Diabetes News - November 14th, 1999

"Old Drug" May Prevent Type 2 Diabetes

Ramipril, an ACE inhibitor used widely for years for high blood pressure or heart disease, appears to be the first drug ever to prevent diabetes. In a large study just published, Ramipril reduced the rate of diabetes by 30% in patients participating in research because of their high risk for heart disease. It was also found to reduce the risk of death from heart disease by 20% as well as death rates from stroke by 30%. 

ACE inhibitors are traditionally used in treating high blood pressure and kidney disease, but this study suggests people at risk for heart attack, stroke or diabetes may also be candidates. Researchers at McMaster University in Hamilton, Ontario, tested ramipril for almost five years on 9,297 men and women in North and South America and Europe who were considered at high risk of heart disease, even though they were already taking a range of other heart drugs. 

The patients were considered ``high risk'' for heart disease because they had either vascular disease or diabetes plus one other factor, such as high blood pressure, elevated cholesterol or smoking. None of the patients had heart failure, which is a condition rampiril is often used to treat. The patients received either daily ramipril or placebo for the duration of the study. At the end of the study, only 14% of patients taking ramipril had died or suffered a heart attack or stroke, compared with 17.7% of placebo-treated patients. This is a significant difference of 22%. 

Salim Yusuf and colleagues reported their findings at the American Heart Association's annual scientific meeting in Atlanta. The research is to be published in the New England Journal of Medicine in January, but the results are so promising for immediate application that the Journal released the study on its web site early. 

ACE (angiotensin converting enzyme) inhibitors lower blood pressure by preventing a natural product called angiotensin I from converting into angiotensin II, which causes blood vessels to constrict and increases blood pressure. The results of this study suggest that ramipril does more than just lower blood pressure. It is not clear how it works, but it may improve the function of the cells that line the blood vessel and interact with various components of the blood. These results extend the use of ACE inhibitors broadly from lowering blood pressure to lowering the risk for heart attack, stroke, and diabetes.

The patients in this study were taking other drugs, as well as the rampiril. Two-thirds were taking aspirin, 40 percent were taking beta-blockers, 20 percent were on diuretics. This research suggests that people with high risk for heart disease should be taking ACE inhibitors along with the other drugs, typically aspirin, beta blockers and cholesterol-lowering drugs, already recommended. In fact, they should take rampiril even if they don't have high blood pressure or if it is well controlled by other drugs. 

The primary side effect of ACE inhibitors seen in about 5% of those who take it is a dry cough. The drug is marketed in the United States by King Pharmaceuticals of Bristol, Tennessee, under the name Altace.

Diabetic Nerve Damage Reversed

Scientists have reversed some diabetes-related nerve damage by injecting a protein that is an insulin-like growth factor into rats. The findings published in the American Journal of Pathology (AJP: 1999; v 155:pgs 1651-1660) suggests that the protein may similarly treat the nerve damage often found in diabetes in humans. 

Insulin-like growth factor-I (IGF-I) appears to be needed for nerve function, including nerve impulse conduction and regrowth of axons. With diabetes, people often develop a range of neuropathies, because nerve cells are damaged by high blood sugar levels. Nerve damage results in numbness, tingling, or burning, particularly in the feet and hands, and with loss of control of basic functions like intestinal movement. 

Dr. Robert E. Schmidt, lead author of the study conducted at Washington University School of Medicine in St. Louis, Missouri, used diabetic rats to investigate IGF-I's impact on nerve damage. Although blood sugar levels in the rats were not brought under control, nerve repair occurred. The study's results were even more impressive given the ongoing damage that would be expected from the high blood sugar environment. In treating nerve damage in humans, the first step is usually to bring the blood sugars into good control.

IGF-I may cause side effects in large doses because the protein also promotes growth in organs and systems of the body other than nerves, and it may increase growth in an existing cancer. Nevertheless, IGF-I appears promising as a treatment for diabetic neuropathy.

Obesity Causes Early Heart Disease 

An average obese person develops heart disease seven years earlier and dies four years earlier than the person of normal weight, according to a study presented at the American Heart Association. 

Common medical wisdom has long known that carrying extra weight increases the risk of heart disease. To see if this risk could be quantified, a research team led by Dr. Eric Eisenstein at Duke University Medical Center analyzed existing research. The research they analyzed was 12 years of detailed data gathered from more than 9,000 heart patients who came to their clinic. 

