Presented

by:
Paul
imel

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 Diabet
es
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.

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 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.

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 Diabe
TYPE II DIABETES
tes

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.

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 Diabe
GESTATIONAL DIABETES tes

•Some women develop it during pregnancy.

•Few symptoms
•Disappears when pregnancy ends

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 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…
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 RISK FACTORS

•Obesity and overweight

•Lack of exercise
•Unhealthy diet
•A family history of diabetes
•High blood pressure
•High cholesterol
•Increased age
•Ethnicity.

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 INSULIN Diabetes
 Secreted by beta cells of islets of langerhans.
 PREPROINSULIN

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- muscarinic activation

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

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 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

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in muscules and other cells.
 Diabetes
MECHANISM OF ACTION

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 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

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 TYPES OF INSULIN Diabetes

•Rapid acting insulin

•Short acting insulin

•Intermediate acting insulin

•Mixed insulin

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 Diabetes
RAPID ACTING INSULIN

Novo Rapid (Insulin Aspart)

Humalog (Lispro)

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 SHORT ACTING Diabetes

•Actrapid

•Humulin

•Hypurin Neutral (bovine - highly purified

beef insulin)

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 Diabetes
INTERMEDIATE ACTING

•Protaphane

•Humulin NPH

•Hypurin Isophane (bovine)

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 LONG ACTING Diabetes

• Lantus (Glargine)

• Levemir (Detemir)

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 Diabetes
INSULIN SYRINGES

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 Diabetes
INSULIN PENS

• NovoPen 3, NovoPen Demi, Innovo and

HumaPen

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 Diabetes
INSULIN PUMP

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 CLASSIFICATION
Tolbutamide
1st Chlorpropami
Generation de
Sulphonylure
as Glibenclamid
2nd
e Glipizide
Generation
Glimepiride
Phenformin
Biguanides
Metformin
Oral
Hypoglycaemi Rosiglitazo
cs Thiazolidined ne
iones Pioglitazon
e
Repaglinid
Meglitidine
e
Derivatives
Nateglinide

Glucosidase Acarbose
Inhibitors Miglitol
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 Diabetes

SULPHONYLUREAS

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 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

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 PHARMACOKINETICS

 Well absorbed orally.

90% or more is bound to plasma protein.
Low Volume of distribution

DRUGS PLASMA DURATION CLEARANCE NO. OF

t(1/2) hr OF ACTION ROUTE DOSES PER
(hr) DAY

Tolbutamid 6 – 8 6-8 Liver 2-3

e
4–6 18 – 24 Liver 1-2
Glibenclami
de 5-7 24 Liver 1

Glimepiride

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 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.

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 PHARMACOKINETICS

DRUGS PLASMA DURATION CLEARANCE NO. OF

t(1/2) hr OF ACTION ROUTE DOSES PER
(hr) DAY

Metformin 1.5-3 6-8 Excreted 2-3

unchanged
by kidney

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 ADVERSE EFFECTS

• Abdominal pain, anorexia, nausea,

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

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 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.

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 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 missed.

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 NATEGLINIDE

• It is a D- phenylalanine derivative.
• Stimulates 1st phase insulin secretion
resulting in rapid onset .
• Shorter duration of hypoglycaemic action
than repaglinide.

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 PHARMACOKINETICS

Diabetes

DRUG PLASMA DURATION CLEARANCE NO. OF

t(1/2)hr OF ROUTE DOSES
ACTION PER DAY
(hr)

REPAGLINIDE<1 3-5 METABOLIZE 3-4

D
IN LIVER

NATEGLINID 1.5 2-3 METABOLIZE 3-4

E D
IN LIVER

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 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.

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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.

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PHARMACOKINETICS Diabetes
DRUG PLASMA DURATION CLEARANCE NO. OF
t(1/2) hr OF ROUTE DOSES
ACTION PER DAY
(hr)

Rosiglitaz 4 12-24 Metaboliz 1-2

one ed in liver

Pioglitazo 3-5 24 Metaboliz 1

ne ed in liver

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 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.

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α Glucosidase
Inhibitors
ACARBOSE
• Complex oligosaccharides. Diabetes

• Reversibly inhibits α − glucosidase(final

enzymes for digestion of
carbohydrates).
• Decrease digestion.
• Decreases absorption of
polysaccharides& sucrose.
• Acarbose is a mild antihyperglycaemia.

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 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.

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 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

Analogues other distinct receptors ATP dependent K
channels-> depolarisation->insulin release.

Thiazolidinediones Selective agonist for the nuclear peroxisome

proliferator-activated receptor (PPAR).

a-Glucosidase Reversibly inhibits a- glucosidase

Inhibitor

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 Hope through Diabetes
Research

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.

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 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.

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 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. SIESCOMS Group 5 45
 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.

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 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.

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 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

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 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

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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

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References :
 THANK
YOU
October 3, 2009 SIESCOMS Group 5 52