INTRO

Hehehehehehehe ……………..The one thing which has made a substitute for INSULIN…………….the only drug of choice for a early diagnosed and well diet controlled patient with Non insulin diabetes mellitus  ……….

Oral hypoglycemic agents commonly are referred to as sulfonylureas, a class of compounds. Sulfonylurea compounds are among the most widely prescribed medications in the world. The drugs are frequently used to treat patients with type II diabetes. Wide availability of these medications increases potential for either intentional or unintentional overdose in pediatric and adult populations.

First-generation sulfonylurea compounds became widely available in 1955. They are acetohexamide, chlorpropamide, tolazamide, and tolbutamide. First-generation agents have longer half-lives (eg, 49 hours for chlorpropamide). Second-generation sulfonylureas were introduced in 1984. Known as glipizide, glyburide, and glimepiride, second-generation sulfonylureas are more potent and have shorter half-lives than the first-generation sulfonylureas.

Other agents besides sulfonylureas are used to treat type II diabetes, including biguanides, alpha-glucosidase inhibitors, and troglitazone. Metformin (Glucophage in the United States) is one such agent. Even in excessive dosage, these agents do not decrease serum glucose below euglycemia; consequently, they are referred to appropriately as antihyperglycemic agents rather than hypoglycemic agents.

The Joslin Diabetes Center released a clinical guideline for the pharmacological management of type II diabetes in 2007.

CLASSIFICATION OF DRUGS

1. SULFONYL UREA’S
2. BIGUANIDES
3. ALPHA GLUCOSIDASE INHIBHITORS
4. MEGLITINIDES
5. THIAZOLINEDIONES

SULFONYLUREA’S

Sulfonylureas work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal.

preparation of sulfonylurea

The sulfonylureas are often classified as belonging to the first or second generation.

The First generation sulfonylureas:

• Acetohexamide
• Chlorpropamide
• Tolazamide
• Tolbutamide.

The Second generation sulfonylureas :

• Glibenclamide
• Glyburide
• Glipizide
• Glicazide
• Glimepiride

The first generation sulfonylureas are rarely used now.

NEWER DRUGS ARE Glimipiride (Amaryl) and Glicazide MR and XR ………Nowadays new medicine is used vastly in the practice of longterm NIDDM cases (Non insulin dependant Diabetes Mellitus)……..

Also available in 60 mg and even in XR(xtended release)

The SU class of oral hypoglycemic agents (insulin secretagogues) has been in existence since tolbutamide was introduced in 1956.

The sulfonylurea drugs have effects which are still not completely understood. Initially, they work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal. They are potassium channel blockers whose effect on the pancreatic beta-islet cells is to allow an influx of calcium into the cell, which causes an increase in the release of insulin.

depletion of Beta cells

However, after several months, blood levels of insulin return to pre-medication levels, yet blood glucose levels remain reduced. Clearly, the sulfonylurea drugs must have other effects. Several have been identified, among them: sulfonylurea medications slow the rate at which the liver releases glucose into the bloodstream, and they increase the number of insulin receptors on cell membranes, thus increasing insulin efficiency.

The efficacy of the first- and second-generation sulfonylureas is similar, although second-generation agents are better formulated and, although costlier than the older sulfonylureas, have some advantages. Second-generation sulfonylureas:

Are more potent on a per milligram basis
Tend to produce fewer side effects
In addition, the pharmacokinetics of these second-generation agents allows for more effective once-a-day dosing, which enhances compliance.

Although some consider SUs to be dated compared with the newer oral hypoglycemic drugs, there remains a large number of patients that will continue to benefit from them.

BIGUANIDES

Two drugs in this category are phenformin and metformin.

Metformin_500mg_Tablets

Biguanides work mainly by

• Suppressing excessive hepatic glucose production
• Increasing glucose utilization in peripheral tissues to a lesser degree.
• Possibly reduce food intake and thus reduce intestinal glucose absorption

Metformin structure

As the biguanides do not stimulate endogenous insulin secretion, hypoglycemia does not occur when they are used alone and therefore they are sometimes called anti-hyperglycemic agents rather hypoglycemic agents.

The use of phenformin has decreased considerably and it is usually metformin that is now used when a biguanide is prescribed.

