22 December, 2010

DPP IV

ALOGLIPTIN - ONE MORE EXPECTED IN

Alogliptin (codenamed SYR-322) is an investigational anti-diabetic drug in the DPP-4 inhibitor class, being developed by Takeda Pharmaceutical Company. Takeda has submitted a New Drug Application for alogliptin to the U.S. Food and Drug Administration, after positive results from Phase III clinical trials.


OTHER GLIPTINS EXPECTED ARE

Dutogliptin (being developed by Phenomix Corporation),Phase III
Gemigliptin (being developed by LG Life Sciences,Korea)

LINAGLIPTIN - ONE MORE WEAPON TO CONTROL DIABETES??


Treating type 2 diabetes patients using Boehringer Ingelheim’s oral candidate, linagliptin, leads to statistically significant and sustained reductions in blood sugar levels, according to data from four Phase III trials. The international placebo-controlled studies showed that when used as monotherapy or in combination with either metformin, pioglitazone, or metformin plus a sulfonylurea, treatment using linagliptin led to significant reductions in blood levels of hemoglobin A1c (HbA1c), fasting plasma glucose and postprandial glucose. The Phase III trial data was presented at the recent American Diabetes Association Scientific Sessions in Orlando.

Treatment using the once-daily oral drug candidate also led to improvements in beta cell function, the decline in which is believed to represent a key factor in the progression of type 2 diabetes, Boehringer Ingelheim states. Additional data from the trials showed that in patients with mild and moderate renal impairment, linagliptin blood plasma levels were comparable to those in type 2 diabetes patients with normal renal function. Boehringer Ingelheim says this finding is consistent with data suggesting linagliptin may have a primarily nonrenal route of excretion.

Linagliptin is a once-daily oral dipeptidyl peptidase-4 inhibitor designed to target the incretin hormones GLP-1 and GIP.

STRESS!

AM BACK!!

HI GUYS....
AM BACK FROM MY HIBERNATION PERIOD. FEELS LIKE LIVING IN STONE AGE WITHOUT INTERNET...

03 November, 2010

NEONATAL DIABETES

Neonatal diabetes mellitus is a monogenic form of diabetes that occurs in the first 6 months of life. It is a rare disease, occurring in only one in 100,000 to 500,000 live births. Infants with NDM do not produce enough insulin, leading to an increase in blood glucose. NDM can be mistaken for the much more common type 1 diabetes, but type 1 diabetes usually occurs later than the first 6 months of life. In about half of those with NDM, the condition is life long and is called permanent neonatal diabetes mellitus (PNDM). In the rest of those with NDM, the condition is transient and disappears during infancy but can reappear later in life; this type of NDM is called transient neonatal diabetes mellitus (TNDM). Specific genes that can cause NDM have been identified.
Symptoms of NDM include thirst, frequent urination, and dehydration. NDM can be diagnosed by finding elevated levels of glucose in blood or urine. In severe cases, the deficiency of insulin may cause the body to produce an excess of acid, resulting in a potentially life-threatening condition called ketoacidosis. Most fetuses with NDM do not grow well in the womb and newborns are much smaller than those of the same gestational age, a condition called intrauterine growth restriction. After birth, some infants fail to gain weight and grow as rapidly as other infants of the same age and sex. Appropriate therapy improves and may normalize growth and development.

20 October, 2010

ACCUPUNCTURE - USEFUL OR PLACEBO??

Acupuncture is the procedure of inserting and manipulating needles into various points on the body to relieve pain or for therapeutic purposes. The earliest written record of acupuncture is the Chinese text Shiji with elaboration of its history in the second century BCE medical text Huangdi Neijing. Different variations of acupuncture are practiced and taught throughout the world.
Acupuncture has been the subject of active scientific research both in regard to its basis and therapeutic effectiveness since the late 20th century, but it remains controversial among medical researchers and clinicians. Research on acupuncture points and meridians is preliminary and has not conclusively demonstrated their existence or properties. Clinical assessment of acupuncture treatments, due to its invasive and easily detected nature, makes it difficult to use proper scientific controls for placebo effects.
 Evidence supports the use of acupuncture to control some types of nausea and pain but evidence for the treatment of other conditions is equivocal and several review articles discussing the effectiveness of acupuncture have concluded it is possible to explain through the placebo effect.
 The World Health Organization and the United States' National Institutes of Health (NIH) have stated that acupuncture can be effective in the treatment of neurological conditions and pain, though these statements have been criticized for bias and a reliance on studies that used poor methodology. Reports from the USA's National Center for Complementary and Alternative Medicine (NCCAM), the American Medical Association (AMA) and various USA government reports have studied and commented on the efficacy (or lack thereof) of acupuncture. There is general agreement that acupuncture is safe when administered by well-trained practitioners using sterile needles, and that further research is needed.

27 September, 2010

Making Healthy Food Choices!!

Knowing what to eat can be confusing.

Everywhere you turn, there is news about what is or isn't good for you. Some basic principles have weathered the fad diets, and have stood the test of time.

Here are a few tips on making healthful food choices for you and your entire family.

  1. Eat lots of vegetables and fruits. Try picking from the rainbow of colors available to maximize variety.
  2. Eat non-starchy vegetables such as spinach, carrots, broccoli or green beans with meals.
  3. Choose whole grain foods over processed grain products. Try brown rice with your stir fry or whole wheat spaghetti with your favorite pasta sauce.
  4. Include dried beans (like kidney or pinto beans) and lentils into your meals.
  5. Include fish in your meals 2-3 times a week.
  6. Choose lean meats like cuts of beef and pork that end in "loin" such as pork loin and sirloin. Remove the skin from chicken and turkey.
  7. Choose non-fat dairy such as skim milk, non-fat yogurt and non-fat cheese.
  8. Choose water and calorie-free "diet" drinks instead of regular soda, fruit punch, sweet tea and other sugar-sweetened drinks.
  9. Choose liquid oils for cooking instead of solid fats that can be high in saturated and trans fats. Remember that fats are high in calories. If you're trying to lose weight, watch your portion sizes of added fats.
  10. Cut back on high calorie snack foods and desserts like chips, cookies, cakes, and full-fat ice cream.
Eating too much of even healthful foods can lead to weight gain. Watch your portion sizes.

25 September, 2010

CRITICISMS TO CONCEPT OF GLYCEMIC INDEX!!

If a person consumes 50% of his or her calories from carbohydrates, the glycemic index can enable him or her to consume the same number of calories and have lower, more stable glucose and insulin levels. The use of the glycemic index, however, is limited by several factors:

The glycemic index does not take into account other factors besides glycemic response, such as insulin response, which is measured by the insulin index and can be more appropriate in representing the effects from some food contents other than carbohydrates.

The glycemic index is significantly altered by the type of food, its ripeness, processing, the length of storage, cooking methods, and its variety (white potatoes are a notable example, ranging from moderate to very high GI even within the same variety


The glycemic response is different from one person to another, and even in the same person from day to day, depending on blood glucose levels, insulin resistance, and other factors.

The number of grams of carbohydrate impacts blood sugar levels more than the glycemic index. Lowering glycemic index leads to small improvements in the blood sugar level, but consuming fewer calories, losing weight, and carbohydrate counting would benefit the blood sugar level more.Carbohydrate impacts glucose levels most profoundly, and two foods with the same carbohydrate content are, in general, comparable in their effects on blood sugar. A food with a low glycemic index may have a high carbohydrate content or vice versa; this can be accounted for with the glycemic load. Consuming carbohydrates with a low glycemic index and calculating carbohydrate intake would produce the most stable blood sugar levels.

Most of the values on the glycemic index do not show the impact on glucose levels after two hours. Some diabetics may still have elevated levels after four hours.

The GI of foods is determined under experimental conditions after an overnight fast, and might not apply to foods consumed later during the day because glycemic response is strongly influenced by the composition of the previous meal, particularly when meals are consumed within an interval of few hours. Indeed, it has been shown that a high-GI breakfast cereal (GI = 124) elicited a lower increase in blood glucose concentrations at lunch than at breakfast. Also, the difference in glycemic responses induced by the low- and the high-GI breakfast cereals at lunch were lower than that predicted by the large difference in their GI, which was determined at breakfast.

