Striding into the future

Lately, India has seen many new tests emerging to detect diabetes. Jayata Sharma takes you through the new diagnostic tests in the block

Who can forget the advertisement where former Pakistan cricket skipper Wasim Akram endorses a product for diabetes monitoring? Though there are many such commercials which underscore the importance of diabetes monitoring, the grim fact is that primary detection rate of diabetes is abysmally low and cases of diabetes are known only by chance. Analysts say that only 10 per cent of diabetes cases are diagnosed on time and the rest are highlighted when the patient has acquired a more deadly problem, like a heart attack or loss of sight. Early detection and appropriate treatment are the cornerstones for delaying the onset and progression of diabetic complications like diabetic retinopathy, nephropathy, neuropathy, stroke, peripheral vascular disease and ischemic heart disease. Experts say that of the people suffering heart attacks and loss of eyesight, 50 per cent are always diabetic.

Estimates point out that India has a burden of over four crore people suffering from diabetes and the figure will escalate by 60 per cent by the year 2025. Also, it would not be long before every fifth diabetic person in the world will be an Indian. In a metropolis like Mumbai, every tenth person is a diabetic, and the figure will reach to every fifth person in the coming years. Still, the understanding about this silent killer is dismal.

Why The Low Level Of Awareness

There is a possibility that the percentage of cases diagnosed on time will reach almost 35 per cent from the current 10 per cent in the next ten years, if some factors are addressed. The reasons for dismal awareness are manifold. To begin with, India currently has 2,000 diabetologists and a mere 200 endocrinologists. These numbers are inadequate for this world capital of diabetes. The Government has not taken any proactive steps to increase awareness among the masses. Besides, hardly any effort is made to spread awareness in villages. Most of the camps are held in the urban areas, which distances our rural population. "In fact, even in the cities, knowledge is being spread from merely the past seven to eight years," says Dr VN Rajasekaran, Medical Director, Meenakshi Mission Hospital and Research Centre, Madurai.

Diabetes is not accompanied by pain or fever, making the person feel absolutely normal. "Doctors should play a proactive role and tell their patients to get tested for diabetes," says Dr AV Velumani, Managing Director, Thyrocare Technologies, Mumbai. Doctors must advise every person they know above 40 years to go for a diabetes diagnostic test, say experts.

Old Diagnostic Tools

While people with type 1 diabetes, formerly called as juvenile diabetes, are detected in the early stages of their life, type 2 diabetes strikes a person much later because of wrong eating habits and hectic lifestyle. All the tests mentioned below are common for type 1, type 2 and gestational diabetes.

Before discussing the new diagnostic tests, it is important to understand some old tests, which are slowly being replaced by new advanced tests. For many years, Folin and Wu, discovered in 1920 and which works on the colorimetric method, was widely used. Explaining why it is not popular anymore, Dr A Ramachandran, Director, MV Diabetes Hospital and Research Centre, Chennai, says, "These methods were not specific for glucose and measured all the other reducing substances present in blood." To which Dr Sushil Shah, Chairman, Metropolis Clinical Laboratories, Mumbai, adds, "It is a slow reacting method and takes hours to give out results. Also, it is not possible to test minute samples of 20 microlitres in this method."

Nelson, which came to market in 1944, is a technician-dependent method. The faster and more accurately the technician works, the sooner one can get the results. But this test too, takes long hours to give results. "Nelson was an improved version of Folin and Wu, but the problem with this method is that it cannot test more than 5-10 samples at a time," informs Dr Vipul Patel, General Manager, Medical Affairs, Metropolis Clinical Laboratories, Mumbai.

"GOD & POD diabetes test only diagnoses the glucose in the blood and not other sugars" - Dr Sushil Shah Chairman Metropolis Clinical Laboratories, Mumbai

Next to enter the market in 1969 was Glucose Oxidase (GOD) And Peroxidase (POD), which is an enzymatic procedure that indicates the biochemicals reactions taking place in the blood. And why it is not preferred today? "GOD & POD only diagnoses the glucose in the blood and not other sugars," explains Dr Shah.

Latest Techniques

The earlier tests are now gradually being replaced by latest techniques. The newer tests, which hit the market in the late 1980's, were more accurate, less complicated and delivered results faster. Amidst the new tests, Fasting Blood Glucose, Post-meals Glucose testing and in the end HbA1c (to confirm the average blood glucose and used mainly for monitoring purposes) are important for all patients. The other tools are subject to individual requirements.

