Results from an updated meta-analysis published in the Archives of Internal Medicine indicate that rosiglitazone therapy is associated with an increased risk for myocardial infarction (MI), but not cardiovascular (CV) mortality.

The results add weight to recent suggestions by some researchers that rosiglitazone should be withdrawn from the market or placed under severe restrictions, as reported by MedWire News.

Steven Nissen and Kathy Wolski from the Cleveland Clinic in Ohio, USA, included all randomized controlled trials of rosiglitazone with a duration of at least 24 weeks and similar treatment periods for rosiglitazone and the control drug.

In total, 56 trials were included with a combined cohort of 35,531 patients: 19,509 who received rosiglitazone and 16,022 who received control therapy (any drug other than rosiglitazone including placebo).

They found that rosiglitazone therapy was associated with a 28% increased relative risk for MI versus control therapy.

However, CV mortality was not significantly increased in rosiglitazone treated patients compared with those treated with control therapy.

“The results of the current meta-analysis suggest an unfavorable benefit to risk ratio for rosiglitazone use,” write the authors.

They add that the implication of these results warrant further discussion as “even a modest increase in the risk of MI in a diabetic population would have serious consequences.”

A US Food and Drug Administration (FDA) advisory committee recently voted to keep rosiglitazone on the market, at least until results from the ongoing Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE) trial are released. A similar review is currently being carried out by the European Medicines Agency.

The FDA committee also voted for the addition of increased safety warnings to the rosiglitazone drug label, but exact changes have yet to be finalized.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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A variant located in the acetyl-coenzyme A carboxylase beta gene (ACACB) is linked to increased risk for nephropathy in Chinese Type 2 diabetics, report researchers.

The risk allele of the ACACB single nucleotide polymorphism (SNP) rs2268388 has previously been linked to nephropathy in Type 2 diabetics from Japanese and European-American populations.

To investigate whether this association is also present in Chinese patients, Sydney Tang (The University of Hong Kong, China) and colleagues genotyped for eight ACACB SNPs, including rs2268388, in 592 Chinese Type 2 diabetics from Hong Kong or Southern China aged 66.6 years on average.

Of the participants, 295 had advanced diabetic nephropathy and 300 had long-standing diabetes but no nephropathy.

As reported in the journal Nephrology Dialysis Transplantation, the researchers found that patients with diabetic nephropathy were 2.39 times more likely than patients with Type 2 diabetes alone to be carriers of the risk-associated T allele of the rs2268388 SNP.

None of the remaining seven SNPs were associated with diabetic nephropathy, however, and there was no evidence of haplotypic association when genotypes were combined.

“These results in the Chinese replicate the association between Type 2 diabetic nephropathy and rs2268388, as seen in Japanese and European Americans,” conclude Tang et al.

Tang and co-authors suggest that fatty acid oxidation pathways could be involved in the pathogenesis of Type 2 diabetic nephropathy, as previous experiments have shown that mice with a dysfunctional ACACB gene are apparently healthy, and although they consume more food than other mice, appear to be less prone to obesity and diabetes than mice with a functional version of the gene.

“Targeting this pathway may provide novel treatment options for the prevention of diabetic nephropathy,” say the team.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Results from a genome-wide association study show that a variant of the gene HHEX-IDE previously associated with Type 2 diabetes is also linked to elevated childhood body mass index (BMI).

“Previously we thought that this gene affects insulin production during adulthood, but we now see that it may play an early role in influencing insulin resistance through its impact on body size during childhood,” said Struan Grant (University of Pennsylvania School of Medicine, Philadelphia, USA).

“One implication is that if we can develop medicines to target specific biological pathways in childhood, we may be able to prevent diabetes from developing later in life.”

The team investigated the association of pediatric BMI with 20 single nucleotide polymorphisms (SNPs) at 18 previously discovered genetic loci associated with Type 2 diabetes. The study cohort comprised 7184 children of European ancestry who were randomly divided into a “discovery” cohort (n=3592) and a “replication” cohort (n=3592) for the purposes of this study.

Grant and co-investigators found that presence of the Type 2 diabetes risk-conferring G allele of the rs7923837 SNP of HHEX-IDE was associated with significantly increased pediatric BMI in both the discovery and the replication cohorts between the ages of 3 and 16 years.

The HHEX-IDE association with childhood BMI was the only one of statistical significance, with the exception of the previously established association between BMI and the rs3751812 SNP of the FTO gene.

“This finding suggests that there may be genetic activity during childhood that lays the foundation for the later development of Type 2 diabetes,” concluded Grant.

The results of this study are published in the journal Diabetes.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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The results of a meta-analysis suggest that the benefits of aspirin treatment for cardiovascular (CV) risk reduction are similar for diabetics and nondiabetics.