GLYCEMIC INDEX

The glycemic index, glycaemic index, or GI is a measure of the effects of carbohydrates on blood sugar levels. Carbohydrates that break down quickly during digestion and release glucose rapidly into the bloodstream have a high GI; carbohydrates that break down more slowly, releasing glucose more gradually into the bloodstream, have a low GI. The concept was developed by Dr. David J. Jenkins and colleagues in 1980–1981 at the University of Toronto in their research to find out which foods were best for people with diabetes.

A lower glycemic index suggests slower rates of digestion and absorption of the foods' carbohydrates and may also indicate greater extraction from the liver and periphery of the products of carbohydrate digestion. A lower glycemic response usually equates to a lower insulin demand but not always, and may improve long-term blood glucose control and blood lipids. The insulin index is also useful, as it provides a direct measure of the insulin response to a food.

The glycemic index of a food is defined as the area under the two hour blood glucose response curve (AUC) following the ingestion of a fixed portion of carbohydrate (usually 50 g). The AUC of the test food is divided by the AUC of the standard (either glucose or white bread, giving two different definitions) and multiplied by 100. The average GI value is calculated from data collected in 10 human subjects. Both the standard and test food must contain an equal amount of available carbohydrate. The result gives a relative ranking for each tested food.

The current validated methods use glucose as the reference food, giving it a glycemic index value of 100 by definition. This has the advantages of being universal and producing maximum GI values of approximately 100. White bread can also be used as a reference food, giving a different set of GI values (if white bread = 100, then glucose ≈ 140). For people whose staple carbohydrate source is white bread, this has the advantage of conveying directly whether replacement of the dietary staple with a different food would result in faster or slower blood glucose response. The disadvantages with this system are that the reference food is not well-defined and the GI scale is culture dependent.

18 September, 2010

FLATBUSH DIABETES - TYPE 1 or TYPE2??

Flatbush diabetes is named after an area in New york where it was described some years ago.

Etiology

Exact etiology is not clear as of now. it has been suggested that some patients may develop Flatbush diabetes as they are extremely sensitive to transient damage to Beta cells by Glucotoxicity & Lipotoxicity. when this condition is reversed with diet , oral hypoglycemic agents or Insulin the beta cells are able to recover.

Why is the knowledge about Flatbush Diabetes important??


There is a lot we do not know about flatbush diabetes but the more we are aware that such a form of diabetes exists ,the more our physicians will be apt to spot patients who have it, and the more patients are correctly Diagnosed, the better their treatment will be!!

Characteristics of Flatbush Diabetes

Patients present with very high blood sugars (>700mg/dl)
No antibodies as seen in type 1 Diabetes
Ketosis might be present
Obesity
family history of type2 diabetes
patients have signs of insulin resistance
Patients respond well to OHA ( oral hypoglycemic agents) 

08 September, 2010

Hypoglycemic agents - Extinct, Present & Future

Sensitizers

Biguanides -Metformin, Buformin ( withdrawn from market),Phenformin ( withdrawn from market)
TZDs (PPAR) - Pioglitazone, Rivoglitazone ( in clinical trials), Rosiglitazone ( about to be withdrawn from market), Troglitazone ( withdrawn from market)
Dual PPAR agonists - Aleglitazar ( in clinical trials), Muraglitazar ( dropped during clinical trials), Tesaglitazar ( dropped during clinical trials)

Secretagogues

Sulfonylureas - 1st generation: Acetohexamide, Carbutamide, Chlorpropamide ,Gliclazide, Tolbutamide, Tolazamide.
2nd generation: Glibenclamide (Glyburide),Glipizide, Gliquidone, Glyclopyramide
3rd generation: Glimepiride

Meglitinides/"glinides" - Nateglinide, Repaglinide, Mitiglinide

GLP-1 analogs -Exenatide, Liraglutide, Taspoglutide( in clinical trials), Albiglutide ( in clinical trials)

DPP-4 inhibitors - Alogliptin ( in clinical trials), Linagliptin( in clinical trials), Saxagliptin, Sitagliptin, Vildagliptin

Analogs/other insulins -
Fast acting (Insulin lispro, Insulin aspart, Insulin glulisine)
Short acting (Regular insulin)
Long acting (Insulin glargine , Insulin detemir)
Inhalable insulin (Exubera)- withdrawn from market
NPH insulin

Alpha-glucosidase inhibitors -Acarbose, Miglitol , Voglibose

Amylin analog - Pramlintide

SGLT2 inhibitors - Canagliflozin ( in clinical trials) , Dapagliflozin ( in clinical trials) , Remogliflozin( in clinical trials) , Sergliflozin( in clinical trials)

Others - Benfluorex , Tolrestat ( withdrawn from market)

Insulin tolerance test

An insulin tolerance test (ITT) is a medical diagnostic procedure during which insulin is injected into a patient's vein to assess pituitary function, adrenal function, and sometimes for other purposes.

Insulin injections are intended to induce hypoglycemia. In response, Adrenocorticotropic hormone (ACTH) and Growth Hormone (GH) are released as a part of the stress mechanism. ACTH elevation causes the adrenal cortex to release cortisol. Normally, both cortisol and GH serve as Counterregulatory hormones, opposing the action of insulin.

Thus ITT is considered to be a Gold standard for assessing the integrity of the hypothalamo-pituitary-adrenal axis. Sometimes ITT is performed to assess the peak adrenal capacity, e.g. before surgery. It is assumed that the ability to respond to insulin induced hypoglycemia translates into appropriate cortisol rise in the stressful event of acute illness or major surgery.

Side Effects


Side effects include sweating, palpitations, loss of consciousness and rarely convulsions due to severe hypoglycemia which may cause coma. If extreme symptoms are present, glucose should be given intravenously. In subjects with no adrenal reserve an Addisonian crisis may occur. For cortisol stimulation, the ACTH stimulation test has much less risk

Contraindications to ITT

Age > 60 years
This test should not be performed on children outside a specialist pediatric endocrine unit
Ischemic heart disease
Epilepsy
Severe panhypopituitarism, hypoadrenalism
Hypothyroidism impairs the GH and cortisol response. Patients should have corticosteroid replacement commenced prior to thyroxine as the latter has been reported to precipitate an Addisonian crisis with dual deficiency. If adrenal insufficiency is confirmed, the need for a repeat ITT may need to be reconsidered after 3 months thyroxine therapy.

Interpratation -

The test cannot be interpreted unless hypoglycaemia (< 2.2 mmol/L) is achieved.

Hypopituitarism

An adequate cortisol response is defined as a rise to greater than 550 nmol/L. Patients with impaired cortisol responses (less than 550 but greater than 400 nmol/L) may only need steroid cover for major illnesses or stresses. An adequate GH response occurs with an absolute response exceeding 20 mU/L.

Cushing's syndrome

There will be a rise of less than 170 nmol/L above the fluctuations of basal levels of cortisol.

Physiological Effects Of Insulin!!

Insulin binds to its receptor, which in turn starts many protein activation cascades.

These include-

Translocation of Glut-4 transporter to the plasma membrane and influx of glucose, glycogen synthesis, glycolysis and fatty acid synthesis.

The actions of insulin on the human metabolism level include:


Control of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about ⅔ of body cells).
Increase of DNA replication and protein synthesis via control of amino acid uptake.
Modification of the activity of numerous enzymes.

