Marys Medicine

0076_2_

Available online at www.ijntps.org ISSN: 2277 – 2782
INTERNATIONAL JOURNAL OF NOVEL TRENDS IN PHARMACEUTICAL SCIENCES
REVIEW ARTICLE
A Review on Diabetes Mellitus
K.Harikumar*, B. Kishore Kumar, G.J.Hemalatha, M.Bharath Kumar, Steven Fransis Saky Lado Department of Pharmacology, Sri Venkateswara College of Pharmacy, RVS Nagar, Chittoor, Andhra Pradesh-517127 Abstract
Diabetes is a chronic disease that occurs when the pancreas does not generate enough insulin, or when the
body cannot effectively use the insulin it produces. Hyperglycaemia, or raised blood sugar, is a common
effect of uncontrolled diabetes and over time leads to severe damage to many of the body's systems,
especially the nerves and blood vessels. DM can also occur secondary to genetic defects in beta cell function
or insulin action, pancreatic diseases or other endocrinopathies, medications, toxic chemicals, or uncommon
forms of immune-mediateddiabetes, e.g., "stiff man syndrome" or the presence of anti-insulinreceptor
antibodies.
Key words: Diabetes, stiff man syndrome, Hyperglycaemia.

INTRODUCTION
Diabetes mellitus (DM) is a group of metabolic
mg/dl. "Casual" is defined as any time of the day diseases characterized by hyperglycemia resulting without regard to time since the last meal. Classic from defects of insulin secretion and/or increased symptoms of hyperglycemia include polyuria, cellular resistance to insulin. Chronic hyperglycemia polydipsia, and unexplained weight loss. and other metabolic disturbances of DM lead to long-term tissue and organ damage as well as C. Fasting plasma glucose greater than or equal to dysfunction involving the eyes, kidneys, and 126 mg/dl. "Fasting" means no caloric intake for at nervous and vascular systems [1-3]. The definitions least 8 hours. A test yielding an abnormal result and categories of DM used in this document are must be repeated on a different day. based on the most recent classifications reported by the American Diabetes Association [4-5]. D. Two-hour plasma glucose greater than or equal to 200 mg/dl during an oral glucose tolerance test (OGTT), using a 75-g glucose challenge, as The Classification Of DM Has Undergone The
described by the World Health Organization (WHO) Following Important Changes
1. The designations "type 1 diabetes" and "type 2 diabetes," using Arabic numerals, replace the terms A. Type 1 diabetes mellitus
"insulin dependent diabetes mellitus" (IDDM) and The American Diabetes Association provides clear "non-insulin dependent diabetes mellitus" (NIDDM). definitions of the various types of diabetes and 2. A new term, "IFG" (impaired fasting glucose), classification, diagnosis, and clinical care of defines glucose values that are greater than or diabetes. Type 1 DM, which results from destruction equal to 100 mg/dl and up to 125 mg/dl. of beta cells in the pancreas, accounts for 3. The revised diagnostic criteria for DM are: approximately 10 percent of all patients with DM in A. A1C level ≥ 6.5%. Diagnosis should be confirmed the United States. It leads to absolute insulin with repeat A1C test unless clinical symptoms and deficiency. There are two forms of type 1 DM. One glucose levels ≥ 200 mg/dl are present. (Prior is an immune-mediated disease with autoimmune criteria should be used in the absence of A1C To whom correspondence should be addressed: B. Symptoms of hyperglycemia plus casual plasma glucose concentration greater than or equal to 200 VOLUME 5 NUMBER 3 JUN 2015 201 K. Harikumar et al., A review on Diabetes Mellitus markers such as islet cell antibodies (ICAs), insulin remain undiagnosed for years. Upper body obesity autoantibodies (IAAs), and autoantibodies to is a recognized risk factor because it results in glutamic acid decarboxylase (GAD). As many as peripheral insulin resistance. The beta cells compensate for this resistance by increasing insulin hyperglycemia are positive for one or more of these markers. Strong human leukocyte antigen (HLA) tolerance. Eventually, the hyperglycemia worsens, associations also exist. A second form of type 1 DM, glucose toxicity ensues, and insulin secretion and now called idiopathic diabetes, has no known cause. action decrease. Ultimately, the loss of beta cell Only a minority of patients fall into this group, mass can lead to insulin dependency. The expanded which occurs mainly in individuals of African and definition of the insulin resistance syndrome now Asian origin. Idiopathic diabetes is strongly heritable, but it lacks autoimmune markers and is not HLA associated. Although it can occur at any age, type 1 DM is more common in persons less plasminogen activator inhibitor (PAI-1) levels, than 30 years of age. The rate of pancreatic reduced sex-binding globulin, coronary artery destruction is variable and is generally more rapid disease, and diffuse atherosclerosis. These findings in infants and children and slower in adults. may be the basis for the marked increase in Patients tend to be acutely symptomatic at onset, coronary heart disease reported in type 2 DM. often complaining of polydipsia, polyphagia, polyuria, unexplained weight loss, dry mouth, C. Impaired fasting glucose and impaired
pruritus, leg cramps or pains, delayed healing of glucose tolerance
skin wounds, and recurrent infections of the skin, Patients with hyperglycemia at levels that are below genitalia, or urinary tract. The primary characteristic the diagnostic criteria for DM are diagnosed with of type 1 DM is absolute dependence on impaired fasting glucose (IFG) or impaired glucose exogenous insulin to prevent ketoacidosis. tolerance (IGT), depending on the test used: IFG, by the fasting plasma glucose (FPG) test; IGT, by the B. Type 2 diabetes mellius
oral glucose tolerance test (OGTT). In IFG, the Type 2 is the most common form of DM worldwide, fasting glucose levels are greater than or equal to and its prevalence is increasing. Its underlying 100 mg/dl and up to 125 mg/dl; for IGT, the 2-hour defects can vary from predominant insulin plasma glucose value is greater than or equal to resistance with relative insulin deficiency to a 140 mg/dl and up to 199 mg/dl. Most individuals predominant insulin secretory defect with insulin with IFG and IGT are euglycemic in daily life and resistance. A great deal of heterogeneity exists, and often have normal glycosylated hemoglobin most patients with type 2 DM do not initially (HbA1C) levels. Both IFG and IGT are risk factors for require insulin therapy. future DM. Serial testing shows that such patients Accounting for approximately 90 percent of all may improve, remain stable, or worsen. Neither IFG cases of DM in the United States, type 2 DM occurs nor IGT is associated with the microvascular more frequently in adults than in children, and the complications of DM, but they have been linked incidence increases with age, especially after age with macrovascular disease. 40. However, the prevalence of type 2 DM in children is increasing, especially in the high-risk D. Gestational diabetes mellitus