“Several guidelines, including those of the American Diabetes Association, recommend aspirin for the primary prevention of cardiovascular events in patients with diabetes,” say Victor Montori (Mayo Clinic, Rochester, Minnesota, USA) and colleagues.

However, the findings of several studies previously reported by MedWire News have suggested that diabetics may gain less CV benefit from aspirin therapy than nondiabetics.

To assess this further, Montori and co-workers carried out a meta-analysis of nine randomized controlled trials involving 89,392 participants in total.

To be eligible for analysis, the studies had to have enrolled patients with diabetes and no prior history of myocardial infarction (MI) or stroke and assessed the efficacy of aspirin at any dose. Study duration ranged from 2.3 to 10.1 years, and researchers followed participants up for mortality, MI, and stroke.

As reported in the journal Diabetes Care, the team found that when patients with diabetes who were taking aspirin were compared with nondiabetics taking aspirin there were no statistically significant differences in mortality, MI, or ischemic stroke.

“While there are insufficient data among patients with diabetes to conclusively show a benefit of aspirin therapy for the primary prevention of cardiovascular events, our data suggest, but do not confirm, that the relative benefit of aspirin is similar in patients with and without diabetes,” conclude Montori et al.

“Additional evidence from randomized controlled trials and individual-patient-data meta-analyses may help to further clarify this issue.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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Low-dose aspirin therapy shows no CVD benefit for Type 2 diabetics
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Alanine-aminotransferase (ALT) is an independent predictor for impaired glucose tolerance (IGT), a precursor to Type 2 diabetes, show results from a German worksite population.

The BASF (Baden Aniline and Soda Factory) Occupational Medicine and Health Protection Department offered a diabetes screening program to its 33,000 employees in 2006, of whom 1594 had their diabetes risk tested.

Michael Morcos and fellow researchers from the University of Heidelberg found that of all the employees tested, 374 had the metabolic syndrome according to the International Diabetes Federation criteria.

They also found that 285 had a medium-to-high risk for IGT and Type 2 diabetes according to the Finrisk scoring system, of whom 157, aged 49 years on average, underwent the oral glucose tolerance test.

Of the 157 individuals tested, 18% had either IGT (n=22) or Type 2 diabetes (n=5).

Following adjustment for various confounding factors including age and gender, fasting glucose and ALT were the only independent predictors of IGT.

More specifically, mean fasting glucose was 97 mg/dl in individuals with normoglycemia and 103 mg/dl in those with IGT. In addition, ALT levels were 28 U/l in normoglycemic participants and 36 U/l in those with IGT.

Participants in the upper quartile for ALT and fasting glucose had a significant 4.8 and 5.5-fold increased risk for Type 2 diabetes compared with the lower quartile, respectively.

“These data point to an important role of the liver in insulin resistance and the development of IGT in the relatively young and small population studied,” conclude the authors in the journal Acta Diabetologia.

They add: “Our data support the intention to study ALT as a potential predictive marker of IGT and diabetes Type 2 in more detail in a larger population in a prospective, randomized study.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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Diabetic neuropathy patients with high triglycerides have increased myelinated fiber density (MFD) loss compared with neuropathy patients with lower triglycerides, report researchers.

Peripheral neuropathy, involving damage to nerves in the hands, arms, legs, and feet, is the most common complication of diabetes, affecting 60% of Type 1 and 2 diabetic patients.

In this study, Eva Feldman (University of Michigan, USA) and colleagues investigated mechanisms underlying the progression of diabetic neuropathy in 427 patients (78% Type 2 diabetes) using indices of sural nerve morphometry obtained at baseline and after 1 year.

Progression of neuropathy was defined as a loss of 500 fibers/mm² or more in sural nerve MFD over 1 year. The researchers found that individuals who had progressing MFD had a 25% decrease in MFD from baseline compared with those whose condition was unchanged.

As reported in the journal Diabetes, the researchers found that elevated triglycerides and decreased peroneal motor nerve conduction velocity (NCV) at baseline were significantly associated with MFD loss at 1 year.

The association with raised triglycerides was independent of disease duration, age, diabetes control, or other variables.

Of note, peroneal NCV, although significant, was only 5% different between groups and therefore did not contribute much to the predictive model.

“These results set the stage for clinicians to be able to address lowering lipid counts with their diabetes patients with neuropathy as vigilantly as they pursue glucose control,” said Feldman.

Co-investigator Rodica Pop-Busui, also from the University of Michigan, added: “Our findings in this study reinforce the tight links between cardiovascular disease and peripheral neuropathy in patients with diabetes.

“We demonstrated that the same lipid particles that contribute to the progression of atherosclerosis are also very important players in peripheral nerve fiber loss.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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