Training module: Diabetes & Drugs

Training Module Diabetes

BY DEVANSH MEHTA

M.PHARM.(PHARMACOLOGY)

M.B.A.(PHARMACEUTICAL MARKETING AND HOSPITAL ADMINISTRATION)

B.PHARMACY

CONTACT NO.:+91-8171552727

[email protected]

Objective of Training Today !Brief about Human Physiology

Human Body Systems

Metabolism

What is Insulin ?

What is Diabetes ?

How many types of Diabetes are there ?

What are the major causes of Diabetes ?

Objective of the TrainingWhich type of Diabetes is More Prevalent ?

What are the factors causing the more prevalent Diabetes ?

What are the World Figures of Diabetes ?

How do we diagnose Diabetes ?

Treatment of Diabetes ?

What are the major Drugs classification for Diabetes ?

What is world diabetic drug market ?

What is the Indian market for Diabetic treatment ?

What is your Scope ?

Human Physiology The major systems of the human body are as follows

Integumentary System: Skin, Hair, Nails, Sweat and other Exocrine glands

Skeletal System: Bone supporting the body and its organs

Nervous System: Collects and processes information from the senses via nerves and brain and tells the muscle to contract to cause physical actions

Cardiovascular System: Circulates blood around the body via the heart, arteries and veins, delivering oxygen and nutrients to organs and cells and carrying their waste products away

Systems of Human Body Endocrine System: Provides chemical communications within the body using hormones

Muscular System: Enables the body to move using muscles

Lymphatic System: Supplies and drains lymph fluid in support of the cardiovascular and immune system

Respiratory System: The lungs and trachea that bring air into the body

Systems Urinary System: Part of the Excretary System

Excretary System: Eliminates waste from the body

Reporductive System: The sex organs

Digestive System: Mechanical and chemical processes that provide nutrients via mouth, esophagus, stomach and intestines

Immune System: Defends the body against disease causing agents

What is Metabolism

Metabolism is Change Reaction in body !

Metabolism (from Greek: μεταβολή metabolē, "change") is the set of life-sustaining chemical transformations within the cells of living organisms. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to all chemical reactions that occur in living organisms, including digestion and the transport of substances into and between different cells, in which case the set of reactions within the cells is called intermediary metabolism or intermediate metabolism.

Metabolism is usually divided into two categories. Catabolism, that breaks down organic matter and harvests energy by way of cellular respiration, and anabolism that uses energy to construct components of cells such as proteins and nucleic acids.

Classification of organisms based on their metabolismEnergy source

sunlight photo-

-troph

Preformed molecules chemo-

Electron donor

organic compound

organo-

inorganic compound

litho-

Carbon source

organic compound

hetero-

inorganic compound

auto-

Catabolism

Catabolism is the set of metabolic processes that break down large molecules. These include breaking down and oxidizing food molecules. The purpose of the catabolic reactions is to provide the energy and components needed by anabolic reactions. The exact nature of these catabolic reactions differ from organism to organism and organisms can be classified based on their sources of energy and carbon (their primary nutritional groups), as shown in the table below. Organic molecules are used as a source of energy byorganotrophs, while lithotrophs use inorganic substrates and phototrophs capture sunlight as chemical energy. However, all these different forms of metabolism depend on redoxreactions that involve the transfer of electrons from reduced donor molecules such as organic molecules, water, ammonia, hydrogen sulfide or ferrous ions to acceptor molecules such as oxygen, nitrate or sulfate. In animals these reactions involve complex organic molecules that are broken down to simpler molecules, such as carbon dioxide and water. In photosynthetic organisms such as plants and cyanobacteria, these electron-transfer reactions do not release energy, but are used as a way of storing energy absorbed from sunlight.

Anabolism Anabolism is the set of constructive metabolic processes where the energy released by catabolism is used to synthesize complex molecules. In general, the complex molecules that make up cellular structures are constructed step-by-step from small and simple precursors. Anabolism involves three basic stages. First, the production of precursors such as amino acids, monosaccharides, isoprenoids and nucleotides, secondly, their activation into reactive forms using energy from ATP, and thirdly, the assembly of these precursors into complex molecules such as proteins, polysaccharides, lipids and nucleic acids.