The biguanides were introduced in 1957. Both phenformin and metformin have been widely used here, although in recent times, the use of phenformin has decreased significantly and most people now use metformin when a biguanide is to be used.

Metformin works mainly by suppressing excessive hepatic glucose production, although it may increase glucose utilization in peripheral tissues to a lesser degree, by decreasing insulin resistance in muscle cells. Metformin may also improve glucose levels by reducing intestinal glucose absorption.

Metformin is not metabolized and is excreted unchanged by the kidneys.

Metformin effects

Metformin has many characteristics that are ideal for treating type 2 diabetes, including weight loss, insulin sensitization, positive lipid effect, mild hypotensive effect, and low or no incidence of hypoglycemia.

Because metformin does not stimulate endogenous insulin secretion, hypoglycemia does not occur when this dose is used alone, although hypoglycemia may occur if metformin is taken with insulin, a sulfonylurea, or an excessive amount of alcohol.

Treatment with metformin has beneficial effects on plasma lipids (it lowers triglyceride and low-density lipoprotein [LDL] cholesterol levels while increasing high-density lipoprotein [HDL] cholesterol) that are greater than expected from improved glucose control alone.

In addition, metformin therapy has been associated with weight loss or no weight gain. This may be particularly helpful in obese patients with type II diabetes.

Metformin is effective as monotherapy or in combination with sulfonylureas, alpha-glucosidase inhibitors, and insulin. The combination of metformin and troglitazone has also been shown to be safe and effective, although this combination is not an USA FDA- approved indication and extensive published data on this combination is lacking.

ALFA GLUCOSIDASE INHIBHITORS

miglitol structure

There are Acarbose and Miglitol. Acarbose (Precose) is an alpha-glucosidase inhibitor that slows down the breakdown of disaccharides and polysaccharides and other complex carbohydrates into monosaccharides. The enzymatic generation and subsequent absorption of glucose is delayed and the postprandial blood glucose values, which are characteristically high in patients with type II diabetes, are reduced with acarbose. AGIs do not prevent the absorption of carbohydrates and complex sugars, but they do delay their absorption.

Acarbose structure

Delaying the absorption of carbohydrates is a unique mechanism among oral diabetic medications for lowering HgbA1c levels. The effectiveness of this mechanism is one of the physiologic characteristics of type 2 diabetes. Patients with type 2 diabetes demonstrate a delayed or sluggish insulin response from the pancreas to a glucose (a meal) load. By delaying the absorption of glucose, the insulin response is more matched to the serum glucose, resulting in less postprandial hyperglycemia and a lowering of the HbA1c. The AGIs also demonstrate a lowering of total insulin output of the pancreas, increased insulin sensitivity, a variable but mild decrease in triglycerides, with no effect on patient weight.

One disadvantage with the use of acarbose is that it is to be taken along with the first bite of a meal. Moreover, it has to be taken three times daily with meals. These factors often lead to non compliance and a decrease in the efficacy of the drug.

MEGLITINIDES +AMINOACID DERIVATIVES

A very recent addition to the OHA group. It is a ultra short acting drug which acts directly on the the beta cells of the pancreas and increases the secretion of insulin. It also corrects the problems with the pulsatile release of insulin which is seen in Type II diabetes.

Repaglinide from the meglitinide drug class, acts like an extremely short-acting SU (an insulin secretagogue) and is potentially useful as a SU replacement. The effect of repaglinide on the pancreas is very similar to that of the SUs. Repaglinide, like the SUs, blocks the potassium channels on the pancreatic islet beta-cells, which causes an influx of calcium into the cell and increasing the secretion of insulin. There appears to be 2 similar potassium channels on islet beta-cells, one of which is predominantly affected by repaglinide and the other is predominantly affected by SUs.

Repaglinide structure

The repaglinide-affected potassium channel appears to be glucose dependent, which may partially explain why repaglinide is associated with a much lower incidence of hypoglycemia.

novonorm- repaglinide

What makes repaglinide clinically different from the SUs is its ultra-short half-life (1 hour). Repaglinide is taken just before or with meals, and the stimulation of the pancreas is limited only to a brief time around meals. Because of the short duration, the patient does not have continuous high levels of insulin and the resulting adverse effects.

