DIABETIC DRUG

A widely used class of diabetes medications appears to be associated with an increased risk for fractures, according to a report in the April 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

“The insulin-sensitizing thiazolidinediones are a relatively new and effective class of oral antidiabetic agents that have gained wide use in clinical conditions characterized by insulin resistance,” the authors write as background information in the article. Two drugs in this category, pioglitazone and rosiglitazone, account for 21 percent of oral diabetes medications prescribed in the United States and 5 percent of those in Europe. Recent studies have suggested that these therapies may have unfavorable effects on bone, resulting in slower bone formation and faster bone loss.

Christian Meier, M.D., of University Hospital Basel, Basel, Switzerland, and colleagues studied 1,020 patients with diabetes who had fractures diagnosed at British general practitioners’ offices between 1994 and 2005. For each of those patients, up to four control patients with diabetes who were the same age and sex and had the same physician but did not have fractures were selected, for a total of 3,728 matched controls.

After adjusting for other risk factors, individuals who were currently taking rosiglitazone and pioglitazone had approximately double or triple the odds of hip and other non-spine fractures than those who did not take these drugs. The odds for fracture were increased among patients who took the drugs for approximately 12 to 18 months and the risk was highest for those with two or more years of therapy.

“This analysis provides further evidence of a possible association between long-term use of thiazolidinediones and fractures, particularly of the hip and wrist, in patients with diabetes mellitus,” the authors conclude. “No such effect was seen for other antidiabetic drugs in this study population. These findings, although they are consistent with recently reported data from a randomized trial, are based on relatively few thiazolidinedione-exposed patients and need to be confirmed by additional observational studies and by controlled clinical trials.”

Nicotine Linked to Infections and Inflammation

Nicotine, a component of tobacco smoke, can make the body more prone to infections and inflammation, a research team has found.

The study, published in Cell Biology, was led by David Scott, a University of Louisville oral health researcher.

Scott’s team found that nicotine affects the production of one type of white blood cells, one of the body’s primary defenses against infection and disease. White blood cells are produced in bone marrow and the cells mobilize in the bloodstream to attack disease-causing bacteria. The researchers learned that cells tainted with nicotine were less able to seek and destroy bacteria than normal cells.

The researchers determined that nicotine suppresses an important cell function that helps kill invading bacteria and, at the same time, increases levels of a substance that promotes the breakdown of healthy tissues.

“Both of these findings partially explain chronic tobacco users’ increased susceptibility to bacterial infection and inflammatory diseases,” said Scott.

Although nicotine has been known to affect the immune response, this is the first study to examine how nicotine affects production of bacteria-fighting cells in the bone marrow and their mobilization into the bloodstream.

Aspirin Increases Insulin Production

Aspirin-like compounds (salicylates) can claim another health benefit: increasing the amount of insulin produced by otherwise healthy obese people. Obesity is associated with insulin resistance, the first step toward type 2 diabetes.

Aspirin and other salicylates are known to reduce blood glucose in diabetic patients. New research accepted for publication in the Journal of Clinical Endocrinology & Metabolism reveals a similar beneficial effect among obese individuals by increasing the amount of insulin secreted into the bloodstream.

“The administration of a salicylate led to the lowering of serum glucose concentrations,” said Jose-Manuel Fernandez-Real of the Institut d’Investigacio Biomedica de Girona and CIBEROBN Fisiopatologia de la Obesidad, Spain, and lead author of the study. “These findings highlight the importance of further research on the possible therapeutic benefit of aspirin in the fight against type 2 diabetes.”

For their study, Fernandez-Real and his colleagues evaluated the effects of triflusal (a derivative of salicylate) on 28 subjects (nine men and 29 women). The average age of the participants was 48 years old and their average Body Mass Index (BMI) was 33.9. A BMI of over 30 is considered obese. During three, four-week treatment periods, the study participants received a 600 mg dose, a 900 mg dose, or a placebo once per day.