The actions of insulin on cells include:

Increased glycogen synthesis
– insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin, which is directly useful in reducing high blood glucose levels as in diabetes.
Increased fatty acid synthesis – insulin forces fat cells to take in blood lipids, which are converted to triglycerides; lack of insulin causes the reverse.
Increased esterification of fatty acids – forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters; lack of insulin causes the reverse.
Decreased proteolysis – decreasing the breakdown of protein.
Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse.
Decreased gluconeogenesis – decreases production of glucose from non-sugar substrates, primarily in the liver (remember, the vast majority of endogenous insulin arriving at the liver never leaves the liver); lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.
Decreased autophagy - decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely.
Increased amino acid uptake – forces cells to absorb circulating amino acids; lack of insulin inhibits absorption.
Increased potassium uptake – forces cells to absorb serum potassium; lack of insulin inhibits absorption. Insulin's increase in cellular potassium uptake lowers potassium levels in blood.
Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; lack of insulin reduces flow by allowing these muscles to contract.
Increase in the secretion of hydrochloric acid by Parietal cells in the stomach.

06 September, 2010

Question for All...

does anybody have information on DEGLUDEC ?
Any information on new gliptins in the pipeline?

16 August, 2010

Fenofibric acid

Fenofibric acid is a lipid regulating agent available as delayed release capsules for oral administration.
Fenofibric acid activates the peroxisome proliferator activated receptor a (PPARa).
PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses.

fenofibric Acid is specifically indicated for

1) Co-administration Therapy with Statins for the Treatment of Mixed Dyslipidemia
To reduce TG and increase HDLC in patients with mixed dyslipidemia and CHD or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL-C goal.
2) Treatment of Severe Hypertriglyceridemia
3) Treatment of Primary Hyperlipidemia or Mixed Dyslipidemia
To reduce elevated LDL-C, Total-C, TG, and Apo B, and to increase HDL-C.

The recommended intial dose of the drug for co-administration therapy with statins for the treatment of mixed dyslipidemia is 135 mg daily. Co-administration with the maximum dose of a statin should be avoided.

The recommended initial dose of the drug for severe hypertriglyceridemia is 45 to 135 mg once daily.

The recommended initial dose of the drug for primary hyperlipidemia or mixed dyslipidemia is 135 mg once daily.


Mechanism of Action


fenofibric acid is a lipid regulating agent available as delayed release capsules for oral administration. Fenofibric acid activates the peroxisome proliferator activated receptor a (PPARa). Through this mechanism, fenofibric acid increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of Apo CIII (an inhibitor of lipoprotein lipase activity). The resulting decrease in triglycerides produces an alteration in the size and composition of LDL from small, dense particles to large buoyant particles, which have a greater affinity for cholesterol receptors and are catabolized rapidly. PPARa activation also induces an increase in the synthesis of HDL-C and Apo AI and AII.

Side Effects


* Muscle Pain
* Tenderness
* Weakness
* Tiredness
* Fever
* Abdominal Pain
* Nausea
* Vomiting

Bromocriptine & Type 2 Diabetes

Bromocriptine (Parlodel, Cycloset), an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease (PD), Hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.

Indications


Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly may all be caused by pituitary problems, such as hyperprolactinaemia, and therefore, these problems may be treated by this drug. In 2009, bromocriptine mesylate was approved by the FDA for treatment of type 2 diabetes under the trade name Cycloset (VeroScience). It is currently unknown how this drug improves glycemic control, but it has been shown to reduce HbA1c by ~0.5%.

Side effects


Most frequent side effects are nausea, orthostatic hypotension, headaches and vomiting through stimulation of the brainstem vomiting centre.
Bromocriptine can cause worsening of liver problems.
Vasospasms with serious consequences such as myocardial infarction and strong have been reported in connection with the puerperium, appears to be extremely rare event.
Bromocriptine use has been anecdotically associated with causing or worsening psychotic symptoms (its mechanism is in opposition of most antipsychotics, whose mechanisms generally block dopamine).
Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.

30 July, 2010

Gymnema sylvestre


Gymnema sylvestre is a herb native to the tropical forests of southern and central India where it has been used as a naturopathic treatment for diabetes.

Sanskrit Name : Meshasringi, Madhinasini or madhoolika, Hindi: Gurmar, Tamil and Malayalam are Sirukurinchaan(சிறுகுரிஞ்சான்), Amudhapushpam, Chakkarakkolli.


Chemical composition

The major bioactive constituents of Gymnema sylvestris are a group of oleanane type triterpenoid saponins known as gymnemic acids. The latter contain several acylated (tigloyl, methylbutyroyl etc.,) derivatives of deacylgymnemic acid (DAGA) which is 3-O-glucuronide of gymnemagenin (3, 16, 21, 22, 23, 28-hexahydroxy-olean-12-ene)2. The individual gymnemic acids (saponins) include gymnemic acids I-VII, gymnemosides A-F, gymnemasaponins

G. sylvestre leaves contain triterpene saponins belonging to oleanane and dammarene classes. Oleanane saponins are gymnemic acids and gymnemasaponins, while dammarene saponins are gymnemasides. Besides this, other plant constituents are flavones, anthraquinones, hentri-acontane, pentatriacontane, α and β- chlorophylls, phytin, resins, d-quercitol, tartaric acid, formic acid, butyric acid, lupeol, β-amyrin related glycosides and stigmasterol. The plant extract also tests positive for alkaloids. Leaves of this species yield acidic glycosides and anthroquinones and their derivatives.

Gymnemic acids have antidiabetic, antisweetener and anti-inflammatory activities. The antidiabetic array of molecules has been identified as a group of closely related gymnemic acids after it was successfully isolated and purified from the leaves of Gymnema sylvestre. Later, the phytoconstituents of Gymnema sylvestre were isolated, and their chemistry and structures were studied and elucidated.


While it is still being studied, and the effects of the herb are not entirely known, the herb has been shown to reduce blood sugar levels when used for an extended period of time. Additionally, Gymnema reduces the taste of sugar when it is placed in the mouth, thus some use it to fight sugar cravings. From extract of the leaves were isolated glycosides known as Gymnemic acids, which exhibit anti-sweet activity.


This effect lasts up to about 2 hours. Some postulate that the herb actually reduces cravings for sugar by blocking sugar receptors in the tongue. This effect was observed in rats in a 2003 study conducted by CH Lemon, et al. It is currently being used in an all natural medication for diabetes with other ingredients such as cinnamon, chromium, zinc, biotin, banaba plant, huckleberry and bitter melon.
The active ingredient is thought to be gurmenic acid which has structure similar to saccharose. Extracts of Gymnema is not only claimed to curb sweet tooths but also for treatment of as varied problems as hyperglycemia, obesity, high cholesterol levels, anemia and digestion. According to the Sushruta of the Ayurveda it helps to treat Madhumeha ie glycosuria.

In 2005, a study made by King’s College, London, United Kingdom, showed that a water-soluble extract of Gymnema Sylvestre, caused reversible increases in intracellular calcium and insulin secretion in mouse and human β-cells when used at a concentration (0.125 mg/ml) without compromising cell viability. Hence forth these data suggest that extracts derived from Gymnema Sylvestre may be useful as therapeutic agents for the stimulation of insulin secretion in individuals with Type 2 Diabetes.

Alternative names
The plants also goes under many other names such as; Gurmari, Gurmarbooti, Gurmar, periploca of the woods and Meshasringa. The Hindi word Gur-mar (Madhunaashini in Sanskrit, Chakkarakolli in Tamil), literally means sugar destroyer. Meshasringa (Sanskrit) translates as "ram's horn", a name given to the plant from the shape of its fruits. Gymnema probably derives from the Latin word meaning naked and sylvestre means from the forest.

30 June, 2010

Fenugreek (Trigonella foenum-graecum)


Fenugreek (Trigonella foenum-graecum) is an herbal supplement often claimed to be beneficial for the following uses:

Lowering blood sugar in people with diabetes
Helping with a loss of appetite
Lowering cholesterol
Lowering triglycerides
Stimulating milk production in breastfeeding women.



Fenugreek contains sotolon, trigonelline, and 4-hydroxyisoleucine, compounds that are thought to be the active components of it. 4-hydroxyisoleucine may stimulate the secretion of insulin, which is why fenugreek may theoretically lower blood sugar. The seeds also contain fiber and pectin, a complex carbohydrate, both of which may slow down the digestive tract, which can help lower blood sugar. However, it is important to know that there is not enough scientific evidence to show that fenugreek is indeed effective for these uses.

