Ablilasha Ashish Divya Gayatri Sarita Shrutika:: Presented by

Presented by:
Ablilasha
Ashish
Divya
Gayatri
Sarita
Shrutika
October 3, 2009 SIESCOMS Group 5 1
Diabete
s
DIABETES
• Chronic disease which arises when pancreas do not produce

 enough insulin or when body cannot use the insulin it produces .

• Characterized by hyperglycemia, glycosuria, hyperlipidemia.



TYPES OF DIABETES
2 Types of Diabetes

Insulin dependent diabetes mellitus.
Autoimmune disorder.
Insulin circulation is low.
Antibodies that destroy β -cells of islets of langerhans

detected in blood.
Juvenile diabetes.

TYPE II DIABETES Diabet
es
Non insulin dependent mellitus
Pancreas produce adequate insulin but body craves for more.

Insulin resistance
Causes may be
oAbnormality in gluco-receptor of B-cells
oExcess of hyperglycemic hormones
oMost common form of diabetes.
o
o

Diabet
GESTATIONAL DIABETES es
Some women develop it during pregnancy.

Few symptoms
Disappears when pregnancy ends




SYMPTOMS Diabetes

Frequent urination
Excessive thirst
Increased hunger
Weight loss
Tiredness
Lack of interest and concentration
Vomiting and stomach ache
Tingling sensation in foot
Blurred vision
Slow healing wounds

MOST PEOPLE WITH DIABETES DO NOT NOTICE ANY
SIGNS…

RISK FACTORS

Obesity and overweight
Lack of exercise
Unhealthy diet
A family history of diabetes
High blood pressure
High cholesterol
Increased age
Ethnicity.



INSULIN Diabetes
vSecreted by beta cells of islets of langerhans.
vPREPROINSULIN
v
REGULATION OF INSULIN SECRETION:
Chemical, Hormonal and Neural mechanisms.
1. Chemical: Activation of glucoreceptor
2. Neural I. Adrenergic alpha-2 receptor

II. Adrenergic beta-2 stimulation
III. Cholinergic- muscarinicactivation

Diabetes
3. Hormonal: PGE inhibits insulin release.
I. Beta cells
II. Alpha cells
III. Delta cells

ACTION OF INSULIN
It facilitates glucose transport across cell membrane.

Exercise has insulin sparing effect.
Phosphorylation of glucose is enhanced by insulin through

increased production of glucokinase.
It inhibits phosphorylase.
Insulin inhibits gluconeogenesis in liver by gene mediated

decreased synthesis of phosphoenol pyruvate carboxykinase.
It inhibits lipolysis in adipose tissue and favours triglyceride

synthesis.
It stimulates transcription of vascular endothelial lipoprotien

lipase.
It facilitates amino acid entry and their synthesis into protiens
in muscules and other cells.


Diabetes
MECHANISM OF ACTION

DIAGNOSIS Diabetes
Fasting blood glucose test
Gestational diabetes is diagnosed based on blood glucose levels

measured during the OGTT.
Glucose levels are normally lower during pregnancy, so the cut

off levels for diagnosis of diabetes in pregnancy are lower


TYPES OF INSULIN Diabetes
Rapid acting insulin
Short acting insulin
Intermediate acting insulin
Mixed insulin

Diabetes
RAPID ACTING INSULIN
Novo Rapid (Insulin Aspart)
Humalog (Lispro)

SHORT ACTING Diabetes
Actrapid
Humulin
Hypurin Neutral (bovine - highly purified
beef insulin)

Diabetes
INTERMEDIATE ACTING
Protaphane
Humulin NPH
Hypurin Isophane (bovine)

LONG ACTING Diabetes


Lantus (Glargine)

Levemir (Detemir)



Diabetes
INSULIN SYRINGES

INSULIN PENS Diabetes
NovoPen 3, NovoPen Demi, Innovo and HumaPen

Diabetes
INSULIN PUMP

CLASSIFICATION
Tolbutamide
Chlorpropamide
1st Generation
Sulphonylureas
Glibenclamide Glipizide Glim
2nd Generation
Biguanides Phenformin
Metformin
Oral Hypoglycaemics
Thiazolidinediones Rosiglitazone
Pioglitazone
Meglitidine Derivatives Repaglinide