ethnic groups, such as Native Americans, Hispanic By definition, gestational diabetes mellitus (GDM) is Americans, African Americans, and Asian Americans. any degree of glucose intolerance with onset or first Most of these children are between 10 and 19 years diagnosis during pregnancy. Usually diagnosed old, have had symptoms longer, have infrequent or during the second or third trimester, GDM occurs mild diabetic ketoacidosis, are obese, and have a inapproximately 4 percent of pregnancies or strong family history of diabetes. A characteristic 135,000 cases annually. The prevalence rate of 1−14 finding is darkening of the skin (acanthosis percent depends upon the population studied. nigricans) and there is an increased incidence of Glucose tolerance usually returns to normal within 6 insulin resistance [7-8]. weeks after pregnancy ends, at which time the Because the onset is frequently insidious, many woman needs to be reclassified. Most GDM patients patients with type 2 DM are asymptomatic and do not develop DM later in life, but some will VOLUME 4 NUMBER 6 DEC 2014 202 K. Harikumar et al., A review on Diabetes Mellitus develop IFG, IGT, type 2 DM, or even type 1 DM. • 120 BCE
Because increased fetal mortality and morbidity Greek physician Aretaeus of Cappodocia gives the have been associated with GDM, prompt detection first complete medical description of diabetes, and aggressive treatment are important. GDM which he likens to ‘the melting down of flesh and remains a subgroup within the new classification, limbs into urine. but the screening criteria have been revised. No longer do all pregnant women require screening; Diabetes first appears in the English language as those exempted must meet all of the following the Middle English word ‘diabete'. • 16th Century
1. Less than 25 years of age Swiss physician Phillipus Aureolus Paracelsus – 2. Normal weight before pregnancy considered the ‘Martin Luther of Medicine' – 3. Member of an ethnic group with low identifies diabetes as a serious general disorder. prevalence of DM 4. No known DM in first-degree relatives In his treatise Pharmaceutice rationalis, Professor 5. No history of abnormal glucose tolerance Thomas Willis of Oxford University describes the ‘wonderfully sweet' flavour of urine in diabetes 6. No history of poor obstetric outcome Risk assessment should be conducted early in the pregnancy and glucose testing should be English physician Matthew Dobson of Liverpool evaporates two quarts of urine from a patient with characteristics. For women with risk characteristics diabetes. The resulting residue is granulated and whose initial screening shows no sign of GDM, follow-up screening should be performed between establishing the presence of ‘saccharine materials' 24 and 28 weeks, using an OGTT [9]. as a diagnosis of diabetes. E. Other Specific Types of Diabetes
Scottish physician John Rollo creates the first DM can also occur secondary to genetic defects in medical therapy to treat diabetes. He prescribes an beta cell function or insulin action, pancreatic ‘animal diet' for his patients of ‘plain blood diseases or other endocrinopathies, medications, puddings' and ‘fat and rancid meat' so to manage toxic chemicals, or uncommon forms of immune- the disease with foods their bodies could assimilate. mediateddiabetes, e.g., "stiff man syndrome" or the presence of anti-insulinreceptor antibodies. The German medical student Paul Langerhans discovers defects in beta cell function are better characterized the islet cells of the pancreas but is unable to since linkage of chromosome 7 to the glucokinase explain their function. The find is dubbed the ‘islets deficiency found in maturity-onset diabetes of the young (MODY) 2. MODY 3 is linked to chromosome 12 and MODY 1 to chromosome 20.49 Although French physician Apollinaire Bouchardat notices the few patients have DM related to these other disappearance of glycosuria in his diabetes patients entities, the clinician interpreting blood glucose during food rationing of food under the Siege of screening results must consider the patient's Paris in the Franco-Prussian War, and formulates medical history. individualized diets to treat the condition. THE HISTORY OF DIABETES
Scientists Oskar Minkowski and Joseph von Mering The historical aspects of diabetes are: of the University of Strasbourg, France demonstrate • 1552 BCE
how removing a dog's pancreas produces diabetes. Egyptian physician Hesy-Ra of the 3rd Dynasty makes the first known mention of diabetes – found American pathologist Eugene Opie of John Hopkins on the Ebers Papyrus and lists remedies to combat University in Baltimore establishes a connection the ‘passing of too much urine. between the failure of the islets of Langerhans in • 250 BCE
the pancreas and the occurrence of diabetes. Diabetes described by Arateus as ‘the melting down of flesh and limbs into urine. VOLUME 4 NUMBER 6 DEC 2014 203 K. Harikumar et al., A review on Diabetes Mellitus Prof. John J.R. Macleod writes a monograph on • Dec. 30, 1921
diabetes entitled ‘Diabetes: Its Banting, Macleod, Best and Collip present the results of their research at a session of the American • Dec. 1916
Physiological Society at Yale University. The paper Boston pathologist Elliott Joslin compiles 1,000 of initially generates little interest. The paper – ‘The his own cases and creates the textbook The Internal Secretion of the Pancreas' – is published Treatment of Diabetes Mellitus. In it he reports that two months later in the prestigious Journal of ‘the mortality of patients was approximately 20 per Laboratory and Clinical Medicine. cent lower than for the previous year', due to ‘the • January 1922
introduction of fasting and the emphasis on regular Leonard Thompson, 14, a ‘charity patient' at the exercise.' This book and Joslin's subsequent Toronto General Hospital, becomes the first person research over the next five decades establishes his to receive and injection of insulin to treat diabetes. reputation as one of the world's leading expert in Thompson lives another 13 years before dying of pneumonia at age 27. • May 3, 1922
Dr. Frederick Allen of the Rockefeller Institute in The word ‘insulin' is used in public for the first time New York publishes his Total Dietary Regulations in when Macleod presents the paper ‘The Effect the Treatment of Diabetes that introduces a therapy Produced on Diabetes by the Extracts of Pancreas' of strict dieting – dubbed the ‘starvation treatment' to the Association of American Physicians annual as a way to manage diabetes meeting in Washington, D.C. The results of the • Oct. 31, 1920
Toronto group's experiments is hailed as ‘one of the Banting conceives of the idea of insulin after greatest achievements of modern medicine'. reading an article in the journal Surgery, • May 30, 1922
Gynecology and Obstetrics by Moses Barron, an Pharmaceutical manufacturer Eli Lilly & Co. of American pathologist, titled ‘The Relation of Islets Indianapolis and the University of Toronto enter a of Langerhans to Diabetes with Special Reference to deal for the mass production of insulin. Cases of Pancreatic Lithiasis.' He moves to Toronto • Aug. 16, 1922
and over the next year, with the support of Prof. Elizabeth Evans Hughes, 13, daughter of U.S. Macleod of the University of Toronto, and the Secretary of State Charles Evans Hughes, arrives in assistance of Best, a medical student, and Dr. James Toronto to be treated by Banting for her diabetes. Collip, continues his research using a variety of Weighing only 45 pounds and barely able to walk, different extracts on depancreatized dogs. Elizabeth responds immediately to the insulin • Summer 1921
treatment, and goes on to live a productive life. She Banting's work leads to the discovery of insulin. On dies in 1981 at age 73. July 30, Dog 410 is the first to receive the extract. • Oct. 25, 1923
On August 4 the extract is called ‘Isletin' for the first Banting and Macleod are awarded the Nobel Prize in Physiology or Medicine. Banting shares his award • Nov. 14, 1921