Its biggest advantage over the other oral hypoglycemic medications is that it allows for flexible timing and missed meals.

Repaglinide has been approved for use with metformin, and the combination appears to be a very effective. There are no clinical trials of repaglinide with the alpha-glucosidase inhibitors, and of the TZD class, only 1 clinical trial with troglitazone has been reported. There are theoretical interactions between repaglinide and the TZDs through their common metabolism in the P450 pathway, so more clinical trials are clearly needed.

THIAZOLIDINEDIONES

Rosiglitazone structure

Thiazolidinediones are a new class of oral antidiabetic agents (commercially known as glitazones) that enhance insulin sensitivity in peripheral tissues. Troglitazone was the first glitazone introduced to the market, and though widely used, it has now been withdrawn from the market as its use has been linked with hepatocellular injury and death secondary to liver failure.

Rosiglitazone and Pioglitazone are now available for clinical use and are extremely potent in reducing peripheral insulin resistance.

The thiazolidinedione (TZD) class of oral hypoglycemics ( popularly known as glitazones) was developed in 1997 and offers a new mechanism for treatment of type 2 diabetes. The first, troglitazone was taken off the market in 1999 because of its association with hepatic toxicity. Rosiglitazone and pioglitazone have been available since 1999, and have recently been introduced in the Indian market.

The primary effect of TZDs is peripheral, with increasing insulin sensitivity and increased glucose uptake. The TZDs have some effect on hepatic glucose uptake and sensitivity to a lesser degree. They do not stimulate the pancreas to produce more insulin.

TZDs are hepatically metabolized and thus can be used safely in patients with renal dysfunction. They can be dosed once daily, although rosiglitazone works better with twice-daily dosing. Reports have suggested that rosiglitazone works better in women, but the reason for this is not known.

Both pioglitazone and rosiglitazone are approved for monotherapy and in combination with metformin, SUs, and insulin.

Besides their effect in lowering the blood glucose levels, both drugs also have notable effects on lipids. The current data show that pioglitazone has a minimal effect on low-density lipoprotein (LDL) cholesterol levels and a favorable effect on high-density lipoprotein (HDL) cholesterol and triglyceride levels. Rosiglitazone has a favorable effect on HDL cholesterol levels but a negative effect on LDL cholesterol levels.

With use of glitazones, patience is required. Blood sugar levels may show a significant reduction statistically in as little as two to four weeks, but the maximum effects are not seen until two or three months have passed.

CONCLUSION

So i dont have a conclusin yet……………………Postin it soon !!!!!!!!!!!!!!!!!!!!!!!!

INTRODUCTION

Sri krishna Hospital is at New Military Road, Avadi, Chennai -600062 . Dr.C.Jayapal BSc MD (CARDIOLOGY) has also recieved a lot a rewards from the Institute of Diabetology and has been very very sucessful in his diabetic practice and has been receiving a lot of good outcome from most of his patients …………………I was shell shocked the first day i joined there …that was 02/01/2010 ….a day that gave my life  a big big change ……..

ABT THE PRACTICE THERE

All patients there are interesting xcept for a few malingering cases ……………..the first case of my life was a TB patient at BH(Bombay hospital) a very well pronouned Hospital in the world ……………..but a lot of cases die out of poor patient care by the staff nurses ……bcoz the docs are trained better there and the nurses are not upto the mark…………………His name was Trilok /45/m from wadala(mumbai)…………..he was a businessman and suffered from TB ….Non smoker / Non drinker and also  a Vegeterian……….But he only survived of a very innate care take by Dr.K.Ramamoorthy MD the messiah of the Hospital………But here the story stands all behind the sucess of a single hero who has made his life so long in the history of medicine and who has dedicated himself to medicine ……………………..He is Dr.C.Jayapal MD from Krishna Hospital …..“Its like everyday learning hahahha ” the same words ……I just stole it from his mouth ….Looks nice to hear ….but more nicer  to xperience ………he always makes  a proper History taking and Xamines every single patient from hair to toe nail …….and also follows the course of the disease and treats according to the disease and not according to the symptom…….Bcoz it may cost him a lot of workin hours ……He is also a great devotee of Lord krishna and a life member of the ISKON trust ….and also has his own temple abt a 2 km   from Avadi. …..So he has a very good power on Speech and thought and learn like no 2 moro…..and teaches like the god krishna himself ,,,,,,,But the class he follows is very very simple …….he is like a 2nd yr MBBS student xaminig each case thoroughly very rarely missin any …….but his staffs are also not upto mark ……so his maintanence of inpatients has been not that sucessful compared to his blaring practice ….there are patients from even differents states and districts …….But his teaching has been a very good mark on my medical life ….Im very happy to inform u that he is my Chacha (chitappa, Kochuacchan, Fathers yunger brother )……

