Recent trends in the Treatment of Diabetes

Diabetes is not a newly born disease, it has been with human race from long back but, we came to knew about it in 1552 B.C. Earliest known record of diabetes mentioned on 3rd Dynasty Egyptian papyrus by physician Hesy-Ra; mentions polyuria (frequent urination) as a symptom. Today it is defined as a chronic disease, which occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. This leads to an increased concentration of glucose in the blood (hyperglycemia).

Diabetes Burden in India

India is home to thirty-five million people with diabetes—nearly 15 percent of the global diabetes burden—and projections show that this will increase to seventy million by 2025. Diabetes disproportionately affects people of working ages and accounts for US.2 billion in annual health care costs in India alone. Because India has a population of 1.1 billion, 40 percent of whom are under age eighteen, investment in the health of India’s future workforce is crucial.

Diabetes is part of a larger global epidemic of noncommunicable diseases. Because these diseases share many risk factors; policies that encourage healthy eating and active living will prevent not only diabetes, but also obesity, cardiovascular disease (CVD), chronic respiratory illnesses, and diet-related cancers. An integrated system can maximize disease prevention while avoiding the need to develop separate courses of action. Strategies proposed here are prioritized according to their ability to be aligned and integrated into a comprehensive movement that addresses all non-communicable diseases.

Diabetes is a widespread disease, a metabolism disease, with an increasing number of patients. This increasing number of diabetes patients globally is proving a boon for diabetes drugs market. The number of diabetic patients in the world (Type 1 and Type 2) is estimated to reach at more than 250 Million in 2009. An additional 200 million people are likely to have impaired glucose tolerance, a precursor for type 2 diabetes, and this is expected to rise to 420 million by 2025. An estimated 12-14 years of life lost to premature death. Type 2 diabetes is projected to have its heaviest impact on developing countries, and the epidemic is no longer confined to affluent urban residents. In developing countries, the disease disproportionately strikes people of economically active ages, resulting in loss of human capital and productivity, perpetuating poverty faced by many, and potentially stifling development. India comprises 85% of the adult population of SEA and therefore the major contribution to diabetic population in SEA is from India.

As discussed in the new visiongain report – World Diabetes Market Analysis, 2009-2023 – The World Health Organization estimates the number of diabetics to exceed 350 million by 2030. Governments and other healthcare providers around the world are investing in health education, diagnosis and treatments for this chronic, debilitating – but controllable – disorder.  In 2007, the diabetes treatment market worldwide was worth over billion, and had double-digit growth from the year before. Consequently, it is one of the largest sectors in the global healthcare industry in term of market value.

Brief Introduction to Diabetes

Diabetes mellitus refers to a group of common metabolic disorder that shares the phenotype of hyperglycemia. Several distinct types of diabetes mellitus exist and are caused by a complex interaction of genetics and environmental factors. The metabolic dysregulation associated with DM causes secondary pathophysiological changes in multiple organ system that imposes a tremendous burden on the individual with diabetes and on the health care system. The elevated blood glucose associated with diabetes mellitus results from absent or inadequate pancreatic insulin secretion, with or without concurrent impairment of insulin action.

The disease states underlying the diagnosis of diabetes mellitus are now classified into four categories: type 1, “insulin-dependent diabetes,” type 2, “noninsulin-dependent diabetes,” type 3, “other,” and type 4, “gestational diabetes mellitus” (Expert Committee 2002, Mayfield, 1998). This insulin dependent group (type 1) represents 5–10% of the diabetic population in the USA. Most type 2 diabetics do not require exogenous insulin for survival, but many need exogenous supplementation of their endogenous secretion to achieve optimum health. It is estimated that as many as 20% of type 2 diabetics in the USA (2–2.5 million people) are presently taking insulin. Gestational Diabetes (GDM) is defined as any abnormality in glucose levels noted for the first time during pregnancy. Gestational diabetes is diagnosed in approximately 4% of all pregnancies in the USA.