with Best, while Macleod shares his with Collip. Dr. Banting and Charles Best deliver a preliminary • October 1923
report of their research to the Journal Club of the Insulin is made commercially available in the United University of Toronto, Department of Physiology. States and Canada. • Nov. 17, 1921
Banting and Best discover that extract from cattle In a series of research papers, Sir Harold Himsworth foetal pancreas lowers blood sugar levels of of the University College Hospital in London finds that diabetes falls into two types based on ‘insulin plentiful, cheap sources for insulin. Experiments insensitivity.' This discovery later leads to the begin to test the long-term effectiveness of insulin diabetes classifications of type 1 and type 2. • December 1921
Hans Christian Hagedorn, founder of Novo Nordisk, Dr. James Bertram Collip, a biochemist on sabbatical discovers that adding protamine to insulin prolongs from the University of Alberta, joins the Banting and the duration of action of the medication. Best team to assist in refining the quality of extracts. • Feb. 21, 1941
VOLUME 4 NUMBER 6 DEC 2014 204 K. Harikumar et al., A review on Diabetes Mellitus At the height of the Second World War, Major in London, Ontario. As a symbol of hope, the flame Banting is killed in an airplane crash over will burn until a cure for diabetes is found. Newfoundland while on a secret mission to • November 5, 1991
As part of the 100th anniversary of Dr. Banting's birth, a time capsule created by the International The standard insulin syringe is introduced so to Diabetes Federation Youth Representatives is make diabetes management more uniform. entombed by Governor General Ray Hnatyshyn at Banting House in London, Ontario. The capsule will Best co-founds the Diabetic Association of Ontario. be opened when a cure for diabetes is found. Canadian Diabetes Association is established and The Canadian Diabetes Association's Clinical Camp Banting, Canada's first camp for children with Practice Guidelines published in the Canadian diabetes, opens near Ottawa. Medical Journal. Researchers identify type 1 diabetes (insulin After 10 years of clinical study, the Diabetes Control dependent) and type 2 diabetes (non-insulin and Complications Trial (DCCT) report is published and clearly demonstrates that intensive therapy delays the onset and progression of long-term First pancreas transplant performed at the complications in individuals with type 1 diabetes. University of Manitoba • Sept. 14, 1971
Canadian Diabetes Association launches its website Anton Hubert Clemens receives the first patent for a which quickly becomes a source of diabetes-related portable blood glucose meter called the Ames information for people all over the world. Reflectance Meter. Dr. Richard K. Bernstein, an insulin dependent physician with diabetes, uses the 75th Anniversary of the discovery of insulin is meter to monitor his blood glucose at home, and celebrated around the world. subsequently publishes a report on his experiences. The United Kingdom Prospective Diabetes Study A group of interested physicians form the Clinical (UKPDS) scientifically inks the control of glucose and Scientific Section (C&SS) of the Canadian levels and blood pressure control to the delay and Diabetes Association possible prevention of type 2 diabetes. The Canadian Diabetes Association establishes the The Clinical Practice Guidelines for the Management Diabetes Educators Section (DES) to represent of Diabetes in Canada is released by the Canadian nurses, dietitians, physicians, social workers and Diabetes Association, and become a model for other healthcare professionals. other nations health programs. • March 1999
David Goeddel from pharmaceutical firm Genentech Scientists conduct the first successful islet indicated that the first rDNA human insulin was transplant at the University of Alberta Hospital. The surgical procedure becomes known as The pharmaceutical firm Eli Lilly signed an agreement to Edmonton Protocol. commercialize biosynthetic human insulin. • July 7, 1999
Banting House is officially declared a National The first biosynthetic human insulin – Humulin – Historic Site. In a designation ceremony at Dr. that is identical in chemical structure to human Banting's historic home, Governor General Romeo insulin and can be mass produced was approved to LeBlanc unveils the Historic Sites and Monuments market in several countries. Board of Canada plaque. • July 7, 1989
• Dec. 15, 2003
Her Majesty Queen Elizabeth The Queen Mother Canadian Diabetes Association posts the 2003 kindles the Flame of Hope at Banting House Clinical Practice Guidelines on its website as the first National Historic Site – ‘The Birthplace of Insulin' – searchable, download-capable medical guidelines available online. VOLUME 4 NUMBER 6 DEC 2014 205 K. Harikumar et al., A review on Diabetes Mellitus • Dec. 20, 2006
The United Nations recognizes diabetes as a global consciousness. As the lungs heaved desperately to threat and designates World Diabetes Day, expel carbonic acid (as carbon dioxide), the dying November 14 – in honour of Frederick Banting's diabetic took huge gasps of air to try to increase his birthday – as a UN Day to be observed every year capacity. 'Air hunger' the doctors called it, and the starting in 2007. whole process was sometimes described as 'internal • Dec 17, 2008
suffocation.' The gasping and sighing and sweet This article was originally published in Diabetes smell lingered on as the unconsciousness became a Health in November, 1996. deep diabetic coma. • For 2,000 years diabetes has been recognized as a
• The Miraculous Discovery-Insulin
devastating and deadly disease. In the first century • Then in 1921 something truly miraculous occurred
A.D. a Greek, Aretaeus, described the destructive in Ontario, Canada. A young surgeon Frederick nature of the affliction which he named "diabetes" Banting, and his assistant Charles Best, kept a from the Greek word for "siphon." Eugene J. severely diabetic dog alive for 70 days by injecting Leopold in his text Aretaeus the Cappodacian it with a murky concoction of canine pancreas describes Aretaeus' diagnosis: ".For fluids do not extract. With the help of Dr. Collip and Dr. Macleod, remain in the body, but use the body only as a Banting and Best administered a more refined channel through which they may flow out. Life lasts extract of insulin to Leonard Thompson, a young only for a time, but not very long. For they urinate boy dying of diabetes. Within 24 hours, Leonard's with pain and painful is the emaciation. For no dangerously high blood sugars had dropped to essential part of the drink is absorbed by the body near normal levels. Until the discovery of insulin, while great masses of the flesh are liquefied into most children diagnosed with diabetes were expected to live less than a year. In a matter of 24 • Physicians in ancient times, like Aretaeus,
hours the boy's life had been saved. News of the recognized the symptoms of diabetes but were miracle extract, insulin, spread like wildfire across recommended oil of roses, dates, raw quinces, and • In 1935 Roger Hinsworth discovered there were
gruel. And as late as the 17th century, doctors two types of diabetes: "insulin sensitive" (type I) and prescribed "gelly of viper's flesh, broken red coral, "insulin insensitive" (type II). By differentiating sweet almonds, and fresh flowers of blind nettles". between the two types of diabetes, Hinsworth • Early Discoveries-Human Guinea Pigs
helped open up new avenues of treatment. • In the 17th century a London physician, Dr.
