Omega-3 v diabetes.

Scientists have worked out how omega-3 can reverse type-2 diabetes by shutting down inflammation in obese mice.

Prof Jerrold Olefsky found that omega-3 fatty acids, particularly DHA and EPA, bound to a particular receptor (GPR120) of the immune system, which resulted in potent blocking of inflammation. As the inflammation subsided, insulin sensitivity returned and blood glucose levels came under control.

The dose of omega-3 given to the mice was enough to double the level of omega-3 in their bloodstream. The omega-3 treatment was as effective, or even more effective, than the popular insulin-sensitizing drug rosiglitazone (Avandia).

In the US, Lovaza is FDA-approved for treatment of very high triglycerides, on a daily dose of 4 capsules each containing 465mg EPA and 375mg DHA as the active ingredients.

Grapefruit delight.

In 2003 (published 2006, Journal of Medicinal Food), Dr Ken Fujioka showed that grapefruit produced modest, but significant, weight loss when added to the diet of obese Americans for 12 weeks.

Before each meal the subjects ate one of – placebo plus apple juice, placebo plus grapefruit juice, grapefruit tablet plus apple juice or half a fresh grapefruit.

This was not the Hollywood Diet, which is severely calorie-restricted.

With Fujioka, the only change to normal intake was the pre-load.

Considering all subjects, each of the grapefruit combinations beat the apple juice + placebo, but only the half a grapefruit was clinically significant.

However, when looking at people with metabolic syndrome, each of the grapefruit combinations produced significant weight loss and improved insulin resistance.

Dr Fujioka was unable to give a precise mechanism why this might work.

This week, Dr Yaakov Nahmias published a lab study of liver action covering how grapefruit works.

Technically, it raises PPARalpha and PPARgamma and blocks LXRalpha. This mimics drug combinations such as lipid-lowering Fenofibrate and the anti-diabetic Rosiglitazone.

The effect is to burn fat rather than carbohydrates and to cut production of vLDL (‘bad’ cholesterol).

According to Dr Martin L Yarmush “It is a process which is similar to the Atkins diet, without many of the side effects”.

Grapefruit is known to interfere with many prescription drugs, so a check is required in this case.

Diabetes drugs v fractures.

Dr William H Herman has published a study of the association between popular drugs for diabetes 2 and the risk of bone fractures.

The team looked at nearly 800 cases of fractures in patients with diabetes and compared against over 2,500 diabetic patients without fractures.

The drugs checked were both in the thiazolidinedione class (TZDs) – pioglitazone (Actos) and rosiglitazone (Avandia).

In men who took both loop diuretics (water tablets) and TZDs, there was an increased risk of fractures. This risk did NOT show up in men who were taking TZDs only.

In postmenopausal women, taking TZDs was associated with an increased risk of fractures, and in this case, the risk was dose-dependent.

The results for Actos and Avandia were similar, suggesting this is a feature of TZDs.

According to Dr Herman “Physicians should be aware of this risk and weigh the benefits and risks of therapy when they initially prescribe or renew prescriptions for TZDs.”

Avandia row rumbles on.

The British Medical Journal has published a review of studies and articles that commented on rosiglitazone (Avandia) and risk of heart attacks in patients using the drug to treat diabetes. The review found those commenting favourably on Avandia were much more likely to have a financial conflict of interest than those commenting negatively.

In February, the US Food and Drug Administration said it would hold a public meeting in July to consider Avandia. This came after the New York Times released FDA internal documents that appeared to show Avandia is riskier than Actos. TeamMcCallum covered this here.

In the BMJ, the reviewers used a test of direct financial interest in rosiglitazone or general financial interest in drugs to counter hyperglycaemia.

Corresponding author Mohammad Hassan Murad, and 3 others from the Mayo Clinic, concluded “Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors’ expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies” and that there is a need for better disclosure.

The BMJ review is here.

Avandia v Actos in New York Times.

According to the New York Times –

“Hundreds of people taking Avandia, a controversial diabetes medicine, needlessly suffer heart attacks and heart failure each month, according to confidential government reports that recommend the drug be removed from the market.

The reports, obtained by The New York Times, say that if every diabetic now taking Avandia were instead given a similar pill named Actos, about 500 heart attacks and 300 cases of heart failure would be averted every month because Avandia can hurt the heart. Avandia, intended to treat Type 2 diabetes, is known as rosiglitazone and was linked to 304 deaths during the third quarter of 2009.”

Click here for NY Times report.

Rosiglitazone is marketed as a stand-alone drug by GlaxoSmithKline as Avandia, or mixed with other drugs as Avandamet and Avandaryl.

Actos (US/UK) is also called Glustin (Europe) and Zactos (Mexico) and is pioglitazone, made by Takeda Pharmaceuticals.