NEW IDEAS IN ME

This wondrful xperience of my life shud be shared by my frens and fellow viewers and also my dear readers and my patients and his patients too ….so plannin to write Blogs on Diabetes Mellitus ………………………………. and have to make a safe world and better country …………………………we are leading in oral cancers in the world 80% and next in DM 40 % and mostly in the developed states of the country ……….So there shud be proper education for the pople and the doctors to be well developed in their methods of proper learning abt the disease and the symptom…………………..understand its not the symptom creating the problem its the disease …………………same  way there is no proper treatment without necessary investigations and there is no proper treatment without management of the disease itself …………………………….

Regards

urs always DR.LOKKU (LOGARANGAN MUTHURANGAN)

what is it ????

Refers to diabetes mellitus or, less often, to diabetes insipidus. Diabetes mellitus and diabetes insipidus share the name “diabetes” because they are both conditions characterized by excessive urination (polyuria).

The word “diabetes” is borrowed from the Greek word meaning “a siphon.” The 2nd-century A.D. Greek physician, Aretus the Cappadocian, named the condition “diabetes.” He explained that patients with it had polyuria and “passed water like a siphon.”

When “diabetes” is used alone, it refers to diabetes mellitus. The two main types of diabetes mellitus — insulin-requiring type 1 diabetes and adult-onset type 2 diabetes — are distinct and different diseases in themselves.

What are the Types ???

1.  Type I

2. Type II

3. Gestational Diabetes Mellitus

4. Others

Type I ????

It is also called Insulin Dependent Diabetes (IDDM) or Juvenile Diabetes.

Although, it may occur at any age, but it usually develops in childhood or adolescence, before the age of 25. Equal incidences are seen in both sexes. But there are increased incidences in white population. This type of diabetes accounts for 10-15% of all cases of Diabetes mellitus. This type of Diabetes is acute in onset and progresses rapidly.

Type 1 Diabetes is caused by complete deficiency of Insulin resulting from Beta cell destruction. It can be explained on the basis of three basic factors:

(i) Genetic susceptibility:

(ii) Auto Immunity:

(iii) Environmental Factors:

It may be:

• Viral infections such as –congenital Rubella, Mumps, Measles and coxsackie B virus may lead to the onset of Type 1 Diabetes.
• Exposure to cow’s milk rather then material milk in infancy may lead to development of type 1 DM. It is because the albumin from cow’s milk may react with islet cells of pancreas, leading to their destruction.
• Geography also plays an important role, as the incidences of Type 1 DM are mainly high in Finland and Sardinia

Type II??

This type of Diabetes is also known as Adult onset Diabetes. Non-insulin dependent Diabetes Mellitus (NIDDM), Maturity onset diabetes.

It is more common and constituents 80-90% of all cases of diabetes. It usually occurs in adults over 40 years of age. But now a day few cases are observed in teen years also. Many people with Type 2 diabetes do not known they have it, although it is a serious condition. Generally, when the diagnosis is made, patient is asymptomatic. Routine urine or blood test shows the presence of high glucose levels in the blood or urine. The onset of symptoms in type 2 are slow and does not progresses rapidly.

The main cause of Type 2 Diabetes mellitus is insufficient Insulin secretion by Beta Cells due to their destruction. Due to lack of insulin, there is raised blood sugar level and finally diabetes” type 2 diabetes mellitus also occur due to development of Insulin Resistance where the cells of the body mainly fat and muscle cells does not accept the insulin. The liver of such patients also produces glucose through a process called gluconeogenesis, which further worsens the controlling of glucose level.