Nateglinide
Acarbose
Glucosidase Inhibitors Miglitol
Diabetes
SULPHONYLUREAS

MECHANISM OF ACTION Diabetes
∞Increase Insulin Secretion
∞Act on Sulphonylureas Receptors
∞Reduce conductance of ATP sensitive K+ channels
∞Depolarisation
∞Ca2+ influx increases causes Degranulation
∞Increases Insulin Secretion

PHARMACOKINETICS
üWell absorbed orally.
ü90% or more is bound to plasma protein.
üLow Volume of distribution

DRUGS PLASMA DURATIO CLEARAN NO. OF

t(1/2) hr N CE ROUTE DOSES
OF PER DAY
ACTION
(hr)
Tolbutamid 6 – 8 6-8 Liver 2-3
e
4–6 18 – 24 Liver 1-2
Glibenclam
ide 5-7 24 Liver 1
Glimepirid
Diabetes
BIGUANIDES
MECHANISM OF ACTION

• Suppress hepatic gluconeogenesis.


• Enhance insulin-mediated glucose disposal in muscle& fat.

•
• Retard intestinal absorption of glucose, other hexose, amino acids &
vit B12.

• Interfere with mitochondrial respiratory chain.



PHARMACOKINETICS
DRUGS PLASMA DURATIO CLEARAN NO. OF

t(1/2) hr N CE ROUTE DOSES
OF PER DAY
ACTION
(hr)
Metformin 1.5-3 6-8 Excreted 2-3

unchanged
by kidney

ADVERSE EFFECTS
• Abdominal pain, anorexia, nausea,

metallic taste, mild diarrhoea &
tiredness.
• Metformin does not cause
hypoglycaemia except in overdose.
• Vit B12 deficiency


Diabetes
MEGLITINIDE /
D-PHENYLALANINE
ANALOGUES
REPAGLINIDE Diabetes
• It is a meglitinide analogue oral

hypoglycaemic designed to normalise
meal-time glucose excursions.
• Binds to sulfonylurea receptor as well as
to other distinct receptors closure of ATP
dependent K channels-> depolarisation-
>insulin release.
•
•

SIDE EFFECTS
• Mild headache, dyspepsia , arthralgia &

weight gain.
• Because of short lasting action it may
have a lower risk of serious
hypoglycaemia.
• It should be avoided in liver disease.
•
 DOSAGE
• Administered before each major meal to
control postprandial hyperglycaemia.
• Dose should be omitted if a meal is
October 3, 2009
missed. SIESCOMS Group 5 31
NATEGLINIDE

• It is a D- phenylalanine derivative.
• Stimulates 1st phase insulin secretion
resulting in rapid onset .
• Shorter duration of hypoglycaemic action
than repaglinide.

 PHARMACOKINETICS
 Diabetes
DRUG PLASMA DURATIO CLEARAN NO. OF

t(1/2)hr N OF CE DOSES
ACTION ROUTE PER DAY
(hr)
REPAGLIN <1 3-5 METABOL 3-4
IDE IZED
IN LIVER
NATEGLI 1.5 2-3 METABOL 3-4

NIDE IZED
IN LIVER

 SIDEEFFECTS
• Dizziness, nausea, flu like symptoms and
joint pain.

 DOSAGE
• Ingested 10-20 min before meal.
It is used in type 2DM along with other
antidiabetics, to control postprandial rise

in blood glucose.


THIAZOLIDINEDIONES
ROSIGLITAZONE & PIOGLITAZONE
• Selective agonist for the nuclear

peroxisome proliferator-activated
receptor (PPAR).
• Tend to reserve insulin resistance by
stimulaiting GLUT4 expression &
translocation.
• Activation of gene regulating fatty acid
metabolism &lipogenesis contributes to
the insulin sensitizing action.
• Lowers serum triglyceride level and
raises HDL level without much change
in LDL level.
•
PHARMACOKINETICS Diabetes

DRUG PLASM DURATIO CLEARAN NO. OF
A N OF CE DOSES
t(1/2) hr ACTION ROUTE PER DAY
(hr)
Rosiglitazone 4 12-24 Metabolized 1-2

in liver
Pioglitazone 3-5 24 Metabolized 1

in liver

ADVERSE EFFECTS
•
• Edema, weight gain, headache, & mild
anaemia.
• Hepatic dysfunction & cardiovascular
problem.
• Monitoring of liver function is advised.
• Fractures in elderly women.
• Contraindicated in pregnancy.