Fenugreek may also contain "blood-thinning" compounds known as coumarins, but it is not known if these compounds are present in high enough quantities to actually make a difference in humans. The herb may also stimulate the uterus, heart, and intestines. However, it is important to know that there is not sufficient scientific evidence to show that fenugreek is effective for these uses.

Side Effects

Fenugreek can cause several side effects

Diarrhea
Indigestion or heartburn
Low blood sugar (hypoglycemia)
Body and urine odors that smell like maple syrup.


Is Fenugreek Safe?

Normal doses are probably safe for most people when taken in normal amounts, such as amounts found in food, although higher doses can cause problems. Some people may be more likely to experience problems than others.
Therefore, you should talk with your healthcare provider prior to taking this supplement if you have:

Diabetes
A bleeding disorder
Any allergies, including allergies to foods, dyes, or preservatives.


Also, let your healthcare provider know if you are:

Pregnant or thinking of becoming pregnant
Breastfeeding.

Make sure to tell your healthcare provider about all other medicines you are taking, including prescription and non-prescription medicines, vitamins, and herbal supplements.

It is not known exactly what to expect from a fenugreek overdose, but it is reasonable to assume that taking too much may cause the usual side effects of fenugreek, but they may be more severe. Theoretically, an overdose could cause severe problems, such as internal bleeding or dangerously low blood sugar.

RETINOPATHY IN DIABETES!!


Retina has tiny blood vessels that are easy to damage. Having high blood glucose and high blood pressure for a long time can damage these tiny blood vessels.

Initially these tiny blood vessels swell and weaken. Some blood vessels then become clogged and do not let enough blood through. most patients do not experience any symptoms in this stage

One eye may be damaged more than the other, or both eyes may have the same amount of damage. As diabetic retinopathy becomes worse, new blood vessels grow. These new blood vessels are weak. They break easily and leak blood into the vitreous of eye. The leaking blood keeps light from reaching the retina.

In this stage patients may experience floating spots or almost total darkness. Sometimes, the blood will clear out by itself, in other cases surgery is required to remove it.

Over the years, the swollen and weak blood vessels can form scar tissue and pull the retina away from the back of the eye. If the retina becomes detached, you may see floating spots or flashing lights. You may feel as if a curtain has been pulled over part of what you are looking at. This condition can cause loss of sight or blindness if you don't take care of it right away.

Symptoms

Often, there are no symptoms in the early stages of this diabetic eye disease. Vision may not change until the disease becomes severe, nor is there any pain. Blurred vision may occur when the macula -- the part of the retina that provides sharp, central vision -- swells from the leaking fluid. This condition is called macular edema.

If new blood vessels have grown on the surface of the retina, they can bleed into the eye, blocking vision. Even in more advanced cases, the disease may progress a long way without any noticeable symptoms, so regular eye examinations for people with diabetes are important.

Treatment

There are a number of treatment options for diabetic retinopathy. Your eye doctor may suggest laser treatment, which involves a light beam aimed into the retina of the damaged eye. The beam closes off leaking blood vessels, which may stop blood and fluid from leaking into the vitreous and slow down the loss of sight.

If a lot of blood has leaked into your vitreous and your sight is poor, your eye doctor might suggest you have surgery called a vitrectomy. This procedure removes blood and fluids from the vitreous of your eye. Then, clean fluid is put back into the eye. The surgery often makes your eyesight better.

28 June, 2010

Diabetic Retinopathy !

Diabetic Gastroparesis!!

Diabetic gastroparesis is the result of damage to the vagus nerve, which controls the movement of food through the digestive system. In a person with this condition, the stomach takes too long to empty its contents. Symptoms include heartburn, nausea, vomiting undigested food, and weight loss. In most cases, treatment does not cure the problem.It often occurs in people with type 1 diabetes or type 2 diabetes. -- it is usually a chronic condition.

Signs & Symptoms

Heartburn
Nausea
Vomiting of undigested food
An early feeling of fullness when eating
Weight loss
Abdominal bloating
Erratic blood glucose levels
Lack of appetite
Gastroesophageal reflux
Spasms of the stomach wall.

Treatment options

Dietry pattern

Taking small frequent meals
try several liquid meals a day until your blood glucose levels are stable
avoid high-fat and high-fiber foods

Pharmacotherapy

Metoclopramide - Stimulates stomach muscle contractions to help empty food. It also helps reduce nausea and vomiting. Metoclopramide is taken 20 to 30 minutes before meals and at bedtime. Side effects of this drug are fatigue, sleepiness, and sometimes depression, anxiety, and problems with physical movement.

Erythromycin - This antibiotic also improves stomach emptying. It works by increasing the contractions that move food through the stomach. Side effects are nausea, vomiting, and abdominal cramps.

Domperidone - It is a promotility agent like metoclopramide. Domperidone also helps with nausea.

Newer Options - A gastric neurostimulator has been developed to assist people with diabetic gastroparesis. The battery-operated device is surgically implanted and emits mild electrical pulses that help control nausea and vomiting associated with diabetic gastroparesis.

The use of botulinum toxin has been shown to improve stomach emptying and the symptoms of diabetic gastroparesis by decreasing the prolonged contractions of the muscle between the stomach and the small intestine (pyloric sphincter). The toxin is injected into the pyloric sphincter.

Gastroparesis - other causes

Postviral syndromes
Anorexia nervosa
Surgery on the stomach or vagus nerve
Medications, particularly anticholinergics and narcotics (these drugs slow contractions in the intestine)
Gastroesophageal reflux disease (rarely)
Smooth muscle disorders such as amyloidosis and scleroderma
Nervous system diseases, including abdominal migraine and Parkinson's disease
Metabolic disorders, including hypothyroidism.

27 June, 2010

Gestational / pregnancy induced Diabetes

Gestational diabetes generally resolves once the baby is born. Based on different studies, the chances of developing GDM in a second pregnancy are between 30 and 84%, depending on ethnic background. A second pregnancy within 1 year of the previous pregnancy has a high rate of recurrence.

Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future.
The risk is highest in women who needed insulin treatment,
Had antibodies associated with diabetes (such as antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2),
Women with more than two previous pregnancies,
Women who were obese.

Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years.
The risk appears to be highest in the first 5 years, reaching a plateau thereafter.

Children of women with GDM have an increased risk for childhood and adult obesity and an increased risk of glucose intolerance and type 2 diabetes later in life.
This risk relates to increased maternal glucose values.It is currently unclear how much genetic susceptibility and environmental factors each contribute to this risk, and if treatment of GDM can influence this outcome.

23 June, 2010

FOOT PROBLEMS - HEEL FISSURES!!

Heel fissures, also known as cracked heels can be a simple cosmetic problem and a nuisance, but can also lead to serious medical problems. Heel fissures occur when the skin on the bottom, outer edge of the heel becomes hard, dry and flaky, sometimes causing deep fissures that can be painful or bleed.

Heel fissures can affect anyone, but common risk factors are
Living in a dry climate
Obesity
Walking barefoot or wearing sandals or open-backed shoes
Inactive sweat glands

Treatment and Prevention

Moisturizing the feet regularly can prevent heel fissures. Once they occur, you can use a pumice stone daily to gently decrease the thick and flaky layer of skin. Avoid going barefoot or wearing open-backed shoes, sandals or shoes with thin soles. Shoes with strong shock absorption can help to improve the condition.

Moisturizing the feet at least twice a day and wearing socks over moisturizer while sleeping can also help.

INSULIN HOW TO USE??

NOVOLET






VICTOZA





CLIPS!!

DIABETES MELLITUS






DIABETIC NEPHROPATHY








TYPE 1 DIABETES




21 June, 2010

Common foot problems - Fungal Infection!



Toenail fungus, known as Onychomycosis, Fungal infections occur when microscopic fungi gain entry through a small trauma in the nail, then grow and spread in the warm, moist environment inside the patient's socks and shoes.


Symptoms of toenail fungus, which can be caused by several types of fungi, include swelling, yellowing, thickening or crumbling of the nail, streaks or spots down the side of the nail, and even complete loss of the nail. Toenail color can vary from brown or yellow to white with this condition.