• Starting in the late 1930s, new types of pork and
Thomas Willis, determined whether his patients had beef insulin were created to better manage diabetes or not by sampling their urine. If it had a diabetes. PZI, a longer acting insulin, was created in sweet taste he would diagnose them with diabetes 1936. In 1938 NPH insulin was marketed, and in mellitus- "honeyed" diabetes. This method of 1952 Lente, containing high levels of zinc which monitoring blood sugars went largely unchanged promotes a longer duration of action was invented. until the 20th century. • In the 1950s, oral medications-sulfonylureas were
• Despite physicians' valiant efforts to combat
developed for people with type II. These drugs diabetes, their patients remained little more than stimulate the pancreas to produce more insulin, human guinea pigs. In the early 20th century, helping people with type II diabetes keep tighter diabetologists such as Dr. Frederick Allen prescribed control over their blood sugars. low calorie diets-as little as 450 calories per day for • In the 1960s urine strips were developed. Dorothy
his patients. His diet prolonged the life of people Frank, who has had type I diabetes since 1929, with diabetes but kept them weak and suffering remembers, "In order to test your blood sugars from near starvation. In effect, the most a person there were these do-it-yourself urine kits-blue afflicted with diabetes could do was blindly offer meant there was no sugar present, and orange himself to the medical establishment and pray for a meant you were positive." With the invention of cure. In his book, The Discovery of Insulin, Michael urine strips, it was no longer necessary to play Bliss describes the painful wasting death of many chemist, with a collection of test tubes lined up on people with diabetes before insulin: "Food and the bathroom sink, waiting for the results. drink no longer mattered, often could not be taken. VOLUME 4 NUMBER 6 DEC 2014 206 K. Harikumar et al., A review on Diabetes Mellitus • Becton-Dickinson introduced the single use
compact and can easily be carried in a pocket or syringe in 1961. This greatly reduced the amount of clipped to a belt. pain from injections as well as the time-consuming • In 1979 Derata released the first needle-free
ritual of boiling needles and glass syringes. insulin delivery system-the Derma-Ject. It weighed Diabetes Health board member Dr. Nancy 1-1/2 pounds and cost $925 dollars. The Derma- Bohannon describes the early syringes: "The Ject carried the insulin on the side and had no needles were enormous, and they came with little pressure adjustment feature. One early user of the pumice stones so that you could sharpen them. Derma-Ject decided not to use it after a month They often became dull and developed barbs on because it gave him such a terrible jolt every time the end. And in order to sterilize them they had to he used it. Thankfully, modern needle-free injectors be boiled for twenty minutes." have adjustable pressure, so they are relatively pain • The first portable glucose meter was created in
free. In addition, the newer models are light and 1969 by Ames Diagnostics. Diabetes Health board compact in comparison to the heavier models of member Dr. Richard Bernstein, in his book titled Diabetes Type II, Including Type I, describes his first • The hemoglobin A1c test was devised in 1979 in
Ames meter: "In October of 1969, I came across an order to create a more precise blood sugar advertisement for a new device to help emergency measurement. With the A1c, hemoglobin, the rooms distinguish between unconscious diabetics oxygen-carrying pigment in red blood cells, is used and unconscious drunks when the laboratories were to track glucose changes over a period of four closed at night. The instrument had a four-inch months, the life span of the cell. Hemoglobin links galvanometer with a jeweled bearing, weighed with the glucose in blood; the more glucose three pounds, and cost $650." Dr. Bernstein present, the greater amount of hemoglobin linked describes one particularly bizarre incident he with glucose. The A1c became a standard experienced while carrying his Ames Eyetone Meter. measurement for blood sugar control in the "One day I arrived early at our attorney's office for a comprehensive ten-year study from 1983 to 1993- meeting of the board of directors. I was carrying my the Diabetes Control and Complications Trial meter in a bag, and I hung it up in the coat room. A few minutes later everyone was in a panic, saying a • With the conclusion of the DCCT in 1993, studies
bomb had been found in the coat room. The entire showed that people who were able to keep their 24 story building was being evacuated. It took me blood glucose levels as close to normal as possible some time to convince the bomb squad not to blow had less chance of developing complications, such up my meter." as eye, kidney and nerve disease. Before this, many • Since then, new technologies have brought us
doctors had not put much emphasis on tight glucose meters the size of calculators that can be control of blood glucose levels. The common belief easily carried in a pocket or purse. Thankfully, the for decades was that diligent monitoring of blood days of hefting around a three pound glucose sugars and intensive insulin therapy had little consequence for people with diabetes. Since the • In the late '70s the insulin pump was designed to
DCCT's findings, statistics have proven that tight mimic the body's normal release of insulin. The blood glucose control can be extremely beneficial pump dispenses a continuous insulin dosage for people with diabetes. through a cannula (plastic tube), using a small • In May of 1995, Metformin, an oral medication for
needle that is inserted into the skin. The first people with type II diabetes, was finally approved pumps, created in 1979, were large and bulky and for use in the United States by the FDA. Unlike had to be carried in a backpack. Linda Fredrickson, sulfonylurea drugs, which stimulate insulin release, RN, director of the Professional Education and Metformin does not increase insulin production. Clinical Services at MiniMed, describes her first Instead, it heightens sensitivity to insulin and insulin pump: "My first pump in 1980 was an Auto- increases the muscles' ability to use the insulin. Syringe, which weighed 17 ounces and had blinking Since Metformin promotes weight loss, decreases red lights. People nicknamed them the 'blue brick.'" hyperglycemia, and improves lipid levels, it has • Luckily, technology has allowed for great leaps in
been shown to be an effective tool for people with pump design. The pumps of today are light and type II diabetes when used in conjunction with sulfonylureas. VOLUME 4 NUMBER 6 DEC 2014 207 K. Harikumar et al., A review on Diabetes Mellitus • Precose, an oral medication, was approved for use
Symptoms of Type 2 Diabetes
by people with type II diabetes in September 1995. 1. Excessive Urination and Thirst Precose delays the digestion of carbohydrates, 2. Increased Hunger thereby reducing the sudden rise in blood glucose 3. Unexplained Weight Gain after eating a meal. Precose can be used in 4. Irritability and Fatigue conjunction with diet to lower blood sugars in 5. Blurred Vision people with type II whose glucose levels cannot be 6. Warning Signs of Diabetes regulated through diet alone. a) Decelerated Healing • Lispro, a new fast-acting insulin, was released in
b) Skin and Yeast Infections plus Frequent August of 1996 by Eli Lilly under the brand name Gum and Bladder Infections Humalog. Lispro is designed to simulate the body's natural insulin output. Because of lispro's fast- Other Symptoms
acting tendencies, patients can take this insulin 15 1. Sexual Dysfunction in Men minutes or less before eating a meal, instead of 2. Vaginal Infections in Women waiting as they would with Regular insulin. 3. Numbness/Tingling in hands and feet 4. Itchy or Flaky Skin The Future of Diabetes
• Three thousand years have passed since Aretaeus
spoke of diabetes as "the mysterious sickness." It Cause of type 1 diabetes
has been a long and arduous process of discovery, Type 1 diabetes is caused by a lack of insulin due to as generations of physicians and scientists have the destruction of insulin-producing beta cells in added their collective knowledge to finding a cure. the pancreas. In type 1diabetes an autoimmune It was from this wealth of knowledge that the disease the body's immune system attacks and discovery of insulin emerged in a small laboratory in destroys the beta cells. Normally, the immune Canada. Since insulin saved the life of young system protects the body from infection by Leonard Thompson 75 years ago, medical identifying and destroying bacteria, viruses, and innovations have continued to make life easier for other potentially harmful foreign substances. But in people with diabetes. autoimmune diseases, the immune system attacks • As the 21st century rapidly approaches, diabetes
