July is here and we have interesting headlines as well as research papers to report to you. We are very pleased that so many of you read these articles because we know that knowledge keeps us all as healthy as possible. Again, let us know what you are interested in and we'll look for it. We try to be balanced in our reporting and not to raise false hopes. I've been a type 1 diabetic for 19 years and know how I used to get excited about headlines in the paper, only to lose some of my hope for the future when the "breakthrough" broke down. This month we have many headlines to start with and then we will share articles on Statins and neuropathy, Ghrelin levels and obesity, teaching cells to tolerate donor tissue, Vitamin D analog and treatment of diabetes, and finally underinsurance and mental illness in diabetic children.
First, let's look at those headlines. The New England Journal of Medicine has announced a highly specialized monoclonal antibody designed to prevent the immune system from destroying insulin-producing cells. It has been tried in 12 children with type 1 diabetes. It was tested for dosage and safety, and did well enough that 80 patients between 7 and 27 are being recruited at several medical centers for more advanced clinical trials. This drug is not designed to prevent or cure diabetes, but researchers hope it will allow patients to continue to produce their own insulin for as long as possible. Dr. Kevin Herold at Columbia University did the study. That was the "good" headline. Here is one that counters an old headline. When I first became diabetic, it was thought that giving insulin to prevent the disease was the future. Joslin Diabetes Center reported that although they continue to work on a pill to stem diabetes, in their work with 84,228 participants, of the 339 found to have a five year risk of more than 50 percent to develop diabetes and randomly assigned to undergo insulin injections or just monitoring, both groups developed diabetes at an annual rate of 15 percent.
We all know that diabetics have a high risk factor for hypertension. We, therefore, are always on the lookout for new treatments and medications because there's a good chance that this is most of our futures. Circulation, the Journal of the American Heart Association reported on a new class of drugs that reduces blood pressure better than ACE inhibitors. This is the single-molecule omapatrilat that blocks the production of the potent vasoconstrictor hormone, angiotensin II. It also blocks the breakdown of a family of hormones that cause vessels-especially large arteries-to dilate and become less stiff. Keep reading here and we'll follow-up on this one.
We all know that type 2 diabetes and obesity are linked so we were interested in a newly discovered hormone linked to appetite weight reduction. Finally Reuters reports that a survey of doctors in the UK showed current staff levels of specialist physicians to treat diabetes are at the "shortage" level and expected to get worse as the epidemic of obesity and diabetes continues.
Now, on to the research for the month. Neurology, 2002; 58: 1333-1337 has an article titled Statin drugs increase risk of peripheral neuropathy by Laurie Barklay, MD. Although statins have been linked to increased risk of myopathy, this article suggests that peripheral neuropathy may also be a delayed adverse effect. In the population-based study, researchers used a patient registry to identify all first cases of idiopathic peripheral neuropathy in Funen County, Denmark over a 5 year-year period. Each case was matched to 25 controls of the same sex and age. Those using statins had a 16.1-fold risk of definite idiopathic neuropathy and a 4.6-fold risk considering all cases of neuropathy. In patients receiving statins for 2 or more years, risk of developing neuropathy was 26.4 times that of control patients. These findings should not affect doctor or patients decisions to start using statins because the absolute risk is low. If symptoms occur, patients should talk to their physician and then may reconsider the use of statins. This advice comes from physicians who responded to the research. The research is seen as another provider of "risk" factor information.
The New England Journal Of Medicine 2002; 346: 1623-1630 has an article titled Ghrelin levels linked to regulation of body weight by Dr. David E. Cummings et al. Ghrelin is a recently identified orexigenic hormone which is associated with the long-term regulation of body weight and may be the target for obesity treatment. Dr. Cummings et al, from the Veterans Affairs Puget Sound Health Care System in Seattle, studied 24-hour ghrelin levels in 13 obese patients before and after a 6-month weight loss program. Insulin and leptin levels and insulin sensitivity were evaluated. Ghrelin were also obtained for 5 formerly obese patients who underwent gastric bypass, 5 obese controls, and 10 normal controls. In the patients who lost weight using a low-calorie diet, there was an increase in ghrelin production which suggests that ghrelin production is mediated by body weight. Weight loss following gastric bypass surgery was associated with profound suppression of ghrelin and the absence of any mealtime oscillations in ghrelin levels. Dr. Cummings and colleagues conclude, "These data suggest that ghrelin antagonists may someday be considered in the treatment of obesity". Keep tuned; we'll keep looking. We know how important losing weight is to controlling type 2 diabetes.