Fasting Blood Glucose is considered the gold tandard for diagnosing diabetes, showing the elevated blood sugar level after an overnight fast. The panic button is hit if the result is above 126 mg/dl on at least two occasions in the Fasting Blood Sugar and above 200 mg in the Post Glucose one. Non-diabetics have fasting sugar levels that generally run between 70-100 mg/dl. After this, post-meals test is conducted, wherein the patient is told to test the blood again two hours after eating. "Recently, the upper limit of normal sugar level is standardised to 100 mg/dl," informs Dr RK Lalwani, Diabetologist from Rockland Hospital, New Delhi.

Urine Glucose Testing is a semi-quantitative measurement, which closely parallels the blood glucose concentration. "Urine Glucose testing by Benedict's method or by the test strips using glucose oxidase procedure are equally satisfactory when used with care," informs Dr Ramachandran. Use of the test strips for urine glucose avoids interference by non-glucose substances. However, patients have to be educated about the possibility of changes in the renal threshold. This is especially true in case of elderly patients with long standing diabetes and hypertension, pregnant women and patients on multiple drug therapy. The urine glucose value reflects an average level of blood glucose during the interval since the last voiding and not the level at the time of test.

Urine Ketone test is an important part of monitoring, particularly for type 1 diabetes. All urine samples corresponding to blood glucose levels greater than 200 mg/dl should be tested for ketones. "Rothera's test is commonly used for detecting ketonuria, while quantitative estimations of ketones are rarely done," asserts Dr Lalwani. He further adds, "Urine ketones are now best tested with Ketostix from Bayer."

Lipid Profile is a boon for diseases damaging multiple organs and finds the cholesterol and protein level in the patient. "In diabetes, the kidneys are the first ones to get affected. Lipid Profile helps by testing the urine for finding out the protein levels in the body," informs Dr Saifuddin Mohamedally Bandukwala, Diabetologist and Cardiologist based in Mumbai.

Hexokinase is a test for enzymes. The Hexokinase method has been evaluated in comparison with other methods for glucose and has been proposed as a reference method. This method is suitable for various enzyme analysers, and is unaffected by haemolysis, lipaemia or the presence of increased amounts of urate, ascorbic acid or bilirubin in blood. "Though there are many enzyme-related tests available, their reference range might vary from lab to lab. It depends on the kind of enzyme selected by that particular lab," says Dr Patel. In Hexokinase, drugs affecting some of the oxidase methods do not interfere, but high amounts of anticoagulants may affect the reactions, say experts.

Then there are Islet Antibody and GAD Antibody tests which target different sites in the blood cells and destroy the insulin released by the pancreas. This restricts the insulin function, resulting in high risk for diabetes.

Glycosylated Haemoglobin Test (HbA1c) studies the blood sugar taking the average of three months, and thus, does a much broader study of the patients' blood sugar. There are around 8-10 ways in which this test can be conducted. "However, only the DCCT test, measured by High-Performance Liquid Chromatography (HPLC), is the gold test and the most trusted one," states Dr Shashank Joshi, Endocrinologist with Mumbai-based Lilavati Hospital. "HbA1c test is a relatively new test, and the importance and direct link to diabetes complications were established after the DCCT studies which ended in 1993," says Siddharth Puranik, Marketing Manager, Bio-Rad Laboratories, NCR.

Glycosylation of HbA1c and other proteins in blood is a natural process occurring non-enzymatically. The American Diabetes Association (ADA) recommends measuring HbA1c at least twice a year in diabetic patients with stable glycaemic control and more frequently in patients who do not meet the desired goals.

As diabetes is a result of drop in the insulin level or a resistance to it, hence monitoring insulin through various insulin tests is of utmost importance. Fructosamine test is similar to HbA1c. The only difference being that this measures the blood sugar of the last 15 days. Another is a qualitative test, Auto Antibody Test. "The Auto Antibody is like an insulin eater, as it attacks directly on the pancreas and restricts the flow of insulin," says Dr Patel. The glucose level is managed through insulin, which is released by the pancreas.

As prevention is better than cure, Micro Albumin test helps in the prevention of diabetes and avoids the damage to kidneys as early as before five-six years. Rather than knowing from the protein in the later stages of diabetes, this test helps to diagnose the harm to kidneys earlier. "We can actually reverse the entire medical condition of a person by Micro Albumin test," avers Dr Shah. Of all the diagnostic tools mentioned above, Blood Glucose test is the most popular one. Reasons for it being preferred range from it being a fast-resulting test to being cost-effective.