Organisms differ in how many of the molecules in their cells they can construct for themselves. Autotrophs such as plants can construct the complex organic molecules in cells such as polysaccharides and proteins from simple molecules like carbon dioxide and water. Heterotrophs, on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms can be further classified by ultimate source of their energy: photoautotrophs and photoheterotrophs obtain energy from light, whereas chemoautotrophs and chemoheterotrophs obtain energy from inorganic oxidation reactions.

INSULIN ?? What is INSULIN ???

Insulin Insulin (from the Latin, insula meaning island) is a peptide hormone produced by beta cells in the pancreas. It regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from the blood to skeletal muscles andfat tissue and by causing fat to be stored rather than used for energy. Insulin also inhibits the production of glucose by the liver.

Insulin Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action

Of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.

It was first obtained In pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.

Insulin is a two chain polypeptide having 51 amino acids and MW about 6000. The A-chain has 21 while Beta chain has 30 amino acids.

Insulin is synthesized in the β-cells of pancreatic islets as a single chain peptide Preproinsulin (110 A.A) from which 24 A.A’s are first removed to produce Proinsulin. The connecting or”C” peptide (35 A.A.) is split off by proteolysis in Golgi apparatus; both insulin and ‘C’ peptide are stored in granules within the cell. The ‘C’ peptide is secreted in the blood along with insulin.

Insulin is provided within the body in a constant proportion to remove excess glucose from the blood, which otherwise would be toxic. When blood glucose levels fall below a certain level, the body begins to use stored glucose as an energy source through glycogenolysis, which breaks down the glycogen stored in the liver and muscles into glucose, which can then be utilized as an energy source. As a central metabolic control mechanism, its status is also used as a control signal to other body systems (such asamino acid uptake by body cells). In addition, it has several other anabolic effects throughout the body.

Insulin Release Mechanism Beta cells in the islets of Langerhans release insulin in two phases. The first phase release is rapidly triggered in response to increased blood glucose levels. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar. The description of first phase release is as follows:

Glucose enters the β-cells through the glucose transporters, GLUT2.

Glucose goes into glycolysis and the Krebs cycle, where multiple, high-energy ATP molecules are produced by oxidation, leading to a rise in the ATP:ADP ratio within the cell.

An increased intracellular ATP:ADP ratio closes the ATP-sensitive SUR1/Kir6.2 potassium channel (see sulfonylurea receptor). This prevents potassium ions (K+) from leaving the cell by facilitated diffusion, leading to a buildup of potassium ions. As a result, the inside of the cell becomes more positive with respect to the outside, leading to the depolarisation of the cell surface membrane.

Insulin Release Mechanism On depolarisation, voltage-gated calcium ion (Ca2+) channels open which allows calcium ions to move into the cells by facilitated diffusion.

An increased intracellular calcium ion concentration causes the activation of phospholipase C, which cleaves the membrane phospholipid phosphatidyl inositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol.

Inositol 1,4,5-trisphosphate (IP3) binds to receptor proteins in the plasma membrane of the endoplasmic reticulum (ER). This allows the release of Ca2+ ions from the ER via IP3-gated channels, and further raises the intracellular concentration of calcium ions.

Significantly increased amounts of calcium ions in the cells causes the release of previously synthesized insulin, which has been stored in secretory vesicles.

This is the primary mechanism for release of insulin

When control of insulin levels fails, diabetes mellitus can result. As a consequence, insulin is used medically to treat some forms of diabetes mellitus. Patients with type 1 diabetes depend on external insulin (most commonly injected subcutaneously) for their survival because the hormone is no longer produced internally.[3] Patients with type 2 diabetesare often insulin resistant and, because of such resistance, may suffer from a "relative" insulin deficiency. Some patients with type 2 diabetes may eventually require insulin if dietary modifications or other medications fail to control blood glucose levels adequately. Over 40% of those with Type 2 diabetes require insulin as part of their diabetes management plan.

Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer. The hexamer is an inactive form with long-term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available. The hexamer-monomer conversion is one of the central aspects of insulin formulations for injection. The hexamer is far more stable than the monomer, which is desirable for practical reasons; however, the monomer is a much faster-reacting drug because diffusion rate is inversely related to particle size. A fast-reacting drug means insulin injections do not have to precede mealtimes by hours, which in turn gives people with diabetes more flexibility in their daily schedules.[15] Insulin can aggregate and form fibrillar interdigitated beta-sheets. This can cause injection amyloidosis, and prevents the storage of insulin for long periods

Action of Insulin The overall effects of Insulin are to favor storage of fuel.

Insulin facilitates glucose transport across cell membrane; skeletal muscle and fat are highly sensitive.

The first step in intrcellular utilization of glucose is its phosphorylation to form glucose-6-phosphate. This is enhanced by insulin through increased production of glucokinase. Insulin facilitates glycogen synthesis from glucose in liver, muscle and fat by stimulating the enzyme glycogen synthetase.

Insulin inhibits gluconeogenesis in liver by gene mediated decreased synthesis of phosphoenol pyruvate carboxykinase.

Insulin inhibits lipolysis in adipose tissue and favours triglyceride synthesis.

Insulin stimulates transcription of vascular endothelial lipoprotein lipase and thus increases clearance of VLDL and chylomicrons

Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids. While primarily odd-chain fatty acids can be converted into glucose, it is possible for at least some even-chain fatty acids

Chylomicrons (from the Greek chylø, meaning juice or milky fluid, and micron, meaning small particle) are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids from the intestines to other locations in the body.

Diabetes Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period. Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications. Acute complications include diabetic ketoacidosis and non-ketotic hyperosmolar coma. Serious long-term complications include cardiovascular disease, stroke, chronic kidney failure, foot ulcers, and damage to the eyes.

Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced. There are three main types of diabetes mellitus:

Type 1 DM results from the pancreas' failure to produce enough insulin. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause is unknown.

Type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin may also develop.his form was previously referred to as "non insulin-dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The primary cause is excessive body weight and not enough exercise.

Gestational diabetes, is the third main form and occurs when pregnant women without a previous history of diabetes develop a high blood sugar level.

Prevention and treatment involve a healthy diet, physical exercise, not using tobacco and being a normal body weight. Blood pressure control and proper foot care are also important for people with the disease.

Type 1 diabetes must be managed with insulin injections.

Type 2 diabetes may be treated with medications with or without insulin. Insulin and some oral medications can cause low blood sugar. Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 DM.

Gestational diabetes usually resolves after the birth of the baby.

What Wikipedia Says !As of 2014, an estimated 387 million people have diabetes worldwide, with type 2 diabetes making up about 90% of the cases.

This represents 8.3% of the adult population, with equal rates in both women and men.

From 2012 to 2014, diabetes is estimated to have resulted in 1.5 to 4.9 million deaths each year.

Diabetes at least doubles a person's risk of death.

The number of people with diabetes is expected to rise to 592 million by 2035.

The global economic cost of diabetes in 2014 was estimated to be $612 billion USD. In the United States, diabetes cost $245 billion in 2012.

1) Type 1 diabetes

The body does not produce insulin. Some people may refer to this type as insulin-dependent diabetes, juvenile diabetes, orearly-onset diabetes. People usually develop type 1 diabetes before their 40th year, often in early adulthood or teenage years.

Type 1 diabetes is nowhere near as common as type 2 diabetes. Approximately 10% of all diabetes cases are type 1.

Patients with type 1 diabetes will need to take insulin injections for the rest of their life. They must also ensure proper blood-glucose levels by carrying out regular blood tests and following a special diet.