the body's own cells. In type 1 diabetes, beta cell researchers continue to pave the road toward a destruction may take place over several years, but cure. Today, it is unclear what shape the road will symptoms of the disease usually develop over a take; perhaps another dramatic discovery like short period of time. insulin waits around the corner, or possibly Type 1 diabetes typically occurs in children and researchers will have to be content with the slow young adults, though it can appear at any age. In grind of progress. the past, type 1diabetes was called juvenile diabetes or insulin-dependent diabetes mellitus. SIGNS AND SYMPTOMS
Latent autoimmune diabetes in adults (LADA) may Symptoms Of Type 1 Diabetes
be a slowly developing kind of type 1 diabetes. 1. Frequent urination Diagnosis usually occurs after age 30. In LADA, as in 2. Unusual thirst type 1 diabetes, the body's immune system 3. Extreme hunger destroys the beta cells. At the time of diagnosis, 4. Unusual weight loss people with LADA may still produce their own 5. Extreme fatigue and Irritability insulin, but eventually most will need insulin shots There is a reason why diabetes is termed the silent or an insulin pump to control blood glucose levels killer. It is important to bear in mind that these symptoms may be mistaken for an ailment in themselves or for some other disease. The best Genetic Susceptibility
method to diagnose this condition is to have a Heredity plays an important part in determining blood test taken. And if you have already noticed who is likely to develop type 1diabetes. Genes are this symptom, you should see a doctor at the passed down from biological parent to child. Certain gene variants that carry instructions for making proteins called human leukocyte antigens VOLUME 4 NUMBER 6 DEC 2014 208 K. Harikumar et al., A review on Diabetes Mellitus (HLAS) on white blood cells are linked to the risk of 5. Cystic fibrosis - produces abnormally thick developing type 1 diabetes [13-14]. mucus, which blocks the pancreas 6. Hemochromatosis - causes the body to Autoimmune Destruction of Beta Cells
store too much iron. If the disorder is not In type 1 diabetes, white blood cells called t cells treated, iron can build up in and damage attack and destroy beta cells. the pancreas and other organs. 7. Damage to or removal of the pancreas Environmental Factors
8. Pancreatitis, cancer, and trauma can all Environmental factors, such as foods, viruses, and harm the pancreatic beta cells or impair toxins, may play a role in the development of type 1 insulin production, thus causing diabetes. If diabetes, but the exact nature of their role has not the damaged pancreas is removed, been determined. Some theories suggest that diabetes will occur due to the loss of the environmental factors trigger the autoimmune destruction of beta cells in people with a genetic 9. Endocrine diseases susceptibility to diabetes. 10. Cushing's syndrome and acromegaly are examples of hormonal disorders that can Viruses and Infections
cause prediabetes and diabetes by inducing A virus cannot cause diabetes on its own, but insulin resistance. people are sometimes diagnosed with type 1 11. Autoimmune disorders diabetes during or after a viral infection, suggesting a) Lupus erythematosus a link between the two. Viruses possibly associated b) Stiff-man syndrome with type 1 diabetes include coxsackievirus b, c) Medications and chemical toxins cytomegalovirus, adenovirus, rubella, and mumps. d) Nicotinic acid e) Certain types of diuretics Infant Feeding Practices
f) Anti-seizure drugs Some studies have suggested that dietary factors g) Psychiatric drugs may raise or lower the risk of developing type 1 12. Drugs to treat human immunodeficiency diabetes. For example, breastfed infants and infants virus (HIV), can impair beta cells or disrupt receiving vitamin d supplements may have a reduced risk of developing type 1 diabetes, while 13. Pentamidine, a drug prescribed to treat a early exposure to cow's milk and cereal proteins type of pneumonia, can increase the risk of may increase risk [15]. pancreatitis, beta cell damage, and diabetes 14. Also, glucocorticoids steroid hormones that Causes of Type 2 Diabetes Mellitus
are chemically similar to naturally produced 1. MODY (Mature onset diabetes of youth) cortisol may impair insulin action. 15. Many chemical toxins can damage or destroy beta cells in animals, but only a few 4. Cushings syndrome have been linked to diabetes in humans. 5. Pheochromocytoma 16. For example, dioxin a contaminant of the 6. hyperthyroidism herbicide agent orange, used during the 7. mitochondrial mutations vietnam war may be linked to the 8. insulin gene mutations 9. insulin receptor mutations [16-22]. Lipodystrophy is a condition in which fat tissue is lost or redistributed in the body. OTHER CAUSES OF DIABETES
The condition is associated with insulin 1. Genetic mutations affecting beta cells, resistance and type 2 diabetes. insulin, and insulin action 2. Down syndrome PREVALENCE AND INCIDENCE FOR DIABETES
3. Klinefelter syndrome MELLITUS
4. Turner syndrome Diabetes mellitus is a group of metabolic diseases characterized by elevated blood glucose levels VOLUME 4 NUMBER 6 DEC 2014 209 K. Harikumar et al., A review on Diabetes Mellitus (Hyperglycemia) resulting from defects in insulin damage, amputations, heart disease, and stroke. In secretion, insulin action or both. Insulin is a 1997 an estimated 4.5% of the US population had hormone manufactured by the beta cells of the diabetes. Direct and indirect health care expenses pancreas, which is required to utilize glucose from were estimated at 98 billion [23]. digested food as an energy source. Chronic The type of diabetes is based on the presumed hyperglycemia is associated with microvascular and etiology. This chapter provides information about macrovascular complications that can lead to visual the two most common types of diabetes: Type 1 impairment, blindness, kidney disease, nerve and Type 2 diabetes (see Table 1).
Table 1. Characteristics of the common types of diabetes
Mild-severe; often insidious Insulin secretion Insulin sensitivity Insulin dependence Temporary; may occur later Racial/Ethnic groups at increased All (low in Asians) African Americans, Hispanics, Native Americans, Asian/Pacific Islanders Proportion of those with diabetes Association: Obesity Acanthosis nigricans Autoimmune etiology In type 1 diabetes, the body does not produce The annual incidence of type 1 DM in children from insulin, and daily insulin injections are required. birth to 16 years of age varies with ethnicity and is Over 700,000 people in the United States have type approximately 3−26 new cases per 100,000 persons. 1 diabetes; this is 5-10% of all cases of diabetes For example, among African Americans in San mellitus. Type 1 Diabetes is usually diagnosed Diego, CA, it is 3.3 per 100,000 and among whites in during childhood or early adolescence and it affects Rochester, MN, it is 20.6 per 100,000. Approximately about 1 in every 600 children. 0.3 percent of the population develops the disease Type 2 diabetes is the result of failure to produce by 20 years of age. The annual incidence of type 2 sufficient insulin and insulin resistance. Elevated DM is approximately 2.4 per 1,000 persons over age blood glucose levels are managed with reduced 20. By 65 years of age, 10 percent of the population food intake, increased physical activity and may have type 2 DM. The prevalence is highest in eventually oral medications or insulin. Type 2 Native Americans, followed by Hispanics, African diabetes is believed to affect more than 15 million Americans, and Asians. adult Americans, 50% of whom are undiagnosed. It is typically diagnosed during adulthood. However DIAGNOSIS OF DIABETES
with the increasing incidence of childhood obesity Diabetes Testing
and concurrent insulin resistance, the number of Three blood tests are available to diagnose children diagnosed with type 2 diabetes has also prediabetes and diabetes increased worldwide [24]. • Casual plasma (blood) glucose For example, from 1982 to 1994 in one mid-western • Fasting plasma glucose (FPG) city, the proportion of children with type 2 diabetes • Oral glucose tolerance test increased from approximately 4% to 16%. The prevalence of DM, estimated at 10 percent of Casual Plasma (Blood) Glucose Test
persons over the age of 60 years, rises to 16−20 The criteria for a diagnosis of diabetes with this test percent among those over the age of 80. The is the presence of diabetes symptoms and a blood overall prevalence among adults was 7.4 percent in glucose level of 200 mg/dl or higher. 1995 and is expected to reach 9 percent in 2025. VOLUME 4 NUMBER 6 DEC 2014 210 K. Harikumar et al., A review on Diabetes Mellitus Fasting Plasma Glucose (FPG) Test
2. Parrot green color = >120 mg/dl A diagnosis of diabetes is made when the fasting 3. Dark yellow color = >180mg/dl blood glucose level is 126 mg/dL or higher on at 4. Reddish brown color = +++ > 250 mg/dl least two tests. Values of 100–125 mg/dl indicate 5. Brown color = ++++ > 350 mg/dl prediabetes. A normal fasting blood glucose level is less than 100 mg/dl. Diasticks
These are strips that used to indicate the Oral Glucose Tolerance Test
person having diabetes mellitus or not. The criterion for a diagnosis of diabetes with this These strips tested with urine and based on test is a two-hour blood glucose level of 200 mg/dl the color change only diagnosis the or higher. Prediabetes is diagnosed if the two-hour diabetes mellitus. blood glucose level is 140–199 mg/dl. Glucometers