Fungal infections can affect the fingernails as well as the toenails, but toenail fungus is more difficult to treat because toenails grow more slowly. It occurs most often on the big or small toe, but might occur on any toe.

Cause

Toenail fungus can be picked up in damp areas. Athletes and people who wear tight-fitting shoes or tight hosiery that cause trauma to the toes or keep the feet from drying out are at higher risk. The condition can also spread from one toe to another, or to other parts of the body.

Other risk factors include abnormal PH level of the skin, not drying off the feet thoroughly after bathing or exercise, and a compromised immune system in someone who has been exposed to a fungus. Diabetics have an increased risk of contracting a toenail fungus because their immune system is compromised. They should have their nails cut and debrided by a podiatrist.

Treatment and Prevention


Because it is difficult to treat or eradicate toenail fungus, it is a good idea to try to prevent it.

Wash your feet regularly, and dry them thoroughly when they get wet. Wearing nail polish on the toes is not advised because it can seal in fungus and allow it to grow. Keep toenails trimmed, and be sure to disinfect any pedicure tools before using them.

If you do develop toenail fungus, see your foot doctor. The doctor might remove as much of the nail as possible by trimming, filing or dissolving it. Medicated nail polish might be prescribed for a localized infection, but a serious infection will likely be treated with a prescription oral antifungal medication. These medications can have side effects, so be sure to work closely with your doctor on your treatment plan. Only in severe cases will surgical removal of the nail be recommended.

Common foot problems - Heel Pain!!

Heel pain is a common condition in which weight bearing on the heel causes extreme discomfort.

Cause

There are two different categories of heel pain. The first is caused by repetitive stress which refers to a soreness resulting from too much impact on a specific area of the foot. This condition, often referred to as "heel pain syndrome," can be caused by shoes with heels that are too low, a thinned out fat pad in the heel area, or from a sudden increase in activity.

Plantar fasciitis, a very common diagnosis of heel pain, is usually caused from a biomechancial problem, such as flat feet. The plantar fascia is a broad band of fibrous tissue that runs along the bottom surface of the foot, from the heel through the midfoot and into the forefoot. Flat feet can cause the plantar fascia to be excessively stretched and inflamed, resulting in pain in the heel and arch areas of the foot. Often the pain will be most intense first thing in the morning or after a prolonged period of rest. The pain will gradually subside as the day progresses.

Treatment and Prevention

To properly treat heel pain, you must absorb shock, provide cushioning and elevate the heel to transfer pressure. This can be accomplished with a heel cup, visco heel cradle, or an orthotic designed with materials that will absorb shock and shear forces.

When the condition is pronation related (usually plantar fasciitis), an orthotic with medial posting and good arch support will control the pronation and prevent the inflammation of the plantar fascia.

Footwear selection is also an important criteria when treating heel pain. Shoes with a firm heel counter, good arch support, and appropriate heel height are the ideal choice..

Common foot problems - CORNS






Definition

Corns like calluses develop from an accumulation of dead skin cells on the foot, forming thick, hardened areas. They contain a cone-shaped core with a point that can press on a nerve below, causing pain. Corns can become inflamed due to constant friction and pressure from footwear. Corns that form between the toes are sometimes referred to as soft corns.




Cause

Some of the common causes of corn development are
Tight fitting footwear
High heeled footwear
Tight fitting stockings and socks
Deformed toes
Due to foot sliding forward in a shoe that fits too loosely.

Complications that can arise from corns include bursitis and the development of an ulcer.

Treatment and Prevention

There are very simple ways to prevent and treat the corns.
You should wear properly fitted footwear with extra room in the toe box (toe area).
Avoid shoes that are too tight or too loose.
Use an insole that will absorb shock and shear forces.
Also avoid tight socks and stockings to provide a healthier environment for the foot.

Do not use corn removing solutions and medicated pads. These solutions can sometimes increase irritation and discomfort. Diabetics and all other individuals with poor circulation should never use any chemical agents to remove corns.

If the problem persists, consult a Podiatric surgeon

Pedicure in diabetics!

Soak your feet into your little foot basin containing warm, soapy water or a disinfectant for sore feet.
After 15 minutes, gently brush nails with a nail brush.
Use a pumice stone to rub off dead skin and smoothen heels. A gentle to and from movement helps to scrub off dead cells.
Blot dry excess water from feet and between your toes.
Trim your nails using scissors or nail clipper. Cut it straight across.
Use an emery board or nail file to file nails. Avoid filing the sides of nails as it will lead to ingrown toe nails.
Use a little cuticle cream to ease back cuticles steadily and very gently. Do not cut cuticles as toe nails require them for protection. Just loosen cuticle and push back gently.
A damp cotton wool covered orange stick helps to clean undernails.
Massage in a rich cream or moisturizing lotion.
Give your feet a relaxing massage using long sweeping movements.

20 June, 2010

Thyroid & Diabetes..

Diabetic patients have a higher prevalence of thyroid disorders compared with the normal population. Because patients with one organ-specific autoimmune disease are at risk of developing other autoimmune disorders, and thyroid disorders are more common in females, it is not surprising that up to 30% of female type 1 diabetic patients have thyroid disease. The rate of postpartum thyroiditis in diabetic patients is three times that in normal women. A number of reports have also indicated a higher than normal prevalence of thyroid disorders in type 2 diabetic patients, with hypothyroidism being the most common disorder.


Thyroid disease in the general
population: 6.6%
Thyroid disease in diabetes:
Overall prevalence: 10.8¬13.4%
Hypothyroidism: 3¬6%
Subclinical hypothyroidism: 5¬13%
Hyperthyroidism: 1¬2%
Postpartum thyroiditis: 11%


The presence of thyroid dysfunction may affect diabetes control. Hyperthyroidism is typically associated with worsening glycemic control and increased insulin requirements. There is underlying increased hepatic gluconeogenesis, rapid gastrointestinal glucose absorption, and probably increased insulin resistance. Indeed, thyrotoxicosis may unmask latent diabetes.

First, in hyperthyroid patients, the diagnosis of glucose intolerance needs to be considered cautiously, since the hyperglycemia may improve with treatment of thyrotoxicosis.

Second, underlying hyperthyroidism should be considered in diabetic patients with unexplained worsening hyperglycemia.

Third, in diabetic patients with hyperthyroidism, physicians need to anticipate possible deterioration in glycemic control and adjust treatment accordingly. Restoration of euthyroidism will lower blood glucose level.

Even subclinical hypothyroidism can exacerbate the coexisting dyslipidemia commonly found in type 2 diabetes and further increase the risk of cardiovascular diseases. Adequate thyroxine replacement will reverse the lipid abnormalities.
In young women with type 1 diabetes, there is a high incidence of autoimmune thyroid disorders. Transient thyroid dysfunction is common in the postpartum period and warrants routine screening with serum thyroid-stimulating hormone (TSH) 6¬8 weeks after delivery. Glucose control may fluctuate during the transient hyperthyroidism followed by hypothyroidism typical of the postpartum thyroiditis. It is important to monitor thyroid function tests in these women since approximately 30% will not recover from the hypothyroid phase and will require thyroxine replacement. Recurrent thyroiditis with subsequent pregnancies is common.

18 June, 2010

Thanks Dr.deepa

I would like to thank Dr.Deepa (Diabetologist) for her sincere support. Right from the day I started this blog she has spared a bit of her valuble time to go through the posts in my blog and comment about each and every post. I would like to post a small part of her comments which might be useful to the readers of this blog.


Comments about Otelixizumab


This Drug is effective only if there is some beta cell reserve in the body and only if are known to have some autoantibody. Otherwise no use. This has created an excitement in the type 1 children, which actually might not be useful unless they have a significant c peptide level. Pts having a subnormal reserve of insulin can also be tried on this drug as there are other benefits in retaining the existing B-cells.

Comments about Glucometer


Actually the first blood should be wiped off and only the second drop should be taken without squeezing much. Because the first drop contains more of interstitial fluid more than blood. Most of them forget this pt.

