Presented by

:

Ablilasha Ashish Divya Gayatri Sarita Shrutika

October 3, 2009

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DIABETES

Diabete s

• 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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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 o o 
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oMost common form of diabetes.

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GESTATIONAL DIABETES

Diabet es

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
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

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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 in muscules and other cells.
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 

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MECHANISM OF ACTION

Diabetes

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DIAGNOSIS
Fasting blood glucose test

Diabetes

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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RAPID ACTING INSULIN
Novo Rapid (Insulin Aspart)

Diabetes

Humalog (Lispro)

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

Diabetes

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

Diabetes

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LONG ACTING

Diabetes

  Lantus (Glargine)  Levemir (Detemir)

 

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INSULIN SYRINGES

Diabetes

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INSULIN PENS

Diabetes

NovoPen 3, NovoPen Demi, Innovo and HumaPen

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INSULIN PUMP

Diabetes

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CLASSIFICATION
1st Generation Sulphonylureas Tolbutamide Chlorpropamide

Glibenclamide Glipizide Glim 2nd Generation Biguanides Phenformin Metformin

Oral Hypoglycaemics
Thiazolidinediones

Rosiglitazone Pioglitazone Repaglinide Nateglinide

Meglitidine Derivatives

Glucosidase Inhibitors
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Acarbose Miglitol
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Diabetes

SULPHONYLUREAS

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MECHANISM OF ACTION
∞Increase Insulin Secretion ∞Act on Sulphonylureas Receptors

Diabetes

∞Reduce conductance of ATP sensitive K+ channels ∞Depolarisation ∞Ca2+ influx increases causes Degranulation ∞Increases Insulin Secretion

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PHARMACOKINETICS
üWell absorbed orally. ü90% or more is bound to plasma protein. üLow Volume of distribution 

DRUGS

PLASMA t(1/2) hr

Tolbutamid 6 – 8 e 4–6 Glibenclam 5-7 ide
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DURATIO CLEARAN NO. OF N CE ROUTE DOSES OF PER DAY ACTION (hr) 6-8 Liver 2-3 18 – 24 24 Liver Liver 1-2 1
24

Glimepirid

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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 t(1/2) hr DURATIO CLEARAN NO. OF N CE ROUTE DOSES OF PER DAY ACTION (hr) 6-8 Excreted 2-3 unchanged by kidney

Metformin 1.5-3

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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 October 3, 2009 SIESCOMS Group 5 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 DURATIO CLEARAN NO. OF t(1/2)hr N OF CE DOSES ACTION ROUTE PER DAY (hr) 3-5 METABOL 3-4 IZED IN LIVER METABOL 3-4 IZED IN LIVER

REPAGLIN <1 IDE

NATEGLI 1.5 NIDE

2-3

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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.

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• Lowers serum triglyceride level and raises HDL level without much change in LDL level.

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 

PHARMACOKINETICS
DRUG

Diabetes

PLASM DURATIO CLEARAN NO. OF A N OF CE DOSES t(1/2) hr ACTION ROUTE PER DAY (hr)
12-24 Metabolized 1-2 in liver

Rosiglitazone 4

Pioglitazone 3-5

24

Metabolized 1 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 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.
  
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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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MOA SUMMARY
CLASS Sulphonylureas Biguanides Meglitinide Analogues MOA

Diabetes

Stimulate sulphonylureas receptors on pancreatic b cell membrane Supress Gluconeogenesis
Binds to sulfonylurea receptor as well as to other distinct receptors ATP dependent K channels-> depolarisation>insulin release. activated receptor (PPAR).

Thiazolidinediones Selective agonist for the nuclear peroxisome proliferatora-Glucosidase Inhibitor
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Reversibly inhibits a- glucosidase
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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

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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?
Type 1 Diabetes:

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.
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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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Clinical Trials : Recruiting

Diabetes

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
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