Between 2001 and 2009, the prevalence of type 1 diabetes among the under 20s in the USA rose 23%, according to SEARCH for Diabetes in Youth data issued by the CDC (Centers for Disease Control and Prevention).

http://www.medicalnewstoday.com/info/diabetes/

2) Type 2 diabetes

The body does not produce enough insulin for proper function, or the cells in the body do not react to insulin (insulin resistance).

Approximately 90% of all cases of diabetes worldwide are type 2.

Some people may be able to control their type 2 diabetes symptoms by losing weight, following a healthy diet, doing plenty of exercise, and monitoring their blood glucose levels. However, type 2 diabetes is typically a progressive disease - it gradually gets worse - and the patient will probably end up have to take insulin, usually in tablet form.

Overweight and obese people have a much higher risk of developing type 2 diabetes compared to those with a healthy body weight. People with a lot of visceral fat, also known as central obesity, belly fat, or abdominal obesity, are especially at risk. Being overweight/obese causes the body to release chemicals that can destabilize the body's cardiovascular and metabolic systems.

http://www.medicalnewstoday.com/info/diabetes/

Being overweight, physically inactive and eating the wrong foods all contribute to our risk of developing type 2 diabetes. Drinking just one can of (non-diet) soda per day can raise our risk of developing type 2 diabetes by 22%, researchers from Imperial College London reported in the journal Diabetologia. The scientists believe that the impact of sugary soft drinks on diabetes risk may be a direct one, rather than simply an influence on body weight.

The risk of developing type 2 diabetes is also greater as we get older. Experts are not completely sure why, but say that as we age we tend to put on weight and become less physically active. Those with a close relative who had/had type 2 diabetes, people of Middle Eastern, African, or South Asian descent also have a higher risk of developing the disease.

Men whose testosterone levels are low have been found to have a higher risk of developing type 2 diabetes. Researchers from the University of Edinburgh, Scotland, say that low testosterone levels are linked to insulin resistance.

http://www.medicalnewstoday.com/info/diabetes/

3) Gestational diabetes

This type affects females during pregnancy. Some women have very high levels of glucose in their blood, and their bodies are unable to produce enough insulin to transport all of the glucose into their cells, resulting in progressively rising levels of glucose.

Diagnosis of gestational diabetes is made during pregnancy.

The majority of gestational diabetes patients can control their diabetes with exercise and diet. Between 10% to 20% of them will need to take some kind of blood-glucose-controlling medications. Undiagnosed or uncontrolled gestational diabetes can raise the risk of complications during childbirth. The baby may be bigger than he/she should be.

Scientists from the National Institutes of Health and Harvard University found that women whose diets before becoming pregnant were high in animal fat and cholesterol had a higher risk for gestational diabetes, compared to their counterparts whose diets were low in cholesterol and animal fats.

http://www.medicalnewstoday.com/info/diabetes/

Symptoms Central: POLYDIPSIA, POLYPHAGIA, LETHARGY, STUPOR

Eyes: BLURRED VISION

Breath: Acetone smell

Systemic: Weight loss

Respiratory: Kussmaul breathing (Hyper-ventilation)

Gastric: Nausea, Vomiting, Abdominal pain

Urinary: Polyuria, Glycosuria http://www.medicalnewstoday.com/info/diabetes/

Is Diabetes a Metabolism disorder ??

Diabetes is a metabolism disorder

Diabetes is a metabolism disorder

Diabetes (diabetes mellitus) is classed as a metabolism disorder. Metabolism refers to the way our bodies use digested food for energy and growth. Most of what we eat is broken down into glucose. Glucose is a form of sugar in the blood - it is the principal source of fuel for our bodies.

When our food is digested, the glucose makes its way into our bloodstream. Our cells use the glucose for energy and growth. However, glucose cannot enter our cells without insulin being present - insulin makes it possible for our cells to take in the glucose.

Insulin is a hormone that is produced by the pancreas. After eating, the pancreas automatically releases an adequate quantity of insulin to move the glucose present in our blood into the cells, as soon as glucose enters the cells blood-glucose levels drop.