Monitoring Made Easy

The blood sugar level varies from time to time and hence it is important to monitor it in an appropriate manner. "In India, Bio-Rad is continuously investing in generating awareness on HbA1c by arranging seminars, meets, CMEs and inviting authorities from institutes like NGSP to provide insight," informs Puranik. The testing frequency of HbA1c for diabetic patients is two-three times in a year followed by most developed countries.

The other tool C Peptile, which despite being an effective test, has generated some doubts. It is perceived by many, that if a person takes insulin around the time of the test, the real glucose level will not show. "This is not true, C Peptile is absolutely accurate and the results are not at all affected by any external factors," clarifies Dr Shah.

"We provide many kits of HbA1c whose instrument platforms are based on high pressure liquid chromatography (HPLC) technology. These are Variant Turbo, Variant II, D-10, Diastat and point of care A1C testing instrument called Micromat for doctors," says Puranik.

Dr Velumani opines, "According to studies worldwide, HbA1c is a better test as it covers three months of blood glucose. But, as it is much expensive than the other tests, Hb1Ac is sidelined, especially in India."

However, there is difference of opinion among diabetologists on conducting HbA1c at home. "We strictly go by the guidelines of ADA, which do not allow the HbA1c test at home. It should only be done under the supervision of a trained physician," says Dr PD Sawant, Diabetologist and Chief of Quality, Wellspring Pathlab iagnostics, a Nicholas Piramal Venture, Mumbai.

Monitoring Diabetes At Home

Newer inventions in technology have made our lives simpler than we can enumerate. Disease management is also a part of this. Various classes of Gluco Meters are available in the market by which a diabetes patient can monitor his blood sugar without visiting a doctor. While HbA1c and C Peptile are purely lab tests, Gluco Meters are used to monitor glucose at home.

Gluco Meter is a device useful for patients with both type 1 and type 2 diabetes, as it assists in continuous monitoring of glucose. Recently, a new Gluco Meter was introduced in the market, with a finer needle called Lancet. This has proved to be a boon for patients as it is less painful than the earlier one. "In spite of there being always a slight difference of 10-20 per cent between the results of a lab test and the Gluco Meter, many times we ourselves insist on patients purchasing the home monitoring devices for regular monitoring," says Dr Bandukwala.

There is also a Continuous Glucose Monitor, in which a glucose sensor contained in a small needle is placed under the skin. It wirelessly transmits results to a small recording device (the size of a pager or cell phone) worn on the clothing. This sensor records and displays the blood glucose level every few minutes, and patients maintain the desired blood sugar levels without the risk of hypoglycaemia. "Patients must still measure their blood glucose level with a traditional monitor several times daily to ensure that the continuous monitor is correctly calibrated," advises Dr Lalwani. The costs associated with continuous glucose monitors are much greater than traditional glucose monitoring.

However, most doctors prefer lab tests for monitoring diabetes. "When patients put pressure on the pricked area to release blood, plasma is released, thereafter, the Gluco Meter cannot give proper results," says Dr Rajasekaran, with his 30 years of experience in treating diabetes.

The main players involved in manufacturing of Gluco Meters are Bio-Rad, Meditronics, Novo Nordisk, Johnson & Johnson, Roche Diagnostics, Bayer and OMRON.

Research

Human mind is always on the run and determined to discover better ways to improve the existing factors. Research work is constantly on the go for enhanced detection and monitoring of diabetes.

"We are trying to develop various classes of sensors, to detect several parameters of diabetes" - Dr AQ Contractor Professor Chemistry Research Department IIT, Powai, Mumbai

The much-hyped detection tool that the medical community is looking forward to is Gluco Sensors. If successfully launched, they will prove to be a boon to both type 1 and type 2 diabetics. Sensors work on a spectrophotometry method and their reactions can be monitored either visually or by radio signals. Gluco Sensors test the blood sugar from the capillaries. They are being designed to replace the pricking method with a device which will sense the glucose in the blood and give the results. Research is being conducted at IIT, Powai, Mumbai on a sensory device to diagnose and monitor diabetes. "We are trying to develop various classes of Sensors, so that several parameters can be taken care of," informs Dr AQ Contractor, Professor, Chemistry Research Department, IIT, Powai, Mumbai. Also, Sensors based on glucose oxidase and similar compounds are being tested in a variety of configurations.

"With the help of biochemical markers, it will be possible to find out the sub-types of diabetics" - Dr Shashank Joshi Endocrinologist Lilavati Hospital Mumbai

Even after not following a strict diet, many patients are free from complications, and patients who follow a strict diet many times contract certain problems. Now, doctors have a problem differentiating between such patients. It is vital to know the sub-types of patients to guide them in a better manner. For this, biochemical markers are being developed. "We are working on this concept. With the help of biochemical markers, it will be possible to find out the sub-types of patients," informs Dr Joshi.

