Looking Beyond HbA1c: Research To Find New Diabetes Biomarkers Gains Traction

The discovery of several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes
BETA cells within the pancreas produce and release insulin. Loss of the function of these cells compromises the body’s ability to control blood sugar and underlies the development of diabetes. So, one of the next frontiers of diabetes therapeutics is to change the progression rate of beta cell failure.

Recognizing this as a research priority, the Foundation of the National Institutes of Health (FNIH) Biomarkers Consortium announced Tuesday the launch of a multi-year clinical study to improve tools for measuring the function of insulin-producing beta cells in people with type 2 diabetes mellitus. Researchers hope the initiative will lead to improved techniques for tracking progression of the disease and pave the way for more effective treatments.

The project ‒ “Diabetes Drug Development: Identification and Validation of Markers that Predict Long-Term Beta Cell Function and Mass” ‒ is being managed by the Metabolic Disorders Steering Committee (MDSC) of the FNIH Biomarkers Consortium.

It is a three-year, $5.1 million clinical study to standardize tests for measuring beta cell function in the clinical setting that aims to improve methods for the early prediction of the long-term response to an intervention and for identification of patients at risk for rapid beta cell function deterioration, thereby enabling future clinical studies that examine diabetes progression.

A biomarker is a biochemical feature or facet that can be used to measure the progress of disease or the effects of treatment. So the validation of biomarkers to measure the progression of diabetes will greatly facilitate the development of better medicines to treat and potentially prevent this disease and its often disabling complications.

Experts believe biomarkers will become one of the major driving forces of pharmaceutical research and drug development in the coming years.

Currently, diabetes researchers are working without the benefit of agreed-upon standards for gauging beta cell function and this initiative will give researchers practical tools that can be used to measure beta cell function over time and stimulate research to maintain and improve that function.

The project was developed through a rigorous consensus-building process by a team of experts from across the entire scientific community. The pharmaceutical industry, academic, and government representatives contributed their clinical trials expertise and scientific support to the design and execution of the studies.

Utilizing a collaborative approach, the FNIH Biomarkers Consortium has brought together diabetes experts from the National Institutes of Health (NIH), Food and Drug Administration (FDA), leading academic institutions, the pharmaceutical industry, and non-profit sector to develop the project.

Biomarkers play an integral part in conducting clinical trials and treating patients. In most instances, they help medical practitioners, researchers, and regulatory officials make well-informed, scientifically sound decisions.

However, in clinical studies, there is often uncertainty in how much weight to place on biomarker results versus clinical outcomes. This uncertainty emanates from opposing goals of the drug approval process. On one hand, the process must ensure that all therapeutics tested are safe and that the benefits outweigh the risks. On the other hand, the process should allow therapies to be accessible to patients as quickly as reasonably possible.

Judicious use of biomarkers in the drug development process can bring these goals into alignment. More efficient discovery and use of biomarkers in the development of anti-diabetes drugs will depend on advancing current understanding of the pathogenesis of diabetes and especially its macrovascular (pertaining to the larger blood vessels) complications.

The idea of using biomarkers to predict diabetes is not entirely new. Glycated hemoglobin (HbA1C) values are now routinely being monitored to screen for at-risk patients. A study published in PLoS One last year shows that several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes, and increase our knowledge of the etiology of the disease.

Veikko Salomaa and colleagues from the Department of Chronic Disease Prevention at the National Institute for Health and Welfare in Helsinki, Finland, tested nearly 13,000 people and found almost 600 cases of diabetes during routine follow-up exams.

According to the study, low levels of adiponectin, and high levels of apoB, C-reactive protein (CRP), and insulin, increase the chance that a woman will develop diabetes. When these factors were measured, proper diabetes prediction increased by 14% compared to when doctors only use classic risk factors, such as BMI and blood glucose levels, to predict disease.

The biomarkers that best predicted diabetes in men were low adiponectin, and high levels of CRP, interleukin-1 receptor antagonist (IL-1RA), and ferritin. Accounting for these biomarkers led to a 25% increase in correct diabetes detection in the cohort. Adiponectin is a hormone found in the body that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism.

The use of adiponectin, a hormone derived from fat cells, which is abundant in plasma and easy to measure through commercially available kits, was also confirmed as a robust biomarker predictive of glycemic efficacy in Type 2 diabetes and healthy subjects, after treatment with peroxisome proliferator-activated receptor-agonists (PPAR), but not after treatment with non-PPAR drugs such as metformin by the first project to be completed by the Biomarkers Consortium.