Comment about Alcohol & Diabetes

The reason for using calorie free drink mixers is that, by adding soft drinks, the glucose in it can actually trigger insulin release and worsen the anticipated hypoglycemia. Since there is no calorie in alcohol the insulin release cannot be neutralized. The reason why pt develop hypo after taking alcohol is that it suppresses HGO (Hepatic Glucose Output).And most of the pts skip the food after taking alcohol, so the condition is even more worse.

Once again I would like to thank Dr.Deepa for her comments and hope that her support for my blog will continue in future too!!

05 June, 2010

Can a Diabetic have ALCOHOL??

Beyond all the health and safety concerns about alcohol, if you have diabetes and are on diabetes medications that lower blood glucose, you need to practice caution. Insulin and some diabetes pills can lower blood glucose. So, you should not drink when your blood glucose is low or when your stomach is empty.

Alcohol can cause hypoglycemia shortly after drinking and for 8-12 hours after drinking. So, if you want to drink alcohol, check your blood glucose before you drink and eat either before or while you drink. You should also check your blood glucose before you go to bed to make sure it is at a safe level -- between 100 and 140 mg/dL. If your blood glucose is low, eat something to raise it. The symptoms of too much alcohol and hypoglycemia can be similar -- sleepiness, dizziness, and disorientation.

A Few Guidelines

If you choose to drink alcohol, limit the amount and have it with food. Talk with your health care team about whether alcohol is safe for you.

Women should drink 1 or fewer alcoholic beverages a day (1 alcoholic drink equals a 12 oz beer, 5 oz glass of wine, or 1 ½ oz distilled spirits (vodka, whiskey, gin, etc.)
Men can drink 2 or fewer alcoholic drinks a day.
If you drink alcohol at least several times a week, make sure your doctor knows this before he/she prescribes a diabetes pill.

More Tips to Sip By


Drink only when and if blood glucose is under control.
Do not omit food from your regular meal plan.
Test blood glucose to help you decide if you should drink.
Wear an I.D. that notes you have diabetes.
Sip a drink slowly to make it last.
Have a no calorie beverage by your side to quench your thirst.
Try wine spritzers to decrease the amount of wine in the drink.
Use calorie-free drink mixers -- diet soda, club soda, diet tonic water, or water.
Drink alcohol with a snack or meal. Some good snack ideas are pretzels, popcorn, crackers, fat-free or baked chips, raw vegetables and a low-fat yogurt dip.
Find a registered dietitian to help you fit alcohol into your food plan.
Do not drive or plan to drive for several hours after you drink alcohol.

03 June, 2010

Landmarks in Insulin's journey!!

1922 Banting, Best, Collip use bovine insulin extract in humans
1923
Eli Lilly produces commercial quantities of much purer bovine insulin than Banting et al. had used
1923
Farbwerke Hoechst, one of the forerunner's of today's Sanofi Aventis, produces commercial quantities of bovine insulin in Germany
1923
Hagedorn founds the Nordisk Insulin laboratorium in Denmark – forerunner of today's Novo Nordisk
1926
Nordisk receives a Danish charter to produce insulin as a non-profit
1936
Canadians D.M. Scott, A.M. Fisher formulate a zinc insulin mixture and license it to Novo
1936
Hagedorn discovers that adding protamine to insulin prolongs the duration of action of insulin
1946
Nordisk formulates Isophane porcine insulin aka Neutral Protamine Hagedorn or NPH insulin
1946
Nordisk crystallizes a protamine and insulin mixture
1950
Nordisk markets NPH insulin
1953
Novo formulates Lente porcine and bovine insulins by adding zinc for longer lasting insulin
1955
Frederick Sanger determines the amino acid sequence of insulin
1969
Dorothy Crowfoot Hodgkin solves the crystal structure of insulin by x-ray crystallography
1973
Purified monocomponent (MC) insulin is introduced
1973
The U.S. officially "standardized" insulin sold for human use in the U.S. to U-100 (100 units per milliliter). Prior to that, insulin was sold in different strengths, including U-80 (80 units per milliliter) and U-40 formulations (40 units per milliliter), so the effort to "standardize" the potency aimed to reduce dosage errors and ease doctors' job of prescribing insulin for patients.
1978
Genentech produces biosynthetic 'human' insulin in Escheria coli bacteria using recombinant DNA techniques, licenses to Eli Lilly
1981
Novo Nordisk chemically and enzymatically converts porcine to 'human' insulin
1982
Genentech synthetic 'human' insulin (above) approved
1983
Eli Lilly and Company produces biosynthetic 'human' insulin with recombinant DNA technology, Humulin
1985
Axel Ullrich sequences a human cell membrane insulin receptor.
1988
Novo Nordisk produces recombinant biosynthetic 'human' insulin
1996
Lilly Humalog "lispro" insulin analogue approved.
2000
Sanofi Aventis Lantus insulin "glargine" analogue approved for clinical use in the US and Europe.
2004
Sanofi Aventis Apidra insulin "glulisine" insulin analogue approved for clinical use in the US.
2005
MedActiv invents the world's smallest fridge, the Medifridge, to safely transport insulin for patients.
2006
Novo Nordisk Levemir "detemir" insulin analogue approved for clinical use in the US.

Colour Coding of Insulin!!

28 May, 2010

Type 1 - Recent advances (Otelixizumab) !!

Otelixizumab, also known as TRX4, is a novel monoclonal antibody, which is being developed for the treatment of type 1 diabetes and other autoimmune diseases. The antibody is being developed by Tolerx, Inc. in collaboration with GlaxoSmithKline and is being manufactured by Abbott Laboratories.

As a monoclonal antibody, otelixizumab consists of two heavy chains and two light chains. The heavy chains are humanized γ1 (gamma-1) chains from rats, making otelixizumab an immunoglobulin G1. The light chains are chimeric human/rat λ (lambda) chains.

Mechanism of action

Otelixizumab is one of several investigational monoclonal antibodies that target CD3, a T lymphocyte receptor involved in normal cell signaling. More specifically, otelixizumab targets the epsilon chain of CD3. Data suggest that the drug works by blocking the function of effector T cells, which mistakenly attack and destroy insulin-producing beta cells while stimulating regulatory T cells, which are understood to protect against effector T cell damage, thus preserving the beta cells' normal ability to make insulin.

Clinical progress

The efficacy and safety of otelixizumab for the treatment of autoimmune type 1 diabetes is currently being studied in a pivotal Phase 3 study called DEFEND (Durable-response therapy Evaluation For Early or New-onset type 1 Diabetes). DEFEND is a randomized, placebo-controlled Phase 3 trial designed to enroll approximately 240 adult patients, age 18 to 35, with newly diagnosed autoimmune type 1 diabetes. DEFEND is being conducted at multiple centers in North America and Europe. The trial is designed to evaluate whether a single course of otelixizumab, administered not more than 90 days after the initial diagnosis, will reduce the amount of administered insulin required to control blood glucose levels by inhibiting the destruction of beta cells.

Orphan drug status


Otelixizumab has been granted Orphan Drug Status by the U.S. Food and Drug Administration.

Now whats orphan drug status???


An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease. The assignment of orphan status to a disease and to any drugs developed to treat it is a matter of public policy in many countries, and has resulted in medical breakthroughs that may not have otherwise been achieved due to the economics of drug research and development.

26 May, 2010

Liraglutide

Liraglutide marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, and by the U.S. Food and Drug Administration (FDA) on January 25, 2010.

Liraglutide is marketed under the brandname Victoza in the U.S. and Europe. It has been launched in Germany, Denmark, the Netherlands, the United Kingdom, Ireland, and the United States.

Cancer concerns

On April 2, 2009, an FDA advisory panel reviewed the significance of malignant C-cell carcinoma and thyroid C-cell focal hyperplasia in rats and mice. Some say the tumors were caused by a non-genotoxic, specific receptor-mediated mechanism to which rodents are particularly sensitive whereas non-human primates and humans are not. The Victoza label carries a Black Box Warning, "Because of the uncertain relevance of the rodent thyroid C-cell tumor findings to humans, prescribe Victoza only to patients for whom the potential benefits are considered to outweigh the potential risk". The FDA said that serum calcitonin, a biomarker of medulliary thyroid cancer, was slightly increased in liraglutide patients but still within normal ranges, and it required ongoing monitoring for 15 years in a cancer registry.