Type 2 diabetes is more prevalent because of faulty eating habit, increasing obesity end failure to exercise. There is a direct relationship between the degree of obesity and the risk of developing type 2 diabetes. The chance to become 2 diabetes doubles for every 20% increase form normal body weight. Heredity and Genetic factors play a major role in development of Type-2 Diabetes.

In Europe and North America about 80% of all diabetes have Type-2 Diabetes have Type 2 Diabetes mellitus.

Gestational Diabetes Mellitus (GBM)

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance, with the onset of pregnancy. Women who develop Type –1 diabetes mellitus during pregnancy and women with undiagnosed a symptomatic type –2 diabetes mellitus that is discovered Gestational Diabetes Mellitus. Women with diabetes mellitus before pregnancy are said to have “Pregestational Diabetes”. Many women who have developed gestational diabetes may have controlled glucose level during the first half of the pregnancy and develop insulin

deficiency during the latter half of the pregnancy, leading to hyper-glycaemia.

Gestational Diabetes Mellitus is a complication in approximately 4% of all pregnancies in the United States. Mother with Gestational diabetes mellitus have increased rate of caesarian delivery and chronic hypertension “High blood Glucose levels in early pregnancy may deprive the embryo of oxygen and lead to Birth Defects, especially of the heart and spinal cord. Maintaining blood glucose control continues to be important throughout the pregnancy, but it is particularly important during the first eight weeks, when an embryo’s organs are farming.

To diagnose GDM, a 50 gm glucose-screening test should be performed at 24-28 weeks of gestation known as Glucose Tolerance Test (GTT). By them, the placenta begins to make the hormones that lead to insulin resistance. The screening test measures the blood sugar response to glucose consumed in a drink. Untreated gestational diabetes can lead to problems for both the mother and the child. It can lead to Fat baby syndrome or Microsomatia, in which the baby’s body produces extra fat.

Others ???

Diabetes mellitus of various known reasons is included in this type. It includes:

It is also seen during natal and early childhood.

Treatment ???

Controlling your blood sugar is essential to feeling healthy and avoiding long-term complications of diabetes. Some people are able to control their blood sugar with diet and exercise alone. Others may need to use insulin or other medications in addition to lifestyle changes. In either case, monitoring your blood sugar is a key part of your treatment program.

A healthy diet and exercise should be placed as a priority for diabetes treatment.  Second, you might also try some of the diabetes treatment using alternative medicine.  Third, follow your doctor’s prescriptions.  And last, pancreas or islet cell transplantation may be an option for people whose kidneys are failing or who aren’t responding to other treatments.

1. Monitoring Blood Sugar

a. Food

b. Exercise and Physical activity

c. Medications

d. Illness

e. Alcohol

f. Hormonal Imbalance

2.  Healthy Diet

3.  Healthy Weight

4. Medications

a. Sulphonylurea Drugs

b. Meglitinide

c. Biguanides

d. Apha Glycosidase inhibitors

e. Thiozolidinediones

5. Pancreas transplant

Other Treatment Available !!!

1. Accupunture

2. Biofeedback

3. Chromium

4. Magnesium

5. Vanadium

WAT IS IT????

Stroke is a disease that affects the arteries leading to and within the brain. It is the No. 3 cause of death in the United States, behind diseases of the heart and cancer. A stroke occurs when a blood vessel that carries oxygen and nutrients to the brain is either blocked by a clot or bursts. When that happens, part of the brain cannot get the blood (and oxygen) it needs, so it starts to die.

Is it similar to brain hemorrhage ???

Brain Hemorrhage is a condition caused due to a sudden stroke to a person after blood leaks out from the blood vessels in the brain. This situation occurs due to the break in the wall of blood vessel, the blood spills out of the blood vessel and enters the area where vital tissues and cells of brain reside, killing those tissues and cells; this causes the patient to become seriously ill and needs immediate medication/treatment.

Symptoms ???

Symptoms

If you have symptoms of a stroke, seek emergency medical care. General symptoms of a stroke include:

• Sudden numbness, paralysis, or weakness in your face, arm, or leg, especially on only one side of your body.
• New problems with walking or balance.
• Sudden vision changes.
• Drooling or slurred speech.
• New problems speaking or understanding simple statements, or feeling confused.
• A sudden, severe headache that is different from past headaches.

