ACUMEN 2016 ‘INTERNATIONAL ONLINE ESSAY WRITING CONTEST ORGANIZED BY SCHOOL OF PHARMACEUTICAL MANAGEMENT THE IIHMR UNIVERSITY, JAIPUR, INDIA ON MAY 8TH 2016.

RECENT DEVELOPMENTS IN DIABETES MANAGEMENT

“DIABETES a 7^th leading cause of death needs innovative treatments to manage them. As   we enter in the field of Biosimilars, Monoclonal Antibodies, genetic engineering and transplantation to combat this autoimmune hereditary disease DIABETES.”

Diabetes is a hereditary condition, a metabolic disorder which may be chronic. Diabetes is an abnormal condition in which an increase in the level of glucose in blood stream. It is due to abnormal functioning of either cells (beta cells of islet of Langerhans) or absence of hormone –INSULIN. Diabetes mainly classified as Type -1 diabetes 0r insulin dependent diabetes or Type -2 diabetes or non-insulin dependent. Diabetes mainly associated with polyuria (large volume of urine) and polydipsia (excessive thirst). Other symptoms may include weight loss, hunger, fatigue (type-1) and obesity (type-2).

In this modern epoch where everything going to be advance .day by day with the blink of any eye new research is going to be conducted where we are in the age of genetic engineering technologies, biosimilars, computational theories, monoclonal antibodies, the expansion in management of disease of decades DIABETES done on a daily basis as science has evolved new theories are coming which not only decrease the side effects of the existing diabetic medicine but also open the new pathways in its progress.

Effective diabetic management is done when we are targeting four areas

·         Optimization in controlling blood glucose.

·         Preventing insulin resistance state.

·         Taking insulin early when indicated.

·         Make people aware of diabetes.

In the early diagnosis of diabetes, the treatment of diabetes depends upon the type and severity of the disease. TYPE-1 can be treated by taking insulin injections, regular exercise and diabetic diet. While Type -2 can be manageable by weight reduction, diabetic diet for Type -2 patients and exercise.

Before discussing about the current advancement in diabetes management we can be aware that Type - 1 diabetes cannot be prevented while Type -2 can be. Diabetes is not a only disease a person suffer but in later stage of life it leads to heart diseases, kidney diseases, some problems like polycystic ovary and obesity can turn to Type -2 diabetes in later phase of life.

An in vitro study can be conducted in search of most modern management of diabetes. Biosimilars of insulin are made which is bio-pharmaceutical (a biological medical product therapeutic protein It includes human insulin and insulin analogue) are manufactured by different companies using same techniques. Researches made during 2011-2013 give the data of making several important analogues of insulin used in diabetes treatment which are coming off-patent including Insulin Aspart, Gargine, Lispro.The process of making Biosimilars is complex. The difficulty is not in making Biosimilars but the purification of compound is difficult because impurity in body consider as foreign bodies which in result causes allergic reactions. A new manufacturer can face problems in manufacturing Biosimilars as a quality product in market. Insulin is not the only biopharmaceutical which the manufacturer going to made available in the market. This type of research conducted in production of human growth hormone. These are the targeted therapies which have special biomarkers to work on like people having diabetes with renal failure given recombinant erythropoietin (Epo) to facilitate in countering the effect of anemia. For rheumatoid arthritis, artificial antibodies are available which are causing joint inflammation. Another example of Transtuzumab a monoclonal antibody used as a targeted therapy in the treatment of Herceptin is also available in market. Biosimilars insulin in submitted for approval in regulatory authority. The clinical data for Biosimilars insulin gathered should give the information about its pharmacokinetics (its absorption rate after injection) and pharmacodynamics study –its glucose clamp effect (in which two insulin acts similarly).

Researchers tried to reprogram human skin cells to produce their own insulin in future. The scientist of the University of North Carolina’s Chapel Hill school of Medicine has successfully tried to transformed skin cells to produce insulin. It is a big step in cell based transplantation an innovation in the cell reconstruction. The main drawback of this study is the rejection phenomenon of the body they treat this as a foreign matter.

In islet cell transplantations, the scientist is moving towards the pathways that to increase the life span of beta islet cell transplant in people with diabetes type -1. The new strategy is to conduct an in vitro study to culture that type of islet cell before the transplantation to increase the efficacy of insulin production and a trial was conducted in donor with anti-rejection drugs to observe their influence, efficacy and safety. The technique used that beta cells of islets of Langerhans are taken from donor’s pancreas and implanted in the liver of recipient. The transplantation is of two types allo transplantation (only cells of islets are taken to implant) and auto transplantation (in which pancreatectomy can be done). Scientists are seeking those ways to achieve immune tolerance effects of these transplants to reduce the rejection of cell. The transplants of islets are synthesized which make the immune system of patient more efficient and it no longer recognize the islet cell as foreign. The use of new combination of immunosuppressive medicine are made which are anti-rejection medicine (including Daclizumab, Sirolimus and Tacrolimus). The monoclonal antibodies which have markers for the treatment. They increase the immunity of patients with long term use of immune suppressive medicines. One recent approach in transplantation is to transplant islet encapsulated with special coating which prevent the rejection and work on the target site. 