We don't know if you saw the TV news magazine piece on cell transplantation to cure type 1 diabetes in a woman whose heath was failing. The woman whose diabetes was brittle to the max was verbal about the trade off of insulin and the anti-rejection medications she has to take. Achieving tolerance could free transplant recipients from a lifelong regime of drugs that stave off rejection by suppressing the entire immune system, thus weakening the body's ability to fight infections and tumors. Here we review what researchers in diabetes are saying about what is happening in the field. Dr. Jeffery Blueston, director of the diabetes center at the University of California at San Francisco and director of the Immune Tolerance Network, says that "the challenge is to do it reliably, robustly, with limited drug treatment and in a variety of diseases where it can have the greatest impact." The body has to learn how to distinguish self from non-self. So far, the most successful efforts to achieve tolerance have come through bone marrow or related stem cell transplants. Bone marrow contains stem cells that give rise to the cells of the immune system, so that the immune system of the bone marrow recipient will resemble that of the donor, allowing the patient to accept an organ from the same person. To make the procedure easier, scientists are trying to develop mini-transplants using less radiation and chemotherapy, so that the patients' immune system is not completely wiped out, just suppressed. The immune system, doctors hope, will be a mixture of the donor's and recipients. As a result, some patients have been weaned off of immune suppressing drugs after kidney transplants. The process marches on and we will continue to keep you posted. We all want to be able to have a viable "cure".
Diabetes 2002; 51: 1367-1374 has an article titled Vitamin D analog shows promise in treatment of experimental diabetes model by Dr. Luciano Adorini et al in Milan, Italy. The researchers found that a vitamin D3 analog arrests autoimmune diabetes in a mouse model. Dr. Adorini states that "our vitamin D3 has shown efficacy in a pre-clinical model and there are a lot of indirect data suggesting a beneficial effect of Vitamin D3 in human type 1 diabetes." The researchers treated adult non-obese diabetic mice with a vitamin D3 analog daily for 4 or 8 weeks. Treatment, especially for the longer period of time brought a significantly lower incidence of type 1 diabetes. Treatment halted the recruitment of infiltrating cells into the pancreatic islets and left more functional islet beta-cells. "It remains to be seen if this may translate into a treatment," Dr. Adorini states, "and until then we must remain very cautious".
Our final article is one that may be difficult for those of you to read who have children with diabetes, but do read on. We receive many questions about psychiatric illness and diabetes, and so here is one from JAMA 2002; 287: 2511-2518 titled Underinsurance, mental illness predispose diabetic children to complications by Dr. Arleta Rewers et al of the University Of Colorado School Of Medicine in Denver. This article examines underinsurance, the presence of psychiatric disorders, and an extreme glycosylated hemoglobin level as risk factors for acute complications in children with type 1 diabetes as shown by this large prospective study. The authors indicate that targeted interventions could prevent a large proportion of acute complications that occur among this population. Between 1996 and 2000, Dr. Rewers tracked diabetes-related outcomes among 1243 children. There were an average of eight episodes of diabetic ketoacidosis per 100 person-years and in those 13 years a 1 % increase in hemoglobin A1c increased the risk of ketoacidosis by 50%. Among girls, the incidence of ketoacidosis increased significantly with age, while the incidence of severe hypoglycemia decreased with age. No such relationship with age was observed for boys. In both sexes, ketoacidosis incidence was associated with longer duration of diabetes. The investigators used underinsurance as a proxy for low socioeconomic status and unstable living conditions, and defined it as a lack of enrollment in Medicaid or Child Health Plan Plus. In children age 13 and older, underinsurance was associated with relative risk of 2.18 for ketoacidosis.
The presence of psychiatric disorders led to a relative risk of 1.59 for boys and 3.22 for girls. Severe hypoglycemia was independently predicted by non-Hispanic white ethnicity, longer duration of diabetes, and underinsurance. Among older children, the relative risk was 1.42 for those who were underinsured, and 1.56 for those with a psychiatric disorder. "Children with type 1 diabetes, while managed by a state-of-the-art team, still experienced significant numbers of severe, potentially preventable complications," the authors write. They note that adolescent girls were at the highest risk for ketoacidosis, presumably because they are more likely to omit insulin injections to lose weight. Psychiatric disorders, they hypothesize, lead to severe hypoglycemic episodes, because of less frequent blood glucose testing, and a more chaotic diet and wake/sleep patterns. On the other hand, Dr. Rewers suggests that having diabetes in childhood may lead to psychiatric illness. As time goes by, psychiatric disorders in children increases so that by 20 years of age, 40% of these children have some kind of psychiatric problem. The concept that there is no vacation from diabetes has been thought to play a role in this problem. Certainly, when my husband and I were in practice and at psychiatric hospitals for children and adolescents, we noted that diabetic children were over-represented in the populations. This article is one to read and keep in mind as we raise our children who have diabetes.
BSP