Common symptoms of type 1 diabetes include: excessive thirst; constant hunger; excessive urination; weight loss for no reason; rapid, hard breathing; vision changes; drowsiness or exhaustion. These symptoms may occur suddenly. People with type 2 diabetes may have similar, but less obvious, symptoms. Many have no symptoms and are only diagnosed after many years of onset. As a consequence, almost half of all people with type 2 diabetes are not aware that they have this life-threatening condition. Life style measures alone, but oral drugs are often required, and less frequently insulin, in order to achieve good metabolic control.

GOALS FOR PEOPLE OF DIABETES

Measures

Recommendation goal

Fasting blood glucose - Below 110mg/dl (Below 100 is better)

Post-meal (2-hour) blood glucose - Below 180mg/dl (Below 140 or so is better)

HemoglobinA1c (HbA1c) - Below 7% (Below 6.5% is better)

Cholesterol

Total cholesterol - Below 200mg/dl

LDL (“bad” cholesterol) - Below 100 mg/dl (below 75 is better)

HDL (“good” cholesterol) - Above 40mg/dl for men and 50 mg/dl for women

Triglycerides - Below 150 mg/dl

Blood pressure

Below 130/80 mmHg

Management and Treatment of Diabetes

Monitoring of Glucose Levels

Monitoring of glucose levels can be done by either blood or urine testing. Blood testing is optimal, but if this is not available then urine testing is an acceptable compromise. The frequency of monitoring will depend upon resources available, either to the individual or the country concerned.

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Self-monitoring of glucose levels

Self-monitoring of blood glucose levels should be regarded as essential to improve the safety and quality of treatment. Methods and frequency of self-monitoring depend on the targets and mode of treatment. Blood measurements should be recorded.

Two replicate fasting levels that exceed 126 mg/dl (>7 mmol/L) are diagnostic in the absence of symptoms. The ADA’s definition of the cut point for normal fasting blood glucose levels was dropped from 110 mg/dl to 100 mg/dl, meaning that a value of 100 mg/dl or above would lead to a diagnosis of impaired fasting glucose (IFG), which is included in the term pre-diabetes. Persons with impaired fasting plasma glucose (FPG) levels (FPG= 100-125 mg/dl (5.66.9 mmol/l) and/or with impaired glucose tolerance test (IGT) (2 hour post-load glucose 140-199 mg/dl (78.8 mmol/L-11.1 mmol/L) are at risk of diabetes and should be observed periodically to detect progression to overt diabetes. Replicate, two-hour glycemic responses >200 mg/dl (>11.1 mmol/L) after a standard oral glucose tolerance test also indicates diabetes.

Glucose Level

ADA Evaluation

Normal

 

 

Impaired glucose tolerance(IGT)

 

Diabetes mellitus

Fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol/L), HbA1c <6

 

Fasting plasma glucose (FPG)  100 (5.6 mmol/L) but <126 mg/dL (7.0 mmol/L) or two-hour

plasma glucose level  140 mg/dl (7.8 mmol/L) but <200 mg/dl (11.1 mmol/L), HbA1c <7

 

Fasting plasma glucose FPG =126 mg/dL (7.0 mmol/L) or randomly (or 2 hr OGTT value) =

200 mg/dL (11.1 mmol,

HbA1c >8

 

The American Diabetes Association (ADA) Guidelines for the Evaluation of Glucose Level to Diagnose or Predict Diabetes

 

ADVANCE IN DIABETES MONITERING

Pain Free Glucose Tests

The Food and Drug Administration has approved Amira Medical’s new At Last Blood Glucose System and it’s now available for consumer use. The system allows patients to monitor their blood sugar without the pain of sticking their fingers to get blood samples.

The system is the first to contain both a lancing device and a blood glucose meter all in one. It uses a unique disposable test strip to obtain blood samples from the forearm, thigh or upper arm, areas that have fewer nerve endings so it doesn’t hurt as much as a finger stick.