α Glucosidase
Inhibitors
ACARBOSE

Diabetes
• Complex oligosaccharides.
• Reversibly inhibits α −
glucosidase(final enzymes for
digestion of carbohydrates).
• Decrease digestion.
• Decreases absorption of
polysaccharides& sucrose.
• Acarbose is a mild
antihyperglycaemia.


SIDE EFFECTS
• Regular usage tends to lower
Hb ,body weight and serum
triglyceride.
• Produces flatulence, abdominal
discomfort & loose stools.
DOSAGE:50-100 mg is taken at
beginning of each major meal.

MIGLITOL:is similar to acarbose.

Diabetes
MOA SUMMARY
CLASS MOA
Sulphonylureas Stimulate sulphonylureas receptors on
pancreatic b cell membrane
Biguanides Supress Gluconeogenesis

Meglitinide Binds to sulfonylurea receptor as well as to other distinct
receptors ATP dependent K channels-> depolarisation-
Analogues >insulin release.
Thiazolidinediones Selective agonist for the nuclear peroxisome proliferator-

activated receptor (PPAR).
a-Glucosidase Reversibly inhibits a- glucosidase

Inhibitor
Hope through Research Diabetes
National Institute of Diabetes and Digestive and Kidney

Diseases (NIDDK) conducts research and gathers and analyzes
statistics about diabetes
National Institutes of Health (NIH) conduct and support research

on diabetes-related eye diseases, heart and vascular
complications.
Government agencies:
Indian Health Service

Health Resources and Services Administration

Non-Government agencies: Diabetes
American Diabetes Association (ADA)

Juvenile Diabetes Research Foundation (JDRF)
International American Association of Diabetes Educators
(IAADE)
Advances in diabetes research:
Better ways to monitor blood glucose –t o check their own

blood glucose levels

Development of external insulin pumps to deliver insulin.


What will the future bring? Diabetes
Type 1 Diabetes:
The Environmental Determinants of Diabetes in the Young (TEDDY):

Concentrates to:
Create a central repository of data and biological samples for use by

researchers.


Develop novel approaches to find the causes of type 1 diabetes.


Find ways to understand how the disease starts and progresses.
Discover new methods to prevent, delay, and reverse type 1

diabetes.
Diabetes
Type 2 Diabetes studies in Children and Teens:
The TODAY (Treatment Options for type 2 Diabetes in Adolescents

and Youth) study, a 13-site study sponsored by NIDDK.
One of three treatments:

Taking 1 diabetes medication (metformin).
2 diabetes medications (metformin and rosiglitazone- medication

that fights insulin resistance)
Taking metformin and participating in an intensive lifestyle change

weight loss by cutting calories and increasing physical activity
Goal: Controls blood glucose levels.

Evaluate efficacy of the treatments.

Diabetes
Islet Transplantation:
The Collaborative Islet Transplant Registry (CITR), funded by

NIDDK.
CITR’s mission is to expedite progress and promote safety in islet

transplantation.
Goal of islet transplantation is to infuse enough islets to control

the blood glucose level without insulin injections.

Diabetes
Clinical Trials :
Recruiting
PROCHYMAL™ (Human Adult Stem Cells) for the Treatment of Recently D
:
Conditions:
Type 1 Diabetes Mellitus; Type 1 Diabetes; Diabetes Mellitus,
Insulin-Dependent; Juvenile Diabetes
Interventions:
Drug: PROCHYMAL™; Drug: Placebo
Recruiting
Intranasal Insulin for Prevention of Type 1 Diabetes:
Condition:
Type 1 Diabetes
Intervention:
Drug: daily intranasal administration of insulin