Pharmacodynamics

Studies to date suggest liraglutide improves control of blood glucose. It reduces meal-related hyperglycemia (for 12 hours after administration) by increasing insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

Liraglutide may have advantages over current therapies:

It acts in a glucose-dependent manner, meaning that it will stimulate insulin secretion only when blood glucose levels are higher than normal. Consequently, it shows negligible risk of hypoglycemia.
It has the potential for inhibiting apoptosis and stimulating regeneration of beta cells (seen in animal studies).
It decreases appetite and maintains body weight, as shown in a head-to-head study versus glimepiride.
It lowers blood triglyceride levels.
It has only mild and transient side effects, mainly gastrointestinal.

Pharmacokinetics


Liraglutide is a once-daily GLP-1 derivative for the treatment of type 2 diabetes. GLP-1, in its natural form, is short-lived in the body (the half-life after subcutaneous injection is approximately one hour), so it is not very useful as a therapeutic agent. However, liraglutide has a half-life after subcutaneous injection of 11–15 hours, making it suitable for once-daily dosing
The prolonged action of liraglutide is achieved by attaching a fatty acid molecule at one position of the GLP-1 molecule, enabling it to bind to albumin within the subcutaneous tissue and bloodstream. The active GLP-1 is then released from albumin at a slow, consistent rate. Binding with albumin also results in slower degradation and reduced elimination of liraglutide from the circulation by the kidneys compared to GLP-1

20 May, 2010

Insulin - Tissue clumps to Humulin!!

In 1869 Paul Langerhans, a medical student in Berlin, was studying the structure of the pancreas under a microscope when he identified some previously un-noticed tissue clumps(Islets of Langerhans) scattered throughout the bulk of the pancreas.

Edouard Laguesse later suggested that they might produce secretions that play a regulatory role in digestion. Paul Langerhans' son, Archibald, also helped to understand this regulatory role. The term insulin origins from Insel, the German word for islet/island.

In 1889, the Polish-German physician Oscar Minkowski in collaboration with Joseph von Mering removed the pancreas from a healthy dog to test its assumed role in digestion. Several days after the dog's pancreas was removed, Minkowski's animal keeper noticed a swarm of flies feeding on the dog's urine. On testing the urine they found that there was sugar in the dog's urine, establishing for the first time a relationship between the pancreas and diabetes.

In 1901, another major step was taken by Eugene Opie, when he clearly established the link - Diabetes mellitus … is caused by destruction of the islets of Langerhans and occurs only when these bodies are in part or wholly destroyed. Before his work, the link between the pancreas and diabetes was clear, but not the specific role of the islets.

In 1906 George Ludwig Zuelzer was partially successful treating dogs with pancreatic extract but was unable to continue his work.

Between 1911 and 1912, E.L. Scott at the University of Chicago used aqueous pancreatic extracts and noted a slight diminution of glycosuria but was unable to convince his director of his work's value; it was shut down.

Israel Kleiner demonstrated similar effects at Rockefeller University in 1919, but his work was interrupted by World War I and he did not return to it.

Nicolae Paulescu, a professor of physiology at the University of Medicine and Pharmacy in Bucharest, was the first one to isolate insulin, which he called at that time pancrein,

In October 1920 Canadian Frederick Banting was reading one of Minkowski's papers and concluded that it is the very digestive secretions that Minkowski had originally studied that were breaking down the islet secretion(s), thereby making it impossible to extract successfully. He decided to Ligate pancreatic ducts of the do, Keep dogs alive till acini degenerate leaving islets and try to isolate internal secretion of these and relieve glycosuria.

Banting's method was to tie a ligature (string) around the pancreatic duct, and when examined several weeks later, the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets. They then isolated an extract from these islets, producing what they called isletin ( now know as insulin), and tested this extract on the dogs. Banting and Best were then able to keep a pancreatectomized dog named Alpha alive for the rest of the summer by injecting her with the crude extract they had prepared. Removal of the pancreas in test animals essentially mimics diabetes, leading to elevated blood glucose levels. Alpha was able to remain alive because the extracts, containing isletin, were able to lower her blood glucose levels.

In December 1921, Macleod invited the biochemist James Collip to help with this task and within a month the team felt ready for a clinical test.

On January 11, 1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were canceled.

Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract, and a second dose was injected on January 23. This was completely successful, not only in having no obvious side-effects but also in completely eliminating the glycosuria sign of diabetes.

In one of medicine's more dramatic moments Banting, Best and Collip went from bed to bed injecting an entire ward with the new purified extract. Before they had reached the last dying child the first few were awakening from their coma to the joyous exclamations of their families.

Over the spring of 1922, Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand but the preparation remained impure.

The drug firm Eli Lilly and Company had offered assistance not long after the first publications in 1921 and they took Lilly up on the offer in April. In November Lilly made a major breakthrough and were able to produce large quantities of highly refined, 'pure' insulin. Insulin was offered for sale shortly thereafter.

The amino-acid structure of insulin was characterized in the 1950s and the first synthetic insulin was produced simultaneously in the labs of Panayotis Katsoyannis at the University of Pittsburgh and Helmut Zahn at RWTH Aachen University in the early 1960s.

The first genetically-engineered, synthetic "human" insulin was produced in a laboratory in 1977 by Herbert Boyer using E. coli. Partnering with Genentech founded by Boyer, Eli Lilly went on in 1982 to sell the first commercially available biosynthetic human insulin under the brand name Humulin.

16 May, 2010

Metformin - Corner stone of Type2 Diabetes

The main use for Metformin is in the treatment of Type2 Diabetes, especially in overweight people. Metformin is absorbed from the Small Intestine. Half life of Metformin is around 4-6hours. Oral bioavailablity is around 50-60%. Metformin is excreted unchanged via kidneys

Advantages of Metformin

.For Blood Sugar Control
.HbA1c reduction expected with metformin is approximately 1-2%
.Weight Loss ( Due to its insulin sparing effect)
.Increases Body's sensitivity to insulin ( decreases insulin resistance)
.Useful in females with Polycystic ovaries
.Facilitates normal mensturation and successful pregnancy
.Reduces Triglyceride and Free Fatty Acids level

Dose of Metformin ranges from 250mg - 3000mg/day


Side Effects of Metformin

-Anorexia
-Nausea
-Vomiting
-Diarrhoea
-Dyspepsia
-Lactic Acidosis ( Rare )

When to Avoid Metformin

.Renal Failure
.Hepatic Failure
.Cardiac Failure
.Respiratory Failure
.Alcohol Abuse
.During Contrast Radiological Procedures

History of the wonder drug - Metformin !!

Metformin belongs to Biguanide class of anti-diabetic drugs, which also includes the withdrawn agents Phenformin and Buformin, originates from the French lilac (Galega officinalis), a plant used in folk medicine for several centuries.

Metformin was first described in the scientific literature in 1922, by Emil Werner and James Bell

In 1929, Slotta and Tschesche discovered its sugar-lowering action in rabbits, noting that it was the most potent of the biguanide analogs they studied.

In 1950, metformin Eusebio Y. Garcia, used metformin (he named it Fluamine) to treat influenza; he noted that the drug "lowered the blood sugar to minimum physiological limit" in treated patients and was non-toxic. Garcia also believed metformin to have bacteriostatic, antiviral, antimalarial, antipyretic and analgesic actions but none of these effects were confirmed.

French diabetologist Jean Sterne studied the antihyperglycemic properties of galegine, an alkaloid isolated from Galega officinalis, which is structurally related to metformin

Later, working at Laboratories Aron in Paris, he was prompted by Garcia's report to re-investigate the blood sugar lowering activity of metformin and several biguanide analogs. Sterne was the first to try metformin on humans for the treatment of diabetes; he coined the name "Glucophage" (glucose eater)

Metformin became available in the British National Formulary in 1958. It was sold in the UK by a small Aron subsidiary called Rona.