A person with diabetes has a condition in which the quantity of glucose in the blood is too elevated (hyperglycemia). This is because the body either does not produce enough insulin, produces no insulin, or has cells that do not respond properly to the insulin the pancreas produces. This results in too much glucose building up in the blood. This excess blood glucose eventually passes out of the body in urine. So, even though the blood has plenty of glucose, the cells are not getting it for their essential energy and growth requirements.

What is Diabetes Insipidus ??

Diabetes Insipidus !In DI, there is Hypo-secretion of ADH (Antidiuretic Hormone) also known as Vasopressin, which causes disorder known as Diabetes Insipidus (Excretion of large quantity of dilute urine.).

ADH is released into blood when special osmoreceptors or hypothalamic neurons are stimulated by rise in osmotic pressure of blood, due to loss of water from the body.

In this disorder, person suffers from polyuria, i.e., excessive urine formation and dilute urination (hypotonic and sugar free) several times a day. The quantity is 5 litres or more per day.

There is corresponding increase in water loss from body fluids. It results in excessive thirst or polydipsia and dehydration, appetite increases. Loss of strength and emaciation occurs.

Major Causes of Diabetes•Genetic defects of β-cell function

• Maturity onset diabetes of the young• Mitochondrial DNA mutations

•Genetic defects in insulin processing or insulin action• Defects in proinsulin conversion• Insulin gene mutations• Insulin receptor mutations

•Exocrine pancreatic defects• Chronic pancreatitis• Pancreatectomy• Pancreatic neoplasia• Cystic fibrosis• Hemochromatosis• Fibrocalculous pancreatopathy

•Endocrinopathies• Growth hormone excess (acromegaly)• Cushing syndrome• Hyperthyroidism• Pheochromocytoma• Glucagonoma

•Infections• Cytomegalovirus infection• Coxsackievirus B

•Drugs• Glucocorticoids• Thyroid hormone• β-adrenergic agonists• Statins

Facts and Figures Diabetes Rates May Double Worldwide by 2030

The number of people with diabetes will double worldwide by 2030, according to new estimates from researchers at the World Health Organization (WHO) and several European universities.

The study suggests the greatest relative increases will be in the Middle East, sub-Saharan Africa, and India.

http://www.webmd.com/diabetes/news/20040426/diabetes-rates-worldwide

2000 2030

Rank CountryPeople with diabetes (millions) Country

People with diabetes (millions)

1 India 31.7 India 79.42 China 20.8 China 42.33 U.S. 17.7 U.S. 30.3

4 Indonesia 8.4 Indonesia 21.3

5 Japan 6.8 Pakistan 13.96 Pakistan 5.2 Brazil 11.3

7 Russian Federation 4.6 Bangladesh 11.1

8 Brazil 4.6 Japan 8.9

9 Italy 4.3 Philippines 7.8

10 Bangladesh 3.2 Egypt 6.7

The study shows that the three countries with the most people with diabetes are expected to remain India, China, and the U.S.

Diabetes Global According to the International Diabetes Foundation, there are more than 300 million people living with diabetes worldwide.www.idf.org/millions-unite-diabetes-awareness-world-diabetes-day-2010

Nearly 80 percent of diabetes deaths occur in low- and middle-income countries.www.who.int/diabetes/facts/en/index.html

https://www.einstein.yu.edu/centers/diabetes-research/facts-statistics/

Diabetes Global China, with 92 million diabetics, has overtaken India (80 million) as the world leader in diabetes cases.http://www.idf.org/press-releases/idf-press-statement-china-study

Diabetes cost the global economy at least US $376 billion in 2010, or 11.6% of total world healthcare expenditure.www.idf.org/millions-unite-diabetes-awareness-world-diabetes-day-2010

https://www.einstein.yu.edu/centers/diabetes-research/facts-statistics/

Diabetes Global The World Health Organization estimates that by 2030, more than 347 million people will be suffering from diabetes around the world, 10 times the number affected by HIV/AIDS.http://www.who.int/diabetes/en/