Diabetes
Recruiting
Diabetes Prevention and Control in the Workplace: A Pilot Study
Condition:
Type 2 Diabetes Mellitus
Intervention:
Behavioral: Diabetes Prevention and Control
Recruiting
Study of Intensive, Home-Based Family Therapy to Improve Illness Managem
Condition:
Diabetes Mellitus, Insulin Dependent
Interventions:
Behavioral: Intensive Homebased Family Therapy;
Behavioral: Supportive Telephone Calls

India's first insulin guidelines for management
of diabetes:
Source: (IndiaPRwire.com) & www.biospectrumindia.ciol.com
India's first premix insulin guideline launched by former president

Dr A P J Kalam on the sidelines of 64th annual conference of
Association of Physicians of India, APICON-2009.
The premix guideline is the first-of-its-kind insulin therapy guideline

formulated by 27 experts (Indian National Consensus Group)
comprising diabetologists, physicians and endocrinologists across
India.
Guideline aims to give insights in to:
-Insulin therapy - premix insulin as the optimal choice

-Rationale for using premix insulin therapy in India
-Evidences supporting premix insulin - initiation and titration of premix
insulin

References :
THANK YOU

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• Chronic disease which arises when pancreas do not produce

• Characterized by hyperglycemia, glycosuria, hyperlipidemia.

October 3, 2009 SIESCOMS Group 5 2

Insulin circulation is low.

Antibodies that destroy β -cells of islets of langerhans

Non insulin dependent mellitus

Pancreas produce adequate insulin but body craves for more.

Some women develop it during pregnancy.

October 3, 2009 SIESCOMS Group 5 5

October 3, 2009 SIESCOMS Group 5 6

1. Chemical: Activation of glucoreceptor

2. Neural I. Adrenergic alpha-2 receptor

October 3, 2009 SIESCOMS Group 5 8

October 3, 2009 SIESCOMS Group 5 9

Phosphorylation of glucose is enhanced by insulin through

It inhibits phosphorylase.

Insulin inhibits gluconeogenesis in liver by gene mediated

It inhibits lipolysis in adipose tissue and favours triglyceride

It stimulates transcription of vascular endothelial lipoprotien

October 3, 2009 SIESCOMS Group 5 11

Fasting blood glucose test

Gestational diabetes is diagnosed based on blood glucose levels

Glucose levels are normally lower during pregnancy, so the cut

October 3, 2009 SIESCOMS Group 5 12

Rapid acting insulin

Short acting insulin

Intermediate acting insulin

October 3, 2009 SIESCOMS Group 5 13

Novo Rapid (Insulin Aspart)

October 3, 2009 SIESCOMS Group 5 14

Hypurin Neutral (bovine - highly purified

October 3, 2009 SIESCOMS Group 5 15

Hypurin Isophane (bovine)

October 3, 2009 SIESCOMS Group 5 16

October 3, 2009 SIESCOMS Group 5 17

October 3, 2009 SIESCOMS Group 5 18

NovoPen 3, NovoPen Demi, Innovo and HumaPen

October 3, 2009 SIESCOMS Group 5 19

October 3, 2009 SIESCOMS Group 5 20

Meglitidine Derivatives Repaglinide

October 3, 2009 SIESCOMS Group 5 22

∞Increase Insulin Secretion

∞Act on Sulphonylureas Receptors

∞Reduce conductance of ATP sensitive K+ channels

∞Ca2+ influx increases causes Degranulation

∞Increases Insulin Secretion

October 3, 2009 SIESCOMS Group 5 23

DRUGS PLASMA DURATIO CLEARAN NO. OF

• Suppress hepatic gluconeogenesis.

• Enhance insulin-mediated glucose disposal in muscle& fat.

• Interfere with mitochondrial respiratory chain.

October 3, 2009 SIESCOMS Group 5 26

DRUGS PLASMA DURATIO CLEARAN NO. OF

Metformin 1.5-3 6-8 Excreted 2-3

October 3, 2009 SIESCOMS Group 5 27

• Abdominal pain, anorexia, nausea,

October 3, 2009 SIESCOMS Group 5 28

• It is a meglitinide analogue oral

October 3, 2009 SIESCOMS Group 5 30

• Mild headache, dyspepsia , arthralgia &

October 3, 2009 SIESCOMS Group 5 32