Broad interest in metformin came after the withdrawal of the other biguanides in the 1970s. Metformin was approved in Canada in 1972, but did not receive approval by the U.S. Food and Drug Administration (FDA) for Type 2 diabetes until 1994. Produced under license by Bristol-Myers Squibb, Glucophage was the first branded formulation of metformin to be marketed in the United States, beginning on March 3, 1995. Generic formulations are now available in several countries, and metformin is believed to have become the most widely prescribed anti-diabetic drug in the world

10 May, 2010

Sexual Dysfunction in Diabetes

Sexual function is a complex blend of Anatomic, Neurological, Metabolic, Endocrine & Psychic factors. On an average around 50% male diabetics develop sexual dysfunction

What is essential for normal sexual function?

.Adequate desire & arousal
.Adequate testosterone levels
.Anatomically Normal Penis
.Adequate Arterial blood flow
.Effective Venous Occlusion ( To sustain Erection)
.Intact Nerve Supply

What leads to Sexual Dysfunction in Diabetics?
.Uncontrolled or fluctuating blood sugars
.Diabetic Neuropathy ( As a result of uncontrolled DM or long duration of DM)
.Atherosclerosis
.Endothelial Dysfunction
.Testosterone deficiency
.Smoking
.Alcoholism
.Uncontrolled Hypertension
.Iatrogenic ( Drug induced )

TYPES OF SEXUAL DYSFUNCTION
1)Transient or temporary dysfunction ( Due to blood sugar fluctuation)
2)Progressive Dysfunction ( Diabetic Erectile Failure)

TREATMENT
1)Psychological counseling

2)Pharmacological Agents ( NEEDS STRICT MEDICAL SUPERVISION)

-Sildenafil
-Tadalafil
-Vardenafil

3)Vasoactive agents

-Papaverin injection
-Phentolamine
-Alprostadil

4)Vaccum Constriction Devices ( VCD )


5)Surgical


Vascular bypass ( Iliac-Pudendal, Pudendal-Cavernous, Pudendal-Penile grafts)
Semi rigid or Inflatable penile prosthesis implantation

09 May, 2010

Glucose Tolerance Test.

What is the glucose tolerance test?

The oral glucose tolerance test (OGTT) is the gold standard for making the diagnosis of type 2 diabetes. With an oral glucose tolerance test, the person fasts overnight (at least 8 but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose Blood samples are taken in 1st hour and 2nd hour.

Prerequisites for GTT

The person should be normally active and should not be taking medicines that could affect the blood glucose. For three days before the test, the person should have eaten a diet high in carbohydrates (150- 200 grams per day). The morning of the test, the person should not smoke or drink coffee/tea.

The classic oral glucose tolerance test measures blood glucose levels three times over a period of 2 hours. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.

Glucose tolerance test- inference

Normal response: Fasting value < 100 mg/dl and 2nd hour value < 200 mg/dl

Impaired glucose tolerance: fasting glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.

Diabetes: Fasting glucose is noted as greater than 126 mg/dl and 2nd hour sample more than 200mg/dl

07 May, 2010

Footwear for Diabetics

A very common problem encountered by atleast 30% of diabetics in India is foot ulcers. Ulcers occur mostly at high pressure points due to undue bony prominences or ill fitting footwear. So the first step to prevent a foot ulcer is to select proper footwear.

Criteria for selection of footwear

1)Select footwear made of MCP/MCR
2)Footwear should be light in weight ( Less than 700gms/pair)
3)Soles of foot wear must be Rigid ( To avoid any penetrating injury while walking)
4)Soles should have serrated edges ( To avoid slipping)
5)Heel height should not be more than 5cm
6)Length of the shoe should allow 1/2inch gap between the end of shoe and and longest toe
7)should have a strong heel counter
8)Footwear should have velcro/laces for adjustment in cases of edema ( swelling)
9)There should be extra depth to accommodate deformities and removable insoles
10)Should have high rounded toe box
11)Inner lining of the shoe should be soft to prevent friction injuries
12)Insoles should be soft to allow redistribution of pressure

06 May, 2010

Symptoms of Hypoglycemia & Hyperglycemia

Hypoglycemia

Shakiness
jerky movements
Dizziness
Sweating
sudden Hunger
Headache
Perspiration
Difficulty in speaking
Attention Deficit
Tingling sensations around the mouth
Feeling anxious or weak

Hyperglycemia

Polyphagia - frequent hunger
Polydipsia - frequent thirst
Polyuria - frequent urination
Blurred vision
Fatigue (sleepiness).
Weight loss
Poor wound healing
Dry mouth
Dry or itchy skin
Tingling in feet or heels
Impotence (male)
Recurrent infections
hyperventilation: deep, rapid breathing
Palpitations
Stupor
Coma

05 May, 2010

Type 2 Diabetes - High Risk Population

Obese people ( BMI more than 25 )
Age > 45 years
People with sedentary lifestyle
people with family history of diabetes ( First degree relatives with diabetes)
Women who have delivered Big Babies ( > 4.5kg birth weight )
Hypertensives
Abnormal Lipid Profile ( Cholesterol HDL<35mg/dl & Triglycerides >150mg/dl )
Women diagnosed with Polycystic Ovaries
Glucose Tolerance Test indicating Prediabetes

Metabolic Syndrome - The Deadly Quarlet !!

Metabolic syndrome is a combination of disorders which increases the chances of developing Diabetes ( Type 2 )

Obesity ( Central Obesity )
Triglycerides > 150mg/dl
HDL < 35mg/dl ( Good Cholesterol)
Fasting Blood Sugar > 100mg/dl
Blood Pressure > 130/85mm of Hg

04 May, 2010

History Of Diabetes

The term diabetes was coined by Aretaeus of Cappadocia.
Thomas Willis added the word mellitus, from the Latin meaning "honey"

In 1776, Matthew Dobson confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes.

Diabetes mellitus appears to have been a death sentence in the ancient era.
Sushruta (6th century BCE) identified diabetes and classified it as Madhumeha. He further identified it with obesity and sedentary lifestyle,
The ancient Indians tested for diabetes by observing whether ants were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha).
Avicenna (980–1037) provided a detailed account on diabetes mellitus in The Canon of Medicine, "describing the abnormal appetite and the collapse of sexual functions," and he documented the sweet taste of diabetic urine.
He also described diabetic gangrene, and treated diabetes using a mixture of lupine, trigonella (fenugreek), and zedoary seed, which produces a considerable reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also "described diabetes insipidus very precisely for the first time",
Johann Peter Frank (1745–1821) who first differentiated between diabetes mellitus and diabetes insipidus.

The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards.

In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance insulin, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.

The endocrine role of the pancreas in metabolism, and the existence of insulin, was further clarified in 1921, by Sir Frederick Grant Banting and Charles Herbert Best Banting, Best, and colleagues (especially the chemist Collip) went on to purify the hormone insulin from bovine pancreases.

Banting is honored by World Diabetes Day which is held on his birthday, November 14.

The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made by Sir Harold Percival (Harry) Himsworth, and published in January 1936.
Identification of the first of the sulfonylureas in 1942

Use of biguanides for Type 2 diabetes in the late 1950s.
The initial phenformin was withdrawn worldwide (in the U.S. in 1977) due to its potential for sometimes fatal lactic acidosis.

Metformin was first marketed in France in 1979, but not until 1994 in the US.

The determination of the amino acid sequence of insulin by Sir Frederick Sanger, for which he received a Nobel Prize)

The radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson
Dr Gerald Reaven's identification of the constellation of symptoms now called metabolic syndrome in 1988
Identification of the first thiazolidinedione as an effective insulin sensitizer during the 1990s
In 1980, U.S. biotech company Genentech developed human insulin. The insulin is isolated from genetically altered bacteria (the bacteria contain the human gene for synthesizing human insulin), which produce large quantities of insulin.

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