Postprandial Blood Glucose Test
• These meters are also involving in Measures blood glucose levels 2 hours after eating diagnosing the diabetes mellitus. Within a meal. Postprandial blood glucose is usually done the fraction of seconds these will give in people who have symptoms of hyperglycemia, or results about blood glucose levels. when the results of a fasting glucose test suggest possible diabetes, but are inconclusive. Values of Other Laboratory Tests
200 mg/dL or more indicate diabetes. In addition to measures of blood glucose and HbA1c, initial and subsequent doctor visits may Hemoglobin A1c (HbA1c), also known as the
include tests to check for kidney damage, a glycosylated hemoglobin or glycohemoglobin
common complication of diabetes. These tests include blood urea nitrogen (BUN), blood it is used to monitor the effectiveness of therapy in creatinine, and protein (albumin) in the urine. The people already diagnosed with diabetes. HbA1c risk of coronary heart disease is increased in people measures the amount of glucose attached to with diabetes, so also need blood tests to measure hemoglobin (the oxygen-carrying protein in red levels of triglycerides, total cholesterol, low-density blood cells), which increases as blood glucose levels lipoprotein (LDL) cholesterol, and high-density rise. Since hemoglobin circulates in the blood until lipoprotein (HDL) cholesterol. the red blood cells die (half the red blood cells are replaced every 12 to 16 weeks), the HbA1c test is a Urine Glucose And/Or Ketones
useful tool for measuring average blood glucose Patient self-monitoring is easily done with urine values over the previous 2 to 3 months [27-35]. dipsticks for detecting and semiquantifying glucose and ketones in urine. Purpose of Diagnostics Tests For Diabetes
The fasting, postprandial, and oral glucose tolerance tests are used to diagnose type 1 or type Diabetes mellitus is classified on the basis of 2 diabetes mellitus. pathogenesis which causes hyperglycemia and the • HbA1c is used to monitor the effectiveness two broad categories are Type 1 and Type 2 of dietary or drug therapy in the diabetes mellitus. Type 1 diabetes mellitus occurs management of diabetes mellitus. due to destruction of pancreatic islet β cells, mainly • To detect hyperglycemia (high blood sugar) due to an autoimmune process which can cause and hypoglycemia (low blood sugar). complete or near total insulin deficiency. Type 2 • To screen for diabetes, a common disease diabetes mellitus is a progressive, debilitating that often does not cause early symptoms. metabolic blood glucose disorder due to multiple metabolic abnormalities including impaired insulin Chemical Tests
secretion, insulin resistance, loss of beta cell This involves testing the urine with the Benedict's function, impaired regulation of glucagon secretion reagent. Results indicate the person having diabetes and disturbed incretin physiology (Powers 2008, based on the color formation. Andukuri et al., 2009). Incretins maintain glucose 1. Light color = normal homeostasis along with other hormones like insulin, VOLUME 4 NUMBER 6 DEC 2014 211

K. Harikumar et al., A review on Diabetes Mellitus glucagon and amylin. They are released in response generally, Normoglycaemia is maintained by the to a meal by enteroendocrine cells in the intestine. balanced interplay between insulin action and Incretin dysfunction, along with other defects, has insulin secretion. Importantly, the normal pancreatic been implicated in contributing to the pathogenesis cell can adapt to changes in insulin action i.e., a of type 2 diabetes mellitus (Campbell et al., 2011). A decrease in insulin action is accompanied by new paradigm of drugs thus have been developed upregulation of insulin secretion (and vice versa). which are based on the actions of the incretins and Figure illustrates the curvilinear relation between are injectable long-acting stable analogues of normal cell function and insulin sensitivity. glucagon like peptide-1 (GLP-1) known as incretin Deviation from this hyperbola, such as in the mimetics. The classic point of view regarding T1DM patients with impaired glucose tolerance and Type pathogenesis was that, in genetically predisposed 2 diabetes in figure , occurs when cell function is individuals, some environmental factors may trigger inadequately low for a specific degree of insulin an autoimmune process that leads to β-cell sensitivity. Thus, cell dysfunction is a critical destruction. In the last 4 decades, a dramatic component in the pathogenesis of Type 2 diabetes. increase in the biochemical identification of islet This concept has been verified not only in cross- autoantigens and in the definition of alleles of sectional studies but also longitudinally in Pima genes associated with diabetes susceptibility was Indians progressing from normal to impaired registered. Nowadays, one considers that genes and glucose tolerance to Type 2 diabetes. However, not environmental factors may have deleterious or only deviation from but also progression along the favorable effects and, consequently, the immune hyperbola affects glycaemia. When insulin action equilibrium is directed towards aggression or decreases (as with increasing obesity) the system protection. It is the time to recapitulate here the usually compensates by increasing cell function. main knowledge we have about the pathogenesis However, at the same time, concentrations of blood of autoimmune T1DM. glucose at fasting and 2 h after glucose load will increase mildly. This increase may well be small, but Pathophysiology of Type 2 Diabetes Mellitus
over time becomes damaging because of glucose To understand the cellular and molecular toxicity, and in itself a cause for cell dysfunction. mechanisms responsible for Type 2 diabetes it is Thus, even with (theoretically) unlimited cell reserve, necessary to conceptualise the framework within insulin resistance paves the way for hyperglycaemia which glycaemia is controlled. Insulin is the key and Type 2 diabetes. hormone for regulation of blood glucose and,
Fig 1. Pathophysiology Of Hyperglycaemia And Increased Circulating Fatty Acids in Type 2 Diabetes

VOLUME 4 NUMBER 6 DEC 2014 212 K. Harikumar et al., A review on Diabetes Mellitus Insulin secretion from the pancreas normally can be done to determine if someone who reduces glucose output by the liver, enhances has a family history of type 1 diabetes is at glucose uptake by skeletal muscle, and suppresses increased risk of developing the condition. fatty acid release from fat tissue. The various factors • Geography: The incidence of type 1
shown that contribute to the pathogenesis of type 2 diabetes tends to increase as you travel diabetes affect both insulin secretion and insulin away from the equator. People living in action. Decreased insulin secretion will reduce Finland and Sardinia have the highest insulin signalling in its target tissues. Insulin incidence of type 1 diabetes — about two resistance pathways affect the action of insulin in to three times higher than rates in the each of the major target tissues, leading to United States and 400 times that of people living in Venezuela. hyperglycaemia of diabetes. In turn, the raised concentrations of glucose and fatty acids in the Possible risk factors for type 1 diabetes includes
bloodstream will feed back to worsen both insulin • Viral exposure: Exposure to Epstein-Barr
secretion and insulin resistance. virus, coxsackievirus, mumps virus or autoimmune destruction of the islet cells, or Insulin resistance is strongly associated with obesity the virus may directly infect the islet cells. andphysical inactivity, and several mechanisms • Early vitamin D: Research suggests that
mediating this interaction have been identified. A vitamin D may be protective against type 1 number ofcirculating hormones, cytokines, and diabetes. However, early drinking of cow's metabolic fuels,such as non-esterified (free) fatty milk — a common source of vitamin D — acids (NEFA) originate in the adipocyte and has been linked to an increased risk of type modulate insulin action. Anincreased mass of stored • Other dietary factors: Omega-3 fatty acids
subcutaneous adipose depots, leads tolarge may offer some protection against type 1 adipocytes that are themselves resistant to diabetes. Drinking water that contains theability of insulin to suppress lipolysis. This results nitrates may increase the risk. Consuming inincreased release and circulating levels of NEFA dairy products, particularly cow's milk, may andglycerol, both of which aggravate insulin increase infants' risk of the disease. resistance in skeletal muscle and liver (figure 3). Additionally, the timing of the introduction Excessive fat storage not only in adipocytes but of cereal into a baby's diet may affect risk. "ectopically" in non-adipose cells also has an One clinical trial found that between ages 3 and 7 months appears to be the optimal intramyocellular lipids are associated with skeletal time for introducing cereal. circumstances. The coupling between intrahepatic Some other possible risk factors includes
