syndrome.
Unless lifestyle modifications are made most people with prediabetes
develop type 2 diabetes within 10 years.
37
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HbA1c
Glycosylated haemoglobin
Average blood glucose over last 8-12 weeks
Is not diagnostic

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GHB

MANAGEMENT OF DM
50% ----DIET
25% ----OHD
25%-----INSULIN
Type of treatment is determined by serum insulin level or by
age and weight (<40 or >40, over wt or normal wt)
LIFESTYLE MODIFICATIONS SHOULD BE STRESSED TO
ACHIEVE GOAL

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 Eat less walk more

Reduce calories
Burn calories

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THERAPEUTIC GOAL
NEAR NORMAL METABOLISM
1.
2.
3.

Normal blood sugar

Normal body weight
Normal metabolic profile

ALL WILL LEAD TO RETARD

VASCULAR AND SPECIFIC DIABETIC
COMPLICATIONS

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DIABETIC DIET

2 TYPES
1. LOW ENERGY, WT-REDUCING DIETS FOR
HIGH BMI
2. WT MAINTENANCE DIETS FOR NORMAL
BMI

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AIMS OF DIETRY MANAGEMENT

ABOLISHES HYPERGLYCEMIC SYMPTOMS

REDUCE BLOOD SUGAR
ACHIEVE WT REDUCTION IN OBESE
AVOID HYPOGLYCEMIA
AVOID WT GAIN
AVOID ATHEROGENIC DIET

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ORAL HYPOGLYCAEMIC DRUGS

MOST DEPENDS UPON SUPPLY OF
ENDOGENOUS INSULIN
SUPHONYNUREAS
BIGUNIDES
ALPHA-GLUCOSIDASE INHIBITORS
THIAZOLIDINEDIONES
MEGLITINIDES
INCRETINS
DPP 4 IN HIBITORS
AMYLIN ANALOGUE
SGT INHIBITORS
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SULPHONYLEUREAS

MECHANISMS
INSULIN SECRETOGOGUES
DECREASES HEPATIC RELEASE
INCREASE IN WT AND PRODUCE INSULIN
RESISTANCE
EXAMPLES:
1. FIRST GENERATION---TOLBUTAMIDE AND
CHLORPROPAMIDE
2. SECOND GENERATION---GLICLAZIDE ,
GLIPIZIDE,GLIBENCLAMIDE, GLIMEPRIDE
Primary treatment failure and secondary
treatment failure
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BIGUANIDES
MECHANISMS
INCREASE INSULIN SENSITIVITY NAD
HENCE INCREASE PERIPHERAL UPTAKE
OF GLUCOSE BY TISSUE
IMPAIRS GLUCOSE ABSORPTION FROM
GUT
INHIBITS HEPATIC GLUCONEOGENESIS
PREFERRED IN OBESE
CONTRAINDICATED IN
RENAL, HEPATIC FAILURE AND
ALCOHOLICS
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ALPHA-GLUCOSIDASE INHIBITORS
INHIBITS DISACCHARIDASE OF GUT MUCOSA
AND HENCE DELAY CHO ABSORPTION
CAUSES FLATULENCE,DIARRHOEA AND
ABDOMINAL BLOATING

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THIAZOLIDINEDIONES(TZD,GLITAZ
ONES,PPAR gamma AGONIST)
BINDS AND ACTIVATES PEROXISOME
PROLIFERATOR-ACTIVATED
RECEPTOR GAMMA , THUS
ENHANCING ACTION OF
ENDOGENOUS INSULINGOOD IN
INSULIN RESISTANCE SYNDROM
ROSIGLITAZONE AND PIOGLITAZONE
SHOULD BE COMBINED WITH SU OR
METFORMIN
CAUSES FLUID RETENTION (C/I IN
CCF) AND OBESITY
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MEGLITINIDES(ORAL PRANDIAL OR
FIRST PHASE INSULIN SECRETOR)
REPAGLINIDE AND NATEGLINIDE

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DPP4 inhibitors
Sita glipition
Vilda gliption

SGT inhibitors
KANA , gliflozin

COMBINED ORAL AND INSULIN

IN SECONDARY TREATMENT FAILURE ORAL
AND ISOPHANE INSULIN SHOT AT NIGHT CAN
BE VERY EFFECTIVE TO PREVENT RESIDUAL
BETA CELL FAILURE.
INEFFECTIVE IN C-PEPTIDES NEGATIVE
PATIENTS

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INSULINS(100u/ml)
FAST-ACTING---LISPRO
SHORT-ACTING
SOLUBLE,REGULAR,UNMODIFIED
INTERMEDIATE-ACTING,ISOPHANE ,LANTE,NPH
LONG-ACTING, BOVINE ULTRALENTE
LONG-ACTING,INSULIN ANALOGUE GLARGIN

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Diabetes Mellitus
Medications
Injectable
Humulin

Glucagon

Diabetes Mellitus
Insulin Pumps
Device a little bit larger than a pager that delivers insulin
via a small plastic infusion set usually located in abdomen
Infusion set is usually moved every 2-3 days

INSULIN THERAPY IN DM TYPE - 2

COMBINATION OF OAA & INSULIN
METFORMIN & OR SU AND BEDTIME NPH
IF TARGET NOT REACHED IN 4-8 WKS

INSULIN STAGE 2
(2/3)R/N(1/2) 0 (1/3) R/N (1/1) - 0
INSULIN STAGE 3
(2/3)R/N(1/2) 0 R(1/6) N(1/6)
INSULIN STAGE 4
R(20%) R(25%) R(25%) N(30%)

How to draw insulin?