Of that 347 million, more than 298 million will live in developing countries, where most will not have access to adequate healthcare.http://www.who.int/diabetes/en/

https://www.einstein.yu.edu/centers/diabetes-research/facts-statistics/

http://www.diabetes.org/diabetes-basics/statistics/

The rates of diagnosed diabetes by race/ethnic background are:

7.6% of non-Hispanic whites

9.0% of Asian Americans

12.8% of Hispanics

13.2% of non-Hispanic blacks

15.9% of American Indians/Alaskan Natives

http://www.diabetes.org/diabetes-basics/statistics/

The breakdown among Asian Americans:

4.4% for Chinese

11.3% for Filipinos

13.0 for Asian Indians

8.8% for other Asian Americans.

http://www.diabetes.org/diabetes-basics/statistics/

The breakdown among Hispanic adults:

8.5% for Central and South Americans

9.3% for Cubans

13.9% for Mexican Americans

14.8% for Puerto Ricans.

http://www.diabetes.org/diabetes-basics/statistics/

Deaths Diabetes was the seventh leading cause of death in the United States in 2010 based on the 69,071 death certificates in which diabetes was listed as the underlying cause of death. In 2010, diabetes was mentioned as a cause of death in a total of 234,051 certificates.

Diabetes may be underreported as a cause of death. Studies have found that only about 35% to 40% of people with diabetes who died had diabetes listed anywhere on the death certificate and about 10% to 15% had it listed as the underlying cause of death.

DIAGNOSIS

Hb

The HbA1C test measures your average blood glucose for the past 2 to 3 months

Result HbA1C

Normal less than 5.7%

Prediabetes 5.7% to 6.4%

Diabetes 6.5% or higher

HbA1C

The HbA1C test measures your average blood glucose for the past 2 to 3 months. The advantages of being diagnosed this way are that you don't have to fast or drink anything.•Diabetes is diagnosed at an HbA1C of greater than or equal to 6.5%

Fasting means after not having anything to eat or drink for at least 8 hours before the test.

This test checks your fasting blood glucose levels. Fasting means after not having anything to eat or drink (except water) for at least 8 hours before the test. This test is usually done first thing in the morning, before breakfast. Diabetes is diagnosed at fasting blood glucose of greater than or equal to 126 mg/dl

Result Fasting Plasma Glucose (FPG)

Normal less than 100 mg/dl

Prediabetes 100 mg/dl to 125 mg/dl

Diabetes 126 mg/dl or higher

Oral Glucose Tolerance Test (OGTT)

Result Oral Glucose Tolerance Test (OGTT)

Normal less than 140 mg/dl

Prediabetes 140 mg/dl to 199 mg/dl

Diabetes 200 mg/dl or higher

The OGTT is a two-hour test that checks your blood glucose levels before and 2 hours after you drink a special sweet drink. It tells the doctor how your body processes glucose.•Diabetes is diagnosed at 2 hour blood glucose of greater than or equal to 200 mg/dl

Random (also called Casual) Plasma Glucose Test

This test is a blood check at any time of the day when you have severe diabetes symptoms.

Diabetes is diagnosed at blood glucose of greater than or equal to 200 mg/dl

What is Prediabetes? Before people develop type 2 diabetes, they almost always have "prediabetes" — blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes.

Doctors sometimes refer to prediabetes as impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), depending on what test was used when it was detected. This condition puts you at a higher risk for developing type 2 diabetes and cardiovascular disease.

There are no clear symptoms of prediabetes, so, you may have it and not know it.

Some people with prediabetes may have some of the symptoms of diabetes or even problems from diabetes already. You usually find out that you have prediabetes when being tested for diabetes.

If you have prediabetes, you should be checked for type 2 diabetes every one to two years.