lipids and hepatic insulin resistance seems to be • Having a mother younger than age 25 when she gave birth to you • Having a mother who had preeclampsia RISK FACTORS
during pregnancy Risk Factors Of Diabetes Type 1
• Being born with jaundice There aren't many known risk factors for type 1 • Having a respiratory infection just after diabetes, though researchers continue to find new possibilities. Some known risk factors include: • A family history: Anyone with a parent or
Risk Factors of Diabetes Type 2
sibling with type 1 diabetes has a slightly Researchers don't fully understand why some increased risk of developing the condition. people develop type 2 diabetes and others don't. • Genetics: The presence of certain genes
It's clear, however, that certain factors increase the indicates an increased risk of developing risk, including: type 1 diabetes. In some cases — usually • Weight: Being overweight is a primary risk
through a clinical trial — genetic testing factor for type 2 diabetes. The more fatty VOLUME 4 NUMBER 6 DEC 2014 213 K. Harikumar et al., A review on Diabetes Mellitus tissue you have, the more resistant your • Nerve damage (Neuropathy) cells become to insulin. • Kidney damage (Nephropathy) • Fat distribution: If your body stores fat
• Diabetic cardiomyopathy primarily in your abdomen, your risk of type • Coronary artery disease 2 diabetes is greater than if your body • Stroke (Mainly the ischemic type) stores fat elsewhere, such as your hips and • Diabetic myo-necrosis (Muscle wasting) • Diabetic encephalopathy • Inactivity: The less active you are, the
greater your risk of type 2 diabetes. Physical • Foot damage (Diabetic foot) activity helps you control your weight, uses • Skin and mouth functions up glucose as energy and makes your cells • Osteoporosis more sensitive to insulin. • Pregnancy complications • Family history: The risk of type 2 diabetes
• Hearing problems. increases if your parent or sibling has type TREATMENT OF DIABETES MELLITUS
• Race: Although it's unclear why, people of
The major components of the treatment of diabetes certain races — including blacks, Hispanics, American Indians and Asian-Americans — A) Drug treatment for diabetes are more likely to develop type 2 diabetes B) Non drug treatment for diabetes than whites are. • Age: The risk of type 2 diabetes increases
A) Drug Treatment for Diabetes
as you get older, especially after age 45. Anti-diabetic drugs treat diabetes mellitus by That's probably because people tend to lowering glucose levels in the blood. With the exercise less, lose muscle mass and gain exceptions of insulin, Exenatide, and Pramlintide, all weight as they age. But type 2 diabetes is are administered orally and are thus also called oral hypoglycemic agents or oral ant hyperglycemic children, adolescents and younger adults. agents. There are different classes of anti-diabetic • Prediabetes: Prediabetes is a condition in
drugs, and their selection depends on the nature of which your blood sugar level is higher than the diabetes, age and situation of the person, as normal, but not high enough to be well as other factors. classified as diabetes. Left untreated, Diabetes mellitus type 1 is a disease caused by the prediabetes often progresses to type 2 lack of insulin. Insulin must be used in Type I, which must be injected or inhaled. • Gestational diabetes: If you developed
Diabetes mellitus type 2 is a disease of insulin gestational diabetes when you were resistance by cells. Treatments include agents which pregnant, your risk of later developing type increase the amount of insulin secreted by the 2 diabetes increases. If you gave birth to a pancreas, agents which increase the sensitivity of target organs to insulin and agents which decrease the rate at which glucose is absorbed from the COMPLICATIONS OF DIABETES
gastrointestinal tract. Type 1diabetes can affect major organs in your body, including heart, blood vessels, nerves, eyes and kidneys. Keeping your blood sugar level close Insulin is usually given subcutaneously, either by to normal most of the time can dramatically reduce injections or by an insulin pump. Research is the risk of many complications. underway of other routes of administration. In acute Long-term complications of Type 1 diabetes care settings, insulin may also be given develop gradually, over years. The earlier you intravenously. There are several types of insulin, develop diabetes — and the less controlled your characterized by the rate which they are blood sugar — the higher the risk of complications. metabolized by the body. Insulin is essential for the Eventually, diabetes complications may be disabling treatment of type1 diabetes. For many years it was or even life-threatening. assumed, as an act of faith, that normalizing plasma • Heart and blood vessel disease glucose would prevent diabetic complications. The VOLUME 4 NUMBER 6 DEC 2014 214 K. Harikumar et al., A review on Diabetes Mellitus diabetes control and complications trial (american slowly, and can be matched more effectively by an diabetes association, 1993) showed that this faith impaired insulin response or sensitivity. These was well placed: type1 diabetic patients were delays carbohydrates adsortion, reducing the randomly allocated to intensive or conventional postprondal increase in blood glucose. Eg: Miglitol, Insulin Sensitizers
Peptide Analogs
Incretin Mimetics
Sulfonylureas were the first widely used oral Incretions are insulin secretagogues. The two main hypoglycemic medications. They are insulin candidate molecules that fulfill criteria for being an secretagogues, triggering insulin release by direct incretion are Glucagons-like peptide-1 (GLP-1) and action on the KATP channel of the pancreatic beta Gastric inhibitory peptide (aqua glucose-dependent Insulin tropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues." Their Glucagon-Like Peptide (GLP) Analogs And
mode of action is original, affecting channels. By closing the potassium channels of the pancreatic GLP agonists bind to a membrane GLP receptor. As beta cells, they open the calcium channels, hence a consequence of this, insulin release from the enhancing insulin secretion. Eg: Repaglinide, pancreatic beta cells is increased. Endogenous GLP has a half life of only a few minutes; thus an analogue of GLP would not be practical. Exenatide, Biguanides
Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, Gastric Inhibitory Peptide (GIP) Analogs
including skeletal muscle. Although it must be used DPP-4 Inhibitors
with caution in patients with impaired liver or Dipeptidyl peptidase-4 (DPP-4) inhibitors increase kidney function, motorman has become the most blood concentration of the incretin GLP-1 commonly used agent for type 2 diabetes in children and teenagers. Eg: Metformin, Phenformin, degradation by dipeptidyl peptidase-4 (DPP-4). Vildagliptin, Sitagliptin Amylin Analogues
Thiazolidinediones Amylin agonist analogues slow gastric emptying "glitazones," bind to PPARγ, a type of nuclear and suppress glucagons. They have all the regulatory proteins involved in transcription of incretions actions except stimulation of insulin genes regulating glucose and fat metabolism. These secretion. As of 2007, primitive is the only clinically PPARγ act on Peroxysome Proliferator Responsive available amyl in analogue. Like insulin, it is Elements (PPRE). The PPREs influence insulin administered by subcutaneous injection. sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final B) Non Drug Treatment For Diabetes
result is better use of glucose by the cells. Eg: 1. Life style changes which are used to
Rosiglitazone, Pioglitazone, Troglitazone controlling diabetes
Life style change is defined as the way of living Alpha-Glucosidase Inhibitors
which has been altered by variety manner. Life style Alpha-glycosidase inhibitors are "diabetes pills" but have seven principles of good diabetes care: not technically hypoglycemic agents because they • Learn as much as you can about diabetes do not have a direct effect on insulin secretion or • Get regular care for diabetes sensitivity. These agents slow the digestion of starch • Learn how to control your diabetes in the small intestine, so that glucose from the • Take care of your diabetic ABC's starch of a meal enters the bloodstream more • Monitor your diabetic ABC's VOLUME 4 NUMBER 6 DEC 2014 215 K. Harikumar et al., A review on Diabetes Mellitus • Prevent long term diabetes problems 5. Exercise makes the tissues in your body • Get checked for long term problems and more sensitive to the effects of insulin. This allows insulin to push more glucose out of the blood stream in tour cells, which will 2. Exercise
reduce the level of glucose in our blood. It is an important in helping to prevent diabetes and is having vital role of our treatment. some good qualities of exercise The diet recommends places an emphasis on foods 1. It helps in losing weight that are higher in fiber and low in fat. By it self a 2. It can reduce blood glucose levels and keep high fiber, low fat diet can make body more it low for several hours after words sensitive to insulin. Diet also involves weight loss 3. Exercise can reduce cholesterol and blood which is another way to increase diabetic patient's body sensitivity to the effects of insulin.