Continuous Monitoring Device

The Food and Drug Administration has approved a wristwatch-like device that provides more information for managing diabetes. It is intended for use along with, not as a replacement for, finger stick blood tests to monitor glucose, in order to ensure accurate results.

The GlucoWatch Biographer extracts fluid through the skin by sending out tiny electric currents. The watch may be worn for 12 consecutive hours, producing 3 measurements every hour, even while asleep. An alarm will sound if blood glucose levels are detected to be dangerously low, or if a measurement was skipped, as can occur in the presence of excessive sweat. The device is available only by prescription to detect trends and track patterns in glucose levels in adults age 18 and older. It is manufactured by Cygnus, Inc.

Advance in treatment of Diabetes

New treatment

Islet Cell Transplant

A new islet cell transplant technique has shown promise in people with Type 1 Diabetes, called the ‘Edmonton’ technique. The transplants have resulted in seven patients becoming insulin free for up to 14 months after treatment. Clinical trials are now underway at 10 national diabetes centers to see if the insulin reversal can be successful with more patients. The Edmonton technique uses islet cells (cells from the pancreas) from two or more donor pancreas. The cells are transplanted into a person with diabetes and then special medications are given to prevent rejection of the new cells. One difficulty with the transplants is that even though a person may become free of the need to take insulin, the medications to prevent rejection of new tissue must be taken for a lifetime and these medications have got some side effects.

Gene Therapy
Two recent reports describe research into gene therapy for different aspects of diabetes. These reports are in the forefront of what will no doubt be ongoing and exciting research arising from the decoding of the human genome.

Scientists have identified a gene called SHIP2 that appears to regulate insulin. Such findings make SHIP2 a potential gene therapy target for the treatment of type 2 diabetes aimed at improving the individual’s insulin regulation.
A protein that blocks the overgrowth of blood vessels in the eye is being studied as possible gene therapy for diabetic retinopathy. A recent study showed that treatment with the protein, called pigment epithelium-derived factor, or PEDF, prevented excessive new blood vessel formation in an animal model of retinopathy. It may also be used to treat macular degeneration.

As scientists identify specific genes whose absence or improper functioning are associated with specific conditions, more possibilities for gene therapy are offered – for diabetes as well as all disease.

Vaccine

“Vaccine” against Diabetes on the Horizon

Scientists have developed the world’s first drug that stops the destruction of pancreatic beta cells in humans. It thereby offers the possibility of preventing type 1 diabetes in people at high risk and of halting its progress in people newly diagnosed with it.

Results published in a recent issue of The Lancet showed that three injections of the compound given within six months of diagnosis of type 1 diabetes successfully arrested the progression of the disease in newly diagnosed patients. After treatment, these patients produced insulin and required fewer insulin injections. They did not experience any harmful or major side effects. While this data looks promising, additional studies are under way to confirm its effectiveness and safety.

The drug is a peptide, a type of protein. By modifying a fragment of the protein, the developers created a drug that can selectively block the activity of immune cells that attack the pancreas. It thus deactivates the cells that attack the pancreas without interfering with the rest of the body’s immune system.

Insulin therapy

Insulin is used in the treatment of patients with diabetes of all types. The need for insulin depends upon the balance between insulin secretion and insulin resistance. All patients with type 1 diabetes need insulin treatment permanently, unless they receive an islet or whole organ pancreas transplant; many patients with type 2 diabetes will require insulin as their beta cell function declines over time.

Insulin should be given to all patients with type 1 diabetes, which is due to autoimmune islet-cell injury that eventually leads to virtually complete insulin deficiency. Clinical features which, if present in a patient with diabetes at any age, suggest the need for insulin therapy include marked and otherwise unexplained recent weight loss (irrespective of the initial weight), a short history with severe symptoms, and the presence of moderate to heavy ketonuria. Diabetic ketoacidosis at first presentation usually indicates that the patient has type 1 diabetes and will require lifelong insulin treatment. However, some patients with type 2 diabetes, especially in the Afro-Caribbean populations (so-called “Flatbush diabetes”), may present with ketoacidosis.