Manufactures are on their way to formulate drugs for the treatment of Type -1 diabetes to replace lost insulin, and provide an effective way to decrease life-threatening complications. It involves availability of lifetime insulin injections or an insulin pump. Research studies have shown that ‘immunosuppressant’ drugs (like those used after an organ transplant) weaken the autoimmune attack that causes Type -1 diabetes, which help to prevent the destruction of insulin-producing cells and leading to short-term improvements in blood glucose control. But the drawbacks of this study faced by investigators are by suppressing the immune system makes the body vulnerable to all type of infections, cancers and harmful side effects. Scientist is still on working to synthesize selective medication to attack the diseased immune cells without affecting the defensive cells. They are also in testing phase to synthesize vaccine for diabetes management

                                                                                                                      

The current researches were made in the field which links that all those people who have Vitamin –D deficiency in their early phase of life can be more prone to develop impaired glucose intolerance in their later life .as previously we know that Vitamin –D can be gain naturally by sun light, by diet like taking eggs, fishes and dairy products and even through taking supplements. The key biological purpose of vitamin D is to maintain levels of calcium and phosphorus in the blood help in the absorption of calcium, and to form and maintain strong bones the deficiency of vitamin –D in children causes rickets while in adult it causes osteoporosis or osteomalacia.in type -1 diabetes the receptors for vitamin –D present in most immune cells in beta cells of pancreas they also have vitamin –D receptors interestingly when it combine with 1,25 dihydroxycholecalciferol(D3) it inhibits the proteins which causing the destruction of beta cells which make insulin unavailable. In vivo studies are conducted in mice having vitamin-D deficiency causing Type-1 diabetes and worsening the disease as compare to those having of adequate level of Vitamin-D. Vitamin-D has a positive role in insulin action by affecting the sensitivity to target cells. In vivo studies are made in which vitamin-D made untreatable which shows severe impairment in some cases while some shows normal glucose level. Clinical studies are also conducted in people who are given Vitamin –D supplements in their pre-diabetic stage which shows improvement in controlling blood glucose. Active form of vitamin-D can be used for prophylactic treatment in Diabetic patients. The Search for safe analogue having combination of affects on Beta cells and immune system without having the affect on bone and calcium metabolism is continuing to conquer.

Pharmaceutical manufacturing companies now targeted gut hormone to make innovative drug to lower the blood glucose which is their block buster step in the field of clinical research. The investigations are made and scientist observed a group of intestinal hormones known as “incretins “which diabetic people are deficient. The function of Incretins is to control blood glucose after eating they start secretions. They have two classes of medications which has focal point to work on intestinal hormones. One is injectable of Incretins (Exenatide) which are injected on BD (two times a day) basis; research is made on once a day injectable (Liraglutide) which is still under way to be marketed due to its side effects for regulatory approvals the second class of medication is oral drugs dipeptidyl peptidase IV (DPP-4) inhibitors, which slow the breakdown of the gut hormone to let it remain active longer and lower blood glucose levels. These drugs, including Sitagliptin and the newly approved Saxagliptin, may also assist in weight loss.

Weight gain is another issue in the management of promptly Type-2 diabetes. Obese people are more prone to Type-2 diabetes than normal healthy people. People with increase waist line mostly teenagers (girls) who have certain gynecological problems like poly cystic ovary (PCOs) are in later stage if not treated properly being attacked by type-2 diabetes. Obese people or people on foods having more fats on belly region which increase their chance of getting the Type -2 diabetes in their later life. Experiments are conducted which give us Metformin (anti diabetic agent) serendipity give the treatment for PCOs with other contraceptive treatments. The research is still in progress to reduce the GI side effects which causes severe GI upset in initial treatment so first recommend the test dose of Metformin to make people use to it. The new medicines are made  which are free of these side effects.

Pharmaceutical companies made combination pills to reduce the number of pills you need to take in diabetes management as a second line therapy by US FDA. They are not recommended when the people are early diagnosed by Type-2 diabetes. A combination drug is made (Rosiglitazone+ Metformin); some combination pills of high blood pressure or high cholesterol are made to reduce 6 to 12 medications in multidoses of diabetic medication. 

An advancement in the tests are made despite having fasting and random glucose test another test are still in search called HbA1C –test, it is a measure of blood glucose over a past two –three months for early diagnosis of diabetes in all except pregnant women. To prevent or delay the onset of type-2 diabetes by using Estimated Average Glucose (eAG) which translate your HbA1C into numbers. People who are at high risk of diabetes by early detection (known as Pre-Diabetic patients) are prepared optimistic to lose weight (10- 20 pounds) and become more energetic and active by 150 minutes of physical activity per week.

Research findings show that people having diabetes should control their blood pressure to prevent delay and minimizing the damage in micro vascular in eyes, nerves and others. The main controlling parameter of blood pressure is the daily sodium intake.

The recommendations are

·         For general public                                    = 2300mg daily

·         For people with high blood pressure       = 1500mg daily

·         For African American                                = 1500mg daily

·         For all adult over 50 years                       = 1500mg daily

The 75% of people with diabetes are having high blood pressure. They can lower their levels by reducing sodium intake of 1500mg daily. The health organizations and activists are urged on to lower the sodium counts. Lower the intake of processed food, fast food and by using salts shaker to reduce its level.

In these researches, some are in their preclinical phases, some move towards invitro and in vivo studies, and some have their progress towards their premarketing approvals by regulatory authorities but these trials cannot stop the progression in the development of diabetes management and only remember that….

 “If you are Diabetic then cure it, if you doubt you are diabetic then prevent it. It can be curable, preventable or manageable but cannot be ignored in this fast-growing world.”