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1 vial use

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Humulin-N
or
Humulin-70/30
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GHB

3 Roll the bottle of insulin gently between the palms of your

hands .This will mix the insulin well. Do not shake,
Shaking leaves air bubbles that can get into the syringe

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3 Clean the tip of Bottle with alcohol swab

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1 vial use
for example
40 units
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Take the needle cap off the syringe.

Hold the syringe with needle pointing toward the ceiling .
Keep syringe at eye level , so you can easily see the
markings on the barrel.
You must put air into the insulin bottle before you can get the insulin out
of the bottle .First ,pull the syringe plunger down until the top of the
black tip crosses the mark of the dose to be taken .This draws air
into the syringe. For example : If you take 40 units of insulin , draw
about 40 units of air into syringe .
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Now turn the syringe tip down . Put the needle through
the rubber stopper of the insulin bottle .Push down all the
way on the plunger, and hold the plunger in. This puts air
into the bottle

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Make sure the tip of needle is in the insulin .Pull down slowly
on the plunger . This brings insulin into the syringe .
Pull down slowly on the plunger to the exact line of your insulin
dose . The right amount of insulin now be in your syringe
Look in the syringe for air bubbles .If you see air bubbles , push
the insulin back into the bottle . Then pull the plunger back
to the exact line of your insulin dose .If the bubbles are still
in the syringe, repeat the process until they are gone.
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When all the bubbles are out and you have the right
dose ,pull the bottle straight up and off the needle .Put
the needle cap back on the syringe over the needle .
You will know that its right if the top of the plunger
crosses the right mark on the syringe and there are no
air bubbles.
Now you are ready to give yourself your shot .Take a deep
breath and let it out slowly to help u relax.
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2 vials use
Mixing 2 vials of Insulin
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Humulin-R
and
Humulin-N

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1 Gather all of your equipment :

Syringe
Alcohol swab
Insulin
2 Wash your hands.
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3 Roll the bottle of insulin gently between the palms of your

hands .This will mix the insulin well. Do not shake,
Shaking leaves air bubbles that can get into the syringe

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3 Clean the tip of Bottle with alcohol swab

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GHB

Pull 20 units of air into the empty syringe . Put the

needle through the rubber stopper of the bottle of
cloudy insulin( Humulin N) while its placed on table.
Push air into the bottle .Remove the needle.

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Pull 10 units of air into the same empty syringe .Put

the needle into the Humulin Regular (R) insulin bottle .
This insulin is clear .Push air into the bottle.

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With the needle still in the Regular insulin bottle ,turn the
bottle upside down . Pull plunger halfway down the syringe .
This brings insulin into the syringe .Push the insulin back into
the bottle to get rid of the air bubbles . Now pull your dose of
insulin into the syringe .Carefully measure 10 units of clear
insulin (Humulin R). Pull the syringe out of the bottle

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Turn the cloudy Humulin N insulin bottle upside down .Put

the plunger back slowly to total 30 units .Pull the bottle
off the needle.
Clear the total dosage . The dose should be :
Humulin N (cloudy) 20 units .
Humulin R (clear) 10 units .
Total of 30 units now in the syringe

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Sites of Injection

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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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How to inject Humulin?

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GHB

If desired .clean the spot with alcohol .Let dry

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Remove the top from the needle .Hold the

syringe in one hand as you would hold a
pencil.
With your other hand ,pinch up a couple of
inches of skin .
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Stick the needle straight into the pinched skin .Put the
needle all the way in through the skin with one smooth
motion
Relax the pinch ,and slowly push the plunger all the way
down.
Be sure the insulin is in ,then remove the needle.

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Lightly press down on the side BUT dont RUB. Dont worry if a
drop of blood
appears where the needle was.
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When you are ready to discard your used needles and

syringes , break the needle and put them into a hard plastic
or metal container with a screw-on lid .Label and discard
according to local regulations.
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TELL YOUR PATIENT

TO

Record the insulin dose you just gave yourself in your

diabetes diary.

It may be hard to give yourself a shot for the

first time ,but with practice it will become much
easier.

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ACUTE METABOLIC
COMPLICATIONS

HYPOGLYCAEMIA
DIABETIC KETOACIDOSIS
NON-KETOTIC HYPEROSMOLAR COMA
LACTIC ACIDOSIS

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LONG TERM COMPLICATIONS

DYSLIPIDAEMIA
CARDIOVASCULAR DISEASES
DIABETIC RETINOPATHY
DIABETIC NEPHROPATHY
DIABETIC NEUROPATHY
DIABETIC FOOT
DIABETES AND PREGNANCY
DIABETES AND SURGERY

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a)
b)
c)
d)
e)

Urine for sugar

FBS blood sugar more than 126mmd/l
HBA1C
OGTT
RBS More than 200

Q.2 Which of Following are micro vascular

complications of diabetes?
a)
b)
c)
d)
e)

Retinopathy
Nephropathy
Diabetic foot
Cataract
Neuropathy

Q.3, 50 year patient is going for dental

surgery his blood sugar is 300 which of
following treatment is appropriate?
a)
b)
c)
d)
e)

Metformin
Glimepride
Rapid acting Insulin
Ultra Short Acting Insulin
Insulin determir

Q.4 Which of the following Drugs are not

used in treatment of diabetes with CRF?
a)
b)
c)
d)
e)

Metformin
Insulin
Captopril
Glibenclamide
Meglitinide