Results indicating prediabetes are:

An HbA1C of 5.7% – 6.4%

Fasting blood glucose of 100 – 125 mg/dl

An OGTT 2 hour blood glucose of 140 mg/dl – 199 mg/dl

- See more at: http://www.diabetes.org/are-you-at-risk/prediabetes/?loc=superfooter?referrer=http://www.diabetes.org/?referrer=https://www.google.co.in/#sthash.RRIwm0Nz.dpuf

Drugs for Diabetes

Hypoglycaemic DrugsSulfonylureas: First Generation: Tolbutamide, Chlorpropamide

Second Generation : Glibenclamide, Glipizide, Gliclazide, Glimepride

Biguanides : Phenformin, Metformin

Meglitinide Analogues : Repaglinide, Nateglinide

Thiazolidinediones : Rosiglitazone, Pioglitazone

Alpha Glucosidase Inhibitors : Acarbose, Miglitol

Sulfonylureas All have similar pharmacological profile-sole significant action being lowering of blood glucose levels in normal subjects and in type 2 diabetes, but not in type 1 diabetes.

Mechanism of action: Single dose provoke a brisk release of insulin from pancreas. They act on the so-called sulfonyl ureas receptors on the pancreatic Beta cells membrane-cause depolarization by reducing conductance of ATP sensitive K channels. This enhances Ca+2 influx degranulation.

The rate of insulin secretion at any glucose concentration is increased. In type 2 DM the kinetics of insulin release in response to glucose or meals is delayed and subdued.

The sulfonylureas primarily augment the 2nd phase insulin secretion with little effect on the 1st phase.

Biguanides They differ markedly from sulfonylureas cause little or no hypoglycaemia in non-diabetic subjects and donot stimulate pancreatic Beta cells.

The two biguanides have similar actions, potency differs due to pharmacokinetic differences

Mechanism of action: It is not clearly understood.

Mechanism of action: It is not clearly understood.

Suppress hepatic gluconeogenesis and glucose output from liver: the major action

Enhance insulin mediated glucose disposal in muscle and fat. Though they donot alter translocation of GLUT4 ( the major glucose transporter in skeletal muscle, they enhance GLUT1 transport from intracellular site to plasma membrane. The effect thus differs from that of insulin/

Interfere with mitochondrial respiratory chain – promote peripheral glucose utilization by enhancing anaerobic glycolysis. Metformin binds less avidly to mitochondrial membrane and has weaker inhibitory effect on oxidative phosphorylation than phenformin

Inhibit intestinal absorption of glucose, other hexose, amino acids and vitB12

Meglitinide Analogues These are recently developed quick and short acting insulin releases.

Repaglinide: It is the first member of a new class of oral hypoglycaemics designed to normalize meal time glucose excursions. Though not a sulfonyl urea, it acts in an analogous manner by binding to sulfonylureas receptor as well as to other distinct receptors closure of ATP dependent K+ channels depolarization insulin release.

Thiazolidinediones Two thiazolidinediones Rosiglitazone and Pioglitazone have recently become available, while the first member Thiaglitazone has been withdrawn.

This novel class of oral anti-diabetic drugs are selective agonists for the nuclear peroxisome proliferator-activated receptor which enhances the transcription of several insulin responsive genes. They tend to reverse insulin resistance by stimulating GLUT4 expression and translocation: entry of glucose into muscle and fat is improved.

Hepatic gluconeogenesis is also suppressed.

Activation of genes regulating fatty acid metabolism and lipogenesis in adipose tissue may contribute to the insulin sensitizing action. Improved glycaemic control results in lowering of circulating insulin levels in type 2 DM.

Pioglitazone lowers serum triglyceride level and raises HDL levels without much change in LDL level.

Non-sulfonylurea insulin secretagogues GLP-I : Glucagon like peptide (7-36) amide (GLP-1) is a potent gut hormone playing the role of incretin, i.e., stimulating meal related insulin release from the B cells.

It potentiates the insulin releasing effect of glucose by stimulating adenylate cylase and increasing cAMP in the B cells.

It also suppresses glucagon release. It exerts insulinomimetic effects on gluconeogenesis in liver and muscles and lipogenesis in the adipose tissues. Since the insulin release is glucose dependent, it does not lower blood glucose further from normal blood glucose concentrations, hence decreasing the risk of hypoglycaemia