The researchers found that administration of triflusal led to decreased fasting serum glucose. Contrary to their expectations, insulin sensitivity did not significantly change during the trial. Insulin secretion, however, significantly increased in relation to the dose size.

In conjunction with the human studies, the researchers also conducted laboratory studies on insulin-producing cells (known as islets of Langerhans) from mice and humans. The researchers observed that triflusal significantly increased the insulin secreted by these cells.

“Aspirin therapy has been recognized to improve glucose tolerance and to reduce insulin requirements in diabetic subjects,” said Fernandez-Real. “To our knowledge, this is the first study to show that salicylates lowered serum glucose in non-diabetic obese subjects. We believe that this effect was due to a previously unsuspected increase in insulin secretion rather than enhanced insulin sensitivity.”

Concerned About Lasik? There are Alternatives

Frightened by headlines about Lasik side effects? Lasik gets all the advertising, but there are half a dozen alternate eye surgeries — from a simpler laser approach to implantable lenses — that might solve your squint.

They all have their own risks. A key is finding a surgeon who doesn't have a favorite but is qualified to evaluate patients for all of the options, to find the best fit.

Topping the list is a pre-Lasik laser that's making a comeback thanks to precision-improving computer software. It goes by two names: Surface ablation, or wavefront-guided PRK, which stands for photorefractive keratectomy. What's most important is that it doesn't require cutting a flap into the cornea, the eye's clear covering, like Lasik does, a cut widely considered that procedure's riskiest step.

Other Lasik alternatives have virtually no advertising and attract far fewer patients.

Tragic testimony before the Food and Drug Administration last week reinforced warnings that Lasik does come with risks: lost vision, painful dry eye, glare and other night-vision problems.

But aggressive marketing makes patients falsely believe clear sight is guaranteed, complained Dr. Jayne Weiss of Detroit's Kresge Eye Institute, who chaired the FDA advisory panel.

"Lasik is not a commodity. It's a surgical procedure, but it is being sold as a commodity," she told the meeting.

Lasik alternatives:

— With PRK, a laser reshapes the cornea's surface, no flap-cutting needed — important because making a flap cuts nerve receptors that critics say never fully return to normal, thus increasing the risk of painful dry eye. The trade-off: Patients occasionally suffered haze as their corneas healed, not a Lasik risk.

The updated version is wavefront-guided PRK, using computer software actually developed to improve Lasik. It lets surgeons map subtle irregularities in the cornea before zapping, providing a three-dimensional map that customizes treatment, minimizing but not eliminating side effects in both Lasik and PRK.

The Navy compared wavefront-guided PRK to wavefront-guided Lasik, and 12 months after surgery, "the results of both procedures were almost identical," says Dr. Steven Schallhorn, a San Diego ophthalmologist who oversaw the Navy's refractive surgery program until last year.

— CK, or conductive keratoplasty, corrects farsightedness or astigmatism by beaming radiofrequency waves around the cornea's edge.

— Lasers aside, a hard plastic lens can be implanted through a small incision in the eye, in front of the natural lens. These "phakic intraocular lenses" are for severe nearsightedness, too bad for Lasik and PRK. They refocus light entering the eye for improved distance vision. Because the natural lens stays in place, patients seem to retain close-up vision, too.

But they've been on the market only a few years, so long-term effects aren't yet known.

— Refractive lens exchange goes the next step and replaces the patient's own lens with an artificial one. It's essentially cataract surgery offered to some cataract-free people who wanted Lasik but are bad candidates, perhaps because of extreme near- or farsightedness. Lens options include a multifocal type that can allow for both distance and reading vision. Retinal detachment is a risk.

— Finally, corneal rings are transparent crescents about the thickness of a contact lens implanted to form a ring around the cornea's edge. Called Intacs, their slight weight flattens the cornea without permanently destroying tissue. While they're only for mild nearsightedness, they can be removed if patients suffer side effects such as glare.