Advance in Insulin Therapy

1 – Implantable insulin pumps

Scientists are making progress with an implantable capsule that continuously produces insulin and releases it to the bloodstream. It contains insulin-secreting cells that borrow nutrients from the body to keep producing insulin indefinitely. The University of Illinois biomedical engineer developed the capsule with funding from the National Science Foundation. He presented his results at a recent meeting of the American Vacuum Society; they were also published in the November 2001 issue of Transactions in Biomedical Engineering.

2 – Insulin inhalers

Although daily injections of insulin would still be needed, inhaled insulin is currently in clinical trials and may be headed for a fast track approval by the Food and Drug Administration (FDA). These inhalers are about the size of a flashlight and uses rapid-acting insulin. The sprayed insulin is inhaled into the mouth and coats the mouth, throat and tongue. The insulin passes quickly into the bloodstream.

3 – Insulin Pill
The discovery of a new polymer that may allow development of an effective insulin pill was reported at a recent meeting of the American Chemical Society. When the polymer is used as a pill coating, it allows insulin to get into the bloodstream without being destroyed by the digestive system. So far it has only been tested in animals. Some experts question whether insulin in pill form will prove useful, since dosing is so critical and often variable.

4 – New Insulin’s

In the past year, three new formulations of insulin have become available which have been designed to offer the advantages of simpler regimens and better glucose control for people whose diabetes must be treated with insulin. All are human insulin analogs derived from recombinant DNA technology. They are:

Glargine (from Aventis Co.) is a basal insulin, offering a more continuous activity with much less of a peak than NPH insulin. It can be used with very-rapid-acting insulin such as lispro or aspart, and should provide a flatter basal amount of insulin. Until now this has only been possible with twice daily injections of ultralente or by the basal rate of an insulin pump. This approach tries to permit more normal mealtime patterns individualized to a person’s own habits.
Aspart (from Novo Nordisk) is very-rapid-acting insulin that can be injected 15 minutes prior to eating. Its fast action also allows more freedom in the timing of meals and the amount of food eaten.
A 75/25 lispro mixture is the first of the analog mixtures available (from Eli Lilly); it contains Lilly’s very-rapid-acting lispro and a novel human insulin analog called NPL. It is designed for those who need better control after meals and want to use an insulin pen.

Discussion

Type 2 diabetes has now hit epidemic levels, and is expected to increase further over the coming years with the rise in the age demographic and the escalation in rates of obesity.

The insulin market is dominated by three companies – Eli Lilly, Novo Nordisk and Sanofi-Aventis – but the OAD market is more diverse and more valuable, thus representing more opportunities for entry. The non-invasive insulin’s in development have the potential to revolutionize the insulin market. Currently many type 2 patients are put off using insulin because of its injection delivery and patient compliance a. Thus oral or inhaled insulin would tap into the lucrative type 2 market and encourage further use of insulin. Non-invasive insulin’s will address the key unmet need in the diabetes market. Several pills, inhalers, mouth sprays and patches are in development and this is likely to cause an increase in the number of users in the type 2 patient population cure.

Dual PPAR agonists have blockbuster potential because they can treat both diabetes and heart disease. These drugs have blockbuster potential in halting the progression of both diabetes and heart disease, thus sales of not only diabetes products but also cardiovascular products. However, concerns over safety of such drugs may delay their entry on the market.

TZDs are the highest selling products in the US diabetes market, but have had little market penetration in Europe, due to continued concern about the safety of the class following the withdrawal of Rezulin.

Combining drugs into single-pill formulations has proved to be a valuable life-cycle management tool for several companies, for example GSK has combined Avandia with Metformin to make Avandamet.

Companies can increase their market share by identifying where the major growth opportunities lie and exploiting the unmet needs in each market. They can maximize their products success by understanding markets and tailoring their strategy accordingly. They can drive their company’s future growth prospects by examining the key trends affecting the diabetes market and discover how they are shaping the future of this market.