Diabetes Research

We read with interest that Novo Nordisk announced on Oct 23, 2008, a new research collaboration with the biotech firm Cellartis AB and the Lund University Stem Cell Center to develop using human stem cell which are insulin-producing with the potential of cell transplantation; the company believes this is the most promising approach for type 1 diabetes. Novo Nordisk had been involved in stem cell research studying mice since the beginning of the century. Their scientists aim to find a cure for diabetes and to do this they will need to use human embryonic cells.

This week just happens to coincide with the American Heart Association’ annual scientific meetings in New Orleans so the wires are humming with information those of us with diabetes need to read and understand. Dr. Laura Mauri, an assistant professor of medicine at Brigham and Woman’s Hospital and Harvard Medical School shared research for randomized trials that indicate there is clear efficacy and clear reduction for repeat revascularization with drug –coated stents for patients with diabetes. The safety of drug-coated stents verses conventional bare metal stents has been a matter of controversy for years. Mauri presented a three-year follow-up data for a subgroup of about 5,000 diabetic patients undergoing percutaneous coronary intervention (PCI) with stenting to reopen blocked vessels. Two-thirds of the patients were treated with drug-eluding stents and on-third were treated with bare metal stents. There was an absolute reduction of about 5% in the need for repeat procedures in the target vessel and a small, but significant and surprising decrease in death and subsequent attacks.

As you may remember, this writer is a type 1 diabetic who exercises 6 days a week, however, we all know that there are barriers to physical activity among those of us with the disease. Diabetes Care 31:2108-2109. 2008 had an article written by Anne-Sophie Brazeau, R.D. et al all from Montreal, Canada which used the Barriers to Physical Activity in Diabetes (BAPAD1) and factors associated with these barriers to asses the question. One hundred patients with type 1 diabetes answered the questionnaire and A1c was obtained from the medical chart of each individual. It was not surprising that fear of hypoglycemia was the strongest barrier to physical activity. Greater knowledge about insulin pharmacokinetics and using appropriate approaches to minimize exercise-induced hypoglycemia were factors associated with fewer perceived barriers. Greater barriers were positively correlated with A1c levels and negatively with well-being. It appears that fear of hypoglycemia is the strongest barrier to physical activity in adults with type 1 diabetes and that to counter this education about hypoglycemia management is mandatory.

New Zealand has given the green light for clinical trials involving the transplantation of pig cells into humans in a potential breakthrough treatment of diabetes. Health Minister David Cunliffe said the process, known as xenotransplantation had huge potential for people with diabetes. Biotech entrepreneur Living Cell Technologies (LCT) wants to transfer cells from the pancreas of pigs to produce insulin in people with type 1 diabetes. There are risks involved here given the potential for a pig virus to be transferred that could then become capable of spreading as an infection in people. “It remains clear to me that any such trial will always carry a very residual risk, so the key issue has always been whether this risk is sufficiently small and be successfully managed.” Cunliffe said. According to Professor Bob Elliott, LCT’s medical director a group of Russians injected with New Zealand pig cells last year showed reductions in daily insulin requirements ranging from 23% to as much as 100% and had good control of blood glucose levels in four of five patients. We’ll follow-up on this when the research is published.

Here’s a headline that caught our eye just because we love good red wine. A drug in development that mimics a health-boosting compound found in red wine may be a powerful weapon in the fight against obesity and diabetes. A study of mice showed that GlaxoSmithKline drug SRT1720 was about a thousand times more potent than resveratrol in activating an enzyme that helped the animals burn more energy and lower their insulin and glucose levels. Mice fed a high-fat diet were tricked into switching their metabolisms to a fat-burning mode that takes over when energy levels are low in the article found in the journal Cell Metabolism. “We are activating the enzymes that are activated when people go to the gym,” said Peter Elliott, a vice president at Sirtris Pharmaceuticals, the Glaxo unit developing the drug. “that is why we believe the profile for this drug is very safe.” A Phase 1 trial has shown the treatment is safe and well-tolerated and the company plans to begin a wider Phase 2 trial with diabetics in 2009.

Doctors should not routinely give aspirin to people with diabetes to help guard against a heart attack or stroke, a British study found. While it was effective for those who had already developed heart disease or suffered a stroke, regular aspirin offered no benefit for patients with diabetes and a common circulatory problem. The study published in the British Medical Journal by researchers led by Jill Belch at the University of Dundee in Scotland included data on 1,276 men and women who had never had a heart attack or stroke but who were at high risk because they had diabetes or peripheral arterial disease. The researchers gave some people either aspirin or a placebo and others an antioxidant or placebo. They found that after eight years the number of heart attacks and strokes was about the same. They concluded that there was no evidence to support the use of either aspirin or antioxidants in the primary prevention of cardiovascular events and mortality in people with diabetes. “Aspirin should, however, should still be given for secondary prevention of cardiovascular disease in people with diabetes” While aspirin can cause stomach bleeding, the benefits still outweigh the risks for certain people, researchers added.

The New England Journal of Medicine (19.1056/NEJ/oa0806470) titled 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes by Rury R. Holman, F.R.C.P., et al. During the UK Prospective Diabetes Study (UKPDS) patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. The researchers conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had long-term effect on macrovascular outcomes. They randomly divided 5102 newly diagnosed type 2 diabetics to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend clinics, and all patients in years 6 and 10 were assessed through questionnaires. They examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories. The results showed between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea group, relative reductions in risk persisted at 10 years for any diabetes-related end point, and risk reductions for myocardial infarction and death from any cause emerged over time. As more events occurred in the metformin group, significant risk reductions persisted for any diabetes-related end point and death from any cause. The researchers concluded that despite an early loss of glycemic differences, a continued reduction in microvascular risk emergent risk reduction for myocardial infarction and death from any cause were observed during the 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients.

The Archives of Internal medicine 2008;168(19):2088-2094 had an article titled national Trends in Treatment of Type 2 Diabetes Mellitus, 1994-2007 by G.Caleb Alexander, MD, MS et al. The researchers used the National Disease and Therapeutic Index to analyze medications prescribed between 1994 and 2007 for all US office visits among patients 35 years or older with type 2 diabetes. They used the National Prescription Audit to assess medication coasts between 2001 and 2007. The results indicated that the estimated number of patient visits for treated diabetes increased from 25 million in 1994 to 36 million by 2007. The mean number of diabetes medications per treated patient increased from 1.14 in 1994 to 1.63 in 2007. Monotherapy declined from 82% of visits of visits during which a treatment was used in 1994 to 47% in 2007. Insulin use decreased from 38% of treatment visits in 1994 to a nadir of 25% IN 2000 and increased to 28% IN 2007. Sulfonylurea use decreased from 67% of treatment visits in 1994 to 34% in 2007. By 2007, biguanides and glitazones were leading therapeutic were the leading therapeutic classes. Increasing use of glitazones, newer insulins, sitagliptin phosphate, and exenatide largely accounted for recent increases in the mean cost per prescription ($56 in 2001 to $76 in 2007) and aggregate drug expenditures ($6.7 billion in 2001 to $12.5 billion in 2007). The authors concluded the increasingly complex and costly diabetes treatments are being applied to an increasing population. The magnitude of these rapid changes raises concerns about whether these more costly therapies will result in proportionately improved outcomes.

BSP