From this they calculated the median age when people of differing weights developed heart disease symptoms, such as chest pain and shortness of breath. Normal weight patients who came to their clinic developed heart disease at the median age of 64, overweight patients at 61, and obese at 57. 

The researchers also calculated how many years heart disease shortened a person's life. According to their data, people of normal weight with heart disease had an average life expectancy of 78, those overweight died at 77 and the obese died at 74. The heavier people more often had high blood pressure, diabetes and high blood cholesterol.

Obesity is calculated using body mass index (BMI). A BMI of 24 or less is considered healthy, 25-29 makes a person overweight and 30 or over counts as obese.

New Drug Helps Diabetic Kidney Disease

Pimagedine, a new drug from Alteon, has been shown to reduce protein excreted in the urine by people with kidney disease, resulting from damage caused by Type 1 diabetes. Pimagedine is aminoguanidine that blocks the formation of advanced glycosylation endproducts or AGEs, which form when two neighboring proteins with excess glucose attached to them form a permanent, damaging crosslink.

The drug is being tested to see if it will preserve kidney function in people with Type 1 diabetes and kidney disease. The randomized, double-blind multicenter trial includes 690 patients at 56 clinical sites in North America. All patients receive standard kidney care, including ACE inhibitors. In addition one group received a placebo, a second group received pimagedine at a low dose (300 mg twice a day), a third group received pimagedine at a high dose (600 mg twice a day) and a fourth group received combined therapy. 

Three research studies were presented at the American Society of Nephropathy meeting. One reported that pimagedine reduced the level of total urinary protein in a statistically significant way in patients given good medical therapy, whether low dose of pimagedine, high dose or a combination. The reduction was statistically significant using the low dose, starting at the 6th month and extending until the 36th month. Pimagedine also slowed the progression of kidney disease, especially if the kidney disease is less advanced. 

Also reported, pimagedine mildly slows the progression of retinopathy and loweres lipid levels. Progression of retinopathy occurred in 16% of the placebo group, but progression was reduced to 11% in low dose, 8% in high dose and 10% in combined therapy. Total cholesterol was lowered 5.2 mg/dL (placebo), 21.3 mg/dL (low dose), 18.3 mg/dL, (high dose) and 19.8 mg/dL (combined). LDL cholesterol was lowered 11.7 mg/dL (placebo), 22.3 mg/dL (low dose), 23.5 mg/dL (high dose) and 22.9 mg/dL (combined). 

Side effects included symptoms similar to short term flu, anemia, and creation of autoantibodies. In general, pimagedine was well-tolerated in the low dose group with a safety record similar to the placebo group. Alteon reported preliminary data in November 1998 that showed favorable results in most of the study. However, the extent to which pimagedine showed a reduction of the risk of doubling serum creatinine was disappointing, because the results did not reach statistical significance for this important parameter.

Schools Must Care For Children With Diabetes

A discrimination suit brought by the American Diabetes Association and two Louden County, Virginia, parents over whether their children with diabetes could be given glucagon as a life-saving measure at school was settled when all parties signed a Commitment to Resolve dated October 25, 1999. 

The agreement, drawn up by the federal Office of Civil Rights of the Department of Education (OCR) and Loudoun County Public Schools, responded to a complaint brought by two parents Crystal Jackson and Sandi Pope. They complained to OCR when Loudoun County school officials refused to allow school staff to give life-saving glucagon injections to their three grade school-aged children to counter severe insulin reactions. The officials first said if registered nurses were not available to give the shots, the school should call ``911'' rather than have other school staff give the glucagon. The parents complained this took so long their children could suffer brain damage or even die waiting for emergency personnel to arrive. 

As part of the complaint, the two parents alleged discrimination in violation of Section 504 of the Rehabilitation Act of 1973, which prohibits discrimination based on disability in programs that receive federal funds. 

The ADA and Ms. Jackson and Ms. Pope brought about earlier this year a new law forcing Virginia public schools to train personnel to administer both insulin and glucagon shots. The OCR agreement goes even further by stating that the school district must train school personnel in diabetes care and have them provide service at school and when children with diabetes go on field trips, participate in extra-curricular activities, and ride the bus. Furthermore, the school must develop and implement a Health Care Plan for each student with diabetes providing the reasonable accommodations needed for each child. 

This legislation could provide a precedence throughout the country for other school districts, almost all of whom have students with diabetes.

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