The project conducted a statistical analysis of pooled and blinded pre-existing data from Phase II clinical trials contributed by four pharmaceutical companies and analyzed under the direction of a diverse team of scientists from industry, the National Institutes of Health (NIH), U.S. Food & Drug Administration (FDA), and academic research institutions.

Source: FNIH Biomarker Consortium

Why Do Diabetics Find It Difficult To Exercise, Researchers Wonder

Research being carried out by scientists at the University of Colorado School of Medicine is investigating why exercise feels more difficult for people suffering from type 2 diabetes than it does for people without the disease.

With a recent study showing that under half of all people with type 2 diabetes take any regular exercise, and that people who do not have diabetes are actually more likely to take exercise, the team hope to pinpoint the reasons why this is.

The new study is examining 50 women aged between 50 and 75, with each being questioned about their level of comfort with exercise, and the findings for those with diabetes being compared to that of women without the disease of a similar age, weight and physical ability.

If this study is able to confirm findings from previous research that revealed that exercise felt harder for those people with diabetes, then it is hoped it will be possible to design specific exercise programmes for people with type 2 diabetes.

Diabetes Discovery: Indian Scientists Create Novel Form Of Insulin

A team of Indian scientists has discovered a novel form of insulin that could drastically reduce the suffering diabetics face in controlling their blood sugar.

For the diabetics, daily painful pinpricks to inject doses of insulin is a routine affair, now in a new discovery scientists claim a single shot of insulin could help keep sugar levels under control for more than a month. Today the effect of each insulin injection lasts at best for a day.

India is considered the diabetes capital of the world, with as many as 50 million people suffering from this chronic disease, so any new discovery is welcomed with open arms.

The team spent less than $45,000 and took two years to come with this novel solution. These scientists have already patented the technology, commercialized it and the new insulin could well become a big money spinner in times to come, feels the man who discovered this new form of insulin.

"It is a multi-million dollar technology transfer agreement with royalties once the product goes to the market and if I am not wrong it is one of the biggest scientific innovations to have come from a government owned research laboratory," said Professor Avadhesha Surolia, Director, National Immunology Institute, New Delhi.

The researchers treated natural human insulin at varying temperatures and chemical conditions and one such special formulation does the magic. In experiments done on rats, mice and rabbits the team could control the sugar levels like of these diabetic rats simply by giving an injection once every three months.

Imagine having to do away with multiple injections everyday to control the sugar problem. The simplicity of the discovery and its huge potential has attracted immediate attention.

"Both conceptually and for clinical practice it is an exciting discovery because it uses natural chemically unchanged insulin and clinically it is useful because it provides ease for patients by reducing the number of pin pricks," said Dr Ambrish Mithal, Diabetologist and president, Endocrine Society of India.

It is not often that new drug is discovered in India, but its use in humans could still be many years away.

The new insulin molecule discovered by Indians in India could become a blockbuster drug in times to come as it holds a lot of promise, currently being tested on animals like on rats, it will soon undergo human trials and then it may become available as drug for the treatment of diabetes.

Reported by ndtv.com

Indian Get Diabetes Before Europeans

Underscoring the importance of an individual's genetic make-up in disease development, a new study has confirmed the association of eight gene variants with type 2 diabetes in Indians.

With Genome Wide Association studies worldwide revealing the likely link of about 20 loci with type 2 diabetes, scientists from Centre for Cellular and Molecular Biology (CCMB) and three other institutions in the country investigated the association of eight common and well-established genetic variants with type 2 diabetes in 5,148 Indians.

The study was recently published in ‘Diabetes', a journal brought out by the American Diabetes Association.

According to Giriraj R. Chandak, senior scientist from Centre for Cellular and Molecular Biology, the onset of diabetes among Indians was a decade earlier than in Europeans and at a lower body mass index (BMI), probably because of excess fat around the abdomen.

As a result, the other health problems associated with diabetes too get manifested earlier than in Europeans or others. With each of the variants having its own impact in developing the risk for diabetes, it was found that the effect was much higher in Indians.He said there could be more than the eight variants which were so far found to be associated with diabetes in Indians.

The identified variants increased the risk of diabetes by 21 to 25 per cent. The risk of developing diabetes was found to be higher when an individual carried more than a single variant.

Stating that the study gave a clear idea of how genetics played an important role in development of diabetes, the senior scientist said, it however, remained to be seen how the gene variants interact with other lifestyle risk factors like diet and lack of exercise.

Early identification of such genetic variants could help in prediction of diabetes risk in individuals as also in developing targeted drug therapy.

The other institutes involved in the study are Institute of Genomics and Integrative Biology, Delhi, King Edward Memorial Hospital and Research Centre, Pune and Indian Statistical Institute, Kolkata.

Y Mallikarjun/The Hindu