4. Exercise helps reduce stress
REFERENCES
1. American Diabetes Association. Screening for Report No. 5., Arch Ophthalmol, 1990, 108, 958- diabetes. Diabetes Care, 1998, 21(suppl 1), s20- 11. Zimmet PZ, Tuomi T, Mackay R, Rowley MJ, 2. Expert Committee on the Diagnosis and Knowles W, Cohen M, et al. Latent autoimmune Classification of Diabetes Mellitus. Diagnosis diabetes mellitus in adults (LADA): The role of and Classification of Diabetes Mellitus. Diabetes antibodies to glutamic acid decarboxylase in Care, 2009, 32(suppl 1), s62-s67. 3. American Diabetes Association. All about dependency. Diabetic Med, 1994, 11, 299–303. 12. Humphrey ARG, Mccarty DJ, Mackay IR, diabetes.jsp (accessed 10 Feb 2009). Rowley MJ, Dwyer T, Zimmet P. Autoantibodies 4. American Diabetes Association. Standards of to glutamic acid decarboxylase and phenotypic medical care in diabetes—2007. Diabetes Care, features associated with early insulin treatment 2009, 32(suppl 1), s13-61. in individuals with adult– onset diabetes 5. World Health Organization Study Group. mellitus. Diabetic Med, 1998, 15, 113–119. Prevention of diabetes mellitus. Technical 13. Japan and pittsburgh childhood diabetes Report No. 844, Geneva, 1994. research groups. Coma at onset of young insulin–dependent diabetes in japan: the result International Expert Committee report on the of a nationwide survey. Diabetes, 1985, 34, role of A1C Assay in the diagnosis of diabetes. Diabetes Care, 2009, 32, 1327-1334. 14. Zimmet PZ et al., The pathogenesis and 7. Fagot-Campagna A, Pettitt DJ, Engelgau MM, et prevention of diabetes in adults. Diabetes care, al. Type 2 diabetes among North American 1995, 18, 1050–64. children and adolescents: An epidemiologic 15. Hother Nielsen O, Faber O, Sorensen NS, Beck– review and a public health perspective. J Nielsen H. Classification of newly diagnosed Pediatr, 2000, 136, 664-72. diabetic patients as insulin requiring or non 8. American Diabetes Association. Standards of insulin requiring based on clinical and medical care in diabetes. Diabetes Care, 2009, biochemical variables. Diabetes care, 1988, 11, 32(suppl 1), s15. 9. American Diabetes Association. Standards of 16. Defronzo RA, Bonadonna RC, Ferrannini E, et al. medical care in diabetes. Diabetes Care, 2009, Pathogenesis of NIDDM. International textbook 32(suppl 1), s13-14. of diabetes mellitus. 2nd Edn. Chichester: john wiley, 1997, 635–712. Research Group. Early vitrectomy for severe 17. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley vitreous hemorrhage in diabetic retinopathy. JE, Ravussin E et al., Insulin resistance and Four-year results of a randomized trial. DRVS insulin secretory dysfunction as precursors of non insulin dependent diabetes. Prospective VOLUME 4 NUMBER 6 DEC 2014 216 K. Harikumar et al., A review on Diabetes Mellitus study of pima indians. N Engl J Med, 1993, 329, reaction for the determination of ketone bodies in urine. Queens Bullettin of Northwestern 18. Mooy JM, Grootenhuis PA, DE Vries H, University Medical School 1946, vol. 20, pp. Valkenburg HA, Bouter LM, Kostense PJ et al., Prevalence and determinants of glucose 28. Lee JT, McGilliray MH. Direct fixed-time kinetic intolerance in a dutch population. The hoorn beta-hydroxybutyrate study. Diabetes care, 1995, 18, 1270–73. acetoacetate with a cen-trifugal analyser or a 19. Harris MI, et al. Undiagnosed NIDDM. Clinical computerbacked spectrophotometer. Clinical and public health issues. Diabetes care, 1993, Chemistry, 1980, 26, 1713-1717. 29. Lawrence AK, Amadeo JP. Clinical Chemistry: 20. Campbell PJ, Carlson MG. Impact of obesity on Theory, analysis and correlation, 3rd Ed., St. insulin action in NIDDM. Diabetes, 1993, 42, Louis: Mosby Inc, USA, 1996. 30. Davidson MB. The effects of aging on 21. Bogardus C, Lillioja S, Mott DM, Hollenbeck C, carbohydrate metabolism: A review of the Reaven G. Relationship between degree of English literature and a practical approach to obesity and in vivo insulin action in man. Am J the diagnosis of diabetes mellitus in the elderly. Physiol, 1985, 248, e286– e291. Metabolism, 1979, 28, 688-693. 22. Kissebah AH, Vydelingum N, Murray R, Evans 31. Ngugi MP et al. Hypoglycemic effects of some DF, Hartz AJ, Kalkhoff RK et al., Relationship of Kenyan plants used in management of diabetes mellitus in eastern province, MSc. Thesis, complications of obesity. J Clin Endocrinol Kenyatta University, Kenya, 2006. Metab, 1982, 54, 254–260. 32. Larsen J, Hilsted EK, Philipsen B, Tronier NJ, 23. American Diabetes Association. Economic Chris tensen, Damkjaer M Nielsen, H Worning consequences of diabetes mellitus in the U.S. in H. Glucose counter regulation in diabetes 1997. Diabetes Care, 1998, 21(2), 296-309. secondary to chronic Pancreatitis. Metabolism, 24. Rosenbloom AL, Joe JR, Young RS, Winter WE. 1990, 39, 138-143. Emerging epidemic of type 2 diabetes in youth. 33. Dods RF, Bolmey C. Glycosylated haemoglobin Diabetes Care, 1999, 22(2), 345-354. assay and oral glucose tolerance test compared 25. Pinhas Hamiel O, Dolan L, Daniels SR, for detection of diabetes mellitus. Clinical Standiford D, Khoury PR, Zeitler P. Increased Chemistry 1979, 25, 764-768. incidence of noninsulin-dependent diabetes 34. Guthrow CE, Morris MA, Day JF. Enhanced mellitus among adolescents. J Pediatr, 1999, nonenzy-matic glycosylation of serum albumin in diabetes mellitus. Proceedings of National 26. American Diabetes Association. Type 2 diabetes Academy of Science, 1979, 76, 4528-4531. in children and adolescents. Pediatrics, 2000, 35. Ward WK, Beard JC, Halter JB et al., 105(3 Pt1):671-680. Pathophysiology of insulin secretion in non- 27. Friedemann TE, Sheft BB, Miller VC. An insulin dependent diabetes mellitus. Diabetes assessment of the value of nitroprusside Care, 1984, 7, 491-497. VOLUME 4 NUMBER 6 DEC 2014 217

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