Symptoms vary depending on whether the stroke is caused by a clot or bleeding. The location of the blood clot or bleeding and the extent of brain damage can also affect symptoms.

1)Symptoms of an ischemic stroke (caused by a clot blocking a blood vessel) usually occur in the side of the body opposite from the side of the brain where the clot occurred. For example, a stroke in the right side of the brain affects the left side of the body.

2)Symptoms of a hemorrhagic stroke (caused by bleeding in the brain) can be similar to those of an ischemic stroke but may be distinguished by symptoms relating to higher pressure in the brain, including severe headache, nausea and vomiting, neck stiffness, dizziness, seizures, irritability, confusion, and possibly unconsciousness.

Symptoms of a stroke may progress over minutes, hours, or days, often in a stepwise fashion. For example, mild weakness may progress to an inability to move the arm and leg on one side of the body.

• If a stroke is caused by a large blood clot (ischemic stroke) or bleeding (hemorrhagic stroke), symptoms occur suddenly, within seconds.
• When an artery that is narrowed by atherosclerosis becomes blocked, stroke symptoms usually develop gradually over minutes to hours, or (in rare cases) days.
• If several smaller strokes occur over time, the person may have a more gradual change in walking, balance, thinking, or behavior (multi-infarct dementia).

It is not always easy for people to recognize symptoms of a small stroke. They may mistakenly think the symptoms can be attributed to aging, or the symptoms may be confused with those of other conditions that cause similar symptoms.

Risk Factors??

1)Controllable

• Hypertension
• Atrial Fibrillation
• High Cholesterol
• Diabetes Mellitus
• Smoking and Tobacco chewing
• Alcohol Use
• Obesity or Overweight

2)Non- controllable

• Age >55
• Gender – Males most common , but more women die of stroke
• Race – African American>Hispanic>Asians>caucasions
• Family History
• Previous Stroke or Transient Ischemic attacks or Thrombosis or Embolism

What Are the Types of Stroke?

Stroke can be caused either by a clot obstructing the flow of blood to the brain (called an ischemic stroke) or by a blood vessel rupturing and preventing blood flow to the brain (called a hemorrhagic stroke).

Diagnosis of Stroke??

When someone has shown symptoms of a stroke or a TIA (transient ischemic attack or mini stroke), a doctor will gather information and make a diagnosis. A doctor may use many different tests. The ones listed here are just some of the more common options.

Treatment !!!!

Ischemic Stroke

Acute Treatment

• Clot busters, e.g., tPA
  The most promising treatment for ischemic stroke is the FDA-approved clot-busting drug tPA (tissue plasminogen activator), which must be administered within a three-hour window from the onset of symptoms to work best. Administering tPA or other clot-dissolving agents is complex and is done through an intravenous (IV) line in the arm by hospital personnel. If given promptly, tPA can significantly reduce the effects of stroke and reduce permanent disability. Generally, only 3 to 5 percent of those who suffer a stroke reach the hospital in time to be considered for this treatment.

Preventive Treatment

• 	Click to enlarge

  Anticoagulants/Antiplatelets
  Antiplatelet agents such as aspirin and anticoagulants such as warfarin interfere with the blood’s ability to clot and can play an important role in preventing stroke. click here for  anticoagulants.

• Carotid Endarterectomy
  Carotid endarterectomy is a procedure in which blood vessel blockage is surgically removed from the carotid artery. View a detailed illustration of carotid endarterectomy.

• Angioplasty/Stents
  Doctors sometimes use balloon angioplasty and implantable steel screens called stents to treat cardiovascular disease and reduce fatty buildup clogging a vessel. View a detailed illustration of carotid stent.

Hemorrhagic Stroke (Subarachnoid hemorrhage or AVM)

• Surgical Intervention
  For hemorrhagic stroke (specifically for a subarachnoid hemorrhage), surgical treatment is often recommended to either place a metal clip at the base, called the neck, of the aneurysm or to remove the abnormal vessels comprising an arteriovenous malformation (AVM). Learn more about AVM.

• Endovascular Procedures, e.g., “coils”
  Endovascular procedures are less invasive and involve the use of a catheter introduced through a major artery in the leg or arm, guided to the aneurysm or AVM where it deposits a mechanical agent, such as a coil, to prevent rupture. (wat is  aneurysms).