Studies are being conducted, mainly at the Michigan University and the Buffalo University in the US, to find a method wherein, diabetes can be avoided well before a child is born. Genetic factors will be worked upon and thus, the child will be free of diabetes when he/she is still in the womb. This method will be a boon to children with both parents diabetic.

Infrared light is also being looked at and so is measuring glucose through saliva or tears. There's also a possibility that sweat can be drawn through the skin using a low-level electrical current. "In addition, Texas A&M University is conducting Juvenile Diabetes Foundation (JDF)-funded research into the use of ultrasound to extract interstitial fluid in type 1 diabetics. Other researchers are experimenting with skin patches that pull fluid from the skin and can then be 'read' in a gluco meter," avers Dr Lalwani.

Likewise, a therapy called Arxxant-Riboxisaturin is under investigation for the treatment of moderate to severe non-proliferative diabetic retinopathy (decreased vision and blindness). It works by limiting the over-activation of protein kinase C beta (PKC b), a naturally occurring enzyme that has been linked to the development of diabetic retinopathy.

Research institutes expend a considerable amount of money in their work. MV Diabetes Hospital spends about 12 per cent of its total profit for research. "Additionally, we receive around Rs 50 lakh to Rs one crore from other agencies. Hence, annually we spend approximately Rs one-two crore on research," informs Dr Ramachandran.

Looking Forward

Research is also being conducted on diabetes-related treatment options. Bio-Rad recently launched D-10, which identifies and quantifies the normal and abnormal haemoglobin like HbA, HbA1c, HbF, HbA2, HbD, HbS, HbE and HbC. It also helps in identification of compound cases of thalassemia and haemoglobinopathy when they coexist (S-Beta thal, SD disease).

MV Diabetes Research Centre (DRC) conducts epidemiological surveys time and again to assess the rising prevalence of type 2 diabetes and impaired glucose tolerance in the population. "We completed three diabetic surveys in the urban population, in 1989, 1995 and 2000," says Dr Ramachandran.

An epidemiological study at DRC showed that the prevalence of metabolic syndrome among urban adults was 41 per cent. In 16 months, 10,839 non-diabetic subjects were screened by 2h blood glucose (75gms glucose load) and 1,332 (12.3 per cent) had IGT. On a repeat test, among the 1,025 responders (77 per cent), 531 (51.8 per cent) showed persistent IGT. "Approximately, one in 20 (4.9 per cent) of the screened subjects was eligible for randomisation, if tested twice with GTTs. Persistent IGT was more common in association with a positive family history of diabetes," informs Dr Ramachandran.

Thyrocare has started a one-week course for fresh graduates in medicine called Diabetic Diagnostic Counsellor, wherein these students make home visits to find out whether residents are prone to diabetes, by finding out their eating habits, etc. "We started this course in July this year, and 20 batches have successfully completed it. The objective behind this is to increase the level of awareness amongst common people," informs Dr Velumani.

Points Of Concern

In the US, National Glycosylated Study Group (NGSG) has formed standards to be followed for the HbA1c test. This is because there are certain discrepancies in the test results of various labs. On a regular basis, NGSG issues standards to various labs across the US. Sadly, this system is still to come to India. "We only have the NABL accreditation for the labs, but this still does not guarantee similar results always," says Dr Joshi.

Apart from spreading awareness among the general public, it is also important for doctors to be informed about the latest tests, so that they can also guide the patients for the same. Most doctors feel that the electronic and print media should be used to strengthen awareness. "HIV and AIDS is consuming resources, whereas diabetes and pre-diabetes are major killers too," says a concerned Dr Lalwani. Another stumbling block is that the diabetologists are hesitant to refer their patients to the nephrologists for monitoring purposes. "Kidneys get affected so fast that it is important to know in time the status of infection in kidneys," asserts Dr Sawant. Also, dieticians must guide people to healthy lifestyle and thus bring about a drop in the rate of type 2 diabetes.

Conclusion

The awareness level of Indians about diabetes is only around 10 per cent. Pretty bad? But not when compared to the earlier figure of 0.1 per cent. Diabetes is putting a severe burden on the already fragile healthcare system of India. Adopting result-oriented awareness programmes will drastically reduce the burden on our healthcare system. However, what experts await is a full-fledged and well-managed awareness drive to help them diagnose diabetes early and thus reduce its future hazards.